Risk Factor For Severe Asthma Research Articles

Exogenous Ang-(1-7) inhibits autophagy via HIF-1α/THBS1/BECN1 axis to alleviate chronic intermittent hypoxia-enhanced airway remodelling of asthma

Obstructive sleep apnoea (OSA)-induced chronic intermittent hypoxia (CIH) has been considered a risk factor for severe asthma. Airway remodelling, which could be modulated by autophagy, plays a key role in severe asthma. However, the extent of autophagy’s involvement in CIH-potentiated airway remodelling remains largely unexplored. Furthermore, we had found that angiotensin-(1-7) [Ang-(1-7)] has therapeutic effects on airway remodelling in asthma, but the underlying mechanism is either unclear. This study aimed to explore how CIH aggravates asthma and mechanism of protective effects of Ang-(1-7) on airway remodelling, with a focus on autophagy. We observed that CIH promoted epithelial-to-mesenchymal transition (EMT), indicated by elevated EMT and fibrotic markers such as Snail and Collagen IV, both in vitro and in vivo. CIH intensified cell autophagy, evident from increased LC3B expression and reduced p62 levels. Ang-(1-7) reversed the CIH-enhanced expression of Snail, Collagen IV, and LC3B. To explore how CIH enhanced autophagy in cellular and animal model of asthma, overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and Thrombospondin 1 (THBS1) were identified in CIH-exposure mice lung compared with normal mice lung tissues from the GEO database. Finally, through chromatin immunoprecipitation and immunoprecipitation assays, we verified that Ang-(1-7) inhibits CIH-induced binding of HIF-1α to the promoter of THBS1, and also disrupts the protein-protein interaction between THBS1 and the autophagy-associated protein Beclin 1 (BECN1), ultimately leading to autophagy inhibition. Our findings suggest that exogenous Ang-(1-7) can inhibit autophagy via HIF-1α/THBS1/BECN1 axis, thereby alleviating CIH-enhanced airway remodelling in asthma. These findings imply the potential therapeutic effect of Ang-(1-7) in asthma with OSA.

Genetic variants associated with SARS-CoV-2 infection also affect lung function and asthma severity

BackgroundHost genetic factors may be associated with COVID-19 unfavourable outcomes. The first genome-wide association study (GWAS) conducted in individuals with respiratory failure due to COVID-19 revealed susceptibility loci close to six genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1) and the ABO blood-group gene. We aimed to investigate how polymorphisms in those genes could relate to lung function and severe asthma in a Brazilian population. MethodsDNA samples of 784 individuals following the ProAR (Programa para Controle da Asma e Rinite Alérgica da Bahia) were genotyped by the Multi-Ethnic Global Array panel with ∼2 million polymorphisms (Illumina). Polymorphisms in SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1 and the ABO blood-group gene were evaluated. Logistic regression for severe asthma, airway obstruction and lack of FEV1 reversibility was performed using PLINK software 1.9, in the additive model and was adjusted for sex, age and PCA-1. Pairwise Linkage disequilibrium analyses were performed using Haploview 4.2. The haplotypes and gene score analyses were performed in the SNPstat tool. In silico functions of polymorphisms were analysed using rSNPbase and RegulomeDB plataforms. ResultsWe identified the rs8176733 (G allele) and rs8176725 (A allele) in the ABO blood-group gene as risk factors for severe asthma, lower pulmonary obstruction and lack of FEV1 reversibility. Polymorphisms in CCR9 are risk factors for both severe asthma (A allele of rs34338823) and airway obstruction (A allele of rs6806802). The markers rs13079478 (A allele) and rs75817942 (A allele) in FYCO1 are related to more severe asthma and a lack of FEV1 reversibility, respectively. We identified the A allele of both rs35731912 and rs34338823 in LZTFL1 as risk factors for severe asthma. The marker rs6806802 (C allele) was associated with airway obstruction and rs7614952 (A allele), rs7625839 (G allele) and rs112509260 (A allele) are related to a lack of FEV1 reversibility. The A allele of rs2531747 in the SLC6A20 gene is also associated with severe asthma. Conversely, polymorphisms in XCR1 play a protective role in relation to severe asthma (A allele of rs2036295) and airway obstruction (A allele of rs2036295). Additionally, we found that individuals with a higher number of risk alleles have a greater risk of severe asthma, airway obstruction and FEV1 reversibility. ConclusionOur study suggests that polymorphisms in genes associated with respiratory failure in SARS-CoV-2-infected individuals are associated with greater susceptibility to severe asthma and reduced lung function in subjects with asthma.

