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      Functional ageing in fibrotic interstitial lung disease: the impact of frailty on adverse health outcomes

      , , , , ,
      European Respiratory Journal
      European Respiratory Society (ERS)

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          Abstract

          Background

          Accelerated biological and functional ageing 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 ageing was determined by frailty index and biological age by measurement of absolute telomere length (aTL) from patients' peripheral blood leukocytes. Adverse health outcomes included health-related quality of life (St George's 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 frailty index and aTL.

          Results

          540 patients with fibrotic ILD, including 100 with idiopathic pulmonary fibrosis (IPF), provided 749 frailty index assessments, with 189 patients providing blood samples. The frailty index was strongly associated with quality of life, rate of hospitalisation, time to hospital discharge and mortality, including adjustment for age, sex, disease severity and IPF diagnosis. Mortality prognostication was improved by the addition of the frailty index 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 frailty index, and to a lesser extent by aTL.

          Conclusions

          Functional ageing 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.

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          Most cited references13

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          A multidimensional index and staging system for idiopathic pulmonary fibrosis.

          Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an overall poor prognosis. A simple-to-use staging system for IPF may improve prognostication, help guide management, and facilitate research. To develop a multidimensional prognostic staging system for IPF by using commonly measured clinical and physiologic variables. A clinical prediction model was developed and validated by using retrospective data from 3 large, geographically distinct cohorts. Interstitial lung disease referral centers in California, Minnesota, and Italy. 228 patients with IPF at the University of California, San Francisco (derivation cohort), and 330 patients at the Mayo Clinic and Morgagni-Pierantoni Hospital (validation cohort). The primary outcome was mortality, treating transplantation as a competing risk. Model discrimination was assessed by the c-index, and calibration was assessed by comparing predicted and observed cumulative mortality at 1, 2, and 3 years. Four variables were included in the final model: gender (G), age (A), and 2 lung physiology variables (P) (FVC and Dlco). A model using continuous predictors (GAP calculator) and a simple point-scoring system (GAP index) performed similarly in derivation (c-index of 70.8 and 69.3, respectively) and validation (c-index of 69.1 and 68.7, respectively). Three stages (stages I, II, and III) were identified based on the GAP index with 1-year mortality of 6%, 16%, and 39%, respectively. The GAP models performed similarly in pooled follow-up visits (c-index ≥71.9). Patients were drawn from academic centers and analyzed retrospectively. The GAP models use commonly measured clinical and physiologic variables to predict mortality in patients with IPF.
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            Predicting survival across chronic interstitial lung disease: the ILD-GAP model.

            Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis.
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              Effect of telomere length on survival in patients with idiopathic pulmonary fibrosis: an observational cohort study with independent validation.

              Short telomere lengths are found in a subset of patients with idiopathic pulmonary fibrosis, but their clinical significance is unknown. Our aim was to investigate whether patients with various blood leucocyte telomere lengths had different overall survival.
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                Author and article information

                Journal
                European Respiratory Journal
                Eur Respir J
                European Respiratory Society (ERS)
                0903-1936
                1399-3003
                January 23 2020
                January 2020
                January 2020
                September 19 2019
                : 55
                : 1
                : 1900647
                Article
                10.1183/13993003.00647-2019
                31537699
                cc77305f-aca5-4d07-bd2e-3a21fb758a80
                © 2019

                https://www.ersjournals.com/user-licence

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