Rheumatoid Lung Research Articles

Rheumatoid arthritis associated interstitial lung disease: Trends in epidemiology and mortality in Ontario from 2000 to 2018

BackgroundThe epidemiology and mortality of rheumatoid arthritis related interstitial lung disease (RA-ILD) have not been described in Canada. Our aim was to describe recent trends in RA-ILD prevalence, incidence, and mortality in Ontario, Canada. MethodsThis was a retrospective population-based study using repeated cross-sections from 2000 to 2018. We estimated annual age- and sex-standardized rates for RA-ILD prevalence, incidence and mortality. ResultsAmong 184,400 RA patients identified between 2000 and 2018, 5722 (3.1%) were diagnosed with RA-ILD. Most RA-ILD patients were women (63.9%) and ≥60 years old (76.9%) at the time of RA-ILD diagnosis. RA-ILD incidence rose from 1.6 (95% confidence interval (CI) 1.3–2.0) to 3.3 (95% CI 3.0–3.6) per 1000 RA patients (204% relative increase, p < 0.0001) during this time. RA-ILD incidence increased in both sexes and all age groups over time. The cumulative prevalence of RA-ILD increased from 8.4 (95% CI 7.6–9.2) to 21.1 (95% CI 20.3–21.8) per 1000 RA patients (250% relative increase, p < 0.0001), increasing in both sexes and all age groups. All-cause and RA-ILD related mortality declined in patients with RA-ILD over time [55.1% relative reduction, (p < 0.0001) and 70.9% relative reduction, (p < 0.0001), respectively]. In RA-ILD patients, RA-ILD contributed to the cause of death in approximately 29% of cases. Men and older patients had higher all-cause and RA-ILD related mortality. ConclusionIn a large, diverse Canadian population, the incidence and prevalence of RA-ILD are increasing. RA-ILD related mortality is declining, but remains an important cause of death in this population.

Enhancing the identification of rheumatoid arthritis-associated interstitial lung disease through text mining of chest computerized tomography reports

ObjectivesAlgorithms have been developed to identify rheumatoid arthritis-interstitial lung disease (RA-ILD) in administrative data with positive predictive values (PPVs) between 70 and 80%. We hypothesized that including ILD-related terms identified within chest computed tomography (CT) reports through text mining would improve the PPV of these algorithms in this cross-sectional study. MethodsWe identified a derivation cohort of possible RA-ILD cases (n = 114) using electronic health record data from a large academic medical center and performed medical record review to validate diagnoses (reference standard). ILD-related terms (e.g., ground glass, honeycomb) were identified in chest CT reports by natural language processing. Administrative algorithms including diagnostic and procedural codes as well as specialty were applied to the cohort both with and without the requirement for ILD-related terms from CT reports. We subsequently analyzed similar algorithms in an external validation cohort of 536 participants with RA. ResultsThe addition of ILD-related terms to RA-ILD administrative algorithms increased the PPV in both the derivation (improvement ranging from 3.6 to 11.7%) and validation cohorts (improvement 6.0 to 21.1%). This increase was greatest for less stringent algorithms. Administrative algorithms including ILD-related terms from CT reports exceeded a PPV of 90% (maximum 94.6% derivation cohort). Increases in PPV were accompanied by a decline in sensitivity (validation cohort -3.9 to -19.5%). ConclusionsThe addition of ILD-related terms identified by text mining from chest CT reports led to improvements in the PPV of RA-ILD algorithms. With high PPVs, use of these algorithms in large data sets could facilitate epidemiologic and comparative effectiveness research in RA-ILD.

Stattic alleviates pulmonary fibrosis in a mouse model of rheumatoid arthritis-relevant interstitial lung disease.