Characterization of Obesity in Severe Asthma in the German Asthma Net

Asthma is increasingly recognized as heterogeneous, characterized by different endotypes, with obesity not only a distinct phenotype but a risk factor for severe asthma. We sought to understand the associations of obesity with relevant parameters of severe asthma, including asthma control, disease burden, and lung function. The German Asthma Net registry is a multicenter international real-life registry capturing long-term follow-up data. This analysis included 2213 patients (52 ± 16 years, 58% female, 29% with obesity [body mass index ≥30 kg/m2], 4.2 ± 4.3 exacerbations/year). The primary analysis assessed relationships between BMI and variables through univariate tests, followed by a multiple regression model. Secondary outcomes regarded clinically relevant variables in relation to weight groups. Patients with obesity were more frequently female, more likely to have depression and gastroesophageal reflux, and suffered from worse asthma control, lower quality of life, reduced static lung volumes, more pronounced hypoxemia, and higher blood neutrophil counts, all statistically significant. Blood eosinophils, exhaled nitric oxide, and total IgE were independent of obesity. In the multiple regression analysis, obesity was significantly associated with more frequent reflux and depression, reduced static lung function values, older age, poor asthma control, and long-acting muscarinic antagonist therapy, and inversely associated with bronchiectasis and nonsmoking status. In this large, well-characterized cohort, we identified the association of obesity with a significantly higher disease burden and a similar portfolio of inflammation type 2 markers in patients with and without obesity; therefore, patients with obesity seem similarly eligible for the treatment with biologics targeting these disease endotypes.

Effect of roflumilast on airway remodeling in asthmatic mice exposed to or not exposed to cigarette smoke: Comparison with the effect of dexamethasone

Cigarette smoking constitutes a risk factor for severe asthma, which is frequently linked to remodeling of the airways. Appropriate drug treatment for smokers with asthma is uncertain because many smokers with asthma are less sensitive to glucocorticoid treatment than non-smokers with asthma. The purpose of this study was to compare the anti-airway remodeling effects of dexamethasone (Dex) and roflumilast (Rof), a selective phosphodiesterases-4 inhibitor, in smoking and non-smoking mice with asthma. BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA for two weeks, either with or without concurrent exposure to cigarette smoke (CS). Dex (1 mg/kg body weight), Rof (5 mg/kg body weight), or vehicle alone was given orally to the mice once daily. To assess the histopathological effects of airway remodeling, lung tissue sections were obtained. Repeated OVA challenges resulted in fibrosis, goblet cell hyperplasia, and thickening of the airway but not the smooth muscle layer. The presence of CS did not have an impact on the degree of airway remodeling brought on by repeated OVA challenges. In mice repeatedly exposed to OVA either with or without CS, Dex treatment reduced the remodeling alterations. In these mice group, the Rof Treatment had a less significant impact than the Dex treatment. Dex was still more effective than Rof at reducing airway remodeling in asthmatic smoking mice. According to the current study's findings, Dex effectively prevented airway remodeling in a two-week asthma model in mice exposed to CS or not. In contrast, we found that Rof had little to no inhibitory effect of Rof on the airway in our mouse model of asthma, whether or not it had been exposed to CS. We were unable to find solid proof to support CS-induced steroid resistance to treat airway remodeling.

Determinants of Severe Asthma - A Long-Term Cohort Study in Northern Sweden.

