Short telomeres, telomeropathy, and subclinical extrapulmonary organ damage in patients with interstitial lung disease.
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.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Gautam
G
George
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Ivan O
IO
Rosas
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Ye
Y
Cui
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Caitlin
C
McKane
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Gary M
GM
Hunninghake
Department of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Phillip C
PC
Camp
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Benjamin A
BA
Raby
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Hilary J
HJ
Goldberg
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: Sel-chemaly@partners.org.
Souheil
S
El-Chemaly
D000368:Aged; D001706:Biopsy; D001772:Blood Cell Count; D001853:Bone Marrow / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000473:pathology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018579:Patient Selection; D011446:Prospective Studies; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
D019098:Telomerase