Risk Factor For Childhood Asthma Research Articles

Proteomic analysis reveals potential therapeutic targets for childhood asthma through Mendelian randomization.

Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets. Based on publicly available genome-wide association study summary statistics, we employed a two-sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset. MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase-activating protein 1 [RGAP1], IL-21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype-wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes. Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets.

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze

BackgroundEarly life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. ObjectiveTo investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW). MethodsA total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months. ResultsUpper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively). ConclusionAzithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV. Trial RegistrationThis study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

Prevalence and Risk Factors of Childhood Asthma in Jazan Region, Saudi Arabia.

The prevalence of asthma among children has been on the rise worldwide, leading to significant morbidity and mortality. Our study was conducted to determine the prevalence of asthma and its related risk factors among school-age children in the Jazan Region, Saudi Arabia. The study was a cross-sectional prospective study that used Phase I ISAAC protocol and was conducted from March to June 2023. The sample size was calculated to be 1600 among school-age children in the Jazan Region Saudi Arabia. This study complies with the Declaration of Helsinki. Data was analyzed using SPSS version 23.0, Descriptive statistics were calculated for study variables, and appropriate tests of significance were performed to determine statistical significance. The total study population was 1368 the majority of them, 96.6% (n=1321), were Saudi nationals, and most of them lived in rural areas (70.6%, n=966). The prevalence of life-long wheezing, wheezing in the last 12 months, and exercise-induced wheezing was 28.0%, 29.2%, and 30.9%, respectively. Risk factors such as having indoor plants, having a pet, and a smoker in the household were reported by 48.0%, 24.6%, and 36.4% of participants, respectively. Living near an industrial area was determined as a risk factor in 98 (7.2%) of the children. Asthma-related symptoms were strongly correlated with all risk factors based on the chi-square test, and some risk factors based on multivariate linear regression. The prevalence of asthma among children in the Jazan Region is higher than previously reported, and the reported risk factors are significantly correlated with symptoms of asthma.

Association between parental occupational exposure and the risk of asthma in offspring: A meta-analysis and systematic review.

Previous epidemiological studies have shown inconsistent results regarding the relation between the risk of asthma in offspring and parental occupational exposure. Therefore, we conducted a comprehensive and systematic collection of currently available epidemiological data to quantify the correlation between the 2. Related studies published before March 2023 were identified through searches of the Cochrane Library, Embase, PubMed, and Web of Science databases. The quality of included studies was assessed using the Newcastle-Ottawa Scale, while pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed using fixed-effect or random-effects models. This systematic review included 10 cohort studies, with a total of 89,571 parent-child pairs included in the quantitative analysis. The results exhibited a substantial association between parental occupational exposure to allergens (OR = 1.11; 95% CI: 1.00, 1.23; P = .051) and irritants (OR = 1.19; 95% CI: 1.07, 1.32; P = .001) and an increased risk of asthma in offspring. This association was also observed in the analysis of wheezing (OR = 1.22; 95% CI: 1.11, 1.35; P < .001 and OR = 1.19; 95% CI: 1.08, 1.32; P = .001). Subgroup analysis demonstrated that maternal occupational exposure to allergens (OR = 1.07; 95% CI: 1.02, 1.12; P = .008) and irritants (OR = 1.13; 95% CI: 1.05, 1.21; P = .001) significantly increased the risk of childhood asthma. Furthermore, parental postnatal occupational exposure to allergens (OR = 1.26; 95% CI: 1.10, 1.46; P = .001) and irritants (OR = 1.26; 95% CI: 1.06, 1.49; P = .009) had a more pronounced impact on childhood asthma. Higher levels of exposure (OR = 1.26; 95% CI: 1.10, 1.46; P = .001 and OR = 1.30; 95% CI: 1.16, 1.47; P < .001) were recognized as significant risk factors for childhood asthma. Parental occupational exposure to allergens and irritants increases the risk of asthma and wheezing in offspring, with maternal exposure, postnatal exposure, and high-dose exposure being the primary risk factors for childhood asthma.

Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study.

