In order to interpret our results, we used a positive methacholine inhalational challenge as the standard indicator of the underlying asthmatic condition. It was considered a standard for the following reasons: (1) all agree that the asthmatic state is characterized by increased bronchial reactivity to multiple physical, chemical, and pharmacologic stimuli, such as histamine, carbachol, methacholine, exercise, and cold, dry air; (2) it is widely accepted that bronchial hyperreactivity is present and potentially demonstrable in virtually all symptomatic asthmatic patients; and (3) it has been demonstrated that there is no bronchoprovocation testing agent more sensitive than methacholine, since it will even succeed in unmasking airway hyperreactivity in those asthmatic patients who do not respond to other stimuli.
From our results, four conclusions emerge that merit comment. First, we found that the clinical diagnosis of asthma may be less reliable than generally thought. A history of wheeze was predictive of the presence of hyperreactive airways typical of asthma only 35 percent of the time, a prior clinical diagnosis of asthma by a referring physician was predictive 62 percent of the time, and the physical findings of expiratory monophonic wheeze was predictive only 43 percent of the time. Moreover, our clinical evaluation as pulmonary specialists was also frequently inaccurate. Only 54 percent of the patients considered very likely to have asthma by history and physical examination had hyperreactive airways. The reason why wheeze by history and physical examination was of limited value in determining the presence or absence of hyperreactive airways relates to its non specificity. Wheeze was due to disorders with normal airway reactivity in 65 percent of the patients, to postnasal drip from a variety of conditions in 16 patients, a psychogenic illness in four, industrial bronchitis in one, and an unknown cause in the other. Even though our patients were prospectively studied, we would caution against anticipating the same limited value of history, physical examination, and routine spirometry in a group of patients who were not considered, as ours were, atypical diagnostic problems. Future studies will be required to determine in what groups of patients a clinical diagnosis of asthma can be made with a high degree of reliability. Also, since our data were generated in a group of outpatients referred to a pulmonary subspecialty clinic because the cause of wheeze had eluded the diagnostic and therapeutic maneuvers of at least one referring physician, the spectrum and incidence of the causes of wheeze that we found in our patients should not be generalized to other patient populations.
Second, since a history of wheeze, a prior clinical diagnosis of asthma, or a wheeze heard on physical examination are not reliable predictors of an underlying asthmatic condition, they should not be used alone as epidemiologic markers for asthma. The results of previous studies using such criteria to determine the prevalence of asthma in the general population must be seriously questioned (Read also “Targeting Improvements in Asthma Morbidity in Chicago: Quality Improvement” and “Targeting Improvements in Asthma Morbidity in Chicago: Consortia“). We believe that information on the true prevalence of asthma can only be obtained through studies using reliable bronchoprovocation methods.
<p “=””>Third, methacholine inhalational challenge was an extremely useful diagnostic test, whatever its outcome. Since it differentiated patients who were likely to be asthmatic from those who clearly were not, it guided us in prescribing nearly uniformly successful specific therapy. The treatment regimens used were as specified in the method section. Most patients showed symptomatic improvement within one month of the initiation of treatment and all patients except for the one with familial Mediterranean fever were clearly better at three months of follow-up. Long-term follow-up of a year or longer has shown that no patient with a normal methacholine inhalational challenge has had any clinical evidence of asthma. On the other hand, all 12 patients with an abnormal MIC have experienced episodic exacerbations typical for asthma that have responded to bronchodilator therapy and/or corticosteroids (See “Recommendations for treatment of Asthma“).
Fourth, since the literature and our patients have demonstrated how nonspecific the signs and symptoms of asthma are, we believe that the diagnosis of asthma, whenever possible, should be objectively confirmed. In symptomatic patients without obstruction on baseline spirometry and in the absence of other conditions known to be associated with increased bronchial hyperreactivity, a pharmacologic bronchoprovocation challenge (eg, methacholine) demonstrating bronchial hyperreactivity should be required for diagnosis of asthma. When baseline spirometric evaluation shows more than a minimal decrease in flow rates, a significant response to the administration of a bronchodilator will also confirm the diagnosis of asthma.
Although our study was not designed to determine the pathogenesis of wheeze in our nonasthmatic patients, we offer the following speculations. It is conceivable that the wheeze in our patients with postnasal drip originated from an upper airway source. We believe this for the following reasons: (1) patients with cough secondary to postnasal drip have upper airway obstruction, they frequently give a history of wheeze, and they may also be heard to wheeze on physical examination; and (2) upper airway obstruction can cause wheezing which cannot be distinguished from a lower respiratory tract source. Patients with psychogenic illnesses may have wheezing from dynamic compression of large airways during hyperventilation. The patient with industrial bronchitis probably wheezed from airway obstruction due to excessive mucus. The basis for wheeze in our patient with familial Mediterranean fever was unclear.
The major implication of this study is that the demonstration of bronchial hyperreactivity should be the sine qua non of bronchial asthma, not wheeze, either by history or physical examination. Our results and the literature have shown that wheeze lacks specificity and sensitivity in diagnosing asthma.