Recurrent Asthma Research Articles

Use of Dupilumab in HyperIgE syndrome with ERBIN-deficiency: case report

HyperIgE Syndromes (HIES) are rare primary immunodeficiencies characterized by recurrent infections and Th2 clinical signature (elevated IgE, eosinophilia, asthma, and atopic dermatitis). The major genetic alterations concern loss of function mutations of the STAT3/ERBIN/SMAD2/3 complex. Patients with ERBIN-deficiency have a higher number of Treg and greater IL-4Rα expression on naïve lymphocytes, due to increased activation of the TGF-ß pathway. Dupilumab is an anti-IL-4Rα monoclonal antibody that inhibits IL-4 and IL-13 signalling and the expression of type 2 cytokines. We here discuss a case of Dupilumab treatment in a ERBB2IP mutated patient. At our Rare Diseases referral Centre, we have been following a 20-year-old patient with severe atopic dermatitis, history of recurrent sinopulmonary infections, asthma and IgE level of 8818kU/L. On physical examination, the patient presented diffuse eczema with areas of lichenization, Eczema Area and Severity Index 29, Numeric Rating Scale of itch 9/10, Dermatology Life Quality Index 28/30, saddle nose, prognathism and severe left-convex scoliosis with NIH-HIES score equal to 37. CD4T lymphocytes were mainly Th2 (52%); Th17 were 13%, with normal IgG, IgA and IgM levels. The NGS genetic study found the following mutation of ERBB2IP, which encodes for ERBIN protein, likely pathogenic for HIES, together with a TMC8 and a CASP10 variant, all in heterozygosis. Given the underlying immunodeficiency and the non-response to topical and systemic corticosteroids, therapy with cyclosporine was not considered. Dupilumab was instead started with an induction dose of 600 mg and maintenance of 300 mg every 15 days. At last follow-up (14 months after dupilumab initiation) the patient presents: subjective well-being, skin free from manifestations, EASI score 0, NRS 0/10, DLQI 0/30, normal lung function with optimal control of asthma, IgE still>5000 kU/L. Of note, no more infectious episodes were reported. In our patient, given the anamnestic context of immunodeficiency, the use of target therapy on IL-4/IL-13R signalling proved to be particularly effective and safe in the treatment of skin manifestations related to the loss of function mutation of the ERBIN gene, known for the functional relationship with STAT3 in the regulation of IL-4Rα expression on naïve lymphocytes and of the Th2 response.

Model-estimated impacts of pediatric respiratory syncytial virus prevention programs in Mali on asthma prevalence.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in young children and is associated with subsequent recurrent wheezing illness and asthma (wheeze/asthma). RSV prevention may therefore reduce wheeze/asthma prevalence. We estimated the contribution of RSV LRTI and the impact of RSV prevention on recurrent wheeze/asthma in Mali. We simulated 12 consecutive monthly birth cohorts in Mali and estimated RSV LRTI cases through 2 years and recurrent wheeze/asthma prevalence at 6 years under different RSV prevention scenarios: status quo, seasonal birth-dose extended half-life mAb, and seasonal birth-dose extended half-life mAb followed by 2 doses of pediatric vaccine (mAb+ vaccine). We used World Health Organization (WHO) Preferred Product Characteristics for RSV prevention, demographic and RSV epidemiologic data from Mali, regional recurrent wheeze/asthma prevalence, and relative risk of recurrent wheeze/asthma given early childhood RSV LRTI. Among the simulated cohort of 778,680 live births, 10.0% had RSV LRTI by 2 years and 89.6% survived to 6 years. We estimated that 13.4% of all recurrent wheeze/asthma at 6 years was attributable to RSV LRTI. Recurrent wheeze/asthma prevalence at 6 years was 145.0 per 10,000 persons (RSV LRTI attributable) and 1084.2 per 10,000 persons (total). In mAb and mAb+ vaccine scenarios, RSV LRTI cases decreased by 11.8% and 44.4%, respectively, and recurrent wheeze/asthma prevalence decreased by 11.8% and 44.4% (RSV LRTI attributable) and 1.6% and 5.9% (total). In Mali, RSV prevention programs may have a meaningful impact on chronic respiratory disease, strengthening the case for investment in RSV prevention.

IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case historyWe present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. DiscussionOf these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1–3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele; one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. ImpactThis case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy.Table 1(abstract: 126)ClassificationGeneExon/IntronDNA changeProtein changeZygosityInheritanceOMIMAssociated diseaseUncertain significanceIRF2BP22c.1606C>Tp.Gln536TerHeterozygousAutosomal Dominant615332Immunodeficiency Common variable, 14Uncertain SignificanceLRBA30c.4832C>Tp.Thr1611lleHeterozygousAutosomal Recessive606453Immunodeficiency Common variable, 8, with autoimmunityPathogenicCFTR4c.350G>Ap.Arg117HisHeterozygousAutosomal Recessive602421CFTR- related disorders

Bronchiolitis, Regardless of Its Etiology and Severity, Is Associated With Increased Risk of Asthma: A Population-Based Study.

An association exists between severe respiratory syncytial virus (RSV)-bronchiolitis and a subsequent increased risk of recurrent wheezing (RW) and asthma. However, a causal relationship remains unproven. Using a retrospective population-based cohort study (339 814 children), bronchiolitis during the first 2 years of life (regardless of etiology and severity) was associated with at least a 3-fold increased risk of RW/asthma at 2-4 years and an increased prevalence of asthma at ≥5 years of age. The risk was similar in children with mild bronchiolitis as in those with hospitalized RSV-bronchiolitis and was higher in children with hospitalized non-RSV-bronchiolitis. The rate of RW/asthma was higher when bronchiolitis occurred after the first 6 months of life. Our results seem to support the hypothesis of a shared predisposition to bronchiolitis (irrespective of etiology) and RW/asthma. However, 60% of hospitalized bronchiolitis cases in our setting are due to RSV, which should be paramount in decision-making on imminent RSV prevention strategies.

Comparison of the clinical outcomes of patients with NSAID-exacerbated respiratory disease receiving aspirin or biologicals

Objective NSAID-exacerbated respiratory disease (NERD) is characterized by exacerbation of respiratory symptoms after NSAID intake. While research for specific treatment options continues in patients who cannot tolerate or are unresponsive to aspirin treatment after aspirin desensitization (ATAD), biologicals have emerged as a new therapeutic option in NERD patients. The aim of this study was to compare the quality of life, and the sinonasal and respiratory outcomes of NERD patients treated with ATAD or biologicals. Methods Patients who have been followed up at a tertiary care allergy center and who have been receiving at least one of ATAD, mepolizumab or omalizumab for at least six months were included. Evaluations were made using sinonasal outcome test (SNOT-22), asthma control test (ACT), short form-36 (SF-36), blood eosinophil counts, need for recurrent functional endoscopic sinus surgeries (FESS), and asthma or rhinitis exacerbations requiring oral corticosteroids (OCS). Results A total of 59 patients comprised of 35 (59%) females and 24 (41%) males with a mean age of 46.1 (min-max, 20–70) years were included. The baseline blood eosinophil count was higher, and a significant decrease in blood eosinophil counts was observed in the mepolizumab group compared to ATAD group (p = 0.001, p < 0.001, respectively). At follow-up, the rate of recurrent FESS was lower in the group that received mepolizumab (p = 0.02). Conclusions In NERD patients, mepolizumab significantly decreased blood eosinophil counts and recurrent FESS. There was no significant difference between the patients receiving ATAD or mepolizumab regarding other clinical parameters.

Cohort study of early life environmental factors and risk of decreased lung function at age 6 years in children with a history of severe bronchiolitis

Bronchiolitis is the leading cause of infant hospitalization. Identifying modifiable risk factors for decreased lung function in these children who are already at high-risk for recurrent wheezing and asthma will help guide efforts to prevent additional respiratory morbidity.

