Prevention Of Asthma Research Articles

Preventing progression of preschool wheezing to asthma: Opportunities for intervention.

Recurrent wheezing in preschool children is heterogeneous and results from numerous genetic and environmental risk factors, which result in the same final clinical manifestation of acute episodes of wheezing but have distinct underlying mechanisms. Effective disease-modifying approaches, therefore, need to target the pathways driving the symptoms. We have good evidence to show that targeting airway eosinophilia alone in early-life preschool wheezing and using inhaled corticosteroids is not disease-modifying. Although airway remodelling develops early in preschool wheezing, the challenge is identifying suitable treatments for structural airway changes. There is increasing evidence for the role of lower airway bacterial infection contributing to wheeze episodes, but clinical trials investigating the impact of targeted antibiotic treatment on disease modification are needed. There is also increasing data supporting an association between lower airway neutrophilia and wheezing in a subgroup of preschool children, but direct causation and the role of neutrophil function remain unknown. Finally, there is encouraging preliminary data for the role of inactivated mixed bacterial lysates in children with non-allergic, infection-associated wheeze episodes, but the impact on longer-term outcomes and their mechanism of action is unknown. This review outlines a range of potential novel targets and approaches that may enable secondary prevention of asthma from preschool wheezing. In parallel, the potential for harm when interventions are introduced indiscriminately is highlighted. Some of the challenges that need to be addressed, including trial designs allowing tailored interventions, the need for non-invasive biomarkers for targeted interventions, and ensuring extended and long-term follow-up after intervention, are highlighted.

Dietary choline intake and its association with asthma: A study based on the National Health and Nutrition Examination Survey database.

This work endeavored to examine the correlation between dietary choline intake and the odds of asthma, utilizing data from the National Health and Nutrition Examination Survey (NHANES). Aggregated data from seven cycles (2005-2018) in the NHANES database were utilized. The independent variable was dietary choline intake, and the dependent variable was asthma. The weighted logistic regression method was used to construct a model reflecting the relationship between these two factors. This work employed stratified analysis without adjusting for confounding factors and subgroup analysis with adjusted confounding factors to mine the association between dietary choline intake and asthma. Additionally, restricted cubic spline analysis examined nonlinear associations of the two in age subgroups. Forty five thousand and seven hundreds ninety seven samples were included here. The model indicating the relationship between dietary choline intake and asthma was constructed (OR: 0.86, 95% CI: 0.79-0.93, p<0.001). Stratified analysis indicated that the interaction terms of age (p<0.001) and body mass index (BMI) (p=0.002) with dietary choline intake significantly influenced the relationship model. In the adjusted models, accounting for demographic characteristics, poverty impact ratio, BMI, exposure to environmental tobacco smoke, and total energy intake, an increase in dietary choline intake significantly reduced the odds of asthma (OR: 0.79, 95% CI: 0.72-0.88, p<0.001). Subgroup analyses based on age and BMI revealed a significant negative correlation between dietary choline intake and the odds of asthma in the adult population (OR: 0.76, 95% CI: 0.67-0.86, p<0.001), as well as in individuals with a BMI between 25 and 30kg/m2 (OR: 0.79, 95% CI: 0.63-0.99, p=0.042), and those with a BMI >30kg/m2 (OR: 0.73, 95% CI: 0.60-0.89, p=0.002). Dietary choline intake was significantly inversely correlated with asthma prevalence, especially in adults and overweight/obese individuals, suggesting that increasing choline intake may reduce asthma risk. Further research is needed to explore this relationship and provide tailored dietary recommendations for different age and BMI groups to enhance asthma prevention and management.

Metered-Dose Inhaler Spacer with Integrated Spirometer for Home-Based Asthma Monitoring and Drug Uptake.

