A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality

Hyldgaard, Charlotte; Hilberg, Ole; Pedersen, Alma B; Ulrichsen, Sinna Pilgaard; Løkke, Anders; Bendstrup, Elisabeth; Ellingsen, Torkell

doi:10.1136/annrheumdis-2017-211138

Cited by 326 publications

(247 citation statements)

References 44 publications

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“…This also suggests that articular and pulmonary inflammation may be intrinsically related (28,29). Similar to results of previous studies (1,2,4,13,(30)(31)(32)(33), we observed high mortality rates in patients who developed RA-ILD. More than one-third of patients with RA-ILD died by the end of the follow-up period.…”

Section: Discussionsupporting

confidence: 90%

Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis–Associated Interstitial Lung Disease: A Prospective Cohort Study

Sparks

Huang

et al. 2019

Arthritis & Rheumatology

152

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Objective To evaluate rheumatoid arthritis (RA) disease activity and risk of RA‐associated interstitial lung disease (RA‐ILD). Methods We investigated disease activity and risk of RA‐ILD using the Brigham RA Sequential Study (BRASS, 2003–2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA‐ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA‐ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA‐ILD, using annually updated DAS28 data, with adjustment for known RA‐ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules. Results Among 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA‐ILD during a mean ± SD follow‐up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28–3.82) for RA‐ILD compared to the remission/low disease activity group. Risk of RA‐ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61–3.28) for low disease activity, 2.08 (95% CI 1.06–4.05) for moderate disease activity, and 3.48 (95% CI 1.64–7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA‐ILD increased by 35% (95% CI 14–60%). Results were similar in analyses that included follow‐up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules. Conclusion Active articular RA was associated with an increased risk of developing RA‐ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA‐ILD development.

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Section: Discussionsupporting

confidence: 90%

Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis–Associated Interstitial Lung Disease: A Prospective Cohort Study

Sparks

Huang

et al. 2019

Arthritis & Rheumatology

152

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“…Under the age of 75 years, incidence rates of RA are up to four times higher in women than men. Fibrosing ILD, the most common pulmonary manifestation of disease (occurring in ∼10% of patients), is a major cause of morbidity and mortality in patients with RA and in some cases can be the first symptom of RA [49,[59][60][61]. RA-ILD is believed to be caused by chronic immune activation and inflammation, which stimulates fibroproliferation in the lung parenchyma of genetically susceptible individuals.…”

Section: Ctd-ildmentioning

confidence: 99%

Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases

et al. 2018

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@ERSpublicationsOther chronic ILDs with a progressive-fibrosing phenotype may have a clinical course similar to IPF. Although challenging, identification of these patients is crucial, and requires a multidisciplinary approach, to ensure optimal diagnosis and management.ABSTRACT Although these conditions are rare, a proportion of patients with interstitial lung diseases (ILDs) may develop a progressive-fibrosing phenotype. Progressive fibrosis is associated with worsening respiratory symptoms, lung function decline, limited response to immunomodulatory therapies, decreased quality of life and, potentially, early death. Idiopathic pulmonary fibrosis may be regarded as a model for other progressive-fibrosing ILDs. Here we focus on other ILDs that may present a progressive-fibrosing phenotype, namely idiopathic nonspecific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, connective tissue disease-associated ILDs (e.g. rheumatoid arthritis-related ILD), fibrotic chronic hypersensitivity pneumonitis, fibrotic chronic sarcoidosis and ILDs related to other occupational exposures. Differential diagnosis of these ILDs can be challenging, and requires detailed consideration of clinical, radiological and histopathological features. Accurate and early diagnosis is crucial to ensure that patients are treated optimally.

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“…In some cases, lung manifestations may precede the diagnosis of RA. Patients with idiopathic interstitial lung disease should be observed prospectively for signs of systemic disease [3,67,68]. Differential diagnostic considerations should also be part of the follow up and not only of the initial diagnostic work up.…”

Section: Differential Diagnosismentioning

confidence: 99%

“…The lung is a common site of extra-articular disease. Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most feared manifestations and causes serious morbidity and increased mortality [1][2][3]. Rheumatoid arthritis is the most common of the connective tissue diseases, and a substantial number of patients with RA will consult general practitioners, rheumatologists, and pulmonologists with respiratory symptoms which, in some cases, may be caused by ILD.…”

Section: Introductionmentioning

confidence: 99%

Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians

Bendstrup

Møller

Kronborg-White

et al. 2019

JCM

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Interstitial lung disease (ILD) is a serious complication of rheumatoid arthritis (RA) contributing to significantly increased morbidity and mortality. Other respiratory complications, such as chronic obstructive pulmonary disease and bronchiectasis, are frequent in RA. Infections and drug toxicity are important differential diagnoses and should be considered in the diagnostic work-up of patients with RA presenting with respiratory symptoms. This review provides an overview of the epidemiology and pathogenesis of RA-ILD, the radiological and histopathological characteristics of the disease as well as the current and future treatment options. Currently, there is no available evidence-based therapy for RA-ILD, and immunosuppressants are the mainstay of therapy. Ongoing studies are exploring the role of antifibrotic therapy in patients with progressive fibrotic ILD, which may lead to a new treatment approach for subgroups of patients with RA-ILD.

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A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality

Abstract: ILD is a serious complication in RA, with a significantly increased mortality compared with a large matched cohort of RA comparisons without ILD.

Cited by 326 publications

References 44 publications

Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis–Associated Interstitial Lung Disease: A Prospective Cohort Study

Rheumatoid Arthritis Disease Activity Predicting Incident Clinically Apparent Rheumatoid Arthritis–Associated Interstitial Lung Disease: A Prospective Cohort Study

Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases

Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians

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