IL-10 AND IL-35 AS INFLAMMATION REGULATORS IN PATIENTS WITH ALLERGIC RHINITIS AND MILD ATOPIC ASTHMA

Background. Significantly less is known about the immunoregulative cytokines, especially in allergic airway disease. This study aims to present the involvement of IL-35 and IL-10 in patients with allergic rhinitis (AR) and allergic bronchial asthma (BA). Methodology. The study comprised 71 patients –AR, patients with concomitant AR and mild atopic BA, and healthy controls (HC). We examined the serum levels of IL-35 and IL-10, along with other instrumental examinations, between March and September 2021. Findings. Levels of the regulatory cytokines IL-35 and IL-10 were significantly lower in patients than in HC (87.19±11.90 vs. 96.12±1.79 pg/ml; and 30.26±17.55 vs. 111.56±65.03 pg/ml, respectively). Furthermore, threefold higher serum IL-10 levels were found in healthy subjects compared to patients (p = 0.006). No difference in the levels of interleukins was found between the studied groups. Conclusions. Our results indicate that elevated IL-35 and IL-10 may play an essential role in reducing the activity of underlying allergic inflammation in allergic respiratory diseases, although no difference in the levels of the studied cytokines was found between the different groups of patients. Therefore, we can speculate that the immunosuppressive cytokines IL-35 and IL-10 were involved in maintaining the healthy state of no inflammation.

Food and Aeroallergen Sensitization in IgE -Mediated Asthma in Egypt

Purpose: Identifying the distribution of allergens is valuable to the effective diagnosis and treatment of allergic disease. So, our aim is to explore the sensitization of food and aeroallergens in Egyptian patients with atopic asthma. Methods: Cross-sectional study recruited 268 Egyptian patients with atopic asthma. Asthmatic patients were assessed by the enzyme allegro sorbent test (EAST) method for specific IgE to a panel of 19 common regional inhaled allergens and 15 food allergens. Results and Discussion: One hundred percent of the patients were sensitive to at least one allergen. Allergy to food allergens only was 2.9%; inhaled allergens only were 26.2% and both were70.9%. Fungi (62%) were the most frequent sensitizing aeroallergen amongst our asthmatic patients, followed by the pollen allergens (42.5%) and house dust mites (HDMs) (26%). Cows’ milk (30.5%) was the most frequent sensitizing food amongst our asthmatic patients, followed by eggs (22.4%) and fish (21.6%). Mono-sensitized patients accounted for 6.7% of all cases, while polysensitized was 93.3%. Moderate and severe asthma showed a significantly higher frequency of polysensitization compared to mild asthma. Conclusion: Fungi and cow's milk are the chief sensitizing allergens in Egyptian patients with atopic asthma. This study represents the first report of sensitization in atopic adult asthma using a large extract panel in Upper Egypt.

Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic

BackgroundAsthma is characterised by an aggravated immune response to respiratory viral infections: This phenomenon is a clinically well-recognised driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to virus is unclear.ObjectivesTo describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation.MethodsIn the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 14 (28%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (TLR3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and anti-viral responses of BECs were analysed using RT-qPCR and multiplex ELISA and compared across asthma phenotypes and severity of disease.ResultsPatients with atopic asthma had increased induction of IL-4, IFN-β, IL-6, TNF-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas in patients with eosinophilic asthma only IL-6 and IL-8 induction was higher than in non-eosinophilic asthma. Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Furthermore, induction of IL-33 in response to poly (I:C) was increased in severe atopic and in severe eosinophilic asthma, but TSLP only in severe eosinophilic asthma.ConclusionsThe bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.

