Prevalence Of Allergic Asthma Research Articles

Role of allergen immunotherapy in the prevention of allergic asthma

The prevalence of allergic asthma is still increasing, which affects the quality of life of patients, threatens their lives, and brings enormous social and economic burden. Allergen immunotherapy (AIT) is the only treatment that can alter the progression of the "Atopic March". It has been widely used in the treatment of allergic rhinitis and conjunctivitis, and its role and effect in the treatment of allergic asthma have been gradually recognized. A few studies have shown that AIT may have a preventive effect on the development and progression of allergic asthma. In this article, the definition of tertiary prevention of allergic asthma is described, and the respective role of AIT in primary, secondary and tertiary prevention of allergic asthma is summarized and analyzed. The aim of this article is to provide evidence for the prevention and control of allergic asthma.

A Proposal to Differentiate ACO, Asthma and COPD in Vietnam.

In low- and middle-income countries, such as Vietnam, the population is exposed to multiple risks, leading to frequent allergic asthma, COPD and their overlap (ACO). We aimed to differentiate asthma and COPD, so that recommended treatments can be applied. We hypothesized that during life, the cumulative exposure to noxious particles increases the relative prevalence of COPD, while due to immuno-senescence, the prevalence of allergic asthma decreases with age. Among 568 patients with chronic respiratory symptoms, five phenotypes were defined, based on responsiveness to a bronchodilator (BD), diffusion capacity and cumulative smoking. Then the relative prevalence of each phenotype was related with age. the smoker BD irreversible patients were considered "COPD", while the full BD responders and non-smoking BD incomplete responders were "asthmatics". The other patients were ACO, distributed as "like-COPD" or "like-asthma", based on decreased or normal diffusion capacity. The relative prevalence of asthma, COPD and ACO were 26, 42 and 32% (18% "like-asthma", 14% "like-COPD"). Vietnamese patients with chronic respiratory symptoms were considered as falling into asthma or COPD groups, based on cumulative smoking, spirometry with reversibility and diffusion capacity. The relative prevalence of asthma and COPD were 44 and 56%, respectively, most of which did not require corticosteroids.

Ambient ozone, and urban PM2.5 co-exposure, aggravate allergic asthma via transient receptor potential vanilloid 1-mediated neurogenic inflammation

Allergic asthma is the most common pulmonary inflammatory disease, and epidemiological studies have revealed that PM2.5 or ambient ozone (O3) exposure contribute to the higher prevalence of allergic asthma. Current experimental evidence focus principally on the pathogenic effect of exposure to a single air pollutant, ignoring the possible synergistic effect of combined exposure to a mix of these pollutants, which is a more realistic scenario. In this study, allergic mice and a nociceptor antagonist were used to explore the mechanisms of co-exposure to these two important air pollutants. Compared with exposure to either PM2.5 or O3, combined exposure to both greatly aggravated allergic asthma in a dose dependent manner, including increased airway hyperresponsiveness, goblet cell metaplasia, more severe airway inflammation and higher oxidative stress levels. In addition, co-exposure in the allergic mice resulted in elevation of the expression of transient receptor potential vanilloid 1 (TRPV1), and of the production of substance P (SP), which exacerbated lung inflammation by neurogenic inflammation. TRPV1 antagonist (capsazepine, CPZ) treatment for the co-exposed allergic mice, markedly attenuated TRPV1 expression and SP release, and reduced airway inflammation and oxidative damage, further alleviating airway hyperresponsiveness. We conclude that neuro-immune interactions might be involved in PM2.5 and O3 co-exposure aggravated allergic asthma.

