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      Idiopathic Pulmonary Fibrosis in Elderly Patients: Analysis of the INSIGHTS-IPF Observational Study

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          Abstract

          Background: An association between idiopathic pulmonary fibrosis (IPF) and advancing age is suspected since IPF occurs primarily in patients over 60 years of age. Though, little is known about the disease in the elderly. The aim of this study was to characterize elderly IPF patients using data from the longitudinal, German-wide INSIGHTS-IPF registry.

          Methods: Patients were grouped into elderly (≥75 years) and nonelderly IPF (<75 years) at the time of enrollment into the study. Baseline clinical characteristics, comorbidities, health related quality of life (HRQoL), medical therapy and survival were compared between age groups. Effects of antifibrotic therapy on forced vital capacity (FVC) were analyzed over 24 months.

          Results: Of 1,009 patients, 350 (34.7%) were ≥75 years old. Elderly IPF patients compared to younger patients had a higher number of comorbidities (3.6 ± 2.5 vs. 2.8 ± 2.3; p < 0.001). The mean ± SD EQ-5D score (0.64 ± 0.21 vs. 0.69 ± 0.21; p = 0.005), and the overall WHO-5 score (13.1 ± 5.9 vs. 14.3 ± 6.0; p = 0.015) were significantly lower while the UCSD-SOBQ (52.6 ± 31.2 vs. 45.5 ± 31.2; p = 0.030) was significantly higher in elderly patients, indicating a more impaired HRQoL and more breathlessness. At baseline, 55.4% of elderly and 56.8% of nonelderly patients with IPF were treated with antifibrotic therapy ( p = 0.687). For FVC decline after initiation of antifibrotic therapy, there was neither a significant difference between age groups at the different time points over 24 months (beta: 0.41; 95%-CI: −0.98 to 1.81; p = 0.563) nor over the whole course of time (beta: −0.05; 95%-CI: −0.20 to 0.09; p = 0.478). All-cause mortality was higher in elderly patients (49.1 vs. 37.9%; HR 1.65; 95%-CI 1.36–2.00; p < 0.001). Antifibrotic therapy was associated with improved survival in IPF patients, independent from age (<75 years: beta 0.76; 95%-CI: 0.59–0.99; p = 0.049; ≥75 years: beta 0.71; 95%-CI: 0.51–0.98; p = 0.043).

          Conclusion: In real life, a significant proportion of IPF patients are ≥75 years old, characterized by higher number of comorbidities and global reduced HRQoL. However, the effect of an antifibrotic therapy was similar between age groups and associated with a survival benefit emphasizing the importance for an early antifibrotic therapy in IPF, independent from age.

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          Most cited references39

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          An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management

          American Journal of Respiratory and Critical Care Medicine, 183(6), 788-824
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            Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline

            This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society.
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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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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                16 November 2020
                2020
                : 7
                : 601279
                Affiliations
                [1] 1Comprehensive Pneumology Center (CPC-M), Asklepios Klinik Gauting and Helmholtz Center Munich, Ludwig-Maximilians University , München, Germany
                [2] 2Department of Internal Medicine V, Ludwig-Maximilian University Munich , Munich, Germany
                [3] 3German Center for Lung Research , München, Germany
                [4] 4Epidemiology, German Rheumatism Research Center, A Leibniz Institute , Berlin, Germany
                [5] 5Center for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, University of Heidelberg , Heidelberg, Germany
                [6] 6Klinik für Pneumologie, Medizinische Hochschule Hannover , Hannover, Germany
                [7] 7Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM) , Hannover, Germany
                [8] 8Abteilung für Pneumologie, Department Innere Medizin, Neurologie und Dermatologie, Universitätsklinikum Leipzig AöR , Leipzig, Germany
                [9] 9Institut für Klinische Pharmakologie, Medizinische Fakultät, Technische Universität Dresden , Dresden, Germany
                Author notes

                Edited by: Stefanie Krick, University of Alabama at Birmingham, United States

                Reviewed by: Fabrizio Luppi, University of Milano Bicocca, Italy; Tomoo Kishaba, Okinawa Chubu Hospital, Japan

                *Correspondence: Gabriela Leuschner gabriela.leuschner@ 123456med.uni-muenchen.de

                This article was submitted to Pulmonary Medicine, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2020.601279
                7703706
                33313046
                7a54a367-a468-4d9f-aea5-76e1f784d2c2
                Copyright © 2020 Leuschner, Klotsche, Kreuter, Prasse, Wirtz, Pittrow, Frankenberger, Behr, Kneidinger and the INSIGHTS-IPF Registry Group.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 August 2020
                : 09 October 2020
                Page count
                Figures: 2, Tables: 7, Equations: 0, References: 39, Pages: 12, Words: 8536
                Categories
                Medicine
                Original Research

                aging,elderly,antifibrotic therapy,prognosis,multivariate analysis

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