Pediatric Asthma Research Articles

Diagnosing new-onset asthma in a paediatric clinical trial setting in school-age children.

Asthma is a common chronic disease in children. It is a dynamic condition-symptoms change over time, and the outcome of diagnostic tests can vary. Consequently, evaluating the onset of asthma at a single point in time, perhaps when patients are asymptomatic with limited impairment of the lung function, may result in false diagnostic conclusions. The absence of consistent gold-standard diagnostic criteria in children challenges the ability of any study to ascertain an effect of treatment on asthma prevention. A comprehensive review of the diagnostic criteria used for new-onset asthma in school-age children was conducted based on existing recommendations from published clinical guidance, alongside evidence from paediatric asthma prevention trials. Findings from the review were used to propose suggestions for diagnosing new-onset asthma in future asthma prevention trials. Despite an overall lack of consensus in the published clinical guidance, there are similarities between the various recommendations for diagnosing asthma in children, which typically involve assessing the variable symptoms and supplementing the medical history with objective measures of lung function. For future paediatric asthma prevention trials, we suggest that paediatric clinical trials should use a new-onset asthma definition that incorporates the concepts of "possible", "probable" and "confirmed" asthma. "Possible" asthma would capture self-reported features of chronic symptoms and symptom relief with β2-agonist bronchodilator (suggesting reversibility). "Probable" asthma would include symptom chronicity, self-reported symptom relief with β2-agonist bronchodilator, and objective features of asthma (reversibility or bronchial hyper-responsiveness). A "confirmed" diagnosis would be made only if there is a positive response to controller therapy. These suggestions aim to improve the diagnosis of new-onset childhood asthma in clinical trials, which will be useful in the design and conduct of future paediatric asthma prevention trials.

Clinical efficacy and safety study of Loratadine combined with glucocorticoid nasal spray in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis

Objective To investigate the clinical efficacy and safety of Loratadine combined with Glucocorticoid nasal spray in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. Methods A total of 100 pediatric patients with moderate to severe bronchial asthma and seasonal allergic rhinitis admitted to our hospital between January 2020 and January 2023 were included in this study. All patients met the complete inclusion and exclusion criteria. Based on different treatment interventions, they were divided into the control group (n = 50) and the observation group (n = 50). Patients in the control group received treatment with glucocorticoid nasal spray, while patients in the observation group received combined intervention with Loratadine in addition to the treatment received by the control group. The clinical treatment outcomes, incidence of adverse reactions, as well as the scores of nasal symptoms, asthma control, and peak expiratory flow rates at different treatment time points (baseline, T1: 30 days after treatment, T2: 60 days after treatment, T3: 90 days after treatment) were compared between the two groups. The combined treatment of Loratadine with Glucocorticoid nasal spray demonstrates significant clinical efficacy in the treatment of pediatric bronchial asthma with seasonal allergic rhinitis. It further promotes the recovery of peak expiratory flow rates, improves symptoms of rhinitis and asthma in pediatric patients. Importantly, the application of this combined treatment does not increase the risk of adverse reactions in pediatric patients, indicating its high safety profile. This treatment approach is worthy of clinical application and further promotion.

Combining Federated Machine Learning and Qualitative Methods to Investigate Novel Pediatric Asthma Subtypes: Protocol for a Mixed Methods Study.