BackgroundRisk factors for severe asthma are not well described. The aim was to identify clinical characteristics and risk factors at study entry that are associated with severe asthma at follow-up in a long-term prospective population-based cohort study of adults with asthma.MethodsBetween 1986 and 2001, 2055 adults with asthma were identified by clinical examinations of population-based samples in northern Sweden. During 2012–2014, n = 1006 (71% of invited) were still alive, residing in the study area and participated in a follow-up, of which 40 were identified as having severe asthma according to ERS/ATS, 131 according to GINA, while 875 had other asthma. The mean follow-up time was 18.7 years.ResultsObesity at study entry and adult-onset asthma were associated with severe asthma at follow-up. While severe asthma was more common in those with adult-onset asthma in both men and women, the association with obesity was observed in women only. Sensitization to mites and moulds, but not to other allergens, as well as NSAID-related respiratory symptoms was more common in severe asthma than in other asthma. Participants with severe asthma at follow-up had lower FEV1, more pronounced FEV1 reversibility, and more wheeze, dyspnea and nighttime awakenings already at study entry than those with other asthma.ConclusionAdult-onset asthma is an important risk factor for development of severe asthma in adults, and obesity increased the risk among women. The high burden of respiratory symptoms already at study entry also indicate long-term associations with development of severe asthma.

Geospatial data in pediatric asthma in the United States: a scoping review protocol.

The objective of this scoping review is to identify and describe the literature on the use of geospatial data in pediatric asthma research. Asthma is one of the most common pediatric chronic diseases in the United States, disproportionately affecting low-income patients. Asthma exacerbations may be triggered by local environmental factors, such as air pollution or exposure to indoor allergens. Geographic information systems are increasingly recognized as tools that use geospatial data to enhance understanding of the link between environmental exposure, social determinants of health, and clinical outcomes. Geospatial data in pediatric asthma may help inform risk factors for asthma severity, and guide targeted clinical and social interventions. This review will consider studies that utilize geospatial data in the evaluation of pediatric patients with asthma, ages 2 to 18 years, in the United States. Mixed samples of adults and children will also be considered. Geospatial data will include any external non-clinical geographic-based data source that uses a patient's environment or context. The following databases will be searched: PubMed, Embase, Cochrane CENTRAL, CINAHL, ERIC, Web of Science, and IEEE. Gray literature will be searched in DBLP, the US Environmental Protection Agency, Google Scholar, Google search, and a hand search of recent abstracts from relevant conferences. Articles published in English, Spanish, and French from 2010 to the present will be included. Study screening and selection will be performed independently by 2 reviewers. Data extraction will be performed by a trained research team member following pilot testing.

The A118G single-nucleotide polymorphism in OPRM1 is a risk factor for asthma severity

BackgroundAlthough population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related μ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity. MethodsWe initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response. ResultsAmong 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4+CD4+ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4+ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation. ConclusionsWithout forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN.

Dexamethasone-Induced FKBP51 Expression in CD4+ T-Lymphocytes Is Uniquely Associated With Worse Asthma Control in Obese Children With Asthma.

IntroductionThere is evidence that obesity, a risk factor for asthma severity and morbidity, has a unique asthma phenotype which is less atopic and less responsive to inhaled corticosteroids (ICS). Peripheral blood mononuclear cells (PBMC) are important to the immunologic pathways of obese asthma and steroid resistance. However, the cellular source associated with steroid resistance has remained elusive. We compared the lymphocyte landscape among obese children with asthma to matched normal weight children with asthma and assessed relationship to asthma control.MethodsHigh-dimensional flow cytometry of PBMC at baseline and after dexamethasone stimulation was performed to characterize lymphocyte subpopulations, T-lymphocyte polarization, proliferation (Ki-67+), and expression of the steroid-responsive protein FK506-binding protein 51 (FKBP51). T-lymphocyte populations were compared between obese and normal-weight participants, and an unbiased, unsupervised clustering analysis was performed. Differentially expressed clusters were compared with asthma control, adjusted for ICS and exhaled nitric oxide.ResultsIn the obese population, there was an increased cluster of CD4+ T-lymphocytes expressing Ki-67 and FKBP51 at baseline and CD4+ T-lymphocytes expressing FKBP51 after dexamethasone stimulation. CD4+ Ki-67 and FKBP51 expression at baseline showed no association with asthma control. Dexamethasone-induced CD4+ FKBP51 expression was associated with worse asthma control in obese participants with asthma. FKBP51 expression in CD8+ T cells and CD19+ B cells did not differ among groups, nor did polarization profiles for Th1, Th2, Th9, or Th17 percentage.DiscussionDexamethasone-induced CD4+ FKBP51 expression is uniquely associated with worse asthma control in obese children with asthma and may underlie the corticosteroid resistance observed in this population.

Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide

BackgroundInhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger).MethodsC57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 μg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined.ResultsIn comparison to mice challenged only with A. niger, addition of LPS (1 μg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies.ConclusionsIn contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.

Measuring the Association Between Thunderstorms in the Presence of High Pollen and Risk of Severe Asthma

BACKGROUND AND AIM: Studies have shown an acute association between the occurrence of thunderstorm conditions in the presence of high pollen and severe asthma, but minimal work has studied these events over a multi-year time series, using detailed measurements of storms and pollen. METHODS: We estimate the change in risk between thunderstorm asthma events and asthma-related emergency room visits in the Minneapolis-St. Paul metropolitan area for the years 2007-2018. We defined thunderstorm asthma events as daily occurrence of 2 or more lightning strikes during periods of high pollen, interpolated using weather and pollen monitor data and modeled lightning counts. Daily counts of asthma-related emergency department visits were acquired from the Minnesota Hospital Association. We use a 2-stage approach combining zip code level quasi-Poisson time-series regressions in a meta-analysis to estimate an overall relative risk of hospitalizations during thunderstorm asthma events. RESULTS:We observed a 4.4% (RR = 1.044; 95% CI (1.013,1.076), increase in asthma emergency department visits on the day of thunderstorm asthma event and a 3.2% (RR 1.032; 95% CI (1.003,1.062) increase on the day after the storm event. Our findings were robust to adjustment for temperature, humidity, wind, precipitation, ozone, PM2.5, day of week, and natural splines for seasonal variation in asthma cases. Occurrence of lightning alone or pollen alone shows no association with risk of severe asthma. CONCLUSIONS:Our results support an association between co-occurrence of lightning and pollen and risk of asthma hospitalization. This model, while previously described with specific epidemic events, has not been well studied in a time series model to evaluate long-term risk, using measurement of both lightning and pollen, and never using unique small area exposure assignment and outcome counts. Our findings indicate that thunderstorm asthma may be an unidentified environmental risk factor for severe asthma. KEYWORDS: asthma, pollen, thunderstorms, climate

Small Airway Dysfunction Links Asthma Severity with Physical Activity and Symptom Control

Little is known about the role of small airway dysfunction (SAD) and its complex relation with asthma control and physical activity (PA). To investigate the interrelations among SAD, risk factors for asthma severity, symptom control, and PA. We assessed SAD by impulse oscillometry and other sophisticated lung function measures including inert gas washout in adults with asthma (mild to moderate, n= 140; severe, n= 128) and 69 healthy controls from the All Age Asthma Cohort. We evaluated SAD prevalence and its interrelation with risk factors for asthma severity (older age, obesity, and smoking), type 2 inflammation (sputum and blood eosinophils, fractional exhaled nitric oxide), systemic inflammation (high-sensitivity C-reactive protein), asthma control (AC), and PA (accelerometer for 1 week). We applied a clinical model based on structural equation modeling that integrated causal pathways among these clinical variables. The prevalence of SAD ranged from 75% to 90% in patients with severe asthma and from 53% to 64% in mild to moderate asthma. Severe SAD was associated with poor AC and low PA. Structural equation modeling indicated that age, obesity, obesity-related systemic inflammation, T2 inflammation, and smoking are independent predictors of SAD. Small airway dysfunction was the main determinant factor of AC, which in turn affected PA. Obesity affected AC directly and through its contribution to SAD and low PA. In addition, PA had bidirectional associations with obesity, SAD, and AC. Structural equation modeling also indicated interrelations among distal airflow limitation, air trapping, and ventilation heterogeneity. Small airway dysfunction is a highly prevalent key feature of asthma that interrelates a spectrum of distal lung function abnormalities with risk factors for asthma severity, asthma control, and physical activity.

