RMD Open最新文献

{"title":"Nerandomilast alleviates myositis-associated interstitial lung disease by modulating the non-Smad signalling pathway and activating the cAMP-PKA-RhoA pathway.","authors":"Xi Cui, Wenjun Li, Hui Chai, Yi Jiang, Jin Guo, Jumei Yang, Jiarui Zhu, Sigong Zhang","doi":"10.1136/rmdopen-2025-006683","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006683","url":null,"abstract":"<p><strong>Objectives: </strong>Nerandomilast, a selective phosphodiesterase 4B (PDE4B) inhibitor, has been extensively investigated for the treatment of pulmonary fibrosis; however, its therapeutic potential and mechanisms of action in idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) remain to be elucidated.</p><p><strong>Methods: </strong>A myositis-associated ILD mouse model was treated with nerandomilast (BI 1015550), and lung pathology was assessed histologically. Human lung microvascular endothelial cells-5a were stimulated with neutrophil extracellular traps (NETs) to induce endothelial-mesenchymal transition (EndMT). Western blotting, immunofluorescence, qPCR and ELISA were employed to analyse pathways and cytokines.</p><p><strong>Results: </strong>PDE4B was upregulated in the lungs of patients with IIM-ILD and in mice. Treatment with BI 1015550 significantly reduced lung inflammation and fibrosis scores, decreased inflammatory cytokines in bronchoalveolar lavage fluid and serum, alleviated muscle inflammation and lowered kinase activity without evident hepatorenal toxicity. Immunofluorescence and immunohistochemistry revealed diminished NET markers, reduced inflammatory cell infiltration (CD3, CD11b, F4/80), suppression of EndMT, downregulation of Ras homolog family member A (RhoA) and inhibition of key fibrotic pathways: phosphorylated phosphoinositide 3-kinase (P-PI3K), phosphorylated protein kinase B (P-AKT), phosphorylated p38 mitogen-activated protein kinase (P-P38), phosphorylated extracellular signal-regulated kinase (P-ERK), phosphorylated nuclear factor kappa-B (P-NF-κB). In vitro, BI 1015550 inhibited phorbol 12-myristate 13-acetate-induced neutrophil extracellular trap formation (NETosis) and EndMT.</p><p><strong>Conclusions: </strong>Nerandomilast alleviates IIM-ILD by inhibiting NET formation and suppressing EndMT in lung microvascular endothelial cells, potentially through non-Smad signalling pathway modulation and cAMP-PKA-RhoA pathway activation. These findings suggest that the specific inhibition of PDE4B is a potential therapeutic approach for IIM-ILD.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in bone mineral density and fractures during 2 years of low-dose glucocorticoid treatment for rheumatoid arthritis: a systematic literature review and individual participant data meta-analysis.","authors":"Andriko Palmowski, Tobias Haugegaard, Ingiäld Hafström, Henning Bliddal, Judith Oldenkott, Siegfried Wassenberg, Ernest Choy, John Kirwan, Robin Christensen, Maarten Boers, Frank Buttgereit","doi":"10.1136/rmdopen-2025-006615","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006615","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the effects of 2 years of low-dose glucocorticoid (GC) treatment on bone mineral density and fracture risk in patients with rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>We performed a protocolised (dx.doi.org/10.17504/protocols.io.6qpvr3ombvmk/v1) systematic literature review and individual participant data meta-analysis of randomised trials in early and established RA, which compared GCs at ≤7.5 mg prednisone equivalent/day with placebo or standard of care. All patients could receive background treatment with disease-modifying antirheumatic drugs. Changes in lumbar spine and femoral bone density and participants with ≥1 clinical fracture over 2 years in intention-to-treat analyses were coprimary endpoints. Main analyses were based on one-stage models; I² was estimated from two-stage models. Missing data were handled using multiple imputation. Several sensitivity analyses assessed the robustness of our results.</p><p><strong>Results: </strong>Out of 2336 articles, five out of six identified trials provided individual participant data (1112 participants). Greater bone loss was observed at the lumbar spine in the GC compared with the control group (-0.021 g/cm²; 95% CI -0.037 to -0.005; p=0.034; I²=31%) but not at the femur (0.004 g/cm²; 95% CI -0.008 to 0.016; p=0.47; I²=0%). Subgroup analyses did not reveal groups particularly susceptible to GC-induced bone loss at the lumbar spine. 