Rheumatoid Arthritis-associated Interstitial Lung Disease Research Articles

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

IntroductionAcute 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).MethodsPubMed, 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.ResultsTwenty-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.ConclusionAE-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.RegistrationCRD42023396772.

Serum sCD25 is an indicator for rheumatoid arthritis-associated interstitial lung disease.

CD25 (IL-2Rα) is one of IL-2 receptor's polypeptide subunits, and its soluble form is increased in patients with various inflammatory or autoimmune diseases. This study aimed to evaluate the clinical correlation of serum soluble CD25 (sCD25) with interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. 294 RA patients, including 72 in the discovery cohort (15 patients with ILD, 57 patients without ILD), 222 in the validation cohort (41 patients with ILD and 181 patients without ILD), and 58 healthy controls (HCs) were recruited. High-resolution computed tomography (HRCT) scan provided evidence and patterns of RA-ILD. Serum sCD25 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory data were recorded and the association with sCD25 was also analysed. In the discovery cohort, 16 RA-related molecules including cytokines, chemokines and functional soluble cell surface proteins were investigated. The results showed that sCD25 was significantly higher in RA-ILD than in RA-no-ILD group (p=0.004). ROC analysis also showed RA-ILD was discriminated with RA-no-ILD by sCD25 (AUC=0.695, 95% CI=0.541-0.849). Logistics regression demonstrated that sCD25 was one of the risk factors of RA-ILD. This result was further confirmed in validation cohort (p<0.001). According to the cut-off value in the discovery cohort, the sensitivity and specificity of sCD25 in RA-ILD were 51.2%, 77.3%, respectively. Compared with RA-no-ILD, serum level of sCD25 was also higher in different HRCT patterns including UIP, NSIP and RA-ILA. The ROC curves revealed sCD25 as diagnostic marker in UIP, NSIP and RA-ILA (with AUCs of 0.730, 0.761, and 0. 694, respectively, p<0.05). The result indicated that sCD25 was a biomarker for RA-ILD subtypes. Although sCD25 was not correlated with HRCT scores, it was significantly higher in consolidation pattern by HRCT. sCD25 was significantly elevated in RA-ILD (including UIP, NSIP and RA-ILA) compared to RA-no-ILD and HCs, which supports their value as a potential biomarker in RA-ILD screening and assessment.

Treatment of rheumatoid arthritis-associated interstitial lung disease in a multi-center registry cohort.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is challenging to manage, with a paucity of robust data to guide treatment. Our aim was to characterize the pharmacologic treatment of RA-ILD utilizing a retrospective design in a national multi-center prospective cohort, and to identify associations between treatment and change in lung function and survival. Patients with RA-ILD and a radiological pattern of non-specific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) were included. Unadjusted and adjusted linear mixed models and Cox proportional hazards models were used to compare lung function change and risk of death or lung transplant by radiologic patterns and treatment. Of 161 patients with RA-ILD, UIP pattern was more common than NSIP (55.9% vs. 44.1%). Only 44/161 (27%) patients were treated over median follow-up of 4 years with medication choice appearing unrelated to patient-specific variables. Decline in forced vital capacity (FVC) was not associated with treatment. Patients with NSIP had lower risk of death or transplant, compared to UIP (P=0.0042). In patients with NSIP, there was no difference in time to death or transplant comparing treated to untreated in adjusted models [hazard ratio (HR) =0.73; 95% confidence interval (CI): 0.15-3.62; P=0.70]. Similarly, in patients with UIP, there was no difference in time to death or lung transplant between treated and untreated in adjusted models (HR =1.06; 95% CI: 0.49-2.28; P=0.89). Treatment of RA-ILD is heterogeneous, with most patients in this cohort not receiving treatment. Patients with UIP had worse outcomes compared to NSIP, similar to other cohorts. Randomized clinical trials are needed to inform pharmacologic therapy in this patient population.

NKX2.1 mutation revealed by a lymphoid interstitial pneumonia in an adult with rheumatoid arthritis.

This is the first case of a 37-year-old female patient carrier of a heterozygous NKX2.1 mutation associated with RA-ILD with a histological pattern of LIP. This case illustrates the wide panel of ILD subtypes associated with NKX2.1 mutations. https://bit.ly/3F49OTS.

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.

Estimating cardiopulmonary fitness with a new sampling technology in patients with rheumatoid arthritis-associated interstitial lung disease.