Effect of overweight or obesity on lung function and asthma severity in prepubertal asthmatic children

Purpose: Cluster analysis on pediatric asthma identifying a cluster characterized by obesity, females, and puberty showed that obe-sity is an independent risk factor for severe asthma in this cluster. In the present study, we aimed to investigate the effect of over-weight/obesity on lung function and asthma severity in prepubertal asthmatic children. Methods: One hundred fifty-five prepubertal children (aged 6-10) with asthma were enrolled and divided into 2 groups: the over-weight/obese group (body mass index [BMI] ≥85th percentile, n=44) and the normal BMI group (<85th percentile, n=111). We re-viewed their medical records and analyzed whether there were any differences in clinical features, lung function and degree of bron-chial hyperresponsiveness (BHR) between the 2 groups. The clinical factors associated with asthma severity were also investigated. Results: There was no difference in clinical features between the 2 groups. Pulmonary function tests showed that only forced vital capacity in 1 second/forced vital capacity (FEV1/FVC) was significantly lower in the overweight/obese group than in the normal BMI group (P=0.032). There was no difference in dysanapsis and BHR between the 2 groups. There were significantly more children with moderate-to-severe asthma in the overweight/obese group compared to the normal BMI group (P=0.018). In multivariate logistic regression analysis, overweight/obesity has been identified as an independent risk factor of affecting asthma severity (odds ratio, 2.44; P=0.018), in addition to the already known risk factor, FEV1. Conclusion: Our study showed that overweight/obese prepubertal asthmatic children had lower FEV1/FVC than those with normal BMI. It also suggests that overweight/obesity may be an independent risk factor for severe asthma before puberty. (Allergy Asthma Respir Dis 2021;9:231-237)

Pulmonary emphysema is associated with fungal sensitization in asthma.

BackgroundFungal sensitization is a risk factor for severe asthma. Colonization in the lower respiratory tract is one of the forms of fungal exposure, and it is related to fungal sensitization. Pulmonary emphysema was recently reported to be an underlying disease of fungal colonization. The aim of study was to evaluate the prevalence of pulmonary emphysema in asthmatic patients with and without fungal sensitization.MethodsWe enrolled 108 patients with allergic asthma and divided them into the patients sensitized to Aspergillus and/or Candida (n=56) and those not sensitized to both Aspergillus and Candida (n=52). The presence of pulmonary emphysema on chest CT was evaluated retrospectively.ResultsThe frequency of pulmonary emphysema was significantly higher in the patients sensitized to Aspergillus and/or Candida compared to the patients not sensitized to both fungi (P=0.0040). The frequency of pulmonary emphysema was also significantly higher in the patients sensitized to either Aspergillus or Candida compared to the patient not sensitized to the fungi (P=0.0398 and P=0.0198, respectively). A multivariate logistic regression analysis demonstrated that the presence of pulmonary emphysema was independently associated with the sensitization to Aspergillus and/or Candida (OR 7.84, 95% CI: 1.20–51.10).ConclusionsPulmonary emphysema is associated with sensitization to Aspergillus and/or Candida.

Value of Component Resolved Diagnostics to Aspergillus fumigatus in Patients with Upper Airway Complaints

Introduction: Sensitization to Aspergillus fumigatus is a risk factor for severe asthma. However, little is known about its presence, appearance, and impact on allergic rhinitis. Herein, we investigated the usefulness of component resolved diagnostics in patients sensitized to Aspergillus fumigatus protein extract. Methods: Seventy-eight patients with suspected allergic rhinitis and elevated IgE levels toward Aspergillus fumigatus protein extract were retrospectively evaluated regarding their total and Aspergillus-specific IgE levels and their skin prick test. Furthermore, they were tested for specific IgE antibodies against Asp f 1, 2, 3, 4, and 6. Results: Skin prick test missed 6 patients (7.7%) with elevated IgE toward Aspergillus fumigatus protein extract. Fifty percent of patients (n = 39) were sensitized to at least one component. Even though monosensitization affected all components, all patients with positivity toward more than one component were sensitized to Asp f 1. There was a statistically significant increase of Aspergillus-specific IgE with increasing number of components affected by sensitization. Many patients were oligo- (34.6%) or polysensitized (51.3%). There was a high prevalence of sinusitis (61.8%). Conclusions: Component resolved diagnostic testing toward the major allergen Asp f 1 was less sensitive than skin prick test and serology to Aspergillus fumigatus protein extract. However, sensitivity of component resolved diagnostics might be underestimated. Diagnostics of the species-specific allergens Asp f 1, 2, and 4 might allow to differentiate between genuine and cross-reactive sensitization. In the clinical routine, skin prick test and serology to crude extract remain the methods of choice.

