OP0174 SUBCLINICAL INTERSTITIAL LUNG DISEASE IS FREQUENT AND PROGRESSES ACROSS DIFFERENT CONNECTIVE TISSUE DISEASES
Authors: A. M. Hoffmann-Vold, H. Andersson, S. Reiseter, H. Fretheim, I. Barua, T. Garen, Ø. Midtvedt, R. Gunnarsson, M. Durheim, T. M. Aaløkken, Ø. Molberg
Journal: Annals of the Rheumatic Diseases (2021)

Background: Based on the argument that symptoms define disease, physicians commonly apply the terms “preclinical” or “subclinical” disease to describe patients with disease-related findings but no accompanying symptoms for connective tissue disease associated interstitial lung disease (CTD-ILD). The term subclinical frequently applies to patients with mild ILD changes on high resolution chest tomography (HRCT), normal forced vital capacity (FVC), and without respiratory symptoms. Previous work in systemic sclerosis (SSc)-ILD did show that patients with even minor extent of ILD at baseline often progressed and had increased mortality risk, suggesting that it is not appropriate to define these patients as “subclinical.” Objectives: To identify the prevalence of subclinical ILD across CTD diagnoses, and assess the rate of progression of lung fibrosis compared to CTD without ILD and with clinical ILD. Methods: All CTD patients, including SSc, anti-synthetase syndrome (ASS) and mixed connective tissue disease (MCTD) from the Oslo University Hospital diagnosed before 2015 and assessed for the presence of ILD by HRCT were included. The year 2015 was chosen to secure an observation time of at least five years from ILD diagnosis to study end on 01.01.2021 or time of death. All patients fulfilled the respective CTD classification criteria. Subclinical ILD was defined as an ILD extent &lt;5% by semi-quantitative assessment of baseline HRCT, preserved lung function with FVC &gt;80% predicted and without respiratory symptoms. Clinical ILD was defined as &gt;5% extent of ILD or &lt;5% extent of ILD on HRCT with respiratory symtoms or FVC&lt;80%. The outcome was ILD progression, defined as increasing extent of ILD from basline to follow-up HRCT by semi-quantitative assessment. Vital status was available in all patients and mortality was evaluated. Descriptive statistical analyses were conducted and time to ILD progression determined by Kaplan-Meier estimates. Results: We identified 525 CTD patients, including 296 with SSc, 135 with MCTD and 94 with ASS who had conducted a baseline HRCT. Of these, 227 (43%) had no ILD, 67 (13%) subclinical and 231 (44%) clinical ILD (Table). Of the 67 subclinical ILD patients, 45 (15%) had SSc, 13 (10%) MCTD and 9 (10%) ASS of thespecific cohorts. Over a median time of 4.5 years between baseline and follow-up HRCT, 95/395 (24%) showed progression of ILD, including 72 (26%) SSc and 23 (19%) MCTD patients. Disease progression frequently occurred in both subclinical ILD (38%) and clinical ILD (51%) patients (Figure). Age, gender, underlying CTD, and baseline lung function were not predictive for the progression of lung fibrosis. Progression was too infrequent to allow for meaningful multivariable regression analyses. After a median observation period of 12 years, 153 (29%) of the patients died. The 1-, 5- and 10-year survival rates in those without ILD, subclinical and clinical ILD were 97%/97%/99%, 88%/91%/82%, and 82%/85%/68% (p&lt;0.001), respectively. Table 1. Clinical characteristics, demographics and outcome No ILD (n=227 ) Subclinical ILD (n=67 ) Clinical ILD (n=231 ) Age, y (SD) 50 (15.4) 51 (14.4) 52 (15.3) Male sex, n (%) 89 (39) 22 (33) 111 (48) Deceased, n (%) 50 (22) 12 (18) 91 (39) Observation period, y median (range) 13.7 (18.6) 13.9 (17.9) 11.5 (17.1) FVC% (SD) 97 (18.6) 99 (17.9) 81 (20.9) FVC decline% (SD) -0.70 (11.1) -0.81 (16.5) -1.61 (15.9) DLCO% (SD) 73 (19.4) 73 (16.9) 55 (17.4) Extent of ILD% (SD) 0 (0) 2.3 (1.5) 19.3 (16.8) ILD progression% (SD) 0.08 (1.0) 3.1 (6.2) 3.6 (9.9) ILD progressors, n (%) 3 (2) 20 (38) 72 (51) Figure 1. Time to ILD progression in CTD without ILD, with subclinical and clinical ILD Conclusion: Subclinical ILD is frequently present across CTDs and progresses over time in a substantial subgroup of patients, comparable to patients with clinical ILD. Our findings question the terms sub- and preclinical ILD, which may potentially lead to a suboptimal “watchful waiting management strategy”. Monitoring all CTD patients with any ILD is of high importance to identify disease progression early. Disclosure of Interests: Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Roche, Merck Sharp &amp; Dohme, Lilly and Medscape, Consultant of: Actelion, Boehringer Ingelheim, Bayer, ARXX, and Medscape, Grant/research support from: Boehringer Ingelheim, Helena Andersson: None declared, Silje Reiseter: None declared, Håvard Fretheim Consultant of: Actelion, Bayer., Imon Barua: None declared, Torhild Garen: None declared, Øyvind Midtvedt: None declared, Ragnar Gunnarsson: None declared, Mike Durheim Speakers bureau: Boehringer Ingelheim and Roche, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim, Trond M Aaløkken: None declared, Øyvind Molberg: None declared