Childhood Asthma Research Articles

Exposure to Poly- and Perfluoroalkyl Substances During Pregnancy and Asthma in Childhood: A Systematic Review

Exposure to Poly- and Perfluoroalkyl Substances During Pregnancy and Asthma in Childhood: A Systematic Review

Distinct phenotype and risk factor analysis of persistent airflow limitation among asthmatic children: a case-control study

Distinct phenotype and risk factor analysis of persistent airflow limitation among asthmatic children: a case-control study

Asthma and Memory Function in Children

ImportanceAsthma is a chronic respiratory disease affecting approximately 5 million children in the US. Rodent models of asthma indicate memory deficits, but little is known about whether asthma alters children’s memory development.ObjectiveTo assess whether childhood asthma is associated with lower memory abilities in children.Design, Setting, and ParticipantsThis cohort study used observational data from the Adolescent Brain Cognitive Development (ABCD) Study, a multisite longitudinal investigation that began enrollment in 2015. Approximately 11 800 children aged 9 to 10 years were enrolled at baseline with follow-up at 1 and 2 years. Participants were selected based on exposures described subsequently to determine longitudinal and cross-sectional associations between asthma and memory. Data were analyzed from Month year to Month year.ExposuresAsthma was determined from parent reports. For the longitudinal analysis, children were selected if they had asthma at baseline and at the 2-year follow-up (earlier childhood onset), at the 2-year follow-up only (later childhood onset), or no history of asthma. For the cross-sectional analysis, children were selected if they had asthma at any time point, or no history of asthma. The comparison group of children with asthma history was matched on demographic and health covariates for each analysis.Main Outcomes and MeasuresThe primary outcome was episodic memory. Secondary outcomes included processing speed, inhibition and attention.ResultsFour hundred seventy-four children were included in the longitudinal analysis (earlier childhood onset: 135 children; mean [SD] age, 9.90 [0.63] years; 76 [56%] male; 53 [28%] Black, 29 [21%] Hispanic or Latino, and 91 [48%] White; later childhood onset: 102 children; mean [SD] age 9.88 [0.59] years; 54 [53%] female; 22 [17%] Black, 19 [19%] Hispanic or Latino, and 83 [63%] White; comparison: 237 children; mean [SD] age, 9.89 [0.59] years; 121 [51%] male; 47 [15%] Black, 48 [20%] Hispanic or Latino, and 194 [62%] White). Children with earlier onset of asthma exhibited lower rates of longitudinal memory improvements relative to the comparison group (β = −0.17; 95% CI, −0.28 to −0.05; P = .01). Two thousand sixty-two children were selected for the cross-sectional analysis (with asthma: 1031 children; mean [SD] age, 11.99 [0.66] years; 588 [57%] male; 360 [27%] Black, 186 [18%] Hispanic or Latino, and 719 [54%] White; without asthma: 1031 children; mean [SD] age 12.00 [0.66] years; 477 [54%] female; 273 [21%] Black, 242 [23%] Hispanic or Latino, and 782 [59%] White). Children with asthma (1031 children) showed lower scores on episodic memory (β = −0.09; 95% CI, −0.18 to −0.01; P = .04), processing speed (β = −0.13; 95% CI, −0.22 to −0.03; P = .01), and inhibition and attention (β = −0.11; 95% CI, −0.21 to −0.02; P = .02).Conclusions and RelevanceIn this cohort study, asthma was associated with memory difficulties in children, which may be more severe if asthma onset is earlier in childhood and may extend to executive function abilities.

Effect of treatment on quality of life of rural asthmatic children

Introduction: Medications relieve symptoms of asthma but affected children are significantly bothered by physical, educational and emotional impairments. Urban studies from India evaluated on how this disease affects quality of life. Aim of our study was to evaluate quality of life of rural asthmatic children both before as well as after the treatment. Methods: Asthmatic children 7 to 17 years visiting to rural tertiary care teaching hospital were included. Tool used for the study was Pediatric Asthma Quality of Life Questionnaire - Standard (PAQLQS) which were measured at the time of inclusion and four weeks after treatment. It assessed the QOL (Quality of Life) under symptoms, activity limitation and emotional function domains. Mean difference in pre and post treatment PAQLQ score was assessed. Results: Total 46 children were included from rural setup. Majority were male 60% and had a normal BMI (54%) which was followed by undernutrition (28%). Majority children in both age group 7-11year and 12-17 year, presented with moderate asthma (80%) and (62%) (according to GINA 2022) respectively followed by mild. The rural cohort post treatment showed significant improvement in individual (p<0.005) as well as in overall PAQLQ post treatment (p<0.002). Conclusion: The study has highlighted that good asthma control even after short duration of treatment helped in improvement quality of life of affected children. To maintain quality of life it is expected that the patient remains adhered to proper treatment.

