The Role of Genetic Testing in Pulmonary Fibrosis: A Perspective From the Pulmonary Fibrosis Foundation Genetic Testing Work Group

Abstract

Patients with familial pulmonary fibrosis represent a subset of patients with pulmonary fibrosis in whom inherited gene variation predisposes them to disease development. In the appropriate setting, genetic testing allows for personalized assessment of disease, recognition of clinically relevant extrapulmonary manifestations, and assessing susceptibility in unaffected relatives. However currently, the use of genetic testing is inconsistent, partly because of the lack of guidance regarding high-yield scenarios in which the results of genetic testing can inform clinical decision-making. To address this, the Pulmonary Fibrosis Foundation commissioned a genetic testing work group comprising pulmonologists, geneticists, and genetic counselors from the United States to provide guidance on genetic testing in patients with pulmonary fibrosis. This CHEST special feature presents a concise review of these proceedings and reviews pulmonary fibrosis susceptibility, clinically available genetic testing methods, and clinical scenarios in which genetic testing should be considered.

Keywords: familial pulmonary fibrosis; genetic counseling; genetic testing; genetics; single nucleotide polymorphism.

Figure 1

Example of a pedigree demonstrating features of short telomere syndrome across multiple generations. Arrow points to the proband or index patient. Roman numerals represent the generations from oldest to youngest. Individuals are identified by Roman numeral generation and number in order (eg, III.7).

Figure 2

A, B, Graphs showing examples of clinical reports of telomere length in lymphocytes (A) and granulocytes (B) for a patient with familial pulmonary fibrosis. The points on the telograms represent the telomere length values relative to the expected age-adjusted distribution. Telomere length was measured by flow cytometry and fluorescent in situ hybridization.