Inhalant Allergens Research Articles

INVESTIGATION OF ALLERGEN SENSITIVITY OF SYRIAN REFUGEE CHILDREN WITH ALLERGIC DISEASES

Background: The aim of this study was identification of the allergic sensitivities of Syrian refugee children residing in Western Turkey and diagnosed with various allergic diseases. Materials and methods: Syrian refugee children younger than 18 constituted the target population of this study. A group of patients were assigned to the control group. The levels of total immunoglobulin E, A, G, M, eosinophil counts and percentages, and the results of inhalant and food allergy tests of patients and controls were all recorded. Results: The entire study cohort consisted of 34 patients (23 boys, 11 girls) in the study group and 30 patients (20 boys, 10 girls) in the control group. There were statistically significant relationships between patients and controls about eosinophil counts and percentages (p= 0.005, p < 0.0001, respectively). Conclusion: Our study is the first report investigating the allergic sensitivities of Syrian children to the best of our knowledge. We believe that our findings will enlighten the approach of the clinicians taking care of Syrian children in different countries hosting Syrian refugees. Keywords: inhalant allergen sensitivity, food allergen sensitivity, Syrian refugee, allergic disease

Performance of EAST in diagnosing inhalant allergens in children with allergic rhinitis

The performance of enzyme linked immunosorbent assays (EAST) for identifying six indoor allergens was evaluated using skin prick test (SPT) as reference tests in 154 children with allergic rhinitis. Sensitivity of EAST ranged from 9% (cat) to 54% (HDM) with specificity of 74%(cockroach) to 100% (cat) with an agreement ranged from 58 to 86%. Cut off values ​> ​0.35 kU/L showed best sensitivity and specificity. Our findings agree with extant literature which suggests that the ability of EAST to determine the precipitating allergen is moderate. Assays for definitively identifying the inhalant allergen are currently not available.

Accelerated/rush allergen immunotherapy.

Accelerated allergy shot schedules for inhalant and venom allergens provide individuals with allergy symptom relief but in a shorter time frame than conventional therapy. Accelerated immunotherapy (IT) protocols allow patients to reach therapeutic doses in a shorter time frame while improving adherence and reducing direct costs (e.g., fewer office visits and medications) and indirect costs (e.g., less travel time, missed work or school). Rush IT and cluster IT are believed to work through mechanisms similar to conventional subcutaneous IT (SCIT). The risk for severe systemic reactions during accelerated IT is low when appropriately administered; however, life-threatening and fatal reactions do occur. To reduce the incidence of systemic allergic reactions during cluster and rush IT protocols, premedication is recommended. It is important to exclude individuals at high risk such as those with poorly controlled asthma or those who are on β-blockers to mitigate the risk for developing systemic allergic reactions. However, accelerated SCIT regimens offer increased convenience, faster improvement in allergy symptoms, and the potential to reduce health-care costs while providing equivalent safety outcomes compared with conventional IT protocols.

Allergic and non-allergic asthma in children hospitalized in the University Children’s Hospital in Lublin in 2016-2020

Abstract Introduction. Bronchial asthma is a common disease characterized by chronic inflammation of the airways. Paediatric asthma is still a current problem and children with exacerbation frequently are hospitalized. The aim of the study was to determine the prevalence of allergic and non-allergic asthma in children hospitalized at the Department of Paediatric Pulmonology and Rheumatology of the University Children’s Hospital in Lublin in 2016-2020, and to analyze the most common allergens associated with allergic asthma. Materials and methods. The study group consisted of 667 patients, aged 6 to 215 months (average 64 months). The data collected for this retrospective study includes: gender, age, month, quarter of year, and year of hospitalization, type of asthma and type of allergens. Results. We observed a decrease of hospitalization in the analyzed years: in 2016 – 160 children, and in 2020 – 74. Children with allergic asthma (375 children) were more frequently hospitalized than patients with non-allergic asthma, and we found correlations between age and type of asthma and between age and type of allergy. Non-allergic asthma was observed in the youngest children, while in older children, allergic-asthma dominated. We also observed significant differences in children’s hospitalization depending on the season of the year. The most frequent allergen causing asthma was house dust mites. Conclusions. The incidence of hospitalizations caused by asthma exacerbation is declining. Among the youngest population, exacerbations of asthma related to respiratory tract infection predominate, while in the older, allergy to inhalation allergens is the main cause.