The Impact of Adverse Childhood Experiences on Asthma Severity in US Adults

Background/objectives: The association between adverse childhood experiences (ACEs) and asthma severity among United States (US) adults with asthma has not been well documented. In addition, whether gender differences exist in this association has been underexplored. We aimed to examine the prevalence of asthma severity in the US adult population with asthma and investigate the association between ACEs and asthma severity by using data from non-institutionalized US adults with asthma. Methods: This cross-sectional study used data from the Adult 2019 and 2020 Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-Back Survey (ACBS), a survey of US adults aged 18 years or older in 31 US states and Puerto Rico. A total of 22934 adults with asthma participated in 2019 and 2020 ACBS. The 11 BRFSS ACE variables encompassing abuse and household dysfunction were used as ACE measures. ACE measures were summed up as cumulative ACE scores (continuous) and categorized (zero, one ACE, two ACEs, ≥ three ACEs). Asthma severity was categorized as intermittent or persistent. Weighted logistic regression models were used to assess associations of the cumulative ACE score, categorical ACE measures, and the 11 individual ACE responses with asthma severity controlling confounders. Gender differences were explored by stratifying by gender. Results: The prevalence of persistent asthma among US adults with asthma was 45.3%. The mean cumulative ACE score in adults with intermittent vs. persistent asthma was (2.43 vs. 2.70, p-value < 0.05). About 22% of adults with asthma had no ACEs, 19% had one ACE, 14% had two ACEs, and 45% had three or more ACEs. A one-unit increase in ACEs score was associated with a 5.4% increase in the odds of persistent asthma (adjusted odds ratio, aOR = 1.054 (95% confidence interval, CI = 1.01–1.10). Experiencing ≥ three ACEs compared to no ACEs was associated with 31% increased odds of persistent asthma (aOR = 1.31, 95% CI = 1.01–1.70). Individual ACE items significantly associated with persistent asthma include parent/adult ever touched you sexually (aOR = 1.33, 95% CI = 1.03–1.74), adult tried to make you touch them (aOR = 1.34, 95% CI = 1.01–1.79), any adult forced you to have sex (aOR = 1.44, 95% CI = 1.04–1.20), parental separation/divorce (aOR = 1.31, 95% CI = 1.05–1.63), and household alcohol abuse (aOR = 1.24, 95% CI = 1.01–1.53). In women, experiencing one ACE and ≥ three ACEs (compared to no ACEs) was associated with 51% and 60% increased odds of persistent asthma, respectively (aOR = 1.51, 95% CI = 1.02–2.23; aOR = 1.60, 95% CI = 1.12–2.27). No significant association was observed between ACEs and asthma severity in men; however, experiencing household physical violence (compared to no household physical violence) was associated with persistent asthma in men (aOR = 1.69, 95% CI = 1.18–2.42). Conclusions: In this cross-sectional study of US adults with asthma, exposure to ACEs was associated with higher odds of asthma overall and in women. These findings highlight the importance of preventive strategies and early interventions to reduce ACEs, potentially mitigating asthma’s severity in adulthood.

The Impact of Palivizumab for Respiratory Syncytial Virus Prophylaxis on Preschool Childhood Asthma

Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (–) group). Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (–) groups. Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (–) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84–1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54–1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98–1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93–1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94–1.26, p = 0.3). Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization.

Baseline Impulse Oscillometry Metrics Differentiate Asthmatic Children From Non-Asthmatic Children Across Ethnicity/Race: A Meta-Analysis.

