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Section Editors The content of In the Clinic is drawn from the clinical information and
Christine Laine, MD, MPH education resources of the American College of Physicians (ACP), including
David Goldmann, MD PIER (Physicians’ Information and Education Resource) and MKSAP (Medical
Knowledge and Self-Assessment Program). Annals of Internal Medicine
Physician Writer editors develop In the Clinic from these primary sources in collaboration with
Reynold A. Panettieri the ACP’s Medical Education and Publishing Division and with the assistance
Jr., MD of science writers and physician writers. Editorial consultants from PIER and
MKSAP provide expert review of the content. Readers who are interested in these
primary resources for more detail can consult http://pier.acponline.org and other
resources referenced in each issue of In the Clinic.

The information contained herein should never be used as a substitute for clinical
judgment.

© 2007 American College of Physicians


sthma, which is characterized by airway hyperresponsiveness and in-

A flammation, is one of the most common respiratory illnesses. The


global prevalence of asthma is increasing despite the development of
new therapeutic approaches. Over the past 20 years, asthma mortality in the
United States has declined; however, morbidity, as measured by hospitaliza-
tions and emergency department visits, continues to climb. Currently, about
1 in 20 Americans have asthma; in children, recent estimates suggest an inci-
dence as high as 10%. In certain groups of Americans, such as persons of
lower socioeconomic status and minority ethnicity, asthma morbidity and
mortality are disproportionately high. Such trends are surprising, given the
improvement in air quality in the United States and the availability of new
pharmacologic therapies.

Diagnosis
What symptoms or elements of but clinicians often disagree about
clinical history are helpful in the presence and absence of these
diagnosing asthma? signs (1, 2).
Symptoms that should prompt cli-
nicians to consider asthma are The physical examination is some-
wheezing, dyspnea, cough, difficul- times most helpful in looking for
ty taking a deep breath, and chest evidence of alternative diagnoses.
tightness (1). Characteristically, Persistent dry inspiratory crackles,
asthma symptoms are intermittent focal wet crackles, or an abnormal
and may remit spontaneously or cardiac examination all suggest di-
with use of short-acting broncho- agnoses other than asthma.
dilators. Symptoms often vary How can clinicians determine
1. Li JT, O’Connell EJ.
seasonally or are associated with whether asthma is the cause of
Clinical evaluation of specific triggers, such as cold, exer- chronic cough in adults?
asthma. Ann Allergy
Asthma Immunol. cise, animal dander, pollen, certain Coughing may be the only mani-
1996;76:1-13; quiz 13-
5. [PMID: 8564622]
foods, aspirin or nonsteroidal anti- festation of asthma in some pa-
2. National Heart, Lung, inflammatory drugs, or occupation- tients (3). Up to 24% of patients
and Blood Institute,
National Asthma Edu- al exposures. Clinicians should also presenting to a specialist with
cation and Preven-
tion Program. Expert
consider the diagnosis of asthma in chronic cough after an initial evalu-
Panel Report 2: all adults with chronic cough, espe- ation by a primary care provider
Guidelines for the di-
agnosis and manage- cially if cough is nocturnal, season- may have asthma. Although several
ment of asthma. al, or related to the workplace or a protocols are available for the diag-
Bethesda MD: US De-
partment of Health specific activity. nosis of patients with chronic
and Human Services,
National Institutes of cough, it is not clear which is the
Health, 1997; Publica- What physical examination
tion 97-4051.
best approach. Clinicians often use
findings are suggestive of asthma?
3. Corrao WM, Braman a trial of empirical asthma therapy,
SS, Irwin RS. Chronic A careful history to elicit the nature
cough as the sole but national guidelines recommend
presenting manifes- and timing of symptoms is para- pulmonary function tests for
tation of bronchial mount in diagnosing asthma. The patients with chronic cough of
asthma. N Engl J
Med. 1979;300:633-7. physical examination is less helpful unknown etiology.
[PMID: 763286]
4. McFadden ER Jr. Exer-
unless a patient is having an active
tional dyspnea and exacerbation. The clinician should What are the indications for
cough as preludes to
acute attacks of listen for wheezing during tidal res- spirometry in a patient whose
bronchial asthma. N
Engl J Med.
pirations or prolonged expiratory clinical presentation is consistent
1975;292:555-9. phase of breathing and examine the with asthma?
[PMID: 1110670]
5. Hankinson JL, Oden- chest for hyperexpansion. Studies Fair-quality evidence supports the
crantz JR, Fedan KB.
Spirometric reference
suggest that respiratory signs performance of spirometry in all
values from a sample (wheezing, forced expiratory time, adult patients and older children
of the general U.S.
population. Am J accessory muscle use, respiratory suspected of having asthma. Initial
Respir Crit Care Med. rate, and pulsus paradoxus) may be pulmonary function testing should
1999;159:179-87.
[PMID: 9872837] useful to predict airflow obstruction, include spirometric measurements

© 2007 American College of Physicians ITC6-2 In the Clinic Annals of Internal Medicine 5 June 2007
of the FEV1, FVC, and the FEV1– A number of studies show a poor
FVC ratio. If these measurements correlation among the presence,
reveal airflow obstruction, then severity, and timing of wheezing
they should be repeated after ad- and the degree of airflow obstruc-
ministration of a bronchodilator to tion (7, 8). Patients vary in their
evaluate the reversibility of airflow degree of sensitivity to airflow limi-
tations and can acclimate to the
obstruction. Reversibility of airflow
disability and thus become insensi-
obstruction defines asthma. Pre-
tive to airflow obstruction (9). Be-
dicted normal values for spiromet- cause of the disparity between pa-
ric measures are population-based tient and physician estimates of the
and differ with age and ethnicity. severity of airflow obstruction and
Predictive tables are available (5, objective measures of obstruction,
6). Postbronchodilator improve- pulmonary function tests are im-
ment ≥ 12% of the FEV1 or FVC portant tools to characterize airflow
indicates significant reversibility obstruction and the degree and
and therefore increases the likeli- severity of asthma.
hood of an asthma diagnosis.
Spirometry should adhere to the
Complete pulmonary function test- standards of the American Tho-
ing that includes lung volumes and racic Society (10). Of note, spirom-
diffusing capacity should be con- etry is effort-dependent, and many 6. Nunn AJ, Gregg I.
patients have difficulty with the New regression
sidered when there is evidence of a equations for predict-
FVC maneuver. In these patients ing peak expiratory
lack of airflow reversibility, or re-
(younger children, older adults, or flow in adults. BMJ.
strictive patterns with diminutions patients with severe respiratory dis-
1989;298:1068-70.
[PMID: 2497892]
in the FEV1 and FVC but a normal ease), alternative approaches, such 7. McFadden ER Jr., Kiser
R, DeGroot WJ. Acute
FEV1–FVC ratio. These findings as the FEV6 may be an acceptable bronchial asthma. Re-
lations between clini-
suggest chronic obstructive pul- surrogate to the FVC, with a re- cal and physiologic
monary disease (COPD) or inter- duction in the FEV1–FEV6 ratio manifestations. N
Engl J Med.
stitial lung disease (Table 1). signifying obstruction (11). 1973;288:221-5.
[PMID: 4682217]
8. Shim CS, Williams MH
Jr. Relationship of
wheezing to the
severity of obstruc-
Table 1. Laboratory and Other Studies for Asthma tion in asthma. Arch
Intern Med.
Test Notes 1983;143:890-2.
Spirometry Abnormal spirometry (reversible obstruction) can help to confirm an asthma [PMID: 6679232]
9. Chetta A, Gerra G,
diagnosis, but normal spirometry does not exclude asthma. Foresi A, Zaimovic A,
Peak flow variability A patient with normal spirometry but marked diurnal variability (based on a peak Del Donno M, Chit-
tolini B, et al. Person-
flow diary kept for >2 weeks) may have asthma, which may warrant an empirical ality profiles and
trial of asthma mediations or further testing with bronchoprovocation. breathlessness per-
ception in outpa-
Bronchoprovocation test In a patient with a highly suggestive history of asthma and normal baseline tients with different
spirometry, a low PC20 (the concentration of inhaled methacholine needed to gradings of asthma.
cause a 20% drop in the FEV1) on methacholine challenge testing supports a di- Am J Respir Crit Care
agnosis of asthma. Cold air, exercise, and histamine are other types of provoca- Med. 1998;157:116-
tive tests used. A normal bronchoprovocation test will almost definitively ex- 22. [PMID: 9445288]
10. Standardization of
clude asthma. Spirometry, 1994
Chest radiography Chest radiography may be needed to exclude other diagnoses but is not recom- Update. American
Thoracic Society. Am
mended as a routine test in the initial evaluation of asthma. J Respir Crit Care
Complete blood count with Although mild eosinophilia is not uncommon in persons with asthma, routine Med. 1995;152:1107-
36. [PMID: 7663792]
differential use of a CBC with leukocyte differential is not warranted in the initial evaluation. 11. Swanney MP, Jensen
Sputum evaluation Routine sputum evaluation is not indicated for the initial evaluation of asthma. RL, Crichton DA,
Beckert LE, Cardno
IgE Although elevated levels of IgE are not uncommon for persons with asthma, LA, Crapo RO. FEV(6)
routine measurement of serum IgE is not warranted in the initial evaluation is an acceptable sur-
rogate for FVC in the
Quantitative IgE antibody assays There is a strong association between allergen sensitization, exposure, and spirometric diagno-
and skin testing for immediate asthma. Allergy testing is the only reliable way to detect the presence of specific sis of airway ob-
hypersensitivity to aeroallergens IgE to indoor allergens. Skin testing (or in vitro testing) may be indicated to struction and restric-
tion. Am J Respir Crit
guide the management of asthma in selected patients, but results are not useful Care Med.
in establishing the diagnosis of asthma. 2000;162:917-9.
[PMID: 10988105]

