Exploring CD26-/lo subpopulations of lymphocytes in asthma phenotype and severity: A novel CD4+ T cell subset expressing archetypical granulocyte proteins.

BACKGROUND: Asthma pathology may induce changes in naïve/memory lymphocyte proportions assessable through the evaluation of surface CD26 (dipeptidyl peptidase 4/DPP4) levels. Our aim was to investigate the association of asthma phenotype/severity with the relative frequency of CD26-/lo, CD26int and CD26hi subsets within different lymphocyte populations. METHODS: The proportion of CD26-/lo, CD26int and CD26hi subsets within CD4+ effector T cells (Teff), total CD4- lymphocytes, γδ-T cells, NK cells and NKT cells was measured in peripheral blood samples from healthy (N = 30) and asthma (N = 119) donors with different phenotypes/severities by flow cytometry. We performed K-means clustering analysis and further characterised the CD4+CD26-/lo Teff cell subset by LC-MS/MS and immunofluorescence. RESULTS: Cluster analysis including clinical and flow cytometry data resulted in four groups, two of them with opposite inflammatory profiles (neutrophilic vs. eosinophilic). Neutrophilic asthma presented reduced CD4-CD26hi cells, which negatively correlated with systemic inflammation. Eosinophilic asthma displayed a general expansion of CD26-/lo subsets. Specifically, CD4+CD26-/lo Teff expansion was confirmed in asthma, especially in atopic patients. Proteomic characterisation of this subset with a TEM/TEMRA phenotype revealed upregulated levels of innate (e.g. MPO and RNASE2) and cytoskeleton/extracellular matrix (e.g. MMP9 and ACTN1) proteins. Immunofluorescence assays confirmed the presence of atypical proteins for CD4+ T cells, and an enrichment in 'flower-like' nuclei and MMP9/RNASE2 levels in CD4+CD26-/lo Teff compared to CD4+ T lymphocytes. CONCLUSION: There is an association between CD26 levels in different lymphocyte subsets and asthma phenotype/severity. CD4+CD26-/loTEMRA cells expressing innate proteins specific to eosinophils/neutrophils could be determinant in sustaining long-term inflammation in adult allergic asthma.

Diagnosed and undiagnosed cough-related stress urinary incontinence in women with refractory or unexplained chronic cough: Its impact on general health status and quality of life.

Background: Stress urinary incontinence (SUI) is common in women with chronic cough but may be overlooked. Objective: To determine the frequency of underdiagnosis of cough-related SUI and its impact on women's general health status and quality of life (QoL). Methods: Data were analyzed for 147 women with refractory/unexplained chronic cough. Relevant details were collected from clinical charts and a patient-completed survey. General health status was assessed using the EuroQoL visual analogue scale (EQ-VAS) and QoL with the cough-specific Leicester Cough Questionnaire (LCQ). Results: Women were classified into diagnosed (n = 32; 21.8%) or undiagnosed (n = 33; 22.4%) cough-related SUI, and no SUI (n = 82; 55.6%) groups. Women with versus without cough-related SUI perceived poorer health status and greater impact of cough on everyday lives. Mean LCQ scores were significantly lower in cough-related SUI groups versus no SUI group. In multivariate analysis, the presence of cough-related SUI was significantly associated with lower EQ-VAS and LCQ scores. Conclusion: In our cohort, 44% of women had cough-related SUI, and half were undiagnosed. Irrespective of diagnosis, impairment to everyday lives and QoL was similar. Diagnosing cough-related SUI may identify additional patients who can benefit from therapies to suppress cough and improve QoL.

Outpatient atorvastatin use and severe COVID-19 outcomes: A population-based study.