Identifying the asthmatic early to prevent permanent airway remodeling and the progression of the disease is desirable. In children, baseline impulse oscillometry has been found effective in identifying asthma in some studies but not others. The purpose of our study was to utilize a meta-analysis to determine whether there were significant peripheral airway differences between asthmatic and non-asthmatic children across ethnicity/race, utilizing baseline impulse oscillometry (IOS) to establish its usefulness as a diagnostic tool in this age group. This was a comprehensive search of published literature on pediatric oscillometric studies evaluating younger children (mean age ranging from 4.3 to 6 years) and older children (mean age ranging from 8.7 to 11.4 years) from the United States, Europe, Asia, and Middle East. Inclusion criteria required the primary variable resistance at 5 Hertz (R5) (kPa/L/s) or (cmH2O/L/s) for both control and asthmatic subjects, and excluded studies if asthmatics had uncontrolled disease. Our data show that there are significantly higher R5 and area of reactance (AX) and lower reactance at 5 Hertz (X5) in both younger and older asthmatic children compared to healthy controls from various countries. This meta-analysis firmly establishes that baseline oscillometry metrics, resistance and reactance, are effective in identifying the asthmatic child across age and the ethnicities/races evaluated.

Persistent Airflow Limitation Prediction and Risk Factor Analysis Among Asthmatic Children: A Retrospective Cohort Study.

A minority of asthmatic children develop persistent airflow limitation (PAL), associated with an increased risk of chronic airflow obstruction and poor prognosis. This study aimed to identify risk factors for PAL and develop a prediction model to identify high-risk asthmatic children. This retrospective study included 2072 children (5-16 years) with asthma. After a 2-year follow-up, patients were categorized into non-PAL, reversible PAL (RPAL), and irreversible PAL (IPAL) groups. Logistic regression (LR) was used to identify independent risk factors for RPAL and IPAL. A prediction model based on multivariate LR was developed and validated to identify asthmatic children at high risk of developing PAL. A nomogram was created for visualization. Among the 2072 asthmatic patients, 14.72% (n = 305) developed PAL. Asthma exacerbation history (OR 1.80, 95% CI 1.03-3.01) and poor adherence (OR 1.83, 95% CI 1.26-2.65) were independent risk factors of RPAL. Independent risk factors for IPAL were BMI over 19.0 kg/m2 (OR: 1.81, 95% CI: 1.03-3.21) and a history of pneumonia (OR: 2.40, 95% CI: 1.30-4.26). The prediction model incorporated nine variables and showed good discriminatory ability, with AUC values of 0.79 (95% CI: 0.76-0.81) for the training set, 0.76 (95% CI: 0.76-0.77) for internal validation, and 0.73 (95% CI: 0.64-0.81) for temporal validation. Asthma exacerbation history and poor adherence were independent risk factors for developing RPAL. BMI over 19.0 kg/m2 and a history of pneumonia were risk factors for IPAL. Our prediction model effectively identified asthmatic children at high risk of developing PAL.

Breastfeeding, genetic susceptibility, and the risk of asthma and allergic diseases in children and adolescents: a retrospective national population-based cohort study.

Asthma and allergic diseases (such as allergic rhinitis) are multifactorial chronic respiratory diseases, and have many common pathogenic mechanisms. This study aimed to assess the joint effects of breastfeeding and genetic susceptibility on asthma, allergic disease in children and adolescents and sought to examine whether the effect of breastfeeding was consistent under distinct levels of genetic risk. A total of 351,931 UK Biobank participants were analyzed. Firstly, Cox proportional hazards model was used to evaluate the relation between breastfeeding and asthma, allergic disease and their comorbidity. Next, we incorporated the polygenic risk score as an additional covariate into the model. Then, we explored the role of breastfeeding at each stage of asthma and allergic disease through a multi-state model. Meanwhile, several sensitivity analyses were conducted to evaluate the robustness of our results. Finally, we calculated the attributable protection and population attributable protection of breastfeeding. Breastfeeding was related to a reduced risk of occurring asthma (adjusted hazard ratio [HR] = 0.89, 95% confidence interval [CI] 0.86 ~ 0.93), allergic disease (HR = 0.89, 95%CI 0.87 ~ 0.91) and comorbidity (HR = 0.89, 95%CI 0.83 ~ 0.94). The effect of breastfeeding was almost unchanged after considering PRS and did not substantially differ across distinct genetic risk levels. Breastfeeding showed a stronger risk-decreased impact on individuals who developed from allergic rhinitis to comorbidity (HR = 0.83, 95%CI 0.73 ~ 0.93). Further, the influence of breastfeeding was robust against covariates considered and the confounding influence of adolescent smoking. Finally, due to breastfeeding, 12.0%, 13.0% or 13.0% of the exposed population would not suffer from asthma, allergic diseases and the comorbidity, while 7.1%, 7.6% or 7.6% of the general population would not suffer from these diseases. This study provided supportive evidence for the risk-reduced effect of breastfeeding on asthma, allergic diseases, and the comorbidity in children and adolescents, and further revealed that such an influence was consistent across distinct genetic risk levels.

