Bronchial responsiveness to inhaled methacholine in epidemiological studies: Comparison of different indices

We evaluated the sensitivity and specificity of different indices drawn from the forced expiratory curve in order to detect the best one for evaluating bronchial reactivity in the general population, and particularly, for distinguishing between normal and asthmatic subjects. 654 subjects, between 15 and 64 years of age, who were representative for age and sex of the general population of a small Lombardy town (Italy), were studied. Of the total sample, 448 subjects were clinically normal and asymptomatic, 87 were symptomatic or with acute upper respiratory disease within 30 days before the challenge with methacholine, 43 with allergic rhinitis, 26 asthmatics and 50 chronic bronchitics. All the subjects who had a baseline FEV₁ greater than 85% predicted underwent methacholine challenge. Provocative LnDoses of a 6, 10, 15% fall in FEV₁ (LnPD₆, LnPD₁₀, LnPD₁₅) and provocative LnDose causing FEV₁ to fall more than 2 SD below the mean of 5 FEV₁ measurements following buffer inhalation (LnTD) were evaluated. Furthermore we calculated the 'Dose-Response slope' (SL) proposed by O'Connor. The cut-off value of each index to define a responder was calculated by discriminant analysis of the response to the challenge in normal and in the asthmatic group. Sensitivity, specificity and predictive value of LnPD₆, LnTD and SL were 79, 74, 14%; 71, 74, 13% and 46, 97, 48% respectively. LnPD₁₀ had the best sensitivity (83%) with a high specificity (83%), but, as compared to LnPD₁₅, whose sensitivity was 79% and specificity 89%, a lower predictive value (21% vs 27%). Thus LnPD₁₅ turns out to be the best index to assess bronchial responsiveness in epidemiological studies; with respect to the diagnosis of bronchial asthma however, a low predictivity confirms that the bronchial challenge has only a supplemental role in detecting the disease.