Determination of immunogenic epitopes in major house dust mite allergen, Der p 2, via nanoallergens

BackgroundDespite the high prevalence of allergic asthma, currently, avoidance of the responsible allergens, which is nearly impossible for allergens such as house dust mite (HDM), remains among the most effective treatment. Consequently, determination of the immunogenic epitopes of allergens will aid in developing a better understanding of the condition for diagnostic and therapeutic purposes. Current methods of epitope identification, however, only evaluate immunoglobulin E-epitope binding interactions, which is not directly related to epitope immunogenicity. ObjectiveTo determine and rank the immunogenicity of the epitopes of major HDM allergen, Der p 2. MethodsWe performed degranulation assays with RBL-SX38 cells primed using patient plasma and challenged with nanoallergens which multivalently displayed epitopes to study the relative immunogenicity of various epitopes of Der p 2. Nanoallergens were used to evaluate epitopes individually or in combination. ResultsWhen evaluated using 3 patient samples, 3 epitopes in 2 distal regions of Der p 2 were identified as highly immunogenic when presented in combination, whereas no individual epitope triggered relevant degranulation. One of the epitopes (69-DPNACHYMKCPLVKGQQY-86) was identified to be cooperatively immunogenic when combined with other epitopes. ConclusionOur study highlights the importance of conformational epitopes in HDM-related allergies. This study also provides further evidence of the versatility of nanoallergens and their value for functional characterization of allergy epitopes, by ranking the Der p 2 epitopes according to immunogenicity. We believe that nanoallergens, by aiding in identification and understanding of immunogenic epitopes, will provide a better understanding of the manifestation of the allergic condition and potentially aid in developing new treatments.

Plasma levels of oxysterols 7-ketocholesterol and cholestane-3β, 5α, 6β-triol in patients with allergic asthma

Objective: The prevalence of allergic asthma is increasing on a global scale, reflecting changes in air pollution, climatic changes, and other environmental stimulants. In allergic conditions, oxidative stress occurs as a result of immune system activation. Oxidation of cholesterol leads to the formation of oxysterols. The main purpose of the study was to compare plasma levels of two oxysterols, namely 7-ketocholesterol (7-KC) and cholestane-3β, 5α, 6β-triol (C-triol), and a lipid peroxidation product, malondialdehyde (MDA) in allergic asthma patients with those of healthy controls, in order to provide information about the involvement of lipid peroxidation in allergic asthma. Methods: Oxysterols were quantified by LC-MS/MS in plasma samples of 120 asthma patients (90 females + 30 males) and 120 healthy controls (matched by age and sex). Plasma MDA level was analyzed by a spectrophotometric method. Results: Plasma 7-KC (39.45 ± 20.37 ng/mL) and C-triol (25.61 ± 10.13 ng/mL) levels in patients were significantly higher than in healthy subjects (17.84 ± 4.26 ng/mL and 10.00 ± 3.90 ng/mL, respectively) (P < 0.001). Plasma MDA levels were also higher in asthmatic patients (4.98 ± 1.77 nmol/mL) than in healthy controls (1.14 ± 0.31 nmol/mL) (P < 0.001). All data support that lipid peroxidation products are involved in allergic asthma. Conclusion: Oxysterols were quantified for the first time in allergic asthma. Since the high plasma 7-KC and C-triol levels of allergic asthma patients correlate with high IgE levels, detection of these oxysterols by LC-MS/MS may be helpful in the clinical monitoring of allergic asthma. Current data may also lead to new approaches for the prevention, diagnosis, and treatment of the disease. Supplemental data for this article is available online at at.

Protective Effects of Korean Herbal Remedy against Airway Inflammation in an Allergic Asthma by Suppressing Eosinophil Recruitment and Infiltration in Lung.

