Impact of the pattern of interstitial lung disease on mortality in rheumatoid arthritis: A systematic literature review and meta-analysis.

An important extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD). The relationship between the usual interstitial pneumonia (UIP) pattern and mortality in patients with RA is unclear. The purpose of this study was to complete a systematic literature review and meta-analysis on the association between RA-ILD pattern and mortality risk. We performed a systematic literature review through December 12, 2018. Study characteristics, unadjusted and adjusted relative risks (RR) of mortality for ILD pattern were extracted from the identified studies and quality assessments were performed. RR for mortality (RA-UIP vs. other RA-ILD) was pooled using inverse variance weighting and random effects models. Ten retrospective cohort studies met our eligibility criteria. A total of 1256 RA-ILD patients were included with 484 total deaths. Meta-analysis yielded a pooled RR of 1.66 (95% confidence interval1.07 to 2.56) for death among those with UIP RA-ILD compared with other patterns. In sub-group analysis when pooling studies comparing UIP to NSIP pattern of RA-ILD, the RR was 2.39 (95% CI 0.86-6.68). Through a systematic literature review and meta-analysis, we found UIP pattern to be associated with a higher mortality risk in RA-ILD compared to other patterns of RA-ILD although more recent studies emphasize the importance of pulmonary physiology and the extent of lung involvement as significant predictors of mortality rather than the pattern of RA-ILD. Recognizing the small number of studies satisfying eligibility and inconsistent accounting for confounders, further study of mortality risk in RA-ILD is needed with standardized assessment of various RA, ILD, and patient-related factors.

Singh N ，Varghese J ，England BR ，Solomon JJ ，Michaud K ，Mikuls TR ，Healy HS ，Kimpston EM ，Schweizer ML ... -  《-》

Factors associated with mortality in rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

Interstitial lung disease (ILD) is a common and potentially life-threatening complication for rheumatoid arthritis (RA) patients. However, there is a lack of clear prognostic factors in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) patients. The purpose of this study was to complete a systematic review and meta-analysis of the factors associated with mortality in RA-ILD patients. Medline, EMBASE and the Cochrane Library were searched up to September 1, 2020. The Newcastle-Ottawa Scale (NOS) was applied to assess the methodological quality of the eligible studies. Study characteristics and magnitude of effect sizes were extracted. Then, pooled hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) and pooled risk ratios (RRs) with 95% CIs were calculated to assess the factors associated with mortality in RA-ILD. Twenty-three of 3463 articles were eligible, and ten factors associated with mortality for RA-ILD were evaluated in the meta-analysis. Older age (HRs = 1.04, 95% CI 1.03-1.05), male sex (HRs = 1.44, 95% CI 1.21-1.73), having a smoking history (HRs = 1.42, 95% CI 1.03-1.96), lower diffusing capacity of the lung for carbon monoxide (DLCO)% predicted (HRs = 0.98, 95% CI 0.97-1.00), forced vital capacity (FVC)% predicted (HRs = 0.99, 95% CI 0.98-1.00), composite physiological index (CPI) (HRs = 1.04, 95% CI 1.02-1.06), usual interstitial pneumonia (UIP) pattern on HRCT (HRs = 1.88, 95% CI 1.14-3.10 and RRs = 1.90, 95% CI 1.50-2.39), emphysema presence (HRs = 2.31, 95% CI 1.58-3.39), and acute exacerbation of ILD (HRs = 2.70, 95% CI 1.67-4.36) were associated with increased mortality in RA-ILD, whereas rheumatoid factor (RF) positive status was not associated. Through this systematic review and meta-analysis, we found that older age, male sex, smoking history, higher CPI, lower DLCO% predicted, lower FVC% predicted, UIP pattern on HRCT, emphysema presence and acute exacerbation of ILD were associated with an increased risk of mortality in RA-ILD.

Qiu M ，Jiang J ，Nian X ，Wang Y ，Yu P ，Song J ，Zou S ... -  《RESPIRATORY RESEARCH》

Related factors, increased mortality and causes of death in patients with rheumatoid arthritis-associated interstitial lung disease.

Kakutani T ，Hashimoto A ，Tominaga A ，Kodama K ，Nogi S ，Tsuno H ，Ogihara H ，Nunokawa T ，Komiya A ，Furukawa H ，Tohma S ，Matsui T ... -  《-》

Incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

Acute exacerbation (AE) is a devastating complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and leads to high mortality. This study aimed to investigate the incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease (AE-RA-ILD). PubMed, EMBASE, Web of Science, and Medline were searched through 8 February 2023. Two independent researchers selected eligible articles and extracted available data. The Newcastle Ottawa Scale was used to assess the methodological quality of studies used for meta-analysis. The incidence and prognosis of AE-RA-ILD were investigated. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) and pooled odds ratios (ORs) with 95% CIs were calculated to explore the risk factors of AE in RA-ILD. Twenty-one of 1,589 articles were eligible. A total of 385 patients with AE-RA-ILD, of whom 53.5% were male, were included. The frequency of AE in patients with RA-ILD ranged from 6.3 to 55.6%. The 1-year and 5-year AE incidences were 2.6-11.1% and 11-29.4%, respectively. The all-cause mortality rate of AE-RA-ILD was 12.6-27.9% at 30 days and 16.7-48.3% at 90 days. Age at RA diagnosis (WMD: 3.61, 95% CI: 0.22-7.01), male sex (OR: 1.60, 95% CI:1.16-2.21), smoking (OR: 1.50, 95% CI: 1.08-2.08), lower forced vital capacity predicted (FVC%; WMD: -8.63, 95% CI: -14.68 to - 2.58), and definite usual interstitial pneumonia (UIP) pattern (OR: 1.92, 95% CI: 1.15-3.22) were the risk factors of AE-RA-ILD. Moreover, the use of corticosteroids, methotrexate, and biological disease-modifying anti-rheumatic drugs, was not associated with AE-RA-ILD. AE-RA-ILD was not rare and had a poor prognosis. Age at RA diagnosis, male sex, smoking, lower FVC%, and definite UIP pattern increased the risk of AE-RA-ILD. The use of medications, especially methotrexate and biological disease-modifying anti-rheumatic drugs, may not be related to AE-RA-ILD. CRD42023396772.

Xie M ，Zhu C ，Ye Y 《BMC Pulmonary Medicine》

Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD.

O'Dwyer DN ，Armstrong ME ，Cooke G ，Dodd JD ，Veale DJ ，Donnelly SC ... -  《-》