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Methacholine challenge for diagnosing hyperreactive airways has been valuable in both research and clinical care settings. There are two methods of challenge that are commonly used. With the dosimeter method, five breaths of sequential concentrations of methacholine are inhaled with use of a solenoid valve timing device to standardize the quantity of inhaled methacholine solution. Pulmonary function is assessed after each concentration is inhaled. With the continuous breathing method, each concentration of methacholine is inhaled by tidal volume breathing for 2 min. Pulmonary function is assessed after each concentration. With both methods, a fall in FEV 1 of 20% after inhalation of methacholine is diagnostic of hyperreactive airways. Several evaluations demonstrate that pharmacologic bronchoprovocation with methacholine is more sensitive than exercise challenge for making the diagnosis of hyperreactive airways. If the allergic athlete complains of exercise-related symptoms, such as cough, dyspnea, or chest pain, and an exercise tolerance test fails to reproduce these symptoms, a methacholine challenge should be performed before the possibility of exercise-induced asthma is dismissed. If the allergic athlete has symptoms of cough or dyspnea that are unrelated to exercise, methacholine challenge is the most sensitive method to evaluate airways hyperreactivity indicative of asthma.

The challenge procedure detailed in this article should serve as a useful adjunct to routine pulmonary function testing for the diagnosis of asthma as well as a research tool for a wide variety of applications. Now that methacholine has been approved by the Food and Drug Administration and made available to the clinician in an appropriate form for clinical use (Provocholine, Roche), it is anticipated that the technique of methacholine challenge will become part of the armamentarium of pulmonary laboratories as well as pulmonologists and allergists who diagnose and treat asthma. The technique may be safely conducted in an outpatient setting using the standardized procedures detailed here. When properly applied in appropriate clinical circumstances, the test is a useful and sometimes necessary addition to routine history, physical examination, and pulmonary function tests conducted for the purposes of establishing the presence of hyperactive airways.

We have previously reported that airway responsiveness to inhaled methacholine in subjects with asthma is increased 40 to 60 minutes after challenge with ultrasonically nebulized water. This study reveals that increased responsiveness to methacholine is abolished by administration of cromolyn sodium before the water challenge. The mean dose of methacholine (95% confidence limits) inducing a 20% fall in FEV1 (PD20) was 1.10 mumol (0.43 to 2.80). The PD20 after water challenge was 0.42 mumol (0.17 to 1.01) that was significantly lower (p less than 0.005) than that observed for the initial challenge. Administration of cromolyn before the water challenge abolished this increased responsiveness to methacholine. The mean PD20 was 1.32 mumol (0.47 to 3.68) that was not significantly different from that measured for the initial methacholine challenge. Methacholine responsiveness was unchanged when challenge was performed 40 to 60 minutes after cromolyn alone or after methacholine itself. We conclude that cromolyn abolishes the increased responsiveness to methacholine and probably does so by inhibiting the release of mediators.

Bechtel et al [Am Rev Respir Dis 124:759-761, 1981] have reported a high prevalence of positive methacholine challenge tests in patients with sarcoidosis. We report a patient with sarcoidosis who was identified because of symptoms resulting from exposure to workplace irritants. The presence of hyperreactive airways was confirmed by a positive methacholine challenge.

The effect of passive smoking on the degree of nonspecific bronchial responsiveness (BR) in children was evaluated. In a cross-sectional survey of primary school children (7 to 11 yr) in Latium (Italy), a total of 1,215 methacholine challenge tests was performed. The children were divided into nonresponders (PC20 FEV164 mg/ml) and responders (PC20 FEV1or = 64 mg/ml), the latter including a subgroup of strong responders (PC20 FEV1or = 4.0 mg/ml). The role of passive smoking exposure was analyzed through logistic regression models. Higher odds ratios were found among girls (for strong responders: maternal smoking, OR 2.92; paternal smoking, OR 2.59); moreover, among girls there was a dose-response relationship with the number of cigarettes smoked by the mother. An effect modification was also detected for father's education and household crowding: maternal and paternal smoking were strong predictors of bronchial hyperresponsiveness in families in which the head was less educated and in overcrowded houses. The results were confirmed using a continuous index of BR (slope) and after adjustment for baseline airway caliber. We suggest that the effect of parental smoking on children's bronchial responsiveness is detectable when the conditions for a higher exposure level at home are met; females seem to be more susceptible.

