Interstitial Lung Disease In Rheumatoid Arthritis Research Articles

Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients.

Interstitial lung disease and airway disease (AD) are often complicated with rheumatoid arthritis (RA) and have a poor prognosis. Several studies reported genetic associations with interstitial lung disease in RA. However, few genetic studies have examined the susceptibility to AD in RA patients. Here, we investigated whether single nucleotide variants susceptible to idiopathic pulmonary fibrosis might be associated with interstitial lung disease or AD in Japanese RA patients. Genotyping of rs2736100 [C/A] in TERT and rs1278769 [G/A] in ATP11A was conducted in 98 RA patients with usual interstitial pneumonia, 120 with nonspecific interstitial pneumonia (NSIP), 227 with AD, and 422 without chronic lung disease using TaqMan assays. An association with AD in RA was found for rs2736100 (p = 0.0043, Pc = 0.0129, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77). ATP11A rs1278769 was significantly associated with NSIP in older RA patients (>65 years, p = 0.0010, OR 2.15, 95% CI 1.35-3.40). This study first reported an association of rs2736100 with AD in RA patients and ATP11A rs1278769 with NSIP in older RA patients.

Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort

BackgroundTo introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD.MethodsUsing a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients.ResultsAmong 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021–1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036–2.629), smoking history (OR 2.484, 95% CI 1.071–5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160–5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155–0.412).ConclusionsHigher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.

Risk factors for rheumatoid arthritis-associated interstitial lung disease: a retrospective study.

The objective of this study was to assess clinical and imaging features of rheumatoid arthritis (RA) associated with interstitial lung disease (ILD), (RA-ILD) group, in comparison to RA without ILD (RA-C) and to identify the associated factors to ILD. This was a retrospective comparative study (from June 2015 to March 2022) including RA patients aged ≥18 years. The RA-C control group was matched according to age (±2 years), gender, and RA duration (±2 years). General data, RA characteristics, ILD features, and treatment modalities were recorded. Statistical analysis was performed to determine the predictive factors of ILD. A total of 104 patients were included (52 RA-ILD and 52 RA-C); sex ratio was 0.36. Mean age was 66.3±11 years (RA-ILD) versus 65.6±10.8 years (RA-C) (p=0.72). In comparison to RA-C, RA-ILD patients were significantly higher smokers (p=0.01) and physically inactive (p=0.01). Regarding RA features, RA-ILD patients have significantly increased positive anti-citrullinated peptide antibody (ACPA) (p=0.01), ACPA rate (p<0.001), erosive disease (p<0.001), and disease activity score (p<0.001). Mean time to ILD diagnosis was 5.85±7.16 years. Chest high-resolution computed tomography (HRCT) patterns of disease were identified: nonspecific interstitial pneumonia (NSIP) (28.8%), usual interstitial pneumonia (UIP) (17.3%), organizing pneumonia (OP) (25%), acute interstitial pneumonia (13.5%), and respiratory bronchiolitis (3.8%). Multivariate analysis identified smoking, high baseline DAS28 (disease activity score 28) and ACPA positivity as predictive factors of ILD. Our results confirmed the reported associated factors of ILD in RA (smoking, higher disease activity, ACPA positivity). Thus, we need to target the modifiable factors by supporting and educating RA patients to quit smoking and intensify disease modifying anti-rheumatoid drugs (DMARD) to reach remission.

Factors associated with interstitial lung disease and the progressive fibrosing phenotype in rheumatoid arthritis–related interstitial lung disease

