Clinical Relevance of Lung Function Trajectory Clusters in Middle-aged and Older Adults

Abstract

BackgroundThe determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterize clusters of lung function trajectories in adults aged 45 years and older.MethodsGaussian finite mixture modelling was applied to baseline and annualized change of FEV1, FVC, and FEV1/FVC ratio z-scores in participants of the Rotterdam Study, a prospective population-based cohort study, with repeated spirometry (n=3884; mean age=64.7 (sd=8.9) years). Longitudinal outcomes were all-cause mortality, respiratory outcomes (symptoms, COPD (FEV1/FVC<0.7 in absence of asthma), preserved ratio impaired spirometry (PRISm; FEV1/FVC≥0.7 and FEV1or FVC<80%)), smoking cessation, and weight changes. Independent risk factors, including genetics, were identified by multiple logistic regression.ResultsWe identified eight trajectory clusters, with the reference group having persistently normal spirometry (prevalence=42.8%). Three clusters showed higher mortality, adjusted for confounders: (i) the persistently low FEV1cluster (prevalence=6.8%, HR=1.71 (95%CI:1.37–2.13)), (ii) rapid FEV1decliners (prevalence=4.6%, HR=1.48 (95%CI:1.10–1.99)) and (iii) FVC decliners (prevalence=3.7%, HR=1.49 (95%CI:1.09–2.03)). In contrast, FVC improvers (prevalence=6.7%, HR=0.61 (95%CI:0.41–0.90)) and persistently high FEV1(prevalence=29.2%, HR=0.82 (95%CI:0.69–0.98)) were protective trajectory clusters. Clusters were characterized by differences in genetic predisposition (polygenic scores of FEV1and FEV1/FVC), demographics, cigarette smoking, respiratory symptoms (chronic cough, wheezing, and dyspnoea), cardiovascular factors (BMI, hypertension, and heart failure), and C-reactive protein levels. Frailty, weight changes, and the development of respiratory symptoms, COPD, and PRISm were significantly associated with trajectory clusters.ConclusionsThis study reveals clinically relevant lung function trajectory clusters in older adults of the general population.