Pediatric asthma is a heterogeneous disease; however, current characterizations of its subtypes are limited. Machine learning (ML) methods are well-suited for identifying subtypes. In particular, deep neural networks can learn patient representations by leveraging longitudinal information captured in electronic health records (EHRs) while considering future outcomes. However, the traditional approach for subtype analysis requires large amounts of EHR data, which may contain protected health information causing potential concerns regarding patient privacy. Federated learning is the key technology to address privacy concerns while preserving the accuracy and performance of ML algorithms. Federated learning could enable multisite development and implementation of ML algorithms to facilitate the translation of artificial intelligence into clinical practice. The aim of this study is to develop a research protocol for implementation of federated ML across a large clinical research network to identify and discover pediatric asthma subtypes and their progression over time. This mixed methods study uses data and clinicians from the OneFlorida+ clinical research network, which is a large regional network covering linked and longitudinal patient-level real-world data (RWD) of over 20 million patients from Florida, Georgia, and Alabama in the United States. To characterize the subtypes, we will use OneFlorida+ data from 2011 to 2023 and develop a research-grade pediatric asthma computable phenotype and clinical natural language processing pipeline to identify pediatric patients with asthma aged 2-18 years. We will then apply federated learning to characterize pediatric asthma subtypes and their temporal progression. Using the Promoting Action on Research Implementation in Health Services framework, we will conduct focus groups with practicing pediatric asthma clinicians within the OneFlorida+ network to investigate the clinical utility of the subtypes. With a user-centered design, we will create prototypes to visualize the subtypes in the EHR to best assist with the clinical management of children with asthma. OneFlorida+ data from 2011 to 2023 have been collected for 411,628 patients aged 2-18 years along with 11,156,148 clinical notes. We expect to complete the computable phenotyping within the first year of the project, followed by subtyping during the second and third years, and then will perform the focus groups and establish the user-centered design in the fourth and fifth years of the project. Pediatric asthma subtypes incorporating RWD from diverse populations could improve patient outcomes by moving the field closer to precision pediatric asthma care. Our privacy-preserving federated learning methodology and qualitative implementation work will address several challenges of applying ML to large, multicenter RWD data. DERR1-10.2196/57981.

Enhancing pediatric asthma management through multifaceted health education.

Pediatric asthma is a significant public health issue that impacts the quality of life of children globally. Traditional management approaches focus on symptom control and medication adherence but often overlook the comprehensive educational needs of patients and their families. A multifaceted health education approach may offer a more holistic strategy in managing pediatric asthma, especially in outpatient settings. To evaluate the efficacy of a comprehensive health education strategy in improving disease management, medication adherence, and quality of life among children with asthma in outpatient settings. In total, 100 pediatric patients with severe asthma were enrolled from January 2021 to November 2022 and randomly allocated to a control group (n = 50) or an observation group (n = 50). The control group received standard nursing care, including basic nursing interventions and health education upon admission. In contrast, the observation group was exposed to a broad spectrum of health education methodologies, including internet-based hospital systems, social media channels, one-on-one verbal education, informational brochures, slide presentations, telephone check-ins, animated videos, and illustrated health education manuals. Data on asthma management knowledge, symptom control, quality of life [St. George's Respiratory Questionnaire (SGRQ)], treatment adherence, and nursing satisfaction were collected and analyzed. The scores of the observation group in knowledge areas, such as medication, home care, disease understanding, symptom management, prevention strategies, and nutritional guidance, were significantly higher than those of the control group (P < 0.05). In addition, the observation group exhibited greater symptom control, improved quality of life based on their SGRQ scores, and higher treatment adherence post-intervention (P < 0.05). Nursing satisfaction was also rated higher in the observation group across all evaluated areas (P < 0.05). Implementing a diversified health education approach in pediatric asthma management significantly enhances disease understanding, symptom management, and treatment adherence, leading to improved quality of life for affected children. These findings underscore the importance of multifaceted clinical health education in augmenting disease awareness and facilitating continuous improvements in asthma control rates, highlighting the potential benefits of incorporating comprehensive educational strategies into pediatric asthma care protocols.

Association between dietary carotenoid intakes and the risk of asthma in children and adolescents: evidence from the National Health and Nutrition Examination Survey 2007-2016.