Approximately 20% of rheumatoid arthritis (RA) patients have RA-related interstitial lung disease (RA-ILD). Stattic, an STAT3 inhibitor, has been confirmed to be relevant to both RA and ILD. Therefore, this study explored the effect of Stattic on the progression of joint disease and pulmonary fibrosis in zymosan-treated female SKG mice, an established model for autoimmune arthritis. The experimental mice developed pulmonary interstitial pneumonia, which is similar to human cellular and fibrotic nonspecific interstitial pneumonia. Oral gavage of Stattic (60 mg/kg/d) was initiated 10 weeks after zymosan injection. Arthritis and lung fibrosis outcome scores decreased significantly following Stattic treatment. An obvious decrease in lung collagen levels, measured using hydroxyproline level determination and collagen staining, was detected after 6 weeks in Stattic-exposed mice with established disease. Stattic also dramatically restricted arthritis progression, based on joint evaluation. Transforming growth factor beta 1 (TGF-β1) is a pivotal fibrosis-causing cytokine, used here to treat myofibroblasts, thereby establishing a lung fibrosis cell model. Stattic treatment can mitigate the TGF-β1-triggered inflammatory response, myofibroblast activation, oxidative stress, and hyperproliferation by modulating the JAK1/STAT3 pathway. Our observations support a direct role of Stattic-inhibited STAT3 activation in lung fibrosis, which may be particularly relevant in the RA-ILD context.

Serum antibodies to peptidylarginine deiminase-4 in rheumatoid arthritis associated-interstitial lung disease are associated with decreased lung fibrosis and improved survival

ObjectiveInterstitial lung disease (ILD) is a leading cause of mortality in rheumatoid arthritis (RA), particularly in those with the usual interstitial pneumonia subtype (RA-UIP). Serum antibodies to peptidylarginine deiminase type 4 (anti-PAD4), particularly a subset that cross-react with PAD3 (PAD3/4XR), have been associated with imaging evidence of ILD. We aimed to determine the specificity of anti-PAD4 antibodies in RA-ILD and to examine associations with markers of ILD severity. Methods48 RA-ILD and 31 idiopathic pulmonary fibrosis (IPF) patients were identified from the National Jewish Health Biobank. RA-ILD subtype was defined by imaging pattern on high-resolution chest computed tomography (CT), and serum was tested for anti-PAD4 and anti-PAD3/4XR antibodies. Antibody prevalence, measures of ILD severity (% predicted forced vital capacity, FVC; % predicted diffusion capacity carbon monoxide, DLCO; quantitative CT fibrosis) and mortality were compared between groups. ResultsAnti-PAD4 antibodies were present in 9/48 (19%) subjects with RA-ILD and no subjects with IPF. Within RA-ILD, anti-PAD4 antibodies were found almost exclusively in RA-UIP (89%). Within RA-UIP subjects, % predicted FVC was higher in anti-PAD4+ subjects, and this finding was most strongly associated with anti-PAD3/4XR antibodies. In addition, quantitative CT fibrosis score was lower in anti-PAD4+ RA-UIP subjects, including those with mono-reactive anti-PAD4 antibodies and anti-PAD3/4XR antibodies. Anti-PAD4+ RA-UIP subjects also exhibited decreased mortality. ConclusionsWe demonstrate the presence of serum anti-PAD4 antibodies in a subset of patients with RA-UIP that were notably associated with better lung function, less fibrosis and decreased mortality.

Preclinical or subclinical rheumatoid arthritis-associated interstitial lung disease: misleading terms with potentially deleterious consequences

Interstitial lung disease (ILD) is a leading cause of mortality in patients with rheumatic diseases, including rheumatoid arthritis. 1 Olson AL Swigris JJ Sprunger DB et al. Rheumatoid arthritis-interstitial lung disease-associated mortality. Am J Respir Crit Care Med. 2011; 183: 372-378 Crossref PubMed Scopus (299) Google Scholar The 5-year mortality rate is twice as high in patients with rheumatoid arthritis-associated ILD than in patients with rheumatoid arthritis without ILD. 2 Hyldgaard C Hilberg O Pedersen AB et al. A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality. Ann Rheum Dis. 2017; 76: 1700-1706 Crossref PubMed Scopus (159) Google Scholar Moreover, a report showed that mortality rates in patients with disease codes for rheumatoid arthritis-associated ILD remained unchanged from 2005–18, even though the overall rheumatoid arthritis mortality rate declined during this time period. 3 Jeganathan N Nguyen E Sathananthan M Rheumatoid arthritis and associated interstitial lung disease: mortality rates and trends. Ann Am Thorac Soc. 2021; 18: 1970-1977 Crossref PubMed Scopus (6) Google Scholar Despite the evidence that ILD contributes to premature death in rheumatoid arthritis, screening for ILD in patients with rheumatoid arthritis is not routinely performed in clinical practice and numerous questions remain regarding the management of rheumatoid arthritis-associated ILD. 4 Kelly C Emery P Dieudé P Current issues in rheumatoid arthritis-associated interstitial lung disease. Lancet Rheumatol. 2021; 3: e798-e807 Summary Full Text Full Text PDF Scopus (6) Google Scholar

