A universally accepted definition for bronchial asthma remains an elusive goal. This difficulty has led to controversy regarding diagnostic criteria for asthma. However, one area of agreement is that the asthmatic state is characterized by increased bronchial reactivity to multiple physical, chemical, and pharmacologic stimuli. Although it is widely accepted that this bronchial hyperreactivity is present and demonstrable in virtually all asthmatic patients, the diagnosis is usually made on the basis of a history and physical examination results. Moreover, even though such wheezing is considered to be the sine qua 11011 of bronchial asthma, and therefore the most important finding of the clinical assessment, the sensitivity and specificity of wheeze have not been studied. Therefore, we prospectively studied 34 patients referred to our Pulmonary Medicine Clinic with a history of wheeze to determine the predictive value of wheeze by history and physical examination compared to methacholine inhalational challenge (MIC) in diagnosing asthma.
Methods and Materials
During an 18-month interval, 34 patients referred to our Pulmonary Medicine Clinic with a history of wheeze constituted our study group. In addition to wheeze, 29 of 34 complained of cough, 20 of shortness of breath, 17 of postnasal drip, and four of chest tightness. Seven had a history of allergic rhinitis as manifested by seasonal symptoms of runny nose, sneezing, and itchy eyes. None was a current cigarette smoker or had had an upper or lower respiratory tract viral illness within the prior two months. The group was composed of 22 females and 12 males whose mean age was 40 years, range 14 to 70 years. They represented a group of patients who were considered diagnostic dilemmas by a referring physician because their symptoms had been difficult to control for an average of 3.3 years, range one month to 25 years.
Seven normal, nonsmoking subjects served as our control group. The group was composed of four men and three women whose mean age was 27 years, range 19 to 37 years. None had ever had a history of wheeze, a prior diagnosis of bronchial asthma, or an illness affecting the upper or lower respiratory tract within the prior six months.
Our testing protocol consisted of the performance of a history and physical examination by a pulmonary specialist (M.R.P., R.S.I.), followed by the administration of a standardized respiratory questionnaire, and spirometry, preinhalation and postinhalation of methacholine.
Auscultation of the lungs was performed by asking the patient to breathe deeply in and out through the mouth, with no forced maneuvers. Historic information was obtained directly by a pulmonary specialist and a standardized respiratory questionnaire developed by the American Thoracic Society and the Division of Lung Diseases at the National Institute of Health (NIH) and modified by us to include questions about postnasal drip, throat-clearing, stridor, hoarseness, and seasonal upper respiratory tract allergies. Pulmonary function studies were performed at a time when all patients had discontinued all medication for 96 hours and consisted of spirometry and preinhalation and postinhalation of methacholine. Forced vital capacity (FVC) was performed on a 10-L Collins survey spirometer (No 06031; Warren E. Collins, Inc). From the best of three forced spirographic tracings, maximal midexpiratory flow (FEF25-75%), and forced expiratory volume is one second (FEVi) were measured. The FEV, was then expressed as a percentage of FVC, FEV/FVC%. It is the practice in our laboratory to administer only an MIC to patients whose baseline FEV, and FVC are at least 80 percent of predicted and whose FEV/FVC% is normal. Therefore, only after determining that FVC and FEVj were at least 80 percent and FEV,/FVC% was at least 70 percent were patients given MIC. We define MIC as the response of FEV, to inhaled methacholine (acetyl-beta-methacholine) diluted in physiologic saline solution. A positive response occurred if FEV, decreased 20 percent or greater from baseline. After the establishment of a reproducible baseline, meth-acholine was delivered by a dosimeter consisting of a breath-activated solenoid valve, DeVilbiss No 42 nebulizer, and a compressed air source, at a 5 L/minute flow. Specifications for this delivery system were patterned after the recommendations of a study group on bronchoprovocation testing sponsored by the NIH. All inhalations of methacholine were initiated at functional residual capacity (FRC) during normal tidal volume breathing.
The initial dose was one breath of a 1.25 mg/ml solution of methacholine, which is equivalent to 1.25 dose units (dose units equal concentration of methacholine in mg/ml times number of breaths). Unless the absolute value of FEV, decreased 20 percent or greater from baseline, increasing dose units were given until there was a positive response or until a cumulative total of 195 dose units had been given. The sequence of dose units was 1.25 (one breath of a 1.25-mg/ml solution), 6.25 (five breaths of a 1.25-mg/ml solution), 12.5 (five breaths of a 2.5-mg/ml solution), 25 (five breaths of a 5-mg/ ml solution), 50 (five breaths of a 10-mg/ml solution), and 100 (five breaths of a 20-mg/ml solution), for a potential maximum of a total of 195 cumulative dose units. At one and three minutes after the inhalation of each dose of methacholine, spirometry was performed and the percent decrease in FEV, from the original baseline was determined.
Pretreatment Diagnostic Criteria
To ensure uniformity of interobserver diagnoses, we set up prospective criteria for the clinical diagnoses of postnasal drip, bronchial asthma, bronchitis, and psychogenic illness. These criteria included the results of spirometry preinhalation and postinhalation of methacholine.
Postnasal drip was diagnosed (1) when patients described the sensation of having something drip down into their throats and/or the need frequently to clear their throats, or (2) when physical examination of the nasopharynges and oropharynges revealed mucoid or mucopurulent secretions and/or a cobblestone appearance of the mucosa. The MIC had to be negative for no postnasal drip to be considered the etiologic cause for wheeze. Bronchial asthma was diagnosed when (1) patients complained of episodic wheezing, shortness of breath, and cough, and (2) the MIC was abnormal in the absence of any other condition known to be associated with increased bronchial hyperreactivity.’ Industrial bronchitis was diagnosed when the onset of symptoms coincided with frequent exposure to a known respiratory irritant. Psychogenic illness was a diagnosis of exclusion; it was considered when the history and physical examination findings showed no postnasal drip, the MIC was normal, and when symptoms of anxiety were present and the patients agreed that anxiety could be a contributing factor to their symptoms.
Final Diagnostic Criteria
The diagnosis of the cause of wheeze required fulfillment of the initial pretreatment criteria and improvement or disappearance of all respiratory symptoms with specific therapy. Specific therapy for postnasal drip depended on the etiology, which was diagnosed by clinical criteria. Unless it was clinically obvious, no attempt was made to differentiate perennial allergic from nonallergic rhinitis. Allergic and perennial nonallergic rhinitis were treated with an antihistaminic decongestant preparation (dexbrompheniramine maleate plus d-isoephedrine) and, when feasible, avoidance of environmental factor(s). Sinusitis was treated with a combination of an oral antibiotic, nasal spray (oxymetazoline chloride) and dexbrompheniramine maleate plus d-isoephedrine. Bronchial asthma was treated with bronchodilators alone or with corticosteroids. Industrial bronchitis was treated with avoidance of the offending agent. Psychogenic illness was treated with reassurance, and, when indicated, confrontation.
Data were analyzed by Students unpaired t test and probability statistics.