This work introduces Spiromni, a single device incorporating three different pressurised metered-dose inhaler (pMDI) accessories: a pMDI spacer, an electronic monitoring device (EMD), and a spirometer. While there are devices made to individually address the issues of technique, adherence and monitoring, respectively, for asthma patients as laid out in the Global Initiative for Asthma's (GINA) global strategy for asthma management and prevention, Spiromni was designed to address all three issues using a single, combination device. Spiromni addresses the key challenge of measuring both inhalation and exhalation profiles, which are different by an order of magnitude. Moreover, the innovative design prevents exhalation from entering the spacer chamber and prevents medication loss during inhalation using umbrella valves without a loss in flow velocity. Apart from recording the peak exhalation flow rate, data from the sensors allow us to extract other key lung volume and capacities measures similar to a medical pulmonary function test. We believe this low-cost portable multi-functional device will benefit both asthma patients and clinicians in the management of the disease.

Clinical, immunological, and molecular genetic features in occupational bronchial asthma, depending on the phenotype

Evaluation of clinical data and features of immunopathogenesis, along with molecular genotyping, open up new possibilities for a personalized approach to the prevention and treatment of occupational bronchial asthma. The aim is to determine clinical, immunological and genetic markers of the risk of developing occupational bronchial asthma under exposure to sensitizing substances based on the results of an assessment of polymorphic variants rs2069812 of the IL5 gene. The study included 170 patients with various phenotypes of occupational bronchial asthma and 50 people in the control group. The levels of MCP-1 cytokines and total IgE in blood serum were determined by solid-phase enzyme immunoassay using standard reagent kits. The serum content of vascular endothelial growth factor (VEGF) was studied by sandwich-type solid-phase enzyme immunoassay. Genotyping was performed by polymerase chain reaction. During the study, the features of clinical and immunological manifestations depending on the phenotype of occupational bronchial asthma were established for the first time, genetic markers of the risk of developing this pathology under the influence of sensitizing substances were identified: polymorphic variants rs2069812 of the IL-5 gene.

Causal relationship between iron deficiency anemia and asthma: a Mendelian randomization study

BackgroundObservational studies have suggested an association between iron deficiency anemia (IDA) and asthma, which may affect the occurrence of asthma. However, whether IDA is a new management goal for asthma remains to be determined.ObjectiveWe conducted a two-sample Mendelian randomization(MR)analysis to assess the association between IDA and asthma.MethodsWe performed a two-sample MR study to assess a causal relationship between IDA (ncase = 12,434, ncontrol = 59,827) and asthma (ncase = 20,629, ncontrol = 135,449). Inverse variance weighted (IVW) was used as the primary method for the analyses. Furthermore, we used weighted medians and MR-Egger to enhance robustness. Data linking genetic variation to IDA and asthma were combined to assess the impact of IDA on asthma risk.ResultsThere are five single nucleotide polymorphisms (SNPs) were used as genetic tool variables for exposure factors. Genetically determined IDA was significantly associated with an increased risk of asthma (OR = 1.37, 95% CI: 1.09–1.72, p = 0.007). There was little heterogeneity in the MR studies and no evidence of level pleiotropy was found.ConclusionsIn our MR study, our findings emphasize that IDA may be associated with a high risk of asthma, indicating a potential role for IDA in the development of asthma. Future research needs to elucidate its potential mechanisms to pave the way for the prevention and treatment of asthma.