Tomographic pleuropulmonary manifestations in rheumatoid arthritis: a pictorial essay.

Rheumatoid arthritis (RA) is an autoimmune inflammatory and heterogeneous disease that affects several systems, especially the joints. Among the extra-articular manifestations of RA, pleuropulmonary involvement occurs frequently, with different presentations, potentially in all anatomic thoracic compartments, and may determine high morbidity and mortality. The most common pleuropulmonary manifestations in patients with RA include interstitial lung disease (ILD), pleural disease, pulmonary arterial hypertension, rheumatoid lung nodules, airway disease (bronchiectasis and bronchiolitis), and lymphadenopathy. Pulmonary hypertension and ILD are the manifestations with the greatest negative impact in prognosis. HRCT of the chest is essential in the evaluation of patients with RA with respiratory symptoms, especially those with higher risk factors for ILD, such as male gender, smoking, older age, high levels of rheumatoid factor, or positive anti-cyclic citrullinated peptide antibody results. Additionally, other etiologies that may determine tomographic pleuropulmonary manifestations in patients with RA are infections, neoplasms, and drug-induced lung disease. In these scenarios, clinical presentation is heterogeneous, varying from being asymptomatic to having progressive respiratory failure. Knowledge on the potential etiologies causing tomographic pleuropulmonary manifestations in patients with RA coupled with proper clinical reasoning is crucial to diagnose and treat these patients.

MUC5B promoter variant rs35705950, rare but significant susceptibility locus in rheumatoid arthritis-interstitial lung disease with usual interstitial pneumonia in Asian populations

BackgroundMUC5B variant rs35705950 is the common and most significant risk variant for rheumatoid arthritis-interstitial lung disease (RA-ILD) in Western populations. However, little is known about its significant association with RA-ILD...

Computer-Aided Diagnosis of Pulmonary Nodules in Rheumatoid Arthritis.

(1) Background: Rheumatoid arthritis (RA) is considered a systemic inflammatory pathology characterized by symmetric polyarthritis associated with extra-articular manifestations, such as lung disease. The purpose of the present study is to use CAD in the detection of rheumatoid pulmonary nodules. In addition, we aim to identify the characteristics and associations between clinical, laboratory and imaging data in patients with rheumatoid arthritis and lung nodules. (2) Methods: The study included a number of 42 patients diagnosed with rheumatoid arthritis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, examined from January 2017 to November 2022 in the Departments of Rheumatology and Radiology and Medical Imaging of the University of Medicine and Pharmacy of Craiova. Medical records were reviewed. A retrospective blinded review of CT for biopsy-proven pulmonary nodules in RA using Veolity LungCAD software was performed (MeVis Medical Solutions AG, Bremen, Germany). Imaging was also reviewed by a senior radiologist. (3) Results: The interobserver agreement proved to be moderate (κ = 0.478) for the overall examined cases. CAD interpretation resulted in false positive results in the case of 12 lung nodules, whereas false negative results were reported in the case of 8 lung nodules. The mean time it took for the detection of lung nodules using CAD was 4.2 min per patient, whereas the detection of lung nodules by the radiologist was 8.1 min per patient. This resulted in a faster interpretation of lung CT scans, almost reducing the detection time by half (p &lt; 0.001). (4) Conclusions: The CAD software is useful in identifying lung nodules, in shortening the interpretation time of the CT examination and also in aiding the radiologist in better assessing all the pulmonary lung nodules. However, the CAD software cannot replace the human eye yet due to the relative high rate of false positive and false negative results.

