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Asthma
From Wikipedia, the free encyclopedia

For other uses, see Asthma (disambiguation).

Asthma
Classification and external resources

Peak flow meters are used to measure one'speak expiratory flow rate

ICD-10

J45

ICD-9

493

OMIM

600807

DiseasesDB

1006

MedlinePlus

000141

eMedicine

article/806890

MeSH

D001249

Asthma (from the Greek , sthma, "panting") is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm.[1] Symptoms include wheezing, coughing, chest tightness, and shortness of breath.
[2]

Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in 1 second

(FEV1), and peak expiratory flow rate.[3]Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic).[4] It is thought to be caused by a combination of genetic and environmental factors.[5] Treatment of acute symptoms is usually with an inhaled short-actingbeta-2 agonist (such as salbutamol).[6] Symptoms can be prevented by avoiding triggers, such as allergens[7] and irritants, and by inhalingcorticosteroids.[8] Leukotriene antagonists are less effective than corticosteroids and thus less preferred.[9] Its diagnosis is usually made based on the pattern of symptoms and/or response to therapy over time.[10] The prevalence of asthma has increased significantly since the 1970s. As of 2010, 300 million people were affected worldwide.[11] In 2009 asthma caused 250,000 deaths globally.[12] Despite this, with proper control of asthma with step down therapy, prognosis is generally good.[13]
Contents
[hide]

1 Classification

1.1 Brittle asthma 1.2 Asthma attack 1.3 Status asthmaticus 1.4 Exercise-induced 1.5 Occupational

2 Signs and symptoms

2.1 Gastro-esophageal reflux disease


3 Causes

2.2 Sleep disorders

3.1 Environmental 3.2 Genetic 3.3 Geneenvironment interactions

3.4 Exacerbation 3.5 Hygiene hypothesis 3.6 Socioeconomic factors

4 Diagnosis

4.1 Differential diagnosis

5 Prevention 6 Management

6.1 Lifestyle modification 6.2 Medications 6.3 Other 6.4 Complementary medicine

7 Prognosis 8 Epidemiology


9 History 10 Notes

8.1 Increasing frequency 8.2 Variability

11 External links

[edit]Classification
Asthma is defined by the Global Initiative for Asthma as "a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing particularly at night or in the early morning. These episodes are usually associated with widespread, but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment".[14]

Clinical classification of severity[3]

Severity in patients 12 years of age [15]

Symptom frequency

Night time symptoms

%FEV1 of predicted

Use of short-acting beta2 agonist for FEV1Variability symptom control (not for prevention of EIB)

Intermittent

2 per week

2 per month

80%

<20%

2 days per week

Mild persistent

>2 per week but not daily

34 per month

80%

2030%

>2 days/week but not daily

Moderate persistent

Daily

>1 per week but not nightly

6080%

>30%

Daily

Severe persistent

Throughout the day

Frequent (often 7/week)

<60%

>30%

Several times per day

Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume in 1 second (FEV1), and peak expiratory flow rate.[3] Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic), based on whether symptoms are precipitated by allergens (atopic) or not (non-atopic).[4] While asthma is classified based on severity, at the moment there is no clear method for classifying different subgroups of asthma beyond this system.[16] Finding ways to identify subgroups that respond well to different types of treatments is a current critical goal of asthma research.[16] Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease as this term refers specifically to combinations of disease that are irreversible such asbronchiectasis, chronic bronchitis, and emphysema.[15] Unlike these diseases, the airway obstruction in asthma is usually reversible; however, if left untreated, the chronic inflammation of the lungs during asthma can become irreversible obstruction due to airway remodeling.[17] In contrast to emphysema, asthma affects the bronchi, not the alveoli.[18]

[edit]Brittle

asthma

Main article: Brittle asthma Brittle asthma is a term used to describe two types of asthma, distinguishable by recurrent, severe attacks.
[19]

Type 1 brittle asthma refers to disease with wide peak flow variability, despite intense medication. Type 2

brittle asthma describes background well-controlled asthma, with sudden severe exacerbations.[19]

[edit]Asthma

attack

An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness.[20] While these are the primary symptoms of asthma,
[21]

some people present primarily with coughing, and in severe cases, air motion may be significantly impaired

such that no wheezing is heard.[19] Signs which occur during an asthma attack include the use of accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck), there may be a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest.[22] A blue color of the skin and nails may occur from lack of oxygen.[23] In a mild exacerbation the peak expiratory flow rate (PEFR) is 200 L/min or 50% of the predicted best.
[24]

Moderate is defined as between 80 and 200 L/min or 25% and 50% of the predicted best while severe is

defined as 80 L/min or 25% of the predicted best.[24]

[edit]Status

asthmaticus

Main article: Status asthmaticus Status asthmaticus is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators and steroids. Nonselective beta blockers (such as Timolol) have caused fatal status asthmaticus.[25]

[edit]Exercise-induced
Main article: Exercise-induced asthma A diagnosis of asthma is common among top athletes. One survey of participants in the 1996 Summer Olympic Games, in Atlanta, Georgia, U.S., showed that 15% had been diagnosed with asthma, and that 10% were on asthma medication.[26] There appears to be a relatively high incidence of asthma in sports such as cycling, mountain biking, and longdistance running, and a relatively lower incidence in weightlifting and diving. It is unclear how much of these disparities are from the effects of training in the sport.[26][27] Exercise-induced asthma can be treated with the use of a short-acting beta2 agonist.[15]

[edit]Occupational
Main article: Occupational asthma Asthma as a result of (or worsened by) workplace exposures is a commonly reported occupational respiratory disease. Still most cases of occupational asthma are not reported or are not recognized as such. Estimates by the American Thoracic Society (2004) suggest that 1523% of new-onset asthma cases in adults are work related.[28] In one study monitoring workplace asthma by occupation, the highest percentage of cases occurred among operators, fabricators, and laborers (32.9%), followed by managerial and professional specialists

(20.2%), and in technical, sales, and administrative support jobs (19.2%). Most cases were associated with the manufacturing (41.4%) and services (34.2%) industries.[28] Animal proteins, enzymes, flour, natural rubber latex, and certain reactive chemicals are commonly associated with work-related asthma. When recognized, these hazards can be mitigated, dropping the risk of disease.[29]

[edit]Signs

and symptoms
Wheezing

The sound of wheezing as heard with a stethoscope.

Problems listening to this file? See media help.

Common symptoms of asthma include wheezing, shortness of breath, chest tightness and coughing, and use of accessory muscle. Symptoms are often worse at night or in the early morning, or in response to exercise or cold air.[30] Some people with asthma only rarely experience symptoms, usually in response to triggers, whereas other may have marked persistent airflow obstruction.[31]

[edit]Gastro-esophageal

reflux disease

Gastro-esophageal reflux disease coexists with asthma in 80% of people with asthma, with similar symptoms. Various theories say that asthma could facilitate GERD and/or viceversa. The first case could be due to the effect of change in thoracic pressures, use of antiasthma drugs, could facilitate the passage of the gastric content back into the oesophagus by increasing abdominal pressure or decreasing the lower esophageal sphincter. The second by promoting bronchoconstriction and irritation by chronic acid aspiration, vagally mediated reflexes and others factors that increase bronchial responsiveness and irritation.[32]

[edit]Sleep

disorders

Due to altered anatomy of the respiratory tract: increased upper airway adipose deposition, altered pharynx skeletal morphology, and extension of the pharyngeal airway; leading to upper airway collapse.[33]