IMMUNOGLOBULIN E IN PEDIATRIC ASTHMA: ADVANCES IN UNDERSTANDING AND MANAGEMENT

Asthma, a pervasive chronic inflammatory ailment of the respiratory system, remains a global health conundrum. The Global Burden of Disease Study (GBD) of 2019 underscores its widespread impact, revealing that asthma afflicts 262 million individuals worldwide, translating into an age-standardized prevalence of 3,416 per 100,000 population. The incidence among children is particularly alarming, with nearly 14% of the global pediatric population diagnosed with the condition. This statistic positions asthma as the foremost chronic respiratory disease among children, a trend that is on the rise, especially across Asia and Europe, as evidenced by the International Study of Asthma and Allergies in Childhood (ISAAC). Characterized by variable airflow limitation, bronchial hyperresponsiveness, excessive mucus production, and airway inflammation leading to airway constriction, asthma’s multifaceted nature complicates its management. In the realm of immunology, Immunoglobulin E (IgE) has been identified as a pivotal player. Recognized officially as the fifth class of serum immunoglobulins during the 1968 WHO International Reference Center for Immunoglobulins conference in Lausanne, IgE’s crucial role in the pathophysiology of asthma has been rigorously studied. Serum IgE levels, both total and specific, have been proven instrumental in the diagnosis, treatment, and prevention of pediatric asthma. The landmark approval of Omalizumab by the US Food and Drug Administration in 2003 heralded a new era in the biologic management of asthma, targeting children aged six and above. This was followed by the development of Ligelizumab and Quilizumab, innovative anti-IgE medications currently under investigation for their potential to alleviate symptoms and decelerate the disease’s progression. The integration of Allergy Immunotherapy (AIT) alongside monoclonal antibody therapies like Omalizumab, Ligelizumab, and Quilizumab signifies a monumental shift toward personalized medicine in asthma care. These advances promise not only to ameliorate the quality of life for pediatric asthma patients but also to redefine the landscape of asthma management. Nonetheless, the quest for enhanced treatment modalities for young asthmatics necessitates further in-depth research. The burgeoning field of anti-IgE therapy, in concert with AIT, is poised to set new benchmarks in pediatric asthma management, steering us towards a future where asthma’s grip on children’s health is significantly loosened.

Asthma Management and Prevention in Pregnancy, Labour and Birth

Asthma is one of the most common medical disorders among pregnant women and the prevalence of asthma has been increasing due to rising obesity rates and an increase in urban pollutants. Numerous physiological, lifestyle and environmental factors influence the course of asthma in pregnancy. Management of asthma in pregnancy includes education, monitoring and treatment. Under-treated or poorly controlled asthma poses the biggest risk to mother and baby. Midwives in particular have a role to play in asthma prevention by educating women about the importance of the links between medication, maternal nutrition in pregnancy and the potential risk of future asthma in the child.

Exploring the relationship between school-supervised asthma therapy and social determinants of health in pediatric asthma care.

Social determinants of health (SDoH), including access to care, economic stability, neighborhood factors, and social context, strongly influence pediatric asthma outcomes. School-supervised asthma therapy (SST) is an evidence-based strategy that improves asthma outcomes, particularly for historically marginalized children, by providing support for daily medication adherence in school. However, little is known about the relationship between these programs and the adverse SDoH commonly affecting underrepresented minority and marginalized children with asthma. We examined qualitative data from interviews (n = 52) conducted between 2017 and 2020 with diverse multi-level partners involved in Asthma Link, a SST intervention. Participants included end-users (children and their parents), deliverers (school nurses and pediatric providers), and systems-level partners (e.g., insurers, legislators, and state officials). We used inductive coding to determine themes and subthemes and deductive coding using the Healthy People 2030 SDoH framework. Three themes emerged: (1) SST mitigates adverse SDoH (improves access to preventive healthcare and asthma health literacy), (2) SST benefits children experiencing specific adverse SDoH (provides a consistent medication routine to children with unstable family/housing situations) and (3) specific adverse SDoH impede SST implementation (economic instability, culture and language barriers). This study suggests an important relationship between SDoH and SST that warrants further evaluation in our future work on this community-based asthma intervention. Moreover, our findings underscore the importance of measuring SDoH in the implementation and evaluation of pediatric asthma interventions, particularly given the strong influence of these social factors on child health outcomes.

Pre-asthma: a useful concept? A EUFOREA paper. Part 2-late onset eosinophilic asthma.

The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.

