Wheezing Episodes Research Articles

Foreign Bodies in Lower Airway in Children: Brief Review and Clinical Experience.

Foreign body aspiration is a preventable occurrence that carries a high risk of mortality in the pediatric population. Clinically, foreign body aspiration manifests as cough, followed by choking, which might not be given any consideration by the caregivers of the child. An episode of sudden wheezing can also raise the suspicion of a foreign body in the lower respiratory tract. The clinical findings depend on the type, size, and localization of the foreign body and include persistent cough, localized airway resistance, localized or diffuse wheezing, and difficulty breathing. A bronchoscopy is the procedure of choice for the removal of foreign bodies. Flexible bronchoscopy is increasingly being used as the initial diagnostic procedure in children with an uncertain history of choking, in the absence of physical and radiological lung changes, and in chronic complaints requiring the exclusion of a foreign body in the airways. Thus, the aim of this study was to describe our clinical experience with lower respiratory tract foreign body extraction in children over a period of five years. Over a 5-year period, 154 patients under the age of 18 underwent a bronchoscopy due to a suspected foreign body in the lower respiratory tract. Of these patients, 92% had an incident leading to acute respiratory distress, and 8% had no definite data on such an event in the anamnesis. A foreign body in the respiratory tract was found in and extracted from 50 patients, and foreign bodies were absent in 104 of the cases. If a foreign body enters the lower respiratory tract, immediate and adequate actions are required to solve the problem. A bronchoscopy should be conducted in every suspected case of foreign body aspiration.

A Multicenter, Longitudinal Maternal and Birth Cohort Study in Latin America to Assess Prevalent Respiratory Tract Infections in Children from 0 to 5 Years of Age. The MINERVAL Study

Abstract Background A maternal and birth cohort study can assess the etiology and clinical course of lower respiratory tract infections and offers the opportunity to evaluate the relationship between sociodemographic, clinical, host characteristics and disease severity. In Latin America, a consortium of clinical research centers in Colombia and Panama has demonstrated its ability to conduct long-term longitudinal studies involving active surveillance of thousands of children with consistent retention rates. The MINERVAL cohort study aims to estimate the incidence, etiology, severity, and burden of lower respiratory tract infections (LRTI) and to identify microbiome and transcriptome profiles to help predict risk and assess disease severity in children from birth to 5 years of age. Methods We are establishing a maternal/birth cohort study in four sites (Cali, Bogota, Barranquilla and Panama), and will be recruiting 542 participants per center. Enrolled pregnant women between 24 and 27 weeks of gestation, and newborns under 4 weeks of age, will be closely followed with active surveillance weekly during the first 2 years for early detection of LRTI. Monthly telephone follow-up calls will continue until five years of age to assess the development of long-term respiratory morbidity and complications, including recurrent wheezing episodes. Clinical samples (NP swabs -for respiratory pathogen detection and microbiome analysis-, and blood -for cytokine and transcriptome analysis-) will be obtained in pregnant women, and in infants in the first 4 weeks of life and every 6 months for two years. Women and children who develop LRTI during the longitudinal follow-up will be evaluated clinically and samples will be collected. Results This cohort will provide prospective data and biological samples at crucial stages of children’s development, to allow estimation of the incidence and burden of LRTI by age and etiology, and the identification of risk factors and possible targets for intervention. Furthermore, the use of transcriptional profiling will allow early identification of variables to predict and guide clinical management in children, the use of antivirals and monoclonal antibodies, and to prioritize the population to be vaccinated according to age and risk factors. Conclusion The establishment of observational maternal and birth cohorts in Latin America could provide information to guide the development of strategies to prevent and mitigate the impact of respiratory tract infections in young children. Collaboration among investigators in the region and partnerships with international investigators optimizes resources and allows standardization of good surveillance practices, data exchange and the generation of new knowledge for future studies.

Environmental exposures associated with early childhood recurrent wheezing in the mother and child in the environment birth cohort: a time-to-event study

BackgroundAntenatal factors and environmental exposures contribute to recurrent wheezing in early childhood.AimTo identify antenatal and environmental factors associated with recurrent wheezing in children from birth to 48 months in the...

Population Attributable Risk of Wheeze in 2-

There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

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.

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

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

Genetic predisposition to high BMI increases risk of early life respiratory infections and episodes of severe wheeze and asthma.

High body mass index (BMI) is an established risk factor for asthma, but the underlying mechanisms remain unclear. To increase understanding of the BMI-asthma relationship by studying the association between genetic predisposition to higher BMI and asthma, infections and other asthma traits during childhood. Data were obtained from the two ongoing Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts. Polygenic risk scores for adult BMI were calculated for each child. Replication was done in the large-scale register-based Integrative Psychiatric Research (iPSYCH) cohort using data on hospitalisation for asthma and infections. In the COPSAC cohorts (n=974), the adult BMI polygenic risk score was significantly associated with lower respiratory tract infections (incidence rate ratio (IRR) 1.20, 95% CI 1.08-1.33, false discovery rate p-value (pFDR)=0.005) at age 0-3 years and episodes of severe wheeze (IRR 1.30, 95% CI 1.06-1.60, pFDR=0.04) at age 0-6 years. Lower respiratory tract infections partly mediated the association between the adult BMI polygenic risk score and severe wheeze (proportion mediated: 0.59, 95% CI 0.28-2.24, p-value associated with the average causal mediation effect (pACME)=2e-16). In contrast, these associations were not mediated through the child's current BMI and the polygenic risk score was not associated with an asthma diagnosis or reduced lung function up to age 18 years. The associations were replicated in iPSYCH (n=114 283), where the adult BMI polygenic risk score significantly increased the risk of hospitalisations for lower respiratory tract infections and wheeze or asthma throughout childhood to age 18 years. Children with genetic predisposition to higher BMI had increased risk of lower respiratory tract infections and severe wheeze, independent of the child's current BMI. These results shed further light on the complex relationship between body mass BMI and asthma.

A novel syndrome of silent rhinovirus-associated bronchoalveolitis in children with recurrent wheeze

BackgroundRhinovirus (RV) infections trigger wheeze episodes in children. Thus, understanding of the lung inflammatory response to RV in children with wheeze is important. ObjectiveTo examine the associations of RV on lung lavage (BAL) granulocyte patterns and biomarkers of inflammation with age