Methacholine Reactivity Predicts Changes in Lung Function over Time in Smokers with Early Chronic Obstructive Pulmonary Disease

Methacholine Reactivity Predicts Changes in Lung Function over Time in Smokers with Early Chronic Obstructive Pulmonary DiseaseTashkin DP, Altose MD, Connett JE, Kanner RE, Lee WW, Wise RA Lung Health Study Research Group, Los Angeles, California Am J Respir Crit Care Med 1996;153:1802-1811 Objective. A large, multicenter clinical trial of early intervention in chronic obstructive pulmonary disease (Lung Health Study) evaluated the relationship between baseline methacholine reactivity and subsequent changes in lung function over 5 years of follow-up. Methods. A total of 5,733 smokers with mild to moderate airflow obstruction underwent methacholine challenge testing to assess airway hyperreactivity at baseline before being randomized to usual care or special intervention that included intensive smoking cessation counseling and prescription of inhaled bronchodilator or placebo. Subjects were monitored for 5 years with serial spirometric pulmonary function tests to evaluate the changes in lung function. For this analysis, baseline methacholine reactivity was examined as a predictor of change in FEV1. Covariates controlled for in analysis included baseline lung function, age, sex, baseline smoking history, and changes in smoking status. Results. Methacholine reactivity was found to be a strong and significant predictor of change in FEV1 over 5 years. Significant interactions were found between reactivity and smoking behavior. Subjects who quit smoking showed improvement in FEV1 in the first year compared to continued smokers. Over five years, lung function declined more in sustained quitters compared to continued smokers. Throughout the period of follow-up, the differences between quitters and continued smokers increased as a function of increasing airway reactivity. Conclusions. The authors conclude that airway reactivity is an important predictor of progression of airway obstruction in continuing smokers independent of baseline level of airway obstruction. Comment. The Lung Health Study is a major clinical trial designed to evaluate the effect of smoking cessation, airway hyperreactivity, and bronchodilator therapy on the natural history of chronic obstructive pulmonary disease in smokers with mild lung disease. This analysis indicates that airway reactivity, found in the majority of subjects, is an important predictor of decline in lung function over 5 years. This effect is more important than the baseline level of lung function and indicates the possible importance of identifying and treating airway hyperreactivity, in addition to smoking cessation, in slowing the progression of obstructive lung disease in high-risk smokers.