5 June 2007 Annals of Internal Medicine In the Clinic ITC6-3 © 2007 American College of Physicians
Does normal spirometry rule out a pulmonary function tests who have
diagnosis of asthma? symptoms consistent with asthma.
Abnormal spirometry (reversible
obstruction) can confirm an asthma Spirometry before, during, or after
diagnosis, but normal spirometry exercise may be the only method to
does not rule out asthma. Clini- document bronchoconstriction in
cians should consider further stud- patients with exercise-induced
ies in patients with normal spirom- asthma. As an alternative, monitor-
etry who have a clinical history ing peak flow is easy and inexpen-
suggestive of asthma (Table 1). sive, but the measurement is less
Bronchoprovocation with metha- precise and limited in reproducibil-
choline or histamine can be helpful ity and sensitivity (15). Because
in establishing a diagnosis in pa- spirometry and peak flow have lim-
tients who report that they only itations in sensitivity and specificity,
have symptoms during exercise or they are probably best used as part
at certain times of the year. Alter- of a diagnostic strategy in conjunc-
natively, marked diurnal variability tion with a comprehensive history,
based on measurements recorded in physical examination, and other
a peak flow diary kept for at least 2 laboratory data (16).
weeks can help to establish asthma
How should clinicians classify
as the cause of symptoms. Howev-
er, peak flow measurements are asthma severity?
12. Crapo RO, Casaburi
highly effort-dependent and may The National Heart Lung and
R, Coates AL, Enright
PL, Hankinson JL,
offer no opportunity for quality Blood Institute (NHLBI) Expert
Irvin CG, et al. Guide-
lines for metha- assurance of their accuracy. Panel Report 2 (2) defines asthma
choline and exercise severity according to symptoms and
challenge testing-
1999. This official When should clinicians consider spirometric measurements. As
statement of the
American Thoracic provocative pulmonary testing? shown in Table 2, asthma severity
Society was adopted is classified as intermittent, mild,
by the ATS Board of
Directors, July 1999.
A gold standard for diagnosis of moderate, and severe persistent.
Am J Respir Crit Care asthma remains elusive. However, Each category is defined by the fre-
Med. 2000;161:309-
29. [PMID: 10619836] methacholine hyperresponsiveness quency of rescue inhaler use as well
13. Cockcroft DW, Killian
DN, Mellon JJ, Harg-
in the pulmonary function labora- as nocturnal symptoms in conjunc-
reave FE. Bronchial tory has high reproducibility and tion with the FEV1 or PEFR meas-
reactivity to inhaled
histamine: a method accepted standardization (12). The urement. It is important to note that
and clinical survey.
Clin Allergy.
test is safe but requires sophisticat- decrease in FEV1 correlates with
1977;7:235-43. ed instrumentation and is labor-in- airflow obstruction and not with
[PMID: 908121]
14. Hopp RJ, Bewtra AK, tensive and expensive. In a patient changes due to restrictive lung
Nair NM, Townley with symptoms suggestive of asth-
RG. Specificity and disease.
sensitivity of metha- ma who has normal baseline
choline inhalation
challenge in normal spirometry, a low PC20 (the concen- The initial determination of asthma
and asthmatic chil- tration of inhaled methacholine severity should be made when the
dren. J Allergy Clin
Immunol. needed to induce a 20% decrease in patient is receiving no medications.
1984;74:154-8.
[PMID: 6747136] the FEV1) on methacholine chal- Asthma severity is dynamic—for
15. Jain P, Kavuru MS, lenge testing supports the diagno- example, patients who were ini-
Emerman CL, Ah-
mad M. Utility of sis. Studies of methacholine chal- tially diagnosed as having severe
peak expiratory flow
monitoring. Chest. lenge suggest that it is sensitive and persistent asthma may have symp-
1998;114:861-76. has a high negative predictive value toms consistent with mild persist-
[PMID: 9743179]
16. Perpiñá M, Pellicer C, for the diagnosis of asthma (13, ent asthma while receiving med-
de Diego A, Compte
L, Macián V. Diag- 14). Although cold air and exercise ication. The NHLBI Expert Panel
nostic value of the have been used in research to de- Report 2 (2) suggests annual
bronchial provoca-
tion test with fine mechanisms of bronchocon- spirometry to aid in the classifica-
methacholine in
asthma. A Bayesian
striction, methacholine challenge tion of asthma, but high-quality
analysis approach. remains the provocative test of studies are not available to support
Chest. 1993;104:149-
54. [PMID: 8325060] choice in patients with normal this recommendation.

© 2007 American College of Physicians ITC6-4 In the Clinic Annals of Internal Medicine 5 June 2007
Table 2. The Step Classification of Asthma Severity*
Classification Symptoms† Nocturnal Symptoms Lung Function
Step 1: Mild Symptoms ≤2 per week 2 per month FEV1 or PEFR ≥80% predicted
intermittent Asymptomatic and PEFR variability <20%
normal PEFR between
exacerbations
Exacerbations brief
(a few hours to a few days);
intensity may vary
Step 2: Mild Symptoms >2 per >2 per month FEV1 or PEFR ≥80% predicted
persistent week but <1 per day PEFR variability 20%–30%
Exacerbations may
affect activity
Step 3: Moderate Daily symptoms >1 per week FEV1 or PEFR >60%–<80% predicted
persistent Daily use of inhaled PEFR variability >30%
short-acting ß2-agonist
Exacerbations may affect
activity
Exacerbations ≥2 per week;
may last days
Step 4: Severe Continual symptoms Frequent FEV1 or PEFR <60% predicted
persistent Limited physical activity PEFR variability >30%
Frequent exacerbations
* Adapted from NHLBI Expert Panel Report. The presence of one of the features of severity is sufficient to place a patient in
that category. Assign patient to the most severe grade in which any feature occurs. The characteristics noted in this Table
are general and may overlap because of the high variability of asthma and because an individual’s classification may change
over time. PEFR = peak expiratory flow rate.
† Patients at any level of severity can have mild, moderate, or severe exacerbations. Some patients with intermittent
asthma experience severe, life-threatening exacerbations separated by long periods of normal lung function and
no symptoms.

