Rate of severe and fatal infections in a cohort of patients with interstitial lung disease associated with rheumatoid arthritis: a multicenter prospective study

ObjectiveTo describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD).Patients and methodsThe study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection.ResultsWe followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants.ConclusionPatients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care

Ability to Participate in Social Activities of Rheumatoid Arthritis Patients Compared with Other Rheumatic Diseases: A Cross-Sectional Observational Study

Objectives: To compare the ability to participate in social activities among rheumatoid arthritis patients with other rheumatic disease patients and identify potentially implicated factors. Patients and methods: Between June and November 2019, we consecutively selected patients aged ≥18 years with RA (defined according to ACR/EULAR 2010), SpA (ASAS/EULAR 2010), and SLE (ACR 1997). Main outcome measures: Ability to participate in social roles and activities evaluated using the PROMIS score v2.0 short-form 8a (PROMIS-APS). Secondary outcomes: Participation in social activities according to a series of variables (mobility, depression, satisfaction with social relationships, social isolation, company, emotional support, instrumental support, and support via information). We evaluated the association between the ability to participate in social activities and associated variables using multivariable linear regression analysis. Results: The study population comprised 50 patients with RA (33.1%), 51 patients (33.8%) with SpA, and 50 patients (33.1%) with SLE. The mean PROMIS-APS scores were similar in the three groups. The multivariable analysis for the whole sample showed that the ability to participate in social activities was inversely associated with depression and directly with social satisfaction, mobility, company, and age. The stratified analysis revealed an inverse association between inflammatory activity and ability to participate in social activities in patients with RA and SpA, but not in those with SLE. Conclusion: All patients with RA, SpA, and SLE had a similar ability to participate in social activities. This was associated with other psychosocial factors (social satisfaction, mobility, company, depression) and clinical factors (age and inflammatory activity)

Predictors of Progression and Mortality in Patients with Prevalent Rheumatoid Arthritis and Interstitial Lung Disease: A Prospective Cohort Study

Objectives: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. Patients and methods: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving disease-modifying antirheumatic drugs (DMARDs) between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main endpoint was “Progression to ILD at the end of follow-up” in terms of the following outcomes: (1) improvement (i.e., improvement in forced vital capacity (FVC) ≥10% or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥15% and absence of radiological progression); (2) nonprogression (stabilization or improvement in FVC ≤10% or diffusing capacity of the lungs for carbon monoxide (DLCO) 10% or DLCO >15% and radiological progression); or (4) death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with the worsening of ILD. Results: After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months after diagnosis of ILD. The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (hazard ratio (HR), 2.6 (95%CI, 1.0–6.7)), FVC <80% (HR, 3.8 (95%CI, 1.5–6.7)), anticitrullinated protein antibody titers (HR, 2.8 (95%CI, 1.1–6.8)), smoking (HR, 2.5 (95%CI, 1.1–6.2)), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 (95%CI, 0.2–0.8)). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%). Infection was fatal in 10/18 patients (55.5%) during follow-up. Conclusions: Lung function is stable in most patients with RA-ILD receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs), although one-third worsened or died. Identifying factors associated with worsening in RA-ILD is important for clinical management.Grant for Medical Researchers of the “Fundación Española de Reumatología” 2019.Ye

Characteristics and Predictors of Progression Interstitial Lung Disease in Rheumatoid Arthritis Compared with Other Autoimmune Disease: A Retrospective Cohort Study

