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Review article

Supported by a grant from Zeneca Pharmaceuticals

Clinical evaluation of asthma

James T C Li, MD* and Edward J OConnell, MD
Objective: The purpose of this article is to review the medical history and physical examination of the asthmatic patient. Data Sources: English references identified from relevant articles and book chapters, experts, and MEDLINE search, using asthma, physical diagnosis, and medical history. Study Selection: Clinical studies of the medical history or physical examination in subjects with respiratory disease were selected for review. Results: Symptoms such as wheezing, chest tightness and difficulty in taking a deep breath suggest asthma, while symptoms such as gasping, smothering or air hunger suggest alternative diagnoses. Symptoms of asthma correlate poorly with airway obstruction in one-third to one-half of asthmatic patients. Respiratory signs such as wheezing, breath sound intensity, forced expiratory time, accessory muscle use, respiratory rate and pulsus paradoxus correlate roughly with airway obstruction. However, clinicians disagree on the presence or absence of respiratory signs 55% to 89% of the time. Furthermore, physicians correctly predict pulmonary function based on history and physical examination only about half the time, and correctly diagnose asthma based on the clinical examination 63% to 74% of the time. Conclusions: The medical history and physical examination are moderately effective in diagnosing asthma and estimating its severity. Objective measures of lung function are necessary for the accurate diagnosis of asthma.
Ann Allergy Asthma Immunol 1996;76:114.

INTRODUCTION The clinical evaluation of a new patient with asthma or possible asthma begins with a medical history, proceeds to a physical examination of the patient, and often concludes with selected laboratory studies. A careful and comprehensive medical history is essential for the diagnosis and management of asthma. In this review, we will draw from clinical studies, experiences, and observations to provide an evidentiary framework for the clinical evaluation of asthma. This review is not intended as a comprehensive exposition of the medical
Division of Allergic Diseases and Internal Medicine* and Pediatric Allergy and Immunology, Mayo Clinic and Foundation, Rochester, Minnesota. Received for publication February 27, 1995. Accepted for publication in revised form June 24, 1995.

history and examination of the patient with asthma or possible asthma, an example of which is shown in Table 1. Rather, we will show how published clinical studies can guide the medical history and physical examination in asthma. We will point out where evidence is lacking and when reliance on clinical judgement alone is required. The four major issues we will address are (1) What are the symptoms of asthma? (2) How do symptoms of asthma correlate with the degree of airway obstruction? (3) How accurate is the physical examination in asthma? and (4) How good are physicians at diagnosing asthma and estimating its severity? WHAT ARE THE SYMPTOMS OF ASTHMA? Descriptors Most clinicians would agree that the major symptoms of asthma are wheez-

ing, shortness of breath, chest tightness, and cough. What is the evidence that these, indeed, are the most important symptoms of asthma, and how often are these symptoms described by individuals with asthma? It is very difficult or impossible to offer an accurate answer to this question. However, published studies of symptoms of asthma can shed some light on this issue and provide guidance for the differential diagnosis of asthma. In one study, 53 patients with a variety of cardiopulmonary disorders including asthma were asked to select descriptions of their sensation of breathlessness from a list of 19 descriptors.1 Analysis of the responses suggested that individuals with asthma were more likely to select descriptors such as My breath does not go out all the way, My chest feels tight, I cannot take a deep breath, and My breathing requires more concentration. Individuals with asthma and individuals with chronic obstructive pulmonary disease both selected the descriptor My breathing requires effort or My breathing is heavy. On the other hand, individuals with chronic obstructive pulmonary disease use descriptors such as I am gasping for breath, I cannot get enough air, and My breathing requires more work while individuals with asthma did not. Similarly, individuals with congestive heart failure were more likely to select descriptors such as I feel that my breath is rapid, I feel that I am smothering, My breathing is heavy, and I feel a hunger for more air while individuals with asthma did not. Thus, individuals with asthma use somewhat different terms to describe their symptoms compared


with individuals who have chronic obstructive pulmonary disease or congestive heart failure. It is worth pointing out that wheezing and cough were not included on the dyspnea questionnaire. In a similar way, another study analyzed a dyspnea questionnaire consisting of 45 descriptors of breathing discomfort from 169 patients with cardiopulmonary disorders.2 Ninety-two percent of asthmatic patients selected the descriptor I feel wheezy, 83% selected I feel short of breath or related descriptors, and 81% selected My chest feels tight. The percentage of affirmative responses to these three descriptors were 76%, 82%, and 68%, respectively, for chronic obstructive pulmonary disease and 28%, 54%, and 41%, respectively, for cardiac disease. Thus, almost all patients with asthma include wheezing as one of their symptoms compared with about three out of four patients with chronic obstructive pulmonary disease and about three out of ten patients with heart disease. It may be useful, then, for the physician to elicit the description of respiratory symptoms from the patient in order to form a differential diagnosis. Of course, a detailed and comprehensive medical history would include much more than simply a description of symptoms, such as associated symptoms (eg, chest pain), and triggering or alleviating factors. Interestingly, physiologic study of dyspnea suggests that the descriptor My breath does not go out all the way is associated with an increased functional residual capacity (ie, pulmonary hyperinflation) rather than airway obstruction.35 Deliberate hyperventilation is associated with the descriptor I feel hunger for more air or I cannot get enough air which might be helpful in differentiating asthma from the hyperventilation syndrome.3 Virtually all clinicians will recognize that there is a wide variation in how patients perceive and describe their symptoms of asthma. Studies analyzing the ability of individuals with asthma to detect or describe resistive loading find significant variation

Table 1. The Medical History in Asthma I. Symptoms A. Quality 1. Description a. wheeze, breathlessness, cough, chest tightness, etc. 2. Onset 3. Progression B. Provoking or triggering factors 1. Exercise a. timing, duration, severity b. effect on work, school, recreation 2. Infection a. frequency, severity b. response to treatment 3. Allergens a. season b. animals, pets c. occupational d. risk factors for dust mite exposure e. related to hobbies, recreation f. associated rhinoconjunctivitis g. previous allergy testing 4. Irritant a. fumes, dust, pollution b. smoking c. environmental smoke 5. Cold air a. exercise in cold air 6. Medications a. beta-adrenergic blocking agents b. aspirin and non-steroidal anti-inflammatory drugs c. medications for co-morbid medical condition 7. Emotional/stress a. hyperventilation b. panic attacks 8. Foods a. sulfites C. Alleviating factors 1. Rest, avoidance of physical activity 2. Avoidance of allergens, irritants 3. Medications a. timing and duration (eg, beta-adrenergic agonists, corticosteroids) b. immunotherapy II. Assessment of Severity A. Severity of symptoms 1. Frequency, number of episodes per day or week 2. Duration 3. Description of typical exacerbation 4. Response to treatment B. Limitations of daily activity 1. Walking, distance, pace 2. Stairs, number of flights 3. Exercise, sports 4. Sleep disturbance, early morning symptoms 5. Daily activity C. Hospitalizations 1. Number, frequency, length of stay 2. Intubation 3. Intensive care (continued on next page)


