In:
ERJ Open Research, European Respiratory Society (ERS)
Abstract:
CF lung disease start in infancy and can be assessed for structural lung abnormalities using CT or MR scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of cystic fibrosis (CF) lung disease assessed by MBW in infants and toddlers remain poorly described, why we aimed to describe (i) the trajectory of lung function, (ii) explore risk factors for progression, and (iii) the real-life effect of lumacaftor/ivacaftor. Methods A nationwide observational cohort study (2018–2021) using data collected as part of the clinical routine surveillance program (including MBW, and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of new-born-screening (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statical analyses performed in this study. Main results Fifty-nine children, aged 2–45 months, contributed with 211 MBW occasions (median [interquartile range; IQR] 3 [2; 5] occasions per child) with a follow-up time of median (IQR) 10.8 (5.2; 22.3) months. An overall annual deterioration rate of mean (95% confidence interval; CI) −0.50 (−0.78; −0.22) z-VDE was observed, starting from an estimated mean (95%CI) z-VDE of −1.68 (−2.15; −1.22) at age 0.0 (intercept). Pseudomonas aeruginosa ( PA) “ ever” (N=14; MBWs=50) had a significantly worse z-VDE trajectory versus “never” PA (mean [95%CI] difference: 0.53*year −1 [0.16; 0.89], p=0.0047), and lumacaftor/ivacaftor treatment (N=22; MBWs=46) significantly improved the trajectory of z-VDE (mean [95%CI] difference: +1.72*years −1 [0.79; 2.66], p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment. Conclusion Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. PA isolation ever was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.
Type of Medium:
Online Resource
ISSN:
2312-0541
DOI:
10.1183/23120541.00317-2023
Language:
English
Publisher:
European Respiratory Society (ERS)
Publication Date:
2023
detail.hit.zdb_id:
2827830-6
