revise and consolidate them. the Council feels the time is right to go over the two guidelines again. In both instances. the new Philippine Consensus Report on Asthma Diagnosis and Management 2009. which first appeared in the 2004 PCRADM update. first saw light in 1996. and single-minded determination of the core group of eighteen Asthma Council members who laboured long hours reviewing voluminous number of journal articles. the local consensus report formulated by the Council of Asthma of the Philippine College of Chest Physicians (PCCP). the Council is aiming to find greater acceptance and eventual usage of its updated guidelines by the Filipino physician managing asthmatic patients. Council on Asthma Philippine College of Chest Physicians . more scientific and more rational approach to the diagnosis and management of asthma. fellows-in-training. Applicability of the consensus report to what is the reality in the Philippine setting is the ultimate goal of this updated report. with emphasis placed on the inclusion of current local evidence that will make it more relevant to the Filipino practitioner involved in the asthma care. Dr. our heartfelt gratitude goes to AstraZeneca Philippines. Lastly. pathologic and cellular mechanisms of asthma. we likewise look forward to this report being a useful tool to affect a better. De Guia. M. The completion of this updated report would not be possible without the diligence. the continued efforts of health professionals to update existing guidelines that aimed to rationalize the diagnosis and approach to treatment of this disease. FPCCP Chairman.. Eloisa S. and in the end. After five years. and but also all medical practitioners who manage patients with asthma. We carried over the simpler classification of asthma. the Council is very proud of its differing stand in the classification and approach to treatment of asthma. come up with an updated document that will address the concerns of local practitioners tasked with the management of asthma. despite all odds. It is indeed a complex disease that lends itself to a wide variation of presentation and response to medication and makes a single approach to treatment virtually impossible. however. It was the Council decision that the updated report will be largely based on the 2007 GINA document. TITO C. Over and beyond the similarities with GINA. Much of the credit should go to Dr. The Philippine Consensus Report on Asthma Diagnosis and Management of Asthma (PCRADM). the approach to treatment in this current update is a modification of the original GINA recommendation. The present document is a product of some eight months of hard work. Hence. and an improvement to what was proposed in the 2004 document. With the plans for a nationwide dissemination process of the updated report already in place. managed to meet the set deadlines in finalizing this update report. Likewise. the reader will find obvious similarities in the chapter chronology and discussion of topics between the latest document and our updated report. In this context.D. Diaz who spearheaded the project and was its moving force from conceptualization to final publication. We likewise acknowledge the Herculean efforts of our project secretary. then adapted them using the GINA as “template” to come up with what you now have in your hand. ATIENZA. The relative paucity of published studies on asthma. We. it remains to be a major cause of chronic morbidity and mortality not only in the Philippines but also throughout the world. in the Asthma Council. Dina V. perseverance. however. the product of Asthma Consensus Report Update (ACRU) Project of the Philippine College of Chest Physicians Council on Asthma. research papers and other publications. resident physicians. for their commitment and generous support of this undertaking from start to finish. Somewhere in this document is the list of the core Asthma Council members. The updated 2004 evidence-based report took all of three years to complete. who. Inc. hope that this document will find wide acceptance not only among the pulmonary specialists.PREFACE Despite the fact that much is presently known about the clinical. without that invaluable contribution on this consensus report would not have been possible. internists. makes it imperative that each chapter of our updated report should end with recommendations to bridge such gaps in knowledge on diagnosis and management.

.............................................................................................................................................................................................................................................................................................................. 4....... and Monitor Asthma 1.......................................................................................................... 48 Improving Adherence ........... 3...... 9..................................................................................................................................................................... 55 Chapter 6 – Assess.. 3..................... 50 Chapter 5 – Identify and Reduce Risk Exposure to Risk Factors 1....... Diagnostic Challenges and Differential Diagnosis.............. Introduction......................................................................................................................... 2....................................................................................................................................... 11............................................................................................. 3............................................................................................................................................ 66 Assessing Asthma Control..................................................................................................................... Introduction ................ Introduction ............................................................. 6.................................................................................................................................................................................................................................. 78 Assessment of Severity ........................................................... 89 Treatment ............................................. 87 Laboratory Studies ................................................ 2................................................................................................................. 94 ................... Introduction ................................ 3............................................. Pathophysiologic Mechanisms...................................................................................... 3........................................................................................................................................................................................................................................................... 90 Repeat Assessment ................................................................................................................................ 50 Education of Others ............. 70 Chapter 7 – Acute Exacerbations 1... 92 Impending Respiratory Failure ...................... 4............................................................ 8............................................ 4........................ 5..................................................... 84 Assessment ................................................................................................................ 2........................................................................................................................................................................................................................................................................................................................... Classification of Asthma ........................... 67 Treating to Achieve Control.................................................................................................................................................................................................... v Chapter 1 – Definition and Overview 1........................................................................... 80 Management: Acute Care Setting ................................................................................................... 92 Patient Discharge ...................................................................................................................... Introduction................................... 79 Home Management of Acute Exacerbation ................................................................................................. 3.................................................. Asthma Education ..... Clinical Diagnosis............................................................................................................................... 4....................................... 16 16 21 22 22 Chapter 3 – Asthma Medications 1.................................................................................. Threat....... 5.............................................................TABLE OF CONTENTS Preface..................................................................................... 10.................................................. 2................................................................................................................. 54 Prevention of Asthma Symptoms and Exacerbations ...... 4..... 2.................................................................................................... 32 32 32 37 Chapter 4 – Patient Education 1.................................................. 2.................................................................................................... 92 Hospitalization .... Pathogenesis........................................................................ 67 Monitoring to Maintain Control ....................................................................................................................................................................................................................... Controller Medications .................................................................. 2............................................................................................................ Burden of Asthma.................................................................................................................................................................................. 3........................................................................................................... 2 3 6 8 Chapter 2 – Diagnosis and Classification 1................................................................................................... 7.................................................. Reliever Medications ................................ 54 Asthma Preservation ................................................................ Asthma Severity and Control a new perspective...... Route of Administration .......... Definition............

.............................................................................................................. 106 .................................... 106 Pregnancy ......................... Introduction .......................................................... 2...Chapter 8 – Special Considerations 1.....................................................................................................................

.

.

.

Inc. De Guia. Eloisa S. come up with an updated document that will address the concerns of local practitioners tasked with the management of asthma. Council on Asthma Philippine College of Chest Physicians . internists. After five years. without that invaluable contribution on this consensus report would not have been possible. with emphasis placed on the inclusion of current local evidence that will make it more relevant to the Filipino practitioner involved in the asthma care. the Council feels the time is right to go over the two guidelines again. Dr. however. it remains to be a major cause of chronic morbidity and mortality not only in the Philippines but also throughout the world. We. It was the Council decision that the updated report will be largely based on the 2007 GINA document. With the plans for a nationwide dissemination process of the updated report already in place. and an improvement to what was proposed in the 2004 document. Much of the credit should go to Dr.D. M. we likewise look forward to this report being a useful tool to affect a better. the continued efforts of health professionals to update existing guidelines that aimed to rationalize the diagnosis and approach to treatment of this disease. Likewise. the approach to treatment in this current update is a modification of the original GINA recommendation.. perseverance. Diaz who spearheaded the project and was its moving force from conceptualization to final publication. Somewhere in this document is the list of the core Asthma Council members. despite all odds. research papers and other publications. Hence. We likewise acknowledge the Herculean efforts of our project secretary. the new Philippine Consensus Report on Asthma Diagnosis and Management 2009. makes it imperative that each chapter of our updated report should end with recommendations to bridge such gaps in knowledge on diagnosis and management. and single-minded determination of the core group of eighteen Asthma Council members who laboured long hours reviewing voluminous number of journal articles. The updated 2004 evidence-based report took all of three years to complete. more scientific and more rational approach to the diagnosis and management of asthma. the local consensus report formulated by the Council of Asthma of the Philippine College of Chest Physicians (PCCP). which first appeared in the 2004 PCRADM update. In both instances. The Philippine Consensus Report on Asthma Diagnosis and Management of Asthma (PCRADM). The completion of this updated report would not be possible without the diligence. resident physicians. the Council is very proud of its differing stand in the classification and approach to treatment of asthma. Lastly. The present document is a product of some eight months of hard work. in the Asthma Council. We carried over the simpler classification of asthma. It is indeed a complex disease that lends itself to a wide variation of presentation and response to medication and makes a single approach to treatment virtually impossible. however. fellows-in-training. revise and consolidate them. In this context. the Council is aiming to find greater acceptance and eventual usage of its updated guidelines by the Filipino physician managing asthmatic patients. TITO C. first saw light in 1996. ATIENZA. who. Over and beyond the similarities with GINA. and but also all medical practitioners who manage patients with asthma. The relative paucity of published studies on asthma. managed to meet the set deadlines in finalizing this update report. Applicability of the consensus report to what is the reality in the Philippine setting is the ultimate goal of this updated report. pathologic and cellular mechanisms of asthma. hope that this document will find wide acceptance not only among the pulmonary specialists. for their commitment and generous support of this undertaking from start to finish.PREFACE Despite the fact that much is presently known about the clinical. the reader will find obvious similarities in the chapter chronology and discussion of topics between the latest document and our updated report. Dina V. the product of Asthma Consensus Report Update (ACRU) Project of the Philippine College of Chest Physicians Council on Asthma. then adapted them using the GINA as “template” to come up with what you now have in your hand. FPCCP Chairman. our heartfelt gratitude goes to AstraZeneca Philippines. and in the end.

................................................................................................. Introduction...................................................................................... 92 Patient Discharge ........................................................................................ Introduction ..................................................... 55 Chapter 6 – Assess..................................................................................................................................................................................... 92 Hospitalization ......................................... Introduction...................... 5..................................................................................................................................................................................................... 32 32 32 37 Chapter 4 – Patient Education 1.............................................................................. Clinical Diagnosis.............................................................................................. Burden of Asthma............................ 84 Assessment ................................................................ Route of Administration ........................................................................................................................................................... 50 Education of Others ....................... 2..................................................................................................................................................... Pathogenesis................................. Classification of Asthma ....................................................................................................................... Asthma Education ............................................................................ 3.................................... 4................................................................................................................................................... 3........................................................................................................................................................ 80 Management: Acute Care Setting .................................................................................................................................................... 67 Treating to Achieve Control................................................................................................... 2.............. 89 Treatment ... 94 ..................................................................... 70 Chapter 7 – Acute Exacerbations 1........................................................... 11............................................................................................................................ 2............................. v Chapter 1 – Definition and Overview 1................ 67 Monitoring to Maintain Control . Introduction .................................................................. 3................................................................................................................................................................................................................................................................................................. 90 Repeat Assessment ........................................................................ 78 Assessment of Severity ........................................................................ 4.......................................................................................................................................................................... Diagnostic Challenges and Differential Diagnosis....................... Reliever Medications ......... 10..... 4............................ Asthma Severity and Control a new perspective............................................................ 5...... Threat.......................................................................................................................................................................................... 3.......................................................................................................... 54 Asthma Preservation ...................................................................... 6................................................................................... 2.................................................. 2 3 6 8 Chapter 2 – Diagnosis and Classification 1...............................................................................TABLE OF CONTENTS Preface................................................................................................................................................................................................................................. Controller Medications ........... Definition...... 79 Home Management of Acute Exacerbation ......................................................................................................................................................................................................................................................................................................... 16 16 21 22 22 Chapter 3 – Asthma Medications 1.............................................. 4.............................................. 48 Improving Adherence ........................................................................................................................................................................ 7................................................ 54 Prevention of Asthma Symptoms and Exacerbations ..................................................................................... 3... 92 Impending Respiratory Failure ................................................... 2............................................. Introduction ........ 3...................... 87 Laboratory Studies ......................................................... and Monitor Asthma 1............................................................................................................. 3............................................................................................................................................................................................................................................ 2.............................. 4.............................................................................. 2..... 66 Assessing Asthma Control....... Pathophysiologic Mechanisms......... 8.......................................... 9........................................................ 50 Chapter 5 – Identify and Reduce Risk Exposure to Risk Factors 1...........................

........ 106 ...................................................................................... Introduction ........................ 106 Pregnancy ......................................................................................................................................................................................Chapter 8 – Special Considerations 1..................... 2............................

Chapter 1 Definition and Overview .

and coughing. chest tightness. thus indicating phenotypic differences that may influence treatment responses. with an estimated 300 million affected 1.1). Features of Asthma A number of factors that influence a person’s risk of developing asthma have been identified. In the Philippines. airflow obstruction. persistent changes in airway structure occur.4 Table 1. often accompanied by cough. but since its pathogenesis is not clear. The main physiological feature of asthma is episodic airway obstruction characterized by expiratory airflow limitation. much of its definition is descriptive. The dominant pathological feature is airway inflammation.2 individuals.1 In some patients. bronchial hyperresponsiveness. These episodes are usually associated with widespread. the cost of not treating asthma correctly is even higher. current asthma treatment with anti-inflammatory therapy does not appear to prevent progression of the underlying disease severity. from the perspective of both the patient and society. airflow limitation. and an underlying inflammation (Table 1. including smooth muscle hypertrophy mucus hypersecretion.3 Asthma is a chronic disorder of the airway that is complex and characterized by variable and recurring symptoms.KEY POINTS: DEFINITION Based on clinical. an operational definition of asthma is: 1 Asthma is a chronic inflammatory disorder of the airways which contributes to airway hyperresponsiveness. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing. particularly at night. but evidence is emerging for considerable variability in the pattern of inflammation. Asthma has significant genetic and environmental components. 2 . with 27 to 33% of children and 17 to 22% of adults with definite or probable asthma.1. Although it would seem that. the cost to control asthma is high. there is a high prevalence of asthma in urban areas. physiological and pathological characteristics of asthma. but variable. Wheezing appreciated on auscultation of the chest is the most common physical finding. and disease chronicity. Clinical manifestations of asthma can be controlled with appropriate treatment. breathlessness. Asthma is a problem worldwide. respiratory symptoms. The critical role of inflammation has been further substantiated. sometimes associated with airway structural changes. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment. Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The predominant feature of the clinical history is episodic shortness of breath. These can be divided into host factors (primarily genetic) and environmental factors. injury to epithelial cells. airflow obstruction within the lung that is often reversible either spontaneously or with treatment. subbasement fibrosis and angiogenesis. However. particularly at night or in the early morning.

10 Therefore.143 children between 6 to 7 years and 13 to 14 years old from three urban areas using a pretested Expert Panel Questionnaire. Acute symptoms of asthma usually arise from bronchospasm and require and respond to bronchodilator therapy. which enhances susceptibility to bronchospasm. current science regarding the mechanisms of asthma and findings from clinical trials have led to therapeutic approaches that allow most people who have asthma to participate fully in activities they choose.3 This survey involved 1. treatments will become available to ensure adequate asthma control for all persons and. Three asthma specialists who evaluated all subjects were blinded to the subjects’ responses to the screening questionnaires.6 The concepts involving pathogenesis of asthma has evolved greatly over the past 25 years.2 % (Fig. and natural history of this disease.6. pathophysiology. 13 it appears that the global prevalence of asthma ranges from 1% to 18% of the population in different countries (Fig. 5.8 BURDEN OF ASTHMA Asthma is considered as one of the most common chronic diseases with an estimated 300 million people currently affected worldwide.6 The most recent asthma prevalence data in the Philippines comes from an unpublished study of the National Asthma Epidemiology Survey (NAES) conducted in 2002.1). ideally.9 For some patients.the precise interactions between them that leads to the initiation or persistence of disease have yet to be fully established. and genetics of asthma continue to emerge. the development of chronic inflammation may be associated with permanent alterations in the airway structure— referred to as airway remodeling—that are not prevented by or fully responsive to currently available treatments. The Global Burden report stated that considerably higher estimates can be obtained with less conservative criteria for the diagnosis of clinical asthma. much has been learned about the host–environment factors that determine the airways’ susceptibility to these processes. Acute and chronic inflammation can affect not only the airway caliber and airflow. in some situations. In the Philippines. the relative contributions of either and 3 . However.3%. to reverse and even prevent the asthma processes.1. the successful response to therapy often requires weeks to achieve and.2 Treatment with anti-inflammatory drugs can. to a large extent.6 More recently.11 Based on the application of standardized methods to measure the prevalence of asthma and wheezing illness in children 1. Distinct but overlapping patterns are observed that reflect different aspects of the disease.6 Nonetheless. With further investigations to confirm Similarly. further evaluation of these concepts reveal that various phenotypes of asthma exist and that clinical features of asthma may be linked with genetic patterns. such as intermittent versus persistent or acute versus chronic manifestations. may be incomplete. phenotypes. the specific processes related to the transmission of airway inflammation to specific pathophysiologic consequences of airway dysfunction and the clinical manifestations of asthma have yet to be fully defined. the lack of a precise and universally accepted definition of asthma makes reliable comparison of reported prevalence from different parts of the world problematic.2 and adults. As more scientific information about the pathophysiology. but also underlying bronchial hyperresponsiveness.1. the paradigm of asthma has been expanded from bronchospasm and airway inflammation to include airway remodeling in some persons.2) The concept that asthma may be a continuum of these processes that can lead to moderate and severe persistent disease is of critical importance to understanding the pathogenesis.12 Although the role of inflammation in asthma is generally understood. however. reverse some of these processes.7 Such phenotypic patterns depend on the degree of the underlying airway inflammation which is variable. However. The prevalence estimates through the experts’ consensus was reported at 10.964 adults and 1. from a simple smooth muscle disease to the concept of airway inflammation. the prevalence listed was 6.

3 Permission for use of this figure obtained from J. The rate of asthma also appears to increase as communities adopt western lifestyles and become more urbanized. that the increase in the prevalence of asthma has been associated with an increase in atopic sensitization. It was thus recommended that symptoms suggestive of asthma are prevalent in the community and further investigations are necessary to confirm the disorder or to diagnose another illness. although only 87% of them were confirmed to have definite or probable asthma by the experts. Similarly.15 In 1998.1% of the population who presented with asthma-like illnesses and were classified as probably asthmatic by the expert panel. However. the prevalence rose to 26.18 The explanation for this occurrence has not been adequately explained.7%. Of these.964 Filipino adults16 showed that about 7. it would appear that the local prevalence of asthma is increasing. in others.207 children surveyed in Metro Manila aged 13 to 14 years and self-reported asthma symptoms were noted in 12% of the children. About half of the total population self-reported having experienced at least one symptom in the last year. only 35% were confirmed to have asthma or an asthma-like illness. a prevalence survey of asthma and asthma. the prevalence rate obtained in this study is 4. Previous epidemiologic data which included the Philippines were from the International Survey of Asthma and Allergy in Children (ISAAC) study in 1998. This finding is consistent with current thinking that asthma prevalence has been increasing in some countries. and is paralleled by similar increases in other allergic disorders such as eczema and rhinitis.14 The Philippine survey involved 3. This It has been observed. Asthma Prevalence and Mortality2. Bouquet prevalence rate may be an underestimation.Figure 1-1. prevalence may have stabilized. Based on the expert panel consensus.3%. since there is an additional 18.like illnesses involving 1. however. there is likely to be a marked increase in the number of asthmatics worldwide 4 . Thus. diagnosis of asthma. there are insufficient data to determine the likely causes of for the described variations in prevalence within and between populations.17. This figure is almost similar to the figures reported in Singapore and Japan.1% of respondents reported a prior doctor-diagnosed asthma. if the recent NAES 2002 data is taken into consideration. With the projected increase in the proportion of the world's population that is urban from 45% to 59% in 2025.

The World Health Organization (WHO) has estimated that 15 million disability-adjusted life years (DALYs) are lost annually due to asthma. This number of DALYs lost 5 . asthma accounts for around 1% of all DALYs lost. approximately 1 in every 250 deaths. there may be an estimated additional 100 million persons with asthma by 2025. Mortality does not appear to correlate well with prevalence (Figure 1-1).Figure 1-2. and thought to be due to suboptimal long-term medical care and delay in obtaining help during the final attack. which reflects the high prevalence and severity of asthma. or schizophrenia.20 With regards to mortality. Global Asthma Prevalence20 due to asthma is similar to that for diabetes. What may be more disturbing is the burden that asthma imposes on the sufferer and his or her family. annual worldwide deaths from asthma have been estimated at 250.000.2 Many of the deaths are preventable.1 over the next two decades. cirrhosis of the liver. As such. Worldwide.

Non-medical economic costs of asthma are substantial. the cost to control asthma is high. exercise-associated. Absence from school and days lost from work are reported as substantial social and economic consequences of asthma in studies from the Asia-Pacific region. PGD2). The processes by which these interactive events Airway structural cells There are also airway structural cells that are involved in asthma pathogenesis : epithelial cells. occupational asthma. and patients who smoke). IL-13) that orchestrate eosinophilic inflammation and Ig-E production by Blymphocytes.g. growth factors that may have a role in airway remodeling. Increased mast cell numbers in airway smooth muscle may be linked to airway hyperresponsiveness. Activated mast cells release bronchoconstrictor mediators (histamine. neutrophils (especially in sudden-onset. and duration of disease. airway inflammation remains a consistent pattern. intermittent. the cost of not treating asthma correctly is even higher. the monetary cost of purchasing medicines rests mainly on the patient. smooth muscle cells and endothelial cells. persistence. 6 Inflammatory cells Eosinophils release basic proteins that may damage airway epithelial cells. 6 Social and economic factors are integral to understanding asthma and its care.1 Although it would seem that. persistent. or severe asthma). the United Kingdom. Fibroblasts and myofibroblasts produced 6 . Several observations from comparisons of the cost of asthma in different regions have led to a clear set of conclusions : 1 The costs of asthma depend on the individual patient’s level of control and the extent to which exacerbations are avoided. This problem is aggravated by the fact that. The cellular profile and the response of the structural cells in asthma are quite consistent. IL5. There may also be an increase in natural killer (NK) cells which release large amounts of Th1 and Th2 cytokines. Moreover. and the United States. lymphocytes. from the perspective of both the patient and society. and shortness of breath. Guideline-determined asthma care can be cost effective. along with mast cell activation and epithelial cell injury. Emergency treatment is more expensive than planned treatment. wheeze. however. Increased numbers of neutrophils may be seen but their role is uncertain. does not necessarily vary depending upon disease severity. aspirinsensitive.. IL-9. cysteinyl leukotrienes. whether viewed from the perspective of the individual sufferer. The immunohistopathologic features of asthma include inflammatory cell infiltration with eosinophils. although distinct phenotypes of asthma exist (e. Tlymphocytes release specific cytokines (IL-4. fatal asthma exacerbations. Latin America. These cells are activated by allergens through high-affinity IgE receptors and osmotic stimuli (as seen in exercise-induced bronchoconstriction). Other inflammatory cells are dendritic cells that interact with regulatory T cells and stimulate Th2 production and macrophages which release inflammatory mediators and cytokines that amplify the inflammatory response. in the Philippines.occur and lead to clinical asthma are still under investigation. The pattern of airway inflammation in asthma. As noted in the definition of asthma. airway inflammation involves an interaction of many cell types and multiple mediators with the airways that eventually results in the characteristic pathophysiological features of the disease: bronchial inflammation and airflow limitation that result in recurrent episodes of cough. or entities that pay for health care. India. 1 The economic cost of asthma is considerable both in terms of direct medical costs (such as hospital admissions and cost of pharmaceuticals) and indirect costs (such as time lost from work and premature death). 1 PATHOPHYSIOLOGIC MECHANISMS Inflammation Inflammation has a central role in the pathophysiology of asthma. the health care professional.

1 Difficult-to-treat asthma. airway thickening (airway remodeling).22 Mediators in Asthma Nocturnal asthma. namely : airway smooth muscle contraction. The reasons why some patients develop asthma that is difficult to manage and relatively insensitive to the effects of glucocorticosteroids are not well understood. and melatonin and neural mechanisms such as cholinergic tone.g.24 Airway narrowing Airway narrowing is the final common pathway leading to symptoms and physiological changes in asthma. with resultant increase in mediators that contribute to asthma symptoms. Sensory nerves. Some patients with severe asthma develop progressive airflow limitation that is not fully reversible with currently available therapy.1 Irreversible airflow limitation. Asthma patients who smoke may have a neutrophil-predominant inflammation in their airways and are poorly responsive to glucocorticosteroids. the characteristic functional abnormality of asthma. cortisol. prostaglandin D2) and mediate the complex inflammatory response in the airways. air pollutants . nitric oxide. and mucus hypersecretion (mucus plugging). In these patients airway closure leads to air trapping and hyperinflation.1 Smoking and asthma. However.” such as exercise. Cholinergic nerves may be activated by reflex triggers in the airways and cause bronchoconstriction and mucus hypersecretion. Airway nerves are also involved. Many of these patients have difficult to-treat asthma from the onset of the disease. rather than progressing from milder asthma. Although the pathology appears broadly similar to other forms of asthma. there is an increase in neutrophils. e.23 The characteristic pattern of inflammation is also found in allergic diseases. genetic factors may contribute in some. more small airway involvement. this airway narrowing leads to variable airflow limitation and intermittent symptoms. or “triggers. cytokines. Over 100 different mediators are now recognized to be involved in asthma (e. Common associations are poor compliance with treatment and psychological and psychiatric disorders. The mechanisms accounting for the worsening of asthma at night are not completely understood but may be driven by circadian rhythms of circulating hormones such as epinephrine.connective tissue components. Tobacco smoking makes asthma more difficult to control. This may reflect the changes in airway structure in chronic asthma. and produces a more rapid decline in lung function and an increased risk of death.21 More prolonged worsening is usually due to viral infections of the upper respiratory tract (particularly rhinovirus and respiratory syncytial virus) or allergen exposure which increase inflammation in the lower airways (acute on chronic inflammation) that may persist for several days or weeks. chemokines. and more structural changes.g. such as collagens and proteoglycans that are involved in airway remodeling. Airway hyperresponsiveness is linked to both inflammation and repair of the airways and is partially reversible with therapy. This might reflect a reduction in endogenous antiinflammatory mechanisms. Its mechanisms are incompletely understood. An increase in airway inflammation at night has been reported. results in airway narrowing in a patient with asthma in response to a stimulus that would be innocuous in a normal person In turn. airway edema due to increased microvascular leakage. Several factors contribute to the development of airway narrowing in asthma. which may be sensitized by inflammatory stimuli may release inflammatory neuropeptides and cause reflex changes and symptoms such as cough and chest tightness.. histamine. cysteinyl leukotrienes. 26 Special Mechanisms Acute exacerbations Transient worsening of asthma may occur as a result of exposure to risk factors for asthma 7 . results in more frequent exacerbations and hospital admissions. 25 Airway hyperresponsiveness Airway hyperresponsiveness.20 and even certain weather conditions. 1 symptoms.thunderstorms.

6 Furthermore. PIV parainfluenza virus 8 . such as house-dust mite. such as certain infections (M. and -13) that can mediate allergic inflammation. or hepatitis A). either as overexpression of Th2 or underexpression of Th1. environmental stimuli such as infections will activate Th1 responses and bring the Th1/Th2 relationship to an appropriate balance. (Figure 1. Airway inflammation is characterized by a shift toward a Th2 cytokine-like disease. Host Factors and Environmental Exposures (adapted from NAEPR2)6 Key: LRI. tuberculosis. presence of older siblings and early enrolment in childcare). lower respiratory infections.g. This hypothesis is based on the assumption that the immune system of the newborn is skewed toward Th2 cytokine generation.. 6 There also appears to be a reciprocal interaction between the two subpopulations in which Th1 cytokines can inhibit Th2 generation and vice versa. 6 PATHOGENESIS A number of factors that influence a person’s risk of developing asthma have been identified. -9.4) Th1 cells produce interleukin (IL-2) and interferon-γ (IFN-γ). Alternaria. 6 Figure 1-3. in contrast. Under these conditions. (Figure 1. These can be divided into host factors (primarily genetic) and environmental factors. -5. Th2. -6.The current “hygiene hypothesis” of asthma illustrates how this cytokine imbalance may explain some of the dramatic increases in asthma prevalence in westernized countries.3) 6 Certain conditions appear to reduce the incidence of asthma. Alternatively. Allergic inflammation may be the result of an excessive expression of Th2 cytokines. the child who has a genetic cytokine imbalance toward Th2 will set the stage to promote the production of Ig-E antibodies to key environmental antigens. Following birth. generates a family of cytokines (IL-4. the absence of these lifestyle events is associated with the persistence of a Th2 cytokine pattern. The expression of asthma is a complex.27 Evidence points to an imbalance between Th1 and Th2 cytokine profiles predisposing an individual to development of allergy or asthma. cockroach. measles. interactive process that depends on the interplay between these two major factors that occur at a crucial time in the development of the immune system. recent studies have suggested the Innate Immunity Research has uncovered the role of innate and adaptive immune response in the development and regulation of inflammation. and possibly cat. exposure to other children (e. and less frequent use of antibiotics . which are critical in cellular defense mechanisms in response to infection. RSV respiratory syncytial virus.

