Gastroesophageal reflux disease is associated with a more severe interstitial lung disease in systemic sclerosis in the EUSTAR cohort
Authors: Roth Eliane , Bruni Cosimo , Petelytska Liubov , Becker Mike Oliver , Dobrota Rucsandra , Jordan Suzana , Mihai Carina , Muraru Sinziana , Carreira Patricia E , De Vries-Bouwstra Jeska , Braun-Moscovici Yolanda , Liakouli Vasiliki , Moroncini Gianluca , Bergmann Christina , Mouthon Luc , Denton Christopher P , De Santis Maria , Cauli Alberto , Adler Sabine , Bernardino Vera , Truchetet Marie-Elise , Vonk Madelon , Del Galdo Francesco , Hoffmann-Vold Anna-Maria , Distler Oliver , Elhai Muriel ,   EUSTAR Collaborators, Guiducci Serena , Walker Ulrich , Iannone Florenzo , Becvar Radim , Bielecka Otylia Kowal , Cutolo Maurizio , Ciccia Francesco , Siegert Elise , Rednic Simona , Allanore Yannick , Vlachoyiannopoulos Panayiotis , Montecucco Carlomaurizio , Inanc Murat , Martin Maria , Joven Beatriz , Mendez Cioly , Novak Srdan , Kumánovics Gábor , Iudici Michele , Kotyla Przemyslaw , Zanatta Elisabetta , Perdan-Pirkmajer Katja , Coleiro Bernard , Svegliati Silvia , Benfaremo Devis , Paolini Chiara , Agarbati Silvia , Bancel Dominique Farge , Airò Paolo , Andréasson Kristofer , Radic Mislav , Balbir-Gurman Alexandra , Monaco Andrea Lo , Hunzelmann Nicolas , Iagnocco Annamaria , Idolazzi Luca , Mitrovic Josko , Ong Voon , Nunag Annalyn , Knaapen Hanneke , van Leuven Sander , Thurlings Rogier , Colic Jelena , Henes Jörg , Ortiz-Santamaria Vera , Pflugfelder Johannes , Krasowska Dorota , Rubeli Samuel , Köhm Michaela , Foeldvari Ivan , Bajocchi Gianluigi , da Silva José António Pereira , Stamenkovic Bojana , Tonutti Antonio , Motta Francesca , Ickinger Claudia , Govind Nimmisha , Ananieva Lidia P , Hughes Michael , Klemm Philipp , Müller-Ladner Ulf , Søndergaard Klaus , Engelhart Merete , Szücs Gabriella , de la Puente Carlos , Midtvedt Øyvind , Garen Torhild , Fretheim Håvard , Ramsli Mona-Lovise Talaro , Launay David , Riccieri Valeria , Balanescu Andra , Shah Ami A , Gheorghiu Ana Maria , Wirsching Andreas , Auth Janina , Ramming Alina , Kartalcik Havvanur , Ingegnoli Francesca , Dunogue Bertrand , Chaigne Benjamin , Smith Vanessa , Cantatore Francesco Paolo , Mogensen Mette , von Mühlen Carlos Alberto , Lauffer Felix , Wiland Piotr , Vanthuyne Marie , Alegre-Sancho Juan Jose , Aringer Martin , De Langhe Ellen , Ani Branimir , Yavuz Sule , Granel Brigitte , de Souza Müller Carolina , Agachi Svetlana , Pileckyte Margarita , Stebbings Simon , Vacca Alessandra , Sampaio-Barros Percival D , Solanki Kamal , Veale Douglas , Loyo Esthela , Mohamed Walid Ahmed Abdel Atty , Olas Jacek , Rosato Edoardo , Zhini Figen Yargucu , Tanaseanu Cristina-Mihaela , Foti Rosario , Ancuta Codrina , Maurer Britta , Olesinska Marzena , Kayser Cristiane , Fathi Nihal , Martín Jorge Juan González , Blaise Sophie , Senet Patricia , Chatelus Emmanuel , Litinsky Ira , Koenig Martial , Hoa Sabrina , Senécal Jean-Luc , Cheema Rajvinder , Pitarch Begonya Alcacher , Green Lorraine , Kakkar Vishal , Di Donato Stefano , Seskute Goda , Saketkoo Lesley Ann , Kerzberg Eduardo , Bianchi Breno Valdetaro , Castellví Ivan , Milas-Ahic Jasminka , Visevic Roberta , Limonta Massimiliano , Rimar Doron , Couto Maura , Ribi Camillo , Marcoccia Antonella , Kahl Sarah , Hsu Vivien M , Martin Thierry , Moiseev Sergey , Chung Lorinda S , Schmeiser Tim , Majewski Dominik , Wojteczek Anna , Martínez-Barrio Julia , Khanna Dinesh , Rodrigues Ana Catarina , Riemekasten Gabriela , Santos Lelita , Levy Yair , Rezus Elena , De Araujo Daniel Brito , Talotta Rossella , Bongiovanni Sara , Brzosko Marek , Poormoghim Hadi , Mamani Marta , Kötter Ina , Cuomo Giovanna , Epis Oscar Massimiliano , Sfikakis Petros , Markus Juliana , Furst Daniel , Ramazan Ana-Maria , Scherer Hans Ulrich , Huizinga Tom W J , Lazaro Estibaliz , Lescoat Alain , Matucci-Cerinic Marco , Spierings Julia , Rudnicka Lidia , Oliveira Susana , Atzeni Fabiola , Kuwana Masataka , Mekinian Arsene , Martin Mickaël , Tanaka Yoshiya , Yasuoka Hidekata , Aznar Carmen-Pilar Simeón , Atsumi Tatsuya , Pârvu Magda , Boleto Gonçalo , Del Papa Nicoletta , Kastrati Kastriot , Shimol Jennifer Ben , Bazela-Ostromecka Anna , Selvi Enrico , Kawaguchi Yasushi , Soukup Tomas , Conde Andrea Nuñez , Geroldinger-Simic Marija , Rodríguez-Pintó Ignasi , Voigt Karen , Kubacki Torsten , Garmish Olena , Mosca Marta , Gerth Ulrich , Dzhus Marta , Ishii Tomonori , Karadag Duygu Temiz , Batalov Anastas , Ginosyan Knarik , Mukuchyan Vahan , Vardanyan Valentina , Haroyan Armine , Sokka-Isler Tuulikki , Harty Len , Geneva-Popova Mariela , Naffaa Mohammad , Maglio Cristina , Santos Cristiana Isabel Sieiro , Masato Okada , Iwata Futoshi , Hinchcliff Monique , Tharwat Samar , Cordeiro Ana , Giacomelli Roberto , Benvenuti Francesco 
Published: January 2025

