RESUMEN
BACKGROUND AND OBJECTIVE: Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations. METHODS: We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network. RESULTS: We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation. CONCLUSION: IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.
Asunto(s)
Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Exorribonucleasas , Humanos , Fibrosis Pulmonar Idiopática/genética , Enfermedades Pulmonares Intersticiales/genética , Mutación/genética , Estudios RetrospectivosRESUMEN
: Pulmonary fibrosis (PF) is a very rare condition in children, which may be observed in specific forms of interstitial lung disease. None of the clinical, radiological, or histological descriptions used for PF diagnosis in adult patients, especially in situations of idiopathic PF, can apply to pediatric situations. This observation supports the view that PF expression may differ with age and, most likely, may cover distinct entities. The present review aims at summarizing the current understanding of PF pathophysiology in children and identifying suitable diagnostic criteria.