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway miRNAs during severe bronchiolitis and the risk of developing asthma. In a 17-center prospective cohort study of infants with severe bronchiolitis, we sequenced their nasal miRNA at hospitalization. First, we identified differentially expressed miRNAs (DEmiRNAs) associated with the risk of developing asthma by age 6 years. Second, we characterized the DEmiRNAs based on their association with asthma-related clinical features, and expression level by tissue and cell types. Third, we conducted pathway and network analyses by integrating DEmiRNAs and their mRNA targets. Finally, we investigated the association of DEmiRNAs and nasal cytokines. In 575 infants (median age=3 months), we identified 23 DEmiRNAs associated with asthma development (e.g., hsa-miR-29a-3p, FDR<0.10), particularly in infants with respiratory syncytial virus infection (FDRinteraction<0.05). These DEmiRNAs were associated with 16 asthma-related clinical features (FDR<0.05)-e.g., infant eczema and corticosteroid use during hospitalization. These DEmiRNAs were also highly expressed in lung tissue and immune cells (e.g., TH cells, neutrophils). Third, DEmiRNAs were negatively correlated with their mRNA targets (e.g., hsa-miR-324-3p/IL13), which were enriched in asthma-related pathways (FDR<0.05)-e.g., toll-like receptor, PI3K-Akt, and FcɛR signaling pathways, and validated by cytokine data. In a multicenter cohort of infants with severe bronchiolitis, we identified nasal miRNAs during illness that were associated with major asthma-related clinical features, immune response, and risk of asthma development.

Is sibship composition a risk factor for childhood asthma? Systematic review and meta-analysis.

Following the "hygiene hypothesis", the role of sibship composition in asthma and wheezing has been extensively studied, but the findings are inconsistent. For the first time, this systematic review and meta-analysis synthesized evidences from studies investigating the association of sibship size and birth order with risk of asthma and wheezing. Fifteen databases were searched to identify eligible studies. Study selection and data extraction were performed independently by pairs of reviewers. Meta-analysis with robust variance estimation (RVE) was used to produce pooled risk ratio (RR) effect estimates from comparable numerical data. From 17,466 identified records, 158 reports of 134 studies (> 3 million subjects) were included. Any wheezing in the last ≤ 1.5years occurred more frequently in infants with ≥ 1 sibling [pooled RR 1.10, 95% confidence interval (CI) 1.02-1.19] and ≥ 1 older sibling (pooled RR 1.16, 95% CI 1.04-1.29). The pooled effect sizes for asthma were overall statistically nonsignificant, although having ≥ 1 older sibling was marginally protective for subjects aged ≥ 6years (pooled RR 0.93, 95% CI 0.88-0.99). The effect estimates weakened in studies published after 2000 compared with earlier studies. Being second-born or later and having at least one sibling is associated with a slightly increased risk of temporary wheezing in infancy. In contrast, being second-born or later is associated with marginal protection against asthma. These associations appear to have weakened since the turn of the millennium, possibly due to lifestyle changes and socioeconomic development. Video Abstract.

The prevalence of childhood asthma: interpreting falling rates in the context of shifting measurement and the COVID-19 pandemic.

The estimated prevalence of childhood asthma in the United States, as measured by the National Health Information Survey (NHIS), has decreased by 30% since 2017. This review provides context for observed changes in asthma rates by describing recent shifts in NHIS data collection and analysis, and considers whether the COVID-19 pandemic might impact asthma prevalence in years to come. The NHIS underwent a planned redesign in 2019 with updated sampling weights to better match the U.S. population. In early 2020, the COVID-19 pandemic resulted in unplanned modifications to NHIS implementation, which may have included fewer children from populations at a heightened risk for asthma. Decreasing prevalence estimates in recent years are likely at least in part due to these survey changes rather than true epidemiologic shift. However, pandemic-related changes to risk factors for childhood asthma (including exposure to rhinovirus infections and allergic sensitization) may also influence prevalence in the future. Recent changes in estimated rates of childhood asthma in the USA are likely driven by changes to survey methods and implementation, both before and during the COVID-19 pandemic. Additional years of data are needed to determine whether a true shift in disease prevalence is occurring.

Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study

Severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway microRNAs (miRNAs) during severe bronchiolitis with the risk of developing asthma.

