Normal Range of Methacholine Responsiveness in Relation to Prechallenge Pulmonary Function: Comment

Normal Range of Methacholine Responsiveness in Relation to Prechallenge Pulmonary Function: CommentThe failure of FEVj-specific normal ranges of PD20FEVJ to improve sensitivity or specificity in detecting questionnaire-reported asthma or wheezing has several possible explanations. Measurements of airway responsiveness are imperfect at discriminating between asthmatics and nonasthmatics in population samples,’ and altering the criteria for an abnormal challenge test may have little impact relative to other sources of imprecision and inaccuracy. Furthermore, adjusting the “normal range” of PD20FEVj to remove the influence of level of FEVj on PD20FEVJ will not necessarily improve predictive power if both level of pulmonary function and degree of airway responsiveness contribute to the occurrence of wheezing symptoms and to the likelihood of a clinical diagnosis of asthma in this age group.
The fifth percentile values chosen as the lower limits of normal PD20FEV1 in this analysis were derived from a sample that included both nonsmokers and smokers. The relatively small number of lifetime nonsmokers with no symptoms and normal pulmonary function (n = 157) favored using the data of all 547 asymptomatic men with normal lung function, regardless of smoking history, to define the lower limits of normal PD20FEVr A separate analysis restricted to the 157 never smokers revealed a similar distribution of PD20FEVJ with respect to prechallenge FEVr Furthermore, among Normative Aging Study subjects who deny respiratory symptoms and who have normal pulmonary function, methacholine responsiveness is not significandy related to smoking status (unpublished). We have previously reported that current smoking is associated with slighdy greater methacholine airway responsiveness among atopic subjects; however, that analysis was not restricted to asymptomatic subjects with normal lung function.

In previous reports we have utilized dose-response slope to analyze methacholine responsiveness data. This report focuses on PD20FEVJ because it is the index of responsiveness used by most clinical laboratories employing methacholine challenge as a diagnostic test. A parallel analysis using dose-response slope yielded results similar to those reported above.
The Normative Aging Study cohort is an excellent source of normative data, but it has limitations in terms of evaluating the accuracy of a diagnostic test. Subjects were tested as part of their ongoing participation in the Study and are not directly comparable to patients presenting for evaluation of respiratory symptoms. Asthma and wheeze reported on questionnaire may have different implications from those prompting a visit to a physician. A more appropriate sample with which to compare the accuracy of conventional and FEVj-specific normal rahges for PD20FEVJ would be, for example, a group of patients presenting with persisting unexplained cough in which alternative criteria for abnormal responsiveness could be compared in terms of ability to predict a therapeutic response to inhaled bronchodilator or corticosteroid therapy.
In summary, these data indicate that the “normal range” of methacholine PD20FEVJ varies with prechallenge FEV}, even among persons who deny respiratory symptoms or illnesses and who have normal pulmonary function. Using FEVj-specific criteria for defining the lower limit of “normal” PD20FEVJ, however, did not enhance the sensitivity and specificity of methacholine challenge testing for detecting asthma and wheezing in Normative Aging Study subjects.

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