The increasing prevalence of allergic asthma has become the world’s major health issue. Current treatments for allergic asthma focus on treating symptoms, while permanent cures still remain undiscovered. In this study, we investigated the effect of Korean traditional herbal remedy, Pyunkang-tang (PGT)—composed of six plants—on asthma alleviation in a mouse model. The PGT mixture was orally gavaged to mice (PM group, 20 mg/mouse/day) from 7 days before sensitization with ovalbumin (OVA) (day −7). On day 0 and day 14, mice from OVA-control (n = 9) and PM group (n = 8) were sensitized with OVA and alum through intraperitoneal injection. On days 18~20, OVA was challenged to mice through nasal injection and sacrificed next day. Cell profile in lung tissue was analyzed by flow cytometry and RT-qPCR analysis, and the number of eosinophils and expression of siglec-F were significantly reduced in the PM group. Lung tissue was examined with hematoxylin and eosin (H&E) and Alcian blue/periodic acid–Schiff (AB-PAS) staining. Noticeably reduced eosinophil infiltration around bronchioles was displayed in the PM group compared to the OVA-control group. Furthermore, PGT-treated mice showed a significant reduction in IL-13 and a mild reduction in IL-5 in lungs. A decreasing tendency of IL-5/13 (+) CD4+ T cells and IL-13(+) innate lymphoid cells (ILCs) and a significant reduction in IL5(+) ILCs were also observed. When treating PGT on murine lung epithelial cells stimulated by papain, there was a significant reduction in IL-33 mRNA expression levels. Taken together, oral delivery of PGT successfully alleviated asthmatic responses provoked by OVA in a mouse model and could lead to novel therapies for allergic asthma.

Prevalence of Allergic and Non-allergic Asthma in Kumaun Region of Uttarakhand, India: A Cross-sectional Study

Introduction: Asthma is a heterogenic disease, commonly divided into allergic and nonallergic asthma. It affects people of all age group and is associated with impaired lung function. Previously, it was thought that asthma is a disease of developed countries but at present, world scenario has changed and its prevalence in developing countries is rapidly increasing. Asthma shows large geographical variations in terms of prevalence, severity and mortality. Aim: To establish the prevalence of allergic and nonallergic asthma in adults of Kumaun region of Uttarakhand (India) and to evaluate whether the peripheral blood cell count is associated with the severity of lung impairment in both the subtypes (allergic and nonallergic) of asthma. Materials and Methods: This cross-sectional study was carried out jointly in Department of Physiology and Department of Respiratory Medicine, Government Medical College, Haldwani, Uttarakhand (India), during the period from October 2015 to January 2017. A total of 125 patients of both sexes age above 18 years, who attended the OPD of Respiratory Medicine and diagnosed asthma by the physician were enrolled in the study. The patients associated with tuberculosis, worm infestations, other allergic diseases and systemic diseases were excluded. History of Allergic Rhino-Conjunctivitis (ARC) was used for allergic sensitisation and to define allergic asthma. Classification of severity of airflow limitation was done according to Global Initiative for Asthma (GINA) guidelines. Absolute Leukocyte Counts was determined by using the formula: Absolute leukocyte count=Differential leukocyte count/100×Total leukocyte count. One-way ANOVA followed by Tukey HSD post-hoc analysis and Chi-square was done. Level of statistical significance was set at p-value &lt;0.05. Results: The prevalence of allergic asthma was more in 79 patients (63.2%), in comparison to nonallergic asthma in 46 (36.8%) and it (allergic asthma) was more common in males than females (54:25). Mean age of allergic and nonallergic group asthma patients were 51.00±14.31 and 56.11±13.14 years, respectively. In allergic asthma patients, blood eosinophil count increased significantly (p=0.001) the severity of lung impairment increased and no significant changes were observed in other blood cell counts while in nonallergic asthma over-all neutrophil count was significantly high (p=0.044) with increase in severity. Nonallergic asthma also showed increasing trend of eosinophil count as the severity of airway obstruction increased but there were no significant changes in other counts. Conclusion: The prevalence of allergic asthma is high in comparison to nonallergic asthma among adults of Kumaun region of Uttarakhand, India and it is more prevalent among males in both the groups. Peripheral blood leukocyte count might be used as biological marker to differentiate allergic asthma from nonallergic asthma.