Di-(2-ethylhexyl) phthalate aggravates fine particulate matter-induced asthma in weanling mice due to T follicular helper cell-dependent response

Environmental pollutants fine particulate matter and di-(2-ethylhexyl) phthalate (DEHP) are believed to be the risk factors for childhood asthma. Allergic asthma is basically an immediate hypersensitivity mediated by IgE, the product of humoral immune response. T follicular helper cells (Tfh) have been newly identified as the crucial T helper cells for supporting B cells to produce immunoglobulins in humoral immunity. Tfh cells are therefore potentially to serve as the diagnostic marker and therapeutic target of immune diseases. In this study, we examined the joint effects of fine particulate matter and DEHP on the initiation and progression of asthma and explored the fundamental role of Tfh cells during the process. Weanling C57BL/6 mice (both sexes) were concurrently exposed to DEHP (intragastric administration at 300 μg/kg) and fine atmospheric particulate matter (mean particle diameter < 4 µm, PM4) (oropharyngeal instillation at 2 mg/kg) once every three days for 30 days (10 times). We found that DEHP displayed adjuvant effects to potentiate PM4 allergen-induced expansion of Tfh and plasma cells, production of serum IgE and IgG1, and occurrence of airway hyper-responsiveness and inflammation. Then PM4 and DEHP co-exposure was performed to Cd4 knock-out mice reconstituted with normal wild-type adoptive Tfh cells or non-Tfh cells. The results of immune adoptive transfusion indicated that the joint immunotoxic effects of PM4 and DEHP were dependent on Tfh cells. We further proved that DEHP could adjuvantly boost PM4-induced expression of BCL-6 and c-MAF and secretion of IL-13 and IL-4 in Tfh cells. In conclusion, these data suggest that DEHP metabolites act in an adjuvant-like manner to aggravate PM4 allergen-induced asthma based on anaphylactic IgE response, resulting from excessive IL-13 and IL-4 synthesized by abnormally differentiated Tfh cells.

Risk Factors of Childhood Asthma Among Patients Attending a Tertiary Care Centre in North-East India.

IntroductionAsthma is a chronic lung illness marked by a reversible airway blockage. Both genetic and environmental factors influence higher asthma rates. The present study aims to assess the various socio-demographic and environmental factors influencing the causation of childhood asthma among patients attending the Paediatric Department of Gauhati Medical College and Hospital (GMCH), Assam.Materials and MethodsA total of 150 clinically diagnosed asthma patients of 3–12 years as cases and patients of the same age group free from respiratory diseases with no history of asthma in a 1:1 ratio as controls were selected. A predesigned and pretested proforma was used to collect data, and written informed consent was obtained from all the legal guardians of the participants. Data were analyzed by chi-square test and binary logistic regression using SPSS V20, considering a p-value <0.05 significant.ResultsUrban and male children were found to be at higher risk of developing asthma. Children belonging to the urban locality (OR= 4.53; 95% CI: 1.57–13.09; p<0.05), damp environment (OR= 5.21; 95% CI: 1.23–22.10; p<0.05), lower socioeconomic status (OR= 3.48; 95% CI: 1.34–9.01; p<0.05), presence of pets (OR= 6.77; 95% CI: 1.76–25.99; p<0.05), family history of atopy/ allergy (OR= 43.29; 95% CI: 5.80–323.15 p<0.05), smoking/passive smoking (OR=23.54; 95% CI: 1.41–394.21 p<0.05) and mixed feeding (OR= 4.47; 95% CI: 1.46–13.63 p<0.05) were the significant risk factors of childhood asthma.ConclusionChildren are vulnerable to environmental-induced asthma. Awareness and preventive measures are necessary to control and reduce the burden of childhood asthma.

Nasopharyngeal lipidomic endotypes of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study

BackgroundBronchiolitis is the leading cause of hospitalisation of US infants and an important risk factor for childhood asthma. Recent evidence suggests that bronchiolitis is clinically heterogeneous. We sought to derive...