Table 1. Continued D. Emergency visits 1. Number, frequency 2. Provoking factors 3. Other unscheduled visits E. Days lost from work or school 1. School or work performance F. Medication requirements 1. Systemic coriticosteroid use 2. Beta-adrenergic agonist use a. number of puffs per day b. number of canisters per month 3. Inhaled corticosteroid, nedocromil, cromolyn use, theophylline, ipratropium 4. Changes in medication requirements G. Tests 1. Previous or home peak flow measurements 2. Previous spirometry Associated and Co-Morbid Medical Conditions A. Rhinitis B. Sinusitis; nasal polyposis C. Chronic obstructive pulmonary disease D. Gastroesophageal reflux E. Eczema F. Heart disease G. Hypertension H. Glaucoma I. Psychiatric disorder Current Medications A. Asthma medications B. All other medications C. Non-prescription medications D. Alternative medicine therapy Immunizations A. Childhood B. Influenza C. Pneumococcus Psychosocial A. Residence 1. Slab construction, ventilation 2. Humidity 3. Heating, cooling systems 4. Carpets, furnishings 5. Pets, hobbies 6. Factors for dust mite, cockroach, rodents 7. Change in residence, previous residencies 8. Other household members B. Occupation 1. Current and previous a. building, location b. daily activity c. exposure to allergen and irritants C. School 1. Performance 2. Phobia 3. Physical education 4. Relationship with peers, teachers D. Hobbies 1. Animals 2. Exposure 3. Hobbies of family members (continued on next page)





among individuals.6 8 A few generalizations, however, can be made. First, when the perception of external resistive loading and induced bronchospasm are compared, there is a greater sense of dyspnea with bronchospasm at any given level of resistance.6 This suggests that airway resistance alone is not responsible for all asthmatic symptoms and that other physiologic derangements such as hyperinflation or inflammation may be contributory. Second, psychologic status can affect the description of respiratory symptoms. On one hand, individuals with psychologic profiles of anxiety and dependency exhibit decreased perception of airway obstruction.8 On the other hand, respiratory symptoms such as wheeze and dyspnea are correlated with anxiety, anger, and depression in patients without respiratory disease.9 Third, a study of 21 individuals with asthma showed that 19 subjects reported increased inspiratory rather than expiratory difficulty following methacholine bronchoprovocation.5 Physiologic correlation suggested that the increase in inspiratory capacity (ie, pulmonary hyperinflation) correlated better with symptoms than the change in FEV1 (ie, airway obstruction). This sense of inspiratory dyspnea may be a result of increased inspiratory muscle elastic loading caused by hyperinflation. A review of 119 patients experiencing acute asthma showed that 71% of patients found breathing air in more difficult compared with 19% who found breathing out more difficult.10 Interestingly, 78% of doctors surveys thought that their asthmatic patients found expiration more difficult.10 Fourth, a study of 28 asthmatic individuals undergoing allergen bronchoprovocation suggests that perceived breathlessness is closely related to the rate of fall in FEV1 rather than the absolute degree of airway obstruction.11 Asthmatic individuals thus described a stronger sense of dyspnea during the rapid fall in FEV1 during the early asthmatic response and lower degrees of dyspnea during the slower fall of FEV1 of the late asthmatic response.


Table 1. Continued Education 1. Level of general education 2. Level of asthma education 3. Need for additional asthma education F. Financial 1. Health insurance 2. Impact on patient and family finances G. Patient perceptions 1. Concerns, fears, current understanding of medical problem 2. Concerns, fears, current understanding of family or significant others 3. Impact of medical problem on patient, life, family H. Psychiatric and personality 1. Anxiety, dependence 2. Depression 3. Rebelliousness 4. Marital or family discord 5. Somatization 6. Physical, psychologic, sexual abuse, current or previous 7. Major psychiatric disorder VII. Family History A. Asthma B. Respiratory diseases C. Allergy, rhinitis, eczema D. Marital status E. Marital and family discord F. Impact of medical problem on family E.

Collectively, these observations suggest that wheezing, shortness of breath, and chest tightness are indeed important symptoms of asthma. Furthermore, an accurate medical history should include elicitation of the symptom descriptors, which may be helpful in differentiating asthma from chronic obstructive pulmonary disease, congestive heart failure, and hyperventilation. Symptoms of asthma are caused by pulmonary hyperinflation as well as airway obstruction, and a high rate of change in airway obstruction, characteristic of many asthmatic patients, may result in heightened perception of breathlessness. Finally, individuals with anxious and dependent personality traits may display a decreased sensation of airway obstruction. This latter finding clearly has important clinical significance since patients with asthma who have decreased perception of airway obstruction or hypoxia are at risk for fatal and nearly fatal asthma.12 Chronic cough is an important symptom for many patients with asthma, although by convention is not considered a form of dyspnea.

