METHACHOLINE REACTIVITY PREDICTS CHANGES IN LUNG-FUNCTION OVER TIME IN SMOKERS WITH EARLY CHRONIC OBSTRUCTIVE PULMONARY-DISEASE

As part of a clinical trial of early intervention in chronic obstructi ve pulmonary disease (COPD) (the Lung Health Study), 5,733 smokers wit h mild to moderate airflow obstruction underwent methacholine challeng e tests at baseline. All participants were randomized to receive eithe r usual care (no intervention) or special intervention, consisting of intensive smoking cessation counseling and the prescription of a meter ed-dose inhaler containing either ipratropium bromide or placebo (two inhalations three times daily). For this report, we analyzed the relat ionship between baseline methacholine reactivity and subsequent change in lung function. Methacholine reactivity was expressed as a logarith mic function of the two-point slope of percent decline in FEV(1) over the concentration of methacholine (LMCR). Using a random effects linea r model, LMCR was found to be a strong predictor of change in FEV(1)% predicted, after controlling for baseline lung function, age, sex, bas eline smoking history, and changes in smoking status. Significant inte ractions were found between reactivity and smoking behavior, in the fi rst year, participants who quit smoking showed improvement in FEV(1), whereas continuing smokers showed worsening, and between Years 1 and 5 , lung function declined to a greater extent in continuing smokers tha n in sustained quitters. For both time periods, these quitter/smoker d ifferences increased as a function of airway reactivity. These finding s indicate that methacholine reactivity is an important predictor of p rogression of airway obstruction in continuing smokers with early COPD , independent of the baseline level of obstruction.