Risk factors associated with childhood asthma in 5 – 11 years old children

Background: Various factors are known to precipitate an attack of asthma. Though no obvious causes can be found in these instances however since our climate and environment differ as do our habits and diets from those in other countries it is pertinent to examine whether the trigger factors in Sri Lanka are also different. So, the mothers of the asthmatic children were questioned regarding the likely precipitating factors pertaining to the present attack. Methods: In order to identify the risk factors for childhood asthma in children in the age group 5 – 11 years a community based cross sectional analytical study was conducted in the Colombo Municipal Council area in the Colombo district. The sample size included 683 children in the age group of 6 – 11 years residing in the Colombo Municipal Council area. An interviewer administered questionnaire was used for data collection. Results: Childhood asthma was statistically significantly associated with the following factors: Child’s history of eczema(p&lt;0.05), exclusive breast feeding beyond six months (p&lt;0.05), location of house near dusty environment (p&lt;0.001), main fuel as firewood (p&lt;0.05), place of sleep(p&lt;0.05),the type of mattress cover(p&lt;0.001), burning of mosquito coils (p&lt;0.05),birth weight less than 2.5kg(p&lt;0.001), Family history of asthma(p&lt;0.001), and smoking habits of the father when at home(p&lt;0.001). The other factors which were looked into were the age of starting the complementary feeding (p&gt;0.05), age of starting the formula feeding (p&gt;0.05), family history of allergy (p&gt;0.05), these were not significant. After the logistic regression birth weight less than 2.5 Kg has shown the strongest association with childhood asthma (OR 5.35), Whereas starting of complimentary feeding before 6/12 has a protective effect (OR .24). Conclusion: Birth weight less than 2.5 Kg has shown the strongest association with childhood asthma

Nasopharyngeal airway dual-transcriptome of infants with severe bronchiolitis and risk of childhood asthma: A multicenter prospective study

Severe bronchiolitis (ie, bronchiolitis requiring hospitalization) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. This study sought to examine the integrated role of airway microbiome (both taxonomy and function) and host response in asthma development in this high-risk population. This multicenter prospective cohort study of 244 infants with severe bronchiolitis (median age, 3 months) examined the infants' nasopharyngeal metatranscriptomes (microbiomes) and transcriptomes (hosts), as well as metabolomes at hospitalization. The longitudinal relationships investigated include (1) major bacterial species (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis), (2) microbial function, and (3) host response with risks of developing asthma by age 6 years. First, the abundance of S pneumoniae was associated with greater risks of asthma (P= .01), particularly in infants with nonrhinovirus infection (Pinteraction= .04). Second, of 328 microbial functional pathways that are differentially enriched by asthma development, the top pathways (eg, fatty acid and glycolysis pathways; false discovery rate [FDR]< 1×10-12) were driven by these 3 major species (eg, positive association of S pneumoniae with glycolysis; FDR< 0.001). These microbial functional pathways were validated with the parallel metabolome data. Third, 104 transcriptome pathways were differentially enriched (FDR< .05)-for example, downregulated interferon-α and -γ and upregulated T-cell activation pathways. S pneumoniae was associated with most differentially expressed transcripts (eg, DAGLB; FDR< 0.05). By applying metatranscriptomic, transcriptomic, and metabolomic approaches to a multicenter cohort of infants with bronchiolitis, this study found an interplay between major bacterial species, their function, and host response in the airway, and their longitudinal relationship with asthma development.

Concentrations of indoor gaseous air pollutants and risk factors associated with childhood asthma in Benin City, Nigeria.

Pollutants from various indoor sources account for indoor air pollution mostly in developing countries and pose health risks to children. This study assessed the levels of indoor gaseous pollutants and environmental risk factors associated with asthma in children. A cross-sectional household survey was conducted among 304 children between the ages of 1 and 17years. Indoor pollution at home was investigated using a modified international survey on asthma and allergies in childhood (ISAAC) questionnaire. Concentrations of indoor gaseous pollutants (CO, SO2 and NO2) were measured in two hundred and twenty-five randomly selected households using a MultiRae lite gas meter. The data obtained were analysed using SPSS for windows version 21.0. The risk factors for childhood asthma were obtained as odds ratios (ORs) using multivariate logistic regression. Mean concentrations of indoor gaseous pollutants ranged between 2.34-3.14 and 2.21-2.61mg/m3 (CO), 0.02-0.05 and < 0.002-0.03mg/m3 (NO2) and < 0.002-0.03 and < 0.002-0.02mg/m3 (SO2) in the wet and dry seasons. The mean values of pollutants were within the WHO permissible limits. The morbidity rates of clinical asthma, physician-diagnosed asthma and recurrent wheeze in the past 12months among the respondents were 5.6%, 2.6% and 11.8% respectively. There was no association between asthma prevalence and air pollutant exposures except with CO (R = 0.130). However, the number of occupants, family history of asthma, current smoking, use of kerosene and proximity of residence to the highway with significant (p < 0.05) odds ratios (12.4, 3.51, 2.51, 7.20 and 3.46) were independent contributors to current asthma in children. The study showed that exposure to household risk factors contributed to increased asthma among children in the study locations.