Nitric Oxide Synthase 2 Promoter Polymorphism Is a Risk Factor for Allergic Asthma in Children

Background and Objectives: In paediatric population, atopic asthma is associated with increased eosinophil counts in patients, that correlate with the airway inflammation measured by the concentration of nitric oxide in exhaled air (FeNO). As the FeNO level is a biomarker of atopic asthma, we assumed that polymorphisms in nitric synthases genes may represent a risk factor for asthma development. The purpose of this study was to analyse the association of NOS genetic variants with childhood asthma in the Polish population. Materials and methods: In study we included 443 children—220 patients diagnosed with atopic asthma and 223 healthy control subjects. We have genotyped 4 single nucleotide polymorphisms (SNP) from 3 genes involved in the nitric oxide synthesis (NOS1, NOS2 and NOS3). All analyses were performed using polymerase chain reaction with restriction fragments length polymorphism (PCR-RFLP). Results: We observed significant differences between cases and controls in SNP rs10459953 in NOS2 gene, considering both genotypes (p = 0.001) and alleles (p = 0.0006). The other analyzed polymorphisms did not show association with disease. Conclusions: According to our results, 5′UTR variant within NOS2 isoform may have an impact of asthma susceptibility in the population of Polish children. Further functional studies are required to understand the role of iNOS polymorphism in NOS2 translation and to consider it as a novel risk factor in childhood asthma. The next step would be to apply this knowledge to improve diagnosis and develop novel personalized asthma therapies.

Integrated metabolic and microbial analysis reveals host–microbial interactions in IgE-mediated childhood asthma

A metabolomics-based approach to address the molecular mechanism of childhood asthma with immunoglobulin E (IgE) or allergen sensitization related to microbiome in the airways remains lacking. Fifty-three children with lowly sensitized non-atopic asthma (n = 15), highly sensitized atopic asthma (n = 13), and healthy controls (n = 25) were enrolled. Blood metabolomic analysis with 1H-nuclear magnetic resonance (NMR) spectroscopy and airway microbiome composition analysis by bacterial 16S rRNA sequencing were performed. An integrative analysis of their associations with allergen-specific IgE levels for lowly and highly sensitized asthma was also assessed. Four metabolites including tyrosine, isovalerate, glycine, and histidine were uniquely associated with lowly sensitized asthma, whereas one metabolite, acetic acid, was strongly associated with highly sensitized asthma. Metabolites associated with highly sensitized asthma (valine, isobutyric acid, and acetic acid) and lowly sensitized asthma (isovalerate, tyrosine, and histidine) were strongly correlated each other (P < 0.01). Highly sensitized asthma associated metabolites were mainly enriched in pyruvate and acetyl-CoA metabolisms. Metabolites associated with highly sensitized atopic asthma were mostly correlated with microbiota in the airways. Acetic acid, a short-chain fatty acid (SCFA), was negatively correlated with the genus Atopobium (P < 0.01), but positively correlated with the genus Fusobacterium (P < 0.05). In conclusion, metabolomics reveals microbes-related metabolic pathways associated with IgE responses to house dust mite allergens in childhood asthma. A strong correlation of metabolites related to highly sensitized atopic asthma with airway microbiota provides linkages between the host–microbial interactions and asthma endotypes.

Omalizumab and modification of bronchial asthma natural course

Clinical and molecular heterogeneity of bronchial asthma has been documented in recent years. The search for novel solutions to enhance efficient patient support related first of all to understanding of asthma heterogenic nature and allows to personalize each patient treatment. Biological therapy application can influence to achieve better control at greater extent for patients with severe uncontrolled asthma. Nowadays 5 biological drugs are registered on Russian Federation territory and implemented according to severe asthma phenotypes: anti-IgE, anti-IL-4,13 and anti-IL-5 class therapies. Omalizumab become the first target drug for uncontrolled allergic asthma patients (monoclonal antibody against IgE). This medication is prescribed for uncontrolled moderate and severe allergic (atopic) asthma in patients on basic asthma therapy according GINA step 4 and 5 (Level of evidence A). Clinical trials confidently reported that anti- IgE-therapy reduces the rate of asthma exacerbations, severity of disease in patients with chronic severe asthma on high doses of inhaled steroids or systemic steroids and allows to reduce or withdraw systemic steroids doses in case of steroid-dependent asthma. For the last years special attention led to and demonstrated omalizumab positive effect on airways remodeling and modification of bronchial asthma natural course in adults and children. Antiinflammatory effect of omalizumab is documented. Omalizumab significantly reduces eosinophilic infiltration of submucosal bronchi layer among patients with atopic asthma, sputum eosinophilia, which correlates with reduction of FeNO during biologic treatment, reduces mast cells infiltration of smooth muscle cells in bronchi. Omalizumab significantly reduces the thickness of the bronchial wall, increases the lumen of the bronchi (positive dynamics of CT-scan parameters), which is clinically manifested by increased of FEV1.