[edit]Causes
Asthma is caused by environmental and genetic factors.[5] These factors influence how severe asthma is and how well it responds to medication.[34] The interaction is complex and not fully understood.[35] Studying the prevalence of asthma and related diseases such as eczema and hay fever have yielded important clues about some key risk factors.[36] The strongest risk factor for developing asthma is a history of atopic disease;[37] this increases one's risk of hay fever by up to 5 and the risk of asthma by 34.[38] In children

between the ages of 314, a positive skin test for allergies and an increase in immunoglobulin E increases the chance of having asthma.[39] In adults, the more allergens one reacts positively to in a skin test, the higher the odds of having asthma.[40] Because much allergic asthma is associated with sensitivity to indoor allergens and because Western styles of housing favor greater exposure to indoor allergens, much attention has focused on increased exposure to these allergens in infancy and early childhood as a primary cause of the rise in asthma.[41][42] Primary prevention studies aimed at the aggressive reduction of airborne allergens in a home with infants have shown mixed findings. Strict reduction of dust mite allergens, for example, reduces the risk of allergic sensitization to dust mites, and modestly reduces the risk of developing asthma up until the age of 8 years old.[43][44][45][46] However, studies also showed that the effects of exposure to cat and dog allergens worked in the converse fashion; exposure during the first year of life was found to reduce the risk of allergic sensitization and of developing asthma later in life.[47][48][49] The inconsistency of this data has inspired research into other facets of Western society and their impact upon the prevalence of asthma. One subject that appears to show a strong correlation is the development of asthma and obesity. In the United Kingdom and United States, the rise in asthma prevalence has echoed an almost epidemic rise in the prevalence of obesity.[50][51][52][53] In Taiwan, symptoms of allergies and airway hyperreactivity increased in correlation with each 20% increase in body-mass index.[54] Several factors associated with obesity may play a role in the pathogenesis of asthma, including decreased respiratory function due to a buildup of adipose tissue (fat) and the fact that adipose tissue leads to a pro-inflammatory state, which has been associated with non-eosinophilic asthma.[55] Asthma has been associated with ChurgStrauss syndrome, and individuals with immunologically mediated urticaria may also experience systemic symptoms with generalized urticaria, rhino-conjunctivitis, orolaryngeal and gastrointestinal symptoms, asthma, and, at worst, anaphylaxis.[56] Additionally, adult-onset asthma has been associated with periocular xanthogranulomas.[57]

[edit]Environmental
Many environmental risk factors have been associated with asthma development and morbidity in children. Recent studies show a relationship between exposure to air pollutants (e.g. from traffic) and childhood asthma.
[58]

This research finds that both the occurrence of the disease and exacerbation of childhood asthma are

affected by outdoor air pollutants. High levels of endotoxin exposure may contribute to asthma risk.[59] Viral respiratory infections are not only one of the leading triggers of an exacerbation but may increase one's risk of developing asthma especially in young children.[15][37] Respiratory infections such as rhinovirus, Chlamydia pneumoniae and Bordetella pertussis are correlated with asthma exacerbations.[60]

Psychological stress has long been suspected of being an asthma trigger, but only in recent decades has convincing scientific evidence substantiated this hypothesis. Rather than stress directly causing the asthma symptoms, it is thought that stress modulates the immune system to increase the magnitude of the airway inflammatory response to allergens and irritants.[61][62] Beta blocker medications such as metoprolol may trigger asthma in those who are susceptible.[63]

[edit]Tobacco
Maternal tobacco smoking during pregnancy and after delivery is associated with a greater risk of asthma-like symptoms, wheezing, and respiratory infections during childhood.[64] Low air quality, from traffic pollution or high ozone levels,[65] has been repeatedly associated with increased asthma morbidity and has a suggested association with asthma development that needs further research.[61][66]

[edit]Hygiene hypothesis
Antibiotic use early in life has been linked to development of asthma[67] in several examples; it is thought that antibiotics make children who are predisposed to atopic immune responses susceptible to development of asthma because they modify gut flora, and thus the immune system (as described by the hygiene hypothesis).
[68]

The hygiene hypothesis (see below) is a hypothesis about the cause of asthma and other allergic disease,

and is supported by epidemiologic data for asthma.[69] All of these things may negatively affect exposure to beneficial bacteria and other immune system modulators that are important during development, and thus may cause an increased risk for asthma and allergy. Caesarean sections have been associated with asthma, possibly because of modifications to the immune system (as described by the hygiene hypothesis).[70]

[edit]Volatile organic compounds


Observational studies have found that indoor exposure to volatile organic compounds (VOCs) may be one of the triggers of asthma, however experimental studies have not confirmed these observations.[71] Even VOC exposure at low levels has been associated with an increase in the risk of pediatric asthma. Because there are so many VOCs in the air, measuring total VOC concentrations in the indoor environment may not represent the exposure of individual compounds.[72][73] Exposure to VOCs is associated with an increase in the IL-4 producing Th2 cells and a reduction in IFN- producing Th1 cells. Thus the mechanism of action of VOC exposure may be allergic sensitization mediated by a Th2 cell phenotype.[74] Different individual variations in discomfort, from no response to excessive response, were seen in one of the studies. These variations may be due to the development of tolerance during exposure.[75] Another study has concluded that formaldehyde may cause asthma-like symptoms. Low VOC emitting materials should be used while doing repairs or renovations which decreases the symptoms related to asthma caused by VOCs and formaldehyde.[76] In another study "the indoor concentration of aliphatic compounds (C8-C11), butanols, and 2,2,4-trimethyl 1,3-pentanediol diisobutyrate

(TXIB) was significantly elevated in newly painted dwellings. The total indoor VOC was about 100 micrograms/m3 higher in dwellings painted in the last year". The author concluded that some VOCs may cause inflammatory reactions in the airways and may be the reason for asthmatic symptoms.[77][78]

[edit]Phthalates
There is a significant association between asthma-like symptoms (wheezing) among preschool children and the concentration of DEHP (phthalates) in indoor environment.[79] DEHP (di-ethylhexyl phthalate) is a plasticizer that is commonly used in building material. The hydrolysis product of DEHP (di-ethylhexyl phthalate) is MEHP (Mono-ethylhexyl phthalate) which mimics the prostaglandins and thromboxanes in the airway leading to symptoms related to asthma.[80] Another mechanism that has been studied regarding phthalates causation of asthma is that high phthalates level can "modulate the murine immune response to a coallergen". Asthma can develop in the adults who come in contact with heated PVC fumes.[81] Two main type of phthalates, namely nbutyl benzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP), have been associated between the concentration of polyvinyl chloride (PVC) used as flooring and the dust concentrations. Water leakage were associated more with BBzP, and buildings construction were associated with high concentrations of DEHP.
[82]

Asthma has been shown to have a relationship with plaster wall materials and wall-to wall carpeting. The

onset of asthma was also related to the floorleveling plaster at home. Therefore, it is important to understand the health aspect of these materials in the indoor surfaces.[83]

[edit]Genetic
Over 100 genes have been associated with asthma in at least one genetic association study.[84] However, such studies must be repeated to ensure the findings are not due to chance. Through the end of 2005, 25 genes had been associated with asthma in six or more separate populations:[84]

GSTM1 IL10 CTLA-4 SPINK5 LTC4S

LTA GRPA NOD1 CC16 GSTP1

STAT6 NOS1 CCL5 TBXA2R TGFB1

IL4 IL13 CD14 ADRB2 (-2 adrenergic receptor) HLA-DRB1

HLA-DQB1 TNF FCER1B IL4R ADAM33

Many of these genes are related to the immune system or to modulating inflammation. However, even among this list of highly replicated genes associated with asthma, the results have not been consistent among all of the populations that have been tested.[84] This indicates that these genes are not associated with asthma under every condition, and that researchers need to do further investigation to figure out the complex interactions that cause asthma. One theory is that asthma is a collection of several diseases, and that genes might have a role

in only subsets of asthma.[citation needed] For example, one group of genetic differences (single nucleotide polymorphisms in 17q21) was associated with asthma that develops in childhood.[85]

[edit]Geneenvironment

interactions

CD14-endotoxin interaction based on CD14 SNP C-159T[86]

Endotoxin levels

CC genotype

TT genotype

High exposure

Low risk

High risk

Low exposure

High risk

Low risk

Research suggests that some genetic variants may only cause asthma when they are combined with specific environmental exposures, and otherwise may not be risk factors for asthma.[5] The genetic trait, CD14 single nucleotide polymorphism (SNP) C-159T and exposure to endotoxin (a bacterial product) are a well-replicated example of a gene-environment interaction that is associated with asthma. Endotoxin exposure varies from person to person and can come from several environmental sources, including environmental tobacco smoke, dogs, and farms. Researchers have found that risk for asthma changes based on a person's genotype at CD14 C-159T and level of endotoxin exposure.[86]

[edit]Exacerbation
Some individuals will have stable asthma for weeks or months and then suddenly develop an episode of acute asthma. Different asthmatic individuals react differently to various factors.[87] However, most individuals can develop severe exacerbation of asthma from several triggering agents.[87][88] Home factors that can lead to exacerbation include dust, house mites, animal dander (especially cat and dog hair), cockroach allergens and molds at any given home.[87] Perfumes are a common cause of acute attacks in females and children. Both virus and bacterial infections of the upper respiratory tract infection can worsen asthma.[87]

[edit]Hygiene

hypothesis

Main article: Hygiene hypothesis One theory for the cause of the increase in asthma prevalence worldwide is the "hygiene hypothesis"[15] that the rise in the prevalence of allergies and asthma is a direct and unintended result of reduced exposure to a wide variety of different bacteria and virus types in modern societies, or modern hygienic practices preventing childhood infections.[89] Children living in less hygienic environments (East Germany vs. West Germany,