What comorbid conditions and substantial history of cigarette


alternative diagnoses should smoking. Patients with COPD also
clinicians consider in patients with do not demonstrate reversibility
suspected asthma? with bronchodilators on pulmonary
The differential diagnosis of asth- function testing.
ma includes the following condi- 17. Irwin RS, Curley FJ,
tions: COPD, interstitial lung dis- Lung imaging with radiography or French CL. Difficult-
ease, vocal cord dysfunction, computed tomography is helpful in to-control asthma.
Contributing factors
congestive heart failure, medica- identifying bronchiectasis or lung and outcome of a
systematic manage-
tion-induced cough, bronchiectasis, masses. Echocardiography can help ment protocol.
pulmonary infiltration with to identify cardiovascular disorders, Chest.
1993;103:1662-9.
eosinophilia syndromes, obstructive including ischemic heart disease, [PMID: 8404082]
ventricular dysfunction, and pul- 18. Althuis MD, Sexton
sleep apnea, mechanical airway ob- M, Prybylski D. Ciga-
struction, cystic fibrosis, and pul- monary hypertension. Flow-volume rette smoking and
asthma symptom
monary hypertension. Clinicians loops and direct visualization of the severity among
should consider one of these alter- larynx during an acute episode are adult asthmatics. J
Asthma.
native diagnoses when asthma is useful in evaluating patients for 1999;36:257-64.
[PMID: 10350222]
difficult to control or if the patient vocal cord paralysis. 19. Weiss ST, Utell MJ,
has atypical signs and symptoms. Samet JM. Environ-

These conditions can also coexist in Chronic cough and dyspnea or mental tobacco
smoke exposure and
a patient who has asthma. recurrent wheezing are common asthma in adults. En-
viron Health Per-
signs of COPD, vocal cord dys- spect. 1999;107 Sup-
An important difference between function, cystic fibrosis, obstructive pl 6:891-5.
[PMID: 10592149]
asthma and COPD is the history of sleep apnea, Churg-Strauss syn- 20. Ostro BD, Lipsett MJ,
drome, allergic bronchopulmonary Mann JK, Wiener MB,
smoking. Although 30% of patients Selner J. Indoor air
with asthma in the United States aspergillosis, interstitial lung dis- pollution and asth-
ma. Results from a
smoke, COPD, manifested by ease, bronchiectasis, congestive panel study. Am J
chronic bronchitis and emphysema, heart failure, and pulmonary hyper- Respir Crit Care Med.
1994;149:1400-6.
often occurs in older persons with a tension, or may be side effects of [PMID: 8004290]

5 June 2007 Annals of Internal Medicine In the Clinic ITC6-5 © 2007 American College of Physicians
medications. Evidence shows that ing provocative pulmonary function
Measures to Reduce Dust Mite difficult-to-control asthma may be testing because testing is time- and
and Other Environmental
a result of comorbid conditions and labor-intensive, requiring skilled
Allergen and Irritant Exposure
that standardized evaluation of performance and interpretation.
• Use air conditioning to maintain
humidity <50% patients for comorbidity was Patients presenting with atypical
• Remove carpets associated with improved asthma symptoms, who have abnormal
• Limit fabric household items, control (17). chest radiographs or unusual mani-
such as upholstered furniture, festations of the disease, or who
drapes, and soft toys When should primary care display suboptimal response to
• Use impermeable covers for clinicians consider referring
mattresses and pillows
therapy may benefit from referral to
• Launder bedding weekly in water
patients with suspected asthma a pulmonologist. Referral to an al-
at least 130°F to specialists for diagnosis? lergist may be helpful for patients
• Ensure adequate ventilation— Consultation with a pulmonologist with asthma that seems to have an
may be the only measure neces- should be considered before order- allergic component.
sary for dust mite control in dry
climates
• Exterminate to reduce
cockroaches Diagnosis... A careful history focusing on the nature and timing of symptoms
• Remove cats from the home (wheezing, dyspnea, cough, chest tightness) and potential triggers is essential to
• Reduce dampness in the home
the diagnosis of asthma. Moderate-quality evidence supports the use of spirome-
try in assessment of all adult patients and older children suspected of having
• Avoid wood-burning or unvented
gas fireplaces or stoves asthma. However, normal spirometry does not definitively rule out asthma. Clini-
cians should consider provocative pulmonary testing for patients with normal
• Avoid tobacco smoke
spirometry but characteristic symptoms and no evidence of alternative diagnoses.

CLINICAL BOTTOM LINE

Treatment
What advice about reducing several studies have impugned
21. Institute of Medicine allergen exposure should active and passive cigarette smok-
Committee on the
Assessment of Asth- clinicians give patients? ing as a cause of decreasing lung
ma and Indoor Air.
Executive summary.
Avoidance of triggers is the corner- function in adult asthma (18, 19).
In: Clearing the Air: stone of nonpharmacologic therapy
Asthma and Indoor
of asthma. Clinicians should ques- One study considered associations be-
Air Exposures. Wash-
ington, DC: National tween indoor air pollutants and symptoms
tion the patient about triggers and
Academy Pr; 2000. in 164 adults with asthma and found an
22. National Heart, provide strategies to diminish expo- increase in days of restricted activity (odds
Lung, and Blood In-
stitute, National sure to them (see box). Since many ratio [OR], 1.61 [95% CI, 1.06 to 2.46]) and
Asthma Education patients with asthma are atopic, greater likelihood of increased asthma
and Prevention Pro-
gram. Expert Panel reducing exposure to allergens can symptoms in patients exposed to a smoker
Report: Guidelines
for the Diagnosis
improve outcomes. Other common at home (OR, 2.05 [CI, 1.79 to 2.40]) (20).
and Management of triggers of asthma include aspirin,
Asthma—Update on
Selected Topics nonsteroidal anti-inflammatory What evidence supports the use
2002. Bethesda MD: drugs, and sulfites in food preserv- of indoor air-cleaning devices for
US Department of
Health and Human atives. Limiting exposure to trig- patients with asthma?
Services, National In-
stitutes of Health, gers is difficult to implement or Given the recognition that environ-
2002; Publication 02- sustain in some patients; however, ment plays a critical role in airway
5075.
23. Aronson N, Lefevre F, in most cases such triggers are hygiene, it may seem logical that
Piper M, Manage-
dose-dependent, so even modest indoor air-cleaning devices are ben-
ment of Chronic
Asthma. Summary, remediation can be beneficial. eficial. However, there is little evi-
Evidence dence to suggest that HEPA filters,
Report/Technology
Assessment Number The NHLBI Expert Panel Report air duct cleaning, or dehumidifiers
44. Rockville, MD:
Agency for Health- recognized environmental smoke control asthma. Humidifiers may
care Research and exposure as a common cause of actually increase allergen levels and
Quality; 2001. AHRQ
Publication 01-E044. asthma exacerbations (2), and must be cleaned often. Keeping

© 2007 American College of Physicians ITC6-6 In the Clinic Annals of Internal Medicine 5 June 2007
household humidity below 50% should also receive a short-acting
with dehumidifiers or air condition- β-agonist and advice to keep the Evidence is inadequate to
ers reduces dust mites and mold (21). medication readily available for broadly recommend air
relief of acute symptoms.
A multidisciplinary committee convened cleaning devices for patients
by the Institute of Medicine reviewed avail- Long-Term Controller Therapy
able evidence concerning the impact Patients with mild, moderate, or with asthma.
of ventilation and air cleaning on asthma severe persistent asthma have ab-
(21). Although they concluded that particle
normal baseline pulmonary function
air cleaning may reduce symptoms in cer-
tain situations, evidence is inadequate
and require long-term controller
to broadly recommend air cleaning for therapy. Patients with mild persist-
patients with asthma. ent asthma should receive 1 long-
term controller medication, usually a
How should clinicians select from low-dose inhaled corticosteroid.
among available drug therapy for
asthma? Compared with patients with mild
Table 3 summarizes drugs available intermittent asthma, patients with
to treat asthma. Table 4 presents a mild persistent asthma are more
stepwise approach to using these prone to underlying inflammation
drugs to maximize control of symp- and disease exacerbations. Low-
toms (2, 22). dose inhaled corticosteroids have
been shown to reduce bronchial
Clinicians should tailor drug therapy hyperresponsiveness, reduce rescue
to the severity of asthma (Table 2). β-agonist use, and control symp-
Stepwise therapy consists of agents toms. Secondary alternatives to
for acute relief of symptoms (rescue inhaled corticosteroids are
therapy) and for long-term control. leukotriene-receptor antagonist
Rescue therapy is critically impor- medications (e.g., montelukast,
tant regardless of asthma severity. zafirlukast) or cromolyn.
Patients with persistent symptoms
require long-term control in addi- Patients with moderate persistent
tion to rescue therapy. If control is asthma will probably require 1 or 2
poor, stepping up to more intense long-term controller medications in 24. Greening AP, Ind PW,
addition to short-acting rescue Northfield M, Shaw
therapy is indicated. If symptoms G. Added salmeterol
therapy. The therapy of choice in
are well-controlled, stepping down versus higher-dose
this group includes low-dose corticosteroid in
to less intensive therapy is indicated. inhaled corticosteroids and a long- asthma patients
with symptoms on

