Clinical Year in Review I: Interstitial Lung Disease, Pulmonary Vascular Disease, Pulmonary Infections, and Cardiopulmonary Exercise Testing and Pulmonary Rehabilitation

Abstract

Telomeres, regions of repetitive DNA at the end of chromosomes, shorten with cell division. Short telomeres limit tissue renewal capacity and are thought to play a role in diseases of aging. Telomerases are reverse transcriptase enzymes that add telomere repeats to chromosomes. Germ-line mutations in the components of telomerase (hTERT, hTR) have been associated with familial pulmonary fibrosis in some families (1). However, the role of telomerase mutations in idiopathic pulmonary fibrosis (IPF) is not known. Alder and colleagues (2) examined telomere lengths in leukocytes and alveolar epithelial cells in 64 patients with sporadic idiopathic interstitial pneumonia (IIP), also screening for mutations in hTERT and hTR, and reviewing cases for features of a telomere syndrome such as aplastic anemia or cryptogenic hepatic fibrosis. Telomere length was shorter in IIP cases (both IPF and nonIPF) than in age-matched control subjects, and this was mirrored by shortening of telomeres in leukocytes and alveolar epithelial cells that was of similar amplitude to that observed in familial IPF. A telomerase mutation was observed in only one case, although several individuals had a cluster of idiopathic pulmonary fibrosis and cryptogenic hepatic fibrosis, suggesting a telomere syndrome. These findings suggest that short telomeres are a signature of idiopathic interstitial pneumonia. The linkage between short telomeres and diseases related to aging supports the concept that IPF (and possibly other IIPs) can be viewed as a form of premature aging of the lung. Because known telomerase mutations did not account for short telomere length in this study, further studies are needed to identify the determinants of telomere shortening. The association of short telomere length with both IPF and other IIPs alike suggests the possibility of shared pathogenetic mechanisms between the IIPs. Diagnosis: Nonspecific Interstitial Pneumonia