[90]

families with many children,[91][92][93] day care environments[94]) tend to have lower incidences of asthma and

allergic diseases. This seems to run counter to the logic that viruses are often causative agents in exacerbation of asthma.[95][96][97] Additionally, other studies have shown that viral infections of the lower airway may in some cases induce asthma, as a history of bronchiolitis or croup in early childhood is a predictor of asthma risk in later life.[98] Studies which show that upper respiratory tract infections are protective against asthma risk also tend to show that lower respiratory tract infections conversely tend to increase the risk of asthma.[99]

[edit]Socioeconomic

factors

The incidence of asthma is highest among low-income populations worldwide[specify]. Asthma deaths are most common in low and middle income countries,[100] and in the Western world, it is found in those low-income neighborhoods whose populations consist of large percentages of ethnic minorities.[101] Additionally, asthma has been strongly associated with the presence of cockroaches in living quarters; these insects are more likely to be found in those same neighborhoods.[102] Most likely due to income and geography, the incidence of and treatment quality for asthma varies among different racial groups.[103] The prevalence of "severe persistent" asthma is also greater in low-income communities than those with better access to treatment.[103][104]

[edit]Diagnosis Severity of acute asthma exacerbations[19] Near-fatal asthma High PaCO2 and/or requiring mechanical ventilation Any one of the following in a person with severe asthma:Clinical signs Measurements

Altered level of consciousness Peak flow < 33% Exhaustion Life threatening asthma Arrhythmia Low blood pressure Cyanosis Silent chest Poor respiratory effort Any one of:Peak flow 3350% Acute severe asthma Respiratory rate 25 breaths per minute Heart rate 110 beats per minute Unable to complete sentences in one breath Moderate asthma Worsening symptoms Oxygen saturation < 92% PaO2 < 8 kPa "Normal" PaCO2

exacerbation

Peak flow 5080% best or predicted No features of acute severe asthma

Obstruction of the lumen of the bronchiole by mucoid exudate, goblet cell metaplasia, epithelial basement membrane thickening and severe inflammation of bronchiole in a patient with asthma.

There is currently not a precise physiologic, immunologic, or histologic test for diagnosing asthma. The diagnosis is usually made based on the pattern of symptoms (airways obstruction and hyperresponsiveness) and/or response to therapy (partial or complete reversibility) over time.[10] The British Thoracic Society determines a diagnosis of asthma using a response to therapy approach. If the patient responds to treatment, then this is considered to be a confirmation of the diagnosis of asthma. The response measured is the reversibility of airway obstruction after treatment. Airflow in the airways is measured with a peak flow meter or spirometer, and the following diagnostic criteria are used by the British Thoracic Society:[105] 20% difference on at least three days in a week for at least two weeks; 20% improvement of peak flow following treatment, for example:

10 minutes of inhaled -agonist (e.g., salbutamol); six weeks of inhaled corticosteroid (e.g., beclometasone); 14 days of 30 mg prednisolone.

20% decrease in peak flow following exposure to a trigger (e.g., exercise).

In contrast, the US National Asthma Education and Prevention Program (NAEPP) uses a symptom patterns approach.[106] Their guidelines for the diagnosis and management of asthma state that a diagnosis of asthma begins by assessing if any of the following list of indicators is present.[13][106]While the indicators are not sufficient to support a diagnosis of asthma, the presence of multiple key indicators increases the probability of a diagnosis of asthma.[106] Spirometry is needed to establish a diagnosis of asthma.[106] Wheezinghigh-pitched whistling sounds when breathing outespecially in children. (Lack of wheezing and a normal chest examination do not exclude asthma.)

history of any of the following: Cough, worse particularly at night Recurrent wheeze Recurrent difficulty in breathing Recurrent chest tightness

Symptoms occur or worsen in the presence of: Exercise Viral infection Animals with fur or hair House-dust mites (in mattresses, pillows, upholstered furniture, carpets) Mold Smoke (tobacco, wood) Pollen Changes in weather Strong emotional expression (laughing or crying hard) Airborne chemicals or dusts Menstrual cycles

Symptoms occur or worsen at night, awakening the patient

The latest guidelines from the U.S. National Asthma Education and Prevention Program (NAEPP) recommend spirometry at the time of initial diagnosis, after treatment is initiated and symptoms are stabilized, whenever control of symptoms deteriorates, and every 1 or 2 years on a regular basis.[107] The NAEPP guidelines do not recommend testing peak expiratory flow as a regular screening method because it is more variable than spirometry. However, testing peak flow at rest (or baseline) and after exercise can be helpful, especially in young patients who may experience only exercise-induced asthma. It may also be useful for daily self-monitoring and for checking the effects of new medications.[107] Peak flow readings can be charted together with a record of symptoms or use peak flow charting software. This allows patients to track their peak flow readings and pass information back to their doctor or respiratory therapist.[108]

[edit]Differential

diagnosis

Differential diagnoses include:[106] Infants and Children

Upper airway diseases

Allergic rhinitis and allergic sinusitis

Obstructions involving large airways Foreign body in trachea or bronchus Vocal cord dysfunction Vascular rings or laryngeal webs Laryngotracheomalacia, tracheal stenosis, or bronchostenosis Enlarged lymph nodes or tumor

Obstructions involving small airways

Viral bronchiolitis or obliterative bronchiolitis Cystic fibrosis Bronchopulmonary dysplasia Heart disease

Other causes Recurrent cough not due to asthma Aspiration from swallowing mechanism dysfunction or gastroesophageal reflux Medication induced

Adults

COPD (e.g., chronic bronchitis or emphysema) Congestive heart failure Pulmonary embolism Mechanical obstruction of the airways (benign and malignant tumors) Pulmonary infiltration with eosinophilia Cough secondary to drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors) Vocal cord dysfunction

Before diagnosing asthma, alternative possibilities should be considered such as the use of known bronchoconstrictors (substances that cause narrowing of the airways, e.g. certain anti-inflammatoryagents or beta-blockers). Among elderly people, the presenting symptom may be fatigue, cough, or difficulty breathing,

all of which may be erroneously attributed to Chronic obstructive pulmonary disease(COPD), congestive heart failure, or simple aging.[109]

[edit]Chronic obstructive pulmonary disease


Chronic obstructive pulmonary disease can coexist with asthma and can occur as a complication of chronic asthma. After the age of 65 most people with obstructive airway disease will have asthma and COPD. In this setting, COPD can be differentiated by increased airway neutrophils, abnormally increased wall thickness, and increased smooth muscle in the bronchi. However, this level of investigation is not performed due to COPD and asthma sharing similar principles of management: corticosteroids, long acting beta agonists, and smoking cessation.[110] It closely resembles asthma in symptoms, is correlated with more exposure to cigarette smoke, an older age, less symptom reversibility after bronchodilator administration (as measured by spirometry), and decreased likelihood of family history of atopy.[111][112]

[edit]Others
The term "atopy" was coined to describe this triad of atopic eczema, allergic rhinitis and asthma.[56] Pulmonary aspiration, whether direct due to dysphagia (swallowing disorder) or indirect (due to acid reflux), can show similar symptoms to asthma. However, with aspiration, fevers might also indicateaspiration pneumonia. Direct aspiration (dysphagia) can be diagnosed by performing a modified barium swallow test. If the aspiration is indirect (from acid reflux), then treatment is directed at this is indicated.[citation needed]

[edit]Prevention
The evidence for the effectiveness of measures to prevent the development of asthma is weak.[113] Ones which show some promise include limiting smoke exposure both in utero and after delivery,breastfeeding, increased exposure to respiratory infection per the hygiene hypothesis (such as in those who attend daycare or are from large families).[113]

[edit]Management
A specific, customized plan for proactively monitoring and managing symptoms should be created. Someone who has asthma should understand the importance of reducing exposure to allergens, testing to assess the severity of symptoms, and the usage of medications. The treatment plan should be written down and adjusted according to changes in symptoms.[114] The most effective treatment for asthma is identifying triggers, such as cigarette smoke, pets, or aspirin, and eliminating exposure to them. If trigger avoidance is insufficient, medical treatment is recommended. Medical treatments used depend on the severity of illness and the frequency of symptoms. Specific medications for asthma are broadly classified into fast-acting and long-acting categories.[115][116]

Bronchodilators are recommended for short-term relief of symptoms. In those with occasional attacks, no other medication is needed. If mild persistent disease is present (more than two attacks a week), low-dose inhaled glucocorticoids or alternatively, an oral leukotriene antagonist or a mast cell stabilizer is recommended. For those who suffer daily attacks, a higher dose of inhaled glucocorticoid is used. In a severe asthma exacerbation, oral glucocorticoids are added to these treatments.[106]

[edit]Lifestyle

modification

Avoidance of triggers is a key component of improving control and preventing attacks. The most common triggers include allergens, smoke (tobacco and other), air pollution, non selective beta-blockers, and sulfitecontaining foods.[106][117][118][119] Cigarette smoking and second hand smoke (passive smoke) in regard to people with asthma causes problems in effectiveness of management medications such as steroid/corticosteroid therapies.[120]

[edit]Medications
Medications used to treat asthma are divided into two general classes: quick-relief medications used to treat acute symptoms; and long-term control medications used to prevent further exacerbation.[115] Fast acting

Salbutamol metered dose inhaler commonly used to treat asthma attacks.