The focus on actions of cytokines and chemokines to regulate and activate the inflammatory profile in asthma has provided ongoing and new insights into the pattern of airway injury that may lead to new therapeutic targets. including alterations in the number of type of infections early in life. many genes have been found that are either involved in or linked to the presence of asthma and some of its features. The role of genetics in Ig-E production. a gene-by-environment interaction occurs in which the susceptible host is exposed to environmental factors that are capable of generating Ig-E. The complexity of the genetic involvement in clinical asthma is related to certain phenotypic characteristics. but the genetics involved in the development of asthma remains a complex and incomplete picture. airway responsiveness and dysfunctional regulation of the generation of inflammatory cytokines has captured much Therefore.Figure 1-4. Precisely why the airways of some individuals are susceptible to these allergic events. has not been established. but not necessarily the pathophysiologic disease process or clinical picture itself. and repeated exposure to allergens. the widespread use of antibiotics. and sensitization occurs. Cytokine Balance Th1 Numerous factors.29 To date. may affect the balance between Th1 type and Th2 type cytokine responses and increase the likelihood that the immune response will be dominated by the Th 2 cells and thus will ultimately lead to the expression of allergic diseases such as asthma. however.28. 6 It is well recognized that asthma has an inheritable component to its expression. 9 . adoption of the western lifestyle. (Adapted from NAEPR2) Genetics possibility that the loss of normal immune balance arises from a cytokine dysregulation in which Th1 activity in asthma is diminished.

30 It is not clear how sex and sex hormones. 38.39 and occupational sensitizers are estimated to cause about 1 in 10 cases of asthma among adults of working age.36. However. their widespread application remains to be fully established.43 IgEmediated allergic reactions and cell mediated allergic reactions are involved. 41.Studies to evaluate house-dust mite and cockroach exposure have shown that the prevalence of sensitization and subsequent development of asthma are linked. but it is obviously important. Current studies are investigating the genetic polymorphism in the beta-adrenergic and corticosteroid receptors that may determine response to therapy.37 which is defined as asthma caused by exposure to an agent encountered in the work environment.1 10 .34 Exposure to cockroach allergen is an important cause of allergen sensitization. and complex plant and animal biological products that stimulate the production of Ig-E. However.. dog and cat exposure in early life may actually protect against the development of asthma.46 Very high exposures to inhaled irritants may cause “irritant induced asthma” (formerly called the reactive airways dysfunctional syndrome) even in nonatopic persons. 1 Environmental Factors The two major environmental factors that are most important in the development. Certain mediators such as leptins may affect airway function and increase the likelihood of asthma development. the prevalence of asthma is higher in boys. Sensitization and exposure to house-dust mite and Alternaria are important factors in the development of asthma in children. a risk factor for the development of asthma. the factors that cause some people but not others to develop occupational asthma in response to the same exposures are not well identified.33. 6 Sex Occupational sensitizers In early life. Over 300 substances have been associated with occupational asthma. The most important method of preventing occupational asthma is elimination or reduction of exposure to occupational sensitizers. irritants that may cause an alteration in airway responsiveness. allergic sensitization.40 Asthma is the most common occupational respiratory disorder in industrialized countries.31. or related hormone generation. Allergens The role of allergens in the development of asthma has yet to be fully defined or resolved. attention. The determinant of these diverse outcomes has not been established. Obesity Obesity has also been shown to be a risk factor for asthma. particularly dog and cat.42 Most occupational asthma is immunologically mediated and has a latency period of months to years after the onset of exposure.6 It is also apparent that allergen exposure. were associated with the development of asthma. the sex ratio shifts and asthma appears predominantly in women. are specifically linked to asthma but they may contribute to the onset and persistence of the disease. persistence and severity of asthma in the susceptible host are: airborne allergens and viral respiratory infections. allergen exposure can promote the persistence of airway inflammation and likelihood of an exacerbation. 6 Atopy and tobacco smoking may increase the risk of occupational sensitization. however. These substances include highly reactive small molecules such as isocyanates. Early studies showed that animal danders. At puberty. known immunogens such as platinum salts. but screening individuals for atopy is of limited value in preventing occupational asthma. Although the relevance of these genetic variations is of increasing interest.35 In addition. under some circumstances.44. and respiratory infections are not separate entities but function interactively in the eventual development of asthma. recent data suggest that.45 Levels above which sensitization frequently occurs have been proposed for many occupational sensitizers.32 Occupational asthma arises predominantly in adults.

and a reduced risk of asthma. although the association has not been as clearly established as with allergens and respiratory infections. In early life. air pollution. 6 Increasing rates of obesity have paralleled increasing rates in asthma prevalence. in relation to the development of asthma has been extensively studied. Increased n-6 polyunsaturated fatty acid (found in margarine and vegetable oil). later birth order. 61 Obesity may be a risk factor for asthma due to the generation of Tobacco Smoke Tobacco smoke.53. particularly breast-feeding. the data reveal that infants fed formulas of intact cow's milk or soy protein have a higher incidence of wheezing illnesses in early childhood compared with those fed breast milk..56 Similar associations have been observed in relation to indoor pollutants.. evidence also indicates that certain respiratory infections early in life—including measles and even RSV 49 or repeated viral infections (other than lower respiratory tract infections) 50.60 An association of low intake of antioxidants and omega-3 fatty acids has been noted in observational studies.Respiratory infections smoking has been associated with an increase in asthma severity and decreased responsiveness to inhaled corticosteroids (ICSs).51 can protect against the development of asthma. and viral infections may then influence the development of allergic sensitization. and decreased n-3 polyunsaturated fatty acid (found in oily fish) intakes have contributed to the recent increases in asthma and atopic disease.59 Some data also suggest that certain characteristics of Western diets. daycare attendance. On the other hand.27. The “hygiene hypothesis” of asthma suggests that exposure to infections early in life influences the development of a child’s immune system along a “non-allergic” pathway.g. smoke and fumes from gas and biomass fuels used for heating and cooling. but the interrelation is uncertain. a number of respiratory viruses have been associated with the inception or development of the asthma. such as increased use of processed foods and decreased antioxidant (in the form of fruits and vegetables). leading to a reduced risk of asthma and other allergic diseases. 52. In adults who have asthma.47. although the subsequent development of asthma has not been well defined. Children raised in a polluted environment have diminished lung function.57 but the relationship of this loss of function to the development of asthma is not known. e. risk for asthma development may be related to allergic sensitization. as such. 55 During infancy. respiratory syncytial virus (RSV) and parainfluenza virus in particular. but a direct link as a causative factor has not been established.50 The influence of viral respiratory infections on the development of asthma may depend on an interaction with atopy. One recent epidemiologic study showed that heavy exercise (three or more team sports) outdoors in communities with high concentration of ozone was associated with a higher risk of asthma among school-age children.54 In utero exposure to environmental tobacco smoke increases the likelihood for wheezing in the infant.48 A number of long-term prospective studies of children admitted to hospital with documented RSV have shown that approximately 40 percent of these infants will continue to wheeze or have asthma in later childhood. Diet The role of diet.58 The relationship between increased levels of pollution and increases in asthma exacerbations and emergency care visits has been well documented. The airway interactions that may occur when individuals are exposed simultaneously to both allergens and viruses are of interest but are not defined at present.6 Air Pollution The role of outdoor air pollution in causing asthma remains controversial.48 Symptomatic rhinovirus infections in early life also are emerging as risk factors for recurrent wheezing. The atopic state can influence the lower airway response to viral infections. and cockroach infestations. cigarette 11 . occupations. this association may explain observed associations between large family size. In general. Although the hygiene hypothesis continues to be investigated. cause bronchiolitis that parallels many features of childhood asthma. and diet have also been associated with an increased risk for the onset of asthma. molds.

org 2004. Global Initiative for Asthma. McAlary M. US Dept of Health. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Curr Opin Pulm Med 2005. Holgate ST. de MarcoR. De Togni A. Arossa W. Boushey HA. Clark TJ. 12: 315-35 Beasly R. 60(1):23-9. 344(5):350–62. 1998 Teeratakulpisarn J. Eur Respir J 1998.6 10. 1987-1994. Bugiani M. allergic rhinoconjunctivitis and atopic dermatitis Lancet 1998. Allergy 2004. Stewart AW et al. 85:762-8 National Asthma Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Pedersen SE. Worldwide variations in the prevalence of symptoms f asthma. Inflammatory events in severe acute asthma. 22:789–815 15. Tonnel AB. et al. 17. 59(5):469-78. weather and pollen in England. Poor control increases the economic cost of asthma.Diaz CG. Lancet 2006. The mechanisms. Asthma: mechanisms of disease persistence and progression. Corren J. 11(1):21-6. Kosalaraksa P. Stabilization of asthma prevalence among adolescents and increase among schoolchildren (ISAAC phases I and III) in Spain. J Allergy Clin Immunol 2001. Yan DC.ginasthma. our understanding of asthma pathogenesis and underlying mechanisms now includes the concept that gene-by-environmental interactions are critical factors in the development of airway inflammation and eventual alteration in the pulmonary physiology that is characteristic of clinical asthma. There is a need to establish local systematic monitoring protocols on asthma prevalence. Anderson HR. 5. Pauwels RA. Tan WC. Quiros AB. NIH Publication No. Lanier BQ. Fowler-Taylor A. and eczema in 13. The global burden of asthma: executive summary of the GINA Dissemination Committee report. 368(9537):708–710. Prevalence and severity of symptoms of asthma. Gosset P. Guillen-Grima F. 141 (2):189-98. 12 Bateman ED. 3. Urena IC. and management of severe asthma in adults. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Hardaker P. Asian Pac J Allergy Immunol 2004. allergic rhinoconjunctivitis and atopic dermatitis: ISAAC. Inhaled corticosteroids and asthma prevention. Review. Heng S. 18. 368(9537):780–93. rhinitis. Wiangnon S. 351:1225-32 National Asthma Prevalence Survey. 16. 11(3):694-701. N Engl J Med 2001. Gupta N. . Garcia-Marcos L. von Mutius E. Collier C. unique inflammatory mediators that lead to airway dysfunction. RECOMMENDATIONS: 12. A multicentre population-based study. morbidity and mortality. National Asthma Prevalence Survey. Available from http://www. 2007 update Masoli M. 21. 11. Martinez FD. 59(12):1301-7. Pirina P. Polosa R. GOAL Investigators Group. The economic impact of the cost of asthma care on the Filipino population should be determined. Tsai TL. Gerzeli S. 2. Acute asthma epidemics. Int Arch Allergy Immunol 2006. 7. 2002 (publication pending) Accordini S. ISAAC Steering Committee. Cohn L. Bethesda MD: NHLBI 1997. 108 (2):184–90. Busse WW. Am J Respir Crit Care Med 2004. Taiwan. Elias JA. 8. Lemanske RF Jr. Ou LS. Wu WF. Chupp GL. The Global Burden of Asthma Report. Lancet 2006. Asthma. 4. Allergy 2005. Archibald E. 6 In summary. 14. Tillie-Leblond I. 6. 20. 95(6):579-85. Allergy 2004. diagnosis. References 1. 170(8):836–44. van As A. Annu Rev Immunol 2004. Bousquet J. anti-IgE recombinant humanized monoclonal antibody. 19. Busse WW. Keil U. 97-4051A Busse W. American Thoracic Society. Northeastern Thailand using the ISAAC questionnaire: phase III.to 14year-old children in Taipei. Emberlin J. Education and Welfare. Beasley R. Huang JL. Strachan D.Olivieri M. Global Initiative for Asthma (GINA). Cioppa GD. Newson R. for the treatment of severe allergic asthma.9. Ann Allergy Asthma Immunol 2005. Worldwide variations in the prevalence of symptoms f asthma. Global Strategy for Asthma Management and prevention. Viruses in asthma exacerbations. asthma and pulmonary emphysema. Fabian D. Holt S. Hernandez GG. Surveying the prevalence of asthma. Eur Respir J 1998. 22(4):175-81. Beasley R. allergic rhinitis and eczema in school-children in Khon Kaen. Am Rev Resp Dis 1962. Pearce N. Carrozzi L. Asher MI. Dallari R. Omalizumab. 13. Marinoni A. 22. Definition and Classification of chronic bronchitis.

Taussig LM. Malo JL. 49.23. 41. Chan-Yeung M. Holgate ST. Definition and classification of asthma. Maestrelli P. 36. Sommerfeld C. The asthma epidemic. 48. T-lymphocyte responses to plicatic acid-human serum albumin conjugate in occupational asthma caused by western red cedar. 323(8):502–7. Bjarnason R. 123(3 Suppl):399S-405S. von Mutius E. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Sastre J. 44. and management of occupational asthma. Quirce S. Dawson C. Chaudhuri R. 42. J Allergy Clin Immunol 1999. 33(12):1622-8. Chan-Yeung M. 322(7283):390–5. In: Holgate ST. Lynn H. Lichtenstein LM. Chan-Yeung M. Shiell AW. Am J Respir Crit Care Med 2006. Chan-Yeung M. Halonen M. ed. Calhoun WJ. Etiology of occupational asthma. Sherrill D. Labrecque M. Evidence based guidelines for the prevention. Wenzel S. Morgan WJ. Parameters associated with persistent airflow obstruction in chronic severe asthma. Barnes PJ. Noertjojo K. N Engl J Med 1997. 37. Livingston E. Occup Environ Med 2005. 349(9063):1465-9. Burge PS. 24. Lancet 1997. Wahn U. Fabbri LM. Chan H. Fabbri LM. 355(21):2226–2235. 43. 47. 29. Gautrin D. 25. Heyes CB. Rosenstreich DL. Lancet 1999. and airway hyperresponsiveness. Bergmann R. Genetic and environmental interaction in allergy and asthma. Blanc PD. 1-4. Eur Respir J 1994. Adkinson NF Jr. Pediatrics 1985. Obesity and asthma. Bernstein IL. Fredberg JJ. Occupational allergy. identification. Toren K. eds. J Allergy Clin Immunol 2001. 30. Chest 2003. Asthma in the workplace. Pathogenesis of occupational asthma. 2nd Edition ed. Malo JL. 104(6):1139–46. 24(1):122-8. Eggleston PA. Baker D. Holgate ST. Measles . Caramori G. Nguyen L. BMJ 2001. Gergen P. Niggemann B. Social and familial factors in the development of early childhood asthma. 161(5):1501–7. A prospective study. Stein RT. 336(19):1356–63. ed. Chang JH. Curr Opin Pulm Med 2004. 46. N Engl J Med 1990. Review. Venables KM. 28. McNiff-Mortimer K. 7(2):346-71. Eggleston P. London: Mosby International. Gern JE. Nicholson PJ. Eder W. eds. 1999:p. How much adult asthma can be attributed to occupational factors? Am J Med 1999. Boyle C. McSharry CP. Sutherland ER. Fraser I. Taylor AJ. Allergy. Maestrelli P. Vandenplas O. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Malo JL. 32. 50. Ober C. Wright AL. Bumbacea D. In: Roth RA. Aetiological agents in occupational asthma. 45.116(2):274–8. Cullinan P. Lemiere C. 31. 10(1):57-61. Clin Exp Allergy 2003. New York: Marcel Dekker. Ege MJ. 22(2):364-73. Malo JL. Martinez FD. Busse WW. Keown P. Bernstein DI. 34. Eur Respir J 2003. N Engl J Med 2006. 51. Holberg CJ. Mitchell H. 75(5):859–68. Obesity. et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years.2(2):132–8. Kattan M. Mechanisms of severe asthma. Eur Respir J 2004. Church MK. New York: Marcel Dekker. Beuther DA. Horwood LJ. Relationship of viral infections to wheezing illnesses and asthma. Asthma in the workplace. Spears M. 38. In: Bernstein IL. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. Ownby D. 39. Perspectives on the past decade of asthma genetics. smooth muscle. Frew A. Review. Sigurs N. Sigurbergsson F. McMahon AD. J Allergy Clin Immunol 1998. 35. Lafferty J. Platts-Mills TA. Shore SA. Bernstein DI. 115(5):925-7. J Allergy Clin Immunol 2005 . Aaby P. MAS Group. Review. Thomson NC. Am J Respir Crit Care Med 2000. 107(6):580-7. Robinson D. Park HS. et al. Bernstein IL. 354(9178):541– 5. 62(5):290-9. 2nd edition. 174(2):112-9. 13 Cambridge: Pergamon Press. 33. Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. 1993. 1997:p. Illi S. Kjellman B. Nat Rev Immunol 2002 . 101(6 Pt 1):841-7. Weiss ST. Hall AJ. 26. Comprehensive toxicology: toxicology of the respiratory system. 174(2):127-33. Fergusson DM. Van Natta ML. Barker DJ. Goudiaby A. von Mutius E. Occupational asthma. 40. Shannon FT. Cogswell JJ. Sporik R. Occupational asthma. Malo JL. Shaheen SO. Nocturnal asthma. 27. J Allergy Clin Immunol 2005. et al. Slavin RG. Hamilton RG. Lau S. 107(1):48–54. Huss K. Campbell D. 42535. Am J Respir Crit Care Med 2006 Jul 15. Carr D. House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program.

The role of breastfeeding in the development of allergies and asthma. 115(6):1109-17. Am J Respir Crit Care Med 1999. Lemiere C. What constitutes an adverse health effect of air pollution? Official statement of the American Thoracic Society. Chest 2001. Meyer IH. 351(11):1057-67. Occupational asthma. 53(2):117–23. Gauderman WJ. 55. Devereux G. Gilliland F. Vora H. Margolis HG. N Engl J Med 2004. Gilliland F. London SJ. 359 (9304):386– 91. 161(2 Pt 1):665-73. Strachan DP. Cook DG. 115(6):1238-48. et al. Gauderman WJ. Parental smoking and allergic sensitisation in children. Stocks J. Avol E. J Allergy Clin Immunol 2005. Thorax 1998a. Gautrin D. Curr Opin Pulm Med 2004. 54. Peters JM. Parental smoking and childhood asthma: longitudinal and casecontrol studies. Fagan JK. Seaton A. Thomas D. Berhane K. Dezateux C. Sternfels P. Ford JG. Cook DG. Health effects of passive smoking. American Thoracic Society. 54(4):366. Islam T. Friedman NJ. 14 years of age. 120(4):1129–35. 57. Am J Respir Crit Care Med 2000. Labrecque M. 53(3):204–12. Lancet 2002. Review. Richardson L. Avol E. 61. McConnell R. Malo JL. Health effects of passive smoking. Erratum in: Thorax 1999. Zeiger RS. Fletcher ME. 59. McLean DE. Lancet 1996. 53.52. 6. . Impaired airway function and wheezing in infancy: the influence of maternal smoking and a genetic predisposition to asthma. and atopy in Guinea-Bissau. Asthma in exercising children exposed to ozone: a cohort study. 56. Findley SE. Patterns and predictors of asthma-related emergency department use in Harlem. Thorax 998b. Review. Dundas I. 159(2):403–10. Strachan DP. 5. J Allergy Clin Immunol 2005. 10(1):57–61. Berhane K. 347(9018):1792–6. The effect of air pollution on lung development from 10 to 18 58. 60. Diet as a risk factor for atopy and asthma.

Chapter 2 Diagnosis and Classification .

16 . Examples include Alternaria. Measurements of lung function (spirometry or peak expiratory flow) provide an assessment of the severity of airflow limitation.INTRODUCTION KEY POINTS: A clinical diagnosis of asthma is often prompted by symptoms such as episodic breat hlessness. and chest tightness. wheezing. seas onal v ariability of symptoms and a positive family history of asthma and atopic disease are also helpful diagnostic guides. Clinical control of asthma is defined as: o No (twic e or less/week) daytime symptoms o No nocturnal symptoms or awakenings because of asthma o No (twice or less/week) need for reliever treatment o Normal or near-normal lung function o No exacerbations In some sensitized individuals. To aid in clinical management. precipitation by non-specific irritants. asthma may be exacerbated by seasonal inc reas es in specific aeroallergens 2. or. with the patient being entirely asymptomatic bet ween s easons or it may involve seasonal worsening of asthma symptoms or a background of persistent asthma. COPD. one that is based on the intensity of treatment required to achieve good asthma control i. where misdiagnoses include various forms of bronchitis or croup. This is prompt ed by the recognition of patients with “severe” and “mild” asthma. A correct diagnosis of asthma is essential if appropriat e drug t herapy is to be given 1. but normal lung function. A clinical diagnosis of asthma is often prompt ed by symptoms such as episodic breathlessness. There remains a need to define the concept of asthma severity. and birch. such as smoke. or the breathlessness of old age). The patterns of these symptoms that strongly suggest an asthma diagnosis are variability. and responding to appropriat e asthma therapy. Episodic symptoms after an incidental allergen exposure. CLINICAL DIAGNOSIS Medical History For patients with symptoms consistent with asthma. This is particularly true among children.e. grass. Symptoms 1. and chest tightness 1. severity is assessed during treatment. Useful questions to consider when establishing a diagnosis of asthma are described in Figure 2-1. its reversibility. and its variability. and provide confirmation of the diagnosis of asthma. Measurements of allergic status can help t o identify risk factors that cause asthma symptoms in individual patients. wheezing. measurement of airway responsiveness may help establish the diagnosis. or exercise. and ragweed pollens. Asthma associated with rhinitis may occur intermittently. Asthma symptoms may be intermittent and their significance may be overlooked by patients and physicians. cough. they may result in misdiagnosis (for example of wheezy bronchitis. fumes. cough. strong smells. and lead to inappropriate treatment 1. a classification of asthma by level of control is recommended. worsening at night. because they are non-specific.

in some people with asthma. cold air and less common in hot. patients in this state usually have other physical signs reflecting the exacerbation and its severity.potent triggers 7. postnasal drip. such as cyanosis. use of accessory muscles. humid climates 8. and is often more problematic at night. in severe asthma exacerbations. and possibly a search for sputum eosinophils. and mucus hypersec retion). and intercostal retraction. wheezing may be absent owing to s everely reduced airflow and ventilation. symptom. is particularly important 4. Physical Examination Because asthma symptoms are variable. However. Cough-variant asthma must be distinguished from so-called eosinophilic bronchitis in which patients have cough and sputum eosinophils but normal indices of lung function when assessed by spirometry and airway hyperresponsiveness 5. However. which resolve spontaneously within 30-45 minutes. hyperinflated chest. evaluations during the day can be normal. edema. Exercise-induced bronchoconstriction may occur in any climatic condition. The combination of hyperinflation and airflow limit ation in an asthma exacerbation markedly increases the work of breathing. or sometimes a troublesome cough. Figure 2-1. the physical examination of the respiratory system may be normal. Exercise-induced bronchoconstriction typically develops wit hin 510 minutes after completing exercise (it rarely occurs during exercise). but it is more common when the patient is breathing dry. and for some it is the only cause. It is particularly common in children. Physical activity is an important caus e of asthma symptoms for most asthma patients. Patients with coughvariant asthma 3 have chronic cough as their principal. tachycardia. Some forms of exercise. are more Tests for Diagnosis and Monitoring Measurements of lung function. Other diagnoses to be considered are cough-induced by angiotensin-converting-enzyme (ACE) inhibitors. if not only. drowsiness. and vocal cord dysfunction 6. Features of hyperinflation result from patients breathing at a higher lung volume in order to increase outward traction of the airways and maintain the patency of smaller airways (which are narrowed by a c ombination of airway smooth muscle contraction. difficulty speaking. Cough-variant asthm a. The most usual abnormal physical finding is wheezing on auscultation. Patients experience typical asthma symptoms. wheezing may be absent or only detected when the person exhales forcibly. chronic sinusitis. gastroesophageal reflux. For these patients. Exerci se-induced bronchoconstriction. documentation of variability in lung function or of airway hy perresponsiveness. Questions to consider in the diagnosis of Asthma Rapid improv ement of post-exertional symptoms after inhaled β 2-agonist use. Occasionally. such as running. or their prevention by pre-t reatment with an inhaled β 2-agonist before exercise. Other clinical signs are only likely to be present if patients are ex amined during symptomatic periods. supports a diagnosis of asthma. a finding that confirms the presence of airflow limitation. even in the presence of significant airflow limitation. The diagnosis of asthma is usually based on the 17 .

Spirometry is the recommended method of measuring airflow limitation and reversibility to establish a diagnosis of asthma. sex. Variability may be experienc ed over the course of one day (when it is called diurnal variability). Repeated testing at different visits is advised. However. FVC. Assessment of symptoms such as dyspnea and wheezing by physicians may also be inaccurate. This is because patients with asthma frequently have poor recognition of their symptoms and poor perception of symptom severity. its reversibility and its variability. In addition. greatly enhance diagnostic confidenc e. particularly the measurement of forced expiratory volume in 1 second (FEV 1) and forced vital capacity (FVC). they are useful for judging whether a given value is abnormal or not. (1) spiromet ry. measured within minut es after inhalation of a rapid-acting bronchodilator—for example after 200-400 g salbutamol13—or more sustained improv ement ov er days or weeks after the introduction of effective controller treatment such as inhaled glucoc orticosteroids 13. Because many lung diseas es may result in reduced FEV 1. Spirometry is reproducible. The degree of reversibility in FEV 1 which indicat es a diagnosis of asthma is generally accepted as ≥ 12% and ≥ 200 ml f rom the pre-bronchodilator value13. Predictive equations and values for Filipinos have been det ermined and published61 but have not yet been widely used. a useful assessment of airflow limitation is the ratio of FEV 1 to FV C. and provides confirmation of the diagnosis of asthma. and the highest value of three recordings taken. Obtaining a history of variability is an essential component of the diagnosis of asthma. The FEV1/FVC ratio is normally > 0. These are being continually revised. Therefore. The terms reversibility and variability refer to changes in symptoms accompanied by changes in airflow limitation that occur spontaneously or in response to treatment. proper instructions on how to perf orm the forced expiratory maneuver must be given to patients. presence of characteristic symptoms. from month to month. Measurements of FEV 1 and FV C are undertaken during a forced expiratory maneuver using a spirometer. Predicted values of FEV 1. and (2) peak expiratory flow (PEF) measurement. Recommendations for t he standardization of spiromet ry have been published13-15. especially if their asthma is longstanding 10. variability forms part of the assessment of asthma cont rol. and the test theref ore lacks sensitivity. measurements of lung function. particularly those on treatment.80. t hese measures provide complement ary information about different aspects of asthma control. appropriat e predictive equations for FEV 1 and FVC should be established for each patient. Two methods hav e gained widespread acceptance for use in diagnosis of patients. 18 . from day to day. or seasonally. Although measurements of lung function do not correlate strongly with symptoms or other measures of disease control 11. and particularly the demonstration of reversibility of lung f unction abnormalities. Meas urement of lung function provides an assessment of the severity of airflow limitation. The term reversibility is generally applied to rapid improv ements in FEV 1 (or PEF). The normal range of values is wider and predicted values are less reliable in young people (< age 20) and in the elderly (> age 70). and PEF based on age. and any value less than this suggests airflow limitation. and height have been obtained from population studies.Variability refers to improvement or deterioration in symptoms and lung function occurring over time. but effort-dependent. As ethnic differences in spiromet ric values have been demonstrated. Howev er most asthma patients will not exhibit rev ersibility at each assessment. and wit h the exception of PEF for which the range of predicted values is too wide.