CHARACTERISTIC OF SEVERE FORMS OF BRONCHIAL ASTHMA IN CHILDREN OF THE ANDIJAN REGION

To study the characteristics of severe bronchial asthma, 140 children were examined. A survey, clinical, allergological and functional examinations were carried out. Studies have shown that in boys, asthma becomes severe earlier. Polyvalent sensitization to epidermal allergens and the presence of bronchial asthma in the mother of the child, severe asphyxia at birth are risk factors for severe asthma in children

Association of molds and metrological parameters to frequency of severe asthma exacerbation

BackgroundSensitization to airborne molds may be a risk factor for severe asthma and direct cause of asthma exacerbation (AE).MethodsA prospective, 1-year (April 2016–March 2017) study, done in Kuwait Allergy Centre, investigated the link between AEs with exposure to outdoor molds and the role of meteorological parameters in mold sensitized patients and compared with non-allergic asthma patients who had asthma deterioration. The total of 676 adult asthmatics with moderate-severe AEs were included and divided into atopic (85.65%) and non-atopic group. Atopy was defined by positive skin prick test (SPT) to at least one inhalant allergen. Data regarding atopy and asthma severity were collected from patient’s records. Patients with symptoms and signs of acute respiratory infection and patient sensitized to indoor allergens only were excluded. Daily count of local pollens (Salsola kali, Bermuda grass) and molds (Aspergillus, Alternaria and Cladosporium) were obtained from the Aerobiology department. Daily metrological parameters (atmospheric pressure-AP, temperature-T and relative humidity-RH) were provided by Kuwait Environment Public Authority. Count of spores/m3 and weather variable are shown on weekly basis. The year circle was divided into 4 Seasons (1, 2, 3, 4) accordingly to typical desert climate.ResultsSensitization to molds was relatively high but significantly less (25.0%) if compared to the pollens sensitization. The highest number of AEs was in season 4 for both molds and pollens sensitized patients. Seasonal patterns for both allergens were significant and positively correlated with RH and AP. In season 1 only, mold sensitized patients showed higher rate of AEs. Non-atopic patients have been less sensitive to increased RH than atopic. Negative correlation with T was similar in both atopic and non-atopic patients.ConclusionDespite of high rate of sensitization to molds, their significant role in triggering AE was not found in desert environment. Typical desert climate and high allergencity of local weeds outweigh the influence of the molds.

Regulation of IL-17A and implications for TGF-β1 comodulation of airway smooth muscle remodeling in severe asthma.

Severe asthma develops as a result of heightened, persistent symptoms that generally coincide with pronounced neutrophilic airway inflammation. In individuals with severe asthma, symptoms are poorly controlled by high-dose inhaled glucocorticoids and often lead to elevated morbidity and mortality rates that underscore the necessity for novel drug target identification that overcomes limitations in disease management. Many incidences of severe asthma are mechanistically associated with T helper 17 (TH17) cell-derived cytokines and immune factors that mediate neutrophilic influx to the airways. TH17-secreted interleukin-17A (IL-17A) is an independent risk factor for severe asthma that impacts airway smooth muscle (ASM) remodeling. TH17-derived cytokines and diverse immune mediators further interact with structural cells of the airway to induce pathophysiological processes that impact ASM functionality. Transforming growth factor-β1 (TGF-β1) is a pivotal mediator involved in airway remodeling that correlates with enhanced TH17 activity in individuals with severe asthma and is essential to TH17 differentiation and IL-17A production. IL-17A can also reciprocally enhance activation of TGF-β1 signaling pathways, whereas combined TH1/TH17 or TH2/TH17 immune responses may additively impact asthma severity. This review seeks to provide a comprehensive summary of cytokine-driven T cell fate determination and TH17-mediated airway inflammation. It will further review the evidence demonstrating the extent to which IL-17A interacts with various immune factors, specifically TGF-β1, to contribute to ASM remodeling and altered function in TH17-driven endotypes of severe asthma.

