Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management

Kadura, S.; Raghu, Ganesh

doi:10.1183/16000617.0011-2021

Cited by 155 publications

(158 citation statements)

References 143 publications

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“…Disease-modifying anti-rheumatic drugs (DMARDs), such as corticosteroids, conventional DMARDs (e.g. MTX), biologic drugs and targeted synthetic DMARDs, may increase the risk of infection and drug-induced lung injury [ 3 ]. Joint surgery can result in ventilator-induced lung injury if performed under general anaesthesia and with a ventilator.…”

Section: Discussionmentioning

confidence: 99%

“…Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that predominantly affects the joints [ 1 , 2 ]. Interstitial lung disease (ILD) is a frequent extra-articular manifestation in RA patients and is linked to morbidity and mortality [ 3 ]. According to recent research, although overall RA-related mortality has reduced, RA-ILD mortality has not, indicating that enhanced RA care may have resulted in better overall outcomes but has limited therapeutic effect for the RA-ILD subgroup [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model

et al. 2022

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Background Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), like those with idiopathic pulmonary fibrosis (IPF), might develop an unexpected acute exacerbation (AE)—a rapidly progressing and deadly respiratory decline. Although AE incidence and risk factors in RA-ILD patients are known, their post-AE clinical course remains unknown owing to the rarity of AE-RA-ILD. This multicentre retrospective study evaluated post-AE mortality and prognostic variables in AE-RA-ILD patients and created a mortality prediction model for AE-RA-ILD. Methods This research comprised 58 patients with AE-RA-ILD and 96 with AE-IPF (a control disease). Multivariate Cox regression analysis was performed to identify prognostic variables. A prediction model was created with recursive partitioning (decision tree). Results The post-AE 90-day mortality rate in the overall AE-RA-ILD group was 48.3%; percent predicted forced vital capacity within 12 months before AE onset (baseline %FVC) and PaO2/FiO2 ratio at AE onset (P/F at AE) were independent predictors of mortality. Post-AE 90-day mortality rates were 40.6% and 43.8%, respectively, in AE-RA-ILD and AE-IPF patients propensity score-matched for age, sex, baseline %FVC and P/F at AE (P = 1.0000). In AE-RA-ILD patients, C-indices of baseline %FVC and P/F at AE to predict post-AE 90-day mortality were 0.604 and 0.623, respectively. A decision tree model based on these prognostic factors classified AE-RA-ILD patients into mild, moderate and severe groups (post-AE 90-day mortality rates: 20.8%, 64.0% and 88.9%, respectively; P = 0.0002); the C-index improved to 0.775. Conclusions Post-AE mortality was high in AE-RA-ILD patients similar to AE-IPF patients. The discovered prognostic factors and our mortality prediction model may aid in the management of AE-RA-ILD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model

et al. 2022

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“…Interstitial lung disease is often associated with rheumatic diseases. Its early diagnosis and management are not only difficult, but also crucial, because it is associated with major morbidity and mortality and can be the first cause of death in ARDs (7)(8)(9)(10)(11)(12)(13). We, therefore, aimed to measure consensus between specialists who can be involved in its management: this is one of the very first studies to address consensus between pulmonologists, rheumatologists, and radiologists.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a recent international consensus statement proposed "interstitial pneumonia with autoimmune features" as a new definition for ILD underlined by systemic autoimmune condition and not classifiable as any definite CTD, emphasizing the relationship between ILD and autoimmune response (5,6). In patients with rheumatic diseases, ILD is difficult to diagnose at an early stage, and can be associated with major morbidity and mortality, or even be the leading cause of death (7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Interstitial Lung Disease Associated With Autoimmune Rheumatic Diseases: Checklists for Clinical Practice

Bosello

Beretta

Papa³

et al. 2021

Front. Med.

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Background: Interstitial lung diseases (ILDs) are often associated with rheumatic diseases. Their early diagnosis and management are not only difficult, but also crucial, because they are associated with major morbidity and mortality and can be the first cause of death in autoimmune rheumatic diseases (ARDs).Objectives: By using methodologies, such as Nominal Group Technique (NGT) and Delphi Survey, the aims of this study were (1) to measure consensus between pulmonologists, radiologists, and rheumatologists experienced in the management of ARD-ILD; (2) to highlight the importance of a multidisciplinary approach; and (3) to provide clinicians with a practical tool aimed at improving the prompt recognition and follow-up of ILD associated with ARDs and of any possible rheumatic conditions underlying ILD.Results: During the NGT round, the Steering Committee defined 57 statements to be used in the Delphi survey. A total of 78 experts participated in the Delphi survey, namely 28 pulmonologists, 33 rheumatologists, and 17 radiologists. During this round, consensus on agreement was reached in 47 statements, while disagreement was not reached in any statements. A secondary questionnaire was drafted by the Steering Committee to obtain clearer indications on ILD-ARD “red-flags” and follow-up. Delphi Panelists took part also in the second-questionnaire survey. Answers from both surveys were used to draft two checklists of “red flags” sign or symptom suggestive of ILD and ARD, respectively, and two checklists on identification and monitoring of rheumatoid arthritis (RA) and systemic sclerosis (SSc) ILD.Limitations: This study is a consensus work, which cannot produce empiric data, and is limited to the Italian scenario.Conclusions: This work showed a high level of agreement, but also shows some divergent opinions between different experts. This underlines the importance of a multidisciplinary approach. Eventually, we believe the drafted checklists can help clinicians in the diagnosis and follow-up of ILD-ARD.

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“…This finding allowed concluding that anti-MCV antibodies titers may work as an indicator correlating the disease activity and patient outcome [ 170 ]. Also, an attempt was made to characterize the etiology of rheumatoid arthritis from lung level (NCT03832374), as it was found that diffuse interstitial pneumopathy and bronchial dysfunctions occur in one-third of RA patients, and that some subtypes of ACPAs are preferentially present in the lungs [ 171 ]. This study (NCT03832374), still ongoing, addresses a very important question regarding the subtype(s) of ACPAs with a preferential tropism for the lung, that might be responsible for the infection within parenchyma and pulmonary airways, and the overall increased morbidity and mortality among RA patients with lung co-morbidities.…”

Section: Diagnostic and Therapeutic Potential Of Citrullinationmentioning

confidence: 99%

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Ciesielski

Biesiekierska

Panthu

et al. 2022

Cell. Mol. Life Sci.

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Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed.

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Rheumatoid arthritis-interstitial lung disease: manifestations and current concepts in pathogenesis and management

Cited by 155 publications

References 143 publications

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model

Interstitial Lung Disease Associated With Autoimmune Rheumatic Diseases: Checklists for Clinical Practice

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

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