Clinical relevance of lung function trajectory clusters in middle-aged and older adults

Xander Bertels; James C Ross; Rosa Faner; Michael H Cho; M Arfan Ikram; Guy G Brusselle; Lies Lahousse

doi:10.1183/23120541.00793-2023

Clinical relevance of lung function trajectory clusters in middle-aged and older adults

ERJ Open Res. 2024 Feb 5;10(1):00793-2023. doi: 10.1183/23120541.00793-2023. eCollection 2024 Jan.

Authors

Xander Bertels^{1

2}, James C Ross³, Rosa Faner^{4

5

6}, Michael H Cho^{7

8}, M Arfan Ikram², Guy G Brusselle^{2

9

10}, Lies Lahousse^{1

2}

Affiliations

¹ Department of Bioanalysis, Ghent University, Ghent, Belgium.
² Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Institut d'Investigacions Biomédiques August Pi i Sunyer, Hospital Clinic de Barcelona, Barcelona, Spain.
⁵ Department of Biomedical Sciences, University of Barcelona, Barcelona, Spain.
⁶ Centro Investigaciones Biomédicas en Red, Instituto de Salud Carlos III, Madrid, Spain.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
¹⁰ Department of Respiratory Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Abstract

Background: The determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterise clusters of lung function trajectories in adults aged ≥45 years.

Methods: Gaussian finite-mixture modelling was applied to baseline and annualised change of forced expiratory volume in 1 s (FEV₁), forced vital capacity (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±sd age 64.7±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 FEV₁ or FVC <80%)), smoking cessation and weight changes. Independent risk factors, including genetics, were identified by multiple logistic regression.

Results: We identified eight trajectory clusters, with the reference group having persistently normal spirometry (prevalence 42.8%). Three clusters showed higher mortality, adjusted for confounders: 1) the persistently low FEV₁ cluster (prevalence 6.8%, hazard ratio (HR) 1.71, 95% CI 1.37-2.13); 2) rapid FEV₁ decliners (prevalence 4.6%, HR 1.48, 95% CI 1.10-1.99); and 3) 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 characterised by differences in genetic predisposition (polygenic scores of FEV₁ and FEV₁/FVC), demographics, cigarette smoking, respiratory symptoms (chronic cough, wheezing and dyspnoea), cardiovascular factors (body mass index, hypertension and heart failure) and serum C-reactive protein levels. Frailty, weight changes and the development of respiratory symptoms, COPD and PRISm were significantly associated with trajectory clusters.

Conclusions: This study reveals clinically relevant lung function trajectory clusters in older adults of the general population.