Factors associated with within-individual variability of lung function for people with cystic fibrosis: a longitudinal registry study

Lung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates is not quantified. We performed a longitudinal analysis of data from a cohort of 7099 adults with cystic fibrosis (between 18 and 49 years old) from the UK cystic fibrosis registry, containing annual review data between 1996 and 2020. A mixed-effects location-scale model is used to quantify mean FEV 1 (forced expiratory volume in 1 second) trajectories and FEV 1 within-individual variability as a function of sex, age at annual review, age at diagnosis, genotype and birth cohort. Mean FEV 1 decreased with age and lung function variability showed an approximately quadratic trend by age. Males showed higher FEV 1 mean and variability than females across the whole age range. Individuals who died during follow-up showed on average higher lung function variability than those who survived. This work opens new avenues for further research to understand the role of within-individual lung function variability in disease progression and prediction of key outcomes such as mortality.