Allergy to airborne allergens and menstrual cycles of women treated for infertility

BackgroundAllergy and fertility problems are important issues. Hormonal status can influence the expression of atopic diseases. ObjectiveThe aim of this study was to assess a connection between sensitization to aeroallergens and the menstruation cycle in infertile women. MethodEighty two women (age range 24–42years, mean age 32.5), treated for difficulties with conception were selected. A detailed history was taken from all patients, including history of allergic diseases. They were physically examined, including gynaecological assessment. All women had skin prick tests with the most important inhalatory allergens (HAL allergy, Leiden, Netherlands). ResultsPositive skin prick tests (SPT) to at least one allergen were observed in 33 patients (40.24%). Grass and rye were the most common sensitizing allergen (22% each), followed by mugwort (19.5%), and house dust mites (14.6%). Correlations between positive SPT and the menstrual cycle were analyzed. The age at the time of the first period is associated with positive SPT for mugwort (P<0.05). OR is 0.638, therefore each year of delay of the first period reduced the risk by 36.2%. Length of the cycle is associated with positivity SPT to Dermatophagoides farinae (P<0.05). OR is 1.133, therefore each additional day of the cycle increased the risk by 13.3%. ConclusionIn this study on women treated for infertility, the global rate of sensitization to pneumallergens is 40%. A statistically significant relationship was found between the early onset of menarche and mugwort sensitization; the length of the cycle and sensitization to Dermatophagoides farinae.

Breastfeeding: Maternally Transferred Allergens in Breast Milk: Protective or Sensitizing?

According to a thorough literature search, the following allergen sources have been associated with allergy symptoms in the exclusively breastfed child: hen's egg, cow's milk, peanut, trout. Subsequently, several studies use the advantage of molecular allergology and investigate the potential transfer of single allergens into breastmilk. This is shown for caseins, whey proteins, gliadin, ovalbumin, ovomucoid, the peanut allergens Ara h 2 and Ara h 6, as well as the inhalant allergens Der p 1 and Blo t 5. It is still a matter of debate whether or not food allergens transferred via breastfeeding to the baby promote allergic sensitization or induce tolerance and via which mechanisms they may shift the immune response to the one or other side. Noteworthy, some breastfed children are described to be sensitized to foods before being exposed to solid foods, and this exposure may have occurred through breastmilk. In the light of these findings the investigation of food allergens transferred from the mother's diet into breastmilk and their impact on sensitization or allergy prevention remains a current topic in research. This review describes breastmilk in its composition and provides data on the identification of food allergens therein including human and mouse studies.

Art v 1 IgE epitopes of patients and humanized mice are conformational

Worldwide, pollen of the weed mugwort (Artemisiavulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and thecorresponding HLA have been made. We sought to characterize IgE epitopes of Art v 1-sensitized patients and humanized mice for molecular immunotherapy of mugwort allergy. Four overlapping peptides incorporating surface-exposed amino acids representing the full-length Art v 1 sequence were synthesized and used to search for IgE reactivity to sequential epitopes. For indirect mapping, peptide-specific rabbit antibodies were raised to block IgE against surface-exposed epitopes on folded Art v 1. IgE reactivity and basophil activation studies were performed in clinically defined mugwort-allergic patients. Secondary structure of recombinant (r) Art v 1 and peptides was determined by circular dichroism spectroscopy. Mugwort-allergic patients and humanized mice sensitized by allergen inhalation showed IgE reactivity and/or basophil activation mainly to folded, complete Art v 1 but not to unfolded, sequential peptide epitopes. Blocking of allergic patients' IgE with peptide-specific rabbit antisera identified a hitherto unknown major conformational IgE binding site in the C-terminal Art v 1 domain. Identification of the new major conformational IgE binding site on Art v 1, which can be blocked with IgG raised against non-IgE reactive Art v 1 peptides, is an important basis for the development of a hypoallergenic peptide vaccine for mugwort allergy.