Mortality and survival of patients with rheumatoid arthritis and symptomatic diffuse interstitial lung disease

Introduction: In Spain, few data have been reported on mortality and survival in rheumatoid arthritis with diffuse interstitial lung disease. Objectives: To estimate mortality and survival for patients with symptomatic diffuse interstitial lung disease and rheumatoid arthritis and to analyze the effect of clinical factors. Methods: We performed an observational study between 2007 and 2018 at the Interdisciplinary Rheumatology and Pulmonology Clinic, from a tertiary Hospital. Patients with rheumatoid arthritis and symptomatic of diffuse interstitial lung disease confirmed by high-resolution computed tomography were included. Causes of death and clinical factors were reported. Results: We identified 90 patients with rheumatoid arthritis and symptomatic interstitial lung disease. Twenty-six patients died and diffuse interstitial lung disease was the most frequent cause (50%). The overall mortality rate was 19.7 per 1000 patient-years (95% CI: 13.4 - 29). The multivariate model revealed the predictors of mortality to be a long time between diagnosis of rheumatoid arthritis and lung involvement (HR = 1.17; p = 0.003) and low forced vital capacity (HR = 0.02; p = 0.018). The probability of survival was 50% at 10.2 years from diagnosis of interstitial lung disease. Comparison of survival did not reveal significant differences by type of radiologic pattern (p = 0.823). Conclusions: The fact that almost one-third of patients died and that survival is 50% at 10 years highlights the important role of diffuse interstitial lung disease in rheumatoid arthritis. The radiologic pattern does not seem to be as important for survival as forced vital capacity at diagnosis and the time between diagnosis of rheumatoid arthritis and lung involvement. Key points 1. DILD is associated with shorter survival in patients with RA. 2. The radiologic pattern does not seem to influence the survival in patients with RA and DILD. 3. The FVC at diagnosis is an important factor that influences the prognosis of patients with RA and DILD.

Impact of cigarette smoking on rheumatoid arthritis-associated lung diseases: a retrospective case control study on clinical and radiological features and prognosis.

Our study aimed to investigate the clinical and radiological features and prognosis of male smoker patients with rheumatoid arthritis (RA). We consecutively enrolled male inpatients with RA who received chest HRCT during hospitalization in Peking University Third Hospital from Jan 1st, 2012 to August 1st, 2021. 154 male patients with RA were eligible for analysis, of whom 76.6% (n = 118) were current smokers or had a history of cigarette smoking. Compared to never-smokers, smoker patients had more respiratory symptoms, including cough (31.4% vs 5.6%, p = 0.002) and sputum production (26.3% vs 2.8%, p = 0.002), and a higher positive rate of rheumatoid factor (RF) (77.6% vs 58.8%, p = 0.030). A higher percentage of smoker patients showed emphysema (45.8% vs 16.7%, p = 0.002) and signs of lung fibrosis (51/54, 94.4% vs 7/13, 53.8%, p < 0.001) in those with interstitial lung disease (ILD, n = 67) on chest HRCT. The overall survival rate was different between smoker and never-smoker patients (p = 0.031), but instead of cigarette smoking, lung fibrosis on HRCT was the risk factor for survival of our patients. In conclusion, male patients with RA who were current smokers or had a history of cigarette smoking presented more respiratory symptoms and a higher positive rate of RF. They also showed more emphysema and signs of lung fibrosis on chest HRCT. Cigarette smoking impacted on the overall survival as a confounding factor in this cohort of male patients with RA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00296-022-05219-9.