Critical roles of regulatory B and T cells in helminth parasite-induced protection against allergic airway inflammation.

The prevalence of allergic asthma and incidences of helminth infections in humans are inversely correlated. Although experimental studies have established the causal relation between parasite infection and allergic asthma, the mechanism of the parasite-associated immunomodulation is not fully elucidated. Using a murine model of asthma and nematode parasite Heligmosomoides polygyrus, we investigated the roles of regulatory B cells (Breg ) and T cells (Treg ) in mediation of the protection against allergic asthma by parasite. H. polygyrus infection significantly suppressed ovalbumin (OVA)-induced allergic airway inflammation (AAI) evidenced by alleviated lung histopathology and reduced numbers of bronchoalveolar inflammatory cell infiltration, and induced significant responses of interleukin (IL)-10+ Breg , IL-10+ Treg and forkhead box protein 3 (FoxP3)+ Treg in mesenteric lymph node and spleen of the mice. Adoptive transfer of IL-10+ Breg and IL-10+ Treg cell prevented the lung immunopathology in AAI mice. Depletion of FoxP3+ Treg cells in FoxP3-diphtheria toxin (DT) receptor transgenic mice by diphtheria toxin (DT) treatment exacerbated airway inflammation in parasite-free AAI mice and partially abrogated the parasite-induced protection against AAI. IL-10+ Breg cells were able to promote IL-10+ Treg expansion and maintain FoxP3+ Treg cell population. These two types of Tregs failed to induce CD19+ B cells to transform into IL-10+ Breg cells. These results demonstrate that Breg , IL-10+ Treg and FoxP3+ Treg cells contribute in A discrepant manner to the protection against allergic airway immunopathology by parasiteS. Breg cell might be a key upstream regulatory cell that induces IL-10+ Treg response and supports FoxP3+ Treg cell population which, in turn, mediate the parasite-imposed immunosuppression of allergic airway inflammation. These results provide insight into the immunological relationship between parasite infection and allergic asthma.

Decision-making for pediatric allergy immunotherapy for aeroallergens: a narrative review.

There has been exciting progress in diagnosis and in the treatment of allergic patients. The objective of this review is to summarize the most relevant contributions in the past 10years with a special focus on the pediatric population allergic to aeroallergens and provide the most relevant references and practical issues for the decision-making. Current guidelines on allergy diagnosis recommend a thorough clinical history as the first step, followed by allergen extract testing using an in vivo prick test and/or an in vitro specific IgE test. Molecular diagnosis is recommended when previous tests are inconclusive. In practice, the most important factors to decide the AIT treatment are the actual intensity and duration of the patient's symptoms and the availability of appropriate AIT products for the patient's sensitization profile at high allergen concentrations and with confirmed efficacy and safety from clinical trials. This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. The experts concluded that AIT is efficacious and safe for the treatment of allergic patients that is available for the most frequent aeroallergens.What is Known:• The prevalence of allergic asthma and rhinitis in children has increased in recent decades.• The efficacy and safety of allergen immunotherapy has been shown in multiple studies and systematic reviews.What is New:• This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. Recommendations of expert authors for the decision of the patients more suitable for allergen immunotherapy are included.