Although peak oxygen uptake (VO2peak ) is one of the most important measures in clinical practice, the high cost and time consumption have led to the search for simpler devices and the development of the estimating cardiopulmonary fitness (eCPF) equation. Since the lungs are one of the sites most affected by rheumatoid arthritis (RA), this study aimed to create a predictive equation for VO2peak obtained by simple sampling technology in women with RA-associated interstitial lung disease (RA-ILD). This cross-sectional study evaluated 47 women with RA-ILD. The participants underwent the following evaluations: computed tomography (CT); evaluation of disease activity through the Clinical Disease Activity Index (CDAI); measurement of physical function using the Health Assessment Questionnaire disability index (HAQ-DI); pulmonary function testing, including spirometry, diffusing capacity for carbon monoxide (DlCO ), nitrogen single-breath washout (N2 SBW) test, and impulse oscillometry; and cardiopulmonary exercise testing (CPET) using FitMate™. VO2peak was correlated with age (r=-0.550, p<0.0001), rheumatoid factor (r=-0.443, p=0.002), anti-cyclic citrullinated peptide antibodies (r= -0.410, p=0.004), CDAI (r=-0.462, p=0.001), HAD-DI (r=-0.486, p=0.0005), forced vital capacity (r=0.491, p=0.0004), DlCO (r=0.621, p<0.0001), phase III slope of N2 SBW (r=-0.647, p<0.0001), resonance frequency (Fres , r=-0.717, p<0.0001), integrated low-frequency reactance (r=-0.535, p=0.0001), and the inhomogeneity of respiratory system resistance between 4 and 20Hz (r=-0.631, p<0.0001). In the CT examination, patients with extensive ILD had significantly lower VO2peak than patients with limited ILD (p<0.0001). In the stepwise forward regression analysis, Fres , DlCO and age explained 61% of the VO2peak variability. As assessed by CPET, women with RA-ILD show reduced cardiopulmonary fitness, which can be explained at least in part by the presence of small airway disease, deterioration of pulmonary gas exchange, and advanced age. These associations of pulmonary variables with eCPF may be clinically important and support the use of the eCPF equation to improve patient outcomes.

Novel insights into the management of rheumatoid arthritis: one year in review 2023.

New evidence from 2022 slightly changed some perspectives for rheumatoid arthritis (RA) management. Real-world data on the efficacy and safety of disease-modifying anti-rheumatic drugs strengthened the importance of tailoring treatment decisions based on patient characteristics. Moreover, the research of response biomarkers to therapy underlined the need for precision medicine and remote care applications showed an innovative outlook that supports a patient-centred approach. New developments in vaccinations led to the release of updated guidelines and to a consistent improvement in the prevention of vaccine-preventable infections. New literature data also reconsidered drug management in RA-associated interstitial lung disease and pregnancy. In this paper, the reviewers aim to present the most relevant studies published during the last year in the field of RA management.

Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: A critical review.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovitis as the most common clinical manifestation, and interstitial lung disease (RA-ILD) represents one of the most common and potentially severe extra-articular features. Our current understanding of the mechanisms and predictors of RA-ILD is limited despite the demonstration that an early identification of progressive fibrosing forms is crucial to provide timely treatment with antifibrotic therapies. While high resolution computed tomography is the gold standard technique for the diagnosis and follow-up of RA-ILD, it has been hypothesized that serum biomarkers (including novel and rare autoantibodies), new imaging techniques such as ultrasound of the lung, or the application of innovative radiologic algorithms may help towards predicting and detecting early forms of diseases. Further, while new treatments are becoming available for idiopathic and connective tissue disease-associated forms of lung fibrosis, the treatment of RA-ILD remains anecdotal and largely unexplored. We are convinced that a better understanding of the mechanisms connecting RA with ILD in a subgroup of patients as well as the creation of adequate diagnostic pathways will be mandatory steps for a more effective management of this clinically challenging entity.

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.

Photon-counting computed tomography in the assessment of rheumatoid arthritis-associated interstitial lung disease: an initial experience

Interstitial lung disease (ILD) accounts for a significant proportion of mortality and morbidity in patients with rheumatoid arthritis (RA). The aim of this cross-sectional study is to evaluate the performance of novel photon-counting detector computed tomography (PCD-CT) in the detection of pulmonary parenchymal involvement. Sixty-one patients with RA without a previous definitive diagnosis of ILD underwent high-resolution (HR) (0.4 mm slice thickness) and ultra-high-resolution (UHR) (0.2 mm slice thickness) PCDCT examination. The extent of interstitial abnormalities [ground-glass opacity (GGO), reticulation, bronchiectasis, and honeycombing] were scored in each lobe using a Likert-type scale. Total ILD scores were calculated as the sum of scores from all lobes. Reticulation and bronchiectasis scores were higher in the UHR measurements taken compared with the HR protocol [median (quartile 1, quartile 3): 2 (0, 3.5) vs. 0 (0, 3), P < 0.001 and 2 (0, 2) vs. 0 (0, 2), P < 0.001, respectively]; however, GGO and honeycombing scores did not differ [2 (2, 4) vs. 2 (2, 4), P = 0.944 and 0 (0, 0) vs. 0 (0, 0), P = 0.641, respectively]. Total ILD scores from both HR and UHR scans showed a mild negative correlation in diffusion capacity for carbon monoxide (HR: r = -0.297, P = 0.034; UHR: r = -0.294, P = 0.036). The pattern of lung parenchymal involvement did not differ significantly between the two protocols. The HR protocol had significantly lower volume CT dose index [0.67 (0.69, 1.06) mGy], total dose length product [29 (24.48, 33.2) mGy*cm] compared with UHR scans [8.18 (6.80, 9.23) mGy, P < 0.001 and 250 (218, 305) mGy*cm, P < 0.001]. UHR PCD-CT provides more detailed information on ILD in patients with RA than low-dose HR PCDCT. HR PCD-CT image acquisition with a low effective radiation dose may serve as a valuable, low-radiation screening tool in the selection of patients for further, higher-dose UHR PCD-CT screening.