Genetic, social, and environmental risk factors in rheumatoid arthritis-associated interstitial lung disease

ObjectiveMUC5B and TOLLIP single nucleotide polymorphisms (SNPs) and cigarette smoking were associated with rheumatoid arthritis-interstitial lung disease (RA-ILD) in a predominantly Northern European population. We evaluated whether RA-ILD is associated with these genetic variants and HLA-DRB1 shared epitope (SE) alleles in a large RA cohort stratified by race and smoking history. MethodsHLA-DRB1 SE alleles and MUC5B rs35705950 and TOLLIP rs5743890 SNPs were genotyped in U.S. veterans with RA. ILD was validated through medical record review. Genetic associations with ILD were assessed in logistic regression models overall and in subgroups defined by race and smoking status, with additive interactions assessed by the relative excess risk of interaction (RERI). ResultsOf 2,556 participants (88% male, 77% White), 238 (9.3%) had ILD. The MUC5B variant was associated with ILD (OR 2.25 [95% CI 1.69, 3.02]), whereas TOLLIP and HLA-DRB1 SE were not. The MUC5B variant was less frequent among Black/African American participants (5.8% vs. 22.6%), though its association with RA-ILD was numerically stronger (OR 4.23 [1.65, 10.86]) compared to all other participants (OR 2.32 [1.70, 3.16]). Those with the MUC5B variant and a smoking history had numerically higher odds of ILD (OR 4.18 [2.53, 6.93]) than non-smokers (OR 2.41 [1.16, 5.04]). Additive interactions between MUC5B-race and MUC5B-smoking were not statistically significant. ConclusionIn this large RA cohort, the MUC5B promoter variant was associated with >2-fold higher odds of RA-ILD. While this variant is less common among Black/African American patients, its presence in this population carried >4-fold higher odds of RA-ILD.

SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 1: Epidemiology, risk factors and prognosis

ObjectiveTo develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). MethodsClinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. ResultsSix PICO questions were selected, three of which analysed the incidence and prevalence of RA-ILD, associated risk factors, and predictors of progression and mortality. A total of 6 specific recommendations on these topics, structured by question, were formulated based on the evidence found and/or expert consensus. ConclusionsWe present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions and facilitate decision-making for patients.

SER-SEPAR recommendations for the management of rheumatoid arthritis-related interstitial lung disease. Part 2: Treatment

ObjectiveTo develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD). MethodsClinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made. ResultsSix PICO questions were selected, three of which analysed the safety and effectiveness of glucocorticoids, classical synthetic disease-modifying anti-rheumatic drugs (DMARDs) and other immunosuppressants, biological agents, targeted synthetic DMARDs, and antifibrotic therapies in the treatment of this complication. A total of 12 recommendations were formulated based on the evidence found and/or expert consensus. ConclusionsWe present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions, reduce clinical healthcare variability, and facilitate decision-making for patients.

Pulmonary adenocarcinoma mimicking rheumatoid lung and delaying diagnosis for 8 months

Abstract The clinical and radiological findings of adenocarcinoma and rheumatoid lung disease are non-specific and similar. The final diagnosis should be confirmed by histopathology. We present an adenocarcinoma of lung in known rheumatoid patient presenting as cough and breathlessness for 8 months. The CT chest revealed multiple consolidations, bronchectasis and honeycombing with two times bronchoscopic biopsy negative. All non-resolving lesions with non-specific symptoms should be investigated for all possible causes including malignancy. We advised to do CT guided biopsy in such cases even after bronchial biopsy negative as it has higher yield and cost effective test.

Novel Biomarkers, Diagnostic and Therapeutic Approach in Rheumatoid Arthritis Interstitial Lung Disease-A Narrative Review.

Rheumatoid arthritis (RA) is considered a systemic inflammatory disease marked by polyarthritis which affects the joints symmetrically, leading to progressive damage of the bone structure and eventually joint deformity. Lung involvement is the most prevalent extra-articular feature of RA, affecting 10–60% of patients with this disease. In this review, we aim to discuss the patterns of RA interstitial lung disease (ILD), the molecular mechanisms involved in the pathogenesis of ILD in RA, and also the therapeutic challenges in this particular extra-articular manifestation. The pathophysiology of RA-ILD has been linked to biomarkers such as anti-citrullinated protein antibodies (ACPAs), MUC5B mutation, Krebs von den Lungen 6 (KL-6), and other environmental factors such as smoking. Patients at the highest risk for RA-ILD and those most likely to advance will be identified using biomarkers. The hope is that finding biomarkers with good performance characteristics would help researchers better understand the pathophysiology of RA-ILD and, in turn, lead to the development of tailored therapeutics for this severe RA manifestation.