Clinical Response Predictive Model for Omalizumab in Moderate-to-Severe Asthma Patients

Objective. Our study aimed to develop a predictive model for evaluating the clinical response of omalizumab treatment in moderate-to-severe asthma patients. Methods. This single-center, prospective study collected patients who meet the diagnostic criteria for moderate-to-severe bronchial asthma set by the National Asthma Prevention and Treatment Group in 2016 in the first hospital affiliated with Soochow University. Patients recruited were treated with omalizumab once per four weeks; at the beginning of each injection, blood eosinophils and the level of total serum IgE (IU/mL) were tested. After four injections of omalizumab, asthma control test (ACT), the 15-item Mini Asthma Quality of Life Questionnaire (MiniAQLQ), global treatment effectiveness (GETE), and lung function of all patients were evaluated in the 16th week. We used the selection operator method to build a logistic model and evaluated the clinical response of omalizumab in these patients. Results. This study included 108 moderate-to-severe patients (aged 39.86 ± 14.59 years). Eighty-nine patients finished treatment for 16 weeks, and 74 patients (83.1%) had an excellent or good response. The serum level of total IgE increased significantly after injection of omalizumab, while blood eosinophils count decreased significantly from baseline. Using the GETE as a clinical outcome, several clinical variables were significant predictors of clinical response. The corrected AUC and Brier scores were 0.872 and 0.111, which showed good discrimination. Significant variables included age, weight, family allergic history, acute exacerbations, the ratio of total serum IgE level at the 4th week to the baseline level, forced expiratory volume in one second/forced vital capacity (FEV1/FVC), and commodities of rhinitis. Using the improvement in maximal expiratory flow 25% of the measured value to the predicted value (MEF25%pre) as clinical outcome, the significant variables included weight, duration of asthma, use of oral corticosteroids (OCS), total serum IgE level at the 4th week, and history of rhinitis. Its corrected AUC and Brier scores were 0.674 and 0.225 after internal validation. Conclusion. Omalizumab treatment remarkably improved asthma control and pulmonary function in Chinese patients with moderate-to-severe asthma. The response prediction model we developed provides convenient approaches to help identify better clinical response patients to omalizumab treatment.

Association of Socioeconomic Status and a Broad Combination of Lifestyle Factors With Adult-Onset Asthma: A Cohort Study

BackgroundThe prevalence of asthma is gradually increasing worldwide and there are socioeconomic inequalities in the risk of developing asthma. ObjectiveThis study aimed to evaluate whether the lifestyle is associated with asthma in adults, as well as whether and to what extent healthy lifestyles may modify socioeconomic status (SES) inequities in asthma. MethodsThis study included a total of 223951 participants from the UK Biobank. Smoking, physical activity, alcohol consumption, healthy diet patterns, sedentary time, and sleep duration items were used to construct the lifestyle score. Income, education, and occupation were used to assess SES. Cases of adult-onset asthma were identified based on electronic health records. The Cox proportional hazards regression was used to explore the association of socioeconomic inequality and lifestyle factors with asthma. ResultsCompared with the most healthy lifestyle category, the HRs (95% CIs) of the moderately healthy lifestyle and least healthy lifestyle categories for asthma were 1.08 (1.01-1.15) and 1.29 (1.20-1.39), respectively. A significant interaction (Pinteraction< 0.05) was found between lifestyle categories and socioeconomic status, and the association between them was more pronounced in participants with low socioeconomic status (HR least healthy vs most healthy: 1.58, 95%CI: 1.40-1.80). The joint analysis revealed that the risk of asthma was highest among participants with the lowest SES and the least healthy lifestyles (HR: 2.02, 95%CI: 1.74-2.33). ConclusionsUnhealthy lifestyle factors are associated with an increased risk of asthma in adults, and socioeconomically disadvantaged groups are more negatively affected by unhealthy lifestyles. Public health strategies for asthma prevention may need to be tailored according to socioeconomic status, and social policies to reduce poverty are needed alongside lifestyle interventions in areas of deprivation.

ALKBH5 Modulates Asthma Progression by Downregulating N6-methyladenosine Methylation.