Evidence of the effect of statins on patients with coronavirus disease (2019) COVID-19 is inconsistent. The aim of this study was to evaluate the association between chronic use of statins-both overall and by active ingredient-and severe outcomes of COVID-19 (risk of hospitalization and mortality), progression to severe outcomes, and susceptibility to the virus. We conducted a population-based case-control study with data from electronic records to assess the risk of (1) hospitalization: cases were patients admitted due to COVID-19 and controls were subjects without COVID-19; (2) mortality: cases were hospitalized patients who died due to COVID-19 and controls were subjects without COVID-19; (3) progression: cases were hospitalized COVID-19 subjects and controls were nonhospitalized COVID-19 patients; and (4) susceptibility: cases were patients with COVID-19 (both hospitalized and nonhospitalized) and controls were subjects without COVID-19. We collected data on 2821 hospitalized cases, 26 996 nonhospitalized cases, and 52 318 controls. Chronic use of atorvastatin was associated with a decreased risk of hospitalization (adjusted odds ratios [aOR] = 0.83; 95% confidence interval [CI]: 0.74-0.92) and mortality (aOR = 0.70; 95% CI: 0.53-0.93), attributable in part to a lower risk of susceptibility to the virus (aOR = 0.91; 95% CI: 0.86-0.96). Simvastatin was associated with a reduced risk of mortality (aOR = 0.59; 95% CI: 0.40-0.87). The wide degree of heterogeneity observed in the estimated odds ratios (ORs) of the different statins suggests that there is no class effect. The results of this real-world study suggest that chronic use of atorvastatin (and to a lesser degree, of simvastatin) is associated with a decrease in risk of severe COVID-19 outcomes.

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.

Does asthma-bronchiectasis overlap syndrome (ABOS) really exist?

OBJECTIVE: To analyze the relationship between asthma and bronchiectasis, as well as the necessary conditions that this connection must meet for this group of patients to be considered a special phenotype. DATA SOURCES: We performed a PubMed search using the MeSH terms "asthma" and "bronchiectasis." The literature research was limited to clinical trials, meta-analyses, randomized controlled trials, cohort studies, and systematic reviews, involving adult patients, published until November 30th, 2022. STUDY SELECTIONS: Selected papers were initially evaluated by the Authors, to assess their eligibility in contributing to the statements. RESULTS: The prevalence of bronchiectasis is higher than expected in patients with asthma, particularly in those with more severe disease, and in some patients, between 1.4% and 7% of them, asthma alone could be the cause of bronchiectasis. Both diseases share etiopathogenic mechanisms, such as neutrophilic and eosinophilic inflammation, altered airway microbiota, mucus hypersecretion, allergen sensitization, immune dysfunction, altered microRNA, dysfunctional neutrophilic activity, and variants of the HLA system. Besides that, they also share comorbidities, such as gastroesophageal reflux disease and psychiatric illnesses. The clinical presentation of asthma is very similar to patients with bronchiectasis, which could cause mistakes with diagnoses and delays in being prescribed the correct treatment. The coexistence of asthma and bronchiectasis also poses difficulties for the therapeutic focus. CONCLUSIONS: The evidence available seems to support that the asthma-bronchiectasis phenotype really exists although longitudinal studies which consistently demonstrate that asthma is the cause of bronchiectasis are still lacking.

Gastroesophageal reflux disease and asthma exacerbation: A systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GORD) is highly prevalent and often coexists with asthma exacerbation. Divergent findings about the association between the two diseases were reported. We conducted a systematic review and meta-analysis to determine whether there exists an association between GORD and asthma. METHODS: We searched MEDLINE, EMBASE, and other databases and then performed a manual search, to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using fixed- and random-effect models. We evaluated the quality of included studies, explored heterogeneity between studies, undertook subgroup analyses, assessed publication bias, and performed sensitivity analyses. RESULTS: We identified 32 eligible studies, conducted in 14 countries and including a total of 1,612,361 patients of all ages. Overall, GORD shows a weak association with asthma exacerbation (OR = 1.27; 95% CI 1.18-1.35). This association was observed in cohort, case-control, and cross-sectional designs and in European as well as non-European populations. Subgroup analyses show that GORD is associated with frequent asthma exacerbations (≥3 exacerbations, OR = 1.59; 95% CI 1.13-2.24) and with exacerbations needing oral corticosteroid therapy (OR = 1.24; 95% CI 1.09-1.41). GORD pediatric patients are at higher odds of asthma exacerbation than adults. We did not detect any evidence of publication bias and the association between GORD and asthma exacerbation held in all undertaken sensitivity analyses. CONCLUSIONS: Gastroesophageal reflux disease and asthma exacerbation are weakly associated.