Cough may be the primary or sole presenting symptom of some children or adults with asthma.13,14 A review of cough symptoms in 32 children with asthma whose primary symptom was chronic cough showed that cough was triggered by an upper respiratory tract infection in 100% of patients, the cough was exercise-induced in 78%, the cough was nocturnal in 72%, and was induced by cold air in 44% of patients.13 The idea that cough can be the sole symptom of patients with asthma is closely linked to the demonstration of nonspecific bronchial hyperresponsiveness in these individuals.14 17 The definitive diagnosis of the cause of a chronic cough, however, may take years to elucidate or may never be fully understood in individual patients.18 Recognizing these limitations, the authors of one study estimated that the methacholine bronchial challenge had a negative predictive value of 100% and a positive predictive value of 74% for chronic cough caused by asthma.15 In other words, in this study a negative methacholine challenge ef-

fectively ruled out the presence of asthma while a positive methacholine challenge indicated a 74% chance that the cough was caused by asthma. In this same study, 14 of 45 or 29% of patients presenting with chronic cough were diagnosed as having cough caused by asthma. Importantly, this and other studies19,20 show that interpretation of the medical history is not very effective at predicting the presence or absence of bronchial hyperresponsiveness. For patients with chronic cough, a concomitant history of dyspnea increased the likelihood that the cough was caused by asthma by tenfold.15 A history of wheezing, cough with respiratory tract infection, and a previous diagnosis of asthma were not significantly linked to asthma-induced cough in this study. Cough, therefore, can be an important symptom of asthma. Cough induced by respiratory infections, cold air and exercise, along with nocturnal cough, may be suggestive of asthma. Although the presence of dyspnea in addition to cough is suggestive of asthma, a previous diagnosis of asthma, a history of wheezing, the duration of cough, and personal or family history of allergy are not helpful in predicting whether or not chronic cough is caused by asthma.15,17 A longterm follow-up study of 78 adults who underwent diagnostic methacholine challenge suggests that individuals who had a positive methacholine challenge were more likely to develop symptoms of chest tightness, wheezing, and dyspnea.18 Interestingly, development of cough was not correlated with the results of the previous methacholine bronchial challenge. These results together suggest that a careful medical history will not be sufficient to establish whether or not asthma is the major cause of chronic cough for many patients. The methacholine bronchial challenge is a useful test for many of these patients, although close follow-up and assessing the response to therapy are also very important. Asthma may cause other symptoms such as chest pain, particularly in children. While most studies suggest that


asthma is an important cause of chest pain in about 20% of children presenting with chest pain, one study demonstrated exercise-induced airway obstruction in 73% of such children.21 Respiratory Questionnaires Epidemiologic surveys have used respiratory questionnaires to estimate the prevalence of respiratory symptoms and to correlate these symptoms with cardiopulmonary disease states. In one such survey,22 59% of patients with a new diagnosis of asthma reported wheezing compared with 19% of control patients, and 31% of patients with a new diagnosis of asthma reported shortness of breath with wheezing compared with only 6% of controls. Of interest, 69% of asthmatic patients reported symptoms of rhinitis compared with 39% of control patients. These same data showed that individuals who reported any wheeze or shortness of breath with wheezing were seven times more likely to have asthma compared with those who did not. Individuals who reported rhinitis were more than three times more likely to have asthma compared with those who did not. A history of rhinitis may be moderately useful in the diagnosis of asthma. Reported wheezing is found in up to 30% of survey populations22 and persistent wheezing is present in about 10% of children.23 Similar studies suggest that dyspnea is present in 5% to 25% of the general population.24 26 A study of 1,392 male workers using a standardized respiratory questionnaire showed that individuals reporting wheezing or breathlessness, and especially those with both symptoms, were more likely to show a low PC20 when undergoing a methacholine bronchial challenge. The symptom of chest tightness was not independently correlated with bronchial hyperresponsiveness.27 Another study showed that wheeze and attacks of shortness of breath with wheeze were independently predictive of asthma.28 Surveys using respiratory questionnaires confirm that the symptom of wheezing or wheezing combined with shortness of breath are highly suggestive of asthma.

HOW DO ASTHMATIC SYMPTOMS CORRELATE WITH AIRWAY OBSTRUCTION? The preceding review shows that the symptoms of wheeze, shortness of breath, chest tightness, and cough are important in asthma. How well or how poorly symptoms of asthma correlate with asthma severity is a different question entirely. This issue has great clinical significance since management decisions in asthma are founded in large part on the physicians estimate of the severity of asthma. With few exceptions, the evidence to date clearly indicates that asthmatic symptoms correlate poorly with the degree of airway obstruction for a significant proportion of asthmatic patients; hence, objective measurement of airway obstruction is essential for these individuals. In one study, 255 individuals with asthma estimated the severity of symptoms of asthma using a visual analog scale while measurements of peak expiratory flow rate were taken at the same time.29 Sixty percent of patients showed no significant correlation between subjective asthma scores and peak expiratory flow rate measurements. Study of 82 patients with asthma undergoing methacholine bronchial challenge showed that 15% of patients were unable to subjectively detect reverse airway obstruction (50% predicted or lower).30 A similar study of asthmatic patients undergoing bronchoprovocation showed that although symptoms of breathlessness were statistically correlated with FEV1 (r .88),31 there was a large variation in the severity of breathlessness for any particular degree of airway obstruction. Study of patients with nocturnal asthma shows that the increase in airway obstruction in the early morning hours may go undetected in one-third of patients.32 In another study, 20 children with asthma were studied over a 16-week period with symptom scores, peak expiratory flow readings, and measurement of FEV1.33 During asymptomatic periods, peak expiratory flow rate was

decreased 54% of the time and FEV1 was decreased 36% of the time. When patients recovering from acute asthma were studied, pulmonary function was only between 40% and 50% of predicted normal values when symptoms disappeared.34 Collectively, these observations clearly show that one-third to one-half of asthmatic patients underestimate the severity of asthma when judged by symptoms alone. Apparently, the perception of asthma cannot be learned, inasmuch as home recording of peak expiratory flow rates does not improve the subjective assessment of asthma severity.35 Nor does the use of symptom questionnaires improve the perception of airway obstruction.36 Perhaps one-third to one-half of asthmatic patients can successfully estimate their degree of airway obstruction. One study of ten asthmatic subjects showed that a symptom diary was superior to daily peak flow monitoring in detecting exacerbations of asthma.37 These findings together are important because poor perception of asthma may be a risk factor for fatal asthma. Patients with histories of nearly fatal asthma show reduced chemosensitivity and blunted perception of dyspnea.12 Psychiatric disease and psychologic disturbances are also important risk factors for fatal asthma.38 Such patients may also have blunted perceptions of airway obstruction.7 HOW ACCURATE IS THE PHYSICAL EXAMINATION IN ASTHMA? If symptoms of asthma correlate poorly with airway obstruction in a significant proportion of asthmatic patients, is the physical examination an accurate and inexpensive way to evaluate asthma severity? There is a rough correlation between the presence of wheezing on physical examination and the severity of airflow obstruction.39 41 Although loud wheezing is associated with greater airway obstruction, the degree of correlation between wheezing and airway obstruction is modest and there is great variability.39,40 These and other studies suggest that wheez-