Another method of describing PEF variability is the minimum morning pre-bronchodilat or PEF over 1 week. or during exercise or other activities that may cause symptoms. and involves a simple calculation. or diurnal variation in PEF of more than 20% (with twice daily readings. Because values for PEF obtained with different peak flow meters vary and the range of predicted values is too wide. poorly controlle d asthma. PEF can underestimate the degree of airflow limitation. Wi th trea tment. as seen by the increase in Min% Max (lowest mo rning PEF/High est PEF % ) over one week . particularly in patients with poor perception of symptoms 10. Figure 2-2. However. particularly as airflow limitation and gas trapping worsen. Although spiromet ry is the preferred method of documenting airflow limitation. PEF levels increased. port able. This latter met hod has been suggested to be the best PEF index of airway lability for clinical practice because it requires only a once-daily reading. 19 . more than 10% 21 ) suggests a diagnosis of asthma. PEF monitoring is valuable in a subset of asthmatic patients and can be helpful: To confirm t he diagnosis of asthma. Modern PEF meters are relatively inexpensive. when values are often close to their lowest and last thing at night when values are usually higher. plastic. correlates better than any other index with airway hyper responsiveness . Careful instruction is required to reliably measure PEF because PEF measurements are effort-dependent. Most commonly. It is easier to discern the response to therapy from a PEF chart than from a PEF diary. be fore and a fter the star t of inhal ed glucocorticoster oid tr eatme nt. expressed as a percentage of the mean daily PEF value. The previous best measurement is usually obt ained when the patient is asymptomatic or on full treatment and s erves as a reference value for monitoring the effects of changes in treatment. expressed as a percent of the recent best (Min% Max) (Figure 2-2) 19. Asthma management plans which include selfmonitoring of symptoms or PEF for treatment of exacerbations have been shown to improve asthma outcomes 22. To identify environmental (including occupational) causes of asthma symptoms. and ideal for patients to use in home settings for day-to-day objective measurement of airflow limitation. measurements of PEF are not interchangeable with other measurements of lung function such as FEV 1 16. provided the same c hart format is consistently used23. PEF measurements should pref erably be compared to the patient’s own previous best 18 measurements using his/her own peak flow meter. PEF is measured first thing in the morning before treatment is taken. Measuring PEF Variability* *PEF chart of a 2 7-year old man wi th long -standi ng.Peak expiratory flow measurements are made using a peak flow meter and can be an important aid in both diagnosis and monitoring of asthma. This involves the patient monitoring PEF daily or several times eac h day over periods of suspected exposure to risk factors in the home or workplace. a 60 L/min (or 20% or more of prebronc hodilator PEF) improvement after inhalation of a bronchodilator20. a nd PEF varia bility d ecreased. To improve control of asthma. and averaged over 1-2 weeks 19. and during periods of non-exposure. One method of describing diurnal PEF variability is as the amplitude (the difference bet ween t he maximum and t he minimum value f or the day).

bronchiectasis. There have been attempts in the local s etting to explore the use of low-technology maneuvers like the candle light and light ed matchstick blowing tests. and chronic obstructive pulmonary disease (COP D) 29. and severe airway hyperresponsiveness. requires considerable expertise and can result in life-threatening bronchospasm 35. but is not routinely recommended.hyperresponsiveness has been described in patients with allergic rhinitis 27 and in those with airflow limitation caused by conditions other than asthma. increases the probability of a diagnosis of asthma in patients with respiratory symptoms. an d in asthmatics with mil d. measurements of airway responsiveness to methacholine. Asthmatics have an increased sensitivity and an incre ased maximal bro ncho. Their main limitation is that a Figure 2-3. Moreover. Deliberate provocation of the airways with a suspected allergen or sensitizing agent may be helpf ul in the occupational setting. but offer potential use in a res ourc e-poor country like the Philippines. Other tests for Airway Obstruction. Measurements of allergic status. Levels of FeNO are elevated in people with asthma (who are not taking inhaled glucocorticosteroids) compared to people wit hout asthma.constric tor resp onse to the a gonist. much less validated. levels of exhaled nitric oxide (FeNO) 31 and carbon monoxide (FeCO)32 have been suggested as non-invasive mark ers of airway inflammation in asthma. and allergic rhinitis in particular. such as cystic fibrosis 28. but have limited specificity 25. Because of the strong association between asthma and allergic rhinitis. modera te . This means that a negative test can be useful to exclude a diagnosis of persistent asthma in a patient who is not taking inhaled glucocorticosteroid treatment. mannitol. Measuring Airway Responsiveness *Airway responsiveness to inhaled me thacoline or histamine in a norma l subject. but a positive test does not always mean that a patient has asthma26. In addition. or exercise challenge may help establish a diagnosis of asthma24.34. sometimes called “triggers. 24 Non-invasive markers of airway inflammation. allergic diseases. but these measurements are being evaluated for potential use in determining optimal treatment 33. Skin tests and measurement of serum IgE are met hods used t o determine allergic status. because it is rarely useful in establishing a diagnosis. histamine. yet these findings are Measurement of airway responsiveness. For patients with symptoms consistent wit h asthma. This is because airway not specific for asthma. These have not been rigorously evaluated. The evaluation of airway inflammation associated with asthma may be undertaken by ex amining spontaneously produced or hypert onic saline-induced sputum for eosinophilic or neut rophilic inflammation 30. the presence of allergies. Measurements of airway responsiveness reflect the “sensitivity” of the airways to factors that can cause asthma symptoms. but normal lung function.” and the test results are usually expressed as the provocative concentration (or dose) of the agonist causing a given fall (often 20%) in FEV 1 (Figure 2-3). The r esponse to the ag onist is usua lly expressed as the provocative concen tra tion causing a 2 0% decline in FEV 1 ( PC 20) 20 . the presence of allergies in asthma patients (identified by skin testing or measurement of specific IgE in serum) can help to identify risk factors that cause asthma symptoms in individual patients. These tests are sensitive for a diagnosis of asthma. Neither sputum eosinophilia nor FeNO has been evaluated prospectively as an aid in asthma diagnosis.

cough. Use of beta -blockers.g. breathlessness. Careful assessment and treatment of both the asthma and the comorbidity is often necessary to establish the contribution of each to a patient’s symptoms. DIAGNOSTIC CHALLENGES DIFFERENTIAL DIAGNOSIS AND A careful history and physical examination. A relationship between symptoms and the workplace (improvement in symptoms away from work and worsening of symptoms on returning to work) can be helpful in establishing a link between suspected sensitizing agents and asthma45. The presence of increased symptoms with exercise and at night may add to the diagnostic confusion because t hese symptoms are consistent wit h either asthma or left ventricular failure.. This is particularly true when asthma is associated with hyperventilation. vocal cord dysfunction. The Elderly Undiagnosed asthma is a frequent cause of treatable respiratory symptoms in t he elderly. Sinc e the management of occupational asthma frequently requires the patient to change his or her job. The development of new symptoms of rhinitis. left ventricular failure) Asthma treatment and assessment and attainment of control in the elderly are complicated by several factors: poor perception of symptoms. diffuse parenchymal lung disease) • Non-respiratory causes of symptoms (e. The diagnosis requires a defined history of occupational expos ure to known or suspected sensitizing agents. particularly COPD • Non-obstructive forms of lung disease (e. or a definit e worsening of asthma after employment. acceptance of dyspnea as being “normal” in old age. The following categories of alternative diagnoses need to be considered: • Hyperventilation syndrome and panic attacks • Upper airway obstruction and inhaled foreign bodies 43 • Vocal cord dysfunction 44 Other forms of obstructive lung disease. Wheezing. and reduced expectations of mobility and activity. together with the demonstration of reversible and variable airflow obstruction (preferably by spiromet ry). an absence of asthma symptoms before beginning employment. and the frequent presenc e of co-morbid diseases complicates the diagnosis. positive test does not necessarily mean that the disease is allergic in nat ure or t hat it is causing asthma. the use of whic h is 21 . and/or wheeze particularly in non-smokers should raise suspicion. as some individuals have specific IgE antibodies without any symptoms and it may not be causally involved. or COPD. distinguishing asthma from COPD is particularly difficult. usually clarifies the picture.. A careful history and physical examination.” a misleading term. Detection of asthma of occupational origin requires a systematic inquiry about work history and exposures. the diagnosis carries considerable socioec onomic implications and it is important to confirm the Because asthma is a common disease. Because of its insidious onset occupational asthma is often misdiagnosed as chronic bronchitis or COPD and is therefore either not treated at all or treated inappropriat ely. it can be found in association with any of the above diagnoses. and may require a trial of treatment with bronchodilators and/or oral/inhaled glucocorticosteroids. Occupational Asthma Asthma acquired in the workplace is a diagnosis that is frequently missed. which complicates the diagnosis as well as the assessment of severity and control.discouraged. combined with an E CG and chest X-ray.g. will in most instances confirm the diagnosis. and cough caused by left ventricular failure is sometimes labelled “cardiac asthma. even topically (for glaucoma) is common in this age group. In the elderly.

Etiology Asthma Severity While asthma control is important. even though asthma can us ually be distinguished f rom COPD. in some individuals who develop chronic respiratory symptoms and fixed airflow limitation. or continue to deteriorate. Its assessment should inc orporate the dual components of current clinical control (e. occupational asthma) should be part of the initial assessment to enable the use of avoidance strategies in asthma management. 22 . ASTHMA SEVERITY and CONTROL: A NEW PERSPECTIVE Recently. since single specific causative agents are seldom identified. Describing patients as having allergic asthma is usually of little benefit. symptoms. and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Clinical experience indicates that patients have Many attempts have been made to classify asthma according to etiology.54 available . quantification of severity of asthma needs to be maintained. i. it may be difficult to differentiate t he t wo diseases. CLASSIFICATION OF ASTHMA Asthma Severity: The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control. reliever use and lung f unction) and future risk (e. Reviews have highlighted the importance of different asthma phenotypes. although there are few cent ers with the necessary facilities for specific inhalation testing. A symptom-based questionnaire for differentiating COPD and asthma for use by primary health care professionals is 53. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Individuals with asthma who are exposed to noxious agents (particularly cigarette smoking) may develop fixed airflow limitation and a mixture of “asthma-like” inflammation and “COPD-like” inflammation. Asthma Control: Refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Figure 2-4 shows the current perspective on the relationships between phenotype. exacerbations and lung functions decline). diagnosis objectively.e.However. This may be achieved by specific bronchial provocation testing46. Despite this. Another method is to monitor PEF at least 4 times a day for a period of 2 weeks when the patient is working and f or a similar period away from work 47-50. particularly with regard to environmental sensitizing agents. such a classification is limited by the existence of patients in whom no environmental cause can be identified. an effort to identify an environmental cause for asthma (for example.g. even in t he absence of continued exposure to the offending agent 51. These phenotypes may alter the intensity of the treatment required (severity) and.g. 60 Distinguishing Asthma from COPD Both asthma and COPD are major chronic obstructive airways diseases that involve underlying airway inflammation. emphasizes the need for an early diagnosis so that appropriat e strict avoidance of furthe r exposure and pharmacologic intervention may be applied. their natural history and varying treatment responses. in t urn. The increasing recognition that occupational asthma can persist. is usually progressive. there has been increasing awareness of heterogeneity of the underlying processes in asthma. COPD is characterized by airflow limitation that is not fully reversible. Thus. severity and control. contribut e to the patient’s level of asthma control. Evidence based guidelines contain further information about the identification of occupational asthma 52.

While initial aggressive treatment based on lev el of control may be adequate to get them to a higher lev el or even total control. in terms of the intensity of required treatment to treat the patient’s asthma and to achieve good control. there is clinical need in describing patients not only in relation to their level of asthma control but also their asthma severity.a tendency to seek consult mostly during times of increasing symptoms when treatment regimens are not adhered to and control of triggers are at their lowest. 23 . there are varying levels of s everity based on the medications required to maintain control. Severity may not only dictate the choice of initial treatment but also maintenance therapy based on clinical respons e. Quantification of severity is still important because in clinical practice there exists a wide spectrum of patients whose asthma ranges from mild to severe. including the problems of low ICS us e and overreliance on reliever bronchodilator medications. some patients may actually require less drugs to achieve the same clinical outcome. Moreover. in a population of stable asthmatics. Thus. We recommend using the PCRDMA severity classification (Table 2-1) because it addresses local concerns and realities.

Exacerbations are events that are more common in poorly controlled asthma but may occur at any level of clinical asthma control. the environment (genetic and external) and the response to treatment.g. rapid decline of lung function. Treatment choice may be governed by the underlying phenotype. Relationship between Asthma Phenotypes. 24 . Severity is described by the intensity of the treatment required to ac hieve good control. reliever use and simple “bedside” measures of lung function) and future risks of adverse outcomes (e. Severe asthma includes situations in which good control is still not achieved despite maximal therapy. The level of asthma control results from the interaction of the underlying phenotype. Pathological and physiological markers provide information about the underlying phenotype and the level of residual disease activity on treat ment and may serve as surrogate markers for future risk. The assessment of asthma control has two components: current clinical control (including symptoms. Severity and Control. exacerbations.Figure 2-4. and the intensity of the treatment is usually modified by the clinician as the patient responds to treatment. and side-effects).

but to laboratory markers of inflammation and pathophysiologic features of the disease as well. However.are generally unavailable and costly. it is recommended that treatment be aimed at controlling the clinical features of disease. it refers to control of the manifestations of disease. However. adapted from GINA 2008 *Any exacerbati on sho uld pro mp t r eview o f main ten ance trea tmen t to ensure that i t is adeq uate. There is evidence that reducing inflammation 25 . **Patients who are high risk for as th ma-rel ate d d eaths are ini tially classified here Table 2-2. or even cure. the term cont rol may indicate disease prevention. in asthma. Chronic Asthma Severity While on Treatment *Objective measur es take pr ecedence over subj ective co mpla ints . including lung function abnormalities. where neither of these are realistic options at present. Asthma Control with controller therapy achieves clinical control. This is a working scheme based on c urrent opinion and has not been validated. Table 2-2 provides the characteristics of controlled. because tests such as endobronchial biopsy and meas urement of sputum eosinophils and exhaled nitric oxide 30-34. In general. I deally this should apply not only to clinic al manifestations. Asthma control may be defined in a variety of ways.   By defini tion . an exacerbation in any week makes th at an uncon trolle d as th ma we ek. partly controlled and uncontrolled asthma. ++ Lun g functi on is no t a re liable test for childre n 5 years and younger .Table 2-1. Levels of Asthma Control. The hig her severi ty level o f any do ma in will be t he basis o f the fi nal severity l evel.

1(8651):1346-8. Am J Respir Crit Care Med 2000.57(2):178-82. O'Byrne PM. Med J Aust 2002. Gold PM. Randolph C. Niimi A. Kerstjens HA.induced bronchoconstriction. instruments such as ACT. St Amand TA. Clin Exp Allergy 1998. 5. Levy ML. should be translated in the vernacular and validated. Teoh PC. Fujimura M. and the cost of treatment required to achiev e this goal. ataqinstrument. or during consultations with t heir health care provider. htm)57. Gibson PG. Fletcher M. 26 . Prim Care Respir J 2006. Anderson SD. Symptom perception during acute bronchoconstriction. Irwin RS. Cloutier MM. de Jong PM. even in the primary care setting. Koeter GH. References Validated meas ures for assessing clinical control of asthma score goals are continuous variables and provide numeric al values to distinguish different levels of control. Ann Acad Med Singapore 1985. Brand PL. Chronic cough: eosinophilic bronchitis without asthma. In the local setting. Managing cough as a defense mechanism and as a symptom.Recognizing their potential to improve assessment of asthma control. and the Asthma Control Scoring System 59. 6. 10. Exercise-induced asthma: update on pathophysiology. providing a reproducible objective measure that may be charted over time (week by week or month by month) and representing an improv ement in communication bet ween patient and healt h care professional. Corrao WM. Killian KJ. Their value in clinical use as distinct from research s ettings has yet to be demonstrated but will become evident in coming years. Tan CH. 9. on the internet.114(2 Suppl Managing):133S-81S. Halbert RJ.14(3):465-9. Complete control of asthma is commonly achieved with treatment. Chronic cough as the sole presenting manifestation of bronchial asthma. all efforts should be made to confirm the diagnosis through spiromet ry. The role of climatic conditions and histamine release in exercise. Eosinophilic bronchitis: clinical manifestations and implications for treatment. and treatment.uk/Asthma1. 3. Hoffstein V. Bousquet J. the Asthma Therapy Assessment Questionnaire (ATAQ) (http://www. Yawn BP. Dolovich J.com)56.co. previously published predicted values for Filipinos should be used. 8.28 Suppl 5:104-9. Price DB. suitable for self-assessments by patients. Lancet 1989. Examples of validated instruments are the Asthma Control Test (A CT) (http://www. N Engl J Med 1979. Yssel H.27(2):53-77.162(2 Pt 1):490-6. 7. They hav e the potenti al to improve the assessment of asthma control. Tan WC. Irwin RS. Chest 1998. Hargreave FE. Pene J. Denburg J. The role of IgE in asthma. are available in many languages. the Asthma Control Questionnaire (ACQ) (http://www. potential for adverse effects. Influence of treatment on RECOMMENDATIONS: In patients suspected of having bronchial asthma. Braman SS. Watson R.300(12):633-7.asthmacontroltest. A consensus panel report of the American College of Chest Physicians. clinical diagnosis.qoltech.15(1):20-34.com)58. and in paper form and may be completed by patients prior to. Ramsdale EH. They are being promoted for use not only in research but for patient care as well. 4. Thorax 2002. 1. 2. International Primary Care Respiratory Group (IPCRG) Guidelines: diagnosis of respiratory diseases in primary care.177 Suppl:S61-3. 11. Postma DS. Fuller R. Abbal C. Otis J. Curr Probl Pediatr 1997. et al. Not all of these instruments include a measure of lung function. Boulet LP. Some. the aim of which should be to achieve and maint ain control for prolonged periods 55 with due regard to the safety of treatment. Hausen T. Exercise-induced asthma in children: a marker of airway inflammation. Gibson PG.

Morris MM. Bronchial responsiveness to methacholine in chronic bronchitis: relationship to airflow obstruction and cold air responsiveness. Thorax 1984.28(12):1565-70. Thorax 1994. Herbison GP. Eur Respir J 1997. Spontaneous and induced sputum to measure indices of airway inflammation in asthma. Festen J. Bradding P. Reddel HK. 30. Clin Rev Allergy Immunol 2003.47(3):162-6. Official statement of the European Respiratory Society. Exhaled and nasal nitric oxide measurements: recommendations. Brightling CE. Can peak expiratory flow predict airflow obstruction in children with asthma? Pediatrics 2000. McKenna S. Barnes PJ. 19. Brassett KP. Thorax 1999. Dekker FW.16:1-100. Howell L. Use of exhaled nitric oxide peak expiratory flow and its relation to airway hyperresponsiveness and symptoms. Smith AD. 25. Duiverman EJ. Burgos F.59(2):94-9. Schrier AC. Cowan JO. Roberts RS. Groot CA. Written action plans for asthma: an evidence-based review of the key components. Hargadon B. The European Respiratory Society Task Force. Postma DS. 13. Ramsdale EH. Am J Respir Crit Care Med 1995.12.10(7):1683-93. J Allergy Clin Immunol 1992. 17. Sensitivity and specificity of histamine PC20 determination in a random selection of young college students. Pizzichini E. Asymptomatic airway hyperresponsiveness: a curiosity or an opportunity to prevent asthma? Am J Respir Crit Care Med 2003. Gore BP. Brusasco V.24(1):19-26. Interpretative strategies for lung function tests. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Miles J. Vincent SD. Crapo RO. Fitzharris P. Parker D. 23. Horvath I.360(9347):1715-21. and hyperresponsiveness during long-term treatment with inhaled corticosteroids. Ramsdale EH. et al. Roberts RS. 15. Hargreave FE. Peak flow variation in childhood asthma: correlation with symptoms.105(2):354-8.54(2):103-7. Kharitonov S. Peat JK. 33.59(11):922-4. van Haren EH. Clin Exp Allergy 1999. 32. Salome CM. Eid N. Murdock KY. 29. Hussack P. 1994 Update. Standardized lung function testing. Bronchoprovocation methods: direct challenges. Berscheid BA. et al. The Dutch CNSLD Study Group. Eur Respir J Suppl 1993. Taylor DR. Viegi G. Which index of peak expiratory flow is most useful in the management of stable asthma? Am J Respir Crit Care Med 1995. Powell H. Pearce N. Lancet 2002.89(3):20914.75(5):573-7. 26. The effects of the inhaled corticosteroid budesonide on lung function and bronchial hyperresponsiveness in adult patients with cystic fibrosis. 28. Eddy M. Hargreave FE. Dijkman JH. The need for standardisation of peak flow charts.154(4 Pt 1):866-9. Validity of peak expiratory flow measurement in assessing reversibility of airflow obstruction. American Thoracic Society.60(2):164-7.151(5):1320-5. Cockcroft DW. Jenkins CR. Woolcock AJ. 34. Thorax 1992. Waalkens HJ. Evans S. 21. 20.167(3):371-8. Eur Respir J 2005. gender and smoking habits in a random population sample aged 20-70 yrs. airways obstruction. Asymptomatic bronchial hyperresponsiveness in rhinitis. Lammers JW. Civitico J.89(1 Pt 1):23-30. Gibson PG. Popov TA. Green RH. Standardization of Spirometry. Boulet LP.49(11):1109-15. Am J Respir Crit Care Med 1996. Eur Respir J 1994. van Herwaarden CL. Boezen HM. Alving K. J Allergy Clin Immunol 1985. Thorax 2004.39(12):9128. Lewis S. Beasley R. et al. 27 .26(5):948-68. Respir Med 1995. Classification of asthma severity: should the international guidelines be changed? Clin Exp Allergy 1998. 18. Kerrebijn KF. When can personal best peak flow be determined for asthma action plans? Thorax 2004. Sheikh S. Sawyer G. Marks GB. Schouten JP. Reddel HK. Exhaled monoxides in asymptomatic atopic subjects. Dutch CNSLD Study Group. Pellegrino R. 24. Cockcroft DW. Casaburi R. Reddel HK. 14. Brand PL.152(3):1107-36. Sterk PJ. 31. Barnes PJ. Efthimiadis A. van Essen-Zandvliet EE. Yandell B.7(10):1814-20.29(9):1276-80. Distribution of peak expiratory flow variability by age. 22. Thorax 2005. Morris MM. 16. Heijerman HG. Pizzichini MM. 27. Rijcken B.

56. Desjardins A. Morgan WJ. CMAJ 2003. Long-term inhaled corticosteroids in preschool children at high risk for asthma.19(4):240-1. population-based. Eur Respir J 1997. Martinez FD.16(5):1016-22. et al. Ann Allergy 1985. 42. Serial observations before and after development of symptoms. Frey U. A longitudinal. Hoeppner VH. Boyle C. 46. Nordyke RJ. Cockcroft DW. Eur Respir J 2000.354(19):1985-97. Taylor AJ. Castro-Rodriguez JA.62(5):290-9. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. Flannery EM.162 (4 Pt 1):1403-6. Bright P. Greene JM.73(3):285-95. Tinkelman DG. Evidence based guidelines for the prevention.55:36-7. Thorax 1996. Tinkelman DG. 55. Vocal cord dysfunction. Holberg CJ. 52. Nicholson PJ. Boushey HA. The diagnosis of occupational asthma from serial measurements of lung function at and away from work. Burge PS. Cote J. et al. Liss GM. J Adolesc Health 2000. Martinez FD. Mok Q. Occup Environ Med 2005. J Allergy Clin Immunol 2003. Chan-Yeung M. Am J Respir Crit Care Med 2004. MacLean L.35. Morrison A. Respiration 2006. 50. Sly PD. 49. 54.51(8):857-63. Pediatr Infect Dis J 2003. Specification for signal processing and data handling used for infant pulmonary function testing. Bousquet J. Busse WW.22 (2 Suppl):S76-82. Vandenplas O. et al. Follow-up study of 232 patients with occupational asthma caused by western red cedar (Thuja plicata). Arch Dis Child 1989. Mauger DT. Price DB. Malo JL.85(3):592-8. N Engl J Med 2006. Symptom-based questionnaire for differentiating COPD and asthma. Halbert RJ. European Respiratory Society/ American Thoracic Society. Murdock KY. Sly P. Occupational lung disease. Bates J. Development of the asthma control test: a survey for assessing asthma control. Wheezy bronchitis revisited. Sensitivity and specificity of PC20 and peak expiratory flow rate in cedar asthma. 36.113(1):59-65. and management of occupational asthma.349(15):1414-22. Laboratory challenge testing for occupational asthma.73(3):296-305.308(6928):572-4. Zeiger RS. Cullinan P.352(21):216373. Nonikov D. measurements to guide treatment in chronic asthma. 41.170(8):836-44. 44. Tarlo SM. 53.79(5):792-6. J Allergy Clin Immunol 1990. Inhalation challenges with agents causing occupational asthma. Marcus P.111(4):692-4. Tarlo SM. Paggiaro PL. N Engl J Med 2003.168(7):867-71. J Allergy Clin Immunol 1987. 43. Respiration 2006. Clark TJ. Kennedy S. Chan-Yeung M. Occupational asthma: an approach to diagnosis and management. 51. Stocks J. Schatz M. Intensive Care Med 1993. Halbert RJ. Isonaka S. 8. 47. Wright AL. Isonaka S. Burge PS. Nonikov D. Willan AR.64(8):1194-9.10(11):2612-29. 38. et al. Sorkness CA. Am J Respir Crit Care Med 2000.27(2):125-9. Nordyke RJ. Burton P. A clinical index to define risk of asthma in young children with recurrent wheezing. 28 . Szefler SJ. J Allergy Clin Immunol 2004. identification. 48. Guilbert TW. cohort study of childhood asthma followed to adulthood. BMJ 1994. et al. Severe acute "occupational asthma" caused by accidental allergen exposure in an allergen challenge laboratory. Piesowicz AT. Respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma. Accuracy of mini peak flow meters in indicating changes in lung function in children with asthma. Bateman ED. Chan-Yeung M. Foreign body aspiration mimicking asthma. Li JT. 45. N Engl J Med 2005. Cahill P. Symptom-based questionnaire for identifying COPD in smokers. Place R. Sears MR. Kosinski M. Nathan RA. Am Rev Respir Dis 1992. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Boehmer SJ. 40. 37. Kooner S. 39. et al. Willet K. Price DB. Bronchial hyperresponsiveness and level of exposure in occupational asthma due to western red cedar (Thuja plicata). Pauwels RA. Wiecek EM. Arce E.146(6):1606-9. Wilson NM. Taylor DR.

57. 60. Berger M. Markson LE. 29 . A new perspective on concepts of asthma severity and control. King DR.122(6):2217-23. Taylor DR. Association of asthma control with health care utilization and quality of life. Boulet LP. Sanocki LL. 59.Boulet L-P. Ferrie PJ. Eur Respir J 1999. et al. Am J Respir Crit Care Med 1999. Fitterman L. Vollmer WM. Bateman ED .14:902-7. O'Connor E. 58. Milot J. Eur Respir J 2008. O’Byrne PM. Development and validation of a questionnaire to measure asthma control. How should we quantify asthma control? A proposal. 32 :545-554. Juniper EF. Guyatt GH. Chest 2002. Boulet V.160(5 Pt 1):164752.

30

Chapter 3

Asthma
Medications

acting theophylline, and oral short-acting β2agonists (SABA).

KEY POINTS:
Medications to treat asthma are
classified as either controllers or
relievers.

ROUTE OF ADMINISTRATION
Inhaled medications for asthma are
available as pressurized metered-dose
inhalers (MDIs), breath-actuated MDIs, dry
powder inhalers (DPIs), soft mist inhalers,
and nebulized or “wet” aerosols. Table 3-1
lists the advantages and disadvantages of
various aerosol devices1.

Inhaled therapy has the advantage
of delivering drugs directly into the
airways, producing higher local
concentrations with significantly less
risk of systemic side effects.
Inhaled glucocorticosteroids are the
most effective controller medications
currently available.

Inhaler devices differ in their efficiency of
drug delivery to the lower respiratory tract
and ease with which the device can be used
by the majority of patients.

Rapid-acting β2-agonists are the
medications of choice for relief of
bronchoconstriction and for the pretreatment
of
exercise-induced
bronchoconstriction.

Jet nebulizers, MDIs, and DPIs all produce
equal results in acute situations when the
doses are matched and when the latter two
devices are used under direct supervision2,3.
Intravenous salbutamol does not appear to
provide any benefit over nebulization even
in severe cases4.

Increased use, especially daily use
of reliever medication is a warning
of deterioration of asthma control
and indicates the need to reassess
treatment.

INTRODUCTION

CONTROLLER MEDICATIONS
Inhaled Glucocorticosteroids

The goal of asthma treatment is to achieve
and maintain clinical control. Medications to
treat asthma can be classified as controllers
or relievers. Controllers are medications
taken daily on a long-term basis to keep
asthma under clinical control chiefly through
their anti-inflammatory effects. They include
inhaled and systemic glucocorticosteroids,
leukotriene modifiers, inhaled long-acting β2agonists (iLABA) in combination with inhaled
glucocorticosteroids,
sustained-release
theophylline, cromones, anti-IgE, and other
systemic steroid-sparing therapies. Inhaled
glucocorticosteroids are the most effective
controller medications currently available.
Relievers are medications used on an asneeded basis that act quickly to reverse
bronchoconstriction
and
relieve
its
symptoms. They include rapid-acting inhaled
β2-agonists, inhaled anticholinergics, short-

Inhaled corticosteroids (ICS) are the
mainstay therapy for persistent asthma and
are currently the most effective antiinflammatory medications for the treatment
of persistent asthma.
Long term treatment with ICS suppresses
the disease by affecting the underlying
airway inflammation. Several studies
demonstrate that ICS are effective in
reducing symptoms, improving quality of life,
decreasing frequency and severity of
exacerbations, decreasing the need for
bronchodilator rescue therapy, improving
lung function, and reducing asthma
mortality.
A reduction of airway
inflammation, manifested both by airway
histology findings and improved airway
hyperresponsiveness
has
also
been

32

Table 3.1. Advantages and Disadvantages of Various Aerosol Devices1 33 . However.5-9 The outcome parameter responding most rapidly to the initiation of ICS is symptom relief. deterioration of clinical control follows within weeks to months in a proportion of patients 10. these drugs do not cure asthma and when they are discontinued.documented.11.

cataracts in prospective studies 23. budesonide. the systemic effects differ among the various ICS. first-pass metabolism (conversion to inactive metabolites) in the liver. inhaled steroids do not frequently exhibit clinically important side effects and provide asthmatics a good riskbenefit profile. even if moderate and high doses of exogenous corticosteroids affect the hypothalamic-pituitaryadrenal (HPA) axis. For pressurized MDIs.2. Other systemic side effects of long-term treatment with high doses of ICS include easy bruising. Therefore. gargling. and decreased bone mineral density 17-19. Anti-inflammatory therapy. Local adverse effects from ICS include oropharyngeal candidiasis. greater airway hyper-reactivity. the delivery system. Studies suggest that ICS therapy. The risk of systemic adverse effects from an ICS depends upon its dose and potency.22 but there is no evidence of posterior-subcapsular Long-acting Inhaled β2-agonists Long-acting inhaled β2-agonists. The occurrence and magnitude of adrenal suppression is the most extensively studied systemic effect of ICS. systemic bioavailability. However. In mild persistent asthma early intervention with inhaled budesonide was associated with improved asthma control and less additional asthma medication use and was shown to be a cost-effective and safe treatment 15. more symptoms and greater use of β2 agonists12. in addition to suppressing the disease. including formoterol and salmeterol. diminishes the adverse effects of airway inflammation. specifically ICS when started early in the course of asthma. may also modify the disease outcome if prescribed early enough and given long enough 12-14 . including tuberculosis. At low to moderate doses. the resulting adrenal suppression does not appear to be clinically important. Oral candidiasis may be reduced by mouth washing (rinsing with water. Long standing uncontrolled asthma is associated with lower levels of lung function. should not be used as monotherapy in asthma as these medications do not appear to influence the airway 34 .70 Side Effects. accounting for some degree of systemic bioavailability. Several comparative studies have demonstrated that ciclesonide. as there were no cases of adrenal crisis reported in adults using only ICS. dysphonia. Table 3.2 lists approximately equipotent doses of different inhaled glucocorticosteroids based upon the available efficacy literature. and fluticasone propionate at equipotent doses have less systemic effect 25-28. ICS have also been associated with cataracts and glaucoma in cross-sectional studies20. and half-life of the fraction of systemically absorbed drug (from the liver and possible gut)25. Estimated Equipotent Daily Dose of Inhaled Glucocorticosteroids for Adults70 ICS are absorbed from the lung. There is no evidence that use of ICS increases the risk of pulmonary infections. Current evidence suggests that in adults. Inhaled steroids are relatively safe. Table 3. and ICS are not contraindicated in patients with active tuberculosis 24. and occasionally coughing from upper airway irritation. systemic effects of ICS are not a problem at doses of 400 g or less budesonide or equivalent daily. and spitting out) after inhalation. the prevalence of these effects may be reduced by using certain spacer devices16.21.