35 participants experienced ≥1 fracture; fracture risk was comparable in both groups. Sensitivity analyses yielded consistent results.</p><p><strong>Conclusion: </strong>Low-dose GCs, used for 2 years to treat RA, lead to bone loss at the lumbar spine but not at the femur.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral bisphosphonates and risk of incident osteoarthritis in individuals with osteoporosis: a target trial emulation.","authors":"Masaki Hatano, Yuya Kimura, Akira Okada, Hisatoshi Ishikura, Takeyuki Tanaka, Taku Saito, Sakae Tanaka, Hideo Yasunaga","doi":"10.1136/rmdopen-2026-006832","DOIUrl":"https://doi.org/10.1136/rmdopen-2026-006832","url":null,"abstract":"<p><strong>Objectives: </strong>Owing to the underrepresentation of early-stage disease in randomised trials and inconsistent clinical evidence, using oral bisphosphonates to prevent incident osteoarthritis in adults with osteoporosis lacks consensus. We aimed to analyse the causal relationship between oral bisphosphonates and osteoarthritis.</p><p><strong>Methods: </strong>We performed a sequential nested target trial emulation with propensity score matching using longitudinal health insurance claims data from Japan collected between 2015 and 2024. Eligible individuals were aged ≥50 years with osteoporosis who had been receiving vitamin D therapy. We compared those who initiated oral bisphosphonates with those who did not initiate and continued vitamin D therapy. The primary outcome was incident osteoarthritis. Secondary outcomes included joint-specific osteoarthritis (knee, hip and hand) over a 3-year follow-up period. The absolute risk reduction (ARR) and relative risk (RR) at 3 years were estimated using a Kaplan-Meier estimator.</p><p><strong>Results: </strong>We included 10 844 bisphosphonate initiators and 21 283 non-initiators. The ARR for incident osteoarthritis was 0.4% (95% CI -1.3% to 1.0%), with an RR of 0.97 (95% CI 0.92 to 1.12). In joint-specific analyses, the ARR (95% CI) and RR (95% CI) were 0.5% (-1.1% to 1.0%) and 0.95 (0.90 to 1.12) for knee osteoarthritis; 0.2% (-0.4% to 0.7%) and 0.89 (0.64 to 1.27) for hip osteoarthritis; and -0.3% (-0.7% to 0.3%) and 1.20 (0.81 to 1.50) for hand osteoarthritis, respectively.</p><p><strong>Conclusion: </strong>Oral bisphosphonate use was not associated with a lower risk of incident osteoarthritis among adults with osteoporosis.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetic resonance imaging of hand involvement in polymyalgia rheumatica: a comparison with seropositive rheumatoid arthritis.","authors":"Martin Fruth, Greta Kelmendi-Starova, Philipp Martin-Seidel, Philipp Sewerin, Lars Schimmöller, Xenofon Baraliakos","doi":"10.1136/rmdopen-2026-006838","DOIUrl":"https://doi.org/10.1136/rmdopen-2026-006838","url":null,"abstract":"<p><strong>Background: </strong>Involvement of hands is a frequent finding in polymyalgia rheumatica (PMR) and can lead to misclassification as late-onset rheumatoid arthritis (RA).</p><p><strong>Objective: </strong>To compare the inflammatory pattern as shown by contrast-enhanced MRI (ceMRI) of hand involvement in PMR to seropositive RA (RA+).</p><p><strong>Methods: </strong>MRIs of patients diagnosed with PMR and clinically suspected hand involvement and with RA+, matched for age/sex, were analysed retrospectively. Synovitis, osteitis and erosions of metacarpophalangeal (MCP) joints 2-5 plus tenosynovitis of flexor/extensor compartments were evaluated using the Rheumatoid Arthritis MRI Score. For assessment of periarticular inflammation around MCP joints, a semi-quantitative scoring was introduced.</p><p><strong>Results: </strong>Distribution of synovitis scores differed significantly between the groups with mostly minor and occasionally moderate synovitis in PMR versus uniformly distributed total scores in RA+. Scores of periarticular inflammation were significantly higher in PMR. Tenosynovitis of extensors and flexors was prevalent in both groups, but flexor tenosynovitis was significantly more prevalent in PMR. Detection of erosions and osteitis was absent in PMR cases but prevalent in RA+ (all p<0.001). A combination of minor to moderate synovitis together with severe periarticular inflammation of an MCP joint represented a characteristic finding in PMR and, if evident in at least one MCP joint, differentiated the groups with a sensitivity and specificity of 78.4% and 78.4%, respectively. Specificity improved to 90.2% at the expense of sensitivity (70.6%) when this characteristic inflammatory pattern was present in more than one MCP joint per hand.