ing during inspiration and expiration, loudness of wheezing and prolonged duration of wheezing during the respiratory cycle are associated with greater airway obstruction.39,40,42,43 Wheezing during forced exhalation apparently does not correlate with airway obstruction or bronchial hyperresponsiveness.40,44 The stethoscope and human ear together limit the usefulness of wheezing as a measure of airway obstruction. Analysis of recorded lung sounds shows that there is a good correlation between the duration of wheezing during the breath cycle and the FEV1 (r .89).42,43 Another computer-assisted lung sound analysis showed that lung sound mapping correctly classified about 70% of subjects with a variety of cardiopulmonary disorders such as interstitial pulmonary fibrosis, chronic obstructive pulmonary disease, congestive heart failure, and pneumonia.45 Lung sound analysis of asthmatic children undergoing bronchoprovocation showed that wheezing detected by lung sound analysis was much more sensitive at detecting airway obstruction than respiratory symptoms or wheezing on auscultation.46 Auscultated wheezes during bronchoprovocation are not as sensitive as direct measurement of FEV1, however.47 Since auscultation for wheezing in the office and hospital setting is generally confined to auscultation with the stethoscope, we conclude that there is only a rough correlation between wheezing and airway obstruction. Most clinicians would agree that significant airway obstruction can be present in the absence of wheezing on examination. The respiratory signs of breath sound intensity and forced expiratory time have both been correlated with airway obstruction. Examination of 183 patients referred to a pulmonary function laboratory showed that breath sound intensity correlated with measurements of FEV1.48 Other studies of physical findings in chronic obstructive pulmonary disease support the observation that reduced intensity of breath sounds is associated with air-

way obstruction.49 51 Decreased breath sound intensity presumably is caused by a combination of decreased acoustic transmission through the lung and chest wall combined with decreased inspired and expired lung volumes and flow rates. The forced expiratory time is measured by instructing the subject to inhale maximally and then exhale forcefully through a completed forced vital capacity maneuver. The examiner times the exhalation maneuver and records a forced expiratory time. Comparison of forced expiratory time and FEV1 shows that a prolonged forced expiratory time of six seconds or longer is associated with increased airway obstruction.52,53 As a test for obstructive airway disease, the forced expiratory time has a sensitivity of 74% to 92% and a specificity of 43% to 75%.52,53 Individuals with chronic obstructive pulmonary disease and emphysema may exhibit a constellation of physical findings that is somewhat different from asthma. Increased resonance to percussion, excavation of the supraclavicular fossa, tracheal tug, and accessory muscle activity correlate significantly with airway obstruction in patients with chronic obstructive lung disease.49,50,54,56 As described above, the forced expiratory time and breath sound intensity correlate reasonably well with objective measures of airflow obstruction.49,51 A study of 31 patients with chronic obstructive pulmonary disease showed that of patients with severe obstruction (FEV1 one liter or less), 100% used accessory muscles, 70% had wheezing, 62% had diminished breath sounds, and 44% had increased resonance to percussion.57 In contrast, among patients with milder obstruction (FEV1 1.1 L) approximately 39% showed accessory muscle use, 30% had wheezing, 21% had diminished breath sounds, and 14% had increased resonance to percussion.57 In asthmatic children, severe airway obstruction correlates with accessory muscle use, although prolonged expiration and wheezing predicted airway obstruction poorly.58

The presence of pulsus paradoxus is associated with severe obstructive lung disease including asthma.59,60 A study of 93 patients with asthma showed that a pulsus paradoxus was associated with a peak expiratory flow rate of 33% of predicted values on average.59 Similarly, the respiratory rate correlates modestly (r .42) with peak expiratory flow rates in patients with acute asthma.61 Auscultation at the mouth or trachea shows that wheezing may be transmitted much better through the airways than across the chest wall.62 Wheezing over the neck, particularly when predominantly inspiratory, suggests stridor and upper airway obstruction, rather than asthma.63 In summary, the presence of wheezing, the duration of wheezing as a proportion of the breath cycle, inspiratory and expiratory wheezing, and the loudness of wheezing all correlate roughly with airway obstruction. The intensity of breath sounds and the forced expiratory time both correlate reasonably well with airway obstruction. Both pulsus paradoxus and a rapid respiratory rate are associated with severe airway obstruction. Despite the statistically significant correlation of these respiratory signs with airflow obstruction, it is nevertheless very difficult for clinicians to estimate airway obstruction accurately based on the physical examination alone. One reason for this is the correlation of physical signs with measures of airflow obstruction is not always close enough to be clinically important. Another important reason is the wide observer variability of skill in the physical examination of the chest. One study of interobserver variability in eliciting physical signs in examination of the chest showed that a group of four physicians agreed with the presence or absence of a physical sign only 55% of the time.64 Fortunately, the presence or absence of wheezing seemed somewhat more reliable than other respiratory signs since physicians were in complete agreement 63% of the time. In a separate study of intraobserver and interobserver variability, there was disagree-


ment about physical findings of the chest 11% to 26% of the time.65 Further, medical students demonstrated better self-consistency than pulmonary specialists. Rhonchi (low pitched wheezes)66 and wheezes64 66 seem more reliably detected than other respiratory signs. These studies suggest that physicians agree on the presence or absence of physical signs of the respiratory system 55% to 89% of the time.57,64 66 Although physicians are moderately successful in eliciting respiratory signs, there is considerable disagreement among observers when the same patients are examined, and even significant variation when a single observer examines the same patient on multiple occasions. Nevertheless, most clinicians would agree that the pulmonary examination is important for patients with asthma or possible asthma. For example, the presence of wheezing would suggest clinically important airway obstruction, although the absence of wheezing would not rule it out. In one clinical study, investigators trained actresses to simulate a new patient with asthma.67 The chest was not examined in 61% of 74 consultations. We suggest that all new patients with asthma or possible asthma should undergo a careful examination of the chest and lungs. Although there is no direct evidence to indicate that physical examination of the chest results in improved patient outcomes, clinicians should be aware of the benefits and limitations of the pulmonary examination. HOW GOOD ARE PHYSICIANS AT DIAGNOSING ASTHMA AND ESTIMATING ITS SEVERITY? While it may be useful or interesting to understand the clinical implications of symptoms of asthma and to appreciate the limitations of the pulmonary examination, physicians reach clinical impressions based on the complete medical history and physical examination. There has been some study of the diagnostic usefulness of the medical history in patients with asthma. One study prospectively evaluated 85 patients with dyspnea and found a diagnostic