47. decreases nocturnal asthma. The regular use of rapid acting β2agonists in both short and long acting forms may lead to relative refractoriness to β2-agonists50. and should only be used in combination with an appropriate dose of ICS as determined by a physician. and at a lower dose of ICS than ICS given alone42. decreases the use of rapid-acting inhaled β2agonists36-38.36-41. combination inhalers containing formoterol and budesonide may be used for both rescue and maintenance. they may be used as an add-on therapy to reduce the dose of ICS required by patients54. They are most effective when combined with ICS 29-31. However. budesonide plus formoterol). Therapy with inhaled LABA causes the following systemic adverse effects: cardiovascular stimulation. 35 . Combination treatment of ICS and LABA improves symptom scores. Data indicating a possible increased risk of asthma-related death associated with the use of salmeterol in a small group of individuals51 led to advisories from the US Food and Drug Administration (FDA)‡ and Health Canada§ that long-acting 2-agonists are not a substitute for inhaled or oral glucocorticosteroids. may be more advantageous in the local setting as it may provide greater improvements in lung function and asthma control. ICS + LABA. Side effects. when used alone. For moderate-to.severe persistent asthma.33 which may make formoterol suitable for symptom relief as well as symptom prevention34.48. In patients already on inhaled steroids. The regular use of rapid acting Long-acting β2-agonists (LABA) as a monotherapy for symptom relief however may lead to relative refractoriness to β2-agonists35 and a possible increased risk of asthma-related death and should only be used in combination with an appropriate dose of ICS. skeletal muscle tremor.47 and provide improvements in asthma control at relatively low doses of treatment 34. and hypokalemia. In treating patients with mild persistent asthma. the LABA and the ICS increases the efficacy of both drugs. but there are pharmacological differences between them. Formoterol has a more rapid onset of action than salmeterol 32. and may improve asthma control in patients whose asthma is not controlled with low or high doses of ICS55. reduces the number of exacerbations19. Both components of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance 46. their effects are generally less than that of low dose ICS52. and achieves clinical control of asthma in more patients.inflammation in asthma. In addition. Salmeterol and formoterol provide a similar duration of bronchodilation and protection against bronchoconstrictors. improve compliance and has comparable safety to ICS alone. more rapidly. Leukotriene modifiers The greater efficacy of combination treatment has led to the development of fixed combination inhalers that deliver both glucocorticosteroid and LABA simultaneously (fluticasone propionate plus salmeterol.44.49. improves lung function. Fixed combination inhalers are more convenient for patients. Controlled studies have shown that delivering this therapy in a combination inhaler is as effective as giving each drug separately43. This interaction between Leukotriene modifiers may be given as controller drugs for mild persistent asthma whenever ICS are not in use. may increase compliance45. The additional clinical benefit derived from the fixed combination therapy results not only from the LABAglucocorticoid interaction but also from the steroid-induced transcription of β2-adrenoceptor gene with the resultant increased synthesis of the β2-receptor protein. initial therapy with ICS+LABA. and ensure that the LABA is always accompanied by a glucocorticosteroid. leukotriene modifiers cannot substitute for this treatment without risking the loss of asthma control53.

The apparent association of of leukotriene modifiers with Churg-Strauss Syndrome (CSS) was proposed to be due to the unmasking of the underlying disease noted particularly during the period of oral steroid tapering59. loose stools. and when conditions known to alter theophylline metabolism exist70.61-63 The rationale for this recommendation may arise from findings that low concentrations of theophylline can restore the anti-inflammatory action of corticosteroids in oxidant exposed cells. Side effects. 36 . although less effective. its mechanism of action is related to the inhibition of phosphodiesterase activity. Few.3-dioxalan-2ylmethyl) theophylline) a methylxanthine derivative. when expected therapeutic aims are not achieved. have shown better or at least equivalent results to those of theophylline to relieve bronchial obstruction with less adverse effects.73-77 In addition to its symptomatic and quality of life benefits. remains unknown64. They should be used with caution among patients with liver disease. which may account for its better safety profile65-68. Similarly to theophylline. if any classrelated effects have so far been recognized.Leukotriene modifiers include cysteneinylleukotriene-1 receptor antagonists (montelukast. pranlukast. Studies on doxofylline. Methylxanthine and Derivatives Anti-IgE Theophylline is used primarily for bronchodilation. improve lung function and reduce airway inflammation and asthma exacerbations57. its potential for serious toxicities and drug interactions and the need for serum concentration monitoring limit its usefulness in chronic therapy. omalizumab therapy allows ICS dosage reduction or discontinuation of ICS in many patients. but in contrast. It is available in sustained release formulation that is suitable for once or twice daily dosing.(78-79). Available evidence suggests that it may provide benefit as add-on therapy. than LABA in patients who do not achieve control on ICS alone. and zafirlukast) and a 5lipooxygenase inhibitor (Zileuton). as add-on therapy with ICS. These drugs are beneficial across a range of asthma severities and may have a particular role in exercise-induced asthma. Clinical studies have demonstrated that they have a small and variable bronchodilator effect. Omalizumab has been investigated extensively in the treatment of patients with allergic diseases and is approved for the treatment of patients with moderate-to-severe persistent asthma. although more recent studies failed to implicate direct hepatotoxicity with leukotriene modifiers. aspirin-sensitive asthma. if the patient develops an adverse effect on the usual dose. 69 Monitoring is advised when a high dose is started. cardiac arrhythmias. Omalizumab71-72. However. Side effects. seizures and even death. and individuals with concomitant allergic rhinitis. (7-(1. Adverse effects of theopylline include nausea and vomiting. It is preferably prescribed by some physicians because of the oral administration and relatively low cost. it appears to have decreased affinity towards adenosine A1 and A2 receptors. Data on its relative efficacy as a long-term controller is lacking. reduce symptoms including cough56.65 Doxofylline differs from theophylline in that it contains a dioxalane group in position 7. The exact mechanism however. which are the most common early events. Leukotriene modifiers are safe drugs even for prolonged use. is an effective and well tolerated agent for the treatment of moderate to severe allergic asthma in adolescents and adults. cough variant asthma. premenstrual asthma58. Currently available evidence suggests an association between leukotriene modifiers and CSS that may be causal60.

glaucoma.70 Salbutamol works poorly in some patients. clinical efficacy and tolerability data indicate that omalizumab is a valuable option in the treatment of allergic asthma. There were also no studies that compare specific immunotherapy with pharmacologic therapy for asthma. The role of specific immunotherapy in adult asthma is therefore limited. arterial hypertension. obesity. The side effect profile of long acting oral β2-agonists is higher than that of inhaled β2-agonists. and carries a risk of severe allergic reactions and sometimes fatal anaphylaxis. terbutaline. However. Adverse cardiovascular reactions may also occur with the combination of oral β2-agonists and theophylline. and skeletal muscle tremor. its use is severely limited because of its prohibitive cost.70 Side effects.83-87 37 . The systemic side effects of long-term oral or parenteral glucocorticosteroid treatment include osteoporosis. and includes cardiovascular stimulation (tachycardia). with some reduction in non-specific bronchial hyperreactivity as well. anxiety. skin thinning leading to cutaneous striae and easy bruising. permanent changes in β2-receptor physiology. there was no consistent effect on lung function 82. Antihistamines The role of antihistamines is limited to providing relief of allergic symptoms in some asthmatics81. omalizumab reduces the frequency and incidence of asthma exacerbations. Long acting oral β2-agonists include slow release formulations of salbutamol. Comparisons of omalizumab with other asthma therapies have yet to be conducted. Allergen-specific immunotherapy Systemic glucocorticosteroids Allergen specific immunotherapy. RELIEVER MEDICATIONS Rapid-acting inhaled β2-agonists Moderately short-acting β2-adrenergic agonists such as salbutamol and terbutaline have rapid onsets of action and provide three to four times more bronchodilatation than do methylxanthines and anticholinergics. However. a prodrug that is converted to terbutaline in the body. This phenomenon does not appear to be a function of the medications taken before treatment. Asthma control was well maintained even with reduced ICS dose. cataracts. and muscle weakness. Regular use of long-acting oral β2-agonists as monotherapy is likely to be harmful and these medications must always be given in combination with inhaled glucocorticosteroids. making them the first-line treatment for acute illness. or the presence of fixed obstruction. diabetes. These side effects may be present even on low doses80. It involves having injections of increasing amounts of the allergen under the skin. allergen immunotherapy significantly reduced allergen specific bronchial hyperreactivity. Several studies however have shown that these drugs may be more useful for allergic rhinitis rather than bronchial asthma as there is no decrease in bronchial responsiveness to methacholine after antihistamine treatment.In such patients. and bambuterol. Long-acting oral β2-agonist Long-acting oral β2-agonists are used only on rare occasions when additional bronchodilation is needed. The use of long-term oral glucocoticosteroid therapy in the control of asthma is not recommended because of the risk of significant adverse side effects. A Cochrane review that examined 75 randomized controlled trials (RCTs). In the local setting. has long been a controversial treatment for asthma. also known as hyposensitization or desensitization. hypothalamic-pituitary-adrenal axis suppression.

and reduce the morbidity of the illness. When symptoms have subsided and lung function has approached the patient’s personal best value. No tapering is required over this period. A meta-analysis of trials of inhaled ipratropium bromide used in association with an inhaled β2-agonist in acute asthma showed that the anticholinergic produces a statistically significant. Use of oral β2-agonists given in standard doses is associated with more adverse systemic effects such as tremor and tachycardia than occur with inhaled preparations. fluid retention. arrhythmia. Oral and intravenous routes of corticosteroid administration are equally efficacious89. It has a slow onset of action (60–90 minutes to peak) and medium potency (about 15% increase in PEFR). mood alteration. Corticosteroids should be administered as soon as possible after initiation of bronchodilator therapy88 since the onset antiinflammatory effects of corticosteroids are not seen for several hours. can effectively treat the airway edema and increased secretions associated with the inflammation. or PEFR in the initial treatment of acute asthma attacks. reduce the need for referral to emergency departments and hospitalization. and significantly reduces the risk of hospital admission. They are important in the treatment of severe acute exacerbations because they prevent progression of the asthma exacerbation. failure to achieve a quick and sustained response to β2-agonist treatment during an exacerbation mandates medical attention. the oral glucocorticosteroids can be stopped or tapered.93 Side effects.90-93 The benefits of ipratropium bromide in the longterm management of asthma have not been established.98 Patients discharged from the Emergency Department (ED) who require corticosteroid therapy should be given 30 to 60 mg of prednisone orally (or equivalent) per day for 7 to 14 days. improvement in pulmonary function. and aseptic necrosis of the femur. systemic glucocorticosteroids. The benefits offered however. Increased use. prevent early relapse after emergency treatment. rounding of the face.Rapid-acting inhaled β2-agonists should be used only on an as-needed basis at the lowest dose and frequency required. Adverse effects of short-term high-dose systemic therapy are uncommon but include reversible abnormalities in glucose metabolism. hypertension. The parenteral route is preferred if patients are unable to take medication orally or if they are unable to absorb an oral dose. increased appetite. peptic ulcer.93 Intramuscular injection of glucocorticosteroids has no advantage over a short course of oral glucocorticosteroids in preventing relapse. is a warning of deterioration of asthma control and indicates the need to reassess treatment. albeit modest. Systemic glucocorticosteroids Anticholinergics In acute asthma. are still a matter of debate. The use of anticholinergic drugs as the initial bronchodilator has been consistently reported to be inferior to the use of a β-agonist on improving airflow in acute severe asthma. 38 . weight gain. it is used as second-line therapy. although it is recognized as an alternative bronchodilator for patients who experience such adverse effects as tachycardia. Similarly. Consequently. further improves the FEV1. and may indicate the need for short-term treatment with oral glucocorticosteroids. and tremor from rapid acting β2agonists. especially daily use. 9497 The addition of nebulized ipratropium bromide to salbutamol. provided that treatment with inhaled glucocorticosteroids continues. particularly in patients resistant to β2 agonists.

some studies have shown a reduction in dyspnea. Inhalation of ipratropium can cause a dryness of the mouth and a bitter taste. or burning at the IV site. nausea. lightheadedness. and the lower the initial FEV1 the greater the improvement in FEV1. Minor side effects can include transient flushing. however. did not improve after treatment with magnesium. lethargy. Theophylline has the potential for significant adverse effects. increased PEFR. it has no proven additive bronchodilator effect over adequate doses of rapid-acting 2-agonists. although these can generally be avoided by appropriate dosing and monitoring. 105.102 IV magnesium may be useful for severe exacerbations unresponsive to the initial treatment in the ER to decrease the likelihood of intubation. A few studies have shown that it may benefit respiratory drive. Serious side effects at the infusion rate and dose administered of 2 g are extremely uncommon in patients with adequate renal function. however. Furthermore.improvements were restricted to patients with the most severe airway obstruction. Heliox Heliox may be useful for severe exacerbations unresponsive to the initial treatment in the ER to decrease the likelihood of intubation.99 Methylxanthines Short-acting theophylline may be considered for relief of asthma symptoms. Short-acting theophylline should not be administered to patients already on long-term treatment with sustained-release theophylline unless the serum concentration of theophylline is known to be low and/or can be monitored. Magnesium is relatively inexpensive. readily available.102 Side effects. Complementary and Alternative Medicine The administration of 2 g of magnesium sulfate as an adjunct to standard therapy to patients presenting to the ER with severe asthma causes improvement in pulmonary function.100 Recent guidelines have relegated its use as third line treatment in acute asthma. 101 IV Magnesium The use of magnesium to improve pulmonary function should be considered when treating acutely ill asthmatics in the Emergency Room (ER) with severe airway obstruction. There is no evidence for any adverse effects on mucus secretion. In non-intubated individuals. improved gas exchange. may lower respiratory resistive work long enough to forestall muscle fatigue and/or improve ineffective mechanical ventilation until bronchodilators and steroids can take effect. The The roles of complementary and alternative medicine in adult asthma treatment are limited because these approaches have been insufficiently researched and their effectiveness 39 . there is a decrease in peak inspiratory pressure and PaCO2. and a diminution in pulsus paradoxus103-104 whereas others have not found any benefit. Its temporary use. Intravenous methylxanthine (aminophylline) does not result in any additional bronchodilation compared to standard care with beta-agonists. The frequency of adverse effects is higher with aminophylline. Transient urticaria resolving with discontinuation of magnesium has been reported. The hospital admission rates. No subgroups in which aminophylline might be more effective could be identified. There has been insufficient evidence to support the routine use of magnesium in acute asthma and further studies are still recommended.106The effects of heliox are transitory and disappear when air is once again inhaled. In intubated patients. Heliox. a blend of helium and oxygen. reduces airway resistance and may be a therapeutic option for severe refractory asthma. and easy to administer. The mixture may improve the distribution of inhaled agents and lead to a faster rate of resolution of obstruction.

acupuncture treatment resulted in immediate improvement of FEV1. however. Bigger randomized placebo controlled trials investigating the bronchodilator effects and safety of local herbal preparations are needed. and biofeedback might have a small effect in selected cases. At present there is no definitive evidence to recommend any of the breathing techniques such as the Buteyko breathing method or retraining exercises. In a small randomized double blind study involving 40 subjects. but the degree of improvement is less than that from inhalation bronchodilator. desquamation of the skin over the palms and increased urination. dietary supplements. speleotherapy.is largely unproven. Acupuncture-associated hepatitis B. Ayurvedic medicine. Sahaja yoga. for asthma. Lagundi tablets improve peak expiratory flow rate108. hypnosis. as exemplified by the occurrence of hepatic veno-occlusive disease associated with the consumption of the commercially available herb comfrey sold as herbal teas and herbal root powders. and psychotherapy-related methods such as relaxation. some popular herbal medicines could potentially be dangerous. but have not proven to be superior to placebo. However. a later study of two physiologicallycontrasting breathing techniques showed similar improvements in reliever and ICS use in both groups. chiropractic manipulation. Side effects. 40 . bilateral pneumothorax. and burns have been described. as reported in the studies. Complementary and alternative therapies include herbal medicine. although there were no significant differences between the intervention and control groups at the 2-month follow-up assessment. RESEARCH RECOMMENDATIONS A well-designed study should be conducted to determine how low dose inhaled corticosteroids alone compare with combined low dose inhaled corticosteroid with LABA in controlling the symptoms and improving the lung function of patients with mild persistent asthma as well as their costeffectiveness and safety. Side effects of other alternative and complementary medicines are largely unknown. A cost-effectiveness study between strategies using different combination inhaled LABA and corticosteroids. suggesting that perceived improvement with these methods are the result of nonphysiological factors. hypnosis.113 A systematic review107 was conducted to determine the study quality of articles investigating ayurvedic/collateral herbs. Side effects of Lagundi include vomiting. Butyeko breathing method or retraining exercises. autogenic training.108 There is also insufficient evidence on the benefit of Vitex vigonensis (lagundi). The review concluded that there is insufficient evidence to make recommendations for the use of these herbals. the effectiveness/efficacy and safety profile.112 Psychotherapy-related methods such as relaxation. acupuncture. autogenic training. and biofeedback. At this time. Although one study of the Buteyko breathing method suggested minor benefit. there is insufficient evidence to recommend it as part of the standard therapeutic regimen for asthma.111 A randomized controlled trial indicated that the practice of Sahaja yoga has limited beneficial effects on asthma for some objective and subjective measures. an herbal cough preparation. speleotherapy. In a prospective randomized crossover controlled study in 18 asthma patients.109 A single controlled trial of chiropractic spinal manipulation failed to show benefit of this therapy in asthma110.

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46 .

Chapter 4 Patient Education .

Table 4. Such benefits can be achieved without any increase in consultation times 4. their family and other caregivers with suitable information and training so that they can keep well and adjust treatment according to a medication plan developed wit h a health care professional.KEY POINTS: Table 4. In the GINA 2007 guidelines. Essential Features of the Doctor Patient P artnership to Achieve Guided SelfManagement in Asthm a Patient education is of prime import ance in the management and control of asthma. the patient needs information about: 1. Because of non-adherence to medic ation. Thus. however. The aim of patient educ ation is guided self-management. asthma education is the first step in the treatment recommendations. The main aim for asthma education is to provide the person with asthma. At the INITIAL CONSULTATION6 During the first consultation. and reduced use of health care. Communicative skills hav e been pointed out as one of the key factors for good adherence or complianc e of patients 2-3 (Evidence B). All individuals require core information and skills. the ability of the healthcare professionals to be good communicators should not be overlooked.2 enumerates the key components of asthma education. education is best with a personalized approach and given in a number of steps. It is thus of prime importance that healthcare professionals be educated to improve their communication skills which can result into better outcomes – including increased patient satisfaction. 48 Diagnosis Asthma and its nature should be defined The signs and symptoms of the patient should be explained It should be stressed that spiromet ry be done to have an objective parameter for the diagnosis of asthma . it has been recognized that the adolescent asthmatic is considered difficult to manage1. better health. Table 1 enumerat es the essential features of the doctor-patient part nership needed to achieve guided self-management in asthma 5. ASTHMA EDUCATION Patient education is of prime importance in the management and cont rol of asthma. This can be achieved either through individualized or group education.1. Development of a good doctor-patient relationship facilitates patient education.

Management of acute exacerbations Personal Asthma Action Plan : individualized asthma action plans help asthmatic patients tailor their treatment in response to changes in their level of asthma control based on their symptoms and peak flow measures. Steps to take in the management of exacerbations c.2. in accordance with written predetermined guidelines Individual patient’s asthma action plan should cont ain the following: a. for management relieve about Proper use of inhaler devices The patient must be taught the correct technique of using their inhaler devices so as to maximize medication effect 6. Table 4. Medicines used to symptoms Medicines used to symptoms Specific instructions medication use of 49 1.2. When to seek emergency care Follow-Up Care: Peak flow meter The patient must be taught the proper way to use a peak flow meter The patient must know how to interpret the values obtained Drugs needed asthma control 5. Check inhaler device technique and correct if inadequate. How to identify deteriorating asthma control/exacerbations b. 2. . Education and the patient/Doctor Partnership 3. Triggers It should be stressed to patients that avoidance of triggers is important in the prevention of acute attacks Exercise should not be avoided - 4. PEFR diary – included are symptoms and home peak flow monit oring noted in the diary.

for better medical seeking attention of afflicted Specific advice about asthma and its management should be offered to school teachers and physical education instructors.3. Patient concern about side effects of inhaled glucocorticosteroids whether real or perceived may influence adherence.. 4. do y ou mind telling me how often you actually take the medicine?”) Specific drug and non-drug factors involved in 5 non-adherence are listed in Table 4-3. This way. This will enable them to communicate more effectively to their physicians. An option for busy practitioners would be to refer to the different asthma clubs available in their locality for their patients’ asthma education. parents. caregivers about asthma. the people would be made aware of asthma symptoms and its consequences.3. IMPROVING ADHERENCE Check adherence or compliance to medication plan and recommendations for reducing exposure to risk factors or triggers. Schools may need advice on improving 50 . Review of asthma action plan should be done. . Factors Involved in Non-adherence EDUCATION OF OTHERS individuals. 5 Not only is it important to educate patients. and reduce stigmatization on the part of the patient. participate in planning strategies for controlling their asthma and ev entually normalize their day-t o-day activities. pill counting or drug assay. Non-adherence may be identified by prescription monitoring.g. and several organizations produce mat erials f or this purpose. Studies of adults have shown that around 50% of those on long term therapy failed to take medications as directed at least part of t he time. Asthma clubs provide a good venue where the patients can express their feelings and f ears about asthma. “So that you can plan therapy. Table 4. Non-adherenc e may be defined in a non-judgemental way as the failure of treatment to be taken as agreed upon by the patient and the health care professional. But at a clinical level it is best detected by asking about therapy in a way that acknowledges the likelihood of incomplete adherence. to help dispel misconceptions. it is likewise important to educate the general public as well. (e. The curriculum should cover all those items that should be discussed in an individualized education.

Diagnosis and Management of Asthma 1996 Juniper EF. de Haes JC. 5 Further readings on occupational asthma can be found in Chapter 8 on Special Considerations. Shah s. Doctor-patient communication: a review of the literature. Mazurki EJ. et al. Eur Respir J 1999. Global Initiative for Asthma. Bruce C. Development and validation of a questionnaire to measure asthma control. BMJ 2001.14:902-7 Nathan. Long-term effects of asthma education for physicians on patient satisfaction and use of health services. Peat JK. Li JT. Soc Sci Med 1995. Clark NM. RA. It is also helpful for employers to have access to clear advice about asthma. Effect of peer led programme for asthma education in adolescents: cluster randomized controlled trial. Kaciroti N. Development of the asthma control test: a 51 . 5. Eur Respir J 2000.16(1):15-21.40(7):903-18. 2. 4. References 1. O’Byrne PM. but there may be some circumstances where caution is needed. 322(7286):583-5 Ong LM.113(1):59-65. Hoos AM. CMAJ 1995. Effective physician-patient communication and health outcomes: a review. Wang H. Schork MA. Schatz M. Marcus P. RECOMMENDATIONS: Investigate the impact of asthma clubs on the quality of life of asthmatic patients in the local setting. 8. 2007 update Philippine Consensus on Recognition. Ferrie PJ. Gong M.survey for assessing asthma control. et al. 3. Stewart MA. Kosinski M. Global Strategy for Asthma Management and prevention. Sindhusake D. et al. 6. J Allergy Clin Immunol 2004. Roloff D. the environment and air quality. with sustenanc e of the different asthma clubs.152(9):1423-33. Most occupations are as suitable for those with asthma as for those without. 7. Lammes FB. Sorkness CA. King DR. How to encourage the wide availability of asthma clubs. Evans D. Guyatt GH.

52 .

Chapter 5 Identify and Reduce Exposure to Risk Factors .