Analysis of inhalation allergen of patients with allergic rhinitis in Shenzhen

Objective:To analyzed allergens and screen for common airborne allergens in patients with allergic rhinitis （AR） in Shenzhen, and identified the distribution pattern of allergens in this region. We aimed to provide scientific and feasible statistical and clinical basis for prevention and treatment of allergenic rhinitis. Methods:For 3351 suspected cases of allergenic rhinitis, 18 kinds of airborne allergen serum-specific IgE were determined using a detection system of BioSciTec GmbH company, and statistical analysis was carried out according to sex, age, severity and seasonal allergen. Results:A total of 3,351 cases with allergic rhinitis were positive for airborne allergens. The top five inhalation allergens were Blomia tropicalis （2231, 66.6%）, Dermatophagoides pterronyssinus （2212, 66.0%）, Dermatophagoides farinae （1986, 59.3%）, Cockroach （967, 28.9%）, and Short ragweed （844, 25.2%）. For the severity of the allergen, Dermatophagoides pterronyssinus ≥ level 3 accounted for 41.3% （1385/3351 cases） and Dermatophagoides farinae ≥level 3 accounted for 40.6% （1360/3351 cases）. Blomia tropicalis were classified as level 2, and other allergens were mainly classified as level 1 or 2. The detection rate among different age groups and gender is significantly different. Conclusion:The main airborne allergens in Shenzhen were Blomia tropicalis, Dermatophagoides pterronyssinus, Dermatophagoides farinae, Cockroach, as well as Short ragweed. The distribution of allergens was affected by sex, age and season.

Association of allergic rhinitis with hypothyroidism, asthma, and chronic sinusitis: clinical and radiological features.

BackgroundAllergic rhinitis (AR) is characterized by mucosal inflammation that leads to a variety of symptoms, such as nasal congestion, rhinorrhea, and sneezing. This rhinitis is triggered by inhalation of allergens, such as pollen, and this condition has a negative impact on the quality of life. AR was shown to be associated with a number of co‐morbidities, including hypothyroidism, asthma, and chronic sinusitis.ObjectiveThis study aimed to assess AR‐associated comorbidities in patients presenting symptoms and paranasal sinus computed tomography (CT) scan findings in Taif City, Saudi Arabia.MethodsThis cross‐sectional study evaluated medical and radiological records of AR patients retrospectively from the period of December 2018 to September 2019 in Al‐Hada Armed Forces Military Hospital, Taif City, Saudi Arabia.ResultsA total of 103 AR patients with a mean age of 39.0 ± 15.6 years with 55.3% males and 44.7% females. The three most common associated comorbidities in allergic rhinitis patients were chronic sinusitis (28.2%), hypothyroidism (21.4%), and asthma (8.7%). Nasal obstruction (30.1%) was the symptom most frequently presented by all patients. Mucosal thickening occurred most frequently in patients with associated chronic sinusitis, while bilateral osteomeatal complex obliteration was observed mostly in asthmatic patients, and bony boundary thinning was more prevalent among patients with associated hypothyroidism.ConclusionThe gender distribution of AR was 10% more common among males; however, the most common three comorbidites in allergic rhinitis patients were chronic sinusitis, hypothyroidism, and asthma, and most of those patients were females. Hypothyroidism can be a hidden predisposing factor for AR, while chronic sinusitis can be caused by AR due to secretion stasis or immune system activation.

Identification of an immunodominant IgE epitope of Der p 39, a novel allergen of Dermatophagoides pteronyssinus

BackgroundHouse dust mites (HDMs) are the main source of indoor inhalatory allergens that cause IgE-mediated allergic diseases. The discovery and identification of HDM allergens are important for the diagnosis and treatment of allergic diseases. ObjectiveWe sought to identify a Group 39 Dermatophagoides pteronyssinus (Der p) allergen, namely Der p 39, and explore its immunodominant IgE epitopes. MethodsHomology analysis of amino acid (aa) sequences in HDM and human troponin C (TnC)-like protein was performed. Total RNA of Der p was extracted and used to amplify Der p 39 cDNA with specific primers. Recombinant Der p 39 protein was expressed with a pET-His prokaryotic expression system and purified with Ni-NTA resins. IgE binding was evaluated with western blot, dot blot, and enzyme-linked immunosorbent assay (ELISA) experiments. The IgE binding epitopes of Der p 39 were identified by observing HDM-allergic sera interactions with truncated and hybrid proteins formed from Der p 39 and human TnC-like proteins. ResultsThe Der p 39 open reading frame (ORF) cDNA was found to be 462 base pairs and registered in the NCBI library (GenBank no. MZ336019.1). Der p 39, which encoded 153 aa, was found to have 35.63% and 99.35% homology with human TnC and Dermatophagoides farina (Der f) 39, respectively. IgE-ELISA showed IgE binding with expressed and purified recombinant Der p 39 (18 kDa) in 5/87 (5.75%) HDM-allergic sera samples. Analyses of IgE binding with Der p 39-based truncated and hybrid proteins indicated that IgE binding epitopes are likely located in the C-terminal region and dependent on conformational structure. The data from this study were submitted to the World Health Organization and International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature database. ConclusionDer p 39 was identified as a minor HDM allergen with a conformational IgE binding epitope. These findings could have important theoretical implications in the development of HDM allergy diagnostics and therapeutics.