Short acting beta2-adrenoceptor agonists (SABA), such as salbutamol (albuterol USAN) are the first line treatment for asthma symptoms.[6]

Anticholinergic medications, such as ipratropium bromide, provide additional benefit when used in combination with SABA in those with moderate or severe symptoms.[6] Anticholinergic bronchodilators can also be used if a person cannot tolerate a SABA.[15]

Older, less selective adrenergic agonists, such as inhaled epinephrine, have similar efficacy to SABAs.
[121]

They are however not recommended due to concerns regarding excessive cardiac stimulation.[122]

Long term control

Fluticasone propionate metered dose inhaler commonly used for long term control.

Glucocorticoids are the most effective treatment available for long term control.[115] Inhaled forms are usually used except in the case of severe persistent disease, in which oral steroids may be needed.
[115]

Inhaled formulations may be used once or twice daily, depending on the severity of symptoms.[123]

Long acting beta-adrenoceptor agonists (LABA) have at least a 12-hour effect. They are however not to be used without a steroid due to an increased risk of severe symptoms.[124][125][126] In December 2008, members of the FDA's drug-safety office recommended withdrawing approval for these medications in children. Discussion is ongoing about their use in adults.[127]

Leukotriene antagonists (such as zafirlukast) are an alternative to inhaled glucocorticoids, but are not preferred. They may also be used in addition to inhaled glucocorticoids but in this role are second line to LABA.[115]

Mast cell stabilizers (such as cromolyn sodium) are another non-preferred alternative to glucocorticoids.[115]

Delivery methods

Medications are typically provided as metered-dose inhalers (MDIs) in combination with an asthma spacer or as a dry powder inhaler. The spacer is a plastic cylinder that mixes the medication with air, making it easier to receive a full dose of the drug. A nebulizer may also be used. Nebulizers and spacers are equally effective in those with mild to moderate symptoms however insufficient evidence is available to determine whether or not a difference exists in those severe symptomatology.[128] Adverse effects Long-term use of inhaled glucocorticoids at usually doses carries a low risk for adverse effects.[129] This risk include the potential for cataracts and a slight decrease in height.[130][129]

[edit]Other
When asthma is unresponsive to usual medications, other options are available for both emergency management and prevention of flareups. For emergency management other options include:

Oxygen is used to alleviate hypoxia if saturations fall below 92%.[131] Magnesium sulfate intravenous treatment has been shown to provide a bronchodilating effect when used in addition to other treatment in severe acute asthma attacks.[132][133]

Heliox, a mixture of helium and oxygen, may also be considered in severe unresponsive cases.[133] Intravenous salbutamol is not supported by available evidence and is thus used only in extreme cases.[131] Methylxanthines (such as theophylline) were once widely used, but do not add significantly to the effects of inhaled beta-agonists.[131]

The dissociative anesthetic ketamine is theoretically useful if intubation and mechanical ventilation is needed in people who are approaching respiratory arrest; however, there is no evidence from clinical trials to support this.[134]

For those with severe persistent asthma not controlled by inhaled corticosteroids and LABAs bronchial thermoplasty can lead to clinical improvements.[135] It involves the delivery of controlled thermal energy to the airway wall during a series of bronchoscopies and result in a prolonged reduction in airway smooth muscle mass.[135]

[edit]Complementary

medicine

Many people with asthma, like those who suffer from other chronic disorders, use alternative treatments; surveys show that roughly 50% of asthma patients use some form of unconventional therapy.[136][137] There is little data to support the effectiveness of most of these therapies. Evidence is insufficient to support the usage of Vitamin C.[138] Acupuncture is not recommended for the treatment as there is insufficient evidence to support its use.[139][140] Air ionisers show no evidence that they improve asthma symptoms or benefit lung function; this applied equally to positive and negative ion generators.[141]

Dust mite control measures, including air filtration, chemicals to kill mites, vacuuming, mattress covers and others methods had no effect on asthma symptoms.[142] However, a review of 30 studies found that "bedding encasement might be an effective asthma treatment under some conditions" (when the patient is highly allergic to dust mite and the intervention reduces the dust mite exposure level from high levels to low levels).
[143]

Washing laundry/rugs in hot water was also found to improve control of allergens.[15]

A study of "manual therapies" for asthma, including osteopathic, chiropractic, physiotherapeutic and respiratory therapeutic manoeuvres, found there is insufficient evidence to support their use in treating.[144] The Buteyko breathing technique for controlling hyperventilation may result in a reduction in medications use however does not have any effect on lung function.[116] Thus an expert panel felt that evidence was insufficient to support its use.[139]

[edit]Prognosis
The prognosis for asthma is good, especially for children with mild disease.[13][not in citation given] Of asthma diagnosed during childhood, 54% of cases will no longer carry the diagnosis after a decade.[citation needed] The extent of permanent lung damage in people with asthma is unclear. Airway remodeling is observed, but it is unknown whether these represent harmful or beneficial changes.[145] Although conclusions from studies are mixed, most studies show that early treatment with glucocorticoids prevents or ameliorates decline in lung function as measured by several parameters.[146] For those who continue to suffer from mild symptoms, corticosteroids can help most to live their lives with few disabilities. It is more likely to consider immediate medication of inhaled corticosteroids as soon as asthma attacks occur. According to studies conducted, patients with relatively mild asthma who have received inhaled corticosteroids within 12 months of their first asthma symptoms achieved good functional control of asthma after 10 years of individualized therapy as compared to patients who received this medication after 2 years (or more) from their first attacks.[citation needed] Though they (delayed) also had good functional control of asthma, they were observed to exhibit slightly less optimal disease control and more signs of airway inflammation.[citation needed] Asthma mortality has decreased over the last few decades due to better recognition and improvement in care.
[147]

[edit]Epidemiology

Disability-adjusted life year for asthma per 100,000 inhabitants in 2004.[148]

no data <100 100150 150200 200250 250300 300350

350400 400450 450500 500550 550600 >600

As of 2009, 300 million people worldwide were affected by asthma leading to approximately 250,000 deaths per year.[12][124][149][150] It is estimated that asthma has a 7-10% prevalence worldwide.[151] As of 1998, there was a great disparity in the prevalence of asthma across the world, with a trend toward more developed and westernized countries having higher rates of asthma,[152] with as high as a 20 to 60-fold difference. Westernization however does not explain the entire difference in asthma prevalence between countries, and the disparities may also be affected by differences in genetic, social and environmental risk factors.[61] Mortality however is most common in low to middle income countries,[153] while symptoms were most prevalent (as much as 20%) in the United Kingdom, Australia, New Zealand, and Republic of Ireland; they were lowest (as low as 23%) in Eastern Europe, Indonesia, Greece, Uzbekistan, India, and Ethiopia.[152][dated info] Asthma affects approximately 7% of the population of the United States[124] and 5% of people in the United Kingdom.[154] Asthma causes 4,210 deaths per year in the United States.[151][155] In 2005 in the United States asthma affected more than 22 million people including 6 million children.[147] It accounted for nearly 1/2 million hospitalizations that same year.[147] More boys have asthma than girls, but more women have it than men.[156] In England, an estimated 261,400 people were newly diagnosed with asthma in 2005; 5.7 million people had an asthma diagnosis and were prescribed 32.6 million asthma-related prescriptions.[157]

[edit]Increasing

frequency

The prevalence of childhood asthma in the United States has increased since 1980, especially in younger children.

