FEF_25-75% trajectories from age 7 to 53 years, associations with childhood and parental preconception factors, and midlife COPD risk: a prospective cohort study.

Abstract

Existing trajectory studies have emphasised large-airway indices, but chronic obstructive pulmonary disease (COPD) might originate in smaller airways. This study aimed to investigate mid-to-small-airway function trajectories, their associated factors, and COPD risk. In this prospective cohort study, probands (referred to throughout as offspring) were recruited to the Tasmanian Longitudinal Health Study from local schools across Tasmania, Australia at age 7 years. Pre-bronchodilator mean forced expiratory flow between 25% and 75% of the forced vital capacity (FEF_25-75%) of offspring was measured at age 7 years as a proxy measure of mid-to-small-airway function. Parents completed a comprehensive respiratory health survey on themselves and their offspring. Offspring were followed up at mean ages of 13, 18, 45, 50, and 53 years. Follow-up included pre-bronchodilator spirometry, demographic surveys, lifestyle factors, respiratory symptoms, and illnesses. Post-bronchodilator spirometry was measured at mean ages of 45 and 53 years. Parents were later approached to complete the 2010 Tasmanian Longitudinal Health Study Parents Postal Survey, which collected information on parental preconception factors, including exposures during their own childhood and adolescence. Group-based trajectory modelling was used to identify FEF_25-75% trajectories. Regression models were used to assess associations of FEF_25-75% trajectories with childhood and parental preconception factors, and with COPD risk by age 53 years. Between Feb 23, 1968, and Nov 8, 2016, 2314 offspring from the Tasmanian Longitudinal Health Study were included. Six FEF_25-75% trajectories were identified: persistently low (144 [6·2%]); early normal-reduced growth-rapid decline (168 [7·3%]); early below average-reduced growth (740 [32·0%]); early low-accelerated growth (80 [3·5%]); average (976 [42·2%]; reference); and persistently high (206 [8·9%]). Three impaired trajectories across the lifespan were associated with COPD: persistently low (adjusted odds ratio 112 [95%CI 42-304]), early normal-reduced growth-rapid decline (41 [15-112]), and early below average-reduced growth (3·1 [1·0-9·2]) trajectories. Factors associated with impaired trajectories included no breastfeeding, the presence of asthma or wheeze, allergic rhinitis, and pneumonia or pleurisy during childhood, maternal asthma or wheeze, and parental smoking before conception. The persistently high trajectory was associated with parental preconception microbial-related exposures (ie, fathers sharing a childhood bedroom with three or more siblings and maternal cat keeping before completing puberty). FEF_25-75% across the life course, particularly from early life, could be more relevant to COPD than previously recognised. Several childhood and novel parental preconception factors were associated with FEF_25-75% trajectories, although causality cannot be inferred due to no clear temporality of these associations. Our findings on the relationship between FEF_25-75% and COPD should be interpreted as life-course associations rather than as predictive. As COPD was rare in the average trajectory, the magnitude of effect estimates could be inflated. National Health and Medical Research Council of Australia; The University of Melbourne; Clifford Craig Medical Research Trust; the Victoria, Queensland, and Tasmania Asthma Foundations; The Royal Hobart Hospital Research Foundation; Helen MacPherson Smith Trust; GlaxoSmithKline; China Scholarship Council.