A prospective longitudinal study of methacholine airway responsiveness as a predictor of pulmonary-function decline: the Normative Aging Study

Am J Respir Crit Care Med. 1995 Jul;152(1):87-92. doi: 10.1164/ajrccm.152.1.7599868.


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)

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology*
  • Bronchial Hyperreactivity / diagnosis*
  • Bronchial Hyperreactivity / epidemiology
  • Bronchial Provocation Tests
  • Cohort Studies
  • Humans
  • Linear Models
  • Longitudinal Studies
  • Lung / physiopathology*
  • Lung Diseases, Obstructive / epidemiology*
  • Male
  • Methacholine Chloride
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Spirometry
  • Time Factors


  • Methacholine Chloride