</p><p><strong>Conclusion: </strong>Hand involvement in PMR could be clearly differentiated in ceMRI from RA+ by the intensity of periarticular inflammation of MCP joints.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful treatment of multicentric reticulohistiocytosis with JAK inhibitor: a case series.","authors":"Stéphane Hilliquin, Nicolas Dupin, Nathalie Franck, Sara Laurent-Roussel, Frédérique Larousserie, Jérôme Avouac, Corinne Miceli-Richard","doi":"10.1136/rmdopen-2025-006661","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006661","url":null,"abstract":"<p><p>Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans cell histiocytosis characterised by erosive arthritis and papulonodular skin lesions, frequently associated with autoimmune features. Therapeutic strategies remain empirical despite the potentially severe and disabling course. We report three cases of MRH with heterogeneous systemic involvement, all showing sustained, multidomain responses to Janus kinase (JAK) inhibitors.All patients developed inflammatory arthritis, ranging from arthralgia to destructive arthropathy, and early cutaneous papules predominantly affecting the face and trunk. Systemic manifestations included digital microangiopathy with a scleroderma-like capillaroscopic pattern in one patient and interstitial lung disease with lymphocytic alveolitis in another. Two patients fulfilled criteria for Sjögren's syndrome, and all were positive for anti-Sjögren's-syndrome-related antigen A/Ro52kD antibodies, highlighting the autoimmune overlap of MRH.Diagnosis was confirmed histologically by CD68-positive histiocytic and multinucleated giant cell infiltration. Conventional synthetic disease-modifying antirheumatic drugs and tumour necrosis factor inhibitors were ineffective or poorly tolerated, whereas tofacitinib and upadacitinib induced rapid and durable improvement across articular, cutaneous, vascular and pulmonary domains. These observations support a role for JAK-STAT signalling in MRH and suggest JAK inhibition as a rational therapeutic option in refractory multisystem disease.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of biologic class and treatment line on psoriatic arthritis risk in psoriasis: a population-based cohort study.","authors":"Abdulla Watad, Yoav Elizur, Or Hen, Paula David, Yonatan Shneor Patt, Omer Gendelman, Amit Nachman, Alen Zabotti, Merav Lidar, Dennis McGonagle, Howard Amital","doi":"10.1136/rmdopen-2025-006687","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006687","url":null,"abstract":"<p><strong>Background: </strong>Patients with psoriasis (PsO) are at increased risk of developing psoriatic arthritis (PsA). Emerging evidence suggests that biologic therapies may differentially influence the development of PsA; however, there are no data on the relative ability of second-line biological therapy to prevent PsA.</p><p><strong>Aim: </strong>To evaluate the impact of biologic therapy on the risk of incident PsA in patients with PsO with a focus on second-line biologic therapy.</p><p><strong>Methods: </strong>We identified 2819 patients who initiated biologic therapy for PsO between 2002 and 2022, including Tumor Necrosis Factor (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-23p19 inhibitors and IL-12/23 inhibitors. The primary outcome was incident PsA. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate arthritis-free survival and HRs for the development of PsA. Risk was assessed separately for first-line and second-line biologic therapy.</p><p><strong>Results: </strong>Among 2819 patients with PsO initiating first-line biologic therapy, 400 (14.2%) developed PsA. In multivariable Cox regression, first-line anti-IL-23p19 agents were significantly associated with a lower risk of developing PsA compared with TNF inhibitors (HR 0.13; 95% CI 0.02 to 0.96; p=0.045). Among 1246 patients receiving second-line biologics, 125 (10.0%) developed PsA. Notably, in second-line therapy, only IL-17 inhibitors were independently associated with a statistically significant reduction in PsA risk versus TNF inhibitors (HR 0.37; 95% CI 0.16 to 0.85; p=0.019), with trends observed for anti-IL-12/23 (HR 0.14; 95% CI 0.02 to 1.05; p=0.056) and anti-IL-23p19 (HR 0.46; 95% CI 0.20 to 1.07; p=0.070).