BackgroundThe risk factors for interstitial lung disease (ILD) in rheumatoid arthritis (RA) are inconsistent among previous studies. Furthermore, the factors associated with the emergence of the recently defined progressive fibrosing (PF) phenotype are unknown. Herein, we analyze the risk factors for ILD in RA. We also analyze the factors associated with a PF phenotype. MethodsWe collected the clinical and laboratory details of subjects with RA with (cases) or without (controls) ILD. Scoring of high-resolution computed tomography (HRCT) features of ILD was performed. We identified the subgroup that developed the PF phenotype during follow-up. We analyzed the factors associated with ILD using logistic regression (primary objective). We also compared the characteristics of ILD subjects with or without the PF phenotype (secondary objective). ResultsWe included 60 subjects (30 cases, 30 controls). Subjects with ILD had higher age, lower body mass index, longer duration of RA, and poorer lung function than the controls. Age (p = 0.007) and the duration of RA (p = 0.049) were the only significant predictors of ILD on univariate and multivariate analysis, respectively. Six (20%) subjects with RA-ILD developed a PF phenotype. These subjects were older, had greater frequency of honeycombing, and higher HRCT scores for honeycombing and aggregate fibrosis than those without the PF phenotype. Among subjects with honeycombing, 41.7% developed the PF phenotype. ConclusionsRA-ILD was associated with the duration of RA and age. Subjects with the PF phenotype were older and had higher honeycombing and fibrosis scores on HRCT chest.

Associations between shortened telomeres and rheumatoid arthritis-associated interstitial lung disease among U.S. Veterans

BackgroundShortened telomeres are associated with several different subtypes of interstitial lung disease (ILD), although studies of telomere length and ILD in rheumatoid arthritis (RA) are lacking. MethodsWithin the Veterans Affairs Rheumatoid Arthritis (VARA) registry, we performed cross-sectional and case-control studies of prevalent and incident ILD, respectively. We randomly selected a subset of RA patients with ILD and individually matched them to RA patients without ILD according to age, sex, and VARA enrollment date. Telomere length was measured on peripheral blood leukocytes collected at registry enrollment using quantitative PCR (T/S ratio). Short telomeres were defined as a T/S ratio in the lowest 10th percentile of the cohort. ResultsOur cross-sectional study cohort was comprised of 54 RA-ILD patients and 92 RA-non-ILD patients. T/S ratios significantly differed between patients with and without prevalent ILD (1.56 [IQR 1.30, 1.78] vs. 1.96 [IQR 1.65, 2.27], p < 0.001). Similarly, prevalence of ILD was significantly higher in patients with short vs. normal-length telomeres (73.3% vs. 32.8%, p = 0.002). Short telomeres were independently associated with an increased odds of prevalent ILD compared to normal-length telomeres (adjusted OR 6.60, 95% CI 1.78–24.51, p = 0.005). In our case-control analysis, comprised of 22 incident RA-ILD cases and 36 RA-non-ILD controls, short telomeres were not associated with incident RA-ILD (adjusted OR 0.90, 95% CI 0.06–13.4, p = 0.94). ConclusionShort telomeres were strongly associated with prevalent but not incident ILD among patients with RA. Additional studies are needed to better understand telomere length dynamics among RA patients with and without ILD.

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.

Lack of Association of rs12702634 in RPA3-UMAD1 With Interstitial Lung Diseases in Japanese Rheumatoid Arthritis Patients.

Background:Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in RPA3-UMAD1. We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association.Methods:Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease.Results:No association was detected for rs12702634 with ILD in RA (P = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association (P = .0996, OR 1.52, 95% CI 0.92–2.49).Conclusions:The present study demonstrated no association of RPA3-UMAD1 rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.

Prevalence and clinical characteristics of symptomatic diffuse interstitial lung disease in rheumatoid arthritis in a Spanish population

Background and objectivesIn Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. Materials and methodsIn our hospital’s interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. ResultsOf the 2729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26–2.29) with an age at diagnosis of RA of 57.3 ± 13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. ConclusionsWe have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.

Prevalencia y características clínicas de la enfermedad pulmonar intersticial difusa sintomática en la artritis reumatoide en una población española

