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

Background: Life-course lung function trajectories leading to airflow obstruction, as measured by impaired FEV/FVC (forced vital capacity), precede the onset of chronic obstructive pulmonary disease (COPD). We aimed to investigate whether individuals on impaired FEV/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 FEV/FVC trajectories derived by group-based modelling, then restricted to those without COPD defined by post-bronchodilator airflow obstruction (FEV/FVC <5th percentile) at ages 51-55 years and 47-64 years.

Findings: Six FEV/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 FEV/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 FEV/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 FEV/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.