Food allergy in early childhood increases the risk of oral allergy syndrome in schoolchildren: A birth cohort study.

The level of pollen in Korea has increased over recent decades. Research suggests that oral allergy syndrome (OAS) may be more frequent in childhood than previously recognized. We aimed to investigate the prevalence and characteristics of OAS in children aged 6-10years from a general-population-based birth cohort. We analyzed 930 children from the cohort for childhood origin of asthma and allergic diseases (COCOA). Allergic diseases were diagnosed annually by pediatric allergists. The skin prick tests were performed with 14 common inhalant allergens and four food allergens for the general population of children aged 3 and 7years. Of the 930 eligible children, 44 (4.7%) aged 6-10years were diagnosed with OAS. The mean age at onset was 6.74years. OAS prevalence was 7.2% among children with allergic rhinitis (AR) and 19.1% among those with pollinosis, depending on comorbidity. OAS was more prevalent in schoolchildren with atopic dermatitis, food allergy, and sensitization to food allergens and grass pollen in early childhood. In schoolchildren with AR, only a history of food allergy until the age of 3years increased the risk of OAS (aOR 2.971, 95% CI: 1.159-7.615). Food allergy and food sensitization in early childhood were associated with OAS in schoolchildren with AR. Further study is required to elucidate the mechanism by which food allergy in early childhood affects the development of OAS.

Impact of Leuconostoc Mesenteroides and Lactobacillus Brevis on Pro-Inflammatory Cytokines in Rat Models with Chronic Asthma

Allergic asthma is a chronic inflammatory disorder characterized by immune system changes. Allergen inhalation, which causes hyperactivity, eosinophil recruitment, mast cells, and lymphocytes in the upper and lower respiratory tracts, triggers the inflammation cascade and results in local and systemic inflammation responses. However, the mechanism of probiotics in allergic diseases, both in vivo and in vitro, is not fully understood. This research was conducted to observe the effect of single or combined probiotics on the immune system of Sprague Dawley rats. This research used a pre-post-test only control group design. The research was conducted on 30 Sprague Dawley rat models with chronic asthma induced with ovalbumin, divided into 5 groups (NC: negative control; PC: positive control; Lm: Leuconostoc mesenteriodes; Lb: Lactobacillus brevis; Lm+Lb: a combination of Leuconostoc mesenteriodes and Lactobacillus brevis). The examinations on eosinophil and neutrophil and IL 17, IL 10, and IL 4 were conducted using the ELISA method. The data were statistically tested using IBM SPSS 25. The administration of single or combined probiotics increased IL-10 (p &lt; 0.001) yet decreased IL-17 and IL-4 (p &lt; 0.001) in all treatment groups. The results show that using single probiotics, Leuconostoc mesenterium best increased IL-10 and decreased IL-17 and IL-4. The dosage administration of single or combined probiotics had a systemic effect on overcoming allergic asthma. In this research, the administration of single probiotics had a better effect when compared with that of combined probiotics.

Sensitisation to Imbrasia belina (mopane worm) and other local allergens in rural Gwanda district of Zimbabwe