12 subjects from an experiment on relaxation therapy for asthma were given the Harvard Group Scale of Hypnotic Susceptibility, Form A. Full scale hypnotic susceptibility scores were positively correlated, at a borderline significance, with improvement in the methacholine challenge test, a measure of asthma severity. Performance on the amnesia item of the Harvard Group Scale was correlated with improvement in self-reported symptoms of asthma.

Background: The Link between allergic rhinitis and asthma is well known. Bronchial hyperreactivity (BHR) may be present in rhinitics. The present study is aimed at evaluating a large group of subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR both during and outside the pollen season. Methods: 360 rhinitics (subdivided in 3 groups: seasonal, SAR, perennial, PAR, and polysensitized, PolysR) were investigated by spirometry and methacholine challenge. Results: There was a significant seasonal difference concerning the number of rhinitics with impaired FEV1 (p

Shen, X., V. Bhargava, G. R. Wodicka, C. M. Doerschuk, S. J. Gunst, and R. S. Tepper. Greater airway narrowing in immature than in mature rabbits during methacholine challenge. J. Appl. Physiol. 81(6): 2637–2643, 1996.—It has been demonstrated that methacholine (MCh) challenge produces a greater increase in lung resistance in immature than in mature rabbits (R. S. Tepper, X. Shen, E. Bakan, and S. J. Gunst. J. Appl. Physiol. 79: 1190–1198, 1995). To determine whether this maturational difference in the response to MCh was primarily related to changes in airway resistance (Raw) or changes in tissue resistance, we assessed airway narrowing in 1-, 2-, and 6-mo-old rabbits during intravenous MCh challenge (0.01–5.0 mg/kg). Airway narrowing was determined from measurements of Raw in vivo and from morphometric measurements on lung sections obtained after rapidly freezing the lung after the MCh challenge. The fold increase in Raw was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. Similarly, the degree of airway narrowing assessed morphometrically was significantly greater for 1- and 2-mo-old animals than for 6-mo-old animals. The fold increase in Raw was highly correlated with the degree of airway narrowing assessed morphometrically ( r 2 = 0.82, P < 0.001). We conclude that the maturational difference in the effect of MCh on lung resistance is primarily caused by greater airway narrowing in the immature rabbits.

• Methacholine challenge has been proposed as a diagnostic test in situations where clinical asthma is suspected but reversible airway obstruction cannot be demonstrated spirometrically. Methacholine challenge was used in 14 patients with suspected asthma and five normal controls. Eight individuals (six patients and two controls) had a reduction in the forced expiratory volume at 1 s (FEV 1 ) of 20% or more with 100 inhalation units (IUs) of methacholine; seven additional individuals (six patients and one control) met one or more of the American Thoracic Society's criteria for a positive bronchoprovocation test; and four individuals (two patients and two controls) were not sensitive to methacholine by any criteria. The diagnosis of asthma can be excluded if methacholine does not induce reversible obstruction. However, provocation of reversible obstruction with methacholine is not specific for asthma. More stringent criteria, such as reduction of FEV 1 by 20% by 20 IUs of methacholine, would be less sensitive but more specific for asthma. ( Arch Intern Med 1984;144:938-940)

In Reply.— As Dr Polk points out, methacholine challenge has been used as a research tool for many years. However, its use in the clinical laboratory has lagged. We would agree with Dr Polk that methacholine challenge is not indicated in the obstructed patient who responds to an inhaled bronchodilator such as isoproterenol or epinephrine. In the patient with normal baseline pulmonary function, bronchodilator administration does not distinguish between asthmatics and normal subjects. 1 In this group of patients with unexplained respiratory symptoms, we recommend a methacholine challenge. In more than 600 studies in our laboratory we have had no bronchoconstriction requiring anything more than simple inhalation of isoproterenol. We have found the methacholine challenge to be a safe, simple, and invaluable aid in the diagnosis of obscure asthma.