Effect of intranasal corticosteroids on allergic airway disease in asthma.
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ABSTRACT:
SUBMITTER: Dixon AE
PROVIDER: S-EPMC5503758 | biostudies-literature | 2017 Jul - Aug
REPOSITORIES: biostudies-literature
Publications
Effect of intranasal corticosteroids on allergic airway disease in asthma.
Dixon Anne E AE Castro Mario M Gerald Lynn B LB Holbrook Janet T JT Henderson Robert J RJ Casale Thomas B TB Irvin Charles G CG Black Kendall K Wise Robert A RA Sugar Elizabeth A EA
The journal of allergy and clinical immunology. In practice 20170407 4
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Project description:RationaleIncreased production of mucus is a prominent feature of asthma. IL-13-driven mucous cell metaplasia is associated with decreased expression of the transcription factor FOXA2 and increased expression of the related transcription factor FOXA3 in animal and cell culture models.ObjectivesEstablish how changes in FOXA2 and FOXA3 expression contribute to mucous metaplasia and determine whether FOXA2 and FOXA3 expression is altered in asthma.MethodsMice expressing a Foxa2 transgene in airway epithelial cells and mice deficient in Foxa3 were analyzed after allergen sensitization and challenge. Expression of FOXA2, FOXA3, MUC5AC, and the highly IL-13-inducible gene CLCA1 was analyzed in airway biopsies from subjects with asthma and control subjects.Measurements and main resultsExpression of a Foxa2 transgene reduced allergen-induced mucous metaplasia by 45% compared with control transgenic mice (P < 0.05) whereas inactivation of Foxa3 had no detectable effects on mucous metaplasia. Expression of FOXA2 was reduced in subjects with asthma and was negatively correlated with MUC5AC and CLCA1 levels in subjects with asthma. In contrast, FOXA3 expression was not significantly correlated with MUC5AC and was positively correlated with CLCA1.ConclusionsIncreasing Foxa2 expression reduced mucous metaplasia in an allergic mouse model. Subjects with asthma had decreased FOXA2 expression, suggesting that therapeutic approaches that increase FOXA2 expression or function could be beneficial for reducing mucus production in asthma. Unlike FOXA2, FOXA3 did not regulate mucous metaplasia.
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Project description:BackgroundTo determine medication adherence to intranasal corticosteroid spray (INCS) among allergic rhinitis (AR) patients with comorbid medical conditions.MethodsA cross-sectional study was conducted. Adults above 18 years old with persistent symptoms of AR and comorbid physician-diagnosed asthma, eczema, diabetes mellitus (DM) and hypertension (HPT) were included. The severity of symptoms was assessed by the total nasal symptom score (TNSS), medication adherence was based on the patients' diaries and barriers to adherence were analyzed by the Brief Medication Questionnaire.Results185 participants were enrolled. The medication adherence was 58.9%. Medication adherence was significantly superior in participants with elevated total serum immunoglobulin E (IgE) (χ2 = 8.371, p < 0.05), house dust mite (HDM) allergy to Dermatophagoides pteronyssinus (DP) type (χ2 = 5.149, p < 0.05) and severe TNSS at the first visit (χ2 = 37.016, p < 0.05). Adherence was twice more likely in DP allergy, 2.7 times more likely in elevated total IgE and 15 times more likely in severe TNSS at the first visit. Among the barriers to adherence was lack of symptoms, taking medication only when necessary, fear of adverse effects, running out of medication, experiencing bothersome effects, ineffective response, forgetfulness and taking too many medications. Only lack of symptoms, taking medication when symptomatic, fear of adverse effects and running out of medication were significant. No significant association was found between asthma/eczema (χ2 = 0.418, p > 0.05), HPT/DM (χ2 = 0.759, p > 0.05) and multi-medicine use (χ2 = 1.027, p > 0.05) with medication adherence.ConclusionsPatients having AR with severe nasal symptoms at first presentation, who are sensitized to DP HDM and who have elevated total serum IgE levels have a higher adherence to INCS use. The use of multiple medicines had no impact on the adherence to INCS. As a lack of symptoms was a barrier towards adherence, the benefits of using INCS according to the prescribed dose and frequency must be emphasized to patients with mild and moderate AR at each medical visit. A good rapport between patients and their health care providers is needed to build trust and overcome the barriers, particularly to allay the fears of adverse effects of INCS. The other barriers, such as running out of supply, can be overcome by posting medications directly to patients by the healthcare providers.
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Project description:Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation.
