Functional aging in fibrotic interstitial lung disease: The impact of frailty on adverse health outcomes

Background Accelerated biological and functional aging is common in fibrotic interstitial lung disease (ILD); however, their impact on adverse health outcomes has not been evaluated in this population. Methods Patients were prospectively recruited from a specialised ILD clinic. Functional aging was determined by the frailty index (FI), and biological age by measurement of absolute telomere length (aTL) from patients9 peripheral blood leukocytes. Adverse health outcomes included health-related quality of life (St George9s Respiratory Questionnaire), number and length of respiratory and non-respiratory hospitalisations, medication tolerability, and time to death or lung transplantation. Multivariable models were used to determine the risks and rates of adverse health outcomes associated with the FI and aTL. Results 540 patients with fibrotic ILD, including 100 with idiopathic pulmonary fibrosis (IPF), provided 749 FI assessments, with 189 patients providing blood samples. The FI was strongly associated with quality of life, rate of hospitalisation, time to hospital discharge, and mortality, including with adjustment for age, sex, disease severity, and IPF diagnosis. Mortality prognostication was improved by the addition of the FI to commonly used clinical parameters and previously validated composite indices. Conversely, aTL was not associated with most adverse health outcomes. The effect of chronological age on outcomes was mediated primarily by the FI and to a lesser extent by aTL. Conclusions Functional aging is associated with adverse health outcomes in patients with fibrotic ILD, indicating the need for consideration of the individual functional age into clinical decision-making.