ASTHMA CONTROL AMONG INDIVIDUALS WITH AND WITHOUT COMORBID ALLERGIES

Introduction The prevalence of allergic asthma (AA) among patients with asthma is significant. We evaluated the differences in asthma control in patients with asthma with and without comorbid allergies in a managed care population. Methods A retrospective analysis of patient survey responses and pharmacy claims from the Observational Study of Asthma Control and Outcomes was performed. Patients aged ≥12 years with persistent asthma received 4 identical surveys over 15 months. Allergies were identified by a positive response to a survey question about hay fever/seasonal allergies and ≥1 diagnostic code (ICD-9) for atopic conditions. Asthma control was measured using the 5-, 6-, and 7-item Asthma Control Questionnaire (ACQ; item 7 adds provider-performed lung function testing). ACQ scores ≤0.75 indicate well-controlled asthma, and scores ≥1.5 indicate poorly controlled asthma. An adjusted random-effects generalized least squares regression was used for ACQ scores, and adjusted random-effects logistic regression was used for the analysis of ACQ scores ≤0.75 or ≥1.5. Results In total, 2,681 patients with asthma were included in the study, of whom 971 had AA. Compared with asthmatic patients without comorbid allergies, patients with AA had: ACQ-5 and -6 scores that were higher/worse (0.339 and 0.305 points higher, respectively); lower odds (0.213 and 0.214, respectively) of having well-controlled asthma; and higher odds (3.374 and 3.458, respectively) of having poorly controlled asthma (Table). Conclusions Patients with AA had higher odds of having poorly controlled asthma compared with asthmatic individuals without allergies. Patients with AA may need more vigilant clinical monitoring to ensure adequate asthma control. Comparison of ACQ score, and whether asthma is well-controlled or poorly controlled, in patients with AA vs those with asthma and no comorbid allergies.

MEDICATION USE PATTERNS IN ASTHMATIC PATIENTS WITH AND WITHOUT ALLERGIES

Introduction The prevalence of allergic asthma (AA) among patients with asthma is significant. We examined medication use patterns among individuals with asthma with and without comorbid allergies to explore potential differences. Methods Retrospective analysis of survey and pharmacy claims from the Observational Study of Asthma Control and Outcomes. Eligible patients with persistent asthma aged ≥12 years were sent four surveys over 15 months. Allergies were identified by a positive response to survey question about hay fever/seasonal allergies and at least one diagnostic code (ICD-9) for atopic conditions. Outcomes included the number of asthma prescriptions dispensed (NPD) and any use (yes/no). Random-effects (RE) negative binomial regression was used for NPD and RE logistic regression was used for dichotomous outcomes, adjusting for age, gender, race, ethnicity, income, education, smoking status and season. Results There were 2,681 individuals with asthma of whom 971 also had allergies. Patients with asthma and comorbid allergies received significantly more prescriptions than patients without comorbid allergies for the following asthma medications (TABLE 1: incidence rate ratio [IRR]): controller (1.22), ICS (1.16), high-dose ICS (2.50), OCS (2.31) and SABA (1.18). Patients with comorbid allergies had significantly greater odds of chronic (OR 16.15) and short-term OCS (OR 2.34) use. Conclusions Patients with asthma and allergic comorbidity have significantly greater asthma-related medication burden than patients with asthma but no allergies. The greater medication use among patients with allergic comorbidity is consistent with more severe asthma. Patients with asthma and allergies may need more vigilant clinical oversight to ensure adequate control. Medication Use for Asthmatic Patients with Allergies Compared to those Without Allergies

MiR-146a Mimics Attenuate Allergic Airway Inflammation by Impacted Group 2 Innate Lymphoid Cells in an Ovalbumin-Induced Asthma Mouse Model

Background: The prevalence of allergic asthma has increased dramatically. Previous studies have found that the microRNA 146a (miR-146a) expression in asthma inhibits cell proliferation and promotes apoptosis of bronchial smooth muscle cells. We aimed to investigate the effect of miR-146a mimics on ovalbumin (OVA)-induced asthma in a mouse model. Methods: Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) was measured by flow cytometry. Levels of OVA-specific immunoglobulin E (IgE) in serum and cytokines in BALF were examined by enzyme-linked immunosorbent assay. For monitoring the airway, the Penh value (% baseline) was measured using a whole-body plethysmograph. Results: In OVA-induced asthmatic mice, miR-146a significantly suppressed the infiltration of inflammatory cells in BALF and decreased the levels of OVA-specific IgE and T helper 2 cell type cytokines. In addition, miR-146a inhibited the OVA-induced airway hyperresponsiveness and the group 2 innate lymphoid cell responses. Moreover, the effects of miR-146a mimics were dependent on interleukin 33 stimulation. Conclusions: Our results suggest that miR-146a mimics might serve as an attractive candidate for further preclinical studies as an anti-inflammatory treatment of asthma.

