Advancing Pulmonary Fibrosis Care: Integrating Genomic Insights Into Clinical Practice.

Area of Science:

• Pulmonary Medicine
• Genetics
• Molecular Biology

Background:

• Fibrotic interstitial lung disease (ILD) diagnosis can be challenging.
• Genetic factors and telomere biology are increasingly recognized in ILD pathogenesis.
• A dedicated translational unit can facilitate integrated genetic testing and counseling.

Purpose of the Study:

• To evaluate the diagnostic impact of genetic testing and telomere length analysis in fibrotic ILD.
• To establish and assess a translational genetic testing and counseling unit for ILD patients.
• To determine the frequency of genetic variants and telomere disorders in a referred ILD cohort.

Main Methods:

• Patients with suspected fibrotic ILD were referred to a specialized unit.
• Genetic testing included a pulmonary fibrosis-multigene sequencing panel.
• Telomere length was assessed in lymphocytes and/or granulocytes.

Main Results:

• Genetic testing was completed by 82% of referred patients; 19% had pathogenic/likely pathogenic variants, primarily in telomere pathway genes.
• Telomere lengths were short (≤10th percentile) in 79% of assessed patients.
• Shorter lymphocyte telomere length was associated with a higher likelihood of identifying a genetic cause (OR: 6.26).
• Genetic findings influenced clinical decisions in over half of tested patients.

Conclusions:

• Comprehensive genetic sequencing and telomere length analysis enhance diagnostic accuracy in fibrotic ILD.
• Telomere disorders are a significant, often undiagnosed, cause of fibrotic ILD.
• An integrated clinical model for genetic testing has substantial translational value in patient management.