accuracy of 66% based on the medical history, physical examination, and chest radiograph.68 These patients were seen at a subspecialty clinic and were evaluated by board certified pulmonologists. A similar study based in a general internal medicine clinic showed that internists were able to diagnose patients with dyspnea correctly 74% of the time.69 Study of the medical history in chronic obstructive pulmonary disease suggests that independent predictors of obstructive airway disease from the clinical examination were patient reported wheezing, auscultated wheezing, number of years the patient had smoked cigarettes, forced expiratory time, and peak expiratory flow rate.70 A similar study suggested that a previous diagnosis of chronic obstructive pulmonary disease, 70 pack year smoking history, and diminished breath sounds on examination suggested the diagnosis of chronic obstructive pulmonary disease.71,72 A study of patients admitted to the hospital for dyspnea showed that the referring physicians diagnoses were correct only 66% of the time.73 A study of 162 patients with possible work related asthma suggests that the type and timing of respiratory symptoms was modestly useful in differentiating occupational asthma from asthma that was not work related.74 For example, symptoms at work were reported by 91% of patients with occupational asthma and 86% of patients without occupational asthma. Improvement of symptoms on weekends or on holidays were reported by 77% and 88%, respectively, of patients with occupational asthma and 56% and 76%, respectively, by patients without occupational asthma. The investigators estimate that the predictive value of a history suggesting occupational asthma was 63%. These findings are consistent with the observation that occupational asthma may be correctly diagnosed only 12% of the time.75 Physicians are only moderately successful in predicting the results of

pulmonary function studies in patients with asthma or other respiratory diseases. One study of hospitalized asthmatic patients showed that physicians were able to estimate the peak expiratory flow rate to within 20% of the measured value only 44% of the time based on physical examination alone. The correlation coefficient was 0.66.76 In a similar study, physicians referring patients for pulmonary function tests were asked to predict the nature of the ventilatory defect (eg, obstructive, restrictive, normal) and estimate the severity of the abnormality.77 Physicians correctly predicted airway obstruction in 81% of cases. On the other hand, 61% of the tests gave a result that the physicians predicted as being unlikely, and physicians were unable to predict reversibility of airflow obstruction in patients with obstructive lung disease. Similar conclusions were reached in a study of 71 children presenting to an emergency room with acute asthma.78 Based on the medical history and physical examination, physicians were moderately successful in predicting FEV1 (correlation coefficient 0.47). On the other hand, the addition of spirometry results in a pulmonary medicine continuity clinic altered the clinical management plan in only 5% of patients.79 Patients with severe lung dysfunction or deteriorating clinical status benefited most from spirometry. Physicians are also only moderately successful in predicting nonspecific bronchial hyperresponsiveness. In a study of 34 patients evaluated for unexplained wheezing, the clinical history was only moderately successful in predicting the results of a methacholine bronchial challenge.80 A previous diagnosis of asthma predicted bronchial hyperreactivity 62% of the time; a history of past wheezing, 35% of the time; and expiratory wheezing on examination, 43% of the time. A separate study of 51 patients with possible asthma and normal spirometry showed that physicians were able to predict the re-


sults of a methacholine challenge test successfully only 39% of the time.81 When chest physicians were asked to predict the result of a histamine bronchial challenge in a group of patients with possible asthma, there was no correlation at all between physician predictions (based on a medical history and physical examination) and bronchial hyperresponsiveness.19 Another study showed that patient responses on a medical history questionnaire could not predict bronchial responses to histamine.20 These studies together support the notion that the medical history and physical examination are useful and moderately successful in diagnosing asthma and estimating its severity. Chest specialists and internists can be expected to diagnose asthma correctly about two-thirds or three-quarters of the time. At the same time, these published observations highlight the limitations of the clinical evaluation of asthma, even by specialists. Measures of lung function, in particular spirometry with response to bronchodilator, are needed to confirm a diagnosis of asthma. These limitations become apparent in studies of undiagnosed asthma. A survey of 14,127 patients showed that physician-diagnosed asthma was reported by 6.1% of patients, but that undiagnosed asthma that was active within the previous year was reported by 3.3% of patients.82 This suggests that one-third of asthmatic patients have not been properly diagnosed. Another report suggests that 17% of patients with unexplained dyspnea may have asthma.83 A study of 179 children who reported at least one episode of wheezing showed that only 21 children had been diagnosed with asthma,84 including 11 of 31 children who experienced more than 12 episodes of wheezing per year. When these latter children were treated for asthma, school absenteeism fell tenfold. Children with asthma whose symptoms were a chronic cough rather than wheezing often remained undiagnosed for years.85 Review of 72 physicianreferred adult patients with dyspnea unexplained by initial history, physical

examination, chest radiograph, and spirometry demonstrated that 17% had undiagnosed asthma83; hence, asthma is commonly unrecognized in both adults and children. CONCLUDING COMMENTS Physicians should recognize the limitations of the medical history and physical examination even when conducted by an expert. An unbiased description of symptoms of asthma may be more effectively elicited through open-ended questions such as Please describe your symptoms, rather than directed questions such as Do you have wheezing or shortness of breath? To a limited extent, symptom descriptors such as wheezing and chest tightness may suggest asthma, although a full medical history should include triggering and alleviating factors, response to treatment, and associated symptoms. Physical examination of the chest, especially for the presence and quality of wheezing has moderate predictive value in diagnosing asthma and estimating the degree of airway obstruction. Additional respiratory signs such as breath sound intensity and forced expiratory time may be useful. Physicians should be familiar with the physical signs of other causes of dyspnea such as chronic obstructive pulmonary disease, congestive heart failure, hyperventilation, and foreign body aspiration. A detailed medical history and physical examination of the patient with possible asthma leads to the correct diagnosis about three quarters of the time, even by asthma specialists. Because it is impossible to identify misdiagnosed patients prospectively, additional studies such as peak expiratory flow rate measurements, spirometry, or the methacholine bronchial challenge are needed. Furthermore, even when asthma is diagnosed correctly, both patients and physicians are only moderately successful in estimating the degree of airway obstruction. The National Asthma Education Program recommends that all patients suspected of having asthma