Objectives: To describe the characteristics and progression of interstitial lung disease in patients with associated systemic autoimmune disease (ILD-SAI) and to identify factors associated with progression and mortality. Patients and methods: We performed a multicenter, retrospective, observational study of patients with ILD-SAI followed between 2015 and 2020. We collected clinical data and performed pulmonary function testing and high-resolution computed tomography at diagnosis and at the final visit. The main outcome measure at the end of follow-up was forced vital capacity (FVC) >10% or diffusing capacity of the lungs for carbon monoxide >15% and radiological progression or death. Cox regression analysis was performed to identify factors associated with worsening of ILD. Results: We included 204 patients with ILD-SAI: 123 (60.3%) had rheumatoid arthritis (RA), 58 had (28.4%) systemic sclerosis, and 23 (11.3%) had inflammatory myopathy. After a median (IQR) period of 56 (29.8–93.3) months, lung disease had stabilized in 98 patients (48%), improved in 33 (16.1%), and worsened in 44 (21.5%). A total of 29 patients (14.2%) died. Progression and hospitalization were more frequent in patients with RA (p = 0.010). The multivariate analysis showed the independent predictors for worsening of ILD-SAI to be RA (HR, 1.9 [95% CI, 1.3–2.7]), usual interstitial pneumonia pattern (HR, 1.7 [95% CI, 1.0–2.9]), FVC (%) (HR, 2.3 [95% CI, 1.4–3.9]), and smoking (HR, 2.7 [95%CI, 1.6–4.7]). Conclusion: Disease stabilizes or improves after a median of 5 years in more than half of patients with ILD-SAI, although more than one-third die. Data on subgroups and risk factors could help us to predict poorer outcomes.Ye

Científicos en el aula

El trabajo obtuvo el Primer Premio de la Modalidad B de los 'Premios Tomás García Verdejo' a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso académico 2013/2014Se describe el proyecto llevado a cabo en el IES Campos de San Roque (Valverde de Leganés, Badajoz), orientado a promover en el alumnado el pensamiento científico-técnico y el interés por la investigación y la innovación. Entre las actividades llevadas a cabo destacan: la celebración de la Semana de la Ciencia, realización de proyectos de investigación, participación en la Reunión Científica organizada por la Asociación 'Investigación en Secundaria Meridies' celebrada en el IES Vegas Bajas (Montijo, Badajoz) en 2014 y el desarrollo del concurso 'El problema de la semana'ExtremaduraES

Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs

Background & objectives: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. Patients & methods: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). Results: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. Conclusions: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.Funding sources This study was supported by grants: PI21/00591 and PI20/00079, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union); ‘RD21/0002/0033’ -Health Outcomes-Oriented Cooperative Research Networks-, granted by the “Instituto de Salud Carlos III (ISCIII)” and “Funded by the European Union – NextGenerationEU”, via “Mecanismo de Recuperacion ´ y Resiliencia (MRR)” and “Plan de Recuperacion, ´ Transformacion ´ y Resiliencia (PRTR)”; Fundacion Andaluza de Reumatología (FAR); Consejería de Conocimiento, Investigacion ´ y Universidad de la Junta de Andalucía (P20_01367); and Ministerio de Ciencia, Innovacion ´ y Universidades (PID2022- 141500OA-I00). CL-P was supported by a contract from the Spanish Junta de Andalucía (‘Nicolas Monardes’ programme). TC was supported by ‘Sara Borrell’ programme of the ISCIII (CD21/00187), LMB was supported by a predoctoral grant from the ISCIII, (FI22/00299). CPS and NBP were financed by a contract from MINECO ‘Ramon y Cajal’ program (RYC2021-033828-I and RyC- 2017-23437), cofounded by the European Union ‘NextGenerationEU’/PRTR. Acknowledgements: We are grateful to the patients and healthy control donors who participated in this study

Importance of Vaccination against SARS-CoV-2 in Patients with Interstitial Lung Disease Associated with Systemic Autoimmune Disease.

