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

Objective: To 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 methods: The 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. Results: We 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. Conclusion: Patients 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.

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

OBJECTIVES: To describe comorbid conditions in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and to analyze factors associated with multimorbidity. METHODS: Nested 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. RESULTS: The 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). CONCLUSION: In patients with RA, multimorbidity was associated with ILD, systemic inflammation, and advanced age.

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

OBJECTIVE: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: 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. RESULTS: 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. CONCLUSION: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

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); p < 0.001) and diabetes mellitus (OR (95% CI), 4.923 (1.508−19.097); p = 0.018). Conclusions: Around 13% of patients with ILD-SAD had SARS-CoV-2 infection, which was severe in approximately one-third. Most patients with severe infection were not fully vaccinated.

Efficacy and Safety of Rituximab in Autoimmune Disease-Associated Interstitial Lung Disease: A Prospective Cohort Study.

OBJECTIVES: To analyze the efficacy and safety of rituximab (RTX) in connective tissue disease associated with interstitial lung disease (CTD-ILD). METHODS: We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving rituximab between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline, at 12 months, and at the end of follow-up. 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 (DLCO) > 15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening ILD. RESULTS: We included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7-69.0) months. At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in seven (18.9%); seven patients (18.9%) died. No significant decline was observed in median FVC (72.2 vs. 70.8; p = 0.530) or DLCO (55.9 vs. 52.2; p = 0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR (95% CI), 0.904 (0.8-0.9); p = 0.015), time to initiation of RTX (1.01 (1.001-1.02); p = 0.029), and mycophenolate (0.202 (0.04-0.8); p = 0.034). Only 28 of the 37 patients (75.6%) were still undergoing treatment with RTX: two patients (5.4%) stopped treatment due to adverse events and seven patients (18.9%) died owing to progression of ILD and superinfection. CONCLUSION: Lung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD.

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.

Pulmonary Rehabilitation Only Versus With Nutritional Supplementation in Patients With Bronchiectasis: A RANDOMIZED CONTROLLED TRIAL.

PURPOSE: Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but there is little evidence of its efficacy in these patients. The aim of this study was to assess the effect of PR in normally nourished patients with noncystic fibrosis bronchiectasis compared with the effect of PR plus an oral nutritional supplement (PRONS). METHODS: A single-center randomized controlled trial, parallel treatment design in which participants were randomly assigned to receive PR for 12 wk or PR plus a high-protein nutritional supplement enriched with beta-hydroxy-beta-methylbutyrate. Outcome assessments were performed at baseline, 12 and 24 wk including cardiopulmonary exercise testing, health-related quality of life (HRQOL), bronchorrhea, dyspnea, psychological symptoms, spirometry, and exacerbations. RESULTS: Thirty patients were randomized into 2 groups of 15 participants. In both groups, cardiopulmonary exercise testing, HRQOL, dyspnea, and spirometry parameters significantly increased from baseline at 3 and/or 6 mo. CONCLUSION: PR improved exercise capacity, HRQOL, and respiratory parameters. The use of PRONS did not have a significant effect on the results.

Body Composition Measurement in Bronchiectasis: Comparison between Bioelectrical Impedance Analysis, Skinfold Thickness Measurement, and Dual-Energy X-ray Absorptiometry before and after Pulmonary Rehabilitation.

BACKGROUND: In individuals with bronchiectasis, fat-free mass depletion may be common despite a low prevalence of underweight and is considered a risk factor for increased morbidity and mortality. Techniques to adequately estimate fat-free mass and its changes over time are needed. OBJECTIVE: The purpose of this study was to assess agreement among values obtained with three different body composition techniques: skinfold thickness measurement (STM), bioelectrical impedance analysis (BIA), and dual-energy x-ray absorptiometry (DXA). DESIGN: The study was a secondary analysis of data from a randomized controlled trial. PARTICIPANTS/SETTING: A respiratory rehabilitation program was administered for 3 months to individuals with bronchiectasis from the bronchiectasis unit of the Regional University Hospital in Malaga, Spain, from September 2013 to September 2014. Individuals with a body mass index (calculated as kg/m2) >18.5 who were aged 65 years or younger and those with a body mass index >20 who were older than 65 years were included. MAIN OUTCOME MEASURES: At baseline and at 3 and 6 months, body composition was determined by DXA and STM. STATISTICAL ANALYSES PERFORMED: Statistical concordance was assessed with the intraclass correlation coefficient (ICC), kappa coefficient, and the degree of agreement using the Bland Altman method. For comparison of the quantitative variables at baseline vs at 3 months and 6 months, the paired sample t test (or the Wilcoxon test) was used. RESULTS: Thirty participants were included. Strong agreement was observed between body composition values determined by BIA and DXA in fat mass (ICC: 0.92) and fat-free mass (ICC: 0.87). Strong agreement was observed between STM and DXA in the values for fat-free mass (ICC: 0.91) and fat mass (ICC: 0.94), and lower agreement was observed for the longitudinal data and in the regional values. The mean difference between fat-free mass determined by BIA and DXA was + 4.7 with a standard deviation of 2.4 kg in favor of BIA. The mean difference between fat-free mass determined by STM and DXA was +2.3 with a standard deviation of 2.7 kg in favor of STM. Six individuals were classified as having a low fat-free mass index (20%) by DXA vs four by STM (13%; kappa: 0.76) and only two by BIA (6.6%; kappa: 0.44) compared with DXA. CONCLUSIONS: Despite good statistical agreement among values obtained with DXA, STM, and BIA, the study findings indicate that STM and BIA, above all, tended to overestimate fat-free mass compared with DXA.