Rates of asthma have increased significantly between the 1960s and 2008.[158][159] Some 9% of US children had asthma in 2001, compared with just 3.6% in 1980. The World Health Organization (WHO) reports that some 10% of the Swiss population suffers from asthma today,[160] compared with just 2% some 2530 years ago. In the United States specifically data from several national surveys in the United States reveal the age-adjusted

prevalence of asthma increased from 7.3 to 8.2 percent during the years 2001 through 2009 .[161] Previous analysis of data from 2001 to 2007 had suggested the prevalence of asthma was stable.[161]

[edit]Variability
Asthma prevalence in the US is higher than in most other countries in the world, but varies drastically between diverse US populations.[61] In the US, asthma prevalence is highest in Puerto Ricans, African Americans, Filipinos, Irish Americans, and Native Hawaiians, and lowest in Mexicans and Koreans.[162][163][164] Mortality rates follow similar trends, and response to salbutamol is lower in Puerto Ricans than in African Americans or Mexicans.[165][166] As with worldwide asthma disparities, differences in asthma prevalence, mortality, and drug response in the US may be explained by differences in genetic, social and environmental risk factors. Asthma prevalence also differs between populations of the same ethnicity who are born and live in different places.[167] US-born Mexican populations, for example, have higher asthma rates than non-US born Mexican populations that are living in the US.[168] There is no correlation between asthma and gender in children. More adult women are diagnosed with asthma than adult men, but this does not necessarily mean that more adult women have asthma.[169]

[edit]History
Asthma was first recognized in ancient Egypt and treatment was inhalation of frankincense.[170] Officially recognized as a specific respiratory problem separate from others was first recognized and named by Hippocrates circa 450 BC. During the 1930s50s, asthma was considered as being one of the 'holy seven' psychosomatic illnesses. Its aetiology was considered to be psychological, with treatment often based on psychoanalysis and other 'talking cures'.[171] As these psychoanalysts interpreted the asthmatic wheeze as the suppressed cry of the child for its mother, so they considered that the treatment of depression was especially important for individuals with asthma.[171] among the first papers in modern medicine, is one that was published in 1873 and this paper tried to explain the pathophysiology of the disease.[172] And one of the first papers discussing treatment of asthma was released in 1872, the author concluded in his paper that asthma can be cured by rubbing the chest with chloroform liniment.[173] Among the first times researchers referred to medical treatment was in 1880, when Dr. J. B. Berkart used IV therapy to administer doses of a drug called pilocarpin.[174] In 1886, F.H. Bosworth FH suspected a connection between asthma and hay fever.[175] Epinephrine was first referred to in the treatment of asthma in 1905,[176] and for acute asthma in 1910.[177]

[edit]Notes

1. ^ NHLBI Guideline 2007, pp. 1112 2. ^ British Guideline 2009, p. 3

3. ^ a b c Yawn, BP (September 2008). "Factors accounting for asthma variability: achieving optimal symptom
control for individual patients". Primary Care Respiratory Journal 17(3): 138 147. doi:10.3132/pcrj.2008.00004.PMID 18264646.

4. ^ a b Kumar, Vinay; Abbas, Abul K; Fausto, Nelson; Aster, Jon (2010). Robbins and Cotran Pathologic Basis
of Disease (8th ed.). Saunders. p. 688. ISBN 9781416031215.

5. ^ a b c Martinez FD (2007). "Genes, environments, development and asthma: a reappraisal". Eur Respir
J 29 (1): 17984. doi:10.1183/09031936.00087906.PMID 17197483.

6. ^ a b c NHLBI Guideline 2007, p. 214 7. ^ NHLBI Guideline 2007, pp. 169172 8. ^ GINA 2009, p. 69 9. ^ Fanta CH (March 2009). "Asthma". N Engl J Med 360 (10): 1002
14. doi:10.1056/NEJMra0804579. PMID 19264689.

10. ^ a b Lemanske RF, Busse WW (February 201 http://www.medicinenet.com/asthma/article.htm


Medical Author: Alan Szeftel, MD Medical Author: George Schiffman, MD, FCCP Medical Editor: William C. Shiel Jr., MD, FACP, FACR

Myths, facts, and statistics about asthma What is asthma? From the past to the present The scope of the problem Normal bronchial tubes How does asthma affect breathing? The importance of inflammation Which triggers cause an asthma attack? Allergens Irritants The many faces of asthma Types: allergic (extrinsic) and nonallergic (intrinsic) asthma

Typical asthma symptoms and signs Acute asthma attack What medications are used in the treatment of asthma? Asthma At A Glance Patient Discussions: Asthma - Symptoms Patient Discussions: Asthma - Effective Treatments Find a local Asthma & Allergy Specialist in your town

What do each of these individuals have in common: First, an 18-year-old suddenly develops wheezing and shortness of breath when visiting his grandmother, who happens to have a cat. Second, a 30-year-old woman has colds that "always go into her chest," causing coughing and difficulty breathing. Lastly, a 60-year-old man develops shortness of breath with only slight exertion even though he has never smoked. The answer is that they all have asthma. These are some of the many faces of asthma. We now know that anyone who is exposed to the "proper" conditions can develop the cardinal symptoms of asthma (cough, wheeze, and shortness of breath). Most researchers believe that the different patterns of asthma are all related to one condition. But some researchers feel that separate forms of lung conditions exist. There is currently no cure for asthma, and no single exact cause has been identified. Therefore, understanding the changes that occur in asthma, how it makes you feel, and how it can behave over time is essential. This knowledge can empower people with asthma to take an active role in their own health.

Typical Asthma Symptoms and Signs


The symptoms of asthma vary from person to person and in any individual from time to time. It is important to remember that many of these symptoms can be subtle and similar to those seen in other conditions. All of the symptoms mentioned below can be present in other respiratory, and sometimes, in heart conditions. This potential confusion makes identifying the settings in which the symptoms occur and diagnostic testing very important in recognizing this disorder. The following are the four major recognized asthma symptoms:
Shortness of breath, especially with exertion or at night

Wheezing is a whistling or hissing sound when breathing out

Coughing may be chronic, is usually worse at night and early morning, and may occur after exercise or when exposed to cold, dry air

Chest tightness may occur with or without the above symptoms

Learn more about symptoms and signs of asthma

TOP SEARCHED ASTHMA TERMS:


treatment, attack, signs and symptoms,facts, triggers, management, statistics,wheezing, medication, different types,prevention, prednisone, allergy, inhaler,exercise-induced asthma, causes

Myths, facts, and statistics about asthma


Before we present the typical symptoms of asthma, we should dispel some common myths about this condition. This is best achieved by conducting a short true or false quiz. 1. T or F - Asthma is "all in the mind." 2. T or F - You will "grow out of it." 3. T or F - Asthma can be cured, so it is not serious and nobody dies from it. 4. T or F - You are likely to develop asthma if someone in your family has it. 5. T or F - You can "catch" asthma from someone else who has it. 6. T or F - Moving to a different location, such as the desert, can cure asthma.

7. T or F - People with asthma should notexercise.


8. T or F - Asthma is best controlled when one has an asthma management plan designed by your doctor. This should include the medications used for quick relief as well as maintenance therapy.

9. T or F - Medications used to treat asthma are habit forming.


10. T or F - Someone with asthma can provoke episodes anytime they want in order to get attention. Here are the answers: 1. F - Asthma is not a psychological condition. However, emotional triggers can cause flare-ups. 2. F - You cannot outgrow asthma. In about 50% of children with asthma, the condition may become inactive in the teenage years. The symptoms, however, may reoccur anytime in adulthood. 3. F - There is no cure for asthma, but the disease can be controlled in most patients with good medical care. The condition should be taken seriously, since uncontrolled asthma may result in emergency hospitalization and possible death. 4. T - You have a 6% chance of having asthma if neither parent has the condition, a 30% chance if one parent has it, and a 70% chance if both parents have it. 5. F - Asthma is not contagious. 6. F - A new environment may temporarily improve asthma symptoms, but it will not cure asthma. After a few years in the new location, many people become sensitized to the new environment and the asthma symptoms return with the same or even greater intensity than before.

7. F - Swimming is an optimal exercise for those with asthma. On the other hand, exercising in dry, cold air may be a trigger for asthma in some people.

8. F - Asthma is best controlled by having an asthma management plan designed by your doctor that includes the medications used for quick relief and those used as controllers.

9. F - Asthma medications are not addictive. 10. F - Asthma attacks cannot be faked. In rare cases, there is a psychological condition known by a variety of names (factious asthma, spastic dysphonia, globus hystericus) where emotional issues may cause symptoms that mimic the symptoms of asthma.