In recent years, the incidence of asthma in children has been increasing. As a chronic disease, in addition to drug treatment, dietary management is also important. However, studies of carotenoids and asthma have shown mixed results. This study aimed to evaluate whether the relationship between carotenoid intake and current asthma holds significant importance. We studied 9,118 children aged 6-16 years in the National Health and Nutrition Examination Survey (NHANES) of US from 2007 to 2016, and the relationship of dietary carotenoid and its subgroup with pediatric asthma. Current asthma was assessed by parent-reported, doctor-diagnosed, asthma using a standardized questionnaire. We used multivariate logistic regression to calculate the odds ratio (OR) for current asthma with a 95% confidence interval (CI). Total carotenoid intake was not associated with the risk of current asthma. Compared with the first quantile, the second quantile of β-cryptoxanthin intake was positively correlated with current asthma (Q2: 1.227; 95% CI: 1.025-1.470; P=0.03). The test of trend showed that, as the α-carotene intake increased, the risk of current asthma showed a decreasing trend, which was very close to the statistic confidence cutoff (Model I: P for trend =0.001; Model II: P for trend =0.003; Model III: P for trend =0.08). In subgroup analysis, family history of asthma interacted with carotenoid intake (P=0.005). The population without a family history of asthma, there were significant negative associations between carotenoid intakes and asthma (quartile 4: Model III: 0.720; 95% CI: 0.549-0.943; P=0.02). In this study, pediatric current asthma was not related to total carotenoids in our total participants. Total dietary carotenoid intake has a protective effect on children without a family history of asthma. Meanwhile, β-cryptoxanthin intake is positively correlated with asthma.

Assessing environmental injustice in Kansas City by linking paediatric asthma to local sources of pollution: a cross-sectional study

ObjectiveA grassroots environmental-justice organisation in Kansas City has been examining the disproportionate exposure to air pollution experienced by residents living fenceline to the largest classification railyard in the USA. Prior...

The importance of environmental influences on pediatric asthma initiation and prevention

The importance of environmental influences on pediatric asthma initiation and prevention

Frequency of Severe Asthma and Its Clinical Phenotypes at the Asthma Clinic in One of the Largest Sudanese Tertiary Pediatric Hospitals: A Cross-Sectional Hospital-Outpatient-Based Study.

Asthma is one of the most common non-communicable diseases. Childhood asthma has been increasing in Sudan, with a 13-16% prevalence among Khartoum school children. To achieve and maintain good asthma control, proper diagnosis, assessment of severity, and appropriate medication administration are crucial, with phenotyping being a key factor in determining patients' specific treatment. To study the frequency of severe asthma and the distribution of its different phenotypes and to investigate associations between age and gender and different phenotypes of asthma. This descriptive cross-sectional hospital-based study was conducted in the Asthma Clinic of Mohamed Al-Amin Hamid Pediatrics Hospital. It included 229 patients who were presented to the clinic from September 2021 to April 2022. Data were collected from the patients and/or their caregivers using a modified validated standard questionnaire and were analyzed using SPSS version 26.0. A p-value of 0.05 or less was considered statistically significant. In this study of 229 participants, 14.4% had severe asthma, with 44.5% and 41% exhibiting mild and moderate asthma, respectively. Most were effectively managed in steps 2 or 3. The cohort, primarily aged 5 or younger (40.2%) with a male majority (62%), showed a mean diagnosis age of 2.9 ± 2.8 years. Impressively, 90% maintained well-controlled asthma. Within severe asthma cases (87% atopic), 39.4% represented a severe allergic asthma phenotype. Elevated eosinophil counts were noted in 45.5% (serum) and 78.8% (sputum cytology), while 57.6% had normal serum IgE levels. The predominant symptom pattern in severe asthma was episodic multi-trigger wheezing (48.5%). Age and gender displayed no significant association with severe asthma phenotype. This study reveals a concerning rise in childhood asthma prevalence in Sudan, emphasizing the importance of tailored treatment strategies. Severe asthma, characterized by atopic eosinophilic involvement, necessitates targeted interventions in pediatric asthma care for specific phenotypes.

Effects of Family-Supported Healthcare on Children with Asthma.