BackgroundThe prevalence of allergic diseases is increasing in Zimbabwe and the data relate to local as well as exotic allergen sources. As entomophagy, the practice of eating insects, is a recognised source of local allergens, we sought to measure the prevalence of and risk factors for sensitisation to Imbrasia belina (mopane worm), a popular edible insect. This was investigated alongside other locally relevant allergens in a rural community in Gwanda district, south of Zimbabwe.MethodsA cross sectional study was conducted among 496 adults and children aged 10 years and above in Gwanda district, a mopane worm harvesting area in Zimbabwe. Data on individual characteristics and mopane worm exposure factors were collected using questionnaires. Sensitivity to allergens was assessed by performing skin prick tests at a local clinic using 10 different commercial allergen extracts (Stallergenes, France) and in-house extracts of mopane worm (Imbrasia belina) and mopane leaves (Colophospermum mopane). Data were analysed using Stata version 13 software.ResultsThe prevalence of sensitisation to at least one allergen was 31.17% (n = 144). The prevalence of atopy was higher in adults (33.33%) than in children (23.53%) (p = 0.059). The commonest inhalant allergen sources were mopane worm (14.29%), Tyrophagus putrescentiae (14.29%), mopane leaves (13.42%), Alternaria alternata (6.49%) and Dermatophagoides pteronyssinus (6.49%). Polysensitisation was demonstrated in the study population and of the 108 participants (75%) who were sensitised to two or more allergens, 66 (61%) were women. Sensitisation to mopane worm and mopane leaves often clustered with Tyrophagus putrescentiae amongst adults. Adjusted logistic regression analyses between mopane worm sensitisation and self-reported exposure variables showed that sensitisation was more likely amongst mopane worm harvesters (OR = 1.92, 95%CI = 0.77–4.79), those who cooked or roasted mopane worms during harvesting (OR = 2.69, 95%CI = 0.78–9.31) and harvesting without personal protective equipment (PPE) (OR = 2.12, 95%CI = 0.83–5.44) compared to non-harvesters.ConclusionAtopic sensitization was common in this mopane worm harvesting community in Gwanda district of Zimbabwe. There was frequent co-sensitisation of mopane worm and mopane leaves with Tyrophagus putrescentiae in children and adults. It is important to determine the clinical relevance of our findings, particularly relating to mopane worm sensitisation.

Dibutyl phthalate exposure alters T‐cell subsets in blood from allergen‐sensitized volunteers

Phthalates are ubiquitous environmental contaminants associated with allergic disease in epidemiological and animal studies. This investigation aims to support these associations by interrogating systemic immune effects in allergen-sensitized volunteers after controlled indoor air exposure to a known concentration of dibutyl phthalate (DBP). The phthalate-allergen immune response (PAIR) study enrolled 16 allergen-sensitized participants to a double-blinded, randomized, crossover exposure to two conditions (DBP or control air for 3hr), each followed immediately by inhaled allergen challenge. Peripheral blood immune cell composition and activation along with inflammatory mediators were measured before and after exposure. DBP exposure prior to the inhaled allergen challenge increased the percentage of CD4+ T helper cells and decreased the percentage of regulatory T cells (3hr and 20hr post-exposure), while only modest overall effects were observed for inflammatory mediators. The cells and mediators affected by the phthalate exposure were generally not overlapping with the endpoints affected by allergen inhalation alone. Thus, in distinction to our previously published effects on lung function, DBP appears to alter endpoints in peripheral blood that are not necessarily enhanced by allergen alone. Further studies are needed to clarify the role of phthalate-induced systemic effects in disease pathogenesis.

Molecular profile of specific IgE to allergenic components in allergic adults using allergen nano-bead array.

An increasing interest in the field of molecular diagnosis of allergy has been developed in recent years and it goes to be as the routine in vitro protocol in allergy diagnosis. friendly allergen nano-bead array (FABER) is a new multiplex assay for the evaluation of specific IgE against 244 allergens including whole extracts and allergenic molecules. The research intended to assess the pattern of IgE sensitization to allergenic components of allergens in allergic adults using FABER 244. Sixty patients with allergic diseases entered this cross-sectional study. Specific IgE to 122 whole allergens extracts and 122 allergenic components were assessed using an allergen nano-bead array (FABER) for all patients. This test includes inhalant and food allergens. Thirty-seven patients were male (61.7%). The mean (SD) age of patients was 30.73(±6.87) years. As the allergen nano-bead array results showed, Lolium perenne (63.3%), Phleum pratense (60%) and Platanus acerifolia (51.7%) were considered as the most common IgE sensitizations to the aeroallergen extracts. Moreover, Lol p 1, Phl p 1.0102 and Cup a 1 were found as the most frequent allergenic components in our allergic patients. Among protein families, CCD-bearing proteins, expansin, cysteine protease and profilin families illustrated the highest allergic sensitization. The results of the present study demonstrated that despite the higher prevalence of sensitization to Salsola kali (47.2%) using extract-based assays in the previous phase of this research, allergenic components of grasses (Lol p 1, Phl p 1.0102), Cup a 1 as well as Sal k1 as the major components of Cupressuss arizonica and Salsola kali showed the higher sensitization, respectively, in adults' allergic patients using FABER test.