Background and objectivesIn Spain, epidemiological studies of the prevalence of diffuse interstitial lung disease (ILD) in rheumatoid arthritis (RA) are limited. Our objective was to estimate the prevalence of symptomatic ILD in RA and its characteristics in our area. Materials and methodsIn our hospital's interdisciplinary rheumatology and pulmonology clinic, a prospective longitudinal observational study was designed in which we included RA with respiratory symptoms and ILD confirmed by high resolution computed tomography. ResultsOf the 2,729 people with RA in our area, 47 had symptomatic ILD, estimating a prevalence of symptomatic ILD in RA of 1.72% (95% CI 1.26 - 2.29) with an age at diagnosis of RA of 57.3±13.3 years. It was more frequent in men, 60.6% had a history of smoking, and 84.3% and 84.7% had rheumatoid factor (RF) and anti-cyclic citrullinated peptide (Anti-CCP) antibodies, respectively. The most frequent pattern was usual interstitial pneumonitis (UIP), appearing in 28 (31.1%). Nonspecific interstitial pneumonia (NSIP) was more frequent in women, while the combined pulmonary fibrosis-emphysema (CPFE) syndrome presented exclusively in men. ConclusionsWe have analysed the prevalence of symptomatic RA-ILD in our area, which is lower than expected, probably in relation to the definitions used. We have also described that the UIP pattern is the most frequent in RA in our environment, followed by the NSIP. Lastly, we have analysed the prevalence of CPFE in RA, which reaches 13%, for the first time.

Interstitial Lung Disease and its Associations in Rheumatoid Arthritis: Data from a District General Hospital in Sri Lanka.

Context:Interstitial lung disease (ILD) is a frequent pulmonary manifestation of rheumatoid arthritis (RA). No Sri Lankan studies have determined the prevalence of lung disease in RA and its associations.Aims:To find the prevalence of ILD in RA and its association with rheumatoid factor (RF), erosions, Disease activity score in 28 joints (DAS 28), disease duration, Body mass index(BMI), erythrocyte sedimentation rate (ESR), smoking, and also to determine the prevalence of lung disease with demographic factors like age, sex, and income.Settings and Design:Questionnaire based retrospective study at a District General Hospital in Sri Lanka.Materials and Methods:Diagnosed RA patients included through convenient sampling as it was a simple method that could facilitate data collection in a short duration. Since all patients with a diagnosis of RA were eligible, all consecutive patients with a diagnosis of RA at the rheumatology clinics were included in the study. To reduce the bias a large sample of patients were used as well as patients attending different rheumatology clinics were included and also patients who were referred to the hospital from peripheries were included in the study. The calculated sample size was 384 and according to patient numbers attending clinics, a period of 6 months was decided to select the study sample.Statistical Analysis Used:Chi-Square calculation and logistic regression analysis using Minitab 17 software.Results:From 384 patients, the prevalence of ILD was 14.58%, been 5.4% in early RA (<2 years disease duration). Mean age of ILD group was 52.94 years (95% CI 64.66-41.22). Mean RA duration was 7.69 years (95% CI, 2.38-12.99). Male to female sex ratio of RA was 1:7, and that of ILD was 2:9. DAS 28 was 4.58 (95% CI, 3.48-5.68). Statistically significant associations were noted with ILD and DAS 28 (P = .0006), ESR (P = .005), RF (P = .03), erosions (P < .00001), and smoking (P < .05). Mean BMI was 22.67 kg and 75.78% had low income (<50 000 rupees/month = 327 US $).Conclusions:ILD significantly associates RA severity indices like DAS 28, ESR, erosions, RF, and also with smoking. No significant association was found with BMI or gender difference. Therefore, disease severity indices could be used to predict progression to ILD in RA.

Serum Metabolomic Profiling in Rheumatoid Arthritis Patients With Interstitial Lung Disease: A Case-Control Study.

Objectives: Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers.Methods: Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry.Results: A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate Q = 1.87 × 10−11 and 7.09 × 10−6, respectively), and glycerol was higher (Q = 1.20 × 10−6), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867–0.968, sensitivity 0.880, specificity 0.780).Conclusions: Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.

Performance of Administrative Algorithms to Identify Interstitial Lung Disease in Rheumatoid Arthritis.

