Diffuse parenchymal lung disease caused by surfactant deficiency: dramatic improvement by azithromycin

Abstract

Pulmonary surfactant deficiency caused by mutations in ABCA3 (ATP-binding cassette transporter of the A subfamily, member 3) gene results in diffuse parenchymal lung disease (DPLD) in children. So far, systemic steroids are the main treatment, with however limited efficacy. We report the case of a young boy showing a dramatic long-term improvement of respiratory disease by low-dose azithromycin (AZM) with no side effect after 6 years of treatment. Cellular and molecular studies are ongoing to progress in the understanding of the mechanisms involved. On behalf of the National Reference Center for rare lung diseases in France (Respirare, http://www.respirare.fr), clinical studies on AZM in various forms of DPLD in children have been initiated and should provide information on the types of paediatric DPLD that may benefit from this treatment.

Familial pulmonary fibrosis

“…Homozygous ABCA3 mutations have been reported in children with ILD [50,74]. A large family in which the oldest patients were 41, 52 and 57 years-old, all non-or light smokers with a combination of pulmonary fibrosis and emphysema associated with ABCA3 mutations has been recently reported [75][76].…”

“…Des mutations homozygotes d'ABCA3 ont été rapportées dans des PID de l'enfant [50,74]. Une large famille dont les patients les plus âgés avaient 52 et 57 ans et un patient de 41 ans, tous non ou peu fumeurs et présentant un syndrome emphysème-fibrose associé à des mutations d'ABCA3 ont été récemment rapportés [75][76].…”

Management of suspected monogenic lung fibrosis in a specialised centre

“…Biallelic ABCA3 mutations were first reported in children with ILD and are associated with adult ILD in cases of biallelic missense and nonsense mutations [78,81,82]. Biallelic ABCA3 mutations and heterozygous SFTPC mutations in adults may have a similar clinical and radiological presentation [83,84].…”

Anti-Inflammatory Macrolides to Manage Chronic Neutrophilic Inflammation

“…Although it is reported in chronic macrolide therapy, there are no obvious negative effects and there is a possibility that it contributes to beneficial effects, notably in inflammatory bowel and eye diseases 11 where additional phospholipids correct surfactant deficiencies. 12 Various studies show that phospholipidosis resolves on discontinuation of macrolide therapy and there are no clinical reports of negative outcomes associated with it. Thus phospholipidosis is probably mechanistically linked to effects in immune cells and it seems to present therapeutic opportunities in phospholipid deficiencies rather than any obvious adverse effects in clinical practice.…”