Patient characteristics in German allergological practices - a nationwide survey.

Introduction: In Western societies a significant incidence and prevalence of allergic asthma and other allergic diseases is observable. The present study investigated epidemiological patterns of allergic diseases and the utilization of health care resources by subjects who are already under specialized allergological treatment. Furthermore the study was performed to identify factors which had a significant impact on accessibility to specific immunotherapy (SIT). Methods: The study was based on a cross-sectional survey on patient characteristics, which was performed by participating physicians, who were specialized in the field of allergological disorders and SIT, in collaboration with their patients. The analysis of data was divided into descriptive analyses and an analytical part, in which influencing factors for accessibility to specific immunotherapy were investigated. Logistic regression models to identify several predictor variables were used. Results: 495 physicians documented the data of 19,990 patients. 18,177 patients were included in the analyses. Patients had a mean age of 31.5 ± 15.5 years and 53.2% were female. The most frequent and most severe allergic disorders observable in German allergological practices were conjunctivitis and rhinitis. The seasonal symptoms occurred mainly during March to August, while seasonal disease manifestation was 2.5 times more frequent than perennial forms. The most received anti-symptomatic medications are antihistamines and corticosteroids. Patients who receive SIT were mainly treated using subcutaneous immunotherapy (SCIT) – only in lower age groups, the likelihood of receiving sublingual immunotherapy (SLIT) was increased. Conclusion: In Germany, conjunctivitis and rhinitis are the most severe allergic disorders in allergological practices. Compared to the German general patient population, people who were already in allergological treatment had better access to SIT.

Immunomodulation by vitaminD.

Vitamin D exerts several immunological functions in addition to its homeostatic functions on calcium and bone metabolism. Current data show that relative vitamin D deficiency (< 75 nmol/l 25-hydroxyvitamin D) as well as acquired seasonal vitamin D deficiency (< 50 nmol/l) are frequent in Germany. As confirmed by our own data, UV exposure plays a major role for maintenance of vitamin D status, e.g., in patients with UV-triggered diseases, vitamin D deficiency is more frequent, even throughout the year. The beneficial impact of vitamin D on immune functions is highlighted by epidemiologic, genetic, and experimental evidence. In the past years, numerous publications have presented associations between vitamin D deficiency, on the one hand, and severity and prevalence of allergic asthma in children and adults, on the other hand.

Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016-results from three population surveys.

During the latter half of the 20th century, the prevalence of asthma and many other allergic diseases has increased. Information on asthma prevalence trends among adults after 2010, especially regarding studies separating allergic asthma from non-allergic asthma, is lacking. The aim was to estimate prevalence trends of current asthma among adults, both allergic and non-allergic, from 1996 to 2016. Three cross-sectional samples from the same area of Sweden, 20-69years, participated in surveys with the same questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%), respectively. Allergic rhino-conjunctivitis (ARC) was used as a marker for allergic sensitization to define allergic asthma. The prevalence of current asthma increased from 8.4% (95% CI: 7.8-9.0) in 1996 to 9.9% (95% CI: 9.2-10.6) in 2006 and 10.9% (95% CI: 10.1-11.7) in 2016 (P<.001). Allergic asthma increased from 5.0% (95% CI: 4.5-5.5) in 1996 to 6.0% (95% CI: 5.4-6.6) in 2006 and further to 7.3% (95% CI: 6.6-8.0) in 2016 (P<.001), while the prevalence of non-allergic asthma remained stable around 3.4%-3.8%. The increase in current asthma was most pronounced among women and among the middle-aged. Physician-diagnosed asthma, asthma medication use and ARC also increased significantly, while the prevalence of symptoms common in asthma such as wheeze and attacks of shortness of breath decreased slightly or was stable. The prevalence of current smoking decreased from 27.4% in 1996 to 12.3% in 2016. The prevalence of allergic asthma increased from 1996 to 2006 and further to 2016, while the prevalence of non-allergic asthma remained on a stable prevalence level. The prevalence of symptoms common in asthma decreased slightly or was stable despite a substantial decrease in the prevalence of current smoking. Clinicians should be aware that the previously observed increase in prevalence of allergic asthma is still ongoing.

Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia.

Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor γ-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor γ levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-κB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1α-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.

Age-Dependent Allergic Asthma Development and Cystathionine Gamma-Lyase Deficiency.

The pathogenic mechanisms for the higher prevalence of allergic asthma in children than in adults have not been settled. The aim of the present study is to examine whether the age-dependent development of allergic asthma is caused by age-dependent expression of cystathionine gamma-lyase (CSE), a key enzyme that catalyzes the production of hydrogen sulfide (H2S). Allergic asthma was induced with ovalbumin in wild-type (WT) and CSE knock-out (KO) mice at young and old ages. CSE expression and H2S production were lower in immune cells of young WT mice than in those of old WT mice. Coincidentally, more severe asthmatic symptoms with a greater type-2 immunoreaction were found in young WT mice than old WT mice. H2S supplementation reversed the asthmatic symptoms. Lower expression levels of CSE proteins were also found in human umbilical cord blood mononuclear cells in comparison with that of peripheral blood mononuclear cells from adult people. The age-dependent asthma propensity vanished in CSE-KO mice, but these mice developed more severe asthma than WT mice. More splenocytes were differentiated to type-2 cytokine-generating cells in young WT mice and in CSE-KO mice at all ages. This differentiation was inhibited by H2S donors. GATA3 translocation to the nucleus and type-2 immunoreaction of splenocytes were inhibited after GATA3 was S-sulfhydrated by H2S. Innovation and Conclusion: For the first time, this study demonstrated that lower abundance of CSE expression and H2S production enhances type-2 immunoreaction and renders a higher incidence of allergic asthma at a young age. As such, H2S level may be a biomarker for asthma development and a H2S-based strategy can be perceived for asthma prevention and treatment. Antioxid. Redox Signal. 27, 931-944.

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite–induced asthma in murine offspring

Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. We sought to determine whether maternal HDM exposure influences asthma development in offspring. Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, TH2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, TH2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma.

FUZZY SPATIAL ASSOCIATION RULE MINING TO ANALYZE THE EFFECT OF ENVIRONMENTAL VARIABLES ON THE RISK OF ALLERGIC ASTHMA PREVALENCE

The prevalence of allergic diseases has greatly increased in recent decades, likely due to contamination of the environment with allergy irritants. One common treatment is identifying that allergy irritant, and then avoiding exposure to it. This article studies the relation between the prevalence of allergic asthma and certain allergy irritants that are related to environmental variables. To that end, we use spatial association rule mining to determine the association between the spatial distribution of allergic asthma prevalence and air pollutants such as CO, SO2, NO2, PM10, PM2.5, and O3 (from data compiled by air pollution monitoring stations), as well as other factors, such as the distance of residence from parks and roads. In order to clear up the uncertainties inherent in the attributes linked to the spatial data, the dimensions in question have been defined as fuzzy sets. Results for the case study (i.e. Tehran metropolitan area) indicate that distance to parks and roads, as well as CO, NO2, PM10, and PM2.5 levels are related to allergic asthma prevalence, while SO2 and O3 are not. Finally, we use the extracted association rules in fuzzy inference system to produce the spatial risk map of allergic asthma prevalence, which shows how much is the risk of allergic asthma prevalence at each point of the city.

Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility

Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood. We sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children. The effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes. DEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children. These findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.