11.What is asthma?
12. Asthma is a chronic inflammation of the bronchial tubes (airways) that causes swelling and narrowing (constriction) of the airways. The result is difficulty breathing. The bronchial narrowing is usually either totally or at least partially reversible with treatments. 13. Bronchial tubes that are chronically inflamed may become overly sensitive to allergens (specific triggers) or irritants (nonspecific triggers). The airways may become "twitchy" and remain in a state of heightened sensitivity. This is called "bronchial hyperreactivity" (BHR). It is likely that there is a spectrum of bronchial hyperreactivity in all individuals. However, it is clear that asthmatics and allergic individuals (without apparent asthma) have a greater degree of bronchial hyperreactivity than nonasthmatic and nonallergic people. In sensitive individuals, the bronchial tubes are more likely to swell and constrict when exposed to triggers such as allergens, tobacco smoke, or exercise. Amongst asthmatics, some may have mild BHR and no symptoms while others may have severe BHR and chronic symptoms. 14. Asthma affects people differently. Each individual is unique in their degree of reactivity to environmental triggers. This naturally influences the type and dose of medication prescribed, which may vary from one individual to another.

15.From the past to the present


16. Physicians in ancient Greece used the word asthma to describe breathlessness or gasping. They believed that asthma was derived from internal imbalances, which could be restored by healthy diet, plant and animal remedies, or lifestyle changes. 17. Allergy jargon
Asthma is derived from the Greek word panos, meaning panting. Chinese healers understood that xiao-chiran, or "wheezy breathing," was a sign of imbalance in the life force they called qi. They restored qi by means of herbs, acupuncture, massage, diet, and exercise. The Hindu philosophers connected the soul and breath as part of the mind, body, and spirit connection. Yoga uses control of breathing to enhance meditation. Indian physicians taught these breathing techniques to help manage asthma. Allergy fact Maimonides was a renowned 12th-century rabbi and physician who practiced in the court of the sultan of Egypt. He recommended to one of the royal princes with asthma that he eat,

drink, and sleep less. He also advised that he engage in less sexual activity, avoid the polluted city environment, and eat a specific remedy...chicken soup.

18. The balance of the "four humors," which was derived from the Greco-Roman times, influenced European medicine until the middle of the 18th century. In a healthy person, the four humors, or bodily fluids -- blood, black bile, yellow bile, and phlegm -- were in balance. An excess of one of these humors determined what kinds of disorders were present. Asthmatics who were noted for their coughing, congestion, and excess mucus (phlegm) production were therefore regarded as "phlegmatic." 19. By the 1800s, aided by the invention of the stethoscope, physicians began to recognize asthma as a specific disease. However, patients still requested the traditional treatments of the day, such as bloodletting, herbs, and smoking tobacco. These methods were used for a variety of conditions, including asthma. Of the many remedies that were advertised for asthma throughout the 19th century, none were particularly helpful. 20. Allergy fact
As early as 1892, the famous Canadian-American physician Sir William Osler suggested that inflammation played an important role in asthma.

21. Bronchial dilators first appeared in the 1930s and were improved in the 1950s. Shortly thereafter, corticosteroid drugs that treated inflammation appeared and have become the mainstay of therapy used today.

22.The scope of the problem


23. Asthma is now the most common chronic illness in children, affecting one in every 15. In North America, 5% of adults are also afflicted. In all, there are about 1 million Canadians and 15 million Americans who suffer from this disease. 24. The number of new cases and the yearly rate of hospitalization for asthma have increased about 30% over the past 20 years. Even with advances in treatment, asthma deaths among young people have more that doubled. 25. Allergy fact
There are about 5,000 deaths annually from asthma in the U.S. and about 500 deaths per year in Canada.

26.Normal bronchial tubes


27. Before we can appreciate how asthma affects the bronchial airways, we should first take a quick look at the structure and function of normal bronchial tubes.

28.

29.
30. The air we breathe in through our nose is processed to prepare it for presentation to our lower respiratory tract. This air is moistened, heated, and cleansed prior to passage through the vocal cords (larynx) and into the windpipe (trachea). Dry or cold air presented to our trachea can cause coughing and wheezing as a normal response to this type of irritation. The air then enters the lungs by way of two large air passages (bronchi), one for each lung. The bronchi divide within each lung into smaller and smaller air tubes (bronchioles), just like branches of an inverted tree. Inhaled air is brought through these airways to the millions of tiny air sacs (alveoli) that are contained in the lungs. Oxygen (O2) passes from the air sacs into the bloodstream through numerous tiny blood vessels called capillaries. Similarly, the body's waste product, carbon dioxide (CO2), is returned to the air sacs and then eliminated upon each exhalation. 31. Normal bronchial tubes allow rapid passage of air in and out of the lungs to ensure that the levels of O2 and CO2 remain constant in the bloodstream. The outer walls of the bronchial tubes are surrounded by smooth muscles that contract and relax automatically with each breath. This allows the required amount of air to enter and exit the lungs to achieve this normal exchange of O2 and CO2. The contraction and relaxation of the bronchial smooth muscles are controlled by two different nervous systems that work in harmony to keep the airways open. 32. The inner lining of the bronchial tubes, called the bronchial mucosa, contains: (1) mucus glands that produce just enough mucus to properly lubricate the airways; and (2) a variety of so-called inflammatory cells, such as eosinophils, lymphocytes, and mast cells. These cells are designed to protect the bronchial mucosa from the microorganisms, allergens, and irritants we inhale, and which can cause the bronchial tissue to swell. Remember, however, that these inflammatory cells are also important players in the allergic reaction. Therefore, the presence of these cells in the bronchial tubes causes them to be a prime target for allergic inflammation.

How does asthma affect breathing?


Asthma causes a narrowing of the breathing airways, which interferes with the normal movement of air in and out of the lungs. Asthma involves only the bronchial tubes and does not affect the air sacs or the lung tissue. The narrowing that occurs in asthma is caused by three major factors: inflammation, bronchospasm, and hyperreactivity. Inflammation The first and most important factor causing narrowing of the bronchial tubes is inflammation. The bronchial tubes become red, irritated, and swollen. This inflammation increases the thickness of the wall of the bronchial tubes and thus results in a smaller passageway for air to flow through. The inflammation occurs in response to an allergen or irritant and results from the action of chemical mediators (histamine,leukotrienes, and others). The inflamed tissues produce an excess amount of "sticky" mucus into the tubes. The mucus can clump together and form "plugs" that can clog the smaller airways. Specialized allergy and inflammation cells (eosinophils and white blood cells), which accumulate at the site, cause tissue damage. These damaged cells are shed into the airways, thereby contributing to the narrowing. Bronchospasm The muscles around the bronchial tubes tighten during an attack of asthma. This muscle constriction of the airways is called bronchospasm. Bronchospasm causes the airway to narrow further. Chemical mediators and nerves in the bronchial tubes cause the muscles to constrict. Bronchospasm can occur in all humans and can be brought on by inhaling cold or dry air. Hyperreactivity (hypersensitivity) In patients with asthma, the chronically inflamed and constricted airways become highly sensitive, or reactive, to triggers such as allergens, irritants, and infections. Exposure to these triggers may result in progressively more inflammation and narrowing. The combination of these three factors results in difficulty with breathing out, or exhaling. As a result, the air needs to be forcefully exhaled to overcome the narrowing, thereby causing the typical "wheezing" sound. People with asthma also frequently "cough" in an attempt to expel the thick mucus plugs. Reducing the flow of air may result in less oxygen passing into the bloodstream, and if very severe, carbon dioxide may dangerously accumulate in the blood.

The importance of inflammation


Inflammation, or swelling, is a normal response of the body to injury or infection. The blood flow increases to the affected site and cells rush in and ward off the offending problem. The healing process has begun. Usually, when the healing is complete, the inflammation subsides. Sometimes, the healing process causes scarring. The central issue in asthma, however, is that the inflammation does not resolve completely on its own. In the short term, this results in recurrent "attacks" of asthma. In the long term, it may lead to permanent thickening of the bronchial walls, called airway "remodeling." If this occurs, the narrowing of the bronchial tubes may become irreversible and poorly

responsive to medications. When this fixed obstruction to airflow develops, asthma is then classified in the group of lung conditions known as chronic obstructive pulmonary disease (COPD). Therefore, the goals of asthma treatment are: (1) in the short term, to control airway inflammation in order to reduce the reactivity of the airways; and (2) in the long term, to prevent airway remodeling.
Allergy assist The hallmark of managing asthma is the prevention and treatment of airway inflammation. It is also likely that control of the inflammation will prevent airway remodeling and thereby prevent permanent loss of lung function.

Various triggers in susceptible individuals result in airway inflammation. Prolonged inflammation induces a state of airway hyperreactivity, which might progress to airway remodeling unless treated effectively.

Which triggers cause an asthma attack?