Evaluation of the Arabic version of the Asthma Trigger Inventory among asthmatic pediatric patients in Saudi Arabia

Background Asthma Trigger Inventory (ATI) is available in English, German, and Spanish languages, however, a version in Arabic language specifically tailored for identifying asthma triggers within Saudi Arabia has been missing. Objectives To assess the reliability and validity of the adapted Arabic ATI among parents of asthmatic children in Saudi Arabia. Methods A cross-cultural adaptation of the ATI was conducted, adding seven region-specific triggers to reflect cultural and environmental factors. The Pediatric Asthma Quality of Life Questionnaire (PACQLQ) was used to assess quality of life. Construct validity of the Arabic ATI was evaluated via exploratory factor analysis (EFA), and reliability was measured with Cronbach’s alpha. Results EFA yielded a KMO of 0.634 and a significant Bartlett’s Test (χ2 = 10,005.076, p < 0.001). Six trigger subscales showed high reliability (α > 0.90), though Middle Eastern triggers had lower internal consistency (α = -0.11). Physical and psychological triggers correlated significantly with poorer quality of life (exercise: r = -0.662, p < 0.001; psychological: r = -0.307, p < 0.001). Air pollution and Middle Eastern triggers correlated positively with quality of life (r = 0.222, p < 0.001 and r = 0.245, p < 0.001). Conclusion The Arabic version of the ATI exhibited robust reliability and validity when administered to parents of asthmatic children in Saudi Arabia. Additional research is warranted to further validate its applicability across various Arabic-speaking populations.

Circulating microRNAs associated with bronchodilator response in childhood asthma

BackgroundBronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.ObjectiveThe purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation.MethodsWe used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed.ResultsWe identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.ConclusionMiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.Trial registrationLOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840].

MiR-107 and Its Association With House Dust Mite Sensitisation: Implications for Asthma.

MicroRNAs (miRNAs) have been linked to allergic diseases but their effects on sensitisation to allergens in individuals with asthma are unknown. We aimed to identify miRNAs associated with house dust mite (HDM) sensitisation in childhood asthma. Serum samples from 1126 children with asthma who participated in the Genetics of Asthma in Costa Rica Study (GACRS) were profiled for 304 miRNAs. We first divided according to HDM sensitisation and then tested whether miRNAs were differentially expressed (DE) between the two groups. Gene enrichment analysis for target genes of the DE miRNAs was then performed to identify potential causal pathways. Replication analysis was performed in the Childhood Asthma Management Program (CAMP), in which expression data of 258 miRNAs in 491 children were available. A mediation analysis was conducted to discern relationships between miRNA and phenotype differences according to HDM sensitisation in GACRS cohort. There were 906 (80.5%) and 220 (19.5%) subjects in the GACRS HDM+ and HDM- groups. Compared with HDM- participants, those in the HDM+ group were more likely to be severe in variables including pulmonary function, oral corticosteroid use and blood tests. A total of 17 miRNAs were DE (p < 0.05) between the two groups, with miR-642a-3p, let-7c-5p and miR-107 most significantly associated with HDM sensitisation. In CAMP, there were 39 DE miRNAs, and increased expression of miR-107 in HDM+ children was replicated in this cohort. In both GACRS and CAMP, the cadherin-binding pathway was enriched in an analysis of target genes for DE miRNA. In a mediation analysis, miR-107 showed significant indirect effects on eosinophil count and total IgE that were mediated by HDM sensitisation. In children with asthma, miR-107 is associated with HDM sensitisation. Furthermore, miR-107 was indirectly associated with total IgE and eosinophil count through HDM sensitisation.