should have office spirometry performed, at minimum, for initial assessment.86 We support this recommendation. Some asthma experts suggest that the peak expiratory flow rate can substitute for measurement of FEV1 for patients with asthma. Indeed, there is ample evidence to show that the peak expiratory flow rate and FEV1 are closely correlated in asthma.87,88 These studies also show that there is a significant variation in peak expiratory flow rate for a given measurement of FEV1, typically in the range of 20%.86 Further, the peak expiratory flow rate is often misleading when chronic obstructive pulmonary disease or restrictive lung disease is present. Measurement of the peak expiratory flow rate with a peak flow meter is less expensive than measurement of FEV1 with spirometry; however, misdiagnosis of asthma and underestimating severity of asthma are costly as well. Further studies are needed to determine whether measurement of pulmonary function actually results in intervention that improves symptoms, lung function, frequency of hospitalizations, or days missed from work or school. Further studies may elucidate the relative advantages of peak flow measurement and spirometry. We recommend that physicians caring for patients with asthma continue to develop their interviewing and physical examination skills. At the same time, the best care of the asthmatic patient includes spirometry at the time of initial diagnosis and monitoring of pulmonary function through periodic spirometry and peak expiratory flow rate measurements. REFERENCES
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Allergy Clin Immunol 1987;79:3315. 18. Muller BA, Leick CA, Suelzer M, et al. Prognostic value of methacholine challenge in patients with respiratory symptoms. J Allergy Clin Immunol 1994;94:77 87. 19. Desjardins A, De Luca S, Cartier A, et al. Nonspecific bronchial hyperresponsiveness to inhaled histamine and hyperventilation of cold dry air in subjects with respiratory symptoms of uncertain etiology. Am Rev Respir Dis 1988;137:1020 5. 20. Dales RE, Nunes F, Partyka D, Ernst P. Clinical prediction of airways hyperresponsiveness. Chest 1988;93: 984 6. 21. Wiens L, Sabath R, Ewing L, et al. Chest pain in otherwise healthy children and adolescents is frequently caused by exercise-induced asthma. Pediatrics 1992;90:350 3. 22. Dodge RR, Burrows B. The prevalence and incidence of asthma and asthma-like symptoms in a general population sample. Am Rev Respir Dise 1980;122:56775. 23. Speizer FE. Asthma and persistent wheeze in the Harvard Six Cities Study. Chest 1990;98:191S. 24. Hammond EC. Some preliminary findings on physical complaints from a prospective study of 1,064,004 men and women. Am J Public Health 1964; 54:123. 25. Higgins ITT. Respiratory symptoms, bronchitis and ventilatory capacity in a random sample of an agricultural population. Br Med J 1957;2:1198 203. 26. Fedullo AL, Swinburne AJ, McGuireDunn C. Complaints of breathlessness in the emergency department. The experience at a community hospital. NY State J Med 1986;86:4 6. 27. Enarson DA, Vedal S, Schulzer M, et al. Asthma, asthmalike symptoms, chronic bronchitis and the degree of bronchial hyperresponsiveness in epidemiologic surveys. Am Rev Respir Dis 1987;136:6137. 28. Dodge R, Cline MG, Lebowitz MD, Burrows B. Findings before the diagnosis of asthma in young adults. J Allergy Clin Immunol 1994;94:8315. 29. Kendrick AH, Higgs CMB, Whitfield MJ, Laszlo G. Accuracy of perception of severity of asthma: patients treated in general practice. Br Med J 1993; 307:422 4. 30. Rubinfeld AR, Pain MCF. Perception of asthma. Lancet 1976;1:882 4.

31. Burdon JGW, Juniper EF, Killian KJ, et al. The perception of breathlessness in asthma. Am Rev Respir Dis 1982; 126:825 8. 32. Bellia V, Visconti A, Insalaco G, et al. Validation of morning dip of peak expiratory flow as an indicator of the severity of nocturnal asthma. Chest 1988;94:108 10. 33. Ferguson AC. Persisting airway obstruction in asymptomatic children with asthma with normal peak expiratory flow rates. J Allergy Clin Immunol 1988;82:19 22. 34. McFadden ER Jr, Kiser R, DeGroot WJ. Acute bronchial asthma. Relations between clinical and physiologic manifestations. N Engl J Med 1973;288: 2215. 35. Sly PD, Landau LI, Weymouth R. Home recording of peak expiratory flow rates and perception of asthma. Am J Dis Child 1985;139:479 82. 36. Mahler DA, Rosiello RA, Harver A, et al. Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease. Am Rev Respir Dis 1987;135:1229 33. 37. Gibson PG, Wong BJO, Hepperle MJE, et al. A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid. Clin Exp Allergy 1992; 22:52532. 38. Yellowlees PM, Ruffin RE. Psychological defenses and coping styles in patients following a life-threatening attack of asthma. Chest 1989;95: 1298 303. 39. Shim CS, Williams MH Jr. Relationship of wheezing to the severity of obstruction in asthma. Arch Intern Med 1983;143:890 2. 40. Marini JJ, Pierson DJ, Hudson LD, Lakshminarayan S. The significance of wheezing in chronic airflow obstruction. Am Rev Respir Dis 1979;120: 1069 72. 41. Holleman DR Jr, Simel DL. Does the clinical examination predict airflow limitation? JAMA 1995;273:3139. 42. Baughman RP, Loudon RG. Lung sound analysis for continuous evaluation of airflow obstruction in asthma. Chest 1985;88:364 8. 43. Baughman RP, Loudon RG. Quantitation of wheezing in acute asthma. Chest 1984;86:718 22. 44. King DK, Thompson BT, Johnson DC. Wheezing on maximal forced exhala-














