Rationale: Declines in percent predicted forced expiratory volume in 1 second (ppFEV1) are an important marker of clinical progression of cystic fibrosis (CF). Objectives: We examined ppFEV1 variability in relation to a combined outcome of lung transplant or death. Methods: We estimated the association between ppFEV1 variability and the combined outcome of lung transplant or death. We included children aged 8 years and older with CF and two prior years of ppFEV1 data before baseline between 2005 and 2021. We defined ppFEV1 increased variability as any relative increase or decrease of at least 10% in ppFEV1 from a 2-year averaged baseline. A marginal structural Cox proportional hazards model was used. We examined a cumulative measure of ppFEV1 variability, defined as the cumulative proportion of visits with ppFEV1 variability at each visit. Kaplan-Meier survival curves were generated on the basis of quartiles of the cumulative distribution of ppFEV1 variability. Results: We included 9,706 patients with CF in our cohort. The median age at cohort entry was 8.3 (interquartile range, 8.2-8.4) years; 50% of patients were female; 94% were White; and the median baseline ppFEV1 was 94.4 (interquartile range, 81.6-106.1). The unadjusted hazard ratio for increased ppFEV1 variability on lung transplant/mortality was 4.13 (95% confidence interval, 3.48-4.90), and the weighted hazard ratio was 1.49 (95% confidence interval, 1.19-1.86). Survival curves stratified by quartile of cumulative variability demonstrated an increased hazard of lung transplant/mortality as the proportion of cumulative ppFEV1 variability increased. Conclusions: We found a strong association between ppFEV1 variability and lung transplant or mortality in a cohort of people with CF in the United States.
Keywords: cystic fibrosis; lung function; marginal structural models; registry studies; spirometry.