Asthma symptoms may be activated or aggravated by many agents. Not all asthmatics react to the same triggers. Additionally, the effect that each trigger has on the lungs varies from one individual to another. In general, the severity of your asthma depends on how many agents activate your symptoms and how sensitive your lungs are to them. Most of these triggers can also worsen nasal or eye symptoms. Triggers fall into two categories: allergens ("specific"); nonallergens -- mostly irritants (nonspecific).

Once your bronchial tubes (nose and eyes) become inflamed from an allergic exposure, a reexposure to the offending allergens will often activate symptoms. These "reactive" bronchial tubes might also respond to other triggers, such as exercise, infections, and other irritants. The following is a simple checklist. Common asthma triggers: Allergens

"seasonal" pollens

year-round dust mites, molds, pets, and insect parts

foods, such as fish, egg, peanuts, nuts, cow's milk, and soy

additives, such as sulfites

work-related agents, such as latex, epoxides, and formaldehyde

Allergy fact About 80% of children and 50% of adults with asthma also have allergies.

Irritants

respiratory infections, such as those caused by viral "colds," bronchitis, and sinusitis

drugs, such as aspirin, other NSAIDs (nonsteroidal antiinflammatory drugs), and beta blockers (used to treat blood pressure and other heart conditions)

tobacco smoke

outdoor factors, such as smog, weather changes, and diesel fumes

indoor factors, such as paint, detergents, deodorants, chemicals, and perfumes

nighttime

GERD (gastroesophageal reflux disorder)

exercise, especially under cold dry conditions

work-related factors, such as chemicals, dusts, gases, and metals

emotional factors, such as laughing, crying, yelling, and distress

hormonal factors, such as in premenstrual syndrome

The many faces of asthma


The many potential triggers of asthma largely explain the different ways in which asthma can present. In most cases, the disease starts in early childhood from 2-6 years of age. In this age group, the cause of asthma is often linked to exposure to allergens, such as dust mites, tobacco smoke, and viral respiratory infections. In very young children, less than 2 years of age, asthma can be difficult to diagnose with certainty. Wheezing at this age often follows a viral infection and might disappear later, without ever leading to asthma. Asthma, however, can develop again in adulthood. Adult-onset asthma occurs more often in women, mostly middle-aged, and frequently follows a respiratory tract infection. The triggers in this group are usually nonallergic in nature.

Types: allergic (extrinsic) and nonallergic (intrinsic) asthma


Your doctor may refer to asthma as being "extrinsic" or "intrinsic." A better understanding of the nature of asthma can help explain the differences between them. Extrinsic, or allergic asthma, is more common (90% of all cases) and typically develops in childhood. Approximately 80% of children with asthma also have documented allergies. Typically, there is a family history of allergies. Additionally, other allergic conditions, such as nasal allergies or eczema, are often also present.

Allergic asthma often goes into remission in early adulthood. However, in 75% of cases, the asthma reappears later. Intrinsic asthma represents about 10% of all cases. It usually develops after the age of 30 and is not typically associated with allergies. Women are more frequently involved and many cases seem to follow a respiratory tract infection. The condition can be difficult to treat and symptoms are often chronic and year-round.

Typical asthma symptoms and signs


The symptoms of asthma vary from person to person and in any individual from time to time. It is important to remember that many of these symptoms can be subtle and similar to those seen in other conditions. All of the symptoms mentioned below can be present in other respiratory, and sometimes, in heart conditions. This potential confusion makes identifying the settings in which the symptoms occur and diagnostic testing very important in recognizing this disorder. The following are the four major recognized asthma symptoms:

Shortness of breath, especially with exertion or at night

Wheezing is a whistling or hissing sound when breathing out

Coughing may be chronic, is usually worse at night and early morning, and may occur after exercise or when exposed to cold, dry air

Chest tightness may occur with or without the above symptoms

Asthma fact Asthma is classified according to the frequency and severity of symptoms, or "attacks," and the results of pulmonary (lung) function tests.

30% of affected patients have mild, intermittent (less than two episodes a week) symptoms of asthma with normal breathing tests

30% have mild, persistent (two or mores episodes a week) symptoms of asthma with normal or abnormal breathing tests

40% have moderate or severe, persistent (daily or continuous) symptoms of asthma with abnormal breathing tests

Acute asthma attack


An acute, or sudden, asthma attack is usually caused by an exposure to allergens or an upperrespiratory-tract infection. The severity of the attack depends on how well your underlying asthma is being controlled (reflecting how well the airway inflammation is being controlled). An acute attack is potentially life-threatening because it may continue despite the use of your usual quick-relief medications (inhaled bronchodilators). Asthma that is unresponsive to treatment with an inhaler should prompt you to seek medical attention at the closest hospital emergency room or your asthma specialist office, depending on the circumstances and time of day. Asthma attacks do not stop on their own without treatment. If you ignore the early warning signs, you put yourself at risk of developing status asthmaticus.
Allergy fact Prolonged attacks of asthma that do not respond to treatment with bronchodilators are a medical emergency. Physicians call these severe attacks "status asthmaticus," and they require immediate emergency care.

The symptoms of severe asthma are persistent coughing and the inability to speak full sentences or walk without shortness of breath. Your chest may feel closed, and your lips may have a bluish tint. In addition, you may feel agitation, confusion, or an inability to concentrate. You may hunch your shoulders, sit or stand up to breathe more easily, and strain your abdominal and neck muscles. These are signs of an impending respiratory system failure. At this point, it is unlikely that inhaled medications will reverse this process. A mechanical ventilator may be needed to assist the lungs and respiratory muscles. A face mask or a breathing tube is inserted in the nose or mouth for this treatment. These breathing aids are temporary and are removed once the attack has subsided and the lungs have recovered sufficiently to resume the work of breathing on their own. A short hospital stay in an intensive-care unit may be a result of a severe attack that has not been promptly treated. To avoid such hospitalization, it is best, at the onset of symptoms, to begin immediate early treatment at home or in your doctor's office.
Allergy fact The presence of wheezing or coughing in and of itself is not a reliable standard for judging the severity of an asthma attack. Very severe attacks may clog the tubes to such a degree that the lack of air in and out of your lungs fails to produce wheezing or coughing.

What medications are used in the treatment of asthma?


Most asthma medications work by relaxing bronchospasm (bronchodilators) or reducing inflammation (corticosteroids). In the treatment of asthma, inhaled medications are generally

preferred over tablet or liquid medicines, which are swallowed (oral medications). Inhaled medications act directly on the airway surface and airway muscles where the asthma problems initiate. Absorption of inhaled medications into the rest of the body is minimal. Therefore, adverse side effects are fewer as compared to oral medications. Inhaled medications include beta-2 agonists, anticholinergics,corticosteroids, and cromolyn sodium. Oral medications include aminophylline, leukotriene antagonists, beta-2 agonists, and corticosteroid tablets. Historically, one of the first medications used for asthma was adrenaline (epinephrine). Adrenaline has a rapid onset of action in opening the airways (bronchodilation). It is still often used in emergency situations for asthma. Unfortunately, adrenaline has many side effects, including rapid heart rate,headache, nausea, vomiting, restlessness, and a sense of panic. Medications chemically similar to adrenaline have been developed. These medications, called beta2 agonists, have the bronchodilating benefits of adrenaline without many of its unwanted side effects. Beta-2 agonists are inhaled bronchodilators which are called "agonists" because they promote the action of the beta-2 receptor of bronchial wall muscle. This receptor acts to relax the muscular wall of the airways (bronchi), resulting in bronchodilation. The bronchodilator action of beta-2 agonists starts within minutes after inhalation and lasts for about four hours. Examples of these medications include albuterol (Ventolin HFA, Proventil HFA), levalbuterol(Xopenex), metaproterenol (Alupent), pirbuterol acetate (Maxair), andterbutaline sulfate (Brethaire). Recently, chlorofluorocarbons (CFCs) have been removed from all MDI inhalers because of the environmental effects on the ozone layer. These have been replaced by a new propellant, hydrofluoroalkane (HFA). Patients may notice that the jet they feel in the back of their throat is less intense when compared with the CFC inhaler. They should be instructed that they are still receiving the same amount of medication though it may feel different than their older inhaler. Another very important point that patients must be aware of is that "floating" these new inhalers does not help in determining the amount of medication left in the MDI. In the past, the CFC devices could be floated in a bowl of water. With more medicine in the inhaler, the canister would sink and gradually float as it emptied. This is not the case with the HFA inhalers, as floating will actually clog the inhaler. The number of actuations must be counted to determine if medication is still left in the inhaler. Shaking the inhaler is not an effective method of determining how much medication is left. Often propellant (HFA) will continue to come out of the inhaler even after the medication is used up. Ventolin HFA and Proventil HFA both come with a counter device. This group of inhalers are often referred to as rescue inhalers because they are used when symptoms are anticipated or occur. The following medications are often referred to as maintenance medication because they are used routinely despite symptoms. Depending on the state of control of asthma, the number of medications and/or the dose can be adjusted up or down. This is referred to as step-up therapy and step-down therapy, respectively. A new group of long-acting beta-2 agonists has been developed with a sustained duration of effect of 12 hours. These inhalers can be taken twice a day. Salmeterol xinafoate (Serevent) and formoterol (Foradil) are examples of this group of medications. The long-acting beta-2 agonists should not be used for acute attacks. Beta-2 agonists can have side effects, such as anxiety, tremor, palpitations or fast heart rate, and lowering of blood potassium. There is data to suggest that