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Other than preventing tobacco exposure both in-utero and after birth. • Presently. until such time that measures to prevent the development of asthma has been successful. there is no sufficient evidence on the critical timing and appropriate doses of allergen exposure that would permit intervention in this process. and its development is complex and incompletely understood. present efforts should primarily focus on prevention of asthma symptoms and attacks. Dietary intervention (e. asthma symptoms. Likewise.4 and perinatally. lowered mortality rate. More importantly. asthma. exclusive breast-feeding during the first months after birth is correlated with lower rates of childhood asthma7. • Reduction of an asthmatic's exposure to some categories of risk factors improves the control of asthma. • Asthma exacerbations are usually caused by a variety of risk factors or "triggers" such as allergens and pollutants (both indoor and outdoor). reduced exacerbations. however. Interventional modalities aimed at preventing allergic sensitization or the development of atopy3. however. no strategy can be recommended in this area. few measures for asthma prevention can be recommended because asthma in itself is a variable disease and its development complex and incompletely understood. (and hence prevent asthma development in sensitized individuals) most relevant prenatally3. At present. viral infections and drugs. such a diet could have an adverse effect on maternal and fetal nutrition.2 The role of breast-feeding in relation to the development of asthma has been studied more extensively.KEY POINTS: ASTHMA PREVENTION • Measures to prevent the development of Few measures can be recommended for asthma prevention because the disease is a very variable one. is often impractical and extremely limiting for the patient. there are no proven and accepted interventions that can prevent the development of asthma. especially in high risk groups like 54 . and asthma exacerbations by avoidance or reducing exposure to asthma risk factors should be implemented whenever possible. prescribing an antigenavoidance diet likely to be low in proteins) to a high risk woman during pregnancy has not been proven to decrease the risk of giving birth to an atopic child5. It is an accepted fact that infants fed on formulas of cow’s milk or soy protein have a higher incidence of wheezing compared to infants who are breast-fed6.g. during which time the lungs are still developing. Complete avoidance of these risk factors.1 The former is currently a focus of intensive research and hence. are still in the realm of research. and has significantly improved the quality of life of an asthmatic individual. in the management is the implementation of measures aimed at preventing the development of asthma and asthma symptoms by avoiding and reducing exposure to risk factors. Thus. INTRODUCTION The pharmacologic intervention that has evolved through the years in treating asthma has effectively controlled symptoms. A focal point in any discussion of asthma prevention is the concept of "hygiene hypothesis" which states that little or no exposure to bacteria and viruses during a critical period of infancy can lead to an imbalance in the immune system and result in diseases such as asthma. Just as important.

in the end.2 The hygiene hypothesis has also led to the concept of the role of probiotics in the prevention of allergy and asthma. Severe weather and atmospheric conditions favor the development of asthma exacerbations by a variety of mechanisms. PREVENTION OF ASTHMA SYMPTOMS AND EXACERBATIONS Asthma exacerbations may be caused by a variety of factors. medications to maintain asthma control have an important role in preventing symptoms and exacerbations because patients are often less sensitive to these triggers when their asthma is under good control.15 as well as allergen-specific immunotherapy16. therefore. pollutants. passive smoking increases the risk of allergic sensitization in children12. Though this concept is still unclear. As such. pollens and other allergens. the offending environmental allergen(s). and changes in temperature/humidity. It is feasible that both pollen quantity and allergenicity have already had an impact on asthma reflected in 55 . and preferably the removal of. viral infections. Exposure to tobacco smoke both prenatally and postnatally is associated with measurable and well-documented harmful effects. with numerous contributing factors and interactive effects modified by climate18. Though still largely controversial. strategies should be made to redirect a predisposed child’s immune response toward a Th1 (non-allergic) response or modulate T regulator cells8. referred to as "triggers". including exposure to dust and pollution. A probiotic supplement like Lactobacillus GG apparently can stimulate the immune system and. Again.children who have parents with asthma. Thus. Increasing temperatures (global warming) stimulates the growth of fungus.13. It is highly recommended. Once allergic sensitization has occurred. molds. Central to the prevention or reduction of the occurrence and severity of asthmatic exacerbations is a decrease in. CO2 increases and the plants’ pollenproducing capacity increases. More definite evidence-based data on this matter is presently still lacking. avoiding these factors completely is usually impractical and very limiting to the patient. increases in respirable allergens.19. Global warming itself extends the growing season of such airborne allergens and hence. there are still options and opportunities to prevent the actual development of asthma. The role of H1antagonists and antihistamines14. prevent or at least delay the appearance of early signs of asthma such as wheezing and frequent rhinitis. such strategies at present are in the realm of theories and research and require further investigation. it has gained more attention in the last few years9. that pregnant women and parents of young children should not smoke. including allergens. and drugs. including effects on lung development10 and a greater risk of developing wheezing illnesses in childhood11. Although there is little evidence that maternal smoking during pregnancy has an effect on allergic sensitization12. Since many asthma patients react to multiple factors that are ubiquitous in the environment. Climate changes and Global warming Asthma is an etiologically complex disease. the hypothesis has led to the suggestion that in order to prevent allergic sensitization.17 in the prevention of development of asthma in highlyatopic children remain to be an area of continued investigation. recommended for wide scale adoption as part of management strategies in clinical practice2. no clear-cut recommendation on this matter can be made and definite interventions cannot be The climate change hypothesis proposes that the global rise of asthma is an early impact of anthropogenic climate change20.

avoidance of pet the allergens are found in many home31. Make sure trash is stored in containers with lid that close securely. Thunderstorm asthma is a little understood entity where rain water has been implicated to cause an "osmotic shock" on pollen grains21. the global rise in asthma prevalence and increased severity of asthma episodes. boric acid or traps first before using pesticide sprays. Indoor Allergens There is conflicting evidence on whether measures to create a low-allergen environment in patients' homes and reduce exposure to indoor allergens are effective at reducing asthma symptoms54. dust removal. as ubiquitous and can be environments outside the Fungi. Domestic mites. Cockroaches. sinks. These tiny particles are smaller than pollen and therefore more deeply inhaled. including In tropical and subtropical climates.55. pest management measures/advice include the following: Do not leave food or garbage out. Clean all food crumbs or spilled liquids right away. precipitating attacks in those who are sensitive. Keep counters. Fungal exposure has been associated with exacerbations from asthma and the number of fungal spores can best be reduced by removing or cleaning mold-laden objects36.27. feces and saliva can cause allergic symptoms or trigger asthma symptoms in some individuals.schools32. Furred animals. fungi may grow on the walls of the house due to water 56 . Remove piles of boxes. and cat-free buildings33. Complete allergens is impossible. and reduction of microhabitats favorable to mites has been suggested. Although avoidance measures are only partially effective in removing residual allergens35 (Evidence C). and remove trash daily. and single chemical and physical methods aimed at reducing mite allergens are not effective in reducing asthma symptoms in adults24. even after permanent removal of the animal it can be many months before allergen levels decrease34 and the clinical effectiveness of this and other interventions remains unproven. Although removal of such animals from the home is encouraged. No single measure is likely to reduce exposure to mite allergens. It is likely that no single intervention aimed at reducing allergen load will achieve sufficient benefits to be cost effective2426 . tables and floors clean and clear of clutter. Cockroaches are commonly found in crowded cities and likely play a significant role in asthma in urban areas. Wash dishes as soon as you are done using them.28 (Evidence A). One study showed some efficacy of mattress encasing at reducing airway hyperresponsiveness in children29 (Evidence B). Seat cracks or openings around or inside cabinets. Store food in airtight containers. public transportation. although its efficacy at reducing symptoms has only been confirmed in deprived populations with a specific environmental exposure30 (Evidence B) and a recommendation for its widespread use cannot be made. Fix plumbing leaks and other moisture problems. The air becomes filled with allergenic proteins produced by starch granules from grass pollen grains which are spread by the strong winds of a thunderstorm22. Allergens found in cockroach dried body parts. newspapers and other hiding places for pests from your home. An integrated approach including barrier methods. Try using poison baits.

remaining indoors when pollen and mold counts are highest and using air conditioning if possible. 57 . Secondhand smoke increases the frequency and severity of symptoms in children with asthma. Outdoor Allergens Outdoor allergens such as pollens and molds are impossible to avoid completely. Indoor Air Pollutants The most important indoor pollutant is tobacco smoke.seepage and humidity. Air conditioners and dehumidifiers may be used to reduce humidity to levels less than 50% and to filter large fungal spores. active cigarette smoking reduces the efficacy of inhaled and systemic glucocorticosteroids38. and smoking cessation needs to be vigorously encouraged for all patients with asthma who smoke. Ionizers and Dehumidifiers. liquefied petroleum gas. Parents/caregivers of children with asthma should be advised not to smoke and not to allow smoking in rooms their children use. Avoidance of passive and active smoking is the most important measure in controlling indoor air pollutants. where acute respiratory infection (ARI) morbidity and mortality are highest. ionizers do not work any better than highefficiency particulate air (HEPA) filters or electrostatic filters in removing allergens from the air and may generate unwanted ozone. To avoid this. Some countries use radio. It excludes organic material which has been transformed by geological processes into substances such as coal or petroleum. Electronic filters such as ionizers use electrical charges to attract and deposit allergens and irritants. Mechanical filters such as fan-driven HEPA filters force air through a special mesh that traps particles including allergens like pollen.39 (Evidence B). kerosene or a combination of two or all three. Indoor particulate concentrations in rural areas of developing countries. They also capture irritant particles like tobacco smoke. Exposure may be reduced by closing windows and doors. however. pet dander and dust mites. the walls could be tiled or cleaned as necessary. HEPA devices. The average Filipino woman spends a large amount of her time at home cooking and related work and is thus exposed to emissions from cooking fuels which may take any one of the following types: biomass. Domestic cooking is a significant source of indoor air pollution. However. television.000 g/m3. a renewable energy source which when burned. and the Internet to provide information on outdoor allergen levels. Biomass consists of organic material from trees. Dehumidifiers are more appropriate than ionizers and HEPA filters in reducing house dust mites that thrive in humid environments. In addition to increasing asthma symptoms and causing long term impairments in lung function. The impact of these measures is difficult to assess. air conditioning and sealing of windows have also been associated with increases in fungal and house dust mite allergens37. Mechanical and electrical devices reduce indoor allergen load. It stores solar energy in organic matter and is. There may be a significant association between symptoms of asthma and chronic bronchitis and biomass fuel usage in females living in a rural area40. releases chemical energy as heat. It can be used as fuel or for industrial production. therefore. range from a few hundred to more than 10. however their clinical benefit in reducing asthma symptoms in predisposed individuals remains inconclusive. agricultural crops and other living plant material.

Outdoor Air Pollutants Outbreaks of asthma exacerbations have been shown to occur in relationship to increased levels of air pollution. nitrogen oxides. including heavy metal ions. are easily inhaled into the lungs and may interfere with respiration47. and resulting exacerbations become increasingly severe.which are released into the air. Diesel exhaust (DE) is a complex mixture containing carbonaceous particles. carbon monoxide. emphysema.46. and this may be related to a general increase in pollutant levels or to an increase in specific allergens to which individuals are sensitized41-43. and particulate matter—and symptoms or exacerbations of asthma. and asthma. 58 . Researchers believe that DE causes problems for people with asthma through minute particles of dust. dirt. The potential respiratory symptoms from the inhalation of volcanic ash are short term and are not considered harmful for people without existing respiratory conditions. particularly among urban residents. and some potent sensitizers. soot and smoke .however. have come under scrutiny as stimuli of asthma exacerbations. resulting in greater pollution-related effects on lung function among asthmatics on corticosteroids. In addition DE particles may act as vectors for the delivery to the lung of toxic materials. Volcanic ash.5 microns.49. The observation that a two hour walk along a busy thoroughfare with high density of diesel exhaust can increase asthmatic symptoms. oxides of nitrogen. As the prevalence of asthma. In June 1991. ambient air pollutants. Individuals with chronic bronchitis. should take special precaution to avoid exposure to ash particles and be aware that the use of any respirator other than single-use (disposable) respirators may cause additional cardio-pulmonary stress. Respirable particulates of less than 2.48. and inflammation in the lungs offers support for the hypothesis that diesel exhaust may play a role in causing asthma. it did produce large amounts of tiny particles which increased chlorine's effectiveness at destroying ozone and thus destroying ozone faster than would have otherwise occurred. especially ozone and particulate matter (PM). Occupational Exposures The early identification of occupational sensitizers and the removal of sensitized patients from any further exposure are important aspects of the management of occupational asthma (Evidence B). Diesel Exhaust. acidic aerosols. It appears possible that there is subclinical airway inflammation or preexisting airway remodeling that is "unmasked" by exposure to higher air pollutant levels. Most epidemiological studies show a significant association between air pollutants—such as ozone. aldehydes and other volatile organic carbon species. the level of exposure necessary to induce symptoms may be extremely low. Attempts to reduce occupational exposure have been successful especially in industrial settings. Although the eruption did not permanently increase stratospheric chlorine concentrations. Once a patient has become sensitized to an occupational allergen. Pinatubo in Pampanga spawned 20 million tons of gas and ash as high as 12-18 miles into the stratosphere and as far as the Indian Ocean and with satellites tracking ash clouds several times around the globe44. reduce lung capacity. Mt. has escalated over the past three decades. have been replaced by less allergenic substances50 (Evidence B). such as soy castor bean. hydrocarbons and allergens45.

beer. Drugs Some medications can exacerbate asthma. Respiratory viral infections are major causes of morbidity and mortality in asthma. the level of residual sulfite. Rhinitis. dried fruits. and polyposis. there is lack of specific antiviral strategies in the prevention or reduction of viral-triggered asthma exacerbations. Influenza Vaccination Patients with moderate-to-severe asthma should be advised to receive an influenza vaccination 59 . The role of other dietary substances—including the yellow dye tartrazine. Beta-blocker drugs administered orally or intraocularly may exacerbate bronchospasm (Evidence A) and close medical supervision is essential when these are used by patients with asthma56. and wine) have often been implicated in causing severe asthma exacerbations but the likelihood of a reaction is dependent on the nature of the food. Tarlo et al. and monosodium glutamate—in exacerbating asthma is probably minimal. Aspirin and other nonsteroidal anti-inflammatory drugs can cause severe exacerbations and should be avoided in patients with a history of reacting to these agents54.every year57 or at least when vaccination of the general population is advised. However. including those with difficultto-treat asthma60. shrimp. Food and Food Additives Food allergy as an exacerbating factor for asthma is uncommon and occurs primarily in young children. Patients with asthma are not more susceptible to upper respiratory tract rhinovirus infections than healthy people but suffer from more severe consequences of the lower respiratory tract infection. Chauhan et al. An impaired antiviral immunity to rhinovirus may lead to impaired viral clearance and hence prolonged symptoms. the form of residual sulfite and the mechanism of the sulfite-induced reaction53. Inactivated influenza vaccines are associated with few side effects and are safe to administer to asthmatic adults and children over the age of 3 years. found that participants exposed to high levels of NO2 in the week before the onset of virally induced exacerbation had worse symptom scores and lower peak flows than did participants exposed to low levels of NO2 before their virally induced exacerbations62. When food allergy is demonstrated. routine influenza vaccination of children58 and adults59 with asthma does not appear to protect them from asthma exacerbations or improve asthma control. Food avoidance should not be recommended until an allergy has been clearly demonstrated (usually by oral challenges)51. sinusitis. Infections Sulfites (common food and drug preservatives found in such foods as processed potatoes. confirmation of their relevance requires double-blind challenge before making specific dietary restrictions. the sensitivity of the patient. benzoate. Rhinovirus is the most common respiratory virus present in most patients hospitalized for life-threatening asthma and acute nonlife-threatening asthma.55. However. Studies have shown the association of air pollutants and virally induced exacerbations. food allergen avoidance can reduce asthma exacerbations52 (Evidence D). Recent epidemiologic studies suggest that viruses provoke asthma attacks by additive or synergistic interactions with allergen exposure or with air pollution. reported that asthma exacerbations with colds were associated with higher levels of sulfur dioxide and nitrogen oxides compared with exacerbations without colds61.

67.71 Intestinal Parasites. a constituent of the Gram-negative bacteria [outer membrane (lipopolysaccharide [LPS]. Inhaled LPS can exacerbate airway inflammation and airflow obstruction in allergic asthmatics. Bacterial Infections. Weight reduction in obese patients with asthma has been demonstrated to improve lung function. air pollution. Asthmatics should not avoid exercising. or remain unchanged during pregnancy73.116(1):3-14. RECOMMENDATION: Something related to diesel exhaust and LPG use Biomass fuel in rural areas Other Factors That May Exacerbate Asthma References Obesity. asthma may improve. Increases in body mass index (BMI) have been associated with increased prevalence of asthma. anger. and premenstrual exacerbations have been documented72. Infection or colonization of the airways with mycoplasma pneumonia and chlamydia pneumonia may potentiate asthma in some individuals. or fear) can lead to hyperventilation and hypocapnia.69. although the mechanisms behind this 1. Allergic subjects are more sensitive than nonallergic subjects to the bronchoconstrictive properties of inhaled LPS. Exercise. primarily because extreme emotional expressions (laughing. and health status65 (Evidence B). The lower incidence of asthma in rural subsistence societies has led to the postulate that high degrees of parasite infection might prevent asthma symptoms in atopic individuals. Results of studies are conflicting and any relation between intestinal parasite infection and asthma risk is likely to be species specific. A lack of exercise.association are unclear64. Many women complain that their asthma is worse at the time of menstruation. A randomised trial of vaccine efficacy in children and adults with asthma is needed. Gastroesophageal reflux can exacerbate asthma. and household dusts. which are rare but not exceptional in some patients with asthma. Parasite infections do not in general protect against asthma63. especially in children. Emotional stress may lead to asthma exacerbations.70. J Allergy Clin Immunol 2005. crying. but without pre-existing conditions. Panic attacks. also known as endotoxin) is present in high concentrations in organic dusts. A systematic review and meta-analysis of asthma and intestinal parasite infection found that current infection with Ascaris lumbricoides was associated with a significant increase in the risk of asthma. . worsen. There is very limited evidence to support the routine use of pneumococcal vaccine in people with asthma. However. results in less time being devoted to mechanical stretching of the airways and to promotion of good airway muscle tone through enhancement of an efficient smooth-muscle contractile process. symptoms. Emotional Stress. Menstruation and Pregnancy. it is important to note that asthma is not primarily a psychosomatic disorder. which can cause airway narrowing66. Primary prevention of asthma and allergy. Similarly. morbidity. and asthma sometimes improves when the reflux is corrected. have a similar effect68. 60 Arshad SH. In addition. Previous studies have shown that adults already suffering from asthma have a 200 percent higher chance of developing pneumonia due to bacterial infections than those exposed to the pathogen.

Confalonieri U. 27. Corden JM. N Engl J Med 2004. 19. Cambridge: Cambridge University Press:2007: pp 391-431. editors.120:610-7.55(12):1194-7. Ebi KL. Am J Clin Nutr 2001. Isolauri E. J Allergy Clim Immunol 2005. Global Strategy for Asthma Management and prevention. climate change. Arvilommi H. Friedman NJ. Parental smoking and allergic sensitisation in children. van der Linden PJ and Hanson CE. Mikawa H. 12. The role of breastfeeding in the development of allergies and asthma.317(7166)1105-10. the influence of maternal smoking and a genetic predisposition to asthma. 6.159(2):403-10. Fletcher ME. Salminem S. 15. Mimouni M. 24. Robinson DS. Martinez FD. Bush RK. 2007 update. 11. Johansen HK. Gotzsche PC. Taussig LM. 26. Is the global rise of asthma an early impact of anthropogenic climate change? Environ Health Perspect 2005. placebo-controlled trial: first results of ETAC. 4. BMJ 1998. House dust mite control measures in the management of asthma: meta-analysis. Halonen M. Cook DG.120:530-2. Durham SR. Burr ML. Human health. Probiotics: effects on immunity. Jones CA. Strachan DP. Thorax 1998. Gotzsche PC. Holberg CJ. Impaired airway function and wheezing in infancy. Wijk RG. 5.114(10):1389-97. Mimouni D. J Clin Invest 2004.68(3):233-6. Global Initiative for Asthma. Naspitz CK. Cochrane Database Syst Rev 2000. In: Parry ML. Pediatr Allergy Immunol 1998. Menne B. Johansen HK.CD001187. J Allergy Clin Immunol 2007. Epidemic asthma and the role of the fungal mold Alternaria alternate. Sole D. Baba M.351(11):1134-6. Hammarquist C. Schmidt LM. Indian J Chest Dis Allied Sci 2008. Shah A. The Group Health Medical Associates.317(7166):1105-10.2. Sheffer AL. 8. Akhtar R. Cochrane Database Syst Rev 2004(4). randomized. Yssel H.73(2 Suppl):444S-50S. Marks GB. Prevention of asthma by ketotifen in infants with atopic dermatitis. Sutas Y. 13. 14. et al. House dust mite control measures for asthma.53(2):117-23. Wright AL. Allergen avoidance in the treatment of asthma and rhinitis.332(3):133-8. Strachan DP. Is allergic asthma associated with delayed fetal maturation or the persistence of conserved fetal genes? Allergy 2000.113:915-9. Gotzsche PC. Zeiger RS. Burr M. N Engl J Med 1995. air pollution and allergic asthma. Gotzche PC. Bosquet J. Cochrane Database Syst Rev 2004(4):CD001187. 20. Contribution of Working Group II to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change. Stocks J. Kovats RS. Breast-feeding and the risk of bronchial asthma in childhood: a systematic review with meta-analysis of prospective studies. Morgan WJ. 1. Warner JO.2. Allergen avoidance to reduce asthma-related morbidity. J Allergy Clin Immunol 2007. Kankaanpaa P. Pulimood TB. Canziani OF. Holloway JA. Hammarquist C.139(2):261-6.9(3):116-24. Ann Allergy 1992.Bryden C. Hauengue M.50:259-61. Kramer MS. Larche M. The effectiveness of measures to change the indoor environment in the treatment of allergic rhinitis and 61 . Gdalevich M. Am J Respir Crit Care Med 1999. 7.115:1238-48. Tregs and allergic disease. Does atopic disease start in foetal life? Allergy 2000:55(1):2-10. Adaptation and Vulnerability. Platts-Mills TA. et al. Health effects of passive smoking. 21. Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind. Early Treatment of the Atopic Child. Talaricoficho S.52(10):905-14. Thorax 1997. Parental smoking and allergic sensitisation in children. 3. Palutikof JP. 18. Burr ML. Iikura Y. Custovic A. Climate Change 2007: Impacts. House dust mite control measure for asthma. Maternal antigen avoidance during pregnancy for preventing atopic disease in infants of women at high risk. Dundas I. It’s blowing in the wind: new insights into thunderstorm-related asthma. Nasser SM. N Engl J Med 2003. Health effects of passive smoking. 23. 5. Beggs PJ. Vignola AM. Sharples L. Cook DG. Bambrick HJ. 16. J Pediatr 2001. Burr M. 22.349(3):207-8. House dust mite control measures in the management of asthma: meta-analysis. Asthma and wheezing in the first six years of life. 9. 17. 10. Dezatuex C. Global warming. 25. BMJ 1998. Schmidt LM.

Influence of cigarette smoking on inhaled corticosteroid treatment in treatment of mild asthma. Housedust-mite allergen concentrations (der f 1) and mold spores in apartment bedrooms before and after installation of insulated 38. . McCullough J. Livingston E. Letley L. Thorax 2002. 62 windows and central heating systems. probable dispersal from human clothing. Cahudhuri R. 32. Domestic allergens in public places. 44. Woodcock A. Major grass pollen allergen Lol p1 binds to diesel exhaust particles: implications for asthma and air pollution. McMahon AD. Effect of ozone exposure on airway responses to inhaled allergen in asthmatic subjects. et al. Hogaboam CM. Colquhoun JR. cat.adrc. Dobson M. Enberg RN. 43. et al. Almqvist C.37:1267-85. Eggleston PA. asthma: ARIA update (in collaboration with GA(2)LEN. Eruption of Mount Pinatubo in the Philippines in June 2001. Gruchalla RS. Malmberg P. Am J Respir Crit Care Med 2003. Chapman MD. Forster L. Accessed from http://web. Tager IB. Wood RA. Leupold W. Wickman M. et al. Asian Disaster Reduction Center. Gencer M. 39. Egmar AC. Ownby DR. De Guzman E.168(11):1308-11. Saxon A. O’Connor GT. Morgan WJ. Crain EF. Evans R. Zehir I. Soriano JB.or. Adkinson NF. J Allergy Clin Immunol 2003. Hedren M. Chest 2004. Clin Exp Allergy 1997.55(1):79-83. et al. Wlech BS. Pickering CA. Nel AE. Johnson ND. Hiura T. Ubiquitous presence of cat allergen in cat-free buildings.27:246-51. Kerkmann ML.83(4):730-4. The effect of cat removal on allergen content in household-dust samples. Taggart SC.60(9):1112-5. Borland W. Hering M.56(6):468-71. Girgis ST.102:539-54. Allergy 2000. 40. Uzun K. Clin Exp Allergy 1996. Results of a home-based environmental intervention among urban children with asthma. Removal of cockroach allergen from inner-city homes. Rand C. 35. Thomson L. McSharry CP. Nielsen F. 34. Thunderstorm outflows preceding epidemics of asthma during spring and summer. Smith A. Sunyer J. Morell F.349(3):225-36.pdf Schroeder WH. Christian DL. Macleod KJ.125(6):2328-35.103(6):1012-7. J Allergy Clin Immunol 1989. 45. Little SA. Eggleston PA. Halken S. Control of exposure to mite allergen and allergenimpermeable bed covers for adults with asthma. Chen LL.28. Taylor P et al. 31. Long term outcome of soybean epidemic asthma after an allergen reduction intervention.106880. 30. JAPCA 1987. Eur Respir J 2006. Chen PH. Ng G.57(3):226-30. O’Driscoll BR. Chapman MD. 36. 47. N Engl J Med 2003.70(6):4714. Ozbay B. Ferrando RE. Roca J. Denning DW. Ann Allergy 1993. 33.jp/publications/recoveryrep orts/pdf/Pinatubo. Larsson PH. Peden DB. 42. Toxic trace elements associated with airborne particulate matter: a review.351(11). dog and cockroach allergens in the air in public buildings. Effect of mattress and pillow encasings on children with asthma and house dust mite allergy. et al.104(4 Pt 1):842-6. Wood RA. Thomson NC. School as a risk environment for children allergic to cats and a site for transfer of cat allergen to homes. Hansen LG. et al. Thorax 1999. Thomson NC. 37. Rodrigo MJ. Burkner K. Kattan M. Ceylan E. II: Dog (Can f1) and cockroach (Bla g 2) allergens in dust and mite. J Allergy Clin Immunol 1998. Hansen P. et al. Chalmers GW. Diaz-Sanchez D. Knox RB.27(3):615-26. Thomson LJ. Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system. The link between fungi and severe asthma: a summary of the evidence. Lukk P. Treloar AB. Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Niklassen U. 3rd. Hirsch D.111(1):169-76.26(11):1246-52. Prevalence of chronic bronchitisasthma symptoms in biomass fuel exposed female. N Engl J Med 2004. Martin J. Kane DM. Env Hlth Prev Med 2003. Nixon WJ. J Allergy Clin Immunol 1999. 46.54(8):670-4. Marks GB. Hiirsch T. Green R. Jr. Suphioglu C. Pedersen S. J Allergy Clin Immunol 1999. Allergy 2005. et al. 41. Shanie S. Bowyer P. Matthews E. Vickers M. Niven RM. Koski MH. Host A. Custovic A. 29.8(1):13G Anto JM. Thorax 2001.

Nizankowska E. Mustajoki P. Bernsen RM. Lack G.108:52-8. Am J Respir Crit Care Med 2004. Thorax 2003. Ayres J. Costelo J. 68. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Nguyen-Van-Tam JS. BMJ 2000. McCann DC.58(12):1036-41.320(7238):827-32. Weiss ST. Systematic review and meta. Food allergy. Cates CJ. van Beest I. Poussa T. Isenberg S. Margolis HG. Bochenek G. Occup Environ Med 2005. Roberts G. Sensitivity to sulfited foods among sulfite-sensitive subjects with asthma. 70. Rietveld S. David Pritchard.Bee. Guzzo MR. J Allergy Clin Immunol 2001. Ahmed AH. 62. Ahola S. Chan-Yeung M.Analysis. Labbe R. Tantisira KJ. and management of occupational asthma. Levi-Schaffer F.328:434-41 56.48. Rimmelzwaan GF. Litonjua AA. Linaker CH. Berhane K. Cullinan P. et al. Habibi P. Chauhan AJ.30(1):5-21.174: 514-23. Paton JY. 63. Jefferson TO. Lancet. Nouwen A. Holgate ST. Lehrer PM. Allergy 1997. Freeston MH. Psychol Med 1999. Ylikahri M.117(2 Suppl Mini-Primer):S470-5. Okada M. Immunol Allergy Clin North Am 2005. Lancet 2000. Boulet LP. Jenkins C. Stenius-Aarniala B. 64. Mejza F. et al. 65. Richter JE. Patel N. C. association of body mass with pulmonary function in the Childhood Asthma Management Program (CAMP). Harding SM. 51. Tarlo S. Vaccines for preventing influenza in people with asthma. 57. 67. Gauderman WJ. Safety of a specific COX-2 inhibitor in aspirin-induced asthma. London SJ. Thomas DC et al. Bush RK. Smith S. McGuinness D. Bara AI.81(6):1159-67. Covar RA. Nagraba K. McConnell R. Burge PS. Beuving HJ. 53. and the Parasites in Asthma Collaboration. 58. J Asthma 1993. et al. Environ Health Perspect 1998. Manfreda J. Sicherer SH.25(1):169-90. Holden K. Psychological factors associated with emergency room visits among asthmatic patients. Air pollution and bronchitis symptoms in southern California children with asthma. Selner JC. John Britton. Influenza vaccination in children with asthma: randomized doubleblind placebo-controlled trial. BMJ 2004. Clin Exp Allergy 2001. Stressinduced breathlessness in asthma.345(21):1529-36. The role of acute and chronic stress in asthma attacks in children.62(5):290-9. de Jongste JC. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. Sampson HA. 59. Becker A. 60. van Suijlekorn-Smit LW. Leese J. Fuhlbrigge AL. Evidence based guidelines for the prevention. 63 . Taylor SL. Rowe BH. 2003. Am J Respir Crit Care Med 2006. 66. identification. et al. Cochrane Database Syst Rev 2004(2):CD000364. J Allergy Clin Immunol 2003. Corey P.31(2):219-25.351(9099)326-31. Inskip HM. N Engl J Med 2001. Peden DB. Food allergy as a risk factor for life-threatening asthma in childhood: a casecontrolled study. Avol E. 55. Immediate and long term effects of weight reduction in obese people with asthma: randomized controlled study. Osterhaus AD. Asthma and emotion: a review. Szefler SJ. Swiercrzynska M. 52. 54. Schreiber J. 9. Nicholson PJ. Jo Leonardi.23(2):217-33. Vora H. Ferguson A. Nicholson KG. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. Weiner MB. Everaerd W. Gilliland F. Szczeklik A. Hilary CR.29(6):1359-66. The safety of inactivated influenza vaccine in adults and children with asthma.169(4):488-93. 50. J Allergy Clin Immunol 1988. Taylor AJ. Johnston SL. Sandberg S.356(9234):982-7. J Clin Allergy Immunol 2006. Macomber BA. Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children. Wiselka MJ. Hodge L. Hochron SM. 61. Asthma and current Intestinal Parasite Infection.107(9):1-9. Lurmann F.52(suppl 38):37-44. 49. Medications as asthma triggers.112(1):168-74. Mechanics of pollution-induced airway disease: in vivo studies.361:1939-44. 69. Lancet 1998. Behav Modif 1999. Rogers. Boyle C. Kvamstrom J. Broder I. Nordlee JA. Gronlund EL. The role of symptomatic colds in asthma exacerbations: influence of outdoor allergens and air pollutants.