To determine the performance of administrative-based algorithms for classifying interstitial lung disease (ILD) complicating rheumatoid arthritis (RA). Participants in a large, multicenter RA registry were screened for ILD using codes from the International Classification of Diseases, Ninth Revision (ICD-9) and the ICD-10. Medical record review confirmed ILD among participants screening positive and a random sample of those screening negative. ICD and procedure codes, provider specialty, and dates were extracted from Veterans Affairs administrative data to construct ILD algorithms. Performance of these algorithms against medical record review was assessed by sensitivity, specificity, positive predictive value (PPV), negative predictive value, and kappa using inverse probability weighting to account for sampling methods. Medical records of 536 RA patients were reviewed, confirming 182 (stringent definition) and 203 (relaxed definition) cases of ILD. Initially, we identified ≥2 ICD codes from inpatient or outpatient encounters as optimal discriminating factors (specificity 96.0%, PPV 65.5%; κ = 0.70). Subsequently, we constructed a set of ICD-9 and ICD-10 codes that improved algorithm specificity (specificity 96.8%, PPV 69.5%; κ = 0.72). Algorithms that included a pulmonologist diagnosis or chest computed tomography plus pulmonary function testing or lung biopsy had improved performance (specificity 98.0%, PPV 77.4%; κ = 0.75). PPV increased with exclusion of other ILD causes (78.5%) in comparison with the relaxed ILD definition (82.4%) and in sensitivity analyses (83.4-86.3%). Gains in specificity and PPV with greater algorithm requirements were accompanied by declines in sensitivity. Administrative algorithms with optimal combinations of ICD codes, provider specialty, diagnostic testing, and exclusion of other ILD causes accurately classify ILD in RA.

Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients: Post Hoc Analysis From 21 Clinical Trials.

Background/ObjectiveTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD.MethodsThis post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as “probable” (supportive clinical evidence) or “possible” (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events.ResultsOf 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13–5.21]), current smokers (2.89 [1.33–6.26]), and Disease Activity Score in 28 joints–erythrocyte sedimentation rate score (1.30 [1.04–1.61]) as significant risk factors for ILD events.ConclusionsAcross P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.

SAT0030 A NOVEL ASSOCIATION BETWEEN ANTI-CARBAMYLATED ANTIBODIES AND INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Interstitial lung disease (ILD) is associated with a significant increase in morbidity and mortality in patients with rheumatoid arthritis (RA). Therefore, an early diagnosis is fundamental. Anti-carbamylated proteins (Anti-CarP) have been described in different chronic respiratory diseases without a previous history of RA.Objectives:The aim of this study was to analyse the association between Anti-CarP and ILD in RA patients.Methods:We performed a cross-sectional study, including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised 2 groups: 1) RA patients diagnosed with ILD (RA-ILD group) and 2) RA patients without ILD (non-ILD RA group). ILD was diagnosed by high-resolution tomography and confirmed by a multidisciplinary committee. Three IgG Anti-CarP autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib), and fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarPs and ILD were explored using multivariable logistic regression adjusted by a set of variables known to be related to the development of ILD: smoking, sex, age, RA disease duration, RF and ACPA. An independent replication sample was obtained to validate our findings from another hospital.Results:The main population included 179 patients: 37 were included in the RA-ILD group, and 142 in the non-ILD RA group. Most patients were female (79%), with a mean age of 59.7±13 years with a mean disease duration of 6.6±5 years. Baseline features are shown in table 1. The replication sample was composed of 25 patients in the RA-ILD group and 50 patients in the non-ILD RA group. We found that Anti-CarPs specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs. 43%; Anti-Fib 73% vs. 51%; Anti-CFFHP 38% vs. 19%; Anti-CarP-IgA 51% vs. 20%, p&lt;0.05 for all comparisons). Serum mean titers of Anti-CarPs were higher in RA-ILD patients with significant statistical differences for all of them, except Anti-Fib. The multivariate analysis showed that Anti-CarPs specificities were independently associated with ILD (Anti-FCS (OR: 3.42; CI95%: 1.13-10.40), Anti-Fib (OR: 2.85; CI95%: 0.83-9.70), Anti-CFFHP (OR: 3.11; CI95%: 1.06-9.14) and Anti-FCS-IgA (OR: 4.30; CI95%: 1.41-13.04). In the replication sample our findings were validated only for Anti-FCS (OR: 10.42; CI95%: 1.68-64.46).TABLE 1.Main population demographic, clinical, therapeutic, and autoantibody status features.RA-ILDn:37Non-ILD RAn:142p valueFemale (%)25 (68)116 (82)NSAge mean (±SD)67.3 (10.1)57.7 (12.9)&lt;0.005Mean disease duration (±SD)11.6 (7.1)5.3 (13.3)&lt;0.005Ever smokers (%)21 (57)62 (44)NSSmoking cumulative dose (±SD)30.7 (11.1)21.8 (12)&lt;0.005Caucasian (%)31 (84)120 (85)NSTreatmentGlucocorticoids (%)25 (68)81 (57)NScsDMARDs (%)33 (89)132 (86)NSMTX (%)20 (54)95 (67)NSbDMARDs (%)11 (30)36 (25)NSMean DAS28 (±SD)3.71 (1.35)2.74 (1.05)&lt;0.005Erosive disease (%)26 (70)63 (44)&lt;0.005Mean HAQ-DI (CI-95%)0.69 (0.53-0.85)0.31 (0.24-0.38)&lt;0.005ACPA positive (%)29 (78)99 (70)NSMedian titer ACPA (IQR) CU674 (2,215)143 (1,132)NSRF positive (%)28 (76)83 (59)NSMedian titer RF (IQR) IU105 (298)34 (110)NSConclusion:A strong association between RA-ILD and Anti-CarP was found independently of cofounders, including RF and ACPA. Our findings suggest a possible link between Anti-CarP and the development of ILD.Disclosure of Interests:Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Sebastian Rodriguez-Garcia: None declared, Katherine Cajiao: None declared, Gabriela Jimenez: None declared, Maria Jose Gomara: None declared, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Ivette Casafont-Solé: None declared, Julio Ramirez: None declared, José Gomez Puerta Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Susana Holgado Pérez: None declared, Juan de Dios Cañete: None declared, Isabel Haro: None declared, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer

A Patient with KL-6 Elevation with Anti-TNFα Who Could Receive Long-Term Use without Interstitial Pneumonia after Class Switch of Anti-TNFα

A 40-year-old man with refractory ulcerative colitis (UC) was treated with tumor necrosis factor α inhibitor (anti-TNFα), infliximab. One month later, the chest computed tomography and laboratory test showed noninfectious interstitial lung disease (ILD) and elevation of serum Krebs von den Lungen-6 (KL-6). Fortunately, ILD disappeared after the discontinuation with anti-TNFα. Two and a half years after his first UC treatment, he was treated again with another anti-TNFα, adalimumab, for relapse and he had a second ILD. This course suggested anti-TNFα induced ILD. The characteristics of anti-TNFα-induced ILD in inflammatory bowel disease (IBD) are not well understood. We summarized and investigated the characteristics of such patients based on a literature review including 15 cases. It suggested that anti-TNFα-induced ILD in IBD might be rare and tends to have a better outcome compared with ILD in rheumatoid arthritis.

Clinicoradiological profile of interstitial lung disease in rheumatoid arthritis

Background: The burden of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients in resource limited countries like India is often under-reported. This study was conducted to find out the clinicoradiological profile of ILD in patients with RA in India.&#x0D; Aims and Objectives: (1)To find out the frequency of Interstitial Lung Disease (ILD) in Rheumatoid Arthritis (RA) (2) To correlate the clinical findings with those of radiological(Chest x-ray &amp; HRCT Thorax) and pulmonary function tests including Spirometry, TLCO (Diffusing capacity of the Lung for Carbon monoxide/DLCO Corrected for alveolar volume i.e., DLCO/V) Estimation.&#x0D; Materials and Methods: Thirty consecutive patients of RA (with or without pulmonary symptoms or signs) who fulfill the American Classification of Rheumatology criteria1987 were selected from the patients attending the General Medicine OPD (Rheumatology Division) of B.R. Singh Hospital during the study period regardless of being on any medications for RA. This was a cross-sectional, descriptive study. Results were tabulated in Microsoft office excel worksheet and descriptive statistics were expressed as means, standard deviations (SD) mean for continuous normally distributed data and as percentages. Statistical software SPSS version 19.0 was used for data analysis. Unpaired t test (for continuous data)/Chi square test (for proportion) was used for comparing cases and controls.&#x0D; Results: The frequency of ILD in RA was 60%. Female patients with a positive rheumatoid factor had a greater chance of development of ILD.The frequency was found to be increased after the age of 40 years. Though in this study 60% of patients had restrictive pattern, 31% had obstructive and 3 % had mixed pattern on Spirometry. The patients with deforming RA had greater frequency of restrictive or mixed pattern on Spirometry. 22.22% patients had a decreased TLCO despite having normal CXR. Despite being asymptomatic12 patients had restrictive lung disease and reduced TLCO with HRCT evidence of ILD. Overall, Spirometry &amp; TLCO are the most appropriate tests to detect restrictive lung disease in patients with RA. In fact, HRCT can show evidence of ILD even when clinical parameters and Chest X-ray are normal.On HRCT of thorax reticular pattern and sub-pleural fibrosis (UIP-Usual interstitial pneumonia) are the predominant pattern.&#x0D; Conclusion: The frequency of ILD in RA is quite high. It may be recommended to use Spirometry &amp; TLCO as screening test for detection of restrictive lung disease in patients with RA who should undergo HRCT of chest to confirm presence of ILD in a resource limited setting.