Asthma Phenotypes and Host Risk Factors Associated With Various Asthma-Related Outcomes in Health Workers

Background: Work-related asthma phenotypes in health workers (HWs) exposed to cleaning agents have not been investigated extensively as other occupational exposures. This study aimed to describe asthma phenotypes and to identify important host risk factors associated with various asthma-related outcomes.Methods: A cross-sectional study of 699 HWs was conducted in two large tertiary hospitals. A total of 697 HWs completed questionnaire interviews. Sera collected from 682 HWs were analyzed for atopy (Phadiatop) and IgE to occupational allergens (NRL—Hev b5, Hev b6.02; chlorhexidine and ortho-phthalaldehyde—OPA). Methacholine (MCT), bronchodilator challenge (BDR) and fractional exhaled nitric oxide (FeNO) were performed. An asthma symptom score (ASS) used five asthma-related symptoms reported in the past 12 months. Current asthma was based on use of asthma medication or an asthma attack or being woken up by an attack of shortness of breath in the past 12 months. Nonspecific bronchial hyperresponsiveness (NSBH) was defined as having either a positive MCT or a significant bronchodilator response. Two continuous indices of NSBH [continuous index of responsiveness (CIR) and dose-response slope (DRS)] were calculated.Results: The prevalence of current asthma was 10%, atopic asthma (6%) and non-atopic asthma (4%). Overall, 2% of subjects had work-related asthma. There was a weak positive association between NSBH and FeNO [CIR: Beta coefficient (β) = 0.12; CI: 0.03–0.22 and DRS: β = 0.07; CI: 0.03–0.12]. Combining FeNO ≥ 50 ppb with a BDR [mean ratio (MR) = 5.89; CI: 1.02–34.14] or with NSBH (MR = 4.62; CI: 1.16–18.46) correlated better with ASS than FeNO alone (MR = 2.23; CI: 1.30–3.85). HWs with current asthma were twice as likely to be atopic. FeNO was positively associated with atopy (OR = 3.19; CI: 1.59–6.39) but negatively associated with smoking status (GMR = 0.76; CI: 0.62–0.94). Most HWs sensitized to occupational allergens were atopic.Conclusion: Atopic asthma was more prevalent than non-atopic asthma in HWs. Most asthma-related outcomes were positively associated with allergic predictors suggesting a dominant role for IgE mechanisms for work-related symptoms and asthma associated with sensitization to OPA or chlorhexidine.

B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma

In order to better understand how the immune system interacts with environmental triggers to produce organ-specific disease, we here address the hypothesis that B and plasma cells are free to migrate through the mucosal surfaces of the upper and lower respiratory tracts, and that their total antibody repertoire is modified in a common respiratory tract disease, in this case atopic asthma. Using Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) we have catalogued the antibody repertoires of B cell clones retrieved near contemporaneously from multiple sites in the upper and lower respiratory tract mucosa of adult volunteers with atopic asthma and non-atopic controls and traced their migration. We show that the lower and upper respiratory tracts are immunologically connected, with trafficking of B cells directionally biased from the upper to the lower respiratory tract and points of selection when migrating from the nasal mucosa and into the bronchial mucosa. The repertoires are characterized by both IgD-only B cells and others undergoing class switch recombination, with restriction of the antibody repertoire distinct in asthmatics compared with controls. We conclude that B cells and plasma cells migrate freely throughout the respiratory tract and exhibit distinct antibody repertoires in health and disease.