Muscle Strength and Speed Performance in Youth Soccer Players.

This study aimed to examine the relationship between maximum leg extension strength and sprinting performance in youth elite male soccer players. Sixty-three youth players (12.5 ± 1.3 years) performed 5 m, flying 15 m and 20 m sprint tests and a zigzag agility test on a grass field using timing gates. Two days later, subjects performed a one-repetition maximum leg extension test (79.3 ± 26.9 kg). Weak to strong correlations were found between leg extension strength and the time to perform 5 m (r = -0.39, p = 0.001), flying 15 m (r = -0.72, p < 0.001) and 20 m (r = -0.67, p < 0.001) sprints; between body mass and 5 m (r = -0.43, p < 0.001), flying 15 m (r = -0.75, p < 0.001), 20 m (r = -0.65, p < 0.001) sprints and agility (r =-0.29, p < 0.001); and between height and 5 m (r = -0.33, p < 0.01) and flying 15 m (r = -0.74, p < 0.001) sprints. Our results show that leg muscle strength and anthropometric variables strongly correlate with sprinting ability. This suggests that anthropometric characteristics should be considered to compare among youth players, and that youth players should undergo strength training to improve running speed.

Mediterranean diet is associated on symptoms of depression and anxiety in patients with bronchiectasis.

BACKGROUND: The aim was to measure symptoms of depression and anxiety in patients with bronchiectasis and evaluate their relationship with a Mediterranean diet. METHODS: This cross-sectional study recruited patients with bronchiectasis at four Spanish centers. Patients completed the hospital anxiety and depression scale (HADS) and the Mediterranean diet questionnaire (PREDIMED). Demographic, health and outcome data were recorded from medical charts. Logistic regression was used to determine the predictors of elevated symptoms of depression and anxiety (HADS≥11). RESULTS: Of the 205 participants recruited, 37 (18.0%) had elevated anxiety-related scores and 26 (12.7%) had elevated depression-related scores (HADS≥11). Increased symptoms of depression were significantly associated with being unemployed, a lower education, older age, comorbidity, major dyspnea, worse quality of life (QOL) and a lower PREDIMED score. Increased symptoms of anxiety were significantly associated with more exacerbations, worse QOL and a lower PREDIMED score. Regression analyses indicated that, after adjustment, QOL and the PREDIMED score predicted elevated symptoms of depression and QOL predicted elevated symptoms of anxiety. CONCLUSIONS: The prevalence of elevated symptoms of depression and anxiety is high in patients with bronchiectasis and greater adherence to a Mediterranean diet is associated with a lower likelihood of having these symptoms, particularly for depression.

Validation of a Quality of Life Questionnaire for Bronchiectasis: psychometric analyses of the Spanish QOL-B-V3.0.