Unique Allergic Asthma Phenotypes in Offspring of House Dust Mite-exposed Mice.

Asthma is a heterogeneous inflammatory airway disease that develops in response to a combination of genetic predisposition and environmental exposures. Patients with asthma are grouped into phenotypes with shared clinical features and biomarker profiles to help tailor specific therapies. However, factors driving development of specific phenotypes are poorly understood. Prenatal exposure to maternal asthma is a unique risk factor for childhood asthma. Here we tested whether maternal asthma skews asthma phenotypes in offspring. We compared airway hyperreactivity and inflammatory and neurotrophin lung signatures before and after allergen challenge in offspring born to mice exposed to house dust mite (HDM) or vehicle during pregnancy. Maternal HDM exposure potentiated offspring responses to HDM allergen, significantly increasing both airway hyperreactivity and airway eosinophilia compared with control mice. Maternal HDM exposure broadly skewed the offspring cytokine response from a classic allergen-induced T-helper cell type 2 (Th2)-predominant signature in HDM-treated offspring of vehicle-exposed mothers, toward a mixed Th17/Th1 phenotype in HDM-treated offspring of HDM-exposed mothers. Morphologic analysis determined that maternal HDM exposure also increased airway epithelial sensory nerve density and induced distinct neurotrophin signatures to support airway hyperinnervation. Our results demonstrate that maternal allergen exposure alters fetal lung development and promotes a unique inflammatory phenotype at baseline and in response to allergen that persists into adulthood.

Periconceptional folic acid supplementation is a risk factor for childhood asthma: a case-control study

BackgroundSeveral studies found an association between periconceptional folic acid supplementation and the risk of childhood asthma. But the epidemiologic evidence is still inconsistent and the underlying biological mechanisms remain unclear.MethodsWe conducted a hospital-based case-control study on childhood asthma with 548 cases and 816 normal controls in Shanghai, China. Mothers of the asthma children were asked about folic acid supplementation before and during pregnancy. Unconditional logistic regression models were employed to control for potential confounders.ResultsPericonceptional folic acid supplementation was associated with an increased risk of childhood asthma after adjusting for potential confounders (adjusted OR = 1.28 [95% CI 1.14–1.43]). Moreover, the adjusted OR varied by the timing of starting folic acid supplementation: before gestation: 1.31 [95% CI 1.01–1.70]; in the 1st month of gestation: 1.09 [95% CI 0.96–1.23]; and after the 1st month of gestation: 1.90 [95% CI 1.56–2.30]. We further found that the adjusted OR was the highest when periconceptional folic acid supplementation lasted more than 6 months (< 4 months: 1.21 [95% CI 1.07–1.37]; 4–6 months: 1.06 [95% CI 0.88–1.27]; > 6 months: 1.75 [95% CI 1.35–2.27]).ConclusionsPericonceptional folic acid supplementation was associated with an increased risk of childhood asthma in offspring. Further research on this issue is warranted.

Azithromycin to Prevent Recurrent Wheeze Following Severe Respiratory Syncytial Virus Bronchiolitis