Methotrexate and lung disease in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common chronic inflammatory disease affecting many tissues and resulting in substantial morbidity and increased mortality. Arthritis is the most notable clinical feature, but extra-articular features can have devastating consequences. Pulmonary manifestations are common in RA, with high rates of disease related lung disease and a propensity to pulmonary infections. Respiratory illness remains a leading cause of death among RA populations. Modern medicine greatly reduces the illness burden among patients with RA, particularly through the use of disease-modifying medications. Methotrexate is recommended as the first-line treatment of RA as it effectively reduces disease activity, morbidity and mortality. However, it has long been implicated as a causative agent in lung disease. The evidence for a cause and effect relationship in modern populations is contentious, but critically important. Increasing recognition of the importance and prevalence of interstitial lung disease in RA, and recent studies on the incidence of lung disease among RA and non-RA populations have cast doubt on the role of methotrexate as a causative agent. A correct understanding of the complex pulmonary disease processes in RA is crucial if we are to improve outcomes in this patient group. In this article we will discuss the epidemiology and characteristics of lung disease in rheumatoid arthritis and its possible relationship to methotrexate use.

Rheumatoid arthritis and lung - more than a minor aspect of the disease

Although rheumatoid arthritis (RA) mainly manifests as polyarthritis, there is growing evidence that the initiation of the pathological immune reaction against citrullinated peptides takes place in the lung. However, in spite of this important role of the lung in pathophysiology, clinically manifest lung involvement has been demonstrated only in about 2-5 % of the patients with RA, and therefore is relatively rare. In particular the severe interstitial lung involvement with histological pattern of usual interstitial pneumonia has a bad prognosis and an increased mortality. Methotrexate (MTX), as the most important disease modifying drug for treatment of RA is not associated with the appearance or progression of interstitial lung disease in RA. MTX-induced pneumonitis is a rare, although potentially severe complication of this treatment.

Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature review

ObjectiveTo review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice. MethodsWe performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010–2012 and EULAR 2010–2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes. ResultsThe literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold, 1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEF- and TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs. ConclusionAs previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition.

Interstitial Lung Disease in Rheumatoid Arthritis in the Era of Biologics

Interstitial lung disease (ILD) represents a severe manifestation in connective tissue diseases (CTD), with an overall incidence of 15%, and it is still a challenge for clinicians evaluation and management. ILD is the most common manifestation of lung involvement in Rheumatoid Arthritis (RA), observed in up to 80% of biopsies, 50% of chest Computed Tomography (CT) and only 5% of chest radiographs. Histopatological patterns of ILD in RA may present with different patterns, such as: usual interstitial pneumonia, non specific interstitial pneumonia, desquamative interstitial pneumonia, organizing pneumonia, and eosinophilic infiltration. The incidence of ILD in RA patients is not only related to the disease itself, many drugs may be in fact associated with the development of pulmonary damage. Some reports suggest a causative role for TNFα inhibitors in RA-ILD development/worsening, anyway, no definitive statement can be drawn thus data are incomplete and affected by several variables. A tight control (pulmonary function tests and/or HRCT) is mandatory in patients with preexisting ILD, but it should be also performed in those presenting risk factors for ILD and mild respiratory symptoms. Biologic therapy should be interrupted, and, after excluding triggering infections, corticosteroids should be administered.