Asthma

Editor's Note: This issue of In the Clinic has been updated. Asthma, which is characterized by airway hyperresponsiveness and inflammation, 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 hospitalizations and emergency department visits, continues to climb. Currently, about 1 in 20 Americans have asthma; in children, recent estimates suggest an incidence 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. Clinical Slide Set. Asthma Diagnosis What symptoms or elements of clinical history are helpful in diagnosing asthma? Symptoms that should prompt clinicians to consider asthma are wheezing, dyspnea, cough, difficulty taking a deep breath, and chest tightness (1). Characteristically, asthma symptoms are intermittent and may remit spontaneously or with use of short-acting bronchodilators. Symptoms often vary seasonally or are associated with specific triggers, such as cold, exercise, animal dander, pollen, certain foods, aspirin or nonsteroidal anti-inflammatory drugs, or occupational exposures. Clinicians should also consider the diagnosis of asthma in all adults with chronic cough, especially if cough is nocturnal, seasonal, or related to the workplace or a specific activity. What physical examination findings are suggestive of asthma? A careful history to elicit the nature and timing of symptoms is paramount in diagnosing asthma. The physical examination is less helpful unless a patient is having an active exacerbation. The clinician should listen for wheezing during tidal respirations or prolonged expiratory phase of breathing and examine the chest for hyperexpansion. Studies suggest that respiratory signs (wheezing, forced expiratory time, accessory muscle use, respiratory rate, and pulsus paradoxus) may be useful to predict airflow obstruction, but clinicians often disagree about the presence and absence of these signs (1, 2). The physical examination is sometimes most helpful in looking for evidence of alternative diagnoses. Persistent dry inspiratory crackles, focal wet crackles, or an abnormal cardiac examination all suggest diagnoses other than asthma. How can clinicians determine whether asthma is the cause of chronic cough in adults? Coughing may be the only manifestation of asthma in some patients (3). Up to 24% of patients presenting to a specialist with chronic cough after an initial evaluation by a primary care provider may have asthma. Although several protocols are available for the diagnosis of patients with chronic cough, it is not clear which is the best approach. Clinicians often use a trial of empirical asthma therapy, but national guidelines recommend pulmonary function tests for patients with chronic cough of unknown etiology. What are the indications for spirometry in a patient whose clinical presentation is consistent with asthma? Fair-quality evidence supports the performance of spirometry in all adult patients and older children suspected of having asthma. Initial pulmonary function testing should include spirometric measurements of the FEV1, FVC, and the FEV1-FVC ratio. If these measurements reveal airflow obstruction, then they should be repeated after administration of a bronchodilator to evaluate the reversibility of airflow obstruction. Reversibility of airflow obstruction defines asthma. Predicted normal values for spirometric measures are population-based and differ with age and ethnicity. Predictive tables are available (5, 6). Postbronchodilator improvement 12% of the FEV1 or FVC indicates significant reversibility and therefore increases the likelihood of an asthma diagnosis. Complete pulmonary function testing that includes lung volumes and diffusing capacity should be considered when there is evidence of a lack of airflow reversibility, or restrictive patterns with diminutions in the FEV1 and FVC but a normal FEV1-FVC ratio. These findings suggest chronic obstructive pulmonary disease (COPD) or interstitial lung disease (Table 1). Table 1. Laboratory and Other Studies for Asthma A number of studies show a poor correlation among the presence, severity, and timing of wheezing and the degree of airflow obstruction (7, 8). Patients vary in their degree of sensitivity to airflow limitations and can acclimate to the disability and thus become insensitive to airflow obstruction (9). Because of the disparity between patient and physician estimates of the severity of airflow obstruction and objective measures of obstruction, pulmonary function tests are important tools to characterize airflow obstruction and the degree and severity of asthma. Spirometry should adhere to the standards of the American Thoracic Society (10). Of note, spirometry is effort-dependent, and many patients have difficulty with the FVC maneuver. In these patients (younger children, older adults, or patients with severe respiratory disease), alternative approaches, such as the FEV6 may be an acceptable surrogate to the FVC, with a reduction in the FEV1-FEV6 ratio signifying obstruction (11). Does normal spirometry rule out a diagnosis of asthma? Abnormal spirometry (reversible obstruction) can confirm an asthma diagnosis, but normal spirometry does not rule out asthma. Clinicians should consider further studies in patients with normal spirometry who have a clinical history suggestive of asthma (Table 1). Bronchoprovocation with methacholine or histamine can be helpful in establishing a diagnosis in patients who report that they only have symptoms during exercise or at certain times of the year. Alternatively, marked diurnal variability based on measurements recorded in a peak flow diary kept for at least 2 weeks can help to establish asthma as the cause of symptoms. However, peak flow measurements are highly effort-dependent and may offer no opportunity for quality assurance of their accuracy. When should clinicians consider provocative pulmonary testing? A gold standard for diagnosis of asthma remains elusive. However, methacholine hyperresponsiveness in the pulmonary function laboratory has high reproducibility and accepted standardization (12). The test is safe but requires sophisticated instrumentation and is labor-intensive and expensive. In a patient with symptoms suggestive of asthma who has normal baseline spirometry, a low PC20 (the concentration of inhaled methacholine needed to induce a 20% decrease in the FEV1) on methacholine challenge testing supports the diagnosis. Studies of methacholine challenge suggest that it is sensitive and has a high negative predictive value for the diagnosis of asthma (13, 14). Although cold air and exercise have been used in research to define mechanisms of bronchoconstriction, methacholine challenge remains the provocative test of choice in patients with normal pulmonary function tests who have symptoms consistent with asthma. Spirometry before, during, or after exercise may be the only method to document bronchoconstriction in patients with exercise-induced asthma. As an alternative, monitoring peak flow is easy and inexpensive, but the measurement is less precise and limited in reproducibility and sensitivity (15). Because spirometry and peak flow have limitations in sensitivity and specificity, they are probably best used as part of a diagnostic strategy in conjunction with a comprehensive history, physical examination, and other laboratory data (16). How should clinicians classify asthma severity? The National Heart Lung and Blood Institute (NHLBI) Expert Panel Report 2 (2) defines asthma severity according to symptoms and spirometric measurements. As shown in Table 2, asthma severity is classified as intermittent, mild, moderate, and severe persistent. Each category is defined by the frequency of rescue inhaler use as well as nocturnal symptoms in conjunction with the FEV1 or PEFR measurement. It is important to note that decrease in FEV1 correlates with airflow obstruction and not with changes due to restrictive lung disease. Table 2. The Step Classification of Asthma Severity The initial determination of asthma severity should be made when the patient is receiving no medications. Asthma severity is dynamic—for example, patients who were initially diagnosed as having severe persistent asthma may have symptoms consistent with mild persistent asthma while receiving medication. The NHLBI Expert Panel Report 2 (2) suggests annual spirometry to aid in the classification of asthma, but high-quality studies are not available to support this recommendation. What comorbid conditions and alternative diagnoses should clinicians consider in patients with suspected asthma? The differential diagnosis of asthma includes the following conditions: COPD, interstitial lung disease, vocal cord dysfunction, congestive heart failure, medication-induced cough, bronchiectasis, pulmonary infiltration with eosinophilia syndromes, obstructive sleep apnea, mechanical airway obstruction, cystic fibrosis, and pulmonary hypertension. Clinicians should consider one of these alternative diagnoses when asthma is difficult to control or if the patient has atypical signs and symptoms. These conditions can also coexist in a patient who has asthma. An important difference between asthma and COPD is the history of smoking. Although 30% of patients with asthma in the United States smoke, COPD, manifested by chronic bronchitis and emphysema, often occurs in older persons with a substantial history of cigarette smoking. Patients with COPD also do not demonstrate reversibility with bronchodilators on pulmonary function testing. Lung