Asthma is a chronic respiratory disease that is characterized by airway inflammation, excessive mucus production, and airway remodeling. Prevention and treatment for asthma is an urgent issue in clinical studies. In recent years, N6-methyladenosine methylation (m6A) has emerged as a promising regulatory approach involved in multiple diseases. ALKBH5 (alkB homolog 5) is a demethylase widely studied in disease pathologies. This work aimed to explore the regulatory mechanisms underlying the ALKBH5-regulated asthma. We established an interleukin-13 (IL-13)-stimulated cell model to mimic the in vitro inflammatory environment of asthma. ALKBH5 knockdown in bronchial epithelial cells was performed using siRNAs, and the knockdown efficacy was analyzed by quantitative PCR (qPCR). Cell viability and proliferation were measured by cell counting kit 8 (CCK-8) and colony formation assay. The ferroptosis was assessed by measuring the total iron, Fe2+, lipid reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The enrichment of N6-methyladenosine methylation (m6A) modification was detected by the MeRIP assay. Knockdown of ALKBH5 significantly elevated the survival and colony formation ability of bronchial epithelial cells in the IL-13 induction model. The levels of total iron, Fe2+, lipid ROS, and MDA were remarkedly elevated, and the SOD level was reduced in IL-13-induced bronchial epithelial cells, and depletion of ALKBH5 reversed these effects. Knockdown of ALKBH5 elevated the enrichment of m6A modification and expression of glutathione peroxidase 4 (GPX4). Knockdown of GPX4 abolished the pro-proliferation and anti-ferroptosis effects of siALKBH5. Knockdown of ALKBH5 improved the proliferation of bronchial epithelial cells and alleviated cell ferroptosis.

Burden and Subtypes of Early Life Infections Increase the Risk of Asthma

Early life respiratory tract infections have been linked to the development of asthma, but studies on the burden and subtypes of common infections in asthma development are sparse. To examine the association between burden of early life infections, including subtypes, with the risk of asthma from age 3 to 10 years and lung function at age 10 years. We included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, for whom infections such as colds, acute tonsillitis, acute otitis media, pneumonia, gastroenteritis, and fever were registered prospectively in daily diaries at age 0 to 3 years and asthma was diagnosed longitudinally from age 3 to 10 years. The association between the burden of infection and subtypes and risk of asthma was analyzed by generalized estimating equations. The children experienced a median of 16 infections (interquartile range, 12-23 infections) at age 0 to 3 years. Children with a high burden of infections (above the median) had an increased risk of asthma at age 3 to 10 years (adjusted odds ratio= 3.61; 95% CI, 2.39-5.45; P < .001), which was driven by colds, pneumonia, gastroenteritis, and fever episodes (P < .05) but not by acute otitis media and tonsillitis. Lower lung function measures at age 10 years were associated with the burden of pneumonia but not the overall infection burden. The association between colds and the risk of asthma was significantly higher in children with allergic rhinitis at age 6 years (P interaction= .032). A high burden of early life infections in terms of colds, pneumonia, gastroenteritis, and fever is associated with an increased risk of developing asthma, particularly in children with respiratory allergy. Strategies to diminish these early life infections may offer a path for the primary prevention of childhood asthma.

METTL3 mediates SOX5 m6A methylation in bronchial epithelial cells to attenuate Th2 cell differentiation in T2 asthma

