A comparison of histamine, methacholine, and exercise airway reactivity in normal and asthmatic subjects

Airway reactivity is commonly assessed by inhalation exposure to pharmacologic agents as methacholine and histamine or by exercise challenge. To evaluate the relationship of pharmacologic challenge with exercise-induced bronchoconstriction and to determine the test that best differentiates asthmatics from normal subjects, 10 normal and 15 asthmatic subjects were studied. Allergic status was defined by the presence of one or more positive prick skin tests to 8 common allergens. Pharmacologic sensitivity was defined as the log dose of agonist producing a 20% fall in FEV₁ or a 35% fall in specific conductance. Exercise consisted of 6 min of steady-state treadmill exercise at 90% of the age predicted maximal heart rate at a temperature of 22.3 ± 1.1°C (mean ± standard deviation) and humidity of 40.1 ± 13.3%. A high degree of exercise stress was achieved as documented by heart rate (171.5 ± 11.7), O₂ consumption (2.19 ± 0.65 L/M), and minute ventilation (77.1 ± 24.0 L). Although histamine and methacholine sensitivity correlated (r = 0.70, p < 0.01), methacholine was better than histamine in differentiating asthmatics from normal subjects. On the other hand, 6 of the 15 asthmatics did not respond to exercise with a 10% fall in FEV₁, whereas 1 of the 10 normal subjects did. Therefore, maximal exercise challenge may not be an adequate screening test for airway hyperreactivity in asthma because many asthmatics did not develop bronchoconstriction and had similar responses to normal subjects. The development of postexercise bronchospasm in the asthmatics correlated poorly with minute ventilation (r = 0.20) and with respiratory heat loss (r = 0.17). However, exercise response was related to pharmacologic sensitivity, correlating better with methacholine (r = 0.54, p < 0.05) than with histamine airway reactivity (r = 0.44, p > 0.1).