Expansion of different subpopulations of CD26−/low T cells in allergic and non-allergic asthmatics

CD26 displays variable levels between effector (TH17 ≫ TH1 > TH2 > Treg) and naïve/memory (memory > naïve) CD4+ T lymphocytes. Besides, IL-6/IL−6R is associated with TH17-differentiation and asthma severity. Allergic/atopic asthma (AA) is dominated by TH2 responses, while TH17 immunity might either modulate the TH2-dependent inflammation in AA or be an important mechanism boosting non-allergic asthma (NAA). Therefore, in this work we have compared the expression of CD26 and CD126 (IL-6Rα) in lymphocytes from different groups of donors: allergic (AA) and non-allergic (NAA) asthma, rhinitis, and healthy subjects. For this purpose, flow cytometry, haematological/biochemical, and in vitro proliferation assays were performed. Our results show a strong CD26-CD126 correlation and an over-representation of CD26− subsets with a highly-differentiated effector phenotype in AA (CD4+CD26−/low T cells) and NAA (CD4−CD26− γδ-T cells). In addition, we found that circulating levels of CD26 (sCD26) were reduced in both AA and NAA, while loss of CD126 expression on different leukocytes correlated with higher disease severity. Finally, selective inhibition of CD26-mRNA translation led to enhanced T cell proliferation in vitro. These findings support that CD26 down-modulation could play a role in facilitating the expansion of highly-differentiated effector T cell subsets in asthma.This work was supported by grants from Sociedad Española de Neumología y Cirugía Torácica, (SEPAR) (121/2012) and Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Fondo de Investigación Sanitaria, FIS; co-financed by European Union ERDF funds) (PI13/02046). JJN-F is a recipient of a Xunta de Galicia Fellowship (co-financed by European Social Fund (ESF))S

The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

LPS-ligation to CD14/TLR-4 on monocytes/macrophages triggers the production of IL-12-family cytokines. IL12/18 promote TH1-differentiation, counteracting the TH2-driven asthma. Therefore, CD14 modulation could alter the TH2-differentiation and should be taken into account when studying asthma. To analyse the alteration in CD14 levels and its association with CD14 (−159 C/T) SNP (rs2569190) in Caucasian adults with stable allergic asthma, we performed a cross-sectional study (277 healthy subjects vs. 277 patients) where clinical parameters, CD14 values and the CD14 (−159 C/T) SNP were studied. Apart from typical biomarkers, we found an increment of neuron-specific enolase (NSE) in allergic asthma, probably linked to monocyte activity. Indeed, we evidenced increased monocyte numbers, but lower CD14 expression and normalised sCD14 values in patients. Moreover, we noticed an association of the T allele (P = 0.0162) and TT genotype (P = 0.0196) of the CD14 SNP with a decreased risk of allergic asthma and augmented sCD14 levels. In conclusion, monocyte CD14 expression and normalized sCD14 values were reduced in stable state asthmatics, and this could be related to the presence of an expanded CD14low monocyte subset. This study also demonstrates that the CD14 (−159 C/T) polymorphism is a risk factor for moderate-severe allergic asthma in adult CaucasiansThis study was funded by grants from Sociedad Española de Neumología y Cirugía Torácica, (SEPAR) (121/2012) and Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Fondo de Investigación Sanitaria, FIS; co-financed by European Union ERDF funds) (PI13/02046). JJNF is a recipient of a Xunta de Galicia Fellowship (Co-financed by European Social Fund (ESF))S

Association of Rhinitis With Asthma Prevalence and Severity

Multicenter study[Abstract] Asthma and rhinitis often co-exist in the same patient. Although some authors observed a higher prevalence and/or greater severity of asthma in patients with rhinitis, this view is not homogeneous and the debate continues. The aim of our study is to describe the prevalence of rhinitis in children and adolescents and to analyse their relationship with the prevalence of asthma. A multicentre study was conducted using the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC). The target population of the study was all those school children aged 6-7 and 13-14 years from 6 of the main health catchment areas of Galicia (1.9 million inhabitants). The schools required were randomly selected, and all children in the targeted age ranges were included. Multiple logistic regression was used to obtain adjusted prevalence odds ratios (OR) between asthma symptoms of the schoolchildren and rhinitis prevalence. The results were adjusted for parental smoking habits, maternal education level, cat and dog exposure, and obesity. A total of 21,420 valid questionnaires were finally obtained. Rhinitis was associated with a significant increase in the prevalence of asthma in both age groups. The highest OR were 11.375 for exercise induced asthma (EIA) for children with recent rhinoconjunctivitis and 9.807 for children with recent rhinitis in 6-7 years old group. The prevalence OR's are higher in EIA and severe asthmatics. Rhinitis in children and adolescents is associated with a higher prevalence and severity of asthma.This work was funded by the Maria Jose Jove Foundatio

High-resolution variability of dissolved and suspended organic matter in the Cape Verde Frontal Zone

21 pages, 8 figures, 4 tables.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)Distributions of dissolved (DOM) and suspended (POM) organic matter, and their chromophoric (CDOM) and fluorescent (FDOM) fractions, are investigated at high resolution (< 10 km) in the Cape Verde Frontal Zone (CVFZ) during fall 2017. In the epipelagic layer (< 200 m), meso- and submesoscale structures (meanders, eddies) captured by the high resolution sampling dictate the tight coupling between physical and biogeochemical parameters at the front. Remarkably, fluorescent humic-like substances show relatively high fluorescence intensities between 50 and 150 m, apparently not related to local mineralization processes. We hypothesize that it is due to the input of Sahara dust, which transports highly re-worked DOM with distinctive optical properties. In the mesopelagic layer (200-1500 m), our results suggest that DOM and POM mineralization occurs mainly during the transit of the water masses from the formation sites to the CVFZ. Therefore, most of the local mineralization seems to be due to fast-sinking POM produced in situ or imported from the Mauritanian upwelling. These local mineralization processes lead to the production of refractory CDOM, an empirical evidence of the microbial carbon pump mechanism. DOM released from these fast-sinking POM is the likely reason behind the observed columns of relatively high DOC surrounded by areas of lower concentration. DOM and POM dynamics in the CVFZ has turned out to be very complex, in parallel to the complexity of meso- and submesoscale structures present in the area. On top of this high resolution variability, the input of Sahara dust or the release of DOM from sinking particles have been hypothesized to explain the observed distributionsThis work was funded by Spanish National Science Plan research grants FERMIO (CTM2014–57334–JIN) and FLUXES (CTM2015-69392-C3), co–financed with FEDER funds, and e-IMPACT (PID2019-109084RB-C21 and –C22). RC, SV and NB were supported by predoctoral fellowships from the Spanish Ministry of Science and Innovation (BES-2016-076462, BES- 2016-079216 and BES-2016-077949). BF-C was supported by a Juan de la Cierva Formación fellowship (FJCI-641-2015-25712) and by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 834330 (SO-CUP). JA was partly supported by the project SUMMER (AMD-817806-5) from the European Union’s Horizon 2020 research and innovation programPeer reviewe

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.17.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days >= 30%,>= 50%,>= 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

publishersversionPeer reviewe

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]