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Treat and Monitor Asthma .Chapter 6 Assess.

the National Asthma Epidemiology study (NAES). Out-of-pocket settlement is by far the prevalent mode of health care payment in the country. only about 10% of adult respondents had an action plan and about half of the patients still used maintenance oral bronchodilators. reliever medication should be provided for quick relief of symptoms as needed. probably because days to weeks are needed for asthma control to be felt. 66 . Lung. Seventy-five percent (75%) admitted to discontinuing their asthma medications when their symptoms had resolved for a week. A local survey. International guidelines agree that the goal of asthma treatment is to achieve and maintain clinical control. As the above studies have shown. treating to achieve and monitoring to maintain control should be adopted. In the Philippines. patients should be assessed according to their level of control. treatment can be stepped down. When control is maintained for at least three months. Indeed.2 A different survey. Treatment should be adjusted in a continuous cycle. the Asthma Insights and Reality in Asia-Pacific study. can be reached in a majority of patients with a pharmacologic intervention strategy developed in partnership between the patient/family and the doctor. Subsequently. If asthma is not controlled on the current regimen. When this is not achieved. Ongoing monitoring is essential to maintain control and to establish the lowest step and dose of treatment to minimize cost and maximize safety. loss of lung function and drug-related adverse events. adherence to drug therapies that take time to manifest symptomatic improvement is low. The US National Heart. Aiming at achieving this goal cannot be overemphasized in the local population. treatment adjustment should also follow the level of control. reported that only less than 10% of Filipino asthmatics admitted to current use of inhaled steroids.1 GINA 2008 states that this goal can be achieved with a pharmacologic intervention strategy developed in partnership between the patient/family and the doctor. showed that while a majority of selfreported Filipino asthmatics living in urban areas had consulted a physician for the disorder. patients will usually seek consultation with a different doctor who can prescribe quick-relief medications. the majority of asthmatics consult only when symptoms become bothersome. with patients directly paying for their medical consultations. drug therapy should be stepped up until control is achieved.INTRODUCTION KEY POINTS: The goal of asthma treatment. the NAES survey2 reported that the use of inhaled steroids alone as controllers among definite asthmatics is rather unpopular (1%). lowdoses of a fixed-dose combination steroidLABA inhaler may be started as initial treatment for symptomatic patients.3 For patients already on controller medications. Inhaled steroids are the recommended first line controllers. hospitalization and medications. The PCRDMA 2004 recommends the use of the severity classification of asthma at the initial medical consultation and for patients who are not on any controller medication (‛controller-naïve‛ patients) or are nonadherent to previously prescribed controller medications. Local practice also reveals that there is demand for rapid improvement for every peso paid. even if about 40% had persistent symptoms. and Blood institute’s 2007 National Asthma Education Program Expert Panel Report 3 further expands the therapeutic targets to aim at reducing impairment and reducing risk of recurrent exacerbations. At each step. The GINA ‚5-step‛ treatment strategy to assessing. Thus. to achieve and maintain clinical control.

and the patient’s satisfaction with the level of control achieved. whether their asthma is controlled. the regular use of reliever medication is one of the elements defining uncontrolled asthma and is an indicator of the need to increase controller treatment. (See Figure 6. is recommended for local adaptation. Uncontrolled asthma may lead to an exacerbation. If asthma is not controlled on the current treatment regimen. Each step represents treatment options that. The panel is thus recommending the adaptation of a more aggressive approach in initiating chronic maintenance therapy. hopefully as a means of enhancing long term compliance.2. The GINA ‚5-treatment steps‛ cyclic strategy to assessing. This involves a detailed accounting of their current treatment regimen and adherence to it and appraisal of daytime and nighttime symptoms. Steps 1 to 5 provide options of increasing efficacy. ASSESSING ASTHMA CONTROL The PCRDMA 2004 severity classification of asthma (Table 2.2. If control has been maintained for at least three months. treating to achieve and monitoring to maintain control should still be adopted. Treatment is then modified continuously as the asthma control status changes.1.. are alternatives for controlling asthma. a patient is assigned an appropriate step. (See Table 2. Subsequently. depending on his current level of control. have extremely favorable therapeutic ratios. an increase in treatment should be considered.) TREATING TO ACHIEVE CONTROL The GINA long-term management approach based on asthma control.2.In the development of the current consensus guidelines. either shortacting or long-acting) should be provided for quick relief of symptoms.. If asthma is partly controlled. in order to regain asthma control. when compared with medications used for other chronic diseases.1) is recommended at the initial medical consultation and for patients who are not on any controller medication (‛controllernaïve‛ patients) or are non-adherent to previously prescribed maintenance medications. a reliever medication (rapid-onset bronchodilator. At each treatment step. (See Table 2.g. subject to whether more effective options are available (e. reducing or eliminating the need for reliever treatment is both an important goal and a measure of the success of therapy. increased dose or an additional treatment). Management recommendation for exacerbations can be found in Chapter 7.2 and Figure 6. The Five-Step Treatment Strategy for Achieving Control Most of the medications available for asthma patients. The treatment action plan that will be prescribed during each consultation will be determined by a patient’s assessed current level of control and his or her current medications. Thus.) At each consultation. the need for rescue medication use and level of lung function. all patients should be assessed according to their level of asthma control (i. limitation of activities due to asthma.) Any adverse event related to drugs taken must also be elicited. addressing the patients’ need for early perception of relief. safety and cost of possible treatment options. as shown in Figure 6. treatment can be stepped down with the aim of establishing the lowest step and dose of treatment that maintains control (see Monitoring to Maintain Control below). Its recognition and prompt treatment is mandatory. except for Step 5 where issues of availability and safety influence the selection of treatment. the expert panel thoughtfully considered the aforementioned insights and ‘realities’ of the Filipino patients’ attitude and practices when dealing with their asthma. partly controlled or uncontrolled). although not of identical efficacy. drug therapy should be stepped up until control is achieved. but with local modifications. 67 . However.e.

Between episodes. appropriate particularly for patients who are unable or unwilling to use inhaled glucocorticosteroids. Step 1: As-needed reliever medication. Step 1 treatment with an as-needed reliever medication is reserved for patients who are assessed to have asthma of intermittent severity or untreated patients with occasional daytime symptoms (cough. or who experience intolerable side effects such as persistent hoarseness from inhaled glucocorticosteroid treatment and those with concomitant allergic rhinitis (Evidence C). A leukotriene modifier is an alternative (Evidence A). For those patients who still experience exerciseinduced bronchoconstriction despite otherwise well-controlled asthma. In addition to stepping up of treatment with maintenance controller medications. a rapid-acting inhaled ß2-agonist (short. and stepping up controller therapy generally results in the reduction of exercise-related symptoms. taken prior to exercise or to relieve symptoms that develop after exercise. When symptoms are more frequent. is recommended.5 ” 1 mg/kg/day may be considered in very symptomatic patients. or short-acting theophylline may be considered as alternatives. dyspnea occurring twice or less per week) of short duration. patients should be prescribed regular controller treatment (see Steps 2 or higher) in addition to as-needed reliever medication (Evidence B). However. Symptomatic patients who are controller-naive or were non-adherent to previously prescribed therapy and have mild-to-moderate persistent asthma can start their treatment at Step 3. and/or worsen periodically. to prevent worsening and to achieve more rapid resolution of the uncontrolled asthma. and for those in whom In the local setting where cost and availability are main considerations. the consensus is to start at step 3. For the majority of patients in Step 1. in the local setting. and for some it is the only cause. This will ensure not only rapid relief of symptoms but also control of the underlying inflammation. Once control is achieved.4 68 . However. although they have a slower onset of action and higher risk of side effects (Evidence A). short-acting oral 2-agonist. Training and sufficient warm-up also reduce the incidence and severity of exercise-induced bronchoconstriction (Evidence B). This may also promote adherence to maintenance therapy (Evidence D). for the majority of symptomatic patients. the patient is asymptomatic with normal lung function and has no nocturnal awakening. wheeze. which at low daily doses (to achieve a plasma concentration of ~5mg/ml) has been found to exert anti-inflammatory action with fewer side effects compared to higher doses. Step 2: Single controller plus a reliever medication. All patients with persistent asthma should be assessed within treatment steps 2 through 5. such as sustained-release theophylline. a trial of a 5-to-10 day course of an oral steroid given at 0. treatment can be brought down to step 2. with low doses of a fixed-dose steroidLABA combination inhaler. At Step 2. Alternative controller medications include leukotriene modifiers (Evidence A). Physical activity is an important cause of asthma symptoms for most asthma patients. These patients must receive at least one regular controller and an as-needed reliever medication to achieve and maintain control. exerciseinduced bronchoconstriction often indicates that the patient's asthma is not well controlled. a low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for asthma patients of all ages (Evidence A). cheaper oral controller medications may also be alternative options.exercise-induced bronchoconstriction is the only manifestation of asthma. An inhaled anticholinergic. a rapidacting inhaled ß2-agonist is the recommended reliever treatment (Evidence A). Exercise-induced bronchoconstriction.or long-acting).

A study which sought to compare the adherence and effectiveness of LABAs and ICS administered either concurrently or in combination demonstrated that those patients The preferred treatment at Step 4 is to combine a medium. Step 4: More than two controllers plus reliever medication. this approach may encourage the increased use of inhaled steroids in the country (Evidence D). Step 3: Two controllers plus a reliever medication.14 If a combination inhaler containing formoterol and budesonide is selected. reduce oropharyngeal side effects.or high-dose ICS with LABA. This approach has been shown to result in reductions in exacerbations and improvements in asthma control in adults and adolescents at relatively low doses of treatment (Evidence A). al. the increase from a medium. and reduce systemic absorption (Evidence A). physicians and patients should be aware that side effects may be present over time. For patients on medium. Where possible. The use of inhaled long acting 2-agonists as the single first-line controller in asthma is strongly discouraged. However. use of a spacer device is recommended to improve delivery to the airways. Low doses of fixed-dose steroid-LABA combination inhalers are recommended as firstline controller in symptomatic patients with persistent asthma. the authors concluded that in developing countries where inhaled steroids are not widely available and there is no alternative to oral steroids. even at a daily low dose of 5 mg/day. the low-dose steroid is usually sufficient.to a high-dose of ICS provides relatively little additional benefit (Evidence A). upon evidence of their relative efficacy in clinical trials. it may be used for both rescue and maintenance.Maintenance low dose oral steroids have been used in developing countries as replacement for inhaled steroids or in addition to low dose inhaled steroid to control asthma and limit costs. A meta-analysis by Mash et. However. However. As noted previously. At Step 3. the order in which additional medications should be added is based. and need only be increased if control is not achieved with this regimen (Evidence A). The authors concluded that combination therapy might be preferable for patients with low adherence to controller therapy. compared inhaled versus low dose oral steroids in asthmatics over the age of 15 years and found that such trials were small and no data could be pooled. The high dose is recommended only on a trial 69 . the lowest effective dose (prednisolone 7. Whether this approach can be employed with other combinations of controller and reliever requires further study.5 Nevertheless.5-12 mg/day. which appears to be as effective as 300-2000 g/day ICS). Because of the additive effect of this combination. Studies and meta-analyses have reported increased risk for asthma-related complications with the use of LABAs.6-12 All current guidelines recommend that inhaled LABAs should only be used in combination with inhaled steroids. prompting a US FDA review.or high-dose of inhaled glucocorticosteroid delivered by a pressurized metered-dose inhaler. 13 Another option at Step 3 is to combine a lowdose ICS with leukotriene modifiers (Evidence A) or low-dose sustained-release theophylline (Evidence B). using the medications in combination were 17% less likely to stop their medication and were also 17% less likely to have a moderate-to-severe asthma exacerbation than the latter. patients who are not controlled on Step 3 treatments should be referred to a pulmonary specialist with expertise in the management of asthma for investigation of alternative diagnoses and/or causes of difficultto-treat asthma. Few studies have looked at the efficacy and safety of such strategies. The selection of treatment at Step 4 depends on prior selections at Steps 2 and 3. in most patients. may be prescribed. either in a combination inhaler device or as separate components (Evidence A). the recommended option for adolescents and adults is to use a low-dose inhaled steroid with an inhaled long-acting 2-agonist. as far as possible.

which minimizes the cost and maximizes the safety of treatment. After an exacerbation. Typically. in all patients the minimum controlling dose of treatment must be sought through a process of regular follow-up and staged dose reductions. patients are seen one to three months after the initial visit. follow-up should be offered within two weeks to one month (Evidence D). At medium. MONITORING TO MAINTAIN CONTROL When asthma control has been achieved. but the full benefit may only be evident after 3 or 4 months. efficacy may be improved with more frequent dosing (four times daily) (Evidence B). Leukotriene modifiers as add-on treatment to medium-to high-dose ICS have been shown to provide benefit (Evidence A). Prolonged use of high-dose ICS is also associated with increased potential for adverse effects. and the patient’s training and confidence in playing a role in the ongoing control of his or her asthma.or high-dose ICS-LABA may also provide benefit (Evidence B). and every three months thereafter. but may reflect the reversal of some of the consequences of long-term inflammation of the airways. With budesonide..g.dose of treatment necessary. and treatment has to be adjusted periodically in response to loss of control as indicated by worsening symptoms or the development of an exacerbation. asthma is a variable disease. Patients should be counseled about potential side effects and all other alternative treatments must be considered. improvement begins within days of initiating treatment.2 or a validated composite measure of control. Step 5: Reliever medication plus additional controller options. this can take even longer. The frequency of health care visits and assessments depends upon the patient’s initial clinical severity. On the other hand. when control has not been achieved on combinations of other drugs including high-doses of inhaled or oral glucocorticosteroids (Evidence A). leukotriene modifiers or sustained-release theophylline) (Evidence B). basis for 3 to 6 months when control cannot be achieved with medium dose ICS”LABA and/or a third controller (e. Duration and Adjustments to Treatment For most classes of controller medications. The addition of a low-dose of sustained release Theophylline to medium. Higher doses of anti-inflammatory medication may be required to achieve this benefit than to maintain it. In severe and chronically undertreated disease. The reduced need for medication once control is achieved is not fully understood. The addition of anti-IgE treatment to other controller medications has been shown to be effective in allergic asthma.and high-doses. Its major drawback is its cost. but usually less than that achieved with the addition of a LABA (Evidence A). twice-daily dosing is necessary for most but not all inhaled glucocorticosteroids (Evidence A). ongoing monitoring is essential to maintain control and to establish the lowest step and 70 . asthma may go into remission particularly in children aged 5 years and younger and during puberty. Rarely. Alternatively. Whatever the explanation. the reduced need for medication might simply represent spontaneous improvement as part of the cyclical natural history of asthma. Asthma control should be monitored by the health care professional and preferably also by the patient at regular intervals. using either a simplified scheme as presented in Table 2. The addition of oral glucocorticosteroids to other controller medications may be effective (Evidence D) but is associated with severe side effects (Evidence A) and should only be considered if the patient’s asthma remains severely uncontrolled on Step 4 medications with daily limitation of activities and frequent exacerbations.

Repeated dosing with bronchodilators in this class provides temporary relief until the cause of the worsening symptoms passes. The need for repeated doses over more than one or two days signals the need for review and possible increase of controller therapy. in most patients’ treatment may be switched to oncedaily dosing (Evidence A). the dose of inhaled steroid should be reduced by 50% until a low-dose is reached.g. 71 . as described above (Evidence D).“ When asthma is controlled with inhaled glucocorticosteroids in combination with controllers other than long-acting 2agonists. “ Inhaled glucocorticosteroids. a 50% reduction in dose should be attempted at 3month intervals (Evidence B). at which time. However. some recommendations can be made based on the current evidence: Treatment has to be adjusted periodically in response to worsening control. “ When inhaled glucocorticosteroids alone in medium to high-doses are being used. formoterol) for combined relief and control. Controller treatment may be stopped if the patient’s asthma remains controlled on the lowest dose of controller and no recurrence of symptoms occurs for one year (Evidence D). Temporarily doubling the dose of inhaled glucocorticosteroids has not been demonstrated to be effective. then the combination treatment can be stopped. short-acting or long-acting 2agonist bronchodilators. the LABA may be stopped (Evidence D). A second alternative is to discontinue the long-acting 2agonist at an earlier stage and substitute the combination treatment with inhaled glucocorticosteroid monotherapy at the same dose contained in the combination inhaler. the preferred approach is to begin by reducing the dose of inhaled steroid by approximately 50% while continuing the inhaled LABA (Evidence B). which may be recognized by the minor recurrence or worsening of symptoms. The higher dose should be maintained for seven to fourteen days but more research is needed in both adults and children to standardize the approach. Treatment options are as follows: “ Rapid-onset. If control is maintained. with full discussion of potential consequences including reappearance of symptoms and increased risk of exacerbations. Combination of inhaled glucocorticosteroids and rapid and long-acting 2-agonist bronchodilator (e. and is no longer recommended (Evidence A). “ When asthma is controlled with a combination of inhaled glucocorticosteroid and longacting 2-agonist. and magnitude of treatment reductions in asthma. sequence. These changes should ideally be made by agreement between patient and health care professional. and the approach will differ from patient to patient depending on the combination of medications and the doses that were needed to achieve control. Stepping Up Treatment in Response to Loss of Control Although further research on stepping down asthma treatment is needed. An alternative is to switch the combination treatment to once-daily dosing. for some patients these alternative approaches lead to loss of asthma control (Evidence B). A four-fold or greater increase has been demonstrated to be equivalent to a short course of oral glucocorticosteroids in adult patients with an acute deterioration (Evidence A). further reductions in the inhaled steroid should be attempted until a lowdose is reached. Stepping Down Treatment When Asthma Is Controlled There is little experimental data on the optimal timing. “ Where control is achieved at a low-dose of inhaled glucocorticosteroids alone.

a high-dose of 2-agonist and a burst of systemic glucocorticosteroids administered orally or intravenously.) Following treatment for an exacerbation of asthma. (Refer to Chapter 7 for more information.1 Algorithmic Approach to Asthma Assessment and Management 72 . Patients who do not reach an acceptable level of control at Step 4 can be The usual treatment for an acute exacerbation is Figure 6. provided inhaler technique has been checked. the alternative approaches described in this section should be used for patients on other controller therapies. some patients will not do so even with the best therapy. Difficult-to-Treat Asthma Although the majority of asthma patients can obtain the targeted level of control. The benefit in preventing exacerbations appears to be the consequence of early intervention at a very early stage of a threatened exacerbation since studies involving doubling or quadrupling doses of combination treatment once deterioration is established (for 2 or more days) show some benefit but results are inconsistent. other than budesonide/formoterol. Because there are no studies using this approach with other combinations of controller and relievers. In this case.The use of the combination of a rapid and longacting 2-agonist (formoterol) and an inhaled glucocorticosteroid (budesonide) in a single inhaler both as a controller and reliever is effective in maintaining a high level of asthma control and reduces exacerbations requiring systemic glucocorticosteroids and hospitalization (Evidence A). maintenance treatment can generally be resumed at previous levels unless the exacerbation was associated with a gradual loss of control suggesting chronic undertreatment. a step-wise increase in treatment (either in dose or number of controllers) is indicated.

Regular dosing with short and long-acting β2-agonist is not advised unless accompanied by regular use of an inhaled glucocorticosteroid. Figure 6. and shortacting theophylline. However. Instead. some long-acting β2-agonists. and require higher doses of inhaled glucocorticosteroids than are routinely used in patients whose asthma is easy to control. In particular.2. these medications remain a mainstay of therapy for difficult-to-treat asthma. the presence of COPD must be excluded. Investigate and confirm compliance with treatment. Vocal cord dysfunction must be considered. 73 . These patients may have an element of poor glucocorticosteroid responsiveness. Incorrect or inadequate use of medications remains the most common reason for failure to achieve control. while additional diagnostic and generalized therapeutic options can and should also be considered: considered to have difficult-to-treat asthma. adapted from GINA 2008 Alternative reliever treatments include inhaled anticholinergics. dose optimization should be pursued by stepping down to a dose that maintains the maximal level of control achieved on the higher dose. Because very few patients Confirm the diagnosis of asthma. short-acting oral β2-agonists.are completely resistant to glucocorticosteroids. Management Approach Based on Level of Control. there is currently no evidence to support continuing these high doses of inhaled glucocorticosteroids beyond 6 months in the hope of achieving better control.

National Asthma Epidemiology Study. Cochrane Database Syst Rev 2001. David-Wang AS. http://www. In such patients. Weiss ST. 4. BMJ 2005. Am J Respir Crit Care Med 2003.nih. 1. frequent use of rescue medication is accepted. et al. Inhaled versus oral steroids for adults with chronic asthma. Cebu. The objective is then to minimize exacerbations and need for emergency medical interventions while achieving as high a level of clinical control with as little disruption of activities and as Although lower levels of control are generally associated with an increased risk of exacerbations. Bheekie A. 6. Danish A.1:CD002160. and daily symptoms have frequent exacerbations. Prevalence survey of asthma in Filipino adults living in urban communities (Metro Manila. Asthma control in the Asia-Pacific region: the Asthma Insights and Reality in Asia-Pacific Study. Bleecker ER et al. and this is only partly attributable to the presence of fixed airflow obstruction. Greenstone IR.nhlbi. current or past. Chronic sinusitis. Reductions should be made cautiously and slowly at intervals not more frequent than 3 to 6 months. J Allergy Clin Immunol 2003. the ability to improve asthma control by doing so remains unconfirmed.11(2)263-8. 7. Diaz DV. Psychological and psychiatric disorders should also be considered. 3. current smoking reduces the effectiveness of inhaled and oral glucocorticosteroids. Consider smoking.htm Roa CC. Bronchodilator treatment and deaths from asthma: case-control study. If found. Kim YY et al.few daily symptoms as possible. Davao). gastroesophageal reflux. Report submitted to the Department of Health and World Health Organization . these comorbidities should be addressed and treated as appropriate. as carryover of the effects of the higher dose may last for several months and make itdifficult to assess the impact of the dose reduction (Evidence D). Patients categorized as allergic might benefit from anti-IgE therapy. Long acting  2-agonists versus placebo in addition to inhaled corticosteroids in children . aspirin sensitive. Investigate the presence of co-morbidities that may aggravate asthma. Jones P.gov/guidelines/asthma/a sthgdln. as is a degree of chronic lung function impairment. nevertheless.330:117-23. Ayres JG. et al. and/or eosinophilic asthma. References 5.167:813-8. and obesity/obstructive sleep apnea have been reported in higher percentages in patients with difficult-to-treat asthma. de Guia TS. January 2004. and encourage complete cessation. Counseling and smoking cessation programs should be offered to all asthma patients who smoke. Nelson HS. Barnes PJ. In addition. A history of past tobacco smoking is associated with a reduced likelihood of complete asthma control. and leukotriene modifiers can be helpful for patients determined to be aspirin sensitive (who are often eosinophilic as well). Sturdy PM. a compromise level of control may need to be accepted and discussed with the patient to avoid futile over-treatment (with its attendant cost and potential for adverse effects). Theophylline: New perspectives for an old drug. 2. Ni Chroinin M. 74 Mash BRK. 8. Anderson HR.129:15-26. the lowest level of treatment that retains the benefits achieved at the higher doses of treatment should be employed. et al. Referral to a physician with an interest in and/or special focus on asthma may be helpful and patients may benefit from phenotyping into categories such as allergic. Lai CK. When these reasons for lack of treatment response have been considered and addressed. For these difficult-to-treat patients. Chest 2006. not all patients with chronically impaired lung function. reduced activity levels. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol.

and effectiveness of combination therapy among adult patients with asthma. Sears MR. and adults with chronic asthma. 12. Persistence. Postgrad Med J 2008. Salpeter EE. Ottosson A.33:21-32. Suissa S.9. Eur Respir J 2009. Harwood M. Safety of long-acting b-agonists: urgent need to clear the air remains. Ornistorn TM. Eur Respir J 2008. Radner F. 11.medpagetoday.144:904-12.118:574-81. J Allergy Clin Immunol 2006. Perrin K. et al. Wijesinghe M. Marceau C. 14. et al. adherence. Buckley NS. Salpeter SR. 75 .com/Pulmonary/A sthma/12117 Beasley R. The risk of asthma mortality with long-acting inhaled beta-agonists.33:3-5. Cochrane Database Syst Rev 2005. 10. Berbiche D. http://www. Ann Intern Med 2006. Lemiere C. Meta-analysis: effect of longacting  -agonists on severe asthma exacerbations and asthma-related deaths. Martinez FD. USFDA. Hackshaw A. 13.84:467-72.4:CD005535. al. et. Long-acting b-agonists: a review of formoterol safety data from asthma clinical trials.

76 .

Chapter 7 Acute Exacerbations .

wheezing.o KEY POINTS: Asthma exacerbations (“asthma attacks”) are acute or subacute episodes of progressive worsening of shortness of breath. Patients at high risk of asthma-related death also require closer attention. Recognition of early signs of worsening asthma and taking prompt action (Evidence A). and increasing use of reliever medications can be managed at home or in a community setting.1 Patient education. Exacerbations are characterized by significant decreases in PEF or FEV1 which are more reliable indicators of severity of airflow obstruction than degree of symptoms. A peak flow-based plan may be particularly useful for patients who have difficulty perceiving airflow obstruction and worsening asthma (Evidence D). relieve airway obstruction and hypoxemia as soon as possible and prevent future relapses. 1 Severity of exacerbations may range from mild to life-threatening deterioration usually progresses over hours or days. including a written asthma action plan to guide patient self-management of exacerbations at home. or chest tightness or some combination of these symptoms.1. Removal or withdrawal of the environmental factor contributing to the exacerbation. Early treatment of asthma exacerbations is the best strategy for management. INTRODUCTION Severe exacerbations are potentially life threatening and their treatment requires close supervision.1 Severity of exacerbations should be evaluated using clinical as well as objective measurements of lung function (PEF or FEV1).1 o o Aims of treatment are to restore lung function to normal.1 Exacerbations of asthma (“asthma attacks”) are episodes of progressive worsening of shortness of breath. cough.1 The primary therapies for exacerbations include repetitive administration of inhaled 2-agonists. cough. 3 Patients with milder exacerbations characterized by a reduction in peak flow of less than 20% nocturnal awakening. Most patients with severe asthma exacerbations should be treated in an acute care facility setting (clinic or hospital emergency room). and oxygen supplementation. early introduction of systemic steroids. wheezing or chest tightness or some combination of these symptoms. inadequate action at the onset of exacerbation and under-treatment of the exacerbation. especially for patients who have moderate or severe persistent asthma and any patient who has a history of severe exacerbations (Evidence B). but may occasionally happen precipitously over some minutes. Morbidity and mortality are most often associated with underassessment of exacerbation’s severity. Important elements of early treatment at the patient’s home include (EPR-2 199726): Treatment of exacerbations depends on the patient and the physician’s experience with what 78 . Respiratory distress is common.

11 Full recovery from asthma exacerbations is usually gradual. Patients at high risk of asthma-related deaths require intensive patient education. The severity of exacerbation determines the treatment required. The presence of several parameters. Tables 7. In addition to symptoms and physical signs which are not accurate indicators of airflow obstruction. Rodrigo et al 2004 Weber et al 2002).1 and 7.12. FEV1 or PEF appears to be more useful in adults for categorizing the severity of the exacerbation and the response to treatment and in predicting the need for hospitalization. Decision to admit or discharge can be recommended based on these lung function values. or if the patient is at high risk from asthma-related death historically.21. pulse rate. The primary therapy in the ideal situation includes the repetitive administration of inhaledβ2-agonist and an early introduction of systemic steroids and oxygen 1. especially those with more than one canister monthly6 Psychiatric disease or psychosocial problems.10. Treatment should continue until measurements of lung function return to normal or to the patient’s previous personal best.1 *Serial measurements of lung function.14. Any deterioration requires prompt intervention.therapies are most effective for the particular patient. A more severe grading should be given if the patient has no or minimal response to initial treatment. Likewise.2 *Signs and symptoms scores Some multifaceted prediction models have been tested and shown to improve slightly on the accuracy of the FEV1 or PEF alone 10. or are unable to perform lung function measures. Pulse oximetry is indicated for patients who are in severe distress.2 provide a guide to the severity of an exacerbation of asthma at the time the examination is made. McCarren et al 2000.8.1 ASSESSMENT OF SEVERITY The aims of treatment are to126: Relieve airway obstruction as quickly as possible Relieve hypoxemia Restore lung function to normal as early as possible Plan and avoidance of future relapses Develop a written action plan in cases of future exacerbations. response to treatment should be assessed clinically as well as objectively by lung function (PEF or FEV1). Kelly et al 2004.13. but not necessarily all. close monitoring and prompt care. and respiratory rate. particularly PEFR.3 supplementation. It may take many days for lung function to return to normal and weeks for airway hyperresponsiveness to decrease. and pulse oximetry should be monitored during treatment.7. Repeated FEV1 or PEF measures to the Emergency room (ER) and 1 hour after treatment were the strongest single predictor of hospitalization among adults who present to the ER with an asthma exacerbation (Karass et al 2000. if the attack progressed quickly.9. Kelly and colleagues 7 used multiple signs and symptoms to determine the level of the severity of the exacerbation at 1 hour after the first ER 79 . indicates the general classification of the exacerbation. These include patients with a history of any of the following1.126: Current use of or recent withdrawal from systemic corticosteroids Emergency care visit for asthma in the past year History of near-fatal asthma requiring intubation or mechanical intubation4 Not currently using inhaled glucocorticoids5 Overdependence on rapid acting inhaled b2 agonists. PEF monitoring should be performed. including the use of sedatives Noncompliance with asthma medication plan Indices of severity. have FEV1 or PEF <40% of predicted.

defined by a reduction in peak flow of less than 20%. and increased use of short acting β2-agonists can usually be treated in a community setting. home avoids treatment delays. prevents exacerbations from becoming severe. General guidelines for managing exacerbations at home are presented in Figure 7-12. It is recommended2 that the preparation of patients for home management of asthma exacerbations should include the following: Teach all patients how to monitor signs and symptoms so they can recognize early signs of deterioration and take appropriate action (Evidence A) particularly since many HOME MANAGEMENT OF ACUTE EXACERBATION Milder exacerbations. The degree of care provided in the home depends on the patients’ abilities and experience and on the availability of emergency care. the presence of drowsiness in a patient is a useful predictor of impending respiratory failure and reason to consider immediate transfer of the patient to a facility equipped to deal with ventilatory support (Cham et al 2002)15. nocturnal awakening. and also adds to patients’ sense of control over their asthma.Table 7-1. Classifying Severity of Asthma Exacerbations in the Urgent or Emergency Care Setting treatment as well as the duration of symptoms (either <6 hours or ≥6 hours) before the patient’s arrival at the ER (Kelly et al. 2002b)13 and found the additional measures improved the prediction rate by 5–10 percent. For EDs that have limited resources.1 Beginning treatment at 80 .