Healthcare is essential for asthma control, however, whether family-supported healthcare improves therapeutic effects in childhood asthma remains unclear. The enrolled patients were randomly divided into control and intervention groups. The pulmonary function was evaluated by forced expiratory volume in 1 s as a percentage of forced vital capacity (FEV1/FVC) and fractional exhaled nitric oxide (FeNO). Asthma control and life quality were assessed via a childhood asthma control test and pediatric asthma quality of life questionnaire. Inflammatory cytokines interleukin-6 (IL-6) and interleukin-17 (IL-17) were determined by enzyme-linked immunosorbent assay. No significant differences existed in the basic characteristics of asthma children and their parents among two groups. The increase of FEV1/FVC was higher in the intervention group versus the control group (76.47 ± 10.76% vs 69.76 ± 8.88%, p = 0.001 at the time of post-intervention), and the decrease of FeNO was greater in the intervention group (30.43 ± 6.85 bbp vs 35.64 ± 6.62 bbp, p = 0.003 at the time of post-intervention). Family-supported healthcare highly improved asthma control and quality of life in childhood asthma post-treatment. Meanwhile, the inflammatory cytokines IL-17 (118.14 ± 25.79 pg/mL in intervention group vs 142.86 ± 28.68 pg/mL in control group, p = 0.004 at the time of post-intervention) and IL-6 (103.76 ± 23.11 pg/mL in intervention group vs 119.73 ± 22.68 pg/mL in control group, p = 0.009 at the time of post-intervention) significantly decreased by family-supported healthcare intervention. Importantly, acute exacerbation (80.8% in intervention group vs 95.7% in control group, p = 0.030) and rehospitalization cases (88.5% in intervention group vs 100% in control group, p = 0.028) also decreased by family-supported healthcare intervention. Family-supported healthcare improves pulmonary function and quality of life while alleviates inflammation, acute exacerbation, and rehospitalization in childhood asthma post-routine treatment.

Asthma prevention and recent advances in management

Asthma is the most frequent chronic disease of childhood, affecting up to 20 % of children worldwide. The authors present the current literature focusing on primary and secondary prevention of both early and late childhood asthma and the recent advances in management. The therapeutic tools for pediatric asthma have expanded significantly for both the non-severe and severe forms. The use of anti-inflammatory treatment, even for the mildest cases, and the withdrawal of symptomatic bronchodilation as monotherapy have been included in the most recent guidelines. The different biological therapies have revolutionized the therapeutical approach for severe uncontrolled asthma in children and adolescents.The main guidelines on asthma maintenance therapy in pediatrics suggest different approaches and describe different stages of asthma to determine the most appropriate treatment.

Pediatric asthma and eosinophilia: insights from nasal and blood smear analyses

Pediatric asthma and eosinophilia: insights from nasal and blood smear analyses

Addressing critical barriers for sustainability of asthma stock inhaler policy implementation and resultant programming

BackgroundAsthma is a prevalent health concern among Illinois (IL) children, and management is significantly influenced by social determinants. There were 17 states who have adopted stock inhaler laws, but implementation varies widely. ObjectiveTo assess critical barriers to implementation and address sustainability of stock inhaler programming in school-based asthma care in IL. MethodsSemistructured interviews were conducted with high asthma burden school districts in IL to assess barriers in implementing stock inhaler policies and resultant programming. Thematic analysis was performed using Atlas.ti (Scientific Software Development GmbH, Berlin, Germany) to identify and code “threats” to future sustainability. Data were synthesized and presented to stakeholders for barrier mitigation. A schematic flowchart outlining steps to support sustainability was created. ResultsA total of 18 interviews were conducted with key community partners across 8 IL school districts, representing rural, urban, and suburban areas. Analysis revealed 25 barriers, with several identified as “threats” to future sustainability, including liability concerns, follow-up care assurance, funding/resources, pharmacy dispensing practices, district-level readiness to change, and nurse staffing. Stakeholders formed a statewide coalition to address these barriers, increase awareness, plan evaluations, and advise on state funding allocation. A national stock inhaler toolkit tailored to school administrative needs was developed to support sustainability efforts. ConclusionStrategic stakeholder and community engagement are vital for establishing and sustaining stock inhaler programs that adhere to policy mandates. Many districts face challenges initiating and maintaining such programs without critical barrier mitigation and support. Collaborative solutions are necessary to ensure effective school-based asthma management and mitigate persistent pediatric asthma health disparities.