Association of Newborn Metabolite Concentrations with Recurrent Wheeze and Asthma in Childhood

Association of Newborn Metabolite Concentrations with Recurrent Wheeze and Asthma in Childhood

Nasal TSLP and periostin in infants with severe bronchiolitis and risk of asthma at 4 years of age

BackgroundSevere bronchiolitis is often associated with subsequent respiratory morbidity, mainly recurrent wheezing and asthma. However, the underlying immune mechanisms remain unclear. The main goal of this study was to investigate the association of nasal detection of periostin and thymic stromal lymphopoietin (TSLP) during severe bronchiolitis with the development of asthma at 4 years of age.MethodsObservational, longitudinal, post-bronchiolitis, hospital-based, follow-up study. Children hospitalized for bronchiolitis between October/2013 and July/2017, currently aged 4 years, included in a previous study to investigate the nasal airway secretion of TSLP and periostin during bronchiolitis, were included. Parents were contacted by telephone, and were invited to a clinical interview based on a structured questionnaire to obtain information on the respiratory evolution. The ISAAC questionnaire for asthma symptoms for 6–7-year-old children, was also employed.ResultsA total of 248 children were included (median age 4.4 years). The mean age at admission for bronchiolitis was 3.1 (IQR: 1.5–6.5) months. Overall, 21% had ever been diagnosed with asthma and 37% had wheezed in the last 12 months. Measurable nasal TSLP was detected at admission in 27(11%) cases and periostin in 157(63%). The detection of nasal TSLP was associated with the subsequent prescription of maintenance asthma treatment (p = 0.04), montelukast (p = 0.01), and the combination montelukast/inhaled glucocorticosteroids (p = 0.03). Admissions for asthma tended to be more frequent in children with TSLP detection (p = 0.07). In the multivariate analysis, adjusting for potential confounders, the detection of TSLP remained independently associated with chronic asthma treatment prescription (aOR:2.724; CI 1.051–7.063, p:0.04) and with current asthma (aOR:3.41; CI 1.20–9.66, p:0.02).Nasal detection of periostin was associated with lower frequency of ever use of short-acting beta2-agonists (SABA) (p = 0.04), lower prevalence of current asthma (p = 0.02), less prescription of maintenance asthma treatment in the past 12 months (p = 0.02, respectively). In the multivariate analysis, periostin was associated with lower risk of asthma at 4 years, independently of the atopic status (aOR:0.511 CI 95% 0.284–0.918, p:0.025).ConclusionsOur results show a positive correlation between nasal TSLP detection in severe bronchiolitis and the presence of current asthma, prescription of asthma maintenance treatment and respiratory admissions up to the age of 4 years. By contrast, we found a protective association between nasal periostin detection and current asthma at 4 years, ever diagnosis of asthma, maintenance asthma treatment prescription, and respiratory admissions.

GenIDA, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with Koolen-de Vries syndrome

PurposeGenIDA is an international patient registry for individuals diagnosed with intellectual disability, autism spectrum disorder, and/or epilepsy, which is based on an online questionnaire that is completed by parent caregivers. In this study, the GenIDA data on Koolen-de Vries syndrome (KdVS) was analyzed illustrating the value of GenIDA and patient/caregiver participation in rare genetic neurodevelopmental disorders (NDDs). MethodsRecruitment was done on the GenIDA website from November 2016 to February 2022. Clinical information on individuals with KdVS was extracted for in-depth analysis and for comparison with the GenIDA data of individuals diagnosed with other NDDs. ResultsA total of 1417 patients/caregivers across 35 genetic conditions answered to the GenIDA questionnaire, including caregivers of 237 individuals with KdVS. GenIDA findings on KdVS were consistent with the existing literature, and there were no significant differences between individuals with a 17q21.31 microdeletion and those with a pathogenic variant in the KANSL1 gene. GenIDA provided detailed clinical information including features that are over-represented in KdVS compared with other NDDs (eg, laryngomalacia). Modeling of the natural history showed a positive development of speech and language over time and relatively good reading ability in KdVS. Valproate and oxcarbazepine were reported as effective antiepileptic drugs, and responses to open-ended questions indicated that childhood recurrent pneumonia and asthma are clinically relevant comorbidities that were not described in KdVS before. ConclusionGenIDA is a powerful registry to collect and harness valuable data on rare NDDs. The study shows that caregiver-driven data collection is effective in terms of global recruitment and centralization of clinical data.