Clinicians should review therapy acting β-agonist or a moderate dose existing inhaled cor-
ticosteroid. Allen &
every 1 to 6 months, depending on of a single long-term controller Hanburys Limited
medication. Evidence suggests UK Study Group.
asthma severity. Asthma is a chron- Lancet.
that patients who remain sympto- 1994;344:219-24.
ic disease that often requires long-
matic while taking moderate doses [PMID: 7913155]
term therapy. Given the complexity of inhaled corticosteroids benefit
25. Ukena D, Harnest U,
Sakalauskas R, Mag-
of airway inflammation, multiple from the addition of a long-acting yar P, Vetter N, Stef-
drugs with different actions against fen H, et al. Compari-
bronchodilator such as theophylline, son of addition of
the various aspects of the inflamma- salmeterol, or formoterol. The theophylline to in-
haled steroid with
tory response are often necessary. additive effect of the long-acting doubling of the
dose of inhaled
bronchodilator improves lung phys- steroid in asthma.
Rescue Therapy iology, decreases use of rescue β- Eur Respir J.
Patients with mild intermittent agonists, and reduces symptoms 1997;10:2754-60.
[PMID: 9493656]
asthma may only need a quick relief better than doubling the dose of an 26. Woolcock A, Lund-
medication (short-acting β-ago- inhaled corticosteroid (23–26). back B, Ringdal N,
Jacques LA. Compar-
nists) on an as-needed basis. Short- However, there is little evidence to ison of addition of
acting β-agonists are the drugs of guide the best choice of combina-
salmeterol to in-
haled steroids with
choice for reversal of acute bron- tions. Clinicians and patients must doubling of the
dose of inhaled
chospasm and are safe and well- weigh the reduced risk for adverse steroids. Am J Respir
tolerated. Patients with persistent effects of steroids against the use of Crit Care Med.
1996;153:1481-8.
asthma (mild, moderate, or severe) more complicated regimens. It is [PMID: 8630590]

5 June 2007 Annals of Internal Medicine In the Clinic ITC6-7 © 2007 American College of Physicians
Table 3. Drug Treatment for Asthma
Class/Agent Mechanism of Action Benefits Side Effects Notes
Short-acting ß-agonists: Relaxes bronchial Fastest improvement Tachycardia, Should be carried by all patients with
Albuterol smooth muscle, in airflow physiology palpitations, tremors, asthma at all times. Drug class of choice
Metaproterenol improves airflow of all anti-asthma hypokalemia for acute bronchospasm. Use only as
Terbutaline medications needed. Effective at preventing symptoms
Pirbuterol of asthma when used before exercise.
Assessment of quantity of ß-agonist use may
identify patients who require a "step-up" in thera-
py. Use of >1 canister during a 1-month period
suggests inadequate control. Oral preparations
available, but inhaled is preferred due to better
side effect profile.
Inhaled corticosteroids: Anti-inflammatory, Improved airflow Local: cough, Each type of inhaled corticosteroid has a
Beclomethasone blocks late reaction physiology, reduced dysphonia, and thrush. different profile in terms of dosing potency
dipropionate to allergen, and need for rescue Systemic: cortisol and possible risks for any of the known
Beclomethasone reduces airway medications (short- suppression, adrenal side effects.
hydrofluoroalkane hyperresponsiveness acting ß-agonists), suppression, potential Drug deposition in the lower airway and
Budesonide prevents exacerbations osteoporosis, cataracts, systemic absorption and toxicity are
Flunisolide and hospitalizations glaucoma conditioned by the drug and preparation,
Fluticasone propionate inhalation technique, and use of a spacing
Triamcinolone acetonide chamber. There is little information on
Ciclesonide how to monitor effectiveness and toxicity
Mometasone of inhaled corticosteroids, especially
considering the varying degrees of seasonal in-
flammations or following differing stimuli/
exposures.
Inhaled corticosteroids are the most potent and
effective anti-inflammatory medications avail-
able for asthma.
Long-acting inhaled Smooth muscle Improved a.m. peak Tachycardia, skeletal Use only in conjunction with anti-
ß-agonists: relaxation flow, improved muscle tremor, inflammatory therapy.
Salmeterol nocturnal symptoms, prolongation of QT Protection against exercise-induced
Formoterol effective in preventing interval in overdose symptoms may decrease over time.
symptoms of exercise- Salmeterol has slower onset and both have
induced asthma for up longer duration of action compared with
to 12 hours after a short-acting ß-agonists. May provide more
single dose effective symptom control when added to stan-
dard doses of inhaled corticosteroids compared
to increasing corticosteroid dosage. The FDA has
warned that these agents may increase the
chances of a severe asthma episode. This
seems more likely in blacks.
Combined fixed-agent Anti-inflammatory Improved airflow Dysphonia, thrush, Should not be initiated in patients during
controllers: moiety blocks late physiology, reduced nausea, headaches rapidly deteriorating or potentially life-
Fluticasone and salmeterol reaction to allergen, need for short acting threatening episodes of asthma.
Budesonide and formoterol and reduces airway ß-agonists, prevents Do not use in conjunction with inhaled
hyperresponsiveness, exacerbations and long-acting ß-agonists.
and long-acting hospitalizations; Combined preparations prevent the use of
ß-agonist leads to improved a.m. peak long-acting ß-agonists without inhaled
smooth muscle flow, improved corticosteroids.
relaxation nocturnal symptoms
Leukotriene modifiers: Work by inhibition Improvements in Transient elevation in Oral tablets may be easier to use than
Montelukast of synthesis or symptoms and liver enzymes occurs inhaled medications and may enhance
Zafirlukast antagonism of pulmonary function, with Zileuton and compliance; therapeutic benefits are less
Zileuton receptor site for decreased exacerbation mandates monitoring than those of inhaled corticosteroids.
cysteinyl leukotrienes rate, reduced need of liver enzymes with May be of particular benefit in patients
for rescue ß-agonist initiation of therapy; with aspirin intolerance and/or nasal
there is controversy polyps. May allow for safe reduction in
over possible link with inhaled and oral corticosteroids. May be
Churg-Strauss angiitis an alternative to increasing dose of
(causation has not inhaled corticosteroid.
been established)
Theophylline Smooth muscle Modest improvement Dose-related acute Studies show a benefit in the addition of
relaxation, may have in expiratory flow toxicities include theophylline to inhaled corticosteroids
secondary effects of rates tachycardia, nausea
inhibiting airway vomiting,
inflammation and tachyarrhythmias (SVT),
enhancing diaphragm CNS stimulation,
contractility headache, seizures
Sometimes adverse
effects are seen at
therapeutic levels

