Longitudinal Decline of Diffusing Capacity of the Lung for Carbon Monoxide in Community Subjects With the PiMZ α1-Antitrypsin Phenotype

BackgroundIt is well known that homozygous deficiency of α1-antitrypsin, PiZZ, is associated with an increased risk of emphysema. However, studies evaluating associations between the heterozygous form PiMZ with emphysema and impaired lung function have provided conflicting results.Study objectiveThe goal of this study was to determine if the phenotype PiMZ is associated with an accelerated decline in diffusing capacity of the lung for carbon monoxide (Dlco).Design and methodsThe Tucson Epidemiologic Study of Airway Obstructive Disease is a prospective, population-based cohort study initiated in 1972. Participants completed standardized questionnaires in up to 12 periodic surveys and Dlco assessments in up to 4 surveys. Random-effects models were used to determine the effects of α1-antitrypsin phenotypes on percentage of predicted (% predicted) Dlco levels among 1,075 subjects ≥ 18 years old.Results% predicted Dlco declined more rapidly in subjects who smoked compared to nonsmoking subjects. Additionally, in smokers, the PiMZ phenotype was associated with borderline % predicted Dlco deficits at age 40 years (8.6%; p = 0.075) and significant % predicted Dlco deficits at age 60 years (15.2%; p = 0.001) and 80 years (21.9%; p = 0.003), as compared with the PiMM phenotype.ConclusionsDlco may be a more sensitive indicator of the long-term effects of intermediate levels of α1-antitrypsin on lung function especially in subjects who smoke.