PURPOSE: Bronchiectasis is a chronic disease, leading to worsening of health-related quality of life. This study evaluated the psychometric properties of a new patient-reported outcome for non-cystic fibrosis bronchiectasis, the Quality of Life Questionnaire Bronchiectasis, translated into Spanish (QOL-B-Sp-V3.0). METHODS: This prospective study recruited clinically stable patients with non-cystic fibrosis bronchiectasis at 4 Spanish centers. Health status was assessed with multiple indicators (dyspnea, exacerbations, bronchorrhea, etc.), microbiological, radiological, spirometric, and anthropometric parameters plus St-George Respiratory Questionnaire (SGRQ). Psychometric analyses included internal consistency, test-retest reliability, convergent validity, predictive validity, and responsivity to change. RESULTS: The 207 stable patients (mean age 57.2 years) had a Bhalla score of 11.53 ± 7.39 and FEV1% of 68.3 ± 22.2 %. One hundred and sixty-one stable patients repeated the test 2 weeks later, and 80 patients who had an exacerbation within 6 months of the assessment also repeated it. Internal consistency was high across all scales (Cronbach's alpha >0.70). Thirty-six of 37 items correlated more strongly with their assigned scale than a competing scale. Test-retest coefficients were strong (intraclass correlations r = 0.68-0.88). All scales, except Treatment Burden, discriminated significantly between patients with mild, moderate, and severe disease according to FEV1% and other respiratory parameters. Strong convergence was found between the QOL-B-Sp-V3.0 and SGRQ. Significant correlations were found between QOL-B-Sp-V3.0 and various clinical, spirometric, radiological, and anthropometric variables. Significant differences were found on all QOL-B-Sp-V3.0 scales, except emotional functioning, between the baseline responses and onset of an exacerbation; robust sensitivity to change was observed on the Respiratory Symptoms scale. CONCLUSIONS: The QOL-B-Sp-V3.0 questionnaire demonstrated strong reliability and validity. Scores were reproducible after 2 weeks, and it discriminated between patients who varied in severity and was responsive to changes related to exacerbation.

Depression and anxiety symptoms in bronchiectasis: associations with health-related quality of life.

BACKGROUND AND PURPOSE: Bronchiectasis causes pulmonary infections and loss of lung function, resulting in chronic respiratory symptoms and worsening health-related quality of life. The aims of this study were to measure symptoms of depression and anxiety in a sample of patients with bronchiectasis and evaluate their relationship to health outcomes and health-related quality of life. METHODS: This cross-sectional study included adolescents and adults with bronchiectasis. Patients completed the hospital anxiety and depression scale and the St. George respiratory questionnaire. Health outcome data, including clinical, radiological and spirometric values, were recorded from medical charts. RESULTS: Ninety-three participants with bronchiectasis of any aetiology were recruited: 20 % had elevated depression-related scores and 38 % had elevated anxiety-related scores. Increased symptoms of depression and anxiety were significantly associated with age; anxiety was associated with more frequent exacerbations. Regression analyses indicated that after controlling for demographic (gender and age) and clinical variables (exacerbations frequency, daily sputum, aetiology and spirometry), both depression and anxiety symptoms predicted significantly worse health-related quality of life. In comparison with other predictors, psychological symptoms explained the largest amount of variance in health-related quality of life. CONCLUSIONS: Symptoms of depression and anxiety were significant predictors of health-related quality of life in patients with bronchiectasis, independently of respiratory involvement, gender, age or other variables.

Fatty acid supplements improve respiratory, inflammatory and nutritional parameters in adults with cystic fibrosis.

INTRODUCTION AND AIMS: Chronic inflammation plays a major role in lung deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies have beneficial effects. To study the changes seen after a one-year course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation, pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), quality of life and anthropometric parameters. PATIENTS AND METHOD: Seventeen adult subjects with CF received 324 mg of eicosapentaenoic, 216 mg of docosahexaenoic, 480 mg of linoleic and 258 mg of gammalinolenic acid daily. We assessed inflammation markers, spirometry parameters, number and severity of respiratory exacerbations, antibiotic consumption, quality of life (St George's QoL), anthropometric parameters and serum phospholipid fatty acid composition. RESULTS: At the end of the treatment period TNF alpha levels fell significantly and its soluble receptors (60 and 80) rose significantly. Levels of IgG and IgM anti-oxidized LDL antibodies fell significantly. Spirometry improved significantly. Annual respiratory exacerbations and days of antibiotic treatment fell significantly. The improvement in QoL was not significant. Serum levels of docosahexaenoic, total omega-3 and linoleic acid rose significantly and more favourable profiles were seen in monoenoic acids, arachidonic acid and the arachidonic/docosahexaenoic ratio. The fat-free mass and hand grip dynamometry improved significantly. CONCLUSIONS: Low-dose supplements of n-3 and gammalinolenic fatty acids over a long period (one year) appears to improve pulmonary status (lung function, respiratory exacerbations and antibiotic consumption), inflammatory and anthropometric parameters in adults with CF.