AB0686 ACUTE RESPIRATORY WORSENING IN RMD-ILD IS ASSOCIATED WITH INCREASED RISK OF DEATH AND LUNG TRANSPLANTATION
Authors: P. P. Diep, M. M. Aabel, N. Moe, T. M. Aaløkken, E. Langballe, Ø. Molberg, H. Mangseth, M. L. T. Ramsli, H. Didriksen, M. Durheim, A. M. Hoffmann-Vold
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Episodes of acute respiratory worsening, termed 'acute exacerbations' (AE), are in idiopathic pulmonary fibrosis (IPF) a feared complication as approximately half of the patients die within three months of their exacerbation (1). Acute respiratory worsening may complicate the course of all interstitial lung diseases (ILD) regardless of etiology. However, only very few prospective studies exist evaluating acute respiratory worsening in ILD associated with rheumatic and musculoskeletal diseases (RMD-ILD). Importantly, for AE in ILD other than IPF no disease specific definitions exist, but very recently a definition for RMD-ILD was suggested (2). <h3>Objectives:</h3> To assess the incidence, patient characteristics, and triggers of acute respiratory worsening in RMD-ILD, and to evaluate its impact on transplant-free survival. <h3>Methods:</h3> At total of 113 RMD-ILD patients were prospectively followed at Oslo University Hospital with comprehensive assessments at baseline, 12 months, and when clinically indicated. We evaluated disease specific characteristics, lung function tests, respiratory symptoms, HRCTs and the incidence of acute respiratory worsening over the 12-month study period. Acute respiratory worsening was defined using a modified version of the recently suggested definition for AE in RMD-ILD; acute worsening or development of dyspnea with &lt; 1 month duration that could not be fully explained by cardiac failure, fluid overload or disease modifying anti-rheumatic drug (DMARD) use. HRCT was not included in the definition. We assessed variables associated with and triggers for acute respiratory worsening, defined as respiratory tract infection, use of DMARDs and gastro esophageal reflux disease (GERD) using logistic regression. The impact of acute respiratory worsening on transplant-free survival was assessed by Kaplan Meier estimates and COX regression using acute respiratory worsening as a time-dependent variable. <h3>Results:</h3> Over 12-months, we identified 49 episodes of acute respiratory worsening occurring in 33/113 (29 %) RMD-ILD patients (Table 1). While patients with MCTD-ILD did not develop any acute respiratory worsening, the incidence within the other RMDs did not significantly differ (Figure 1a). We did not identify any significant association between age, sex, RMD subtype, radiologic UIP pattern, use of DMARDSs or baseline lung function and acute respiratory worsening. Of the 49 episodes, 46 (97 %) were due to respiratory tract infections. Of the 33 patients experiencing at least one acute respiratory worsening, 18 patients (51%) had one or more acute hospitalisations due to respiratory worsening (Table 1). Among the 18 hospitalised patients, 8 had rheumatoid arthritis, 5 antisyntethase syndrome, 4 systemic sclerosis and 1 had primary Sjögren's syndrome. While respiratory tract infections was a trigger for nearly all acute respiratory worsenings, we did not identify GERD or DMARD use as triggers. An exception was the use of rituximab which was non-significantly associated with acute respiratory worsening (OR 2.07 (95 % CI 0.908, 4.716), p= 0.084). Of all, 4 (3.5%) patients underwent lung transplantation and 7 (6.2%) died over a median follow-up time of 19.2 months. Acute respiratory worsening was significantly associated with impaired transplant-free survival with HR 4.85 (95 % CI 1.40, 16.76, p= 0.013), and with 1-year survival of 77 % comparted to 98 % in patients without acute respiratory worsening (p=0.006) (Figure 1b). <h3>Conclusion:</h3> Acute respiratory worsening is a frequent complication across most RMD-ILDs and nearly always associated with respiratory tract infections. They have a major impact on survival, highlighting the importance of preventing and aggressively managing acute respiratory worsenings. <h3>REFERENCES:</h3> [1] Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, et al. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report. Am J Respir Crit Care Med. 2016;194(3):265-75. [2] Luppi F, Sebastiani M, Salvarani C, Bendstrup E, Manfredi A. Acute exacerbation of interstitial lung disease associated with rheumatic disease. Nat Rev Rheumatol. 2022;18(2):85-96. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Phuong Phuong Diep Boehringer-Ingelheim, Yes (to my institution): Boehringer-Ingelheim, Magdalena Maria Aabel: None declared, Natasha Moe: None declared, Trond M Aaløkken: None declared, Emily Langballe Boehringer-Ingelheim, Øyvind Molberg: None declared, Henrik Mangseth: None declared, Mona Lovise Talaro Ramsli: None declared, Henriette Didriksen: None declared, Michael Durheim AstraZeneca and Pfizer, Yes (to my institution): Roche and Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Boehringer-Ingelheim, Boehringer Ingelheim, Janssen, Medscape, Merck Sharp &amp; Dohme, Novartis and Roche, ARXX, BMS, Boehringer Ingelheim, Genentech, Janssen, Medscape, Merck Sharp &amp; Dohme and Roche, Boehringer Ingelheim, Janssen.