ObjectiveAsthma, a chronic inflammatory disease in which type 2 T helper cells (Th2) play a causative role in the development of T2 asthma. N6-methyladenosine (m6A) modification, an mRNA modification, and methyltransferase-like 3 (METTL3) is involved in the development of T2 asthma by inhibiting Th2 cell differentiation. Sex determining region Y-box protein 5 (SOX5) is involved in regulating T cell differentiation, but its role in T2 asthma was unclear. The objective of this study was to explore the role of METTL3 and SOX5 in T2 asthma and whether there is an interaction between the two. Materials and methodsAdults diagnosed with T2 asthma (n = 14) underwent clinical information collection and pulmonary function tests. In vivo and in vitro T2 asthma models were established using female C57BL/6 mice and human bronchial epithelial cells (HBE). The expressions of METTL3 and SOX5 were detected by Western blot and qRT-PCR and Western blot. Th2 cell differentiation was determined by flow cytometry and IL-4 level was detected by ELISA. m6A methylation level was determined by m6A quantitative assay. The relationship between METTL3 expression and clinical parameters was determined by Spearman rank correlation analysis. The function of METTL3 and SOX5 genes in asthma was investigated in vitro and in vivo. The RNA immunoprecipitation assay detected the specific interaction between METTL3 and SOX5. ResultsPatients with T2 asthma displayed lower METTL3 levels compared to healthy controls. Within this group, a negative correlation was observed between METTL3 and Th2 cells, while a positive correlation was noted between METTL3 and clinical parameters as well as Th1 cells. In both in vitro and in vivo models representing T2 asthma, METTL3 levels decreased significantly, while SOX5 levels showed the opposite trend. Overexpression of METTL3 gene in HBE cells significantly inhibited Th2 cell differentiation and increased m6A methylation activity. From a mechanism perspective, low METTL3 negatively regulates SOX5 expression through m6A modification dependence, while high SOX5 expression is positively associated with T2 asthma severity. Cell transfection experiments confirmed that METTL3 regulates Th2 cell differentiation and IL-4 release through SOX5. ConclusionsOverall, our results indicate that METTL3 alleviates Th2 cell differentiation in T2 asthma by modulating the m6A methylation activity of SOX5 in bronchial epithelial cells. This mechanism could potentially serve as a target for the prevention and management of T2 asthma.

БРОНХИАЛЬНАЯ АСТМА – ФАРМАКОЭПИДЕМИОЛОГИЧЕСКИЙ СРЕЗ ЗНАНИЙ ВРАЧЕЙ. ИТОГИ ИССЛЕДОВАНИЯ «ASSA–III»

Introduction. Number of bronchial asthma (BA) cases increases every year. Despite the improvement of clinical guidelines proposed by national societies and GINA (Global Strategy for Asthma Management and Prevention) expert committee, BA is still an urgent and significant public health problem. In some basic issues of etiology, pathogenesis, diagnosis, and pharmacotherapy, there is still a deficiency in healthcare professionals’ knowledge. Aim. To study the basic bronchial asthma knowledge of physicians from different regions. Materials and Methods. A multicenter anonymous survey was conducted among medical specialists regarding their knowledge of and preferences in the topic of bronchial asthma. This is the third stage of the ASSA (Assessment of Senior Medical Students in Bronchial Asthma) project. Statistical data were processed using the Pearson chi-square criterion (χ2) and complementary adjustments. Results and Discussion. Over the years 2019-2023, an anonymous survey of 472 physicians was conducted in ten cities and regions of Russia. In general, the level of basic specialists was found to be relatively satisfactory: An average of 65.8 % according to the study. At the same time, a deeper understanding was noted in the basic and theoretical aspects of the BA etiopathogenesis and diagnosis (the average result in the pool of questions was 84.1%), while the pool of questions regarding the disease treatment turned out to be more difficult for the respondents (their average result was 52.1%). The respondents gave the best answers to questions regarding the reference to a prolonged suffocation attack (95.6%), the levels of asthma control (93.6%), and the key methods of BA diagnosis (91.3%); the worst results were obtained for questions related to the choice of reasonable treatment tactics for mild asthma at therapy stages 1 (34.7%) and 2 (32.2%), indications for sublingual immunotherapy (12%), and indications for adding tiotropium (33.6%). Conclusion. According to the findings, it was concluded that physicians generally had a relatively satisfactory level of knowledge on the main issues related to the BA definition, etiopathogenesis, and diagnosis. However, their knowledge regarding the advanced approaches to pharmacotherapy is insufficient, and these issues require in-depth and additional studies. We also identified the specific changes in the physicians’ knowledge depending on their seniority.

Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells

Sublingual allergen immunotherapy (SLIT) is an emerging treatment option for allergic asthma, and a potential disease modifying strategy for asthma prevention. The key cellular events leading to such long term tolerance remains to be fully elucidated. We administered prophylactic SLIT in a mouse model of house dust mite (HDM) driven allergic asthma. HDM extract was sublingually administered over 3 weeks followed by intratracheal sensitization and intranasal challenges with HDM. Prophylactic SLIT prevented allergic airway inflammation and hyperreactivity with a low lab-to-lab variation. The HDM specific Th2 (CD4 T helper) response was shifted by SLIT towards a regulatory and Th17 response in lung and mediastinal lymph node (MLN). By using Der p 1 specific CD4+ T cells (1-DER), we found that SLIT blocked 1-DER T cell recruitment to the MLN and dampened IL-4 secretion following intratracheal HDM sensitization. Sublingually administered Der p 1 protein activated 1-DER T cells in the cervical lymph node (CLN) via CCR7+ migratory dendritic cells (DC). DCs migrating from the oral submucosa to the CLN after SLIT induced Foxp3+ regulatory T cells. When mice were sensitized with HDM, prior prophylactic SLIT increased Der p 1 specific Tregs and lowered Th2 recruitment in the lung. By using Foxp3-DTR mice, Tregs were found to contribute to the immunoregulatory prophylactic effect of SLIT on type 2 immunity. These findings in a mouse model suggest that DC-mediated functional Treg induction in oral mucosa draining LNs is one of the driving mechanisms behind the disease modifying effect of prophylactic SLIT.

Knowledge on prevention and management of Chronic Obstructive Pulmonary Disease and Asthma among medical officers: a multi-centerpre and post-test study

Background: Despite Chronic Obstructive Pulmonary Disease (COPD) and Asthma being one of the leading causes of morbidity and mortality in India, knowledge about these diseases among healthcare professionals seems inadequate. Aims: This study aimed to assess the knowledge gained by medical and paramedical staff in the prevention and management of COPD and asthma following a two-day training program. Settings and methods: This quasi-experimental (before-after) study was carried out among medical and paramedical staff of public health systems of the government of India in three training centers in Maharashtra. Aquestionnaire was given in the form of a pre-test before a two-day training program. The training was comprised of prevention and management of COPD and asthma. After completion of training, a post-test was given, and scores were calculated. Statistical analysis: A two-tailed paired sample t-test was used to assess knowledge gain. P&lt;0.05 was considered statistically significant. Results: A total of 77 participants completed both pre-test and post-test before and after the training programme. Twenty-Five (32.5%) were female and 52 (67.5%) were male. The mean age of participants was 42.7± 7.9 years. The majority (92.2%) of the participants were medical professionals. Only nine participants (11.7%) had ever attended a training program on COPD or asthma. The mean pre-test score was 14.68±3.88, while the mean post-test score was 25.60±6.52. There was a statistically significant improvement in knowledge scores at all three training centers, among both genders and across all qualifications (p&lt;0.001). Conclusion: Adequate training of medical and para-medical staff in public health systems across the country can result in effective and timely diagnosis, treatment, and referral for patients with COPD and Asthma. This will ensure a reduction in the social and economic burden of disease.