Retention Rate and Safety of Biologic and Targeted Synthetic DMARDs in Patients with RA-Associated Interstitial Lung Disease: A KOBIO Registry Study

This study aimed to evaluate the long-term retention and safety of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) and identify the factors associated with drug withdrawal in patients with rheumatoid arthritis (RA) with interstitial lung disease (ILD) enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry. We investigated adults with RA (n=2266) administered with bDMARDs or tsDMARDs between 2012 and 2021. Propensity score matching (1:3) was performed between patients with RA with ILD(RA-ILD) and without ILD (RA-no ILD). The Kaplan-Meier method was used to analyse drug survival and a logistic regression model to identify withdrawal-related factors in RA-ILD. One hundred and fifty-nine patients with RA-ILD were matched with 477 patients with RA-no ILD. The 5-year drug retention rate was lower in RA-ILD than in RA-no ILD (log-rank p=0.020), and both the ILD and no-ILD groups had statistical differences of drug retention rate among agents (log-rank p=0.019 and 0.020, respectively). In the RA-ILD group, Janus kinase inhibitors had the highest drug retention rate (64.3%), and tumour necrosis factor-α inhibitors showed the lowest retention rate (30.6%). Approximately 58.5% and 48.4% of the patients with RA-ILD and RA-no ILD, respectively, withdrew from their regimen, and the main cause of withdrawal in RA-ILD was adverse events, followed by inefficacy. In the logistic regression analysis, current smoking had a negative effect on drug retention (odds ratio [OR]: 9.938, 95% confidence interval [CI]: 2.550-38.733; p<0.001), while concomitant corticosteroid use had a protective effect against withdrawal (OR: 0.284, 95% CI: 0.008-0.917; p=0.035) in RA-ILD. The patients with RA-ILD had lower bDMARD and tsDMARD retention rates than those with RA-no ILD. In the RA-ILD group, current smoking and concomitant corticosteroid use were associated factors affecting drug withdrawal.

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

Autoantibodies against citrullinated and native proteins and prediction of rheumatoid arthritis-associated interstitial lung disease: A nested case-control study.

To identify fine specificity anti-citrullinated protein antibodies (ACPA) associated with incident rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This nested case-control study within the Brigham RA Sequential Study matched incident RA-ILD cases to RA-noILD controls on time of blood collection, age, sex, RA duration, and rheumatoid factor status. A multiplex assay measured ACPA and anti-native protein antibodies from stored serum prior to RA-ILD onset. Logistic regression models calculated odds ratios (OR) with 95% confidence intervals (CI) for RA-ILD, adjusting for prospectively-collected covariates. We estimated optimism-corrected area under the curves (AUC) using internal validation. Model coefficients generated a risk score for RA-ILD. We analyzed 84 incident RA-ILD cases (mean age 67 years, 77% female, 90% White) and 233 RA-noILD controls (mean age 66 years, 80% female, 94% White). We identified six fine specificity antibodies that were associated with RA-ILD. The antibody isotypes and targeted proteins were: IgA2 to citrullinated histone 4 (OR 0.08 per log-transformed unit, 95% CI 0.03-0.22), IgA2 to citrullinated histone 2A (OR 4.03, 95% CI 2.03-8.00), IgG to cyclic citrullinated filaggrin (OR 3.47, 95% CI 1.71-7.01), IgA2 to native cyclic histone 2A (OR 5.52, 95% CI 2.38-12.78), IgA2 to native histone 2A (OR 4.60, 95% CI 2.18-9.74), and IgG to native cyclic filaggrin (OR 2.53, 95% CI 1.47-4.34). These six antibodies predicted RA-ILD risk better than all clinical factors combined (optimism-corrected AUC=0·84 versus 0·73). We developed a risk score for RA-ILD combining these antibodies with the clinical factors (smoking, disease activity, glucocorticoid use, obesity). At 50% predicted RA-ILD probability, the risk scores both without (score=2·6) and with (score=5·9) biomarkers achieved specificity ≥93% for RA-ILD. Specific ACPA and anti-native protein antibodies improve RA-ILD prediction. These findings implicate synovial protein antibodies in the pathogenesis of RA-ILD and suggest clinical utility in predicting RA-ILD once validated in external studies. National Institutes of Health.