Multi-ancestry genome-wide association study of asthma exacerbations.

BACKGROUND: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. METHODS: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10-5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. RESULTS: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele ) = 0.82, p = 9.05 × 10-6 and replication: ORT allele  = 0.89, p = 5.35 × 10-3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele  = 0.85, p = 3.10 × 10-5 and replication: ORC allele  = 0.89, p = 1.30 × 10-2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. CONCLUSIONS: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Monoclonal antibody treatment for severe uncontrolled asthma in Spain: analytical map.

BACKGROUND: Monoclonal antibodies (mABs) have become available to treat more efficiently patients with severe uncontrolled asthma (SUA). However, the use of mABs is lower than expected given the prevalence of SUA, with significant disparities in the use of these treatments. OBJECTIVE: To evaluate the proportion of patients with SUA treated with mABs in Spain, and to analyze some of the factors that could determine these prescription patterns. METHODS: An analysis was performed on the data provided from the Hospitals National Health System (NHS) 2018 catalogue where Chest Diseases Department and a Hospital Pharmacy were available. Random sampling was performed to determine the sample size, stratifying proportionally by geographic area and hospital level. Characteristics of the participating sites, as well as the prescribing of mABs were collected, which included geographic area, hospital levels, prescribing medical specialities, types of clinics, and mABs prescribed. RESULTS: Data from 90 hospitals were analyzed (Response rate 64.3%). Level 4 hospitals, the Canary Islands geographical area, and the presence of a high complexity Asthma Healthcare Unit (ACU) were associated with a higher probability that the SUA was treated with mABs. CONCLUSION: The map of the prescribing of mABs for SUA in Spain shows a significant variation by geographic area, hospital level, type of clinic, and the accreditation level of the ACUs. At the current time, there appears to be significant under-prescribing of these treatments.

Impact of anxiety and depression on the prognosis of copd exacerbations.

BACKGROUND: Frequent and highly prevalent as comorbidities in Chronic Obstructive Pulmonary Disease (COPD) patients, both depression and anxiety seem to have an impact on COPD prognosis. However, they are underdiagnosed and rarely treated properly. AIM: To establish the prevalence of depression and anxiety in patients admitted for Acute Exacerbation of COPD (AECOPD) and determine their influence on COPD prognosis. METHODS: Prospective observational study conducted from October 1, 2016 to October 1, 2018 at the following centers in Galicia, Spain: Salnés County Hospital, Arquitecto Marcide, and Clinic Hospital Complex of Santiago de Compostela. Patients admitted for AECOPD who agreed to participate and completed the anxiety and depression scale (HADS) were included in the study. RESULTS: 288 patients (46.8%) were included, mean age was 73.7 years (SD 10.9), 84.7% were male. 67.7% patients were diagnosed with probable depression, and depression was established in 41.7%; anxiety was probable in 68.2% and established in 35.4%. 60.4% of all patients showed symptoms of both anxiety and depression. Multivariate analysis relates established depression with a higher risk of late readmission (OR 2.06, 95% CI 1.28; 3.31) and a lower risk of mortality at 18 months (OR 0.57, 95% CI 0.37; 0.90). CONCLUSION: The prevalence of anxiety and depression in COPD patients is high. Depression seems to be an independent factor for AECOPD, so early detection and a multidisciplinary approach could improve the prognosis of both entities. The study was approved by the Ethical Committee of Galicia (code 2016/460).

Blood eosinophil count as predictor of asthma exacerbation. A meta-analysis.