BackgroundEarly-life severe respiratory syncytial virus (RSV) bronchiolitis is a risk factor for childhood asthma. Because azithromycin may attenuate airway inflammation during RSV bronchiolitis, we evaluated whether it would reduce the occurrence of post-RSV recurrent wheeze.MethodsWe prospectively enrolled 200 otherwise healthy 1- to 18-month-old children hospitalized with RSV bronchiolitis in this single-center, double-blind, placebo-controlled study and randomly assigned them to receive oral azithromycin (10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days) or placebo. Randomization was stratified by recent open-label antibiotic use. The primary outcome was the occurrence of recurrent wheeze, defined as a third episode of post-RSV wheeze over the following 2 to 4 years.ResultsAs an indication of the biologic activity of azithromycin, nasal wash interleukin-8 levels, at day 14 after randomization, were lower among azithromycin-treated participants (P<0.01). Despite evidence of biologic activity, azithromycin did not reduce the risk of post-RSV recurrent wheeze (47% in the azithromycin group vs. 36% in the placebo group; adjusted hazard ratio, 1.45; 95% confidence interval [CI], 0.92 to 2.29; P=0.11). Azithromycin also did not modify the risk of recurrent wheeze among participants already receiving other antibiotic treatment at the time of enrollment (hazard ratio, 0.94; 95% CI, 0.43 to 2.07). There was a potential signal among antibiotic-naïve participants who received azithromycin to have an increased risk of recurrent wheeze (hazard ratio, 1.79; 95% CI, 1.03 to 3.1).ConclusionsAzithromycin therapy for 14 days during acute severe RSV bronchiolitis did not reduce recurrent wheeze occurrence over the following 2 to 4 years. Our data suggest no benefit of azithromycin administration with the goal of preventing recurrent wheeze in later life. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02911935.)

Effect of ketogenic diet on obesity asthma

Recently investigators pay more attention to the relationship between obesity and bronchial asthma (asthma).Obesity is increasingly recognized as a possible risk factor for childhood asthma, and 70% of patients with difficult-to-treat asthma are overweight or obese. In recent years, ketogenic diet, as one of the natural therapies, has been shown to have positive effects on weight loss process; and recent studies showed that ketogenic diet reduced airway inflammation in asthma. This review summarized the mechanisms of associations between obesity and asthma, and described the potential mechanisms of ketogenic diet affecting obese asthma, such as controlling body weight, reducing inflammatory response, regulating intestinal flora and modifying epigenetics, to provide new ideas for the prevention and treatment of obesity asthma.

Azithromycin to Prevent Recurrent Wheeze Following Severe RSV bronchiolitis: The APW-RSV II Clinical Trial

Early life severe Respiratory Syncytial Virus (RSV) bronchiolitis is a risk factor for childhood asthma. As azithromycin may attenuate airway inflammation during RSV bronchiolitis, we evaluated if it would reduce the occurrence of recurrent wheeze (RW).

Transcriptomic and metabolomic associations with exposures to air pollutants among young adults with childhood asthma history

Ambient air pollutants are well-known risk factors for childhood asthma and asthma exacerbation. It is unknown whether different air pollutants individually or jointly affect pathophysiological mechanisms of asthma. In this study, we aim to integrate transcriptome and untargeted metabolome to identify dysregulated genetic and metabolic pathways that are associated with exposures to a mixture of ambient and traffic-related air pollutants among adults with asthma history. In this cross-sectional study, 102 young adults with childhood asthma history were enrolled from southern California in 2012. Whole blood transcriptome was measured with 20,869 expression signatures, and serum untargeted metabolomics including 937 metabolites were analyzed by Metabolon, Inc. Participants’ exposures to regional air pollutants (NO2, O3, PM10, PM2.5) and near-roadway air pollutants averaged at one month and one year before study visit were estimated based on residential addresses. xMWAS network analysis and joint-pathway analysis were performed to identify subnetworks and genetic and metabolic pathways that were associated with exposure to air pollutants adjusted for socio-characteristic covariates. Network analysis found that exposures to air pollutants mixture were connected to 357 gene markers and 92 metabolites. One-year and one-month averaged PM2.5 and NO2 were associated with several amino acids related to serine, glycine, and beta-alanine metabolism. Lower serum levels of carnosine and aspartate, which are involved in the beta-alanine metabolic pathway, as well as choline were also associated with worse asthma control (p < 0.05). One-year and one-month averaged PM10 and one-month averaged O3 were associated with higher gene expression levels of HSPA5, LGMN, CTSL and HLA-DPB1, which are involved in antigen processing and presentation. These results indicate that exposures to various air pollutants are associated with altered genetic and metabolic pathways that affect anti-oxidative capacity and immune response and can potentially contribute to asthma-related pathophysiology.