Abstract

Objectives
Gastroesophageal reflux disease (GERD) is frequent in systemic sclerosis (SSc) and could predict progression of interstitial lung disease (ILD). We aimed to analyse (1) the prevalence of GERD among SSc-ILD patients, (2) its association with disease characteristics and (3) predictive factors for ILD progression in SSc-ILD patients with GERD.

Methods
SSc patients from the EUSTAR database with ILD were included. GERD was labelled as present if reflux/dysphagia was reported at the baseline visit or before. Disease characteristics of patients with and without GERD were compared at baseline. ILD progression was defined as relative FVC decline ≥10% or relative FVC decline between 5–9% in association with relative DLCO decline of ≥15% over 12 ± 3 months of follow-up. Prognostic factors for ILD progression, overall survival and progression-free survival in SSc-ILD patients with GERD were tested by multivariable Cox regression.

Results
A total of 5462 SSc-ILD patients were included, 4400 (80.6%) had GERD. Patients with GERD presented more frequently with diffuse cutaneous SSc (OR: 1.44 [1.22–1.69], P &lt; 0.001) and more severe lung involvement with lower FVC (85.8 ± 22.1 vs 90.2 ± 20.1, P &lt; 0.001), lower DLCO (60.8 ± 19.7 vs 65.3 ± 20.6, P &lt; 0.001) and worse performance at the 6-min walking test. Female sex (HR: 1.39 [1.07–1.80], P = 0.012) and older age (HR: 1.02 [1.01–1.03], P &lt; 0.001) independently predicted ILD progression in SSc-ILD patients with GERD.

Conclusion
SSc-ILD patients with GERD appear to suffer from a more severe SSc disease. In this population, female sex may be considered a risk factor for ILD progression.