Autoimmune Progressive Fibrosing Interstitial Lung Disease: Predictors of Fast Decline

Alexandra Nagy, Tamas Nagy, Abigel Margit Kolonics-Farkas, Noemi Eszes, Krisztina Vincze, Eniko Barczi, Adam Domonkos Tarnoki, David Laszlo Tarnoki, György Nagy, Emese Kiss, Pal Maurovich-Horvat, Aniko Bohacs, Veronika Müller, Alexandra Nagy, Tamas Nagy, Abigel Margit Kolonics-Farkas, Noemi Eszes, Krisztina Vincze, Eniko Barczi, Adam Domonkos Tarnoki, David Laszlo Tarnoki, György Nagy, Emese Kiss, Pal Maurovich-Horvat, Aniko Bohacs, Veronika Müller

Abstract

A subset of interstitial lung diseases (ILDs) with autoimmune traits-including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)-develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 (n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group (p < 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients (n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group.

Keywords: antifibrotics; autoimmune disease; connective tissue disease (CTD); interstitial pneumonia with autoimmune features (IPAF); progressive fibrosing interstitial lung disease (PF-ILD); treatment.

Conflict of interest statement

VM, AB, KV, NE received consultation fees from Boehringer Ingelheim during the last 5 years. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Nagy, Nagy, Kolonics-Farkas, Eszes, Vincze, Barczi, Tarnoki, Tarnoki, Nagy, Kiss, Maurovich-Horvat, Bohacs and Müller.

Figures

FIGURE 1
FIGURE 1
Study population. ILD, interstitial lung disease; IIP, idiopathic interstitial pneumonia; HP, hypersensitivity pneumonitis; CTD-ILD, connective tissue disease-associated interstitial lung disease; IPAF, interstitial pneumonia with autoimmune features.
FIGURE 2
FIGURE 2
Longitudinal follow-up of CTD-ILD and IPAF patients: percent change in FVC. (A) Changes according to treatment; (B) respective patients according to underlying disease. CTD-ILD, connective tissue disease-associated interstitial lung disease; IPAF, interstitial pneumonia with autoimmune features; FVC, forced vital capacity; PF-ILD, [progressive fibrosing ILD; AF, antifibrotic treatment; AF + ISU, antifibrotic treatment with immunosuppressive agent; Comb-ISU, combined immunosuppressive treatment; Mono-ISU, one immunosuppressive agent; NT, no treatment].

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