A Prospective Longitudinal Study of Methacholine Airway Responsiveness as a Predictor of Pulmonary-Function Decline: The Normative Aging Study

It has been hypothesized that nonspecific airway hyperresponsiveness is a risk factor for accelerated pulmonary-function decline during aging and the development of chronic airflow obstruction. We tested this hypothesis in a prospective, longitudinal study of 912 middle-aged and older men (median age, 60 yr; range, 41 to 86 yr) participating in the Normative Aging Study (NAS). Subjects underwent methacholine challenge testing and spirometry at the time of a regularly scheduled NAS examination, and follow-up spirometry was performed after a median interval of 3.3 yr. Allergy skin testing with a panel of four aeroallergens (mixed grasses, mixed trees, ragweed, and house dust) was also performed at the initial examination. Methacholine responsiveness was expressed as the dose-response slope (DRS) (i.e., the slope of a line connecting the origin with the last point of the methacholine dose-response plot) in units of percent decline FEV1/mumol methacholine. The relationship of the methacholine DRS to the subsequent rate of annual decline in lung function (FEV1, FVC, and FEV1/FVC) was examined using multiple linear-regression models with the rates of pulmonary-function decline as the outcome variables. After adjusting for age, height, smoking status, and initial level of lung function, the log10 DRS was a significant predictor of the rate of decline of FEV1 (regression coefficient beta = 12.8, p = 0.03) and FEV1/FVC x 100 (beta = 0.506, p = 0.0001), and a borderline significant predictor of FVC (beta = 15.3, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)