tion in the diagnosis of atypical asthma. Ann Intern Med 1989;110: 4515. Bettencourt PE, Del Bono EA, Spiegelman D, et al. Clinical utility of chest auscultation in common pulmonary diseases. Am J Respir Crit Care Med 1994;150:12917. Beck R, Dickson U, Montgomery MD, Mitchell I. Histamine challenge in young children using computerized lung sounds analysis. Chest 1992;102: 759 63. Noviski N, Cohen L, Springer C, et al. Bronchial provocation determined by breath sounds compred with lung function. Arch Dis Child 1991;66:9525. Pardee NE, Martin CJ, Morgan EH. A test of the practical value of estimating breath sound intensity. Breath sounds related to measured ventilatory function. Chest 1976;70:341 4. Bohadana AB, Peslin R, Uffholtz H. Breath sounds in the clinical assessment of airflow obstruction. Thorax 1978;33:34551. Schneider IC, Anderson AE Jr. Correlation of clinical signs with ventilatory function in obstructive lung disease. Ann Intern Med 1965;62:477 85. van Schayck CP, van Weel C, Harbers HJM, van Herwaarden CLA. Do physical signs reflect the degree of airflow obstruction in patients with asthma or chronic obstructive pulmonary disease? Scand J Prim Health Care 1991; 9:232 8. Kern DG, Patel SR. Auscultated forced expiratory time as a clinical and epidemiologic test of airway obstruction. Chest 1991;100:636 9. Schapira RM, Schapira MM, Funahashi A, et al. The value of the forced expiratory time in the physical diagnosis of obstructive airways disease. JAMA 1993;270:731 6. Anderson CL, Shankar PS, Scott JH. Physiological significance of sternomastoid muscle contraction in chronic obstructive pulmonary disease. Respir Care 1980;25:9379. Stubbing DG, Mathur PN, Roberts RS, Campbell EJM. Some physical signs in patients with chronic airflow obstruction. Am Rev Respir Dis 1982;125: 549 52. Godfrey S, Edwards RHT, Campbell EJM, Newton-Howes J. Clinical and physiological associations of some physical signs observed in patients with chronic airways obstruction.

Thorax 1970;25:2857. 57. Godfrey S, Edwards RHT, Campbell EJM, et al. Repeatability of physical signs in airways obstruction. Thorax 1969;24:4 9. 58. Commey JOO, Levison H. Physical signs in childhood asthma. Pediatrics 1976;58:537 41. 59. Shim C, Williams MH Jr. Pulsus paradoxus in asthma. Lancet 1978;1: 530 1. 60. Rebuck AS, Pengelly LD. Development of pulsus paradoxus in the presence of airways obstruction. N Engl J Med 1973;288:66 9. 61. Kesten S, Maleki-Yazdi R, Sanders BR, et al. Respiratory rate during acute asthma. Chest 1990;97:58 62. 62. Loudon R, Murphy RLH Jr. Lung sounds. Am Rev Respir Dis 1984;130: 66373. 63. Baughman RP, Loudon RG. Stridor: differentiation from asthma or upper airway noise. Am Rev Respir Dis 1989;139:14079. 64. Spiteri MA, Cook DG, Clarke SW. Reliability of eliciting physical signs in examination of the chest. Lancet 1988;1:8735. 65. Mulrow CD, Dolmatch BL, Delong ER, et al. Observer variability in the pulmonary examination. J Gen Intern Med 1986;1:364 7. 66. Gjorup T, Bugge PM, Jensen AM. Interobserver variation in assessment of respiratory signs. Acta Med Scand 1984;216:61 6. 67. OHagan JJ, Botting CH, Davies LJ. The use of a simulated patient to assess clinical practice in the management of a high risk asthmatic. N Z Med J 1989; 102:252 4. 68. Pratter MR, Curley FJ, Dubois J, Irwin RS. Cause and evaluation of chronic dyspnea in a pulmonary disease center. Arch Intern Med 1989;149:2277 82. 69. Schmitt BP, Kushner MS, Wiener SL. The diagnostic usefulness of the history of the patient with dyspnea. J Gen Intern Med 1986;1:386 93. 70. Holleman DR Jr, Simel DL, Goldberg JS. Diagnosis of obstructive airways disease from the clinical examination. J Gen Intern Med 1993;8:63 8. 71. Badgett RG, Tanaka DJ, Hunt DK, et al. Can moderate chronic obstructive pulmonary disease be diagnosed by historical and physical findings alone? Am J Med 1993;94:188 96. 72. Badgett RG, Tanaka DJ, Hunt DK, et al. The clinical evaluation for diagnos-

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ing obstructive airways disease in high-risk patients. Chest 1994;106: 142731. Wallace JI, Coral FS, Rimm IJ, et al. Diagnosing the breathless patient. Lancet 1982;1:907 8. Malo J-L, Ghezzo H, LArcheveque J, Lagier F, et al. Is the clinical history a satisfactory means of diagnosing occupational asthma? Am Rev Respir Dis 1991;143:528 32. Burge PS. Problems in the diagnosis of occupational asthma. Br J Dis Chest 1987;81:10515. Shim CS, Williams MH Jr. Evaluation of the severity of asthma: Patients versus physicians. Am J Med 1980;68: 113. Russell NJ, Crichton NJ, Emerson PA, Morgan AD. Quantitative assessment of the value of spirometry. Thorax 1986;41:360 3. Kerem E, Canny G, Tibshirani R, et al. Clinical-physiologic correlations in acute asthma of childhood. Pediatrics 1991;87:481 6. Owens MW, Anderson W McD, George RB. Indications for spirometry in outpatients with respiratory disease. Chest 1991;99:730 4. Pratter MR, Hingston DM, Irwin RS. Diagnosis of bronchial asthma by clinical evaluation. An unreliable method. Chest 1983;84:427. Adelroth E, Hargreave FE, Ramsdale EH. Do physicians need objective measurements to diagnose asthma? Am Rev Respir Dis 1986;134:704 7. Hahn DL, Beasley JW, Wisconsin Research Network (WReN) Asthma Prevalence Study Group. Diagnosed and possible undiagnosed asthma: A Wisconsin Research Network (WReN) Study. J Fam Pract 1994;38:3739. DePaso WJ, Winterbauer RH, Lusk JA, et al. Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year study. Chest 1991; 100:12939. Speight ANP, Lee DA, Hey EN. Underdiagnosis and undertreatment of asthma in childhood. Br Med J 1983; 286:1253 6. Konig P. Hidden asthma in childhood. Am J Dis Child 1981;135:10535. National Asthma Education Program. Expert Panel Report. Guidelines for the Diagnosis and Management of Asthma. U.S. Department of Health and Human Services. Public Health



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Request for reprints should be addressed to: James T C Li, MD Mayo Clinic & Foundation 200 First St, SW Rochester, MN 55905