Table 7-2. Formal Evaluation of Asthma Exacerbation Severity in the Urgent or Emergency Care Setting 81 .

peak flow meter) for treating exacerbations at home (Evidence A). When using PEF expressed only as a percent of personal best. Recommendations for pharmacologic therapy for home management of exacerbations: 82 . 19. Initiate oral systemic corticosteroid treatment under certain circumstances (Evidence A).fatal asthma exacerbations occur out of hospital16. Patients should be taught how to adjust their medications early in an exacerbation13 and when to call for further help or seek medical care. in a person whose personal best is only 160 L/min. including self-adjustment of medications in response to acute symptoms or changes in PEF measures in the event of an exacerbation. Short courses or “bursts” of oral corticosteroids reduce the duration and may prevent hospitalizations and relapse following an acute exacerbation 14. other tools may be required.. Mild exacerbations respond to 2 to 4 puffs every 3 to 4 hours. especially in the group of people who are “poor perceivers” and have failed to recognize previous exacerbations or symptom deteriorations early17.5 to 1 mg of prednisolone/kg or equivalent during a 24hour period) should be used to treat exacerbations especially if they develop after instituting the other short-term treatment options recommended for loss of control.1 Teach all patients how to monitor lung function by using PEF to facilitate early and accurate assessment of exacerbations and response to treatment (Evidence B). Exacerbations recognized and treated within 6 hours of onset may be less likely to result in hospitalizations13. Provide all patients with a written asthma action plan that includes daily management and recognizing and handling worsening asthma. For example. repeated administration of rapid-acting inhaled β2agonists (2 to 4 puffs every 20 minutes for the first hour) is usually the best and most cost-effective method of achieving rapid reversal of airflow limitation. Advise patients who have moderate or severe persistent asthma or a history of severe exacerbations to have the medication (e. corticosteroid tablets or liquid) and equipment (e. 20. A written asthma action plan should state when to seek medical help. the dose of β2-agonist required will depend on the severity of the exacerbation. For mild to moderate exacerbations. treatment does not give rapid. the patient should be referred to an acute care facility. Oral glucocorticosteroids (0. sustained improvement or there is further deterioration..g. Increase the frequency of SABA treatment (Evidence A). No additional medication is necessary if the rapid-acting inhaled β2-agonist produces a complete response (PEF returns to greater than 80% of predicted or personal best) and the response lasts for 3 to 4 hours. Patients should seek medical help earlier if the exacerbation is severe. a drop to 60 percent of personal best represents life-threatening airflow obstruction. After the first hour. the impact of any irreversible airflow obstruction must be considered.18. therefore.g. Signs and symptoms imperfectly mirror airflow obstruction. if there is a lack of response.

23. starting at the first appearance of worsening symptoms.Merely doubling the dose of an ICS in those patients already receiving ICS therapy has not been effective at reducing the severity or preventing progression of exacerbations21. mood changes. For patients who experience substantial adverse effects with oral systemic corticosteroids (e. high-dose ICS (beclomethasone >1000- Figure 7. Management of Asthma Exacerbations: Home Treatment 83 .. may prevent exacerbations requiring oral systemic corticosteroids25.22. Preliminary evidence indicates that quadrupling the dose of an ICS for 7 days. worsening diabetes).1.24 (Evidence B).g.

moist air (e. Therefore.. the improvement is quite gradual. with addition of inhaled ipratropium bromide in severe exacerbations (Evidence A). with symptom relief in 1–2 days for moderate exacerbations but in 3 or more days for severe exacerbations (See figure 7–1. frequent treatment. review of inhaler techniques whenever possible. but their use should not delay seeking medical care Although pursed-lip and other forms of controlled breathing may help to maintain calm during respiratory distress. require close observation for deterioration. patients should seek medical care rather than rely on bronchodilator therapy in excessive doses or for prolonged periods (e. patients’ greater use of SABA should be continued until symptoms and PEF are stable. such as intravenous magnesium sulfate or heliox. SABA to relieve airflow obstruction.e.). Continue more intensive treatment for several days26.. Effective initial therapies (i. Consideration of adjunct treatments.. Systemic corticosteroids to decrease airway inflammation in moderate or severe exacerbations or for patients who fail to respond promptly and completely to a SABA (Evidence A). in the urgent care setting or emergency room (ER) includes: 84 . For many persons. evidence of inflammation in the airways may continue for up to 2–3 weeks27.g. Emergency Room and Hospital Management of Asthma Exacerbations Severe exacerbations of asthma are potentially life threatening. Preventing relapse of the exacerbation or recurrence of another exacerbation by providing: referral to follow up asthma care within 1–4 weeks. most severe exacerbations of asthma require prompt transfer to an ER for more complete therapy 14. SABA and the means of giving it by aerosol and a source of supplemental oxygen) should be readily available in a doctor’s clinic. in severe exacerbations unresponsive to the initial treatments listed above (Evidence B). 20.g.2000 ug/day or its equivalent)source: GINA Figure 3-1 may be an effective alternative for mild to moderate exacerbations. Oxygen to relieve hypoxemia in moderate or severe exacerbations26. Even when symptoms have resolved.. these methods do not bring about improvement in lung function. Recovery from an exacerbation varies. Serious exacerbations. and repetitive measurement of lung function. however. the mist from a hot shower) Using over-the-counter products such as antihistaminics or cold remedies. an ER asthma discharge plan with instructions for medications prescribed at discharge and for increasing medications or seeking medical care if asthma worsens. approximately 10–25 percent of ER patients MANAGEMENT: ACUTE CARE SETTING Management of asthma exacerbations requiring urgent medical care (e. Despite appropriate therapy. and consideration of initiating inhaled corticosteroids (ICSs) The following home management techniques are not recommended26: Drinking large volumes of liquid or breathing warm. Over-the-counter bronchodilators may provide transient bronchodilation. In managing an exacerbation at home.g. >12 puffs/day for more than 24 hours). Care must be prompt. Hence.

85 .

In the hospital. . Figure 7-2. Management of Acute Exacerbation: ER Department and Hospital Based Care 86 ..who have acute asthma will require 38 hospitalization37. multidisciplinary (e. nursing and respiratory care) clinical pathways for asthma appear to be effective in reducing hospital length-of-stay and inpatient costs.g. but they have less clear impact on clinical outcomes39. An overview of the treatment strategies in ERs and hospitals is presented in Figure 7–2.

be familiar with the symptoms and signs of severe and life-threatening exacerbations and have procedures for facilitating immediate patient transfer to an Initial assessment should include a brief history. for most patients. All clinicians treating patients who have asthma should be prepared to treat an asthma exacerbation. 87 . and. objective measures of lung function.Figure 7-3. but they are not required for most patients. and they should not delay initiation of asthma treatment26. Dosages of Drugs for Acute Exacerbation ASSESSMENT emergency care facility26. Initial laboratory studies may be helpful. brief physical examination.

6. and hospitalizations for asthma. Treatment should begin immediately following recognition of a moderate.g. 4. Severity of symptoms especially compared with previous exacerbations. lung function26. 3. based on at least vital signs and an overall physical assessment (e. In the hospital. ER visits. function Obtain a brief history to determine26: FEV1 or PEF values provide important information about the level of airflow obstruction both initially and in response to treatment. Any prior episodes of respiratory insufficiency due to asthma (loss of consciousness or intubation and mechanical ventilation). signs. particularly within the past year.g. FEV1 measurements are preferable if they are readily available 1. FEV1 or PEF should be measured on admission and 15–20 minutes 88 .42. ability to breathe well enough to talk). Other potentially complicating illnesses.. peptic ulcer. FEV1 or PEF are not indicated (Evidence D).)..43. triaged immediately.45. In the initial assessment of a lifethreatening asthma exacerbation.43(Evidence C). FEV1 or PEF should be obtained on arrival and 30–60 minutes after initial treatment (Evidence B). While treatment is given. lung Serial pulse oximetry measurements can be useful to assess both the severity of the exacerbation and improvement with treatment (Evidence B). Pulse oximetry is indicated for any patient who is in severe distress or has an FEV1 or PEF <40 percent of predicted to assess the adequacy of arterial oxygen saturation (SaO2)40. Time of onset and any potential causes of current exacerbations. and obstructive ventilatory disorders (e. in the clinic or ER. hypertension. Obtain objective measurements. pneumonia).g.41. neuromuscular weakness. especially of asthma medications. the clinical presentation should suffice for clinical assessment and prompt initiation of therapy (Evidence D). 5. in such cases. asthma). severe. when possible. Because low PEF values cannot distinguish between poor effort. and response to any treatment given before admission to ER. or. restrictive ventilatory disorders (e.after bronchodilator therapy during the acute phase and at least daily thereafter until discharge (Evidence C). By contrast. Very severe exacerbations may preclude performance of a maximal expiratory maneuver and. All current medications and time of last dose. and psychosis). Estimate of number of previous unscheduled clinic visits. all patients presenting with a reported asthma exacerbation must be evaluated and Any FEV1 or PEF value <25 percent of predicted that improves by <10 percent after treatment or values that fluctuate widely are potential indications for ICU admission and close monitoring for respiratory failure (Evidence C). Take a more detailed history and complete physical examination and perform laboratory studies only after initial therapy has been completed (Evidence D). a single pulse oximetry value on admission is of relatively little value for predicting hospital admission 44. 2. Monitor oxygen saturation. or life-threatening exacerbation by assessment of symptoms.. obtain a brief. focused history and physical examination pertinent to the exacerbation (See figure 5–2. (Evidence D). In less severe exacerbations. In the ER. especially other pulmonary or cardiac disease or diseases that may be aggravated by systemic corticosteroid therapy (such as diabetes.

organic diseases of the larynx. such as congestive heart failure. or diabetes). these will influence management of the asthma exacerbation. magnesium. epiglottitis. and unexpectedly complete resolution of airflow obstruction with intubation. Both intrathoracic and extrathoracic central airway obstruction can cause severe dyspnea and may be diagnosed as asthma. including level of alertness. Assess overall patient status. further evaluation is indicated by flow-volume curves and by referral for laryngoscopy Chest radiography is not recommended for routine assessment but should be obtained for patients suspected of a complicating cardiopulmonary process. or lobar atelectasis. Assess the severity of the exacerbation. monophonic wheezing loudest over the central airway.detection of actual or impending respiratory failure. fluid status. severe distress. they must not delay initiation of asthma treatment26. 2. pneumonia. and extrinsic and intrinsic tracheal narrowing. extremely severe obstruction may be accompanied by a “silent chest”46. in rare cases. and presence of cyanosis. pneumomediastinum. pneumonia. pneumonia. It may be prudent to measure serum electrolytes in patients who have been taking diuretics regularly and in patients who have coexistent cardiovascular disease because frequent SABA administration can cause transient decreases in serum potassium. Other objectives include detection of theophylline toxicity or conditions that complicate the treatment of asthma exacerbations (such as cardiovascular disease. When upper airway obstruction is suspected. 4. Clues to the presence of alternative reasons for dyspnea include dysphonia. vocal cord dysfunction. Causes include upper airway foreign bodies.g. although rare. (Note: Respiratory drive is typically increased in asthma exacerbations. normal values for PO2. Wheezing can be an unreliable indicator of obstruction. It must be noted that modest leukocytosis is common in asthma exacerbations and that corticosteroid treatment causes a further outpouring of polymorphonuclear leukocytes within 1–2 hours of administration. Electrocardiograms are not required routinely.) Complete blood count (CBC) is not required routinely but may be appropriate in patients who have fever or purulent sputum. inspiratory stridor. or another pulmonary process such as pneumothorax. respiratory distress. 3. but a baseline electrocardiogram and continual monitoring of cardiac rhythm are appropriate in patients older than 50 years of age and in those who have coexistent heart disease or chronic LABORATORY STUDIES Most patients who have an asthma exacerbation do not require any initial laboratory studies. Identify possible complications (e. or pneumomediastinum). and wheezing. pneumothorax. Rule out upper airway obstruction. The most important objective of laboratory studies is 89 . so a “normal” PCO2 of 40 mmHg indicates severe airflow obstruction and a heightened risk of respiratory failure. as indicated by the findings listed in Table 7-2. or FEV1 or PEF ≤25 percent of predicted after initial treatment. and phosphate.. Consider arterial blood gas (ABG) measurement for evaluating arterial carbon dioxide tension (PCO2) in patients who have suspected hypoventilation. If laboratory studies are ordered. Perform Initial brief physical examination to26: 1.

obstructive pulmonary disease.

The repetitive or continuous administration of
SABA is the most effective means of reversing
airflow obstruction48,49,50,51. In the ER, three
treatments of SABA spaced every 20–30
minutes can be given safely as initial therapy.
Thereafter, the frequency of administration
varies according to the improvement in airflow
obstruction and associated symptoms and the
occurrence of side effects. Continuous
administration of SABA may be more effective in
more severely obstructed patients48, 52.

TREATMENT
Recommended initial treatments in acute care
settings include: oxygen for most patients; SABA
for all patients; adding multiple doses of
ipratropium bromide for ER patients who have
severe exacerbations (but ipratropium bromide
is not recommended during hospitalization1);
and systemic corticosteroids for most patients.
(For recommended doses, see Figure 5–3.).
For severe exacerbations unresponsive to the
initial
treatments,
adjunct
treatments
(magnesium
sulfate
or
heliox)
merit
consideration to decrease the likelihood of
intubation.
The following are not recommended26:
methylxanthines, antibiotics (except as needed
for comorbid conditions), aggressive hydration,
chest physical therapy, mucolytics, or sedation.

In mild or moderate exacerbations, equivalent
bronchodilation can be achieved either by high
doses (4–12 puffs) of a SABA by MDI with a
valved holding chamber (VHC e.g., VolumaticTM)
in infants, children, and adults under the
supervision of trained personnel or by nebulizer
therapy53, 54. However, nebulizer therapy may be
preferred for patients who are unable to
cooperate effectively in using an MDI because of
their age, agitation, or severity of the
exacerbation.

For patients who have mild exacerbations give
SABA therapy and assess the patient’s
response before deciding whether additional
therapy is necessary.

The onset of action for SABA is less than 5
minutes; repetitive administration produces
incremental bronchodilation. In about 60–70
percent of patients, response to the initial three
doses in the ER will be sufficient to discharge
them, and most patients will have a significant
response after the first dose 55,56,57.

Oxygen
Administer supplemental oxygen (by nasal
cannulae or mask, whichever is best tolerated)
to maintain an SaO2 >90 percent (>95 percent in
pregnant women and in patients who have
coexistent heart disease). Monitor SaO2 until a
clear response to bronchodilator therapy has
occurred.
When SaO2 monitoring is not
available, give supplemental oxygen to patients
who have significant hypoxemia and to patients
who have FEV1 or PEF <40 percent of
predicted.

Duration of action of bronchodilation from SABA
in severe asthma exacerbations is not precisely
known, but duration can be significantly shorter
than that observed in stable asthma.
A recent meta-analysis of six trials suggests that
the use of nebulized magnesium sulfate in
combination with SABA may result in further
improvements in pulmonary function58, but
further research is needed.

Inhaled ipratropium bromide.

Inhaled SABA.

In the ER, adding multiple high doses of
ipratropium bromide (0.5 mg nebulizer solution
or 8 puffs by MDI in adults; 0.25–0.5 mg

SABA treatment is recommended for all patients
(Evidence A)

90

nebulizer solution or 4–8 puffs by MDI in
children) to a selective SABA produces
additional bronchodilation, resulting in fewer
hospital admissions, particularly in patients who
have severe airflow obstruction59,60. (Evidence A)
Two controlled clinical trials in children failed to
detect a significant benefit from the addition of
ipratropium to treatment after hospitalization for
severe acute asthma61,62.
Studies among
hospitalized adults are not available.

before arrival at the acute care setting or in the
ER, adjunct treatments may be considered to
decrease
the
likelihood
of
intubation:
intravenous magnesium or heliox may be useful
(Evidence B). (Refer to Chapter 3)

Systemic corticosteroids.

Theophylline/aminophylline is not recommended
for acute exacerbations because it appears to
provide no additional benefit to optimal SABA
therapy and increases the frequency of adverse
effects. (Evidence A). Therapy with oral or
intravenous methylxanthines does not improve
lung function or other outcomes in hospitalized
adults72. Most studies show no benefit, but
increased toxicity, with theophylline in children
who are hospitalized with severe asthma73. A
meta-analysis reported that those patients
receiving intravenous aminophylline had a small
(8–9 percent) increase in percent predicted
FEV1 but did not result in significant differences
in length of stay, ICU admission or stay, or
symptoms. There were significantly greater
numbers of patients in the theophylline group
who discontinued therapy due to adverse
effects.74

The following
recommended:

treatments

are

NOT

Methylxanthines.

In the ER: Give systemic corticosteroids to
patients who have moderate or severe
exacerbations and patients who do not respond
completely to initial SABA therapy (Evidence A).
These medications speed the resolution of
airflow obstruction and reduce the rate of
relapse and may reduce hospitalizations63,64,65.
Oral administration of prednisone has been
shown to have effects equivalent to those of
intravenous methylprednisolone (Evidence A)
66,67
and is usually preferred because it is less
invasive. Give a 5- to 10-day course following
ER discharge to prevent early relapse26.
Give supplemental doses of oral corticosteroids
to patients who take them regularly, even if the
exacerbation is mild (Evidence D).

Antibiotics

High doses of an ICS may be considered in the
ER, although current evidence is insufficient to
permit conclusions about using ICS rather than
oral systemic corticosteroids in the ER
(Evidence B).

Antibiotics are not generally recommended
for the treatment of acute asthma
exacerbations except as needed for
comorbid conditions (Evidence B). Bacterial,
Chlamydia,
or
Mycoplasma
infections
infrequently contribute to exacerbations of
asthma; therefore, the use of antibiotics is
generally reserved for patients who have fever
and purulent sputum and for patients who have
evidence of pneumonia3. When the presence of
bacterial sinusitis is strongly suspected, treat
with antibiotics.

In the hospital: Give systemic corticosteroids to
patients who are admitted to the hospital
(Evidence
A)
because
oral
systemic
corticosteroids speed the resolution of asthma
exacerbations70,71.

Adjunct Treatments
For severe exacerbations unresponsive to the
initial treatments listed above, whether given

Chest physical therapy

91

For most exacerbations, chest physiotherapy is
not beneficial and is unnecessarily stressful for
the breathless asthma patient. Because mucus
plugging is a major contributing cause of fatal
asthma73, further studies are needed on the role
of improved airway clearance in near-fatal
exacerbations. (Evidence D).

discussion of laboratory studies).

HOSPITALIZATION
The decision to hospitalize a patient should be
based on the duration and severity of symptoms,
severity of airflow obstruction, response to ER
treatment, course and severity of prior
exacerbations, medication use at the time of the
exacerbation, access to medical care and
medications, adequacy of support and home
conditions, and presence of psychiatric illness
(Evidence C)76,77.

Mucolytics
Avoid mucolytic agents (e.g., acetylcysteine,
potassium iodide) because they may worsen
cough or airflow obstruction. (Evidence C)
Leukotriene modifiers

In general, the principles of care in the hospital
and recommendation for treatment resemble
those for care in the ER and involve both
treatment (with oxygen, aerosolized SABA, and
systemic corticosteroids and, perhaps, adjunct
therapies) and frequent assessment, including
clinical assessment of respiratory distress and
fatigue as well as objective measurement of
airflow (PEF or FEV1) and oxygen saturation26.

There is little data to suggest a role for
leukotriene modifiers in acute exacerbations of
asthma1
Sedation
Sedation should be strictly avoided during
asthma exacerbations (Evidence D). Anxiolytic
and hypnotic drugs are contraindicated because
of their respiratory depressant effect. In
asthmatic patients who have severe emotional
impact, and possible comorbid anxiety disorder,
therapy should stay focused on the asthma
exacerbation. The benefit of short-acting
sedatives is not known.

IMPENDING RESPIRATORY FAILURE
Intubation must not be delayed once it is
deemed necessary. Exactly when to intubate is
based on clinical judgment (Evidence D). Most
patients respond well to therapy. However, a
small minority will show signs of worsening
ventilation, whether from worsening airflow
obstruction, worsening respiratory muscle
fatigue, or a combination of the two. Signs of
impending respiratory failure include inability to
speak, altered mental status, intercostal
retraction, worsening fatigue, and a PCO2 of
≥42 mmHg78. Because respiratory failure can
progress rapidly and can be difficult to reverse,
early recognition and treatment are critically
important.

REPEAT ASSESSMENT
Repeat assessment of patients who have severe
exacerbations should be made after the initial
dose of a SABA and after three doses of a
SABA (60–90 minutes after initiating treatment)
(Evidence A).26
The response to initial treatment in the ER is a
better predictor of the need for hospitalization
than is the severity of an exacerbation on
presentation.7,8,11-13,15 The elements to be
evaluated include the patient’s subjective
response, physical findings, FEV1 or PEF, and
measurement of pulse oximetry or ABG (if the
patient meets the criteria described in the earlier

Adjunct treatments such as magnesium sulfate
or heliox may be considered to avoid intubation,
but intubation should not be delayed once it is
deemed necessary (Evidence B).26 Because
intubation of a severely ill asthma patient is

92

and noninvasive ventilation. Heliox Consider heliox-driven albuterol nebulization for patients who have life-threatening exacerbations and for those patients whose exacerbations remain in the severe category after 1 hour of intensive conventional therapy (Evidence B). however. Intravenous β2-agonists remain a largely unproven treatment. Other adjunct therapies to avoid intubation include intravenous β2-agonists. and the treatment did not improve hospital admission rates. Because intubation should not be delayed once it is deemed necessary.difficult and associated with complications. a mixture of helium and oxygen (heliox) could improve gas exchange in patients who have airway obstruction85. not all individual studies have found positive results81. However. it is often performed in the 93 . and depression of mental status strongly suggest the need for ventilatory support (Evidence D). and one study84 found that intravenous magnesium sulfate improved pulmonary function only in patients whose initial FEV1 was <25 percent predicted.80 show that intravenous magnesium sulfate (2 grams in adults and 25–75 mg/kg up to 2 grams in children) added to conventional therapy reduces hospitalization rates in ER patients who present with severe asthma exacerbations (PEF <40 percent). There are no other absolute indications for endotracheal intubation. Other investigators recently described two randomized controlled trials (RCTs) of adults that demonstrated more rapid and greater Intubation Patients who present with apnea or coma should be intubated immediately26. Noninvasive ventilation is another experimental approach for treatment of respiratory failure due to severe asthma exacerbation. Metaanalyses of studies of both children and adults79. but data are very limited96. before the crisis of respiratory arrest. Intubate semielectively. because intubation is difficult in patients who have asthma26. improvements in peak flow and dyspnea scores in patients who presented with severe exacerbations and received initial treatment with heliox versus oxygen-driven albuterol therapy (Lee et al. some studies have neglected to account for the different effect of heliox versus oxygen (or room air) on respirable mass90. exhaustion. Current evidence does not suggest an improved benefit from intravenous β2-agonists compared to aerosol 91 92 administration .83. but data are sparse on the benefit of adding an intravenous βeta2-agonist to high-dose nebulized therapy. More importantly.82. however. Because of helium’s low density. intravenous leukotriene receptor antagonists (LTRAs). but persistent or increasing hypercapnia. Consider intravenous magnesium sulfate in patients who have life-threatening exacerbations and in those whose exacerbations remain in the severe category after 1 hour of intensive conventional therapy (Evidence B). two in pediatric patients) performed between 1996 and 2002 did not find a statistically significant improvement in pulmonary function or other measured outcomes in patients receiving heliox compared to oxygen or air86. insufficient data are available to make recommendations regarding these possible adjunct therapies (Evidence D). additional treatments are sometimes attempted. 2005)89. However. The treatment has no apparent value in patients who have exacerbations of lesser severity. Intravenous Magnesium Sulfate. a meta-analysis of six studies (four in adults. The discrepancy in findings may result from small sample sizes.

although no RCTs provide evidence for or against this practice103. Adjustments are made to the tidal volume. should provide patients with necessary medications and education on how to use them. with consideration given to factors listed in Figure 7–2 (Evidence C). (Evidence C) It involves administration of as high a fraction of inspired oxygen as is necessary to maintain adequate arterial oxygenation.100. Even without intubation.102.104. ventilator rate. a referral for a follow-up appointment. discharge is appropriate if FEV1 or PEF has returned to ≥70 percent of predicted or personal best and symptoms are minimal or absent. The following actions are recommended for discharging patients from the ER: In general. because hypotension commonly accompanies the initiation of positive pressure ventilation. where they can be monitored closely and intubated if it is indicated. Criteria for Hospital Admission: 94 . because mechanical ventilation of patients who have severe refractory asthma is complicated and fraught with risk. Criteria for ICU Admission: Although many issues require consideration at the time of intubation. PATIENT DISCHARGE Permissive hypercapnia provides adequate oxygenation and ventilation while minimizing high airway pressures and barotrauma99. and treatment of respiratory acidosis with intravenous sodium bicarbonate. and the patient is subsequently transferred to an ICU appropriate to the patient’s age. acceptance of hypercapnia. ventilated patients is recommended. clinicians should pay close attention to maintaining or replacing intravascular volume. patients who have severe exacerbations and are slow to respond to therapy may benefit from admission to an ICU. Continuation of a SABA in Clinicians.ER or inpatient ward. and instruction in an ER asthma discharge plan for recognizing and managing relapse of the exacerbation or recurrence of airflow obstruction (Evidence B). and additional therapies are being evaluated. and inspiration-to-expiration ratio to minimize airway pressures.101. Consultation with or co--management by physicians who have expertise in ventilator management is appropriate. before patients’ discharge from the ER or hospital.26 “Permissive hypercapnia” or “controlled hypoventilation”. This ventilator strategy is not uniformly successful in critically ill asthma patients. Patients who have an incomplete response to therapy (FEV1 or PEF 50–69 percent of predicted or personal best) and with mild symptoms should be assessed individually for their suitability for discharge home.

Patients given systemic corticosteroids should continue oral systemic corticosteroids for 3–10 days (Evidence A). 95 . there remains no need to taper if patients are concurrently taking ICS 106. The need for further corticosteroid therapy should be assessed at a follow-up visit. provided there is sufficient monitoring and nursing care105. A retrospective review of a large patient database found a significant reduction in the risk of subsequent ER visits among patients Extended treatment and observation in a holding area. or overnight unit to determine the need for hospitalization may be appropriate. Emergency Department – Asthma Discharge Plan Patients who have a rapid response should be observed for 30–60 minutes after the most recent dose of bronchodilator to ensure their stability of response before discharge to home. there is no need to taper the dose. For 10-day courses. Prescribe sufficient medications for the patient to continue treatment after discharge. Consider initiating an ICS at discharge. in addition to oral systemic corticosteroids (Evidence B). clinical decision unit.Figure 7-4. For corticosteroid courses of less than 1 week.

especially for patients who had severe exacerbations or who do not have regular asthma care. preventative therapy if possible. The follow-up visit should also include a detailed review of the patient’s medications. referral of patients in the ER to an asthma specialist for consultation was associated with a reduced rate Consider issuing a peak flow meter and giving appropriate education on how to measure and record PEF to patients who have difficulty perceiving airflow obstruction or symptoms of worsening asthma (Evidence D). asthma-oriented ER discharge plan will suffice. and development of a comprehensive written asthma action plan that will help prevent subsequent exacerbations and urgent or emergency care visits. Refer to Chapter 4 (Patient Education). the health care provider should try to ascertain the cause of the exacerbation and institute appropriate. a thoughtful. for many patients. Although evidence from RCTs is limited. providing a 1–2 month supply) at discharge from ER should be considered.using ICS therapy after ER discharge107.26 Review discharge medications with the patient and provide patient education on correct use of an inhaler (Evidence B) Give the patient an ER asthma discharge plan with instruction for medications prescribed at discharge and for increasing medications or seeking medical care if asthma should worsen (Evidence B). inhaler and peak flow meter technique. regular care in an outpatient setting. Having fewer general practice contacts in the previous year has been independently associated with an increased risk of fatal asthma110. the provision of a more detailed plan may be appropriate.68. Patients already taking ICS therapy should continue it following discharge. A Cochrane review 109 noted that two other relapse trials did not report similar benefit.. A clinical RCT comparing ER patients discharged with and without ICS demonstrated that ICS added to oral systemic corticosteroids halved patients’ risk of relapse events108.46 to 1. the strong evidence that long-term-control ICS therapy reduces exacerbations in patients who have persistent asthma. given the potential for ICS is to reduce subsequent ER visits. At the follow-up appointment.g. Initiating ICS therapy (e. of subsequent ER visits111. If appropriate. consider referral to an asthma self-management education program (Evidence B). and an observational study found that having follow-up appointments within 30 days of an asthmarelated ER visit was associated with a reduced 90-day readmission rate107. 96 . If local staff and resources permit. and refer the patient for a follow-up asthma care appointment within 1– 4 weeks (Evidence B).02). however. Emphasize the need for continual. specific. and that the initiation (and continuation) of ICS therapy at ER discharge can be an important effort to bridge the gap between emergency and primary care for asthma. Likewise. A visit to the ER is often an indication of inadequate longterm management of asthma or inadequate plans for handling exacerbations. but the review found that the combined estimate of the three available trials had borderline statistical significance (odds ratio 0. 95 percent CI 0.