Predictors of long-term prognosis in rheumatoid arthritis-related interstitial lung disease.

The aim of the study was to identify specific clinical and serum protein biomarkers that are associated with longitudinal outcome of RA-associated interstitial lung disease (RA-ILD). 60 RA patients with clinical and serological profiles were assessed by HRCT and pulmonary function tests (PFTs) at baseline (Year 0) and 5 years post enrollment (Year 5). Progression versus non-progression was defined based on changes in Quantitative Modified HRCT scores and PFTs over time. Specific serum protein biomarkers were assessed in serum samples at baseline and Year 5 by Multiplex enzyme-linked immunosorbent assays (ELISAs). At Year 5, 32% of patients demonstrated progressive RA-ILD, 35% were stable, and 33% improved. Baseline age and rheumatoid factor (RF) were significantly different between RA-ILD outcomes of progression vs. no-progression (p < 0.05). Changes in levels of CXCL11/I-TAC and MMP13 over 5 years also distinguished pulmonary outcomes (p < 0.05). A final binary logistic regression model revealed that baseline age and changes in serum MMP13 as well as CXCL11/I-TAC were associated with RA-ILD progression at Year 5 (p < 0.01), with an AUC of 0.7772. Collectively, these analyses demonstrated that baseline clinical variables (age, RF) and shifts in levels of selected serum proteins (CXCL11/I-TAC, MMP13) were strongly linked to RA-ILD outcome over time.

A retrospective study of the efficacy of JAK inhibitors or abatacept on rheumatoid arthritis-interstitial lung disease

ObjectivesTo examine the effectiveness of Janus-kinase inhibitors (JAKis) or abatacept (ABA) in patients with rheumatoid arthritis-interstitial lung disease (RA-ILD).MethodsPatients with RA-ILD receiving JAKis or ABA were retrospectively evaluated at baseline and after 18 months of treatment. A computer-aided method (CaM) was used to assess the extent of high-resolution computed tomography (HRCT) fibrosis percentage. According to HRCT fibrosis changes, patients were classified as “worsened” (progression of 15% or more), “stable” (changes within 15%) or “improved” (reduction of 15% or more). Correlations between RA characteristics and JAKis or ABA responses were studied using a multivariate regression model.ResultsSeventy-five patients (69.3% women) were evaluated, 31 received a JAKi while 44 received ABA. In the JAKis group, five patients (16.1%) showed RA-ILD progression, 20 patients (64.5%) were considered stable, and six patients (19.4%) demonstrated RA-ILD improvement. In the ABA group, five patients (11.3%) showed RA-ILD progression, 32 patients (72.7%) were stable, and seven patients (16.0%) demonstrated RA-ILD improvement. In both groups, the percentage of current smokers was different between those classified as "worsened" and those classified as "improved/stable" (p = 0.01). In multivariate regression analysis, current smoking habit (p = 0.0051) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in ABA-treated patients, whereas in JAKis-treated patients, the only RA-ILD progression-related variable was disease duration of RA (p < 0.001).ConclusionsTreatment with JAKis or ABA was related to stability or improvement of RA-ILD in 83.9% and 88.6% of patients, respectively. RA duration is the only variable associated with worsening RA-ILD in JAKis-treated patients.

