Serum exosome inflamma-miRs are surrogate biomarkers for asthma phenotype and severity.

BACKGROUND: Asthma is a heterogeneous disease with several phenotypes, endotypes and severity degrees, in which different T-cell subpopulations are involved. These cells express specific miRNAs (i.e. inflamma-miRs) that can be released to serum in exosomes after activation and be used as biomarkers of underlying inflammation. Thus, we aim to evaluate specific T-cell miRNA signatures in serum exosomes from different subgroups of asthmatic patients. METHODS: Samples from healthy donors (N = 30) and patients (N = 119) with different asthma endotypes (T2high -Atopic/T2high -Non-atopic/T2low ) and severity degrees (mild/MA and moderate-severe/MSA) were used. Demographic, clinical, haematological and biochemical characteristics were collected. Twelve miRNAs previously associated with different Th subsets were preselected and their levels in serum exosome samples were measured using RTqPCR. RESULTS: We detected five miRNAs with high confidence in serum exosomes: miR-16-5p, miR-21-5p, miR-126-3p, miR146a-5p and miR-215-5p. All of them, except miR-16-5p were upregulated in MSA patients compared to MA. A logistic regression model including each of these miRNAs was created to discriminate both conditions, rendering a ROC curve AUC of 0.896 (0.830-0.961). miR-21-5p and miR-126-3p, both involved in Th1/Th2 differentiation, were specifically augmented in T2high -Atopic patients. Of note, all these changes were found in samples collected in autumn. On the contrary, IL-6high patients with MSA, which were more obese, older, with higher neutrophil and basophil counts and TNF levels, displayed a decrease of miR-21-5p, miR-126-3p and miR-146a-5p. CONCLUSION: Immune-related miRNAs, including miR-21-5p, miR-126-3p, miR-146a-5p and miR-215-5p, can be used as clinically relevant non-invasive biomarkers of the phenotype/endotype and severity of asthma.

Autoimmune findings in patients with silicosis in Spain.

Background: Occupational exposure to silica is related to autoimmune diseases and features of autoimmunity, mainly autoantibodies. The study objectives were to estimate the prevalence of silicosis with associated autoimmune findings or diagnosed autoimmune diseases in Spain, and to assess the clinical and functional characteristics of affected patients. Methods: This is a multicentre prospective study in patients diagnosed with silicosis. Autoantibodies analysed were antinuclear antibodies, isotypes IgA, IgM and IgG, rheumatoid factor, anticyclic citrullinated peptide, anti-Scl70, anti-Ro, and anti-LA. Pulmonary function tests were performed. Results: Autoimmunity was assessed in 105 patients. Autoimmune findings were recorded in 29 (27%) patients, including antinuclear antibodies (n=21), anti-Ro (n=7), rheumatoid factor (n=5) and anti-Scl70 (n=3). Autoimmune disease was diagnosed in 16 (15%) patients, mainly rheumatoid arthritis (n=7) and systemic lupus erythematosus (n=4). Patients with silicosis and autoimmune findings had a lower mean time of exposure to silica and showed a trend toward lower values in pulmonary function tests. Conclusions: Autoimmune findings and diagnosis of autoimmune diseases were frequent in patients with silicosis in Spain.

Prognostic factors of progressive fibrotic hypersensitivity pneumonitis: a large, retrospective, multicentre, observational cohort study.

Background: Fibrotic hypersensitivity pneumonitis (fHP) is an immune-mediated interstitial lung disease caused by sensitisation to chronic allergen inhalation. This study aimed to determine prognostic indicators of progression and mortality in fHP. Methods: This was a retrospective, multicentre, observational, cross-sectional cohort study of consecutive patients diagnosed with fHP from 1 January 2012 to 31 December 2021. Multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals for predictors of progression and survival. Results: A total of 403 patients were diagnosed with fHP: median (interquartile range) age 66.5 (14.0) years, 51.9% females and 55.1% never-smokers. The cause of fHP was mainly fungal (39.7%) or avian (41.4%). Lung biopsy was performed in 269 cases (66.7%). In the whole cohort the variables that were related to mortality or lung transplant were older age (HR 1.08; p<0.001), percentage predicted forced vital capacity (HR 0.96; p=0.001), lymphocytosis in bronchoalveolar lavage (BAL) (HR 0.93; p=0.001), presence of acute exacerbation during follow-up (HR 3.04; p=0.001) and GAP (gender, age and lung physiology) index (HR 1.96; p<0.01). In the group of biopsied patients, the presence of fibroblastic foci at biopsy (HR 8.39; p<0.001) stands out in multivariate Cox regression analyses as a highly significant predictor for increased mortality or lung transplant. GAP index (HR 1.26; p=0.009), lymphocytosis in BAL (HR 0.97; p=0.018) and age (HR 1.03; p=0.018) are also predictors of progression. Conclusions: The study identified several prognostic factors for progression and/or survival in fHP. The presence of fibroblastic foci at biopsy was a consistent predictor for increased mortality and the presence of lymphocytosis in BAL was inversely related to mortality.

Efficacy of mepolizumab in usual clinical practice and characteristics of responders.

BACKGROUND: Severe eosinophilic asthma is a high-burden disease. Mepolizumab has been effective in several randomized clinical trials. However, such success might not be applicable to patients treated in usual clinical practice. The objectives of this article are to evaluate the efficacy of mepolizumab in severe uncontrolled eosinophilic asthma under usual clinical practice, and to determine characteristics associated with the response to this treatment. METHODS: We have conducted a retrospective, multicentre study, including all adult patients with severe uncontrolled eosinophilic asthma in Galicia, Spain, on whom mepolizumab treatment was started before June 2020, at least 6 months before the time of inclusion, and had received at least one dose of the drug. Patient characteristics, clinical data, respiratory function and comorbidities were collected at baseline and at the 6-month-follow-up. Responders and super-responders were defined according to clinical response and requirement of systemic corticosteroids. RESULTS: 122 patients (mean age 58 years old) were included. In the follow-up treatment 6 months later, 75.4% of the patients were well-controlled, displaying a significant reduction in blood eosinophil counts (p < 0.001), hospital admissions and disease exacerbations (p < 0.001), and had their systemic glucocorticosteroid dose significantly reduced (p < 0.001). The inhaled corticosteroid dose was also lowered (p < 0.01) after 6 months of treatment. Around two-thirds had a clinically significant increase in FEV1, 95% of the patients were considered responders and 43% super-responders. CONCLUSION: In routine clinical practice, mepolizumab is effective in patients with severe eosinophilic asthma and it has a good safety profile.

Toxicidad pulmonar por riluzole / Pulmonary toxicity by riluzole

No disponible

Ampollas, úlceras y costras en paciente con infección VIH / Blisters, scars and healing crusts in a HIV infected patient

No disponible

Infiltración pulmonar linfoproliferativa: una opción diagnóstica a tener presente ante infiltrados pulmonares en un paciente con leucemia linfoide crónica / Lymphoproliferative pulmonary infiltration: A diagnosis to keep in mind in pulmonary infiltrates in patient with chronic lymphocytic leukemia

No disponible