Rheumatoid Arthritis-associated Lung Disease Research Articles

A novel humanized model of rheumatoid arthritis associated lung disease

Cigarette smoking has been implicated in the pathogenesis of seropositive rheumatoid arthritis (RA), as well as RA-associated lung disease. Fibrotic interstitial lung disease as well as emphysema occur in RA and cause substantial morbidity. We used arthritis-susceptible HLA-DQ8 transgenic mice to generate RA-associated lung disease. Mice were exposed to cigarette smoke (CS) prior to induction of arthritis, and subsequently injected with a low dose of bleomycin intra-tracheally to induce lung injury. Exposure of arthritic mice to both CS and bleomycin led to a significant reduction in lung compliance consistent with development of diffuse lung disease. Morphologic evaluation of the lung demonstrated areas of emphysematous change and co-existent fibrosis, consistent with a combined pattern of fibrosis and emphysema. These changes were accompanied by inflammatory cell infiltration and upregulation of fibrosis-associated genes. This humanized mouse model can serve as a valuable research tool to understand the pathogenesis of RA associated lung disease.

Predictors of mortality in rheumatoid arthritis-associated lung disease: A retrospective study on ten years.

Rheumatoid arthritis (RA)-associated lung involvement is a cause of mortality. This study aimed to evaluate mortality rate and mortality-associated factors in RA patients with high-resolution computed tomography (HRCT)-proven lung involvement. Patients followed-up for RA between 2010 and 2018 were evaluated regarding HRCT-proven lung involvement. The present study was designed as a single-centre, retrospective and descriptive study. The HRCT reports of patients were re-evaluated for three major patterns: UIP, nonspecific interstitial pneumonia (NSIP), and isolated airway disease (AD). Mortality rates and its associated factors (demographic characteristics, RA-related factors and lung-involvement-related factors) were determined. The study included 156 patients (females, 68.3%) with radiologically confirmed RA-associated lung disease. The mean age was 55.5 (12.1) years at RA diagnosis and 62.7 (9.7) years at the diagnosis of lung involvement. The patterns of lung involvement on HRCT were UIP in 89 (57.0%) patients, NSIP in 51 (32.7%) patients, and isolated AD in 16 (10.3%) patients. The RA patients were followed-up for a mean of 10.2 (7.4) years and they were followed-up for a mean of 4.5 (3.7) years after interstitial lung disease (ILD) diagnosis. Overall, 40 (25.6%) patients died. The 5-year survival rate was 78%. Multivariate analysis revealed UIP pattern (log-rank test, P<0.01), pleural effusion (log-rank test, P<0.05), and a shorter time interval (<3 years) between the diagnoses of RA and RA-ILD (log-rank test, P<0.01) to be independent predictors of mortality. In addition to the UIP, a known risk factor, pleural effusion and the short time between the diagnoses of RA and ILD were also found to be associated with mortality.

Rheumatoid arthritis-associated lung disease in black Africans: Descriptive study of 28 cases in Lomé.

Background Several studies have shown that lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA). Objectives To describe the lung manifestations in the RA population in Lomé, Togo. Methods The study was conducted from October 2018 to July 2019 at the pulmonology unit of the Sylvanus Olympio University teaching hospital, in collaboration with rheumatology centres in Lomé, Togo. Patients meeting the American College of Rheumatology criteria for RA were prospectively enrolled. They underwent clinical examination, spirometry, a 6-minute walk test (6MWT) and a chest X-ray (CXR). All information collected and surveys gathered were subjected to statistical analysis. Results Twenty-four out of 28 patients were women (85.7%). The mean (standard deviation (SD)) duration of illness was 4.1 (2.8) years. Thirteen patients out of 28 (46.4%) had respiratory symptoms. On CXR, interstitial lung disease was the only pleuropulmonary lesion (17.8%). Spirometry was abnormal in 25% of cases, with a predominance of restrictive ventilatory disorder (21.4%). The 6MWT was abnormal in 25% of patients. A total of 20 patients (71.4%) had at least one lung manifestation. We noted that there were significantly more patients with respiratory symptoms and no radiographical abnormalities than those with both respiratory symptoms and radiographical abnormalities (p=0.013). Conclusion Lung changes affect a significant proportion of RA patients in Lomé. Studies conducted with appropriate respiratory investigations and combining cardiovascular explorations will bring us closer to an understanding of the effects of RA-associated lung disease.