taking long-acting beta-2 agonists alone may be life-threatening and both of these agents come with an FDA-issued box warning. They are best taken along with inhaled corticosteroids (see below). Just as beta-2 agonists can dilate the airways, beta blocker medications impair the relaxation of bronchial muscle by beta-2 receptors and can cause constriction of airways, aggravating asthma. Therefore, beta blockers, such as the blood pressure medications propranolol (Inderal) and atenolol(Tenormin), should be avoided by asthma patients if possible. Sometimes, however, the benefits of these agents outweigh the risks. Your physician's clinical judgement will take into account the balance of these conflicting properties. The anticholinergic agents act on a different type of nerves than the beta-2 agonists to achieve a similar relaxation and opening of the airway passages. These two groups of bronchodilator inhalers when used together can produce an enhanced bronchodilation effect. An example of a commonly used anticholinergic agent is ipratropium bromide (Atrovent). Ipratropium takes longer to work as compared with the beta-2 agonists, with peak effectiveness occurring two hours after intake and lasting six hours. A long-acting anticholinergic, tiotropium (Spiriva), has recently be shown to be of benefit in treating asthma. When symptoms of asthma are difficult to control with beta-2 agonists, inhaled corticosteroids (cortisone) are often added. Corticosteroids can improve lung function and reduce airway obstructionover time. Examples of inhaled corticosteroids include beclomethasonedipropionate (Beclovent, Qvar, and Vanceril), triamcinolone acetonide(Azmacort), mometasone (Asthmanex), budesonide (Pulmocort), andflunisolide (Aerobid). The ideal dose of corticosteroids is still unknown. The side effects of inhaled corticosteroids include hoarseness, loss of voice, andoral yeast infections. Early use of inhaled corticosteroids may prevent irreversible damage to the airways. To decrease the deposition of medications on the throat and increase the amount reaching the airways, spacers can be helpful. Spacers are tube-like chambers attached to the outlet of the MDI canister. Spacer devices can hold the released medications long enough for patients to inhale them slowly and deeply into the lungs. A spacing device placed between the mouth and the MDI can improve medication delivery and reduce the side effects on the mouth and throat. Rinsing out the mouth after use of a steroid inhaler also can decrease these side effects. Combination inhaler therapy is now available for the treatment of asthma. These medications include Advair (fluticasone and salmeterol), Symbicort (budesonide and formoterol), and Dulera (mometasone and formoterol). Symbicort and Dulera use the standard MDI inhaler device with a dose counter. Advair has a unique powdered delivery system with a built-in counter. Cromolyn sodium (Intal) prevents the release of certain chemicals in the lungs, such as histamine, which can cause asthma. Exactly how cromolyn works to prevent asthma needs further research. Cromolyn is not a corticosteroid and is usually not associated with significant side effects. Cromolyn is useful in preventing asthma but has limited effectiveness once acute asthma starts. Cromolyn can help prevent asthma triggered by exercise, cold air, and allergic substances, such as cat dander. Cromolyn may be used in children as well as adults. Theophylline (Theo-Dur, Theolair, Slo-bid, Uniphyl, Theo-24) and aminophylline are examples of methylxanthines. Methylxanthines are administered orally or intravenously. Before the inhalers

became popular, methylxanthines were the mainstay of treatment of asthma. Caffeine that is in common coffee and soft drinks is also a methylxanthine drug! Theophylline relaxes the muscles surrounding the air passages and prevents certain cells lining the bronchi (mast cells) from releasing chemicals, such as histamine, which can cause asthma. Theophylline can also act as a mild diuretic, causing an increase in urination. For asthma that is difficult to control, methylxanthines can still play an important role. Dosage levels of theophylline or aminophylline are closely monitored. Excessive levels can lead to nausea, vomiting, heart-rhythm problems, and evenseizures. In certain medical conditions, such as heart failure or cirrhosis, dosages of methylxanthines are lowered to avoid excessive blood levels. Drug interactions with other medications, such as cimetidine (Tagamet),calcium channel blockers (Procardia), quinolones (Cipro), and allopurinol(Zyloprim) can further affect drug blood levels. Corticosteroids are given orally for severe asthma unresponsive to other medications. Unfortunately, high doses of corticosteroids over long periods can have serious side effects, including osteoporosis, bone fractures,diabetes mellitus, high blood pressure, thinning of the skin and easybruising, insomnia, emotional changes, and weight gain. Expectorants help thin airway mucus, making it easier to clear the mucus by coughing. Potassium iodide is not commonly used and has the potential side effects of acne, increased salivation, hives, and thyroid problems.Guaifenesin (Entex, Humibid) can increase the production of fluid in the lungs and help to decrease the apparent thickness of the mucus but can also be an airway irritant for some people. In addition to bronchodilator medications for those patients with atopic asthma, avoiding allergens or other irritants can be very important. In patients who cannot avoid the allergens, or in those whose symptoms cannot be controlled by medications, allergy shots are considered. The benefits of allergy shots (desensitization) in the prevention of asthma has not been firmly established. Some doctors are still concerned about the risk of anaphylaxis, which occurs in one in 2 million doses given. Allergy shotsmost commonly benefit children allergic to house dust mites. Other benefits can be seen with pollens and animal dander. In some asthma patients, allergy antibodies of one form known as immunoglobulin E (IgE) may play a key role. If these substances are elevated in the blood, a new form of medication may be helpful for severe asthma. An antibody to IgE, known as omalizumab (Xolair) has been developed. This must be administered by injection in a doctor's office. This is extremely expensive. However, for patients with asthma that is difficult to manage, this option may be helpful. In some asthma patients, avoidance of aspirin, or other NSAIDs (commonly used in treating arthritis inflammation) is important. In other patients, adequate treatment of backflow of stomach acid (esophageal reflux) prevents irritation of the airways. Measures to prevent esophageal reflux include medications, weight loss, dietary changes, and stopping cigarettes, coffee, and alcohol. Examples of medications used to reduce reflux includeomeprazole (Prilosec) and ranitidine (Zantac). Patients with severe reflux problems causing lung problems may need surgery to strengthen the esophageal sphincter in order to prevent acid reflux (fundoplicationsurgery).

Asthma At A Glance

Asthma is a chronic inflammation of the bronchial tubes (airways) that causes swelling and narrowing (constriction) of the airways. The bronchial narrowing is usually either totally or at least partially reversible with treatments. Asthma is now the most common chronic illness in children, affecting one in every 15. Asthma involves only the bronchial tubes and usually does not affect the air sacs or the lung tissue. The narrowing that occurs in asthma is caused by three major factors: inflammation, bronchospasm, and hyperreactivity. Allergy can play a role in some, but not all, asthma patients. Many factors can precipitate asthma attacks and they are classified as either allergens or irritants. Symptoms of asthma include shortness of breath, wheezing, cough, and chest tightness. Asthma is usually diagnosed based on the presence of wheezing and confirmed with breathing tests. Chest X-rays are usually normal in asthma patients. Avoiding precipitating factors is important in the management of asthma. Medications can be used to reverse or prevent bronchospasm in patients with asthma.

REFERENCES: Davies, S. Peak expiratory flow rate monitoring in asthma. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2005. Kohler, C. Metered dose inhaler techniques in adults. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2005. Murray, J. and J. Nadel. Textbook of Respiratory Medicine. Third edition. Philadelphia: W.B. Saunders Company, 2000. Peters, et al. "Tiotropium Bromide Step-Up Therapy for Adults With Uncontrolled Asthma." NEJM 363 (2010): 1715-1726. Medically reviewed by: Ellen Reich, MD, Board Certified in Allergy and Immunology, Board Certified in Pediatrics

Last Editorial Review: 12/3/2010