CME Examination Identification N 016-001 Questions 120, Li JTC and EJ OConnell. 1996;76:114. CME Test Questions 1. Which of the following chest symptoms is most closely associated with congestive heart failure? A. My breath does not go out all the way. B. I cannot take a deep breath. C. I feel wheezy. D. I feel that I am smothering. E. I cannot take a deep breath. 2. What percentage of patients with chronic obstructive pulmonary disease admit to wheezing? A. 100% B. 75% C. 50% D. 25% E. 0% 3. Which of the following statements about the symptom of inspiratory dyspnea is true? A. Associated with increased PEFR B. Associated with decreased RV/TLC ratio C. Rarely described during a positive methacholine bronchial challenge D. Rarely reported by patients experiencing acute asthma E. Reported by the majority of patients experiencing acute asthma 4. Which of the following statements about chest pain in children is true? A. About 20% of chest pain in children is caused by asthma. B. Only 5% of chest pain in children is caused by asthma. C. Chest pain is rarely described in exercise-induced asthma. D. Chest tightness is rarely described in exercise-induced asthma. E. Lipid screening is recommended. 5. The prevalence of wheezing in the general population is about A. 5% or less B. 10% to 25% C. 50% to 65% D. 75% to 90% E. Prevalence studies of wheezing have not been conducted 6. Which of the following is associated with nearly fatal asthma? A. Wheezing B. Use of home peak flow diary C. Increased use of inhaled nedocromil D. Increased use of inhaled corticosteroids E. Reduced chemosensitivity to hypoxia 7. Which of the following characteristics about wheezing is associated with increased airway obstruction? A. Wheezing during exercise B. Low pitched wheezing C. Low intensity wheezing D. Wheezing during inspiration and expiration E. Wheezing with forced exhalation 8. Which of the following lung sounds are called continuous adventitious sounds? A. Expiratory wheezes B. Inspiratory rales C. Expiratory rales D. Fine crackles E. Coarse crackles 9. As a test of airway obstruction, a prolonged forced expiratory time has a sensitivity of about A. 5% or less B. 10% to 25% C. 50% to 65% D. 75% to 90% E. 99% 10. Which of the following signs is associated with obstructive lung disease? A. Decreased breath sound intensity B. Tracheal tag C. Increased resonance to percussion D. Pulsus paradoxus E. All of the above 11. When physicians evaluate patients for unexplained dyspnea about what percentage of the time do they reach the correct diagnosis based on the medical history and physical examination? A. 5% to 15% B. 25% to 35% C. 45% to 55% D. 65% to 75% E. 95% to 100% 12. Which of the following components of the medical history is an independent predictor of



obstructive lung disease in adults? A. Fatigue B. Exercise intolerance C. Significant smoking history D. Chest pain E. Family history of emphysema 13. Deliberate hyperventilation is most likely to produce which of the following symptoms? A. I feel hunger for more air. B. I cannot take a deep breath. C. My chest feels tight. D. My breath does not go out all the way. E. My breathing requires more concentration. 14. In children whose primary symptom is chronic cough, upper respiratory tract infections trigger cough in what percentage of patients? A. 10% to 20% B. 30% to 40% C. 50% to 60% D. 70% to 80% E. 90% to 100% 15. When patients recovering from acute asthma in the hospital are studied, symptoms of asthma disappear when pulmonary function is A. 0% to 10% of predicted normal values B. 20% to 30% of predicted normal values C. 40% to 50% of predicted normal values

D. 60% to 70% of predicted normal values E. 80% to 90% of predicted normal values 16. Which of the following respiratory signs does not have a statistically significant association with FEV1 or PEFR? A. Breath sound intensity B. Forced expiratory time C. Wheezing D. Increased resonance to percussion E. Bibasilar fine crackles 17. All of the following have a statistically significant correlation with severe airway obstruction except A. Wheezing throughout the respiratory cycle B. Forced expiratory time greater than two seconds C. Excavation of the supraclavicular fossa D. Pulsus paradoxus E. Respiratory rate 18. The major finding in pulsus paradoxus is A. A drop in systolic blood pressure of 10 mm or greater during exhalation (normal tidal breathing) B. A drop in systolic blood pressure of 10 mm or greater during inspiration (normal tidal breathing) C. A drop in systolic blood pressure of 10 mm or greater during forced exha-

lation (forced vital capacity maneuver) D. A drop in systolic blood pressure of 5 mm or greater during inspiration E. A drop in systolic blood pressure of 5 mm or greater during a Valsalva maneuver 19. For adult patients with asthma or suspected asthma, The National Asthma Education Program Expert Panel Report recommends spirometry A. For all patients, at initial assessment B. For patients with moderate or severe asthma only, at initial assessment C. Every three months for patients with moderate or severe asthma D. Every six months for patients with moderate or severe asthma E. Every six months for patients with severe asthma 20. For adult patients with known asthma, the National Asthma Education Program Expert Panel Report recommends strong consideration of home peak flow monitoring for A. All patients B. Patients with moderate and severe asthma C. Patients with severe asthma only D. Patients taking salmeterol E. Patients taking nedocromil



Instructions for Category I CME Credit

Certification. As an organization accredited for continuing medical education, the American College of Allergy, Asthma, & Immunology (ACAAI) certifies that when the CME material is used as directed it meets the criteria for two hours credit in Category I of the American College of Allergy, Asthma, & Immunology CME Award and the Physicians Recognition Award of the American Medical Association. Instructions. Category I credit can be earned by reading the text material, taking the CME examination and recording the answers on the perforated answer sheet entitled, Continuing

Medical Education, which can be found after the examination. Please record your ACAAI identification number and the quiz identification number in the spaces and scanning targets provided on the answer sheet. Your ACAAI identification number can be found on your ACAAI membership card, nonmembers of the College will be assigned an ACAAI identification number and this should be left blank on the answer sheet. The quiz identification number can be found at the beginning of the CME examination. Use a No. 2 or soft lead pencil for marking the answer sheet. You may

erase but do so completely in order to prevent computer reading errors. Your ACAAI identification number and quiz identification number will be used to record your credit hours earned on the CME transcript system. No records of individual performance will be maintained. Tear out the perforated answer sheet and print your name and address in the spaces provided. Return it within one month after the Annals is received to the American College of Allergy, Asthma, & Immunology, 85 West Algonquin Rd, Suite 550, Arlington Heights, IL 60005. Answers will be published in the next issue of the Annals of Allergy, Asthma, & Immunology.

Answers to CME examinationAnnals of Allergy, Asthma, & Immunology, December 1995 (Identification No 015-012) Spector SL. Leukotriene inhibitors and antagonists in asthma. Ann Allergy, Asthma, & Immunol 1995; 75:46374. 1. d 6. e 11. b 16. a 2. c 7. c 12. e 17. c 3. b 8. a 13. d 18. a 4. a 9. d 14. b 19. c 5. e 10. e 15. d 20. b