© 2007 American College of Physicians ITC6-8 In the Clinic Annals of Internal Medicine 5 June 2007
Table 3. Drug Treatment for Asthma (continued)
Class/Agent Mechanism of Action Benefits Side Effects Notes
Mast cell stabilizers: Anti-inflammatory, Improved airflow Cromolyn: no The therapeutic response to this class of
Cromolyn blocks early and late physiology, reduced significant side effects drugs is less predictable than to cortico-
Nedocromil reaction to allergens, need for rescue Nedocromil: 15%–20% steroids, but they continue to be used due
and stabilizes mast medications (short- of users complain of to their safety profile
cell membranes; acting ß-agonists), unpleasant taste
inhibits eosinophil prevents exacerbations
activation and
mediator release
Systemic corticosteroids: Anti-inflammatory, Improved airflow Short-term: increased Most effective medication for severe
Prednisone blocks late reaction physiology, reduced appetite and weight exacerbations and long-term control for
Prednisolone to allergen, and need for rescue gain, fluid retention, patients with severe persistent asthma
Methylprednisolone reduces airway medications (short- reversible abnormalities who are otherwise uncontrolled.
Triamcinolone hyperresponsiveness acting ß-agonists), in glucose metabolism, Always seek lowest possible effective dose.
prevents exacerbations mood alterations Patients on corticosteroids (either daily or
and hospitalizations Long-term: dermal ≥2 corticosteroid prescriptions for 5-10
thinning, cortisol days/yr) and undergoing surgery or with
suppression, adrenal acute severe illness should be assessed for
suppression, hyper- adrenal reserve or treated presumptively
tension, diabetes with short-term systemic corticosteroid.
mellitus, osteoporosis, Studies show that it is safe to give a short
avascular necrosis of course of oral corticosteroids (7-10 days)
femoral head, without tapering.
cataracts, glaucoma
Anticholinergic agents: Bronchodilation Improved airflow Blurred vision if Treatment of choice in ß-blocker induced
Ipratropium bromide mediated by physiology contact with eyes, bronchospasm; may give added broncho-
Glycopyrrolate otropium antagonism of dry mouth and dilation to ß-agonists.
muscarinic receptors respiratory symptoms Meta-analysis of the use of ipratropium
of airway smooth bromide in the treatment for acute severe
muscle asthma shows that there is a modest
physiologic benefit in the addition of
ipratropium to albuterol, with negligible risk of
adverse side effects.
Tiotropium has been suggested as an alternative
to long-acting ß-agonists, but suitable effective-
ness studies are lacking.
Intravenous Smooth muscle Bronchodilatation Minor effects;
magnesium sulfate relaxation in acute severe flushing, lethargy,
asthma failing to nausea, or local
respond to reaction at the
nebulized IV site
bronchodilators-
Omalizumab A monoclonal Reduction in The main danger is Anaphylaxis may occur after any dose of
antibody that binds exacerbations in anaphylaxis. Injections omalizumab (including the first dose), even
to IgE used in patients with severe should be administered if there was no adverse reaction to the first
patients aged 12 persistent asthma by trained personnel, dose. The symptoms and signs of
years or older with on the best and patients should anaphylaxis include bronchospasm,
moderate to severe available therapy be observed for 2 hours hypotension, syncope, urticaria, and
persistent asthma, after every injection. angioedema of the throat or tongue. In
proven IgE-mediated Anaphylaxis has been the major trials, there was a small increase
sensitivity to perennial reported up to 24 hours in new or recurrent cancer compared to
aeroallergens, and after injection, and the control group
poor response to patients receiving
standard treatment. omalizumab treatment
Binding of IgE by should be fully prepared
monoclonal antibody to begin treatment for
inhibits binding to anaphylaxis with an
high-affinity IgE epinephrine autoinjector
receptors on mast
cells and basophils

*Readers can access detailed information on dosing in PIER at http://pier.acponline.org/physicians/diseases/d146/drug.tx/d146-s7.html. CNS = central
nervous system; FDA = Food and Drug Administration

unclear whether controlling the In a 12-week, randomized, controlled trial of


disease with high-dose inhaled corti- 447 patients who remained symptomatic on
costeroids or moderate-dose inhaled treatment with inhaled corticosteroids, a
dry-powder inhaler containing salmeterol
corticosteroids plus a long-acting and fluticasone was more effective in im-
bronchodilator results in a better proving physiologic endpoints, reducing res-
long-term outcome. cue therapy use, and reducing exacerbations

5 June 2007 Annals of Internal Medicine In the Clinic ITC6-9 © 2007 American College of Physicians
Table 4. Stepwise Approach for Managing Asthma in Adults
STEP Classification Long-Term Control Quick Relief Education
Step 1: Mild No daily medication needed Short acting bronchodilator: Teach basic facts about asthma;
intermittent inhaled ß2-agonists* as needed teach inhaler/spacer/holding chamber
for symptoms technique; discuss roles of medications;
develop self-management plan; develop
action plan for when to take rescue
medications, especially for patients
with a history of severe exacerbations;
discuss appropriate environmental con-
trol measures to avoid exposure to
known allergens and irritants
Step 2: Mild One daily medication: Short-acting bronchodilator: Step 1 actions, plus teach
persistent • Anti-inflammatory*: either inhaled corticosteroid inhaled ß2-agonists* as needed self-monitoring; refer to
(low doses) or cromolyn* or nedocromil* (children for symptoms group education if
usually begin with a trial of cromolyn or nedocromil) available; review and update
• Sustained-release theophylline to serum self-management plan
concentration of 5-15 µg/mL is an alternative, but
not preferred, therapy.
• Montelukast, zafirlukast, or zileuton may also be
considered for patients age 12 and older,
although their position in therapy is not fully
established
Step 3: Moderate Preferred treatment: Short acting bronchodilator: Step 1 actions, plus teach
persistent • Low-to-medium dose inhaled corticosteroids and inhaled ß2-agonists* as needed self-monitoring; refer to
long-acting inhaled ß2-agonists. for symptoms group education if
Alternative treatment: available; review and update
Increase inhaled corticosteroids within medium- self-management plan
dose range
OR
• Low-to-medium dose inhaled corticosteroids and
either leukotriene modifier or theophylline.
OR
• If needed (particularly in patients with recurring
severe exacerbations): Increase inhaled corticosteroids
within medium-dose range, and add long-acting inhaled
ß2-agonists.
Alternative treatment:
Increase inhaled corticosteroids to medium-dose
range, and add either leukotriene modifier or
theophylline
Step 4: Severe Preferred treatment: Short-acting bronchodilator: Step 2 and 3, plus refer to
persistent High-dose inhaled corticosteroids inhaled ß2-agonists* as needed individual education/
AND for symptoms. counseling
Long-acting inhaled ß2-agonists
AND, if needed,
Corticosteroid tablets or syrup long-term (2 mg/kg/d,
generally do not exceed 60 mg/d). (Make repeated
attempts to reduce systemic corticosteroids and maintain
control with high-dose inhaled corticosteroids.)

*Intensity of treatment depends on severity of exacerbation. Use of short-acting inhaled ß2-agonists on a daily basis, or increasing use, indicates the need for additional long-
term control therapy

than was the addition of montelukast to hospitalization (OR, 2.6 [CI, 1.6 to 4.3]), life-
the inhaled corticosteroid fluticasone (27). threatening exacerbations (OR, 1.8 [CI, 1.1
to 2.9]), and asthma-related deaths (OR,
Long-acting β-agonists may help 3.5 [CI, 1.3 to 9.3]; risk difference, 0.07%)
27. Nelson HS, Busse improve asthma symptoms, but they (28). Risks were similar for salmeterol and
WW, Kerwin E,
Church N, Emmett may also increase risks for adverse formoterol and in children and adults. Sev-
A, Rickard K, et al. outcomes. Patients started on these eral trials did not report information about
Fluticasone propi-
onate/salmeterol medications should be followed potential harms, and the number of re-
combination pro-
closely. ported deaths was small. Black patients
vides more effective
asthma control than and patients not using inhaled corticos-
low-dose inhaled A meta-analysis of 19 randomized, con- teroids seemed to be at high risk for these
corticosteroid plus
montelukast. J Aller- trolled trials found that, compared with outcomes. These results suggest that long-
gy Clin Immunol. placebo, long-acting ß-agonists in- acting ß-agonists should not be used
2000;106:1088-95.
[PMID: 11112891] creased severe exacerbations requiring alone in asthma (28).