IgE sensitization and sociodemographic conditions as determinant factors in asthma severity

In Latin America there are few data about the factors that influence the control and severity of asthma. To describe the association between IgE sensitization to intra-home allergens and housing conditions in the severity of asthma. Sensitization to aero-allergens was evaluated by skin prick test and socio-demographic data by a questionnaire in a population between 6 and 14 years of age with diagnosis of asthma. Asthma control was measured according to spirometric results and to the application of the ACT (Asthma Control Test); the severity and symptom control was evaluated according to the GINA guideline. A total of 150 resident patients from the Aburra Valley (Colombia) were included. The median age of participants was 11 years, 95 (63.3 %) male. 92 % of the patients resided in the urban area. Mite sensitization was the most prevalent in controlled and uncontrolled patients. Sensitization to cockroach and some poverty conditions were risk factors for asthma severity. Poverty conditions appear to favor the development of severe asthma and in turn IgE sensitization to cockroaches. This sensitization could serve as a biomarker of severity.

IL-8 Gene Variants and Expression in Childhood Asthma.

PurposeTo examine the IL-8 expression levels and association of genetic variants with the risk of childhood persistent asthma prognosis.MethodsOverall, 170 asthmatic children and 170 healthy controls were included in this case–control study. The human IL-8 serum levels were measured using ELISA. The IL-8 mRNA expression levels were assessed by a real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) methods.ResultsThe IL-8 expression at both protein and mRNA levels was found to be significantly elevated in asthmatic children compared to healthy subjects (P < 0.0001, P = 0.004; respectively). Higher levels of IL-8 mRNA are detected in subjects with moderate to severe asthma. The presence of IL8-251 A/T (rs4073) and + 781C/T (rs2227306) polymorphisms was significantly associated with an increased risk of asthma (P = 0.002, P = 0.036, respectively). In addition, we noted a significant association between these polymorphisms and an elevated risk of atopic asthma (P < 0.05). For rs2227306 SNP, the highest median level of IgE was detected for the presence of TT genotype (865 ± 99.74 IU/mL). Although, the rs4073 polymorphism conferred a higher risk to develop asthma at an advanced stage of severity (P = 0.008). The rs4073 T and rs2227306 C alleles are considered as risk factors for asthma development. The rs4073 T allele is represented also as a risk factor for asthma severity in Tunisian children.ConclusionsBoth IL-8 gene and protein expression may play a key role in asthma pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00408-017-0058-6) contains supplementary material, which is available to authorized users.

High prevalence of severe asthma in a large random population study

The prevalence of asthma severity is not well described at a population level. We sought to determine the prevalence of phenotypic signs of asthma severity among asthmatic patients in a general population and to describe risk factors for asthma severity. We performed an epidemiologic study conducted between 2008 and 2012 (West Sweden Asthma Study). Apostal questionnaire was sent to a random population (n=30,000) in west Sweden, with 18,087 responses. Atotal of 2,006 subjects were carefully phenotyped. Only subjects with "active asthma" (symptoms or medication in the last year, n=744) were analyzed in this study to determine the degree of severity of the disease within an asthma cohort. Phenotypes of severity were calculated based on (1) multiple symptoms during the day despite ongoing use of asthma medications, (2) FEV1 of less than 70% of predicted value, (3) daily or almost daily use of rescue medications, (4) nighttime symptoms once a week or more, and (5) oral corticosteroid use/emergency department visits. Asthmatic patients were grouped as having nonsevere disease, 1sign of severity, or 2 or more signs of severity. A total of 36.2% of asthmatic patients expressed at least 1 sign of asthma severity, and 13.2% had 2 or more signs. The group with 2 or more signs was older in age and had higher body mass index, a higher rate of tobacco smoking, and lower lung function. Bronchial hyperreactivity, airway inflammation, and sensitization were significantly different among the 3 groups. At a population level, the prevalence of asthma severity was 3.1% for 1 sign and 1.3% for at least 2 signs. More than 1 in 3 asthmatic patients show at least 1 sign of asthma severity. The phenotypes of asthma severity are highly diverse, which is important to consider when implementing personalized medicine in asthmatic patients.