Figure 7-8. If the decision is made to start the patient on an ICS.123. Hospitalized patients may be particularly receptive to information and advice about their illness monitoring. Low levels of adherence to asthma medications are common. the ICS should be started before the course of oral corticosteroids is completed. because this tool may prevent delays in treating exacerbations. It would be appropriate to query patients hospitalized for asthma about their smoking status and encourage smoking cessation along with their asthma discharge plan. even in patients recently hospitalized for severe asthma exacerbations121.124. Checklist for Hospital Discharge of These “poor perceivers” may particularly benefit Patients who have Asthma from action plans based on peak flow appointment Consider initiating ICS therapy for patients who did not use an ICS prior to the hospital admission (Evidence B). particularly in patients who have low levels of health literacy119. Some studies report that 35 percent of adult patients presenting to the ER are current smokers120. the purposes and correct uses of treatment (including inhaler ) An exacerbation severe enough to require hospitalization may reflect a failure of the patient’s self-management. Discharge medications should include a SABA and sufficient oral systemic corticosteroids to complete the course of therapy (Evidence A) and instructions to continue long-term control therapy — Referral to an asthma specialist should be considered for patients who have a history of life-threatening exacerbations or multiple hospitalizations (Evidence B)122. — Educate patients about their discharge medications and the importance of taking medications as prescribed and attending their followup visit (Evidence B). Studies document that some patients are unable to perceive signs of deterioration that would indicate a need to increase medication116. The following actions are recommended for discharging patients from the hospital: Prior to discharge. because their onset of action is gradual118. 117. 97 . Provide patient education: o Review patient understanding of the causes of asthma exacerbations.125.until the follow-up (Evidence B). adjust the patient’s medication to an outpatient regimen26 During the first 24 hours after this medication adjustment. Starting the ICS therapy before discharge gives the patient additional time to learn and demonstrate appropriate technique. observe the patient for possible deterioration.

15. 11. Spitzer WO. Bethesda. Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. instructions for discharge medications and returning for care if asthma worsens. 4. Expert panel report: guidelines for the diagnosis and management of asthma.168(7):740–59. Validation of a predictive model for asthma admission in children: how accurate is it for predicting admissions? J Clin Epidemiol 1999. (EPR Update 2002). 6.157(6 Pt 1):1804‐9. 2. June 2003. 2007 update. Krishnan JA. Kelly AM. Tan WP.14(2):142–5. Mortality in patients hospitalized for asthma exacerbations in the United States. Powell C. FritzGerald JM. Suissa S. may be quite simple (e.nhlbi. Merriman B. Diette GB. Kerr D. Department of Health and Human Services. Louis. National Heart. Chey T. EPR Update 2002. Habbick B.174(6):633–8. Kelly AM. Hanson R.7(4):327–34.nih. McDermott M. Karras DJ. symptoms. 16. Sammon ME. Global Initiative for Asthma. Patients with a longer duration of symptoms of acute asthma are more likely to require admission to hospital.Am J Respir Crit Care Med 2006. The preparation for discharge from the hospital should be more complete (See Figure 7–8. Ernst P. Clinically meaningful changes in quantitative measures of asthma severity. FitzGerald JM. . Clark S. JAMA 1992. 14. 98 McCarren M. Noertjojo K. Lung. Kerr D. McFadden ER Jr. Woodruff PG.113(5):371– 8. contact with a health care provider. Pollack CV Jr. Cockcroft D. et al. Eur J Emerg Med 2002. Terregino CA. 1996. Turner MO. 13. Global Strategy for Asthma Management and prevention. and rheumatology..gov/guidelines/asthma/asthm afullrpt.7(9):1602‐9. Status asthmaticus. The plan should describe the signs. eds.g. and/or peak flow values that should prompt increases in self-medication. Am J Med 2002. Griswold SK. Review or develop a written plan for managing either relapse of the exacerbation of recurrent symptoms or exacerbations (Evidence B). immunology. Powell C. Kaur K. Jalaludin B. Risk factors for near‐fatal asthma. Predicting recovery from acute asthma in an emergency diagnostic and treatment unit. MD: US. Acute severe asthma. 9. Hansel NN. Acad Emerg Med 2000. Cham GW. Is severity assessment after one hour of treatment better for predicting the need for admission in acute asthma? Respir Med 2004. Rodrigo C. Leeder S. Lopez BL. Fauci AS. 5th edition. Emerg Med (Fremantle ) 2002b. MO. Am J Respir Crit Care Med 1998. Callaham ML.). Camargo CA Jr. Rodrigo GJ. Krishnan V. Bilderback AL. and Blood institute. Am J Respir Crit Care Med 2003. Hall JB. Zalenski RJ. Bai T. A detailed written asthma action plan for comprehensive long-term management and handling of exacerbations should be developed by the regular provider at a follow-up visit. Soh CH. 7.125(3):1081–102. NIH Publication No. Vedal S. Update on selected topics 2002. A prospective multicenter study of factors associated with hospital admission among adults with acute asthma. Arnold GK. Clinical predictors of acute respiratory acidosis during exacerbation of asthma and chronic obstructive pulmonary disease. 12. p63-7. Chest 2004.— Recommend peak flow monitoring to patients who have a history of severe exacerbations or who have moderate or severe persistent asthma (Evidence B) and those who poorly perceive airflow obstruction or worsening asthma (Evidence D).52(12):1157–63. 02-5074. National Asthma Education and Prevention Program. see Figure 7–7). Acute asthma in adults: a review. 10.7(1):28–35. St. 5. Blais L. Rand CS.9(3):225–32. Patterns of increasing beta-agonist use and the risk of fatal or near‐ fatal asthma.268(24)):3462-4.pdf.98(8):777–81. Available at http://www. Earnest A. Mosby. Horwitz Ri. References 1. Acad Emerg Med 2000. Weber EJ. 3. Silverman RA. Crump S. Ernst P. Eur Respir J 1994. Suissa S. National Institutes of Health. or return for emergency care. The plan given at discharge from the ER 8. A case‐control study in hospitalized patients with asthma. Current therapy in allergy. Grunfeld A. In: Lichtenstein LM.

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104 .

Chapter 8 Special Consideration .

KEY POINTS: It is safer for pregnant women with asthma to be treated pharmacologically than to continue to have asthma symptoms and exacerbations. gastroesophageal reflux.4 Although concern exists with the use of medications in pregnancy.they provoke wheezing and increased symptoms in many patients. resulting in complications which include increased risk of perinatal mortality. surgery. Modest reductions in peak flow rate at the time of menstruation for affected women compared to unaffected women were noted. in one-third asthma becomes less severe. occupation. poorly controlled asthma can have an adverse effect on the fetus. and type of anesthesia. PREGNANCY During pregnancy the severity of asthma often changes. aspirin intake.7 and neonatal hypoxia. Medical management should be given for the relief of reflux symptoms as it is often effective. low birth weight. but these were not usually associated with clinical deterioration.6. respiratory infections. The overall perinatal prognosis for children born to women with asthma that is Upper airway diseases like rhinitis. Anaphylaxis is a potentially lifethreatening condition that can both mimic and complicate severe asthma. and anaphylaxis. and patients may require close follow-up and adjustment of medications. 1 The mechanism involved in exercise-induced asthma (EIA) may be due to the humidification and heating function of the nose being by-passed and cold air reaching the airways.2. Respiratory infections have an important relationship to asthma as 106 . the type of surgery.3. sinusitis. menstrual cycle. Cold air may likewise produce a humoral effect or a nerve reaction in the small airways that leads to airway narrowing. preterm birth. but it is not a substitute for adequate avoidance. Although the mechanisms behind this relationship have not been established. A diagnosis of gastroesophageal reflux in patients with asthma can best be made by simultaneously monitoring esophageal pH and lung function. In approximately one-third of women asthma becomes worse. INTRODUCTION The likelihood of intraoperative and postoperative respiratory complications depends on the severity of asthma at the time of surgery. Pharmacologic therapy for occupational asthma is identical to therapy for other forms of asthma.5. inflammation likely plays a similarly critical role in the pathogenesis. intrauterine growth retardation. sinusitis and nasal polyps can influence lower airway function in some patients with asthma. rhinitis. Special considerations are required in managing asthma in relation to pregnancy. Effective treatment of anaphylaxis demands early recognition of the event. and in the remaining one third it remains unchanged during pregnancy. which in turn produces bronchial spasm. The use of perioperative steroids to control asthma does not put the asthmatic at greater risk for peri-operative complications. exercise.. and nasal polyps.

optimal treatment of asthma during pregnancy includes treatment of comorbid allergic rhinitis (AR) which can trigger or aggravate asthma symptoms. inhaled glucocorticosteroids. For most medications used to treat asthma. Table 8.13.1.14 The current second-generation antihistamines of choice are loratadine or cetirizine. using medications to obtain optimal control of asthma is justified even when their safety in pregnancy has not been unequivocally proven. The factors most likely contributing to worsening asthma during pregnancy include upper respiratory tract infections and patient non-compliance with medical regimen. Inhaled glucocorticosteroids have been shown to prevent exacerbations of asthma during pregnancy. Common Allergic Rhinitis Medications in Pregnant Asthmatics Appropriately monitored use of theophylline. the focus of asthma treatment must remain on control of symptoms and maintenance of normal lung function. there is little evidence to suggest an increased risk to the fetus. Acute exacerbations should be treated aggressively in order to avoid fetal hypoxia. Asthma generally remains quiescent during labor and delivery in about 90% of pregnant women. and leukotriene modifiers (specifically montelukast) are not associated with an increased incidence of fetal abnormalities. . Intranasal corticosteroids are recommended for treatment of allergic rhinitis as a comorbid condition because they have a low risk of systemic effect.well managed during pregnancy is comparable to that for children born to women without asthma.10 LTRAs can also be used. Treatment should include nebulized rapid-acting β2-agonists and oxygen and systemic glucocorticosteroids should be instituted when necessary. β2-agonists. According to the Asthma and Pregnancy Working Group (APWG) of the National Asthma Education and Prevention Program. women with more severe asthma prior to pregnancy are likely to deteriorate during pregnancy. intranasal decongestants should not be used (even by nonpregnant patient) for more than 9 days.8 For this reason.16 As a rule.15.12. Whatever the course of asthma 107 .9. *ARIA – Allergic Rhinitis and its Impact on Asthma As in other situations.1 Note: ARIA* advises that due to the risk of rhinitis medicamentosa. but minimal data are available on their use during pregnancy.11. Table 1 shows the common allergic rhinitis medications and their FDA pregnancy risk categories. The peak of exacerbations appears between the 24th36th weeks of age of gestation (AOG).7.

may be during pregnancy. 108 .23. 26.2. Prostaglandins have previously been reported to have bronchoconstrictive effects. US FDA Pregnancy Risk Categories for Asthma Medications While all patients should have adequate opportunity to discuss the safety of their medications. there seems to be no deterioration in airway reactivity.8 Asthma and the Menstrual Cycle Premenstrual asthma (PMA) is a phenomenon first described by Frank in 1931.22. It is safer for pregnant women with asthma to be treated pharmacologically than to continue to have asthma symptoms and exacerbations. placenta previa. maternal hypertension. 28 It must be emphasized. this may lead to cyclic changes in airway responsiveness in women prone to perimenstrual exacerbation of asthma. endogenous prostaglandin synthesis. but these were not usually associated with clinical deterioration. hyperemesis gravidarium.18. has not been shown to correlate with occurrence of premenstrual asthma.20 Table 2 shows US FDA pregnancy risk categories for asthma medications. however.25 further influence asthma leading to symptomatic deterioration and dyspnea. that there is no real relationship between airway function and absolute levels of progesterone.1. Although an increase in asthma symptoms and a decrease in peak expiratory flow rates have been demonstrated in the luteal phase of menstrual cycle. seem to suggest that 30-40% of female asthmatics experience a premenstrual worsening of symptoms but these were retrospective and based on patient-recorded recollections of subjective data without any objective finding of increased asthma in severity. Several small studies. and induced and 17 complicated labors. Table 8. Thus. pregnant patients with asthma should be advised that the greater risk to their baby lies with poorly controlled asthma. uterine vaginal hemorrhage. toxemia.19.29.30 Progesterone levels fall in the days before menstruation and it has a relaxant effect on airway smooth muscle contractility. and the safety of most modern asthma treatments should be stressed. as a symptom of “premenstrual tension”.24 Modest reductions in peak flow rate at the time of menstruation for affected women compared to unaffected women were noted.27 Progesterone-induced hyperventilation may Severe persistent asthma has been related to the development of maternal complications like pre-eclampsia.21 Large scale longitudinal studies have not yet been undertaken to adequately address just how prevalent the condition is. however. however. changes generally revert to pre-pregnancy level of severity within 3 months post-partum.

38.40. animal dander. a brief course of oral glucocorticosteroids should be considered to reduce airflow limitation.33. nasal obstruction is largely due to hyperemia in rhinitis. However.37. H1antagonists) and others against asthma (e. some medications are selectively effective against rhinitis (e. clinical features. and that in planning treatment.g. of prednisone daily or the equivalent).34 These variables need to be assessed prior to surgery and pulmonary function should be measured. and nasal polyps as in asthma. Sinusitis.53 Anti-inflammatory agents including glucocorticosteroids and cromones as well as leukotriene modifiers and anticholinergics can be effective in both conditions. the type of surgery (thoracic and upper abdominal surgeries pose the greatest risks). Although the inflammation of the nasal and bronchial mucosa may be similar.31 The likelihood of these complications depends on the severity of asthma at the time of surgery. while airway smooth muscle contraction plays a dominant role in asthma. the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative recommends that the presence of asthma must be considered in all patients with rhinitis. β2-agonists). and type of anesthesia (general anesthesia with endotracheal intubation carries the greatest risk).54 Use of intra-nasal Rhinitis. and is both a risk factor for the development of asthma45 and is associated with increased severity and health resource use in asthma.46 Rhinitis and asthma share several risk factors: common indoor and outdoor allergens such as house dust mites. and mucus hypersecretion predispose patients with asthma to intraoperative and postoperative respiratory complications. and non-specific factors like aspirin. if the patient’s FEV1 is less than 80% of personal best.36 Prior to surgery. pollen affecting both the nose and bronchi..52.35 Furthermore. the patient may need oral corticosteroids (1mg /kbw. both should be considered together.42 Surgery Airway hyperresponsiveness.50 Both asthma and rhinitis are considered to be inflammatory disorders of the airway.39 To achieve this goal. and Nasal Polyps Upper airway diseases can influence lower airway function in some patients with 109 . This should be rapidly reduced 24 hours following surgery. as prolonged systemic glucocorticosteroid therapy may inhibit wound healing.32. 51 The use of peri-operative steroids to control asthma does not put the asthmatic at greater risk for peri-operative complications. Although the mechanisms behind this relationship have not been established. this evaluation should be undertaken several days before surgery to allow time for additional treatment. Treatment of rhinitis may improve asthma symptoms. If possible.47. inflammation likely plays a similarly critical role in the pathogenesis of rhinitis.48 occupational 49 sensitizers. with a peak flow greater than 80 percent of the predicted personal best value.41.. For these reasons. patients who have received systemic glucocorticosteroids within the past 6 months should have systemic coverage during the surgical period (100 mg hydrocortisone every 8 hours intravenously). less commonly. and treatment approach.asthma. airflow limitation. sinusitis.43 Rhinitis frequently precedes asthma. patients should be free of wheezing. In particular. and.43.g. but there are some differences between the two conditions in mechanisms. Rhinitis The majority of patients with asthma have a history or evidence of rhinitis and up to 30% of patients with persistent rhinitis have or develop asthma.

These agents remain secondary to primary asthma therapies. Delcos.69. allergic rhinitis.68 Sinusitis Sinusitis is a complication of upper respiratory infections. the possibility of Work-Related Asthma (WRA) should be considered and evaluated.56.al. Some patients with recurrent sinusitis will develop chronic tissue inflammation with mucosal thickening and formation of nasal polyps. Occupational Asthma Occupational exposures have been estimated to cause 5-15% of adult-onset asthma. A limited number of patients with glucocorticosteroid-refractory polyps may benefit from surgery.70 Occupational asthma may persist even several years after removal from exposure to the causative agent. In every adult whose asthma begins or worsens while working.com.64 are seen primarily in patients over 40 years old. Physicians should consider the possibility of OA in all adults with asthma.58 allergen-specific immunotherapy. nasal polyps.50. and 29% to 70% of patients with nasal polyps may have asthma.54 Approximately 40-60% of asthmatic patients will show radiographic evidence of sinusitis. pp 667-675. Clinical features of sinusitis lack diagnostic precision. (American Journal of Critical Care Med Vol 175.57 Leukotriene modifiers.asmanet.55.64. 2007).59 and anti-IgE therapy60. an occupational history should be the first step in the initial evaluation of the patient.67 The list of agents can be viewed at http://www. Treatment should also include medications to reduce nasal congestion.62 and CT Scan confirmation is recommended when available.45. et. because a prolonged avoidance of exposure may influence the reliability of diagnostic procedures. Both acute and chronic sinusitis can worsen asthma. use of powdered latex gloves.65 Nasal polyps are quite responsive to topical glucocorticosteroids.61 are effective in both conditions . Therefore. he reported an approximate twofold increase in the likelihood of asthma after entry into a health care profession for tasks involving instrument cleaning and disinfection. Once a diagnosis of occupational asthma is established. and the administration of aerosolized medications. also called chronic hyperplastic sinusitis and nasal polyp formation (CHS/NP). and sometimes with aspirin hypersensitivity. such as topical nasal decongestants or topical nasal or even systemic glucocorticosteroids. and other forms of nasal obstruction. general cleaning products used on indoor building surfaces. The diagnosis should be confirmed as soon as possible to prevent worsening of 69 symptoms and should be investigated when workers are at the workplace. The prevalence of occupational asthma (OA) due to agents with high molecular weight is generally less than 5% while prevalence due to low molecular weight agents is 5-10%. In a recent report on “Occupational Risk Factors and Asthma among Health Care Professionals” by George L. especially when the patient has had symptoms for a long time 110 .70-72 is ideally an important component of management.66. complete avoidance of the relevant exposure . Nasal polyps Nasal polyps associated with asthma and rhinitis. Between 36% and 96% of aspirin-intolerant patients have polyps.glucocorticosteroids for concurrent rhinitis has been found to have a limited benefit in improving asthma and reducing asthma morbidity in some but not all studies.

before cessation of exposure.73,74 Continued
exposure may lead to increasingly severe
and lower probability of subsequent
remission,75 and, ultimately, permanently
impaired lung function.76-79 Pharmacologic
therapy for occupational asthma is identical
to therapy for other forms of asthma, but it is
not a substitute for adequate avoidance.80
Consultation with a specialist in asthma
management or occupational medicine is
advisable. The British Occupational Health
Research Foundation Guidelines for the
prevention, identification, and management
of occupational asthma are available at
http://www.bohrf.org.uk/downloads/asthevre.
pdf.

release, and the appearance of a late
asthmatic response to inhaled antigen.87
Thus, there is evidence that viral infections
are an “adjuvant” to the inflammatory
response and promote the development of
airway injury by enhancing airway
inflammation.88 Treatment of an infectious
exacerbation follows the same principles as
treatment of other asthma exacerbations—
that is, rapid-acting inhaled β2-agonists and
early introduction of oral glucocorticosteroids
or increases in inhaled glucocorticosteroids
by at least four-fold are recommended.
Because increased asthma symptoms can
often persist for weeks after the infection is
cleared, anti-inflammatory treatment should
be continued for this full period to ensure
adequate control.

The Diagnosis and Management of WorkRelated
Asthma:
ACCP
Consensus
Statement has a detailed discussion of the
diagnosis and management of work-related
asthma. 81

The role of chronic infection with Chlamydia
pneumoniae and Mycoplasma pneumoniae
in the pathogenesis or worsening of asthma
is currently uncertain.89 The benefit from
macrolide antibiotics remains unclear. 90-96

Repiratory Infections
Respiratory infections have an important
relationship to asthma as they provoke
wheezing and increased symptoms in many
patients.82 Epidemiological studies have
found that infectious microorganisms
associated
with
increased
asthma
symptoms are often respiratory viruses,83
but seldom bacteria.84 Respiratory syncytial
virus is the most common cause of
wheezing in infancy, while rhinoviruses
(which cause the common cold), are the
principal triggers of wheezing and worsening
of asthma in older children and adults.85
Other respiratory viruses, such as
parainfluenza, influenza, adenovirus, and
coronavirus, are also associated with
increased
wheezing
and
asthma
symptoms.86 A number of mechanisms have
been identified that explain why respiratory
infections trigger wheezing and increased
airway responsiveness, including damage to
airway epithelium, stimulation of virusspecific IgE antibody, enhanced mediator

Parasitic Infections
Parasite infections are very common,
particularly in the developing world, and
systematic eradication programs are being
introduced in many areas.
Although
eradication is undoubtedly beneficial to
many aspects of individual and public
health, the hypothesis that parasite
infections may protect against allergic
disease
raises
the
possibility
that
eradication may increase asthma and other
manifestations of allergy.
Results of studies are conflicting. A
systematic review and meta-analysis
suggest that any relation between intestinal
parasite infection and asthma risk is likely to
be species specific. Parasite infections do
not in general protect against asthma97

111

A diagnosis of gastroesophageal reflux in
patients with asthma can best be made by
simultaneously monitoring esophageal pH
and lung function. Medical management
should be given for the relief of reflux
symptoms as it is often effective. Patients
may be advised to eat smaller, more
frequent meals; avoid food or drink between
meals and especially at bedtime; avoid fatty
meals, alcohol, theophylline, and oral H2agonists; use proton pump inhibitors or H2antagonists; and elevate the head of the
bed. However, the role of anti-reflux
treatment in asthma control is unclear, as it
does not consistently improve lung function,
asthma symptoms, nocturnal asthma, or the
use of asthma medications in subjects with
asthma but without clear reflux-associated
respiratory
symptoms.
Subgroups of
patients may benefit, but it appears difficult
to predict which patients will respond to this
therapy. 107

Gastroesophageal Reflux
The relationship of increased asthma
symptoms,
particularly at
night,
to
gastroesophageal reflux disease (GERD)
remains uncertain, although this condition is
nearly three times as prevalent in patients
with asthma compared to the general
population.98,99 Some of these patients also
have
a
hiatal
hernia;
furthermore,
theophylline and oral β2-agonists may
increase the likelihood of symptoms by
relaxing the lower esophageal ring. A
relationship between GERD and asthma
was first documented in the late 1960s when
asthma patients were reported to be “cured”
of asthma following surgery for hiatal hernia
and/or GERD.100 Additional research has
continued to show that reflux may cause or
trigger asthma symptoms.
There are two accepted mechanisms for the
role of GERD in asthma. The first hypothesis
states that stimulation of esophageal
mucosal
receptors
produces
vagally
mediated bronchospasm. Prolonged reflux
clearance time often causes symptomatic
esophageal disease and esophagitis,
consequently increasing the sensitivity of
esophageal receptors to refluxed material.
Once stimulated, the receptors transmit a
signal that results in constriction of the
bronchioles. The second hypothesis is the
micro-or macro-aspiration of gastric contents
into the lungs, especially in the supine
position of sleep, causing a chemical
pneumonitis.
More
recent
research,
however, has suggested that although
aspiration does occur on rare occasions, it is
unlikely to be the primary reason for refluxtriggered asthma.101-105

Surgery for gastroesophageal reflux is
reserved for the severely symptomatic
patient with well-documented esophagitis
and failure of medical management. In
patients with asthma, it should be
demonstrated that the reflux causes asthma
symptoms before surgery is advised.100,108-113

Aspirin-Induced Asthma (AIA)
Up to 28% of adults with asthma, but rarely
children with asthma, suffer from asthma
exacerbations in response to aspirin and
other nonsteroidal anti-inflammatory drugs
(NSAIDs). This syndrome is more common
in severe asthma. 114
The clinical picture and course of aspirininduced asthma (AIA) are characteristic.115
The majority of patients first experience
symptoms, which may include vasomotor
rhinitis and profuse rhinorrhea, during the
third to fourth decade of life. Chronic nasal
congestion
evolves,
and
physical
examination often reveals nasal polyps.

More recently, a third mechanism being
proposed is heightened bronchial reactivity
secondary
to
esophageal
reflux.
Furthermore, nocturnal esophageal acid
events are associated with lower respiratory
resistance.106

112

Asthma and hypersensitivity to aspirin often
develop subsequently. The hypersensitivity
to aspirin presents a unique picture: within
minutes to one or two hours following
ingestion of aspirin, an acute, often severe,
asthma attack develops, and is usually
accompanied
by
rhinorrhea,
nasal
obstruction, conjunctival irritation, and
scarlet flush of the head and neck. This may
be provoked by a single aspirin or other
cyclooxygnease-1 (COX-1) inhibitor and
include violent bronchospasm, shock, loss of
consciousness, and even respiratory arrest.

AIA should avoid aspirin, products
containing it, other analgesics that inhibit
COX-1, and often also hydrocortisone
hemisuccinate.124 Avoidance does not
prevent progression of the inflammatory
disease of the respiratory tract. Where an
NSAID is indicated, a cyclooxygenase-2
(COX-2) inhibitor125 may be considered with
appropriate physician supervision and
observation for at least one hour after
administration.126
For NSAID-sensitive
patients with asthma who require NSAIDs
for other medical conditions, desensitization
may be conducted in the hospital under the
care of a specialist. 127,128

116,117

Persistent marked eosinophilic inflammation,
epithelial disruption, cytokine production,
and upregulation of adhesion molecules are
found in the airways of patients with
AIA.118,119 Airway expression of interleukin-5
(IL-5), which is involved in recruitment and
survival of eosinophils, is also increased.120
AIA is further characterized by increased
activation
of
cysteinyl
leukotriene
pathways,which may be partly explained by
a genetic polymorphism of the LTC4
synthase gene found in about 70% percent
of
patients.121
However,
the
exact
mechanism by which aspirin triggers
bronchoconstriction remains unknown.122

Generally, asthma patients, especially those
with adult onset asthma and associated
upper airway disease (nasal polyposis),
should be counselled to avoid NSAIDs,
taking acetaminophen/paracetamol instead.

Exercise-Induced Asthma
During exercise, the humidification and
heating function of the nose by bypassed
and cold air reaches the airways,129,130,131
which in turn produces bronchial spasm.132
This theory also suggests that the cold air
may produce a humoral effect or a nerve
reaction in the small airways that leads to
bronchospasm. 133,134
Neurohumoral
transmitters like leukotrienes have also been
implicated in mediating a portion of the
airway narrowing.135

The ability of a cyclooxygenase inhibitor to
trigger reactions depends on the drug's
cyclooxygenase inhibitory potency, as well
as on the individual sensitivity of the patient.
123,124

Leukotrienes have been found to play a role
in airway refractoriness with repeated bouts
of exercise. They may act through release
of inhibitory prostaglandins or by inhibiting
other mediator release. 136

A characteristic history of reaction can only
be confirmed by aspirin challenge, as there
are no suitable in vitro tests for diagnosis.
The aspirin challenge test is not
recommended for routine practice as it is
associated with a high risk of potentially fatal
consequences and must only be conducted
in
a
facility
with
cardiopulmonary
123
resuscitation capabilities.

Non-pharmacologic
treatment
entails
avoiding inclement atmospheres and
choosing a sport that is less likely to induce
an asthmatic attack. A third strategy would
be by inducing the known refractory period a
few times earlier in the day of competition so

Once aspirin or NSAID hypersensitivity
develops, it is present for life. Patients with

113

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