Predicting rheumatoid arthritis-associated interstitial lung disease: filling the void.

Rheumatoid arthritis-associated interstitial lung disease (ILD) is associated with a 5-year mortality of 39·0% (95% CI 34·4–43·5), almost double the mortality observed in patients with rheumatoid arthritis without ILD.1 Around 7% of individuals with rheumatoid arthritis have been reported to develop clinically relevant ILD over a median follow-up of almost 12 years.2

Diffuse lung involvement in rheumatoid arthritis: a respiratory physician's perspective.

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.

Radiomics to predict the mortality of patients with rheumatoid arthritis-associated interstitial lung disease: A proof-of-concept study.

Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients. High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea via the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables. We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36-120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56-55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05-0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06-0.82) and the flatness (HR 0.42, 95% CI 0.18-0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82-2.83) was also retained as a confounder. Radiomic analysis may predict RA-ILD patients' mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease.

Correction to: Annual variation rate of KL-6 for predicting acute exacerbation in patients with rheumatoid arthritis-associated interstitial lung disease.

Correction to: Annual variation rate of KL-6 for predicting acute exacerbation in patients with rheumatoid arthritis-associated interstitial lung disease.

Treatment Outcomes for Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study of the Impact of Immunosuppression on Pulmonary Function Trajectory

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice. How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD? Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed-effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (ie, usual interstitial pneumonia [UIP] vsnon-UIP) on treatment trajectory. Two hundred twelve patients were included in the analysis: 92 patients (43.4%) were treated with azathioprine, 77 patients (36.3%) were treated with mycophenolate mofetil, and 43 patients (20.3%) were treated with rituximab. In the combined analysis of all three agents, an improvement in FVC %predicted was found after 12months of treatment compared with the potential 12-month response without treatment (+3.90%; P≤ .001; 95%CI, 1.95-5.84). Diffusing capacity of the lungs for carbon monoxide (Dlco) %predicted also improved at 12months (+4.53%; P≤ .001; 95%CI, 2.12-6.94). Neither the UIP pattern of ILD nor choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. Immunosuppression was associated with an improved trajectory in FVC and Dlco compared with the pretreatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings.

Using thoracic ultrasound to detect interstitial lung disease in patients with rheumatoid arthritis: a protocol for the diagnostic test accuracy AURORA study

IntroductionPulmonary diseases are significant contributors to morbidity and mortality in patients with rheumatoid arthritis (RA). RA-associated interstitial lung disease (RA-ILD) may be prevalent in up to 30% and clinically evident...

Analysis of comorbidity in rheumatoid arthritis–associated interstitial lung disease: a nested case-cohort study

ObjectivesTo describe comorbid conditions in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity. MethodsNested case-cohort study of 2 prospective cohorts: one with RA-ILD (cases) and another with RA but not ILD (controls). The cohorts were matched for age, sex, and time since diagnosis. Multimorbidity was defined as the co-occurrence of 2 or more chronic diseases, in addition to RA and ILD. We evaluated the comorbid conditions included in the Charlson Comorbidity Index, cardiovascular risk factors, neuropsychiatric conditions, and other frequent conditions in RA. We also recorded clinical-laboratory variables, inflammatory activity according to the 28-joint Disease Activity Score, C-reactive protein (CRP), physical function, and pulmonary function. We performed 2 multivariate analyses to identify factors associated with multimorbidity in RA and RA-ILD. ResultsThe final study population comprised 110 cases and 104 controls. Multimorbidity was more frequent among cases than controls (80 [72.7] vs 60 [57.7]; p = 0.021). In both groups, multimorbidity was associated with ILD (OR [95% CI] 1.92 [1.03–3.59]; p = 0.039), age (OR [95% CI] 1.05 [1.01–1.08]; p = 0.004), CRP (OR [95% CI] 1.16 [1.05–1.29]; p = 0.003), and erosions (OR [95% CI] 1.05 [1.01–1.08]; p = 0.004); in the cases, it was associated with CRP (OR [95% CI] 1.17 [1.01–1.35]; p = 0.027), anti–citrullinated peptide antibody (OR [95% CI] 1.23 [1.14–13.02]; p = 0.049), and forced vital capacity (OR [95% CI] 0.79 [0.96–0.99]; p = 0.036). ConclusionIn patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.