Danielle C M Belgrave1, Raquel Granell2, Steve W Turner3, John A Curtin4, Iain E Buchan5, Peter N Le Souëf6, Angela Simpson4, A John Henderson7, Adnan Custovic1. 1. Section of Paediatrics, Department of Medicine, Imperial College London, London, UK. 2. Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. 3. Child Health, University of Aberdeen, Aberdeen, UK. 4. Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, Manchester, UK. 5. Health Informatics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. 6. School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. 7. Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. Electronic address: a.j.henderson@bristol.ac.uk.
Abstract
BACKGROUND: Maximal lung function in early adulthood is an important determinant of mortality and COPD. We investigated whether distinct trajectories of lung function are present during childhood and whether these extend to adulthood and infancy. METHODS: To ascertain trajectories of FEV1, we studied two population-based birth cohorts (MAAS and ALSPAC) with repeat spirometry from childhood into early adulthood (1046 participants from 5-16 years and 1390 participants from 8-24 years). We used a third cohort (PIAF) with repeat lung function measures in infancy (V'maxFRC) and childhood (FEV1; 196 participants from 1 month to 18 years of age) to investigate whether these childhood trajectories extend from early life. We identified trajectories using latent profile modelling. We created an allele score to investigate genetic associations of trajectories, and constructed a multivariable model to identify their early-life predictors. FINDINGS: We identified four childhood FEV1 trajectories: persistently high, normal, below average, and persistently low. The persistently low trajectory (129 [5%] of 2436 participants) was associated with persistent wheezing and asthma throughout follow-up. In genetic analysis, compared with the normal trajectory, the pooled relative risk ratio per allele was 0·96 (95% CI 0·92-1·01; p=0·13) for persistently high, 1·01 (0·99-1·02; p=0·49) for below average, and 1·05 (0·98-1·13; p=0·13) for persistently low. Most children in the low V'maxFRC trajectory in infancy did not progress to the low FEV1 trajectory in childhood. Early-life factors associated with the persistently low trajectory included recurrent wheeze with severe wheezing exacerbations, early allergic sensitisation, and tobacco smoke exposure. INTERPRETATION: Reduction of childhood smoke exposure and minimisation of the risk of early-life sensitisation and wheezing exacerbations might reduce the risk of diminished lung function in early adulthood. FUNDING: None.
BACKGROUND: Maximal lung function in early adulthood is an important determinant of mortality and COPD. We investigated whether distinct trajectories of lung function are present during childhood and whether these extend to adulthood and infancy. METHODS: To ascertain trajectories of FEV1, we studied two population-based birth cohorts (MAAS and ALSPAC) with repeat spirometry from childhood into early adulthood (1046 participants from 5-16 years and 1390 participants from 8-24 years). We used a third cohort (PIAF) with repeat lung function measures in infancy (V'maxFRC) and childhood (FEV1; 196 participants from 1 month to 18 years of age) to investigate whether these childhood trajectories extend from early life. We identified trajectories using latent profile modelling. We created an allele score to investigate genetic associations of trajectories, and constructed a multivariable model to identify their early-life predictors. FINDINGS: We identified four childhood FEV1 trajectories: persistently high, normal, below average, and persistently low. The persistently low trajectory (129 [5%] of 2436 participants) was associated with persistent wheezing and asthma throughout follow-up. In genetic analysis, compared with the normal trajectory, the pooled relative risk ratio per allele was 0·96 (95% CI 0·92-1·01; p=0·13) for persistently high, 1·01 (0·99-1·02; p=0·49) for below average, and 1·05 (0·98-1·13; p=0·13) for persistently low. Most children in the low V'maxFRC trajectory in infancy did not progress to the low FEV1 trajectory in childhood. Early-life factors associated with the persistently low trajectory included recurrent wheeze with severe wheezing exacerbations, early allergic sensitisation, and tobacco smoke exposure. INTERPRETATION: Reduction of childhood smoke exposure and minimisation of the risk of early-life sensitisation and wheezing exacerbations might reduce the risk of diminished lung function in early adulthood. FUNDING: None.
Authors: Elizabeth C Oelsner; Victor E Ortega; Benjamin M Smith; Jennifer N Nguyen; Ani W Manichaikul; Eric A Hoffman; Xiuqing Guo; Kent D Taylor; Prescott G Woodruff; David J Couper; Nadia N Hansel; Fernando J Martinez; Robert Paine; Meilan K Han; Christopher Cooper; Mark T Dransfield; Gerard Criner; Jerry A Krishnan; Russell Bowler; Eugene R Bleecker; Stephen Peters; Stephen S Rich; Deborah A Meyers; Jerome I Rotter; R Graham Barr Journal: Am J Respir Crit Care Med Date: 2019-09-15 Impact factor: 21.405
Authors: Jing Zhai; Michael Insel; Kenneth J Addison; Debra A Stern; William Pederson; Alane Dy; Joselyn Rojas-Quintero; Caroline A Owen; Duane L Sherrill; Wayne Morgan; Anne L Wright; Marilyn Halonen; Fernando D Martinez; Monica Kraft; Stefano Guerra; Julie G Ledford Journal: Am J Respir Crit Care Med Date: 2019-02-01 Impact factor: 21.405