Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease

Abstract

Background: Human telomere disease consists of a wide spectrum of disorders, including pulmonary, hepatic, and bone marrow abnormalities. The extent of bone marrow and liver abnormalities in patients with interstitial lung disease (ILD) and short telomeres is unknown.

Methods: The lung transplant clinic established a prospective protocol to identify short telomeres in patients with ILD not related to connective tissue disease or sarcoidosis. Patients with short telomeres underwent bone marrow biopsies, liver biopsies, or both as part of the evaluation for transplant candidacy.

Results: One hundred twenty-seven patients met ILD categorization for inclusion. Thirty were suspected to have short telomeres, and 15 had the diagnosis confirmed. Eight of 13 (53%) patients had bone marrow abnormalities. Four patients had hypocellular marrow associated with macrocytosis and relatively normal blood counts, which resulted in changes to planned immunosuppression at the time of transplant. Four patients with more severe hematologic abnormalities were not listed because of myelodysplastic syndrome (two); monoclonal gammopathy of unclear significance (one); and hypocellular marrow, decreased megakaryocyte lineage associated with thrombocytopenia (one). Seven patients underwent liver biopsies, and six had abnormal liver pathology. These abnormalities did not affect listing for lung transplant, and liver biopsies are no longer routinely obtained.

Conclusions: Subclinical bone marrow and liver abnormalities can be seen in patients with ILD and short telomeres, in some cases in the absence of clinically significant abnormalities in peripheral blood counts and liver function tests. A larger study examining the implication of these findings on the outcome of patients with ILD and short telomeres is needed.

Figure 1 –

Study flow diagram. CTD = connective tissue disease; ILD = interstitial lung disease.

Figure 2 –

Lymphocyte telomere length in patients with interstitial lung disease and suspected short telomeres. Telomere length as measured by flow fluorescence in situ hybridization is shown for patients with short telomeres (○) and those with normal telomere length (●). A, Lymphocyte telomere length of tested subjects shown relative to indicated percentiles of a reference cohort as reported in the clinical testing by Repeat Diagnostics (Vancouver, Canada). B, Mean O − E (50th percentile age-adjusted telomere length) for subjects with interstitial lung disease with (○) and without (●) short telomeres. E = expected; O = observed.