Objectives: To describe the frequency of COVID-19 and the effect of vaccination in patients with interstitial lung disease and systemic autoimmune disease (ILD-SAD) and to identify factors associated with infection and severity of COVID-19. Methods: We performed a cross-sectional multicenter study of patients with ILD-SAD followed between June and October 2021. The main variable was COVID-19 infection confirmed by a positive polymerase chain reaction (PCR) result for SARS-CoV-2. The secondary variables included severity of COVID-19, if the patient had to be admitted to hospital or died of the disease, and vaccination status. Other variables included clinical and treatment characteristics, pulmonary function and high-resolution computed tomography. Two logistic regression was performed to explore factors associated with “COVID-19” and “severe COVID-19”. Results: We included 176 patients with ILD-SAD: 105 (59.7%) had rheumatoid arthritis, 49 (27.8%) systemic sclerosis, and 22 (12.54%) inflammatory myopathies. We recorded 22/179 (12.5%) SARS-CoV-2 infections, 7/22 (31.8%) of them were severe and 3/22 (13.22%) died. As to the vaccination, 163/176 (92.6%) patients received the complete doses. The factors associated with SARS-CoV-2 infection were FVC (OR (95% CI), 0.971 (0.946−0.989); p = 0.040), vaccination (OR (95% CI), 0.169 (0.030−0.570); p = 0.004), and rituximab (OR (95% CI), 3.490 (1.129−6.100); p = 0.029). The factors associated with severe COVID-19 were the protective effect of the vaccine (OR (95% CI), 0.024 (0.004−0.170);

Safety and Effectiveness of Abatacept in a Prospective Cohort of Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease.

To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2-42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03-3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70-0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72-0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile

Nutrition iondine status in pregnant women in the sanitary district Sierra de Huelva-Andévalo, south of spain

Background. Iodine is an essential trace element implicated in synthesis of thyroid hormones. Iodine requirements vary throughout life. Yhis iodine requirement is increased during pregnancy and breastfeeding. In a previous study carried out by our group in 2008, we detected an iodine-deficient area in the province of Huelva, specially in dictrict Sierra de Huelva-Andévalo by means of neonatal TSH determinations. Objective. To reinforce the iodine supplementation campaign and its impact on their newborns in order to assess nutrition iodine status in 'pregnant women using questionnaire and ioduria determination. Material and methods. This study has been jointly carried out by Congenital Hypothiroidism Unit of the Clinical Biochemistry Department of the Virgen Macarena University Hosplital (Seville) and the Gynecology and Clinical Analysis Unit of the Río Tinto Hospital (Huelva) during two years. We studied 313 pregnant women. All of them filled out a personal questionnaire to know the iodine nutritional status in their area. Ioduria was determined by high-resolution liquid chromatography. Data from pregnant and results of the studied variables were analyzed with SPSS v.13.0. Conclusions. Pregnant women from the sanitary district Sierra de Huelva-Andévalo present a median for ioduria which corresponds to an insufficient iodine intake according to the WHO classification. The questionnaire suggest that this iodine deficiency is consequence of an insufficient iodine intake and a low adherence to the treatment.YesIntroducción: El yodo es un oligoelemento esencial que interviene en la síntesis de hormonas tioideas (T3 y T4). Las necesidades de yodo se modifican según la edad y circunstancias fisiológicas, alcanzando los mayores requerimientos en el embarazo y la lactancia. En un estudio previo realizado por nuestro grupo en 2008 en la provincia de Huelva, se detectó una zona deficiente de yodo en Huelva y especialmente en el distrito de Sierra de Huelva-Andévalo, mediante la determinación de TSH Neonatal. Objetivo: Reforzar la campaña de suplementación de yodo en esta región, el impacto sobre los recién nacidos y la determinación de la concentración de yodo en orina. Material y métodos: Estudio realizado conjuntamente por la Unidad de Hipotiroidismo Congénito del Departamento de Bioquímica Clínica del Hospital Universitario Virgen Macarena de Sevilla y los Servicios de Ginecología y Análisis Clínicos del Hospital de Río Tinto (Huelva) con duración de dos años (2007-2009). Se incluyeron 313 gestantes en el estudio. Todas cumplimentaron la encuesta para valorar el estado nutricional de yodo de la zona en la que residían. Se determinó la yoduria por HPLC y se realizó una base de datos con los resultados de las encuestas. Conclusiones: Las gestantes del distrito sanitario Sierra de Huelva-Andévalo presentaron una deficiente suplementación de yodo y una deficiencia de yodo. Según los cuestionarios, esta deficiencia se debe a un aporte insuficiente de suplementos y una baja adherencia al tratamiento