Advancing Pulmonary Fibrosis Care: Integrating Genomic Insights Into Clinical Practice

To evaluate the impact of genetic testing and telomere analysis among patients with fibrotic interstitial lung disease, we established a translational genetic testing and counseling unit for patients referred from our pulmonary practice.

We included patients referred to the genetic testing and counseling unit between 2019 and 2023 who presented either with a family history of pulmonary fibrosis, progressive fibrotic disease, clinical indicators of surfactant protein or telomere biology disorders (eg, early greying of hair, etc), or early-onset fibrosis (≤60 years). Patients underwent a pulmonary fibrosis-multigene sequencing panel and telomere length assessment. Clinical data, genetic sequencing results, and telomere measurements were collected and analyzed.

Of 66 referred patients, 54 (82%) completed genetic testing. Common clinical diagnoses were unclassifiable fibrotic lung disease (29%) and idiopathic pulmonary fibrosis (26%). The predominant radiologic pattern was indeterminate for usual interstitial pneumonia (42%). Telomere lengths, measured in 47 patients (71%), were less than or equal to the 10th percentile in lymphocytes and/or granulocytes for age-matched controls in 37 patients (79%). Pathogenic/likely pathogenic variants were identified in 10 patients (19%), predominantly in telomere pathway genes (9 of 10 cases). Shorter lymphocyte telomere length increased odds of identifying a genetic etiology (odds ratio: 6.26; 95% CI: 1.50 to 33.83; P = .01). Importantly, genetic findings impacted clinical decisions in more than half of tested patients.

Comprehensive genetic sequencing combined with telomere length analysis enhances diagnostic accuracy in fibrotic interstitial lung disease, identifying a high proportion of cases attributable to telomere disorders. Our integrated clinical model demonstrates significant translational value, influencing patient management, and therapeutic decision-making.