Prevalence and disease trajectories of pulmonary fibrosis of childhood interstitial lung disease: a register-based, multicentre observational study

Griese M., Reu-Hofer S., Ley-Zaporozhan J., Kammer B., Krüger-Stollfuß I., Micic S., ...Daha Fazla

The Lancet Respiratory Medicine, 2026 (SCI-Expanded, Scopus)

Özet

Background: Pulmonary fibrosis is of critical importance in childhood interstitial lung disease (chILD), yet fibrosis prevalence, impact on clinical progression, and survival have not been systematically evaluated. Therefore, we aimed to determine the prevalence of pulmonary fibrosis and its impact on lung function as well as survival in individuals aged 0–18 years. Methods: Data were extracted from the chILD-EU register, a multicentre cohort study of children and adolescents with chILD from 23 European countries. Data collection included centralised peer review and systematic scoring of CT scans and lung biopsies. The primary outcome was the presence or absence of fibrosing lung disease. Pulmonary fibrosis was determined based on predefined criteria used in the register (fibrosisregister) or in clinical trials (fibrosistrial). Clinical characteristics, disease categories, pulmonary function data, and survival were assessed. This study was registered with ClinicalTrials.gov (NCT02852928) and is ongoing. Findings: Data were collected prospectively between March 3, 2004 and July 23, 2025. Among the 1071 children diagnosed with chILD, 220 of 1071 fulfilled the criteria of fibrosisregister (20·5% [95% CI 18·1–23·0]) and 62 of 534 fulfilled the criteria of fibrosistrial (11·6% [8·9–14·3]). Median age at inclusion was 2·4 years (IQR 0·6–9·2), 570 (53·2%) participants were male and 501 (46·8%) were female, and 882 (76·8%) were European. Pulmonary function, assessed as percent predicted forced vital capacity (ppFVC), in children with fibrosis under both fibrosis definitions was consistently 15–20% lower across all follow-up visits up to 8 years compared with individuals without fibrosing lung disease. Survival after enrolment was lower in children who fulfilled fibrosisregister criteria than in those who did not fulfil fibrosisregister criteria (log-rank p=0·0029; unadjusted hazard ratio (HR) for death or lung transplantation 1·64 [95% CI 1·18–2·28]). The increased hazard of fibrosisregister remained after adjusting for sex, age category, and BMI z-score. A higher BMI z-score was protective for survival with fibrosisregister (HR 0·80). While not statistically significant, children with fibrosistrial criteria had survival and HR trends in the same direction as those with fibrosisregister criteria. Interpretation: The application of standardised criteria for diagnosing pulmonary fibrosis enables identification of affected children among patients with chILD. These children have lower pulmonary function, an increased risk of death, and could benefit from antifibrotic therapies. Funding: Deutsche Forschungsgemeinschaft and Boehringer Ingelheim, Germany.