Methacholine challenge positivity and FEV1/FVC change at clinically determined follow-up

BACKGROUND: We evaluated the exploratory association between methacholine challenge positivity and subsequent spirometric change. RESEARCH DESIGN AND METHODS: This single-center retrospective longitudinal study included adults with an unambiguous baseline methacholine challenge result, forced expiratory volume in 1 second (FEV1) ≥80% predicted, and FEV1/forced vital capacity (FVC) ≥0.70. Outcomes were FEV1/FVC change and FEV1/FVC < 0.70 at the first qualifying examination ≥ 1 year later. Models adjusted for baseline FEV1/FVC and follow-up interval. RESULTS: Of 36,167 eligible individuals, 1,092 (3.02%) had qualifying follow-up spirometry, including 133 with a positive methacholine challenge. Positivity was associated with greater FEV1/FVC decline (adjusted difference, -2.53% points; 95% confidence interval, -3.63 to -1.44). Marginally standardized probabilities of follow-up FEV1/FVC < 0.70 were 8.07% and 2.63% for positive and negative individuals, respectively. Weighting and lower-limit-of-normal analyses yielded associations in the same direction. CONCLUSIONS: Among adults with clinically indicated follow-up spirometry, methacholine challenge positivity was associated with greater FEV1/FVC decline. Its independent prognostic value remains to be established.