Abstract
Interstitial lung diseases (ILD) encompass a group of conditions involving fibrosis and/or inflammation of the pulmonary parenchyma. Telomeres are repetitive DNA sequences at chromosome ends which protect against genome instability. At each cell division, telomeres shorten, but the telomerase complex partially counteracts progressive loss of telomeres by catalysing the synthesis of telomeric repeats. Once critical telomere shortening is reached, cell cycle arrest or apoptosis are triggered. Telomeres progressively shorten with age. A number of rare genetic mutations have been identified in genes encoding for components of the telomerase complex, including telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC), in familial and, less frequently, in sporadic fibrotic ILDs. Defects in telomerase result in extremely short telomeres. More rapidly progressive disease is observed in fibrotic ILD patients with telomere gene mutations, regardless of underlying diagnosis. Associations with common single nucleotide polymorphisms in telomere related genes have also been demonstrated for various ILDs. Shorter peripheral blood telomere lengths compared to age-matched healthy individuals are found in a proportion of patients with fibrotic ILDs, and in idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (HP) have been linked to worse survival, independently of disease severity. Greater susceptibility to immunosuppressant-induced side effects in patients with short telomeres has been described in patients with IPF and with fibrotic HP. Here, we discuss recent evidence for the involvement of telomere length and genetic variations in the development, progression, and treatment of fibrotic ILDs.
Highlights
Interstitial lung diseases (ILD) encompass a group of conditions involving fibrosis and/or inflammation of the pulmonary parenchyma
Major entities include the idiopathic interstitial pneumonias (IIPs) (e.g., idiopathic pulmonary fibrosis (IPF) characterised by a usual interstitial pneumonia (UIP), as the most frequent, followed by fibrotic non-specific interstitial pneumonia (NSIP)), those related to environmental exposure (e.g., hypersensitivity pneumonitis (HP) and pneumoconioses), those secondary to connective tissue disease (CTD) (most frequently scleroderma-ILD (SSc-ILD), rheumatoid arthritis-ILD (RA-ILD), and myositis-associated ILD), pulmonary sarcoidosis, and smokingrelated ILDs
Throughout this review, we have not attempted to rigidly divide telomere findings according to a diagnosis of IPF or non IPF, have attempted to clarify where genetic association were identified with ILDs with known causes or associations, including connective tissue disease or hypersensitivity pneumonitis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Major entities include the idiopathic interstitial pneumonias (IIPs) (e.g., idiopathic pulmonary fibrosis (IPF) characterised by a usual interstitial pneumonia (UIP), as the most frequent, followed by fibrotic non-specific interstitial pneumonia (NSIP)), those related to environmental exposure (e.g., hypersensitivity pneumonitis (HP) and pneumoconioses), those secondary to connective tissue disease (CTD) (most frequently scleroderma-ILD (SSc-ILD), rheumatoid arthritis-ILD (RA-ILD), and myositis-associated ILD), pulmonary sarcoidosis, and smokingrelated ILDs. More newly described entities include idiopathic pleuroparenchymal fibrosis (iPPFE), acute fibrinous and organising pneumonia (AFOP), familial ILD, subclinical ILD, and interstitial lung abnormalities (ILAs), while it is recognised that unclassifiable ILD is encountered in a substantial minority of cases [1,2]. Throughout this review, we have not attempted to rigidly divide telomere findings according to a diagnosis of IPF or non IPF, have attempted to clarify where genetic association were identified with ILDs with known causes or associations, including connective tissue disease or hypersensitivity pneumonitis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