A systematic review and meta-analysis exploring the bidirectional association between asthma and gastroesophageal reflux disease in children

Background: Asthma is the most prevalent chronic respiratory disease in children, and gastroesophageal reflux disease (GERD) is one of its extraesophageal complications of asthma. Both conditions are commonly observed in pediatric outpatient clinics, but the causality between them in children is still debated. Therefore, we conducted a systematic review and meta-analysis to evaluate the bidirectional association between asthma and GERD in children. Methods: We systematically reviewed original studies published from January 2000 to February 2024 by searching the data bases. We also performed manual retrieval and screening to identify studies that met the inclusion criteria. The quality of the final included studies was evaluated by using the Newcastle‐Ottawa Scale, and outcome measures were extracted. Results: We identified nine eligible studies, which included 304,399 children of different ages from seven countries. Overall, the risk of developing GERD in children with asthma (odds ratio [OR] 2.16 [95% confidence interval [CI], 1.6‐2.91) was higher than the risk of developing asthma in children with GERD (OR 1.55 [95% CI, 1.32‐1.82]). Conclusion: Based on the available studies, it can be concluded that asthma and GERD are mutually aggravating factors in children, presenting a bidirectional association. However, the risk of developing GERD in children with asthma is higher to some extent. More large-scale and high-quality prospective cohort studies are needed in the future to provide richer evidence and more research opportunities.

Associations between VOCs and childhood asthma in Shanghai, China: impacts of daily behaviors

Exposure to volatile organic compounds (VOCs) detected in indoor environments may have negative impacts on childhood health. However, the associations between indoor VOCs and childhood asthma, considering daily behaviors, have rarely been conducted. Based on the case-control study with field measurement, we collected air samples from 358 children’s bedrooms. Concentrations of VOCs in air samples were measured by chemical treatment and gas chromatography-mass spectrometer. Logistic regression models were applied to investigate the associations between VOCs with childhood asthma. Meanwhile, stratification analysis was performed to reveal the influences of daily behaviors (window opening during night, using household chemical products, and bedroom cleaning) on the target associations. A new assessment indicator considering multiple VOCs was proposed to investigate the combined effects of multiple VOCs on childhood asthma. High concentrations of toluene (the highest adjusted odds ratio (AOR) was 2.59), o-xylene (AOR: 2.01), xylene (2.24), dodecane (the highest AOR was 2.57), pentadecane (2.82), hexadecane (2.04), α-pinene (1.99), total volatile organic compounds (TVOC) (the highest AOR was 2.94), and the new indicator of aromatics (the highest AOR was 2.59) were significantly associated with childhood asthma. The daily behaviors of the residents can significantly affect the target associations, with the window opening during night having the most significant effect, followed by bedroom cleaning and using household chemical products. Families with lifetime asthmatic children may have specific avoidance behaviors for the potential environmental factors on children’s health. These behaviors could explain that VOCs exposure had significant associations with the decreased odds of childhood asthma.

Windows of susceptibility and joint effects of prenatal and postnatal ambient air pollution and temperature exposure on asthma and wheeze in Mexican children

IntroductionPrenatal and early-life exposure to air pollution and extreme temperatures are associated with childhood asthma and wheeze. However, potential windows of susceptibility and their sex-specific and interactive effects have not been fully elucidated. We aimed to identify critical windows of susceptibility and evaluate sex-specific effects in these associations, and evaluate exposure interactions. MethodsWe analyzed data from 468 mother–child pairs enrolled in the PROGRESS birth cohort in Mexico City. Daily residential levels of PM2.5, NO2, and temperature were generated from our validated spatiotemporally resolved models from conception to age 4 years. Childhood asthma and wheeze outcomes were collected at 4–6 and 7–8 years. Distributed lag nonlinear models (DLNMs) were used to identify susceptible windows for prenatal weekly-specific and postnatal monthly-specific associations of air pollution and temperature with respiratory outcomes adjusting for covariates. To evaluate sex-specific effects, DLNMs were stratified. Joint effects were assessed using relative excess risk due to interaction and attributable proportion. ResultsMid-gestation was a critical window for both PM2.5 (weeks 20–28, cumulative OR: 1.18 [95% CI: 1.01, 1.37]; weeks 19–26, cumulative OR: 1.18 [95% CI: 1.02, 1.36]) and NO2 (weeks 18–25, cumulative OR: 1.16 [95% CI: 1.02, 1.31]) exposure, associated with higher odds of wheeze. Postnatal exposure to PM2.5 and NO2 during the first year of life was also linked to higher odds of wheeze. The warmer and colder temperatures showed mixed effects on respiratory outcomes. We observed a synergistic interaction between high PM2.5 and high temperature exposure during the first year of life, associated with higher odds of current wheeze. The associations of prenatal air pollution and temperature exposure with respiratory outcomes were more pronounced in males. ConclusionsEarly-life air pollution exposure contributes to the development of childhood asthma and wheeze, while exposure to temperature showed mixed associations with respiratory outcomes.