© 2007 American College of Physicians ITC6-10 In the Clinic Annals of Internal Medicine 5 June 2007
Patients with severe persistent asth- asthma per week are candidates for
ma may require 3 controller med- intervention. Patients who have
ications to adequately control normal baseline pulmonary func-
symptoms. Patients with this level tion but experience exercise-in-
of disease are extremely prone to duced symptoms can be treated ef-
exacerbations and have profound fectively with albuterol, cromolyn 28. Salpeter SR, Buckley
NS, Ormiston TM,
underlying inflammation. Direct sodium, or nedocromil 15 to 30 Salpeter EE. Meta-
comparisons of high-dose inhaled minutes before exercise. analysis: effect of
long-acting beta-ag-
corticosteroids to leukotriene- onists on severe
receptor modifiers (such as monte- If exercise-induced symptoms per- asthma exacerba-
tions and asthma-re-
lukast) revealed that the inhaled sist, addition of long-acting bron- lated deaths. Ann In-
corticosteroids were more effective. chodilators or leukotriene antago- tern Med.
2006;144:904-12.
The addition of montelukast to the nists may be helpful. Recent [PMID: 16754916]
regimen of a patient requiring evidence suggesting that mono- 29. Löfdahl CG, Reiss TF,
Leff JA, Israel E, Noo-
high-dose inhaled corticosteroids, therapy with long-acting broncho- nan MJ, Finn AF, et
however, allowed a significant reduc- dilators may cause adverse out- al. Randomised,
placebo controlled
tion in the dose of the inhaled comes in asthma cautions against trial of effect of a
corticosteroid while maintaining using these agents as monotherapy leukotriene receptor
antagonist, mon-
asthma control (29). in exercise-induced asthma (28, 34). telukast, on tapering
Despite these concerns, evidence inhaled corticos-
In a randomized, controlled study of pa- teroids in asthmatic
clearly suggests that formoterol or patients. BMJ.
tients with inadequate symptom control salmeterol is more effective than 1999;319:87-90.
despite low- to moderate-dose inhaled cor- placebo in preventing exercise- [PMID: 10398629]
30. Laviolette M, Malm-
ticosteroid, the addition of montelukast induced bronchoconstriction (35, 36). strom K, Lu S,
improved FEV1 daytime symptoms and Chervinsky P, Pujet
nocturnal awakenings (30).
In a study of patients with mild JC, Peszek I, et al.
stable asthma, once-daily treatment Montelukast added
to inhaled be-
A systematic review of trials comparing the with montelukast protected against clomethasone in
addition of daily leukotriene-receptor an- exercise-induced bronchospasm (37). treatment of asthma.
Montelukast/Be-
tagonists or long-acting ß-agonists to in- clomethasone Addi-
haled corticosteroids in patients with se- The clinician should consider tivity Group. Am J
Respir Crit Care Med.
vere asthma concluded that long-acting exercise-induced asthma in the 1999;160:1862-8.
ß-agonists were better than leukotriene context of the patient’s overall [PMID: 10588598]
antagonists in preventing the need for 31. Coté J, Cartier A, Ro-
therapy. Many patients who pres- bichaud P, Boutin H,
rescue therapy and systemic steroids and ent with putative exercise-induced Malo JL, Rouleau M,
improved lung function and symptoms asthma may have abnormal pul- et al. Influence on
asthma morbidity of
(31, 32) monary function tests at baseline. asthma education
programs based on
Such patients should be treated
Omalizumab is a monoclonal anti- self-management
according to the NHLBI Expert plans following
body that binds to IgE that has treatment optimiza-
Panel Report 2 regimen (2). tion. Am J Respir Crit
been shown to reduce exacerbations Care Med.
in patients with severe persistent When should primary care 1997;155:1509-14.
[PMID: 9154850]
asthma despite best available therapy clinicians refer patients with 32. Ducharme FM,
(33). However, severe anaphylaxis asthma to a specialist for Lasserson TJ, Cates
CJ. Long-acting ß2-
has been reported up to 24 hours
treatment? agonists versus anti-
after injection. Clinicians should leukotrienes as add-
Although definitive evidence about on therapy to
view the drug as an option only in inhaled corticos-
carefully selected cases of severe the effect of specialty care on asthma teroids for chronic
persistent asthma in patients with outcomes is not available, according asthma. Cochrane
database Syst Rev.
proven IgE-mediated sensitivity to to consensus recommendations re- 2006:CD003137.
perennial aeroallergens, and failure ferral to a specialist may be useful in [PMID: 17054161].
33. Humbert M, Beasley
of other therapeutic options. the following clinical situations: R, Ayres J, Slavin R,
Hebert J, Bousquet J,
et al. Benefits of
What therapeutic options are • History of life-threatening omalizumab as add-
effective for patients with exacerbations on therapy in pa-
tients with severe
exercise-induced asthma? • Atypical signs and symptoms persistent asthma
who are inadequate-
In some patients, exercise exacer- • Severe persistent asthma ly controlled despite
bates asthma. Symptoms often oc- • Need for continuous oral corti- best available thera-
py (GINA 2002 step
cur with vigorous exercise in cold, costeroids or high-dose inhaled 4 treatment): INNO-
dry air. Patients who have more steroids or more than 2 courses VATE. Allergy.
2005;60:309-16.
than 2 episodes of exercise-induced of oral steroids in a 1-year period [PMID: 15679715]

5 June 2007 Annals of Internal Medicine In the Clinic ITC6-11 © 2007 American College of Physicians
• Comorbid conditions that com- of those who had a relapse did not signifi-
plicate asthma diagnosis or cantly differ from those who did not have a
treatment relapse after discharge from the emer-
• Need for provocative testing or gency department. However, such histori-
immunotherapy cal features as emergency department or
• Problems with adherence or urgent care visits (OR, 1.3 per 5 visits), use
of a home nebulizer (OR, 2.2), multiple
allergen avoidance
triggers (OR, 1.1 per trigger), and longer
• Unusual occupational or other duration of symptoms (OR, 2.5 for 1 to 7
exposures. days) did predict relapse (38).
Whether to consult an allergist or What factors identify patients
pulmonologist should reflect local
availability and consideration of the with asthma at high risk for fatal
predominant co- or near-fatal events during an
morbid conditions exacerbation?
and complicating Historical factors
features in asthma. Factors Associated with Poor reflect the risk for
For example, a Outcomes of Asthma fatal and near-fatal
patient with sleep Exacerbations asthma-related
34. SMART Study Group.
apnea and asthma • Prior intubation events and should
The Salmeterol Mul-
ticenter Asthma Re- may benefit from • Multiple asthma-related exacer- lower the threshold
search Trial: a com- a pulmonary con- bations for hospitalization
parison of usual
pharmacotherapy sultation, whereas • Emergency room visits for asthma of a person when
in the previous year these factors are
for asthma or usual
pharmacotherapy
the patient who
has asthma with • Nonuse or low adherence to in- present. Such factors
plus salmeterol.
haled corticosteroids
Chest. 2006;129:15- an atopic compo- include asthma his-
26. [PMID: 16424409] • History of depression, substance
35. Nelson JA, Strauss L, nent may benefit abuse, personality disorder, unem-
tory, socioeconomic
Skowronski M, Ciufo from referral to an ployment, or recent bereavement characteristics, and
R, Novak R, McFad-
den ER Jr. Effect of allergist. comorbid conditions
long-term salme- (see Box).
terol treatment on
exercise-induced
When is
asthma. N Engl J hospitalization indicated for a How often should clinicians see
Med. 1998;339:141-
6. [PMID: 9664089] patient with asthma? patients with asthma for routine
36. Nightingale JA, Patients who have a sustained re- follow-up?
Rogers DF, Barnes PJ.
Comparison of the sponse to treatment in outpatient No definitive studies are available
effects of salmeterol settings do not need to be hospital- to guide the frequency of asthma
and formoterol in
patients with severe ized if they understand the impor- follow-up, but consensus suggests
asthma. Chest. tance of continued anti-inflamma- that for patients with newly diag-
2002;121:1401-6.
[PMID: 12006420] tory therapy and close follow-up. nosed asthma, 2 to 4 visits during
37. Leff JA, Busse WW, The decision to hospitalize a pa- the 6 months after diagnosis can
Pearlman D, Bronsky
EA, Kemp J, Hende- tient with asthma should consider help to establish and reinforce the
les L, et al. Mon- patient characteristics, severity of patient’s basic knowledge and man-
telukast, a
leukotriene-receptor disease, and initial response to agement skills. For patients with
antagonist, for the short-term therapy. Patients with asthma who have shown maximum
treatment of mild
asthma and exer- an incomplete response to therapy improvement in pulmonary func-
cise-induced bron- during an exacerbation (PEFR tion and have minimal to no relat-
choconstriction. N ed symptoms, the NHLBI Expert
Engl J Med. >50% but <70% than patient’s best
1998;339:147-52. or of the predicted value) may need Panel Guide suggests routine fol-
[PMID: 9664090]
38. Emerman CL, hospitalization. When posttreat- low-up every 1 to 6 months with
Woodruff PG, Cydul- ment PEFR remains <50% of the annual pulmonary function tests
ka RK, Gibbs MA,
Pollack CV Jr., Camar- predicted value, intensive care unit (2); however, evidence document-
go CA Jr. Prospective admission may be warranted. How- ing the benefit of this strategy is
multicenter study of
ever, data are insufficient to sup- limited. The Report also suggests
relapse following
treatment for acute port the idea that adequate oxygen follow-up within 7 days for patients
asthma among
saturation and PEFR at the time of discharged from the hospital and
adults presenting to
the emergency de- emergency department discharge within 10 days for patients treated
partment. MARC in-
predict a good outcome. as outpatients for an exacerbation.
vestigators. Multi-
center Asthma Studies have shown that relapse
Research Collabora- In a prospective cohort study of adults pre- occurs in about 1% of patients per
tion. Chest.
1999;115:919-27. senting with asthma to urban emergency day until the follow-up visit
[PMID: 10208187] departments in the United States, the PEFR (38–40).