Association between allergen component sensitisation and clinical allergic disease in children.

Allergen component sensitisation testing is becoming increasingly important in the diagnosis of peanut allergy. The aim of the present study was to evaluate the relationship between sensitisation and symptoms of allergic disease in children by testing a large panel of inhalants, food allergens, and allergen components. For 287 children visiting our laboratory for allergy testing, symptoms of allergic disease were recorded by standardised validated questionnaires. Specific IgE to 11 whole allergens was assessed by ImmunoCAP, and to 112 allergen components by ISAC ImmunoCAP assay. We used latent class analysis (LCA) to distinguish clinical phenotypes. Inhalant and food allergen sensitisation was common, irrespective of the children's allergic symptom type. Less than 10% of the variance in symptom scores was explained by variations in the number of allergens (components) that the child was sensitised to. In LCA, 135 children (50.2%) had mild allergy, with few symptoms and sensitisation to no or few allergens, 74 children (27.5%) had more symptoms and sensitisation to inhalant allergens (respiratory allergy) and 60 children (22.3%) showed polysensitisation to a median of six allergens and had more severe symptoms of different organ systems. Adding allergen component test results to LCA failed to result in identifiable classes of allergic disease in children. In this group of children with allergic symptoms, referred for allergy testing by their physician, broad screening for allergen component sensitisation did not contribute to distinguishing phenotypes of allergic disease.

Inhalant Mammal-Derived Lipocalin Allergens and the Innate Immunity.

A major part of important mammalian respiratory allergens belongs to the lipocalin family of proteins. By this time, 19 respiratory mammalian lipocalin allergens have been registered in the WHO/IUIS Allergen Nomenclature Database. Originally, lipocalins, small extracellular proteins (molecular mass ca. 20 kDa), were characterized as transport proteins but they are currently known to exert a variety of biological functions. The three-dimensional structure of lipocalins is well-preserved, and lipocalin allergens can exhibit high amino acid identities, in several cases more than 50%. Lipocalins contain an internal ligand-binding site where they can harbor small principally hydrophobic molecules. Another characteristic feature is their capacity to bind to specific cell-surface receptors. In all, the physicochemical properties of lipocalin allergens do not offer any straightforward explanations for their allergenicity. Allergic sensitization begins at epithelial barriers where diverse insults through pattern recognition receptors awaken innate immunity. This front-line response is manifested by epithelial barrier-associated cytokines which together with other components of immunity can initiate the sensitization process. In the following, the crucial factor in allergic sensitization is interleukin (IL)-4 which is needed for stabilizing and promoting the type 2 immune response. The source for IL-4 has been searched widely. Candidates for it may be non-professional antigen-presenting cells, such as basophils or mast cells, as well as CD4+ T cells. The synthesis of IL-4 by CD4+ T cells requires T cell receptor engagement, i.e., the recognition of allergen peptides, which also provides the specificity for sensitization. Lipocalin and innate immunity-associated cell-surface receptors are implicated in facilitating the access of lipocalin allergens into the immune system. However, the significance of this for allergic sensitization is unclear, as the recognition by these receptors has been found to produce conflicting results. As to potential adjuvants associated with mammalian lipocalin allergens, the hydrophobic ligands transported by lipocalins have not been reported to enhance sensitization while it is justified to suppose that lipopolysaccharide plays a role in it. Taken together, type 2 immunity to lipocalin allergens appears to be a harmful immune response resulting from a combination of signals involving both the innate and adaptive immunities.

Urinary Eicosanoid Levels Reflect Allergen and Diesel Exhaust Coexposure and Are Linked to Impaired Lung Function

Eicosanoids are potent regulators of homeostasis and inflammation. Co-exposure to allergen and diesel exhaust (DE) have been shown to lead to eosinophilic inflammation, impaired airflow, and increased airway responsiveness. It is not clear whether eicosanoids mediate the mechanism by which these exposures impair lung function. We conducted a randomized, double-blinded, and four-arm crossover study. Fourteen allergen-sensitized participants were exposed to four conditions: negative control; allergen-alone exposure; DE and allergen coexposure; coexposure with particle-reducing technology applied. Quantitative metabolic profiling of urinary eicosanoids was performed using LC-MS/MS. As expected, allergen inhalation increased eicosanoids. The prostacyclin metabolite 2,3-dinor-6-keto-PGF1α (PGF1α, prostaglandin F1α) increased with coexposure, but particle depletion suppressed this pathway. Individuals with a high genetic risk score demonstrated a greater increase in isoprostane metabolites following coexposure. Causal mediation analyses showed that allergen induced airflow impairment was mediated via leukotriene E4 and tetranor-prostaglandin D metabolite. Overall, DE exposure did not augment the allergen's effect on urinary eicosanoids, except insofar as variant genotypes conferred susceptibility to the addition of DE in terms of isoprostane metabolites. These findings will add to the body of previous controlled human exposure studies and provide greater insight into how complex environmental exposures in urban air may influence individuals with sensitivity to aeroallergens.