THU0131 LOCALISATION OF RHEUMATOID LUNG NODULES IN PATIENTS WITH RHEUMATOID ARTHRITIS-RELATED INTERSTITIAL LUNG DISEASE: RIGHT OR LEFT?

Background: The frequency of pulmonary rheumatoid nodules closely relates to the diagnostic modality and changes from Objectives: The aim of this study was to describe the general features and localisation of pulmonary rheumatoid nodules in RA-ILD patients followed up in a single tertiary center. Methods: During January 2010 and March 2019, 826 RA patients had lung computerized tomography (CT) in Hacettepe University. Three radiologists re-evaluated lung CTs and 156/826 (18.8%) patients with had RA-ILD. Pulmonary nodules suggesting pulmonary rheumatoid nodules were identified by radiologist from lung CTs. In addition to demographic, clinical and laboratory data; number of the pulmonary rheumatoid nodules, size and localisation of the biggest nodule – named as dominant nodule-, type of ILD (UIP, NSIP and isolated airway disease (AD)) were recorded. p value less than 0.05 was considered as statistically significant. Results: Of 156 patients, 68 (26, 38.2% male) patients (43.5%) had at least one pulmonary rheumatoid nodule. The mean (SD) follow-up duration was 167 (88) months for RA, and 72 (46) months for RA-ILD. Thirty patients had UIP (44.1%), 31 (45.6%) had NSIP and 7 (10.3%) had AD pattern. 35 (51.5%) of patients had exposed smoking (current or past). Rheumatoid factor and anti-CCP were positive in 60/68 (88.2%) and 33/45 (73.3%) patients, respectively. Median number of nodules was 3 (2-3). Median size of the dominant nodule was 6.8 (5.0-11.5) mm. While 41 (60.3%) of dominant nodules localised in right lung, 27 (39.7%) of dominant nodules localised in left lung (p=0.09). In addition, right inferior lobe (21, 39.9%) was the most common localisation and right middle lobe (7, 10.3%) was the least common localisation of dominant nodule (Figure 1). Conclusion: We found a high prevalence of pulmonary rheumatoid nodules in RA-ILD patients and right inferior lobe was the most common localization of dominant nodules. Prospective studies are needed to determine how the presence and localization of pulmonary rheumatoid nodules affect the RA-ILD disease process.

Biomarkers for rheumatoid arthritis associated lung disease

Biomarkers for rheumatoid arthritis associated lung disease

Profibrotic effect of IL-17A and elevated IL-17RA in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated lung disease support a direct role for IL-17A/IL-17RA in human fibrotic interstitial lung disease.

Interleukin (IL)-17 is a T helper 17 cytokine implicated in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Although IL-17A has a well-established role in murine pulmonary fibrosis models, its role in the tissue remodeling and fibrosis occurring in idiopathic pulmonary fibrosis (IPF) and RA-associated interstitial lung disease (RA-ILD) is not very well defined. To address this question, we utilized complimentary studies to determine responsiveness of human normal and pathogenic lung fibroblasts to IL-17A and used lung biopsies acquired from patients with IPF and RA-ILD to determine IL-17A receptor (IL-17RA) expression. Both normal and pathogenic IPF lung fibroblasts express functional IL-17RA and respond to IL-17A stimulation with cell proliferation, generation of extracellular matrix (ECM) proteins, and induction of myofibroblast transdifferentiation. Small interfering RNA (siRNA) silencing of IL-17RA attenuated this fibroblast response to IL-17A on ECM production. These fibroblast responses to IL-17A are dependent on NF-κB-mediated signaling. In addition, inhibiting Janus activated kinase (JAK) 2 by either siRNA or a selective pharmacological inhibitor, AZD1480-but not a JAK1/JAK3 selective inhibitor, tofacitinib-also significantly reduced this IL-17A-induced fibrogenic response. Lung biopsies of RA-ILD patients demonstrate significantly higher IL-17RA expression in areas of fibroblast accumulation and fibrosis, compared with either IPF or normal lung tissue. These observations support a direct role for IL-17A in lung fibrosis that may be particularly relevant in the context of RA-ILD.

