Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicenter prospective cohort of smokers
Authors: McDermott Gregory C , Hayashi Keigo , Yoshida Kazuki , Moll Matthew , Cho Michael H , Doyle Tracy J , Kinney Gregory L , Dellaripa Paul F , Putman Rachel K , Jose Estepar Raul San , Hata Akinori , Hino Takuya , Hida Tomoyuki , Yanagawa Masahiro , Nishino Mizuki , Washko George , Regan Elizabeth , Hatabu Hiroto , Hunninghake Gary M , Silverman Edwin K , Sparks Jeffrey A 
Published: December 2022

ABSTRACTObjectivesInvestigate the prevalence and mortality impact of interstitial lung abnormalities (ILA) in rheumatoid arthritis (RA) and non-RA comparators.MethodsWe analyzed associations between ILA, RA, and mortality in COPDGene, a multicenter prospective cohort study of current or former smokers, excluding known interstitial lung disease (ILD) or bronchiectasis. All participants had research chest high-resolution computed tomography (HRCT) reviewed by a sequential reading method to classify ILA as present, indeterminate, or absent as well as fibrotic or nonfibrotic ILA subtype. RA cases were identified by self-report RA and DMARD use; non-RA comparators had neither an RA diagnosis nor used DMARDs. We examined the association and mortality risk of RA and ILA using multivariable logistic regression and Cox regression.ResultsWe identified 83 RA cases and 8725 non-RA comparators with HRCT performed for research purposes. ILA prevalence was 16.9% in RA cases and 5.0% in non-RA comparators. After adjusting for potential confounders including genetics, smoking, and other lifestyle factors, ILA were more common among those with RA compared to non-RA (OR 4.76 95%CI 2.54 to 8.92). RA with ILA or indeterminate for ILA was associated with higher mortality compared to non-RA without ILA (HR 3.16, 95%CI 2.11 to 4.74) and RA cases without ILA (HR 3.02, 95%CI 1.36 to 6.75).ConclusionsRA was associated with ILA and this persisted after adjustment for smoking and genetic/lifestyle risk factors. RA with ILA in chronic heavy smokers had 3-fold increased mortality, emphasizing the importance of further screening and treatment strategies for subclinical ILD in RA.KEY MESSAGESWhat is already known on this topicUp to a third of patients with rheumatoid arthritis (RA) may have evidence of subclinical interstitial lung abnormalities on computed tomography (CT) scans of the chest.Cigarette smoking and theMUC5Bpromoter variant are known risk factors for RA-associated interstitial lung disease.What this study addsWe found that 17% of RA patients had subclinical interstitial lung abnormalities. RA had 4-fold higher odds of interstitial lung abnormalities than non-RA comparators, adjusted for smoking, theMUC5Bpromoter variant, and other factors.Participants with RA and no interstitial lung abnormalities were not at increased mortality risk while those with interstitial lung abnormalities or indeterminate for ILA had a three-fold increased risk of mortality compared to RA and non-RA patients without interstitial lung abnormalities.How this study might affect research, practice or policyThe presence of subclinical interstitial lung abnormalities confers significant mortality risk in RA and emphasizes the need to establish the clinical utility of screening, prevention, and treatment strategies targeting subclinical lung disease.