Investigating the causal association between heme oxygenase-1 and asthma: A bidirectional two-sample Mendelian randomization analysis in a European population

BackgroundThe association between heme oxygenase-1 (HO-1) and asthma has been a subject of debate in both observational and experimental studies. We aimed to evaluate the potential causal relationship between HO-1 and asthma. Materials and methodsA bidirectional two-sample Mendelian randomization (TSMR) study was conducted to examine the causal relationship between HO-1 and asthma. In the forward Mendelian randomization (MR) analyses, HO-1 was considered as the exposure, while asthma as the outcome. Conversely, in the reverse MR analyses, asthma was regarded as the exposure, and HO-1 as the outcome. Data for HO-1 and asthma were obtained from publicly accessible genome-wide association studies (GWAS). These causal relationships were identified through 5 MR methods, namely MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode. Additionally, sensitivity tests were conducted to assess the robustness of MR study. Finally, additional asthma datasets and childhood asthma were selected to validate the findings. ResultsIn the forward MR analyses, according to the IVW method, genetically predicted HO-1 displays a negative correlation with the risk of asthma (OR 0.947, 95% CI 0.905–0.990). It was not found any SNP overly sensitive or disproportionately responsible for the outcome. No evidence of heterogeneity and pleiotropy between SNPs was observed. Genetically predicted asthma was not associated with HO-1 in reverse MR analyses using the IVW method. The same results were validated in additional asthma datasets and in childhood asthma. ConclusionThe results of MR analysis revealed heme oxygenase-1 as a protective factor for asthma.

Stigmas of dysembryogenesis of undifferentiated connective tissue dysplasia in bronchial asthma

Connective tissue dysplasia is a disturbance of its development during embryogenesis and the postnatal period due to genetically altered fibrillogenesis of the extracellular matrix. Undifferentiated connective tissue dysplasia (UCTD) includes a set of phenotypic characteristics that do not fit into any already known dysplastic syndrome or phenotype. It is this pathology of connective tissue that is widespread and is constantly encountered in the practice of doctors of various profiles, serving as the basis for the formation of various chronic diseases. As for bronchial asthma (BA), it is quite natural that studies have appeared to identify the characteristics of the course of BA with connective tissue dysplasia, primarily in children. It has been shown that asthma in children associated with connective tissue dysplasia has a number of clinical features: an earlier onset of the disease, a higher incidence of concomitant diseases, and a more severe course. The features of the course of bronchial asthma associated with connective tissue dysplasia in adults have been practically not studied. Our very first results from a study of adult patients with BA showed that in patients with a mild course of the disease, up to 3 stigmas of disembryogenesis were recorded, in patients with a moderate course - from 2 to 4, and in patients with a severe course - from 1 to 8 stigmas. Correlation analysis (the data was obtained on a small material, therefore we do not consider it statistically significant) provides a distinct basis for continuing the study. Thus, negative correlations have been identified between the presence of stigmas (myopia, dolichostenomelia, joint hypermobility, wide atrophic scars, varicose veins) and such an important characteristic of the disease as its controllability.

Clinical Significance of Combined Detection of CCL22 and IL-1 as Potential New Bronchial Inflammatory Mediators in Children's Asthma.