</p><p><strong>Conclusions: </strong>This is the first study to evaluate second-line biological therapy in relation to PsA risk. IL-17 inhibitor therapy was significantly associated with a reduced risk of incident PsA compared with TNF inhibitors.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cardiometabolic comorbidities on clinical characteristics, prescription patterns and retention rate of first b/tsDMARD treatment in 5299 European real-world patients with psoriatic arthritis.","authors":"Zohra Faizy Ahmadzay, Lykke Midtbøll Ørnbjerg, Mikkel Østergaard, Kasper Yde Jensen, Jacob Brauner Jørgensen, Jette Heberg, Anne Gitte Loft, Brigitte Michelsen, Gareth T Jones, Pasoon Hellamand, Signe Møller-Bisgaard, Mehrdad Shoae Kazemi, Parham Karimi Reikandeh, Jakub Závada, Pavel Horák, Miguel Bernardes, Elsa Vieira-Sousa, Isabel Castrejón, Lucía Otero-Varela, Catalin Codreanu, Laura Kuusalo, Vappu Rantalaiho, Anne C Regierer, Andreas Reich, Burkhard Möller, Raphael Micheroli, Pawel Mielnik, Sella Aarrestad Provan, Karin Lass, Sigrid Vorobjov, Ziga Rotar, Katja Perdan Pirkmajer, Florenzo Iannone, Fabrizio Conti, Bjorn Gudbjornsson, Daniela Di Giuseppe, Marleen van de Sande, Gary J Macfarlane, Handan Yarkan-Tuğsal, Bente Glintborg, Merete Lund Hetland","doi":"10.1136/rmdopen-2025-006477","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006477","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate associations between cardiometabolic comorbidities and clinical characteristics, prescription patterns and retention of first biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) in patients with psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>Patients with PsA initiating a first b/tsDMARD treatment in 2015 or later were identified in eight European rheumatology registries. Patients with information on five cardiometabolic comorbidities (obesity, dyslipidaemia, diabetes, hypertension, ischaemic heart disease) at treatment start (baseline) were included. All analyses were conducted according to patients' comorbidity burden (count: 0/1/≥2) and status (presence/absence of each comorbidity). Patient characteristics and prescription patterns were described. Twelve-month treatment retention rates were estimated and compared using Kaplan-Meier plots, log-rank tests and multivariable Cox regression analyses.</p><p><strong>Results: </strong>Among 5299 patients, 36% had at least one cardiometabolic comorbidity. Patients with comorbidity were older, had higher disease activity and more disability. Regardless of comorbidity, most patients were prescribed a tumour necrosis factor inhibitor (76%). The use of interleukin-17 inhibitors increased with comorbidity burden (0/1/≥2 comorbidities: 13%/18%/19%), whereas Janus kinase inhibitor use declined (2.3%/1.6%/0.8%). Retention rates were marginally lower with higher comorbidity burden (80%/76%/78%) (log-rank, p=0.036) and obesity (absent 79% vs present 77%) (log-rank, p=0.04). The risk of treatment withdrawal was only marginally higher in patients with higher comorbidity burden (one comorbidity: HR 1.19; 95% CI 1.02 to 1.40; ≥2 comorbidities: HR 1.18; 0.98 to 1.42).</p><p><strong>Conclusion: </strong>Patients with cardiometabolic comorbidities had higher disease activity at treatment initiation of the first b/tsDMARD. Prescription patterns varied with comorbidity burden. Cardiometabolic comorbidity burden, especially obesity, was associated with marginally lower treatment retention.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-arthritis stages of rheumatoid arthritis: from pathology to precision prevention.","authors":"A H M van der Helm-van Mil, K Raza","doi":"10.1136/rmdopen-2026-006858","DOIUrl":"https://doi.org/10.1136/rmdopen-2026-006858","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic impact of rheumatoid arthritis on respiratory-related mortality in non-tuberculous mycobacterial pulmonary disease.","authors":"Takuro Nii, Yuki Hara, Kazuki Hashimoto, Kiyoharu Fukushima, Takuya Kurihara, Takanori Matsuki, Kazuyuki Tsujino, Keisuke Miki, Koichiro Takahi, Hiroshi Kida","doi":"10.1136/rmdopen-2026-006854","DOIUrl":"https://doi.org/10.1136/rmdopen-2026-006854","url":null,"abstract":"<p><strong>Objectives: </strong>The prognostic implications of rheumatoid arthritis (RA) in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) remain unclear. This study aimed to evaluate the impact of RA on survival outcomes.