BACKGROUND: Evidence about the association of high blood eosinophil count with asthma exacerbation is inconsistent and unclear. The objective of this meta-analysis was to determine whether elevated blood eosinophil count predicts asthma exacerbation. METHODS: We searched MEDLINE, EMBASE, and additional databases, without any language restriction. We also checked the reference lists of the included studies and of relevant systematic reviews. The main outcome was the occurrence of asthma exacerbation. We calculated global pooled odds ratios (ORs) and their 95% confidence intervals (CIs) and performed predefined subgroup analyses. We appraised the quality of the studies using Newcastle-Ottawa Scale, examined the heterogeneity between studies, assessed publication bias, and carried out sensitivity analyses. RESULTS: Among 1567 retrieved publications, 23 observational studies comprising 155,772 participants met the inclusion criteria. High blood eosinophil count was associated with higher odds of asthma exacerbation [OR: 1.31 (95% CI: 1.16, 1.49)], specifically with asthma-related outpatient visits [OR: 1.46 (95% CI: 1.25, 1.70)] and emergency department visits [OR: 1.63 (95% CI: 1.29, 2.07)]. A significant association was observed starting from an eosinophils' cutoff value of 200 cells/µl. The association was observed for cohort studies [OR: 1.30 (95%CI: 1.13, 1.49)], North American studies [OR: 1.43 (95%CI: 1.31, 1.57)], Asian populations [OR: 1.67 (95%CI: 1.34, 2.08)], children [OR: 1.38 (95%CI: 1.22, 1.56)], and studies that adjusted for inhaled corticosteroids therapy [OR: 1.42 (95%CI: 1.28, 1.56)]. CONCLUSIONS: Blood eosinophil counts ≥ 200 cells/µL are associated with asthma exacerbation. Blood eosinophil count is a modifiable factor that could be addressed in asthma management strategies.

Application of mindfulness techniques in patients with asthma or COPD.

OBJECTIVE: Mindfulness is the ability to pay attention to the present moment without judgment. Mindfulness interventions have proved to be effective in improving the management of psychological symptoms of chronic patients. The objective of this work is to update the evidence about the effects of mindfulness interventions on psychological symptoms in patients with asthma and chronic obstructive pulmonary disease (COPD). METHODOLOGY: Data sources were PubMed and PsycInfo. From a first set of 109 articles, 12 about mindfulness-interventions in adult populations with asthma or COPD were finally included in the review. RESULTS: Of the total of 12 studies included, 5 were qualitative and 6 quantitative (5 randomized controlled trials). One quantitative study reported long-term psychological effects in asthma patients, two studies reported short-term psychological effects in COPD patients. Relevant themes identified in qualitative studies included increased awareness, development of new relationships with dyspnea, including new cognitive strategies, and slowing down. CONCLUSIONS: Mindfulness interventions could increase psychological resources in situations related to asthma and COPD symptoms. More randomized control trials are needed.

iTRAQ-based proteomic analysis reveals potential serum biomarkers of allergic and nonallergic asthma.

BACKGROUND: Asthma is heterogeneous disease with different phenotypes, endotypes and severities. Definition of these subgroups requires the identification of biomarkers in biological samples, and serum proteomics is a useful and minimally invasive method for this purpose. Therefore, the aim of this study was to detect serum proteins whose abundance is distinctively associated with different asthma phenotypes (allergic vs nonallergic) or severities. METHODS: For each group of donors (32 healthy controls, 43 allergic rhinitis patients and 192 asthmatics with different phenotypes and severities), we generated two pools of sera that were analysed by a shotgun MS approach based on combinatorial peptide ligand libraries and iTRAQ-LC-MS/MS. RESULTS: MS analyses identified 18 proteins with a differential abundance. Functional/network study of these proteins identified key processes for asthma pathogenesis, such as complement activation, extracellular matrix organization, platelet activation and degranulation, or post-translational protein phosphorylation. Furthermore, our results highlighted an enrichment of the "Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)" route in allergic asthma and the lectin pathway of complement activation in nonallergic asthma. Thus, several proteins (eg IGFALS, HSPG2, FCN2 or MASP1) displayed a differential abundance between the different groups of donors. Particularly, our results revealed IGFALS as a useful biomarker for moderate-severe allergic asthma. CONCLUSION: Our data suggest a set of serum biomarkers, especially IGFALS, capable of differentiating allergic from nonallergic asthma. These proteins reveal different pathophysiological mechanisms and may be useful in the future for diagnosis, prognosis or targeted therapy purposes.