Circ_0070934 promotes MGAT3 expression and inhibits epithelial-mesenchymal transition in bronchial epithelial cells by sponging miR-199a-5p

BackgroundCircular RNA (circRNA) has the potential to serve as a crucial regulator in the progression of bronchial asthma. The objective of this investigation was to elucidate the functional dynamics of the circ_0070934/miR-199a-5p/Mannoside acetylglucosaminyltransferase 3 (MGAT3) axis in the development of asthma.MethodsCirc_0070934, miR-199a-5p and MGAT3 in peripheral venous blood of 38 asthmatic patients and 43 healthy controls were detected by qRT-PCR, and the expression of MGAT3 protein was examined by ELISA. The GSE148000 dataset was analyzed for differences in MGAT3. The BEAS-2B cells were transfected with circ_0070934 plasmid and small interfering RNA, miR-199a-5p mimics and inhibitors. The apoptosis level was detected by flow cytometry and MGAT3 was detected by qRT-PCR and Western blot. The expression of E-cadherin, N-cadherin, Vimentin was examined by Western blot. Interleukin-4 (IL-4) and IL-13 were used to co-stimulate BEAS-2B cells as an asthmatic airway epithelial cell model. BEAS-2B cells exposed to type 2 cytokines (IL-4 and IL-13) were treated with circ_0070934 plasmid, and the expression of E-cadherin, N-cadherin, and Vimentin was detected by Western blot. The binding relationships were verified using dual-luciferase reporter assay and miRNA pull-down assay.ResultsThe expression of circ_0070934 and MGAT3 in peripheral venous blood of asthmatic patients was down-regulated, and the expression of miR-199a-5p was up-regulated. And the expression of MGAT3 was reduced in sputum of asthma patients. Down-regulating the expression of circ_0070934 could promote apoptosis of BEAS-2B cells and increase epithelial-mesenchymal transition (EMT), and this effect can be partially reversed by down-regulating miR-199a-5p. Circ_0070934 could inhibit the process of epithelial mesenchymal transition induced by IL-4 and IL-13 in BEAS-2B cells. In addition, miR-199a-5p could respectively bind to circ_0070934 and MGAT3.ConclusionThe findings of this study indicate that circ_0070934 may function as a competitive endogenous RNA (ceRNA) of miR-199a-5p, thereby modulating the expression of MGAT3 and impacting the process of EMT in bronchial epithelial cells. These results contribute to the establishment of a theoretical framework for advancing the prevention and treatment strategies for asthma.

A Functional Bread Fermented with Saccharomyces cerevisiae UFMG A-905 Prevents Allergic Asthma in Mice

BackgroundThe administration of probiotics has been shown to be beneficial in asthma. The administration of Saccharomyces cerevisiae UFMG A-905 prevented asthma development. Traditionally, probiotics are administered using dairy-based matrices, but other vehicles (e.g., fruit juices, biscuits, candies, and breads) can be used. ObjectivesThis study aimed to assess the effect of bread fermented with S. cerevisiae UFMG A-905 in asthma prevention. MethodsThree breads were produced: fermented with commercial yeast, fermented with S. cerevisiae UFMG A-905, and fermented with S. cerevisiae UFMG A-905 with the addition of alginate microcapsules containing live S. cerevisiae UFMG A-905. Characterization of the microbial composition of the breads was performed. Male Balb/c mice were sensitized and challenged with ovalbumin. Breads were administered 10 d before the first sensitization and during sensitization and challenge protocol. Yeast fecal count, in vivo airway hyperresponsiveness, and airway and lung inflammation were assessed. ResultsIn UFMG A-905 bread, there was an increase in yeast number and a decrease in total and lactic acid bacteria. Animals that received S. cerevisiae UFMG A-905 fermented bread with microcapsules had a significant increase in yeast recovery from feces. S. cerevisiae UFMG A-905–fermented breads partially reduced airway inflammation, decreasing eosinophils and IL5 and IL13 concentrations. When adding microcapsules, the bread also diminished airway hyperresponsiveness and increased IL17A concentrations. ConclusionsS. cerevisiae UFMG A-905 was able to generate long-fermentation breads. Microcapsules were a safe and viable way to inoculate the live yeast into food. The administration of breads fermented with S. cerevisiae UFMG A-905 prevented asthma-like characteristics, being more pronounced when the breads contained microcapsules with live yeast.

Clinical implications of airway obstruction with normal or low FEV1 in childhood and adolescence

BackgroundAirway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low...