Defining and identifying early-onset lung disease in cystic fibrosis with cumulative clinical characteristics

Background Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed. Objective To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life. Design We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age. Cough severity, pulmonary exacerbations (PEx), respiratory cultures, and hospitalizations were collected at each CF center visit (every 1-2 months in infancy and quarterly thereafter). These data were used to construct the CFELD system and to classify lung disease into five categories: asymptomatic, minimal, mild, moderate, and severe. Results The most frequent manifestation of CF early lung disease was MD-reported PEx episodes, PEx hospitalizations, and positive Pseudomonas aeruginosa cultures. Parent-reported cough severity was correlated with the number of respiratory hospitalizations (r = 0.48, p < 0.0001). The distribution of CFELD categories was 10% asymptomatic, 17% minimal, 29% mild, 33% moderate, and 12% severe. The moderate and severe categories occurred threefold higher in pancreatic insufficient (PI, 49%) versus sufficient subjects (16%), p < 0.0001. In addition to PI, gastrointestinal and nutrition-related hospitalizations, plasma cytokines interleukin (IL)-6 and IL-10, duration of CFTR modulator therapy, and type of health insurance were significant predictors of CFELD scores. Conclusion The CFELD scoring system is novel, allows systematic evaluation of lung disease prognosis early, and may aid in therapeutic decision-making particularly in the initiation of CFTR modulator therapy.