Blood eosinophils could be useful as a biomarker in chronic obstructive pulmonary disease exacerbations.

Introduction The aim of analysing the usefulness of the blood eosinophil count (BEC) as a prognostic marker in exacerbations of patients with Chronic Obstructive Pulmonary Disease (COPD), evaluating its relationship with hospital mortality, the length of stay and the early and late re-admissions. Materials and Methods We have carried out a retrospective study including all patients who required hospital admission from 1 January 2008 to 31 December 2009, with a diagnosis on hospital discharge of COPD exacerbation. These patients were classified using three cut-off points of BEC: less than 200 vs ≥ 200/µL, less than 300 vs ≥ 300/µL and less than 400 vs ≥ 400/µL. Results There were a total of 1626 hospital admissions during the study period with the diagnosis of exacerbation of COPD. In this study we have included 358 patients. The probability of any late re-admission increased with a BEC ≥ 300/µL (odds ratio: 1.684) and for those with a BEC ≥ 400/µL (odds ratio: 2.068). The BEC does not appear to be related to hospital mortality or the probability of early re-admission after an exacerbation of COPD. Conclusions In our study an elevated BEC is associated with a higher incidence of late hospital readmissions in COPD exacerbations.

Assessing adherence to inhaled medication in asthma: Impact of once-daily versus twice-daily dosing frequency. The ATAUD study.

INTRODUCTION: This study was aimed at evaluating whether once-daily regimens (od-r) show benefits in adherence when compared to twice-daily (td-r). METHODS: Prospective, multicenter, 6-month follow-up study with two visits. The main objective was to compare adherence assessed by the electronic prescription refill rate (EPRR) and by the 10-item Test of Adherence to Inhalers (TAI) in patients with od-r and td-r. Suboptimal adherence was defined as TAI < 50 or EPRR ≤ 80%. The effect of suboptimal adherence on meaningful clinical outcomes and the concordance between EPRR and TAI were also examined. RESULTS: One hundred and ninety-seven patients (47.3 ± 15.9 years, 65% women) were included and 180 completed the study. TAI score was <50 in 29.8% od-r patients and 46.9% in td-r (p = 0.01) and EPRR was ≤80% in 22.6% and 37.5% respectively (p = 0.02). The correlation between the two methods was moderate (rho = 0.548; p < 0.001). There were no significant differences in FEV1 (%), symptoms or exacerbations between patients with optimal and suboptimal adherence. During follow-up, five patients (6%) with o-dr and 17 patients (17.7%) with t-dr suffered an exacerbation (p = 0.013). At visit two, 13.1% of the patients with o-dr and 31.3% with t-dr had uncontrolled asthma (p = 0.003), although more patients with o-dr were receiving inhaled corticosteroids in the high-dose stratum (25.8% vs. 11.5%; p = 0.001). CONCLUSION: Mean adherence rates were greater with od-r than with td-r, but we did not observe an effect on clinical outcomes.

The association between paracetamol and asthma is still under debate.

OBJECTIVE: To analyse the relationship between paracetamol and asthma. DATA SOURCES: An English literature search using electronic search engines (PubMed and EMBASE) was conducted. STUDY SELECTIONS: Articles published in peer-review journals, from 1990 to December 2015 were included. To perform the search for the most suitable and representative articles, keywords were selected ("asthma," "paracetamol" and "acetaminophen"). The evidence level was rated according to the criteria of the Oxford Centre For Evidence-Based Medicine. RESULTS: The exposure to paracetamol during pregnancy was analysed in several cohort studies, showing an association between the prenatal exposure to paracetamol with suffering from asthma or presence of wheezing in childhood, especially for persistent wheezing. Nevertheless, a recent study concluded that the relationship between asthma and paracetamol is explained, at least in part, by confounding factors. Several works have also associated the exposure to paracetamol in the first years of life or in adults with the development of childhood asthma. Several pathophysiological mechanisms are known that could explain this relationship, such as the glutathione pathway, the decrease in the release of Th1 cytokines that are normally produced during febrile episodes, which would then lead to a predominance of Th2 cytokines, the cytotoxic effect of paracetamol for pneumocytes, a modulator effect on the activity of myeloperoxidase, as well as the possible antigenic effect of paracetamol, mediated by IgE. CONCLUSIONS: There are many arguments that suggest a relationship between the use of paracetamol with the appearance of asthmatic symptoms, however the evidence is inconclusive.