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Project description:BackgroundBlack and Hispanic children growing up in disadvantaged urban neighborhoods have the highest rates of asthma and related morbidity in the United States.ObjectivesThis study sought to identify specific respiratory phenotypes of health and disease in this population, associations with early life exposures, and molecular patterns of gene expression in nasal epithelial cells that underlie clinical disease.MethodsThe study population consisted of 442 high-risk urban children who had repeated assessments of wheezing, allergen-specific IgE, and lung function through 10 years of age. Phenotypes were identified by developing temporal trajectories for these data, and then compared to early life exposures and patterns of nasal epithelial gene expression at 11 years of age.ResultsOf the 6 identified respiratory phenotypes, a high wheeze, high atopy, low lung function group had the greatest respiratory morbidity. In early life, this group had low exposure to common allergens and high exposure to ergosterol in house dust. While all high-atopy groups were associated with increased expression of a type-2 inflammation gene module in nasal epithelial samples, an epithelium IL-13 response module tracked closely with impaired lung function, and a MUC5AC hypersecretion module was uniquely upregulated in the high wheeze, high atopy, low lung function group. In contrast, a medium wheeze, low atopy group showed altered expression of modules of epithelial integrity, epithelial injury, and antioxidant pathways.ConclusionsIn the first decade of life, high-risk urban children develop distinct phenotypes of respiratory health versus disease that link early life environmental exposures to childhood allergic sensitization and asthma. Moreover, unique patterns of airway gene expression demonstrate how specific molecular pathways underlie distinct respiratory phenotypes, including allergic and nonallergic asthma.
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Project description:IntroductionIntranasal antihistamines and corticosteroids are some of the most frequently used drug classes in the treatment of allergic rhinitis. However, there is uncertainty as to whether effectiveness differences may exist among different intranasal specific medications. This systematic review aims to analyse and synthesise all evidence from randomised controlled trials (RCTs) on the effectiveness of intranasal antihistamines and corticosteroids in rhinitis nasal and ocular symptoms and in rhinoconjunctivitis-related quality-of-life.Methods and analysisWe will search four electronic bibliographic databases and three clinical trials databases for RCTs (1) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis and (2) comparing the use of intranasal antihistamines or corticosteroids versus placebo. Assessed outcomes will include the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS) and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. Certainty in the body of evidence for the analysed outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will perform a random-effects meta-analysis for each assessed medication and outcome, presenting results as pooled mean differences and standardised mean differences. Heterogeneity will be explored by sensitivity and subgroup analyses, considering (1) the risk of bias, (2) the follow-up period and (3) the drug dose.Ethics and disseminationEthical considerations will not be required. Results will be disseminated in a peer-review journal.Prospero registration numberCRD42023416573.
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Project description:BackgroundExposure to ozone (O3) is associated with increased risk of exacerbations of asthma, but the underlying mechanisms are not well studied.ObjectiveWe sought to determine whether O3 exposure would enhance airway inflammatory responses to allergen and the GSTM1-null genotype would modulate this enhancement.MethodsIn a crossover design, 10 asthmatic participants (5 with GSTM1-null genotype) who had specific sensitization to Dermatophagoides pteronyssinus (DP) were exposed to 160 ppb O3 or filtered air (FA) control for 4 hours on 2 separate days at least 3 weeks apart. At 20 hours after exposure, endobronchial challenge with DP allergen, and sham normal saline (NS) instillation, were performed in separate bronchi. Six hours later, a second bronchoscopy was performed to collect bronchoalveolar lavage (BAL) from the DP- and NS-challenged segments for analyses of inflammatory biomarkers. Linear regression compared cell and cytokine responses across the 4 exposure groups (FA-NS, O3-NS, FA-DP, O3-DP). Effect modification by GSTM1 genotype was assessed in stratified regressions.ResultsBAL eosinophil counts were increased in segments challenged with DP compared to sham-challenged segments (P < .01). DP challenge compared to sham also caused a significant increase in BAL concentrations of the TH2 cytokines IL-4, IL-5, IL-10, and IL-13 (P < .03 for all comparisons). O3 exposure did not significantly affect BAL cells or cytokine after DP challenge. Compared to GSTM1-present participants, GSTM1-null participants had significantly lower eosinophil (P < .041) and IL-4 (P < .014) responses to DP challenge after O3 exposure.ConclusionsWhile O3 did not cause a clear differential effect on airway inflammatory responses to allergen challenge, those responses did appear to be modulated by the antioxidant enzyme, GSTM1.
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