Clinical Characteristics of Rheumatoid Arthritis-Associated Lung Disease: A Retrospective Study in a Tertiary Referral Center in Taiwan

目的：探討類風濕性關節炎合併肺部疾病患者的臨床特徵。方法：我們回顧性分析了2016年8月至2018年6月期間曾規則接受生物製劑治療的261名類風濕性關節炎患者，並收集了臨床特徵，血清學數據和影像學特徵。類風濕性關節炎相關肺病包括肺實質疾病（間質性肺病，ILD）和氣道疾病（支氣管擴張或閉塞性細支氣管炎），影像由一名風濕病醫師和一名胸腔科醫師依據2013年特發性間質性肺炎（IIP）分類標準而鑑定分類。我們比較類風濕性關節炎有無合併肺病的兩組之間的臨床特徵。結果：在261名類風濕性關節炎患者中，有37例（14.1%）具有類風濕性關節炎相關肺病。與沒有肺病的患者相比，在類風濕性關節炎相關肺病患者中觀察到發病年齡較大，抽菸比例較高，抗環瓜氨酸肽（CCP）抗體陽性率較高（p值＜0.05），且該病患族群的紅血球沉降率（ESR），類風濕因子和抗CCP抗體的最高值也顯著較高（p值＜0.05）。結論：對於具有較高RF或抗CCP抗體的老年吸菸RA患者，應特別留意篩查肺部病變。

Rheumatoid arthritis-associated lung disease.

Comprehensive, up-to-date review of RA-associated lung diseases including pathogenesis and managementhttp://ow.ly/FBaNZ

Thin-section CT findings in rheumatoid arthritis-associated lung disease: CT patterns and their courses.

The purpose of this study was to describe the long-term follow-up CT evaluation in rheumatoid arthritis (RA)-associated lung disease. Thin-section CT scans from 29 patients with RA and suspected associated lung disease were reviewed. Twenty-two patients underwent sequential CT evaluation during 3 to 108 months of follow-up (mean 28 months). Histologic comfirmation of pulmonary involvement was available in 19 patients. Three major patterns were identified: reticulation with or without honey-combing (n = 19), centrilobular branching lines with or without bronchial dilatation (n = 5), and consolidation (n = 5). Reticulation and centrilobular branching lines corresponded to usual interstitial pneumonia (n = 14) and bronchiolitis obliterans (n = 1), respectively. Consolidation corresponded to bronchiolitis obliterans organizing pneumonia (BOOP; n = 3) and coexistent chronic eosinophilic pneumonia (CEP) and BOOP (n = 1). Patients with reticulation had rapid deterioration when there was new appearance of multifocal areas of ground-glass attenuation. Centrilobular branching lines progressed to bronchiectasis in one case. There was mild progression of existing bronchiectasis associated with centrilobular branching lines in one case. Area of consolidation in two patients with BOOP and one with coexistent CEP and BOOP evolved into honeycombing at serial CT. Thin-section CT is a noninvasive technique for monitoring disease morphology in RA-associated lung disease. Initial CT findings and their evolution on sequential examinations may be useful in evaluating prognosis.

Radioiodine uptake in inactive pulmonary tuberculosis.

Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases.