MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study

Correspondence to Dr John S Kim, Medicine, University of Virginia School of Medicine, Charlottesville, VA 22903, USA; [email protected]

WHAT IS ALREADY KNOWN ON THIS TOPIC

• The MUC5B (rs35705950) risk allele (T) and telomere length are associated with pulmonary fibrosis and qualitative assessments of interstitial lung changes on CT. There are fewer studies that have examined their relationship with longitudinal interstitial lung changes among community-dwelling adults.

WHAT THIS STUDY ADDS

• More high-attenuation areas over time on CT were associated with the MUC5B risk allele, particularly those with shorter baseline telomere length, and a higher risk of overall death and interstitial lung disease.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Our study suggests that quantitative CT assessments and their longitudinal measures may be a potential tool to identify earlier stages of interstitial lung disease.

Introduction

Interstitial lung disease (ILD) is a group of chronic respiratory disorders characterised by inflammation and fibrosis of the lung parenchyma.¹ Non-fibrosing ILDs can become fibrotic which may lead to rapid deterioration, chronic respiratory failure and death. By the time of diagnosis, patients often have significant physiological impairments and decreased exercise capacity, with a poor median survival.^{2 3}

An increasing number of studies have focused on visual, qualitative assessment of CT scans for changes suggestive of ILD, termed interstitial lung abnormalities (ILAs), when identified in research studies or incidentally in the clinical context.⁴ These studies have yielded important insights into novel risk factors for progressive fibrosing ILD. A recent Fleischner Society position paper defining the radiological criteria for ILA also highlighted the need for quantitative CT methods for evaluation of disease extent and progression as a key research priority.⁴

One of the strongest known risk factors for pulmonary fibrosis is the MUC5B promoter polymorphism (rs35705950); it is associated with fourfold higher odds of idiopathic pulmonary fibrosis (IPF). Recent studies have shown that this gain-of-function promoter variant is linked to other types of fibrosing ILDs like chronic hypersensitivity pneumonitis and rheumatoid arthritis-related ILD.^5–7 The polymorphism is associated with ILA among the general population and in cohorts of smokers, suggesting that carriers of this allele may be at higher risk of developing fibrosing ILDs.⁸ Shorter telomere length, a marker of accelerated cellular senescence, is another intrinsic...