Once-daily fluticasone furoate/vilanterol vs once-daily fluticasone furoate in patients with asthma aged 5 to 17 years

BackgroundLimited data exist comparing inhaled corticosteroid (ICS) plus adjunctive therapy vs ICS alone in pediatric asthma patients. ObjectiveTo evaluate the efficacy and safety of fluticasone furoate/vilanterol (FF/VI) vs FF in children and adolescents with asthma. MethodsThis phase 3, randomized, double-blind, multicenter study (NCT03248128) included participants aged 5 to 17 years with six months or more asthma history uncontrolled on ICS monotherapy. Participants received 4-week open-label fluticasone propionate (100 µg) twice daily before 1:1 randomization to 24-week double-blind FF (50 µg:100 µg) or FF/VI (50/25 µg:100/25 µg) once daily. Two populations with different primary endpoints were analyzed to meet United States (week 12 weighted mean forced expiratory volume in 1 second [FEV1; 0-4 hours]; participants aged 5–17 years) and European (change from baseline predose morning peak expiratory flow [ΔAM PEF] averaged over weeks 1-12; participants aged 5-11 years) regulatory requirements. ResultsOverall, 902 participants, including 673 children aged 5 to 11 years, were randomized and treated. In participants aged 5 to 17, week 12 weighted mean FEV1 (0-4 hours) was greater with FF/VI vs FF (difference: 0.083 L; P < .001). In participants aged 5 to 11, ΔAM PEF over weeks 1 to 12 showed numerical improvement with FF/VI vs FF but was not statistically significant (difference: 3.2 L/min; P = .228). No drug-related serious adverse events or deaths were reported. ConclusionFF/VI significantly improved weighted mean FEV1 (0-4 hours; participants aged 5-17 years), but not ΔAM PEF (participants aged 5-11 years) vs FF. No new safety concerns were apparent. Trial RegistrationClinicalTrials.gov Identifier: NCT03248128.

Patterns and drivers of disparities in pediatric asthma outcomes among Medicaid-enrolled children living in subsidized housing in NYC

ObjectiveThere are persistent disparities in pediatric asthma morbidity in the U.S. We linked claims data with information on neighborhood-level risk factors to explore drivers of asthma disparities among Medicaid-enrolled children in New York City subsidized housing. MethodsWe constructed a cohort of Medicaid-enrolled children living in public or other subsidized housing, based on residential address, in NYC between 2016 and 2019 (n = 108,969). We examined claims-derived asthma prevalence across age and racial and ethnic groups, integrating census tract-level information and using the Bayesian Improved Surname Geocoding (BISG) algorithm to address high rates of missing data in self-reported race and ethnicity. We used inverse probability weighting (IPW) to explore the extent to which disparities persisted when exposure to asthma risk factors – related to the built environment, neighborhood poverty, and air quality – were balanced across groups. This analysis was conducted in 2022–2023. ResultsClaims-derived asthma prevalence was highest among children <7 years at baseline and among non-Hispanic Black and Hispanic children. For example, among children aged 3–6 years at baseline, claims-derived prevalence was 17.3% and 18.1% among non-Hispanic Black and Hispanic children, respectively, compared to 9.3% and 9.0% among non-Hispanic White and non-Hispanic Asian American/Pacific Islander children. Using IPW to balance exposure to asthma risk factors across racial and ethnic groups attenuated, but did not eliminate, disparities in asthma prevalence. ConclusionsWe found high asthma burden among children living in subsidized housing. Modifiable place-based characteristics may be important contributors to pediatric asthma disparities.

Chapter 3 Epidemiology and risk factors for pediatric asthma and those managements

Chapter 3 Epidemiology and risk factors for pediatric asthma and those managements

Impact of CYP3A5 Polymorphisms on Pediatric Asthma Outcomes.

Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2-18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes. A subset of patients provided saliva samples for SNP analysis and participated in a pharmacokinetic study. Multivariable regression analysis adjusted for age, sex, race, and ethnicity was used to evaluate the impact of CYP3A5 SNPs on asthma outcomes, including asthma control (measured using the asthma symptom tracker, a modified version of the asthma control test or ACT), exacerbations, and hospital admissions. Plasma corticosteroid and cortisol concentrations post-ICS dosing were also assayed using liquid chromatography-tandem mass spectrometry. Of the 751 patients using the e-AT, 166 (22.1%) provided saliva samples and 16 completed the PK study. The e-AT cohort was 65.1% male, and 89.6% White, 6.0% Native Hawaiian, 1.2% Black, 1.2% Native American, 1.8% of unknown race, and 15.7% Hispanic/Latino; the median age was 8.35 (IQR: 5.51-11.3) years. CYP3A5*3/*3 frequency was 75.8% in White subjects, 50% in Native Hawaiians and 76.9% in Hispanic/Latino subjects. Compared with CYP3A5*3/*3, the CYP3A5*1/*x genotype was associated with reduced weekly asthma control (OR: 0.98; 95% CI: 0.97-0.98; p < 0.001), increased exacerbations (OR: 6.43; 95% CI: 4.56-9.07; p < 0.001), and increased asthma hospitalizations (OR: 1.66; 95% CI: 1.43-1.93; p < 0.001); analysis of 3/*3, *1/*1 and *1/*3 separately showed an allelic copy effect. Finally, PK analysis post-ICS dosing suggested muted changes in cortisol concentrations for patients with the CYP3A5*3/*3 genotype, as opposed to an effect on ICS PK. Detection of CYP3A5*3/3, CYPA35*1/*3, and CYP3A5*1/*1 could impact inhaled steroid treatment strategies for asthma in the future.

Asthma Care from Home: Study protocol for an effectiveness-implementation evaluation of a virtually enabled asthma care initiative in children in rural NSW.

Asthma is the leading source of unscheduled hospitalisation in Australian children, with a high burden placed upon children, their parents/families, and the healthcare system. In Australia, there are widening disparities in paediatric asthma care including inequitable access to comprehensive ongoing and planned asthma care for children. The Asthma Care from Home Project is a comprehensive virtually enabled asthma model of care that aims to a. supports families, communities and healthcare providers, b. flexible and locally acceptable, and c. allow for adoption of innovations such as digital technologies so that asthma care can be provided "from home", reduce potentially preventable asthma hospitalisation, and ensure satisfaction at a patient, family, and healthcare provider level. The model of care includes standardisation of discharge care through provision of an asthma discharge resource pack containing individual asthma action plan, follow-up letters for the child's general practitioner (GP) and school/child care, and access to online asthma educational sessions and resource; post-discharge care coordination through text message reminders for families for regular GP review, email correspondence with their child's GP and school/childcare; and virtual home visits to discuss home environmental triggers, provide personalised asthma education and respond to parental concerns relating to their child's asthma. This study is comprised of three components: 1) a quasi-experimental pre/post impact evaluation assessing the impact of the model on healthcare utilisation and asthma control measures; 2) a mixed-methods implementation evaluation to understand how and why our intervention was effective or ineffective in producing systems change; 3) an economic evaluation to assess the cost-effectiveness of the proposed model of care from a family and health services perspective. This study aims to improve access to asthma care for children in rural and remote areas. Implementation evaluation and economic evaluation will provide insights into the sustainability and scalability of the asthma model of care.

Causal associations between pediatric asthma and united airways disease: a two-sample Mendelian randomization analysis.

