Associations between life-course FEV1/FVC trajectories and respiratory symptoms up to middle age: analysis of data from two prospective cohort studies

Abstract

Background

Life-course lung function trajectories leading to airflow obstruction, as measured by impaired FEV₁/FVC (forced vital capacity), precede the onset of chronic obstructive pulmonary disease (COPD). We aimed to investigate whether individuals on impaired FEV₁/FVC trajectories have an increased burden of respiratory symptoms, including those who do not meet the spirometric criteria for COPD.

Methods

We analysed serial life-course data from two population-based cohort studies separately, which included respiratory symptoms and spirometry: the Tasmanian Longitudinal Health Study (TAHS, Australia) cohort was recruited at age 6–7 years and followed up until middle age (mean age 53 years; range 51–55); and the Coronary Artery Risk Development in Young Adults (CARDIA, USA) cohort was recruited at a mean age of 25 years (range 18–30) and followed up to a mean age of 55 years (range 47–64). Participants' symptom profiles at ages 53 and 55 years were derived by latent class analysis. Symptom profiles were compared across pre-bronchodilator FEV₁/FVC trajectories derived by group-based modelling, then restricted to those without COPD defined by post-bronchodilator airflow obstruction (FEV₁/FVC <5th percentile) at ages 51–55 years and 47–64 years.

Findings

Six FEV₁/FVC trajectories previously derived for TAHS were replicated in CARDIA. Optimal models identified five symptom profiles in TAHS (n=2421) and six in CARDIA (n=3153). For both cohorts, the most impaired FEV₁/FVC trajectory (early low, rapid decline in TAHS; low peak, rapid decline in CARDIA) was associated with predominant wheeze (multinomial odds ratio [mOR] 6·71 [95% CI 4·10–10·90] in TAHS and 9·90 [4·52–21·70] in CARDIA) and nearly all respiratory symptoms (4·95 [2·52–9·74] and 14·80 [5·97–36·60]) at age 51–55 years in TAHS and age 47–64 years in CARDIA, compared with the average trajectory. Among individuals belonging to the three most impaired trajectories, the associations with predominant wheeze increased with worsening FEV₁/FVC impairment and persisted when considering only those without spirometry-defined COPD. Additionally, for those belonging to the two rapid decline trajectories, both wheezing and usual phlegm or bronchitis were reported by 54 (20%) of 265 participants younger than 14 years in TAHS and by 31 (25%) of 123 participants aged 30 years or younger in CARDIA.

Interpretation

In two independent cohorts that collected similar data, people on impaired FEV₁/FVC trajectories often had a longstanding history of both wheeze and phlegm or bronchitis, and wheeze was the predominant symptom in individuals aged 47–64 years among those who had not already progressed to COPD.

Funding

National Health and Medical Research Council (Australia); The University of Melbourne; Clifford Craig Medical Research Trust; Victorian, Queensland & Tasmanian Asthma Foundations; Royal Hobart Hospital Research Foundation; Helen MacPherson Smith Trust; GlaxoSmithKline; National Heart, Lung, and Blood Institute of the US National Institutes of Health.