© 2007 American College of Physicians ITC6-12 In the Clinic Annals of Internal Medicine 5 June 2007
Treatment... Patients should avoid asthma triggers. While air conditioners or de-
humidifiers may be helpful, indoor air-cleaning devices are of unclear utility. All
patients with asthma should have short-acting β-agonists available for relief of
acute symptoms. For patients with persistent asthma, treatment with long-term
controller medications should begin with low-dose inhaled corticosteroids and be
stepped up to higher doses and/or additional agents according to asthma severity.
Patients with severe persistent asthma may need as many as 3 long-term con-
troller medications.

CLINICAL BOTTOM LINE

Practice
What do professional exacerbations. Clinicians should in-
Improvement
organizations recommend clude asthma education as part of
regarding the care of patients each office visit, and formal asthma
with asthma? education programs may be particu-
Many of the recommendations larly helpful for patients who have
provided in this overview are from had asthma hospitalizations, emer-
a guideline developed by the gency department visits, or frequent
NHLBI that was most recently up- exacerbations. Important elements
dated in 2002 (22). The guidelines of asthma education include basic
were approved by the 40 organiza-
information, the role of medica-
tions that comprise the National
tions, inhaler and peak flow meter
Asthma Education and Prevention
skills, environmental control meas- 39. McCarren M, McDer-
Program. The document covers mott MF, Zalenski RJ,
pathogenesis, medications, moni- ures, and appropriate use of rescue Jovanovic B, Marder
medications. Demographically and D, Murphy DG, et al.
toring, and prevention and is avail- Prediction of relapse
able free at www.nhlbi.nih.gov/ culturally appropriate educational within eight weeks
after an acute asth-
guidelines/asthma/asthgdln.htm. materials can be used as an adjunct ma exacerbation in
adults. J Clin Epi-
to one-on-one asthma education. demiol. 1998;51:107-
Numerous other organizations have Because many patients use metered- 18. [PMID: 9474071]
40. Rowe BH, Bota GW,
developed recommendations related dose inhalers improperly, all pa- Fabris L, Therrien SA,
to the care of patients with asthma, tients should receive instruction Milner RA, Jacono J.
Inhaled budesonide
including the American Academy on proper use. in addition to oral
of Asthma, Allergy and Immunolo- corticosteroids to
prevent asthma re-
gy (www.aaaai.org); the American Clinicians should develop individu- lapse following dis-
charge from the
Lung Association (www.lungusa. alized self-management plans for emergency depart-
org); and the Asthma and Allergy all patients, taking into considera- ment: a randomized
controlled trial.
Foundation of America (www.aafa. tion underlying disease severity and JAMA.
org). These organizations also pro- 1999;281:2119-26.
the patient’s willingness and ability [PMID: 10367823]
vide demographically and culturally to manage the illness. For patients 41. Effectiveness of rou-
tine self monitoring
sensitive educational programs and with mild disease, clinicians should of peak flow in pa-
teaching tools. consider providing a simple self-
tients with asthma.
Grampian Asthma
Study of Integrated
What is the role of patient management plan that provides in- Care (GRASSIC). BMJ.
education in optimizing the formation on how to handle exac- 1994;308:564-7.
[PMID: 8148679]
outcome of asthma care? erbations, including health care 42. Charlton I, Charlton
G, Broomfield J,
Asthma is a paradigm illness for contacts in case of emergency. For Mullee MA. Evalua-
patient self-management because of patients with moderate-to-severe tion of peak flow
and symptoms only
its intermittent and unpredictable disease, provide a self-management self management
plans for control of
nature. Patients and family mem- plan that incorporates a daily diary asthma in general
bers can recognize changes and ini- and a detailed written action plan practice. BMJ.
1990;301:1355-9.
tiate specific actions to minimize with specific objective and subjective [PMID: 2148702]

5 June 2007 Annals of Internal Medicine In the Clinic ITC6-13 © 2007 American College of Physicians
markers for self-directed change Do U.S. stakeholders consider
Ambulatory Care Quality in therapy. asthma care when evaluating
Alliance Performance the quality of care a physician
Measures for Asthma
Should all patients with asthma delivers?
• Percentage of individuals who were In April 2005, The Ambulatory
identified as having persistent asthma receive peak flow meters?
during the 1 year before the measure- The precision of patients and physi- Care Quality Alliance (AQA) re-
ment year and who were appropri- cians in estimating the degree of air- leased a set of 26 health care quality
ately prescribed asthma medications indicators for clinicians, consumers,
(e.g., inhaled corticosteroids) during flow obstruction based on symptoms and health care purchasers to use in
the measurement year. alone varies greatly, so objective quality improvement efforts, public
• Percentage of individuals with mild, measurement of expiratory flow
moderate, or severe persistent asthma reporting, and pay-for-performance
who were prescribed either the pre- rates could in theory be useful to programs (www.ahrq.gov/qual/
ferred long-term control medication guide therapeutic strategies. How- aqastart.htm ). In May 2005, the
(inhaled corticosteroid) or an Centers for Medicare & Medicaid
acceptable alternative treatment. ever, studies that have randomly as-
signed patients to action plans that Services (CMS) endorsed the de-
Center for Medicare & velopment of these indicators. Of
Medicaid Services (CMS) incorporate PEFR have not shown
the 26 AQA indicators, 2 focus on
Asthma Quality Measures major improvements compared asthma care (see the Box).
• Percentage of patients aged 5 to 40 with action plans based on symp-
years with a diagnosis of mild, toms alone (41, 42). As part of CMS’s Physician Quali-
moderate, or severe persistent
asthma who were prescribed either
ty Reporting Initiative, physicians
inhaled corticosteroid or an accept- Clinicians should ensure that all who successfully report a designat-
able alternative. patients with persistent moderate- ed set of quality measures on claims
• Percentage of patients aged 5 to 40 to-severe asthma have a peak flow for services provided July 1 to
years with a diagnosis of asthma December 31, 2007, may earn a
who were evaluated during at least meter at home and know how to bonus payment. See the Box for the
one office visit within 12 months use it. If patients are unwilling to
for the frequency (numeric) of day- 2 CMS measures related to asthma
time nocturnal asthma symptoms. measure peak flow, provide instruc- (www.cms.hhs.gov/specifications
tion in symptom-based monitoring. _2007-02-04.pdf).

in the clinic
in the clinic http://PIER.acponline.org
Asthma module of PIER, an electronic deci-

Tool Kit sion support resource designed for rapid access


to information at the point of care.

http://pennhealth.com/ency/
presentations/100200_1.htm
Asthma Tutorial on proper use of metered dose
inhalers.

http://pier.acponline.org/qualitym/
asm.html
Tool to assist clinicians in developing strate-
gies to improve adherence to the AQA asthma
performance measures.

www.annals/intheclinic/tools
Download copies of the patient information
sheet that appears on the following page for
duplication and distribution to your patients.