Risk factors for the progression of rheumatoid arthritis-related interstitial lung disease: Clinical features, biomarkers, and treatment options

ObjectivesThe clinical heterogeneity of the progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is high, and there is a lack of consensus on the clinical relevance and medical protocols. The purpose of this study is to explore the impact of clinical characteristics, new biomarkers and treatment options on the prognosis of RA-ILD patients and to explore whether these factors can predict the progression and death of these patients. MethodsWe retrospectively collected case data on RA-ILD patients who visited or were admitted to Changhai Hospital between October 2010 and September 2021. We followed up and finally included 75 patients. The main outcome indicator of disease progression was pulmonary functional impairment, which was assessed by changes of high-resolution computed tomography (HRCT) score or pulmonary function test before and after treatment. The demographics, clinical characteristics, laboratory tests, and treatment plans of RA-ILD patients in the progressive and stable groups were compared and analyzed. Clinically relevant variables were identified, and the incidence of pulmonary dysfunction and adverse events was recorded. Cox regression analysis was used to determine factors related to the progression of ILD. ResultsThe mean age of RA-ILD onset was 64.0 years (SD 10.3), and 53 (70.7%) patients were female. Thirty-two (42.7%) patients had lung dysfunction, who were classified as the progressive group, and 13 (40.6%) of them died. In univariate analyses, male, smoking, high HRCT scores at baseline, RF-IgA>200 RU/ml, diffusing capacity of the lungs for carbon monoxide (DLCO), and usual interstitial pneumonia (UIP) pattern were significant risk factors for disease progression; while use of Leflunomide (LEF) was associated with better prognosis. The multivariate analysis revealed that RF-IgA>200 RU/ml (hazard ratio [HR] 3.17 [95% confidence interval (CI) 1.29, 7.81], P = 0.012), UIP pattern (HR 3.94 [95% CI 1.68, 9.26], P = 0.002), and male (HR 2.52 [95% CI 1.16, 5.46], P = 0.019) were significantly correlated with unfavorable outcomes in patients with RA-ILD. LEF (HR 0.25 [95% CI 0.10, 0.61], P = 0.002) was related to a better prognosis. However, it might be related to investigating medications changes after baseline. ConclusionOur data suggests that male, UIP pattern, and increased RF-IgA may be potential predicting factors for poor prognosis of RA-ILD patients. We report a significant association between high titer of RF-IgA at baseline and RA-ILD progression for the first time, which might be a potentially important biomarker for the prognosis of RA-ILD.

Rheumatoid interstitial lung disease in Canterbury New Zealand: prevalence, risk factors and long-term outcomes—protocol for a population-based retrospective study

IntroductionRheumatoid arthritis (RA) affects approximately 0.5%–1% of the general population. Clinically significant interstitial lung diseases (ILD) develops in just under 10% of people with RA, and subclinical disease is more...

Rheumatoid arthritis-related interstitial lung disease (RA-ILD): a possible association between disease activity and prognosis.

We hypothesized that RA disease activity might be associated with the survival of RA-ILD patients. To evaluate this possibility, we analyzed data on disease activity during follow-up in an RA-ILD cohort and compared disease activity between surviving patients and those who died during follow-up. RA-ILD patients referred for medical evaluation and treatment at a single center, with CDAI scores during all follow up were included. We estimated the HR of the mean of the CDAI score during follow-up with survival. Also, we compared the survival function of patients with high disease activity (CDAI scores ≥ 22) during all follow-up with those with moderate and low disease activity. Thirty-seven patients were included. The mean of the CDAI score during follow-up was higher in death patients (median 30.8 ± 18.5 Vs. 16.8 ± 11.3), and a single unit increase in the mean of the CDAI score was associated with non-survival, HR:1.07 (95% CI: 1.02 -1.12). Patients with high disease activity during all follow-up (CDAI scores > 22) had lower survival function in comparison with moderate and low disease activity (P = 0.042). The results of the study suggest that higher RA disease activity is associated with a worse prognosis of RA-ILD patients. The hypothesis that high disease activity is associated with worse survival in RA-ILD patients must be evaluated in more extensive cohort studies and clinical trials. • RA-ILD patients with high disease activity during follow-up had a worse prognosis than those with moderate or low disease activity. • The study results suggest the hypothesis that patients with RA-ILD must be treated with a treat to target strategy, with the aim of remission or low RA disease activity.