Early onset and familiar Interstitial lung disease: Diagnose molecularly and systematically explore treatment with hydroxychloroquine

Interstitial lung disease (ILD) is an umbrella term for over 200 different rare conditions. The course of many of these diseases is connected to a high morbidity and mortality. Idiopathic pulmonary fibrosis (IPF), usually occurring sporadic and in the elderly, is one of the most frequent diagnosis within this group. Current data indicate that about 3 – 5% of suspected monogenic pulmonary fibrosis in adults is due to surfactant disorders.

The European Childrenʼs Interstitial Lung Disease (chILD-EU) management platform provides an established work flow with an accredited private laboratory to diagnose patients with mutations in SFTPC, SFTPB, ABCA3, and TTF1 (=NKX2 – 1). Workup in early onset (< age 50y) or familial (2 or more first degree related) ILD patients is intended to identify molecularly definable patients (1).

In pediatric ILD there is a long standing history of off-label usage of hydroxychloroquine (HCQ), especially in surfactant dysfunction disorders. HCQ4Surfdefect is an international, randomised clinical trial (ClinicalTrials.gov Identifier: NCT02615938) to investigate the efficacy and safety of HCQ in genetic interstitial lung disease (ILD) of patients with a genetically diagnosed ILD related to surfactant dysfunction disorders of all ages. The trial is supported by the German Center for Lung Research (DZL), open to all other sites and is expanding to international level. Endpoints of the study include among others oxygen saturation, lung function, quality of life and survival (2).

Results (1) Initiate genetic testing of candidate patients via the platform. Completed genetic diagnostics with surfactant panel in 28 patients including infants and children revealed disease causing variants in 6 cases, and in 3 novel variants of unknown significance, likely to be disease causing.

(2) Currently 28 patients are randomised in the hydroxychloroquine study in Germany. Recruitment is ongoing and we anticipate inclusion of additional newly identified patients.

Precise molecular diagnosis will help to personalize treatment in patients suffering from early onset and familiar interstitial lung disease

Supported by DZL and erare.