© 2007 American College of Physicians ITC6-14 In the Clinic Annals of Internal Medicine 5 June 2007
THINGS PEOPLE SHOULD KNOW In the Clinic
Annals of Internal Medicine
ABOUT ASTHMA

A sthma causes a squeezing of the muscle in the walls of the tubes


(airways, bronchi) that bring air to the lungs. Breathing becomes
difficult when this happens.

Web Sites with Good How to Use a Metered Dose Inhaler


Information about Asthma Inhalers deliver a specific dose of medicine to the lungs
in a spray form.
MedlinePLUS
www.nlm.nih.gov/medlineplus/asthma.html 1. Take off the cap and shake the inhaler hard.
2. Breathe out all the way.
American Lung Association 3. Hold the inhaler about 2-fingers width from your
www.lungusa.org mouth.
4. Start to breath in slowly through your mouth as
you press down on the inhaler once and keep
breathing in slowly until you can’t breathe in any
more.
5. Hold your breath and count to 10 slowly.
6. Repeat steps 1 to 5 if your doctor has prescribed
more than 1 puff of medicine, wait about 1 minute
between puffs.

HEALTH TiPS* Asthma makes you cough and wheeze


WHAT YOU CAN DO and can make it hard to breathe.

Patient Information
Here’s what you can do to feel better. Call your doctor or go to the hospital if it is
Stay away from what makes your asthma worse: hard to breathe and your medicines are not
helping
• Dust
• Smoke Things to ask your doctor:
• Animals Which medicines are to keep attacks from
• Cold or dry air happening?
Don’t smoke and stay away from people Which medicines are to stop attacks when they
who do come on?
Asthma-proof your home: Can you show me the right way to use my
• Get special mattress and pillow covers inhaler?
• Get rid of old carpets and drapes
Can I use my inhalers more often if I need to?
• Use air conditioners and dehumidifiers
What are the side effects of my inhalers and
Use your medicines the right way:
my other medicines?
• Take medicines that prevent attacks every
day Do I need a special meter to check my breath-
• Take medicines that stop attacks when you ing at home? How do I use it?
need them How long should I wait to call the doctor or go
• Learn the right way to use your inhalers to the hospital if I am having trouble breathing?
*HEALTH TiPS are developed by the American College of Physicians Foundation and PIER
CME Questions

1. A 46-year-old woman with persistent asth- 3. A 38-year-old woman is evaluated for wors- 5. A 19-year-old woman is evaluated for possi-
ma is evaluated in the clinic for a scheduled ening control of mild persistent asthma. Her ble asthma. She has known seasonal aller-
follow-up visit. Since her most recent visit 6 disease had been under good control on gies that manifest as hay fever in fall and
months ago, her disease has been stable on therapy with moderate-dose inhaled corti- spring. Symptoms are restricted to her nose
a regimen of high-dose inhaled corticos- costeroids plus as-needed albuterol until 6 and eyes, and she has no history of wheez-
teroids plus a long-acting β-agonist and weeks ago when she had an acute respirato- ing or chest tightness. The patient had a
as-needed albuterol, which she uses approx- ry tract infection. Since then she has had methacholine test as part of a research
imately once every 1 to 2 weeks. The patient significant worsening of her symptoms, with study, which showed borderline response.
is pleased with the current therapy, and the nightly cough and wheezing. She uses an al- Which of the following would be the most
as-needed albuterol is continued. buterol rescue inhaler 6 to 8 times per day. appropriate management for this patient?
Which of the following would be the best Which of the following is the most appropri- A. Inhaled corticosteroids and a long-
approach to this patient’s therapy? ate therapy for this patient? acting β-agonist
A. Continue inhaled corticosteroids and A. A 7-day course of a fluoroquinolone B. Seasonal nasal corticosteroids and
the long-acting β-agonist at current antibiotic antihistamine
doses B. Nebulized albuterol–ipratropium C. Albuterol inhaler as needed
B. Discontinue inhaled corticosteroids and bromide at home D. Repeat methacholine challenge
the long-acting β-agonist C. A short course of oral corticosteroid
C. Continue the long-acting β-agonist therapy 6. A 37-year-old man with asthma is evaluated
and reduce the dose of inhaled D. A leukotriene-receptor antagonist because he continues to have frequent at-
corticosteroids tacks and now believes that his short-acting
D. Discontinue the long-acting β-agonist 4. A 28-year-old man is evaluated for a 6- β-agonist is not providing relief. Other med-
and reduce the dose of inhaled month history of episodic dyspnea, cough, ications he reportedly uses include a long-
corticosteroids and wheezing. He had asthma as a child but acting β-agonist inhaler, inhaled high-dose
has been asymptomatic since his early teens. corticosteroids, and a short-acting β-agonist
2. A 75-year-old woman with a long-standing The recent symptoms, which began after an inhaler as rescue medication. He has symp-
history of asthma is evaluated for increased upper respiratory tract infection, are often toms daily and nocturnal symptoms about
nocturnal asthma symptoms and frequent triggered by exercise or exposure to cold air twice per week.
need to use an albuterol inhaler. Her treat- and awaken him from sleep 3 or 4 times per On physical examination, he is in mild respi-
ment regimen now consists of daily moder- month. ratory distress. Temperature is 37°C (98.6°F),
ate-dose inhaled corticosteroids. On physical examination, vital signs are nor- blood pressure is 140/85 mm Hg, pulse rate
On physical examination she has occasional mal. There is scattered wheezing in both is 90 beats/min, and respiration rate is 18
wheezing; the examination is otherwise un- lung fields. Office spirometry shows an FEV1 breaths/min. He has bilateral wheezing and
remarkable. Office spirometry shows an FEV1 75% of predicted with a 15% improvement oral thrush. Office spirometry shows FEV1
of 2.2 L (75% of predicted). (370 mL) after inhaled albuterol. Chest radi- 65% of predicted, which improves with
Which of the following is the most appropri- ographs are normal. bronchodilators to 85% of predicted. He has
ate adjustment to this patient’s therapy? Which of the following is the most appropri- no history of recent viral upper respiratory
ate therapy for this patient? infections, rhinitis, or symptoms of gastroe-
A. Double the inhaled corticosteroid dose sophageal reflux disease.
B. Add theophylline A. Albuterol by metered-dose inhaler
C. Add a leukotriene-receptor antagonist as needed Which of the following is the best next step
D. Add a long-acting β-agonist B. Long-acting β-agonist plus as-needed in this patient’s management?
E. Add anti-IgE antibody albuterol A. Add a leukotriene inhibitor
C. Long-acting β-agonist B. Observe the patient using the metered-
D. Inhaled corticosteroids plus as-needed dose inhaler
albuterol C. Start oral prednisone therapy and have
E. Long-term antibiotic therapy the patient return for a pill count
D. Have the patient return with a symp-
tom and treatment log

Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP). Go to www.annals.org/intheclinic/
to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.

© 2007 American College of Physicians ITC6-16 In the Clinic Annals of Internal Medicine 5 June 2007