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 1420 patients newly diagnosed with NTM-PD between 2012 and 2024. Among them, 66 (4.6%) had RA, including 55 who developed NTM-PD after RA onset. These 55 patients (RA group) were compared with 1354 without RA (non-RA group). Respiratory-related mortality was assessed using Cox regression and propensity score matching. To explore mechanisms underlying the excess mortality associated with RA, we conducted sequential Cox regression with stepwise adjustment and quantified attenuation of the RA effect on the log-hazard scale.</p><p><strong>Results: </strong>RA was an independent predictor of respiratory-related death in multivariable Cox analysis (HR 4.30, 95% CI 2.17 to 8.52). Five-year survival was significantly lower in the RA group than in the non-RA group (74.7% vs 92.9%, log-rank p<0.001) and remained inferior after matching (p=0.029). Sequential adjustment demonstrated substantial attenuation of the RA effect after accounting for interstitial lung disease (ILD), with the HR decreasing from 3.25 to 2.44 (24.5% attenuation), and to 2.09 after adjustment for systemic inflammation burden reflected by C-reactive protein (37.5% attenuation).</p><p><strong>Conclusion: </strong>RA is an independent predictor of respiratory-related mortality in patients with NTM-PD. This excess risk is partly explained by ILD and systemic inflammation burden. These findings highlight structural and systemic pathways contributing to poor prognosis, underscoring the need for comprehensive management in this high-risk population.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat-not-burn tobacco induces protein post-translational modifications and apoptosis in bronchial cells: possible role in rheumatoid arthritis.","authors":"Claudia Ciancarella, Federica Maria Ucci, Valeria Manganelli, Tina Garofalo, Elena Fasciolo, Roberta Priori, Fulvia Ceccarelli, Manuel Sergi, Camilla Montesano, Francesco Bartolini, Antonio Sili Scavalli, Fabrizio Conti, Maurizio Sorice, Cristiano Alessandri","doi":"10.1136/rmdopen-2025-006645","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006645","url":null,"abstract":"<p><strong>Objectives: </strong>Smoking is recognised as one of the strongest environmental risk factors for the development of rheumatoid arthritis (RA). Cigarette smoke increases protein post-translational modifications (PTMs), including citrullination and carbamylation, involved in the pathogenetic mechanisms of RA. Recently, tobacco companies developed new products, such as iQOS, a heat-not-burn cigarette (HNBC), which are becoming increasingly used. To date, only two epidemiological studies have been conducted in the rheumatology field. However, no studies are available on the effects of HNBCs on the pathogenic mechanisms involved in rheumatic diseases. We aimed to evaluate whether HNBCs are associated with an increase in PTMs and their effects on cell death mechanisms, such as apoptosis.</p><p><strong>Methods: </strong>Human bronchial cells (BEAS-2B) were treated with cigarette smoke extracts from traditional cigarettes (TC) and HNBC. Western blot was performed to assess protein citrullination and carbamylation, while apoptosis was assessed by flow cytometry, after staining with annexin V-FITC/PI and western blot through enzyme Parp1 evaluation.</p><p><strong>Results: </strong>The exposure of BEAS-2B to HNBC or TC extracts causes significantly increased citrullination and carbamylation of proteins, compared with untreated cells. Furthermore, it leads to an augmentation of apoptosis, evaluated through annexin V-FITC/PI and enzyme Parp1 levels.</p><p><strong>Conclusion: </strong>Our results show that the extracts of HNBC and TC increase citrullination, carbamylation and influence cell death, causing an activation of apoptosis. This is the first study showing the effects of HNBC on PTMs and cell death mechanisms, raising alarm about the safety of these smoking alternatives in rheumatology. These data allow us to speculate that HNBC, like TC, could represent a risk factor for the development of RA in genetically susceptible individuals.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 2","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}