Prior observational research has indicated a potential link between pediatric asthma and united airways disease (UAD). However, these findings could be subject to confounding factors and reverse causation. Therefore, our study utilizes Mendelian randomization (MR) method to further investigate the causal relationship between pediatric asthma and UAD. We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the association between pediatric asthma and seven groups of UAD, including chronic sinusitis, chronic rhinitis, nasopharyngitis and pharyngitis, chronic diseases of tonsils and adenoids, chronic laryngitis and laryngotracheitis, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD). The present study employed a range of methods for two-sample MR analysis, including inverse variance weighted (IVW), MR-Egger regression, Simple mode, weighted median, and weighted models. The conclusion of the MR analysis primarily relies on the IVW results, while other analytical methods are utilized as supplementary evidence to ensure result robustness in this MR analysis. And sensitivity analyses were conducted, including heterogeneity test, horizontal pleiotropy test, MR-PRESSO test, and leave-one-out analysis to validate the results. The results of the MR analysis indicate significant causal effects of pediatric asthma on chronic rhinitis, nasopharyngitis and pharyngitis (IVW: OR = 1.15, 95%CI: 1.05-1.26, p-value = 0.003), chronic diseases of tonsils and adenoids (IVW: OR = 1.07, 95%CI: 1.00-1.15, p-value = 0.038), chronic bronchitis (IVW: OR = 1.51, 95%CI: 1.42-1.62, p-value <0.001), bronchiectasis (IVW: OR = 1.51, 95%CI: (1.30-1.75), p-value <0.001), and COPD (IVW: OR = 1.43, 95%CI: 1.34-1.51, p-value <0.001). However, no significant causal association was observed between pediatric asthma and chronic sinusitis (IVW: OR = 1.00, 95%CI: 1.00-1.00, p-value = 0.085), chronic laryngitis and laryngotracheitis (IVW: OR = 1.05, 95%CI: 0.90-1.21, p-value = 0.558). Our findings support a potential causal relationship between pediatric asthma and UAD, suggesting that pediatric asthma may be a potential risk factor for various UAD.

Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation.

Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma. To uncover these mechanisms using complementary metabolomic and transcriptomic data, abundance levels of 529 named metabolites and expression levels of 22,772 genes were measured among children with asthma in the Childhood Asthma Management Program (CAMP, N=564) and the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS, N=309) via the TOPMed initiative. Gene-metabolite associations dependent on IgE were identified within each cohort using multivariate linear models and were interpreted in a biochemical context using network topology, pathway and chemical enrichment, and representation within reactions. A total of 1,617 total IgE-dependent gene-metabolite associations from GACRS and 29,885 from CAMP met significance cutoffs. Of these, glycine and guanidinoacetic acid (GAA) were associated with the most genes in both cohorts, and the associations represented reactions central to glycine, serine, and threonine metabolism and arginine and proline metabolism. Pathway and chemical enrichment analysis further highlighted additional related pathways of interest. The results of this study suggest that GAA may modulate total IgE levels in two independent pediatric asthma cohorts with different characteristics, supporting the use of L-Arginine as a potential therapeutic for asthma exacerbation. Other potentially new targetable pathways are also uncovered.

Urinary eosinophil-derived neurotoxin is associated with reduced lung function in pediatric asthma.

Eosinophil-derived neurotoxin (EDN) is a biomarker for eosinophilic activation. Urinary (u) EDN may allow non-invasive monitoring of asthma, but clinical recommendations are lacking. We assessed the potential of uEDN as a marker of disease activity in pediatric asthma. We assessed urine samples of 371 children from the German ALLIANCE study cohort, from which we had: 169 preschool wheezers (<6 years), 80 asthmatics (≥6 years), and 122 healthy controls using the ImmunoCAP™ EDN Assay. Creatinine (Cr)-adjusted uEDN values were analyzed using correlations, association tests, (non) parametric statistics, multiple linear, and multivariable regression. uEDN/uCr values were higher in atopic versus non-atopic preschool-aged subjects (p = .035) and associated with the sum of allergen-specific IgE in younger (r = 0.24, p = .003), and older subjects (r = 0.23, p = .043). uEDN/uCr was marginally a good determinant for atopy (p = .078, for subjects aged <6 years, and p = .058 for subjects ≥6 years). Children with the T2-high phenotype had higher uEDN/uCr (p < .001) versus T2-low-irrespective of using uEDN/uCr or blood eosinophils in combination to allergen sIgE for disease phenotyping. uEDN/uCr significantly correlated with reduced lung function among asthmatics (FEV1 z-scores: r = -0.30, p = .007, and FEV1/FVC z-scores: r = -0.24, p = .038). Using multivariable modeling, uEDN/uCr was an independent determinant of FEV1 (p = .038), and to a lesser extent, FEV1/FVC (p = .080). uEDN/uCr may serve as a non-invasive biomarker for clinical features such as lung function in pediatric asthma. We highlight the utility of uEDN/uCr as a biomarker that can be easily assessed using widely available robust diagnostic immunoassays.