Aerosol Biologics for the Treatment of Eosinophilic Asthma

Asthma is a heterogeneous chronic airway disease comprising of distinct phenotypes characterized by different immunopathophysiologic pathways, clinical features, disease severity, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed cellularity, and paucigranulocytic asthma. Eosinophilic asthma is principally a T helper type 2 (Th2)-mediated airway disease. However, several other immune and structural cells secrete the cytokines implicated in the pathogenesis of eosinophilic asthma. Innate type 2 lymphoid cells, mast cells, basophils, and eosinophils secrete Th2 cytokines, such as interleukin-4 (IL-4), IL-13, and IL-5. Additionally, airway epithelial cells produce alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Alarmins are the key initiators of allergic inflammation at the sentinel mucosal surfaces. Innovative biotherapeutic research has led to the discovery of monoclonal antibodies which target and inhibit the immunopathological effects of the cytokines involved in the pathogenesis of eosinophilic asthma. Parenteral biologics targeting the inciting interleukins, include mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5Rα), dupilumab (anti-4Rα), and tezelizumab (anti-TSLP). They have been shown to significantly reduce annualized exacerbation rates, improve asthma control, lung function, and quality of life. Currently, there are no pulmonary delivered aerosol biologics for topical treatment of asthma. CSJ117 is a potent neutralizing antibody Fab fragment against TSLP, formulated as a PulmoSol TM engineered powder, and is delivered to the lungs by a dry powder inhaler. Phase 2 placebo-controlled clinical trial evaluated the efficacy and safety of CSJ117. CSJ117 delivered as an inhaler attenuated the late asthmatic response (LAR), and the early asthmatic response (EAR) after allergen inhalation challenge (AIC) at day 84 of treatment. The maximum decrease in FVE1 from pre-AIC were significantly lower in the CSJ117 group compared to placebo (P = 029), during LAR. CSJ117 also significantly reduced fractional exhaled nitric oxide before AIC at day 83; and significantly reduced the allergen-induced increase in % sputum eosinophil count. Pulmonary delivery of biologics directly to the airway mucosal surface has several advantages over parenteral routes, particularly in treating airway diseases such as asthma. Inhaler delivered biologics, such as CSJ117 are innovative and attractive methods of future precision treatment of asthma, and other respiratory diseases.

Identification of Per a 13 as a novel allergen in American cockroach

BackgroundCockroaches are an important source of indoor allergens. Environmental exposure to cockroach allergens is closely associated with the development of immunoglobulin E (IgE)-mediated allergic diseases. However, the allergenic components in the American cockroaches are not fully studied yet. In order to develop novel diagnostic and therapeutic strategies for cockroach allergy, it is necessary to comprehensively investigate this undescribed allergen in the American cockroach. MethodsThe full-length cDNA of the potential allergen was isolated from the cDNA library of the American cockroach by PCR cloning. Both the recombinant and natural protein molecules were purified and characterized. The allergenicity was further analyzed by enzyme linked immunosorbent assay, immunoblot, and basophil activation test using sera from cockroach allergic patients. ResultsA novel allergen belonging to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was firstly identified in the American cockroach and named as Per a 13. The cDNA of this allergen is 1255 base pairs in length and contains an open reading frame of 999 base pairs, encoding 332 amino acids. The purified Per a 13 was fully characterized and assessed to react with IgEs from 49.3 % of cockroach allergic patients, and patients with allergic rhinitis were more sensitized to it. Moreover, the allergenicity was further confirmed by immunoblot and basophil activation test. ConclusionsWe firstly identified GAPDH (Per a 13) in the American cockroach, which is a novel type of inhalant allergen derived from animal species. These findings could be useful in developing novel diagnostic and therapeutic strategies for cockroach allergy.