Impact of A Multidisciplinary Team Discussion for Genetic Lung Fibrosis.

Background and objective

Approximately 30% of individuals diagnosed with familial pulmonary fibrosis (FPF) exhibit a pathogenic variant upon genetic analysis. We established a genetic Multidisciplinary Discussion (geneMDD) aimed to enhance expertise in diagnosing and managing FPF. This study aimed at prospectively evaluating the impact of geneMDD on diagnosis and treatment in patients referred to geneMDD.

Methods

In this prospective study, we enrolled all consecutive patients referred to the geneMDD. At each meeting, the impact of the meeting was questioned on the genetic conclusion, the pulmonary diagnosis, and the treatment.

Results

A total of 115 patients were included. Before geneMDD, rare variants were detected in 82 out of 107 patients, among which 65 variants were classified as pathogenic/likely pathogenic. Following geneMDD, 2 pathogenic variants (3%) were reclassified as variants of uncertain significance (VUS) (n = 1) or benign (n = 1). Among the 17 variants initially classified as VUS, 2 (11.8%) were reclassified as likely pathogenic/pathogenic. The pulmonary diagnosis was confirmed for all patients (unclassifiable lung fibrosis was the more frequent diagnosis, n = 38, 33.0%). The therapeutic regimen was changed after geneMDD in 30 patients. Factors associated with therapeutic changes included the pulmonary diagnosis and presence of a pathogenic/likely pathogenic variant. In addition, the French health system allows offering whole genome sequencing (WGS) in patients with a first negative genetic analysis by NGS panel after discussion in geneMDD, but in total, since September 1st, 2021, WGS was negative for the four analysed families.

Conclusion

This study suggests that geneMDD could influence the treatment of FPF patients.

© 2025 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.