Forced Expiratory Volume in 1 Second Variability Predicts Lung Transplant or Mortality in People with Cystic Fibrosis in the United States

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