Specific inhalation challenge: the relationship between response, clinical variables and lung function.

INTRODUCTION: The specific inhalation challenge (SIC) is considered the gold standard for the diagnosis of occupational asthma (OA). However, its use is not standardised, and the intensity of exposure is regulated empirically. The aim of this study was to identify clinical variables and/or pulmonary function variables able to predict the scale of patients' response to SIC. MATERIAL AND METHODS: All patients who underwent SIC at our centre between 2005 and 2013 were studied. Anthropometric characteristics, atopic status, type of causal agent, latency times, pulmonary function tests and SIC results were analysed. RESULTS: Two hundred and one patients (51% men) were assessed, of whom 86 (43%) had positive SIC. In the patients with positive results, 29 (34%) were exposed to high molecular weight (HMW) agents and 57 (64%) to low molecular weight (LMW) agents. Patients with a positive SIC exposed to HMW agents had a higher fall in FEV1 after SIC compared with those exposed to LMW agents (p=0.036). The type of asthmatic reaction after SIC also differed between the groups (p=0.020). The logistic regression analysis showed that patients with a higher PC20 before SIC were less likely to have severe decreases in FEV1 after SIC after adjusting for potential confounders (OR=0.771, 95% CI 0.618 to 0.961, p=0.021). CONCLUSIONS: The scale of the response to SIC is influenced mainly by the degree of bronchial hyper-responsiveness, regardless of whether the causative agent is HMW or LMW, or whether the response is early or late.

Lung cancer in never-smokers: a case-control study in a radon-prone area (Galicia, Spain).

The aim of the study was to assess the effect of residential radon exposure on the risk of lung cancer in never-smokers and to ascertain if environmental tobacco smoke modifies the effect of residential radon. We designed a multicentre hospital-based case-control study in a radon-prone area (Galicia, Spain). All participants were never-smokers. Cases had an anatomopathologically confirmed primary lung cancer and controls were recruited from individuals undergoing minor, non-oncological surgery. Residential radon was measured using alpha track detectors. We included 521 individuals, 192 cases and 329 controls, 21% were males. We observed an odds ratio of 2.42 (95% CI 1.45-4.06) for individuals exposed to ≥200 Bq·m(-3) compared with those exposed to <100 Bq·m(-3). Environmental tobacco smoke exposure at home increased lung cancer risk in individuals with radon exposure>200 Bq·m(-3). Individuals exposed to environmental tobacco smoke and to radon concentrations>200 Bq·m(-3) had higher lung cancer risk than those exposed to lower radon concentrations and exposed to environmental tobacco smoke. Residential radon increases lung cancer risk in never-smokers. An association between residential radon exposure and environmental tobacco smoke on the risk of lung cancer might exist.

Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study.

We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer.

New Vaccines for Chronic Respiratory Patients.

Chronic respiratory diseases (CRD) are responsible for more than four million deaths worldwide and have become especially prevalent in developed countries. Although the current therapies help manage daily symptoms and improve patients' quality of life, there is a major need to prevent exacerbations triggered mainly by respiratory infections. Therefore, CRD patients are a prime target for vaccination against infectious agents. In the present manuscript we review the state of the art of available vaccines specifically indicated in patients with CRDs. In addition to pneumococcus, influenza, pertussis, and SARS-CoV-2 vaccines, recently added immunization options like vaccines and monoclonal antibodies against respiratory syncytial virus, are particularly interesting in CRD patients. As new products reach the market, health authorities must be agile in updating immunization recommendations and in the programming of the vaccination of vulnerable populations such as patients with CRDs. Organizational and educational strategies might prove useful to increase vaccine uptake by CRD patients.