Severe asthma is a significant health burden because children with severe asthma are vulnerable to medication-related side effects, life-threatening deterioration, and impaired quality of life. However, there is a lack of data to elucidate the role of inflammatory variables in asthma. This study aimed to compare the levels of inflammatory factors in serum and sputum in children with acute and stable asthma to those in healthy children and the ability to predict clinical response to azithromycin therapy. This study recruited 95 individuals aged 1-3 years old and collected data from January 2018 to 2020. We examined serum and sputum inflammatory factors and constructed the least absolute shrinkage and selection operator (LASSO) model. Predictive models were constructed through multifactor logistic regression and presented in the form of column-line plots. The performance of the column-line diagrams was measured by subject work characteristics (ROC) curves, calibration plots, and decision curve analysis (DCA). Then, filter-paper samples were collected from 45 children with acute asthma who were randomly assigned to receive either azithromycin (10 mg/kg, n = 22) or placebo (n = 23). Pretreatment levels of immune mediators were then analyzed and compared with clinical response to azithromycin therapy. Of the 95 eligible participants, 21 (22.11%) were healthy controls, 29 (30.53%) had stable asthma, and 45 (47.37%) had acute asthma. The levels of interferon-γ (IFN-γ), tumor necrosis factor-a (TNF-α), chemokine CCL22 (CCL22), interleukin 12 (IL-12), chemokine CCL4 (CCL4), chemokine CCL2 (CCL2), and chemokine CCL13 (CCL13）were significantly higher in the acute asthma group than in the stable asthma group. A logistic regression analysis was performed using CCL22 and IL-1 as independent variables. Additionally, IFN-γ, TNF-α, IL-1, IL-13, and CCL22 were identified in the LASSO model. Finally, we found that CCL22 and IL-1 were more responsive in predicting the response to azithromycin treatment. Our results show that CCL22 and IL-1 are both representative markers during asthma symptom exacerbations and an immune mediator that can predict response to azithromycin therapy.

Outpatient inhaled corticosteroid use in bronchopulmonary dysplasia.

In the outpatient setting, inhaled corticosteroids (ICS) are frequently given to children with bronchopulmonary dysplasia (BPD) for treatment of respiratory and asthma-associated symptoms. In this study we sought to determine if correlations existed between ICS use and ICS initiation and patient characteristics and outpatient respiratory outcomes. This study included children with the diagnosis of BPD (n = 661) who were seen in outpatient pulmonary clinics at the Children's Hospital of Philadelphia between 2016 and 2021. Chart review was used to determine patient demographics, use and timing of ICS initiation, asthma diagnosis, and acute care usage following initial hospital discharge. At the first pulmonary visit, 9.2% of children had been prescribed an ICS at NICU discharge, 13.9% had been prescribed an ICS after NICU discharge but before their first pulmonary appointment, and 6.9% were prescribed an ICS at the completion of initial pulmonary visit. Children started on an ICS as outpatientshad a higher likelihood of ER visits (adjusted odds ratio: 2.68 ± 0.7), hospitalizations (4.81 ± 1.16), and a diagnosis of asthma (3.58 ± 0.84), compared to children never on an ICS. Of those diagnosed with asthma, children prescribed an ICS in the outpatient setting received the diagnosis at an earlier age. No associations between NICU BPD severity scores and ICS use were found. This study identifies an outpatient BPD phenotype associated with ICS use and ICS initiation independent of NICU severity score. Additionally, outpatient ICS initiation correlates with a subsequent diagnosis of asthma and acute care usage in children with BPD.

Bayesian additive regression trees for predicting childhood asthma in the CHILD cohort study

BackgroundAsthma is a heterogeneous disease that affects millions of children and adults. There is a lack of objective gold standard diagnosis that spans the ages; instead, diagnoses are made by clinician assessment based on a cluster of signs, symptoms and objective tests dependent on age. Yet, there is a clear morbidity associated with chronic asthma symptoms. Machine learning has become a popular tool to improve asthma diagnosis and classification. There is a paucity of literature on the use of Bayesian machine learning algorithms to predict asthma diagnosis in children. This paper develops a prediction model using the Bayesian additive regression trees (BART) and compares its performance to various machine learning algorithms in predicting the diagnosis of childhood asthma.MethodsClinically relevant variables collected at or before 3 years of age from 2794 participants in the CHILD Cohort Study were used to predict physician-diagnosed asthma at age 5. BART and six other commonly used machine learning algorithms, namely adaptive boosting, logistic regression, decision tree, neural network, random forest, and support vector machine were trained. Measures of performance including sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve were calculated. The confidence intervals were calculated using Bootstrapping samples. Important predictors and interaction effects associated with asthma were also identified using BART.ResultsBART, logistic regression and random forest showed the highest area under the ROC curve compared to other machine learning algorithms. Based on BART, recurrent wheeze, respiratory infection and food sensitization at 3 years of age were the most important predictors. The three most important interaction effects were found to be interaction terms of respiratory infection at 3 years and recurrent wheezing at 3 years, maternal asthma and paternal asthma, and maternal wheezing and inhalant sensitization of child at 3 years.ConclusionsBART demonstrated promising prediction performance when compared to other machine learning algorithms. Future research could validate the BART in an external cohort to evaluate its reliability and generalizability.