Parametric frailty models using two-parameter xgamma distribution with an application of survival analysis

When the actual observation measurement is expensive and difficult, an effective approach for estimating the population parameters is applied, such as ranked set sampling. In a survival or time-to-event analysis, a frailty model is a random effects model where the random effect (the frailty) has a multiplicative effect on the hazard. One of the traditional distributions, the Xgamma distribution, is frequently utilized in reliability and regular survival models (frailty-free), but not in frailty models. Due to its inherent flexibility, the Xgamma distribution and its generalizations have become significantly important in survival analysis in recent years. In this study, we attempt to fit two-parameter X-gamma baseline distribution (TPXGD) with parametric frailty models and apply them to the two real-life data sets. The study results revealed that TPXGD with Gamma frailty model is good choice for Kidney infection data and recurrent asthma attack in children. To make studies of time-to-event data with covariates easier, we propose the Two-parameter Xgamma baseline distribution (TPXGD) with frailty models as suitable alternate models.

Children with Asthma Exposed to COVID-19 Show a Decrease in Severity from Baseline: A Systematic Review from March 2020 to September 2022

Introduction: During the COVID-19 pandemic, children have been affected by SARS- CoV-2 infection, primarily affecting the respiratory system. Children with chronic respiratory diseases such as asthma, emphysema, and chronic bronchitis can experience an exacerbation of the preexisting conditions. The study's primary aim was to identify the severity of asthma in COVID-19-exposed children aged 4-12 years. Methods: We extracted the data from the PubMed database between March 2020 and September 2022. During the COVID-19 pandemic, PubMed-published articles involving children living with asthma aged 4-12 years were identified. The study included children who had tested positive for SARS-CoV-2 and excluded children with any other comorbidities. Results:We identified 169 PubMed- published articles and filtered 28 articles. Seven articles met the inclusion criteria and were included in the study. The children with asthma hospitalized owing to COVID-19 worldwide was 1% to 2.7%. Incidence was 12.8 times less frequent in children than in adults. Increased expression of the angiotensin-converting enzyme-2 gene in the bronchial epithelium of patients with type 2-low or T1-high asthma tended to have higher known risk factors for COVID-19. Among school-age children (N=277,285), 1.2% were hospitalized, 0.1% had intensive care unit admissions, and &lt;0.1% died. Of those patients (hospitalized, ICU admissions, and those who died from COVID-19), all had at least one underlying medical condition, and 55% had chronic lung disease, including asthma. Conclusion: Most children with recurrent wheezing and asthma were well-controlled by their underlying asthma and did not require significant changes to their maintenance treatments. It concludes that children who tested positive for SARS-CoV-2 had fewer pediatric hospital admissions and attendance at urgent care settings. The reduction in asthma morbidities is due to improved adherence and decreased exposure to allergens and viral infections in children.

A CASE OF RECURRENT RESPIRATORY FAILURE AND EOSINOPHILIA CAUSED BY PAPILLARY RENAL CELL CARCINOMA

<h3>Introduction</h3> Eosinophilia with end organ manifestations secondary to solid tumors is not well described. <h3>Case Description</h3> A 57-year-old female with Aspirin Exacerbated Respiratory Disease had well controlled asthma on aspirin 325mg twice daily and inhaled corticosteroid/long-acting beta-agonist. Suddenly, over 2 months, her asthma significantly worsened requiring 5 emergency room visits and 3 hospitalizations. When placed on high-dose systemic steroids, her respiratory symptoms improved and her absolute eosinophil count (AEC) on 60mg prednisone was 0.2 × 10³/mL. However, when prednisone was tapered below 30mg daily, she twice required emergent intubation for hypercapnic respiratory failure, and her AEC increased to 1.25 × 10³/mL. Respiratory failure was ultimately attributed to status asthmaticus. Extensive eosinophilia workup was negative except chest computed tomography which incidentally demonstrated a new calcified renal mass. The patient underwent nephrectomy, revealing type 2 papillary renal cell carcinoma (RCC). To avoid continued high-dose systemic steroids, mepolizumab was initiated. Post-nephrectomy and on mepolizumab, her asthma remained well-controlled, and her corticosteroids were tapered off. Now, four months post-nephrectomy, mepolizumab has been discontinued and her asthma remains well controlled with an AEC of 0.15 × 10³/mL. <h3>Discussion</h3> To our knowledge, this is the first case of type 2 papillary RCC associated with peripheral eosinophilia. In particular, we suspect her malignancy was associated with an eosinophilia that was not completely responsive to steroids, leading to recurrent severe asthma decompensation. This rare case highlights how sudden changes in asthma control should prompt evaluation as to new underlying triggers and that AEC should always be interpreted in the context of systemic steroid use.

ALL THAT WHEEZES IS NOT ASTHMA: BRONCHIAL PAPILLOMA

ALL THAT WHEEZES IS NOT ASTHMA: BRONCHIAL PAPILLOMA

Biomarker underuse contributes to an inability to phenotype patients with severe uncontrolled asthma.

Background: Biomarker measurements improve the phenotyping of patients with severe uncontrolled asthma (SUA) and predict therapeutic responses. The use of biomarkers in asthma, however, remains underused. Objective: To test the hypothesis that biomarker measurements of patients with SUA remain markedly underused and contributes to asthma morbidity and oral corticosteroid use. Methods: Leveraging claims data linked to electronic health record data, we calculated biomarker use by providers treating patients with SUA from January 2017 to August 2020. Results: From 3.6 million clients, 3817 had a primary diagnosis of asthma; most were between 50 and 60 years old. Also, 63.2% were female patients; those under ages 10 years were primarily boys. Of the 728 patients who reported race, 69.9% were white and 21.8% were African American. Of the 840 who reported ethnicity, 14% were Latinx. A predetermined definition of SUA identified 348 patients with SUA. In a nested sample of 151 patients with SUA, 43% were managed by primary care physicians (PCP), 4% by specialists, and 49.7% by both. Of this sample, 61.5% had a measurement of serum eosinophils, 9.9% total immunoglobulin E values, and 9.3% radioallergosorbent skin tests; 38% received no tests, whereas 9.9% had more than one. Specialists ordered a biomarker test 4.6 times more often than did PCPs, whereas PCPs ordered 70% of the prednisone prescriptions for recurrent asthma exacerbations. Conclusion: Specialists were more likely to order biomarkers than were PCPs. Patients managed exclusively by PCPs were more likely prescribed oral prednisone. Real-world evidence shows that biomarkers are infrequently used to characterize patients with SUA, especially among patients exclusively managed by PCPs. Programs that encouraged biomarker use may improve SUA management and oral corticosteroid burden.

Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions.

Globally, respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in young children, and the association between severe RSV disease and later recurrent wheeze and asthma is well established. Whilst a causal link between RSV and wheeze/asthma is not yet proven, immunological evidence suggests skewing towards a Th2-type response, and dampening of IFN-γ antiviral immunity during RSV infection underpins airway hyper-reactivity in a subset of susceptible children after RSV infection. Age at primary RSV infection, viral co-infection and genetic influences may act as effect-modifiers. Despite the significant morbidity and mortality burden of RSV disease in children, there is currently no licensed vaccine. Recent advancements in RSV preventatives, including long-acting monoclonal antibodies and maternal vaccinations, show significant promise and we are on the cusp of a new era in RSV prevention. However, the potential impact of RSV preventatives on subsequent wheeze and asthma remains unclear. The ongoing COVID-19 pandemic and associated public health measures have disrupted the usual seasonality of RSV. Whilst this has posed challenges for health-care services it has also enhanced our understanding of RSV transmission. The near absence of RSV cases during the first year of the pandemic in the context of strict public health measures has provided a rare opportunity to study the impact of delayed age of primary RSV infection on asthma prevalence. In this review, we summarise current understanding of the association between RSV, recurrent wheeze and asthma with a focus on pathophysiology, preventative strategies and future research priorities.

Parametric frailty models under two-parameter Lindley distribution with applications to time-to-event analysis

A frailty model is a random effects model in survival or time-to-event analysis, where the random effect (the frailty) has a multiplicative effect on the hazard. Lindley distribution is one of the classical distributions, which is widely used in reliability and ordinary survival models (without frailty) but not in the frailty models. In recent years, Lindley distribution and its generalizations have played an important role in survival analysis due to its natural flexibility. In this study, we attempt to fit parametric frailty models with Two-parameter Lindley baseline distribution (TPLD) and apply them to the two real-life disease data sets of the (i) Recurrent asthma attacks in children’s (Asthma attacks) and (ii) Culling of dairy heifer cow’s (Culling) data. Comparison and assed the model's fitness were done using a minimum value of Akaike's Information Criteria (AIC) and Bayesian Information Criteria (BIC). The study results revealed that TPLD with the Lognormal frailty model is a good choice for Culling data and Lindley with Gamma frailty model is the best for Asthma data. So, we suggest that the Two-parameter Lindley baseline distribution (TPLD) with frailty models are potential alternative models and will facilitate analyses of time-to-event data with covariates.

Road traffic density and recurrent asthma emergency department visits among Medicaid enrollees in New York State 2005–2015

BackgroundEnvironmental exposures such as traffic may contribute to asthma morbidity including recurrent emergency department (ED) visits. However, these associations are often confounded by socioeconomic status and health care access.ObjectiveThis study aims to assess the association between traffic density and recurrence of asthma ED visits in the primarily low income Medicaid population in New York State (NYS) between 2005 and 2015.MethodsThe primary outcome of interest was a recurrent asthma ED visit within 1-year of index visit. Traffic densities (weighted for truck traffic) were spatially linked based on home addresses. Bivariate and multivariate logistic regression analyses were conducted to identify factors predicting recurrent asthma ED visits.ResultsIn a multivariate model, Medicaid recipients living within 300-m of a high traffic density area were at a statistically significant risk of a recurrent asthma ED visit compared to those in a low traffic density area (OR = 1.31; 95% CI:1.24,1.38). Additionally, we evaluated effect measure modification for risk of recurrent asthma visits associated with traffic exposure by socio-demographic factors. The highest risk was found for those exposed to high traffic and being male (OR = 1.87; 95% CI:1.46,2.39), receiving cash assistance (OR = 2.11; 95% CI:1.65,2.72), receiving supplemental security income (OR = 2.21; 95% CI:1.66,2.96) and being in the 18.44 age group (OR = 1.59;95% CI 1.48,1.70) was associated with the highest risk of recurrent asthma ED visit. Black non-Hispanics (OR = 2.35; 95% CI:1.70,3.24), Hispanics (OR = 2.13; 95% CI:1.49,3.04) and those with race listed as “Other” (OR = 1.89 95% CI:1.13,3.16) in high traffic areas had higher risk of recurrent asthma ED visits as compared to White non-Hispanics in low traffic areas.ConclusionWe observed significant persistent disparities in asthma morbidity related to traffic exposure and race/ethnicity in a low-income population. Our findings suggest that even within a primarily low-income study population, socioeconomic differences persist. These differences in susceptibility in the extremely low-income group may not be apparent in health studies that use Medicaid enrollment as a proxy for low SES.

Infant Exposure to Acid Suppressant Medications Increases Risk of Recurrent Wheeze and Asthma in Childhood

Acid suppressant medications (ASMs) are commonly prescribed in infancy. Little is known about the relationship between ASM exposure and risk of childhood asthma and atopic conditions. We sought to examine the association between infant ASM exposure and risk for developing recurrent wheeze, allergen sensitization, and asthma in early childhood. We used data from a diverse, multicenter, prospective cohort study of 921 infants with a history of bronchiolitis. ASM exposure (histamine-2 receptor antagonists and/or proton pump inhibitors) during infancy (age: <12 months) was ascertained by parent report and medical record review. The outcomes were recurrent wheeze by age 3 years, early childhood allergen sensitization (serum specific IgE), and asthma by age 6 years. We constructed multivariable Cox proportional hazards models and multivariable logistic regression models adjusting for multiple confounders. Of the 921 children in the cohort, 202 (22%) were exposed to ASMs during infancy. Compared with unexposed children, those exposed to ASM were more likely to develop recurrent wheeze by age 3 years (adjusted hazard ratio: 1.58, 95% confidence interval [CI]: 1.20-2.08, P= .001) and asthma by age 6 years (adjusted odds ratio: 1.66, 95% CI: 1.22-2.27, P= .001). ASM exposure during infancy was not significantly associated with the development of early childhood allergen sensitization (adjusted odds ratio: 1.00, 95% CI: 0.70-1.44, P=.99). Although exposure to ASMs during infancy does not increase the risk of allergen sensitization in early childhood, ASM exposure during infancy increases the risk of recurrent wheeze and asthma during early childhood.

The impact of COVID-19 lockdown on children with recurrent wheezing and asthma in Spain.

AimThe rapid spread of a novel human coronavirus SARS‐CoV‐2 led to drastic measures world‐wide. Most countries were forced to declare a national lockdown. We studied the effect of lockdown measures on the level of asthma control and maintenance treatment in children with recurrent wheezing and asthma during the first wave of COVID‐19 in Spain.MethodsWe analysed children with recurrent wheezing or asthma before and after the implementation of the lockdown, by using a questionnaire aimed to examine pre‐existing respiratory disorders, step treatment and level of asthma control before/after lockdown, COVID history and laboratory testing including IgG SARS‐CoV‐2.ResultsWe enrolled 475 asthmatic and pre‐school wheezers (60.6% males), mean age 5.6 years. There were no differences in asthma treatment comparing both periods: 81.7% maintained the same treatment (P = 0.103). According to child asthma‐control questionnaire, 87.7% remained well controlled during confinement. Nearly, a third of children (34.9%) needed reliever treatment, mainly in older children. Determination of IgG SARS‐CoV‐2 was performed in 233 children (49.1%) of whom 17 (7.3%) tested positive. Seven patients positive to IgG SARS‐CoV‐2 were assisted in the emergency department and two required hospital admission.ConclusionsDuring COVID‐19 lockdown in Spain, most children with recurrent wheezing and asthma remained well controlled from their underlying disease and did not modify greatly their maintenance treatments. Unexpectedly, we also observed that those children who tested positive to SARS‐CoV‐2 IgG showed a significant increase in paediatric hospital admissions and attendances to urgent care settings.

The role of association of ADRB2 gene polymorphism with therapeutic response to β2-agonists in children with recurrent bronchial obstruction

Background. The study of the effect of drugs at the molecular genetic level in the recurrent course of bronchial obstruction (RBО) in children improved the understanding of the pathogenesis of the disease and made it possible to better characterize the reliability of use in therapy. The aim of the study was to assess the clinical significance of the polymorphism of the Arg16Gly loci of the ADRB2 gene with a therapeutic response to β2-agonists in children with RBО of Uzbek ethnicity. Materials and methods. Tested 88 patients aged 6 to 15 years with recurrent bronchial obstruction and bronchial asthma with the polymorphism of the ADRB2 gene loci and determined the effectiveness of salbutamol in these groups of patients. Results. Results of the study of the significance of the polymorphism of the Arg16Gly locus of the ADRB2 gene with a therapeutic response to β2-agonists in children with RBO showed high efficacy of salbutamol in 72.9 % of children, among whom representatives of the A/G and A/A genotypes were found in the largest number. At the same time, the low efficacy of salbutamol was found in the greatest amount in carriers of the mutational genotype G/G of the Arg16Gly locus of the ADRB2 gene. Conclusions. The predictor role of the polymorphic locus rs1042713 (Arg16Gly) was determined in carriers of the unfavorable 46G allele of the G/G genotype of the ADRB2 gene, which was a genetic marker of children’s predisposition to RBO and BA in children. Children with the G/G genotype of the Arg16Gly locus of the ADRB2 gene are at risk for severe RBO and BA in children. Children with RBO carriers (Arg16Gly) of the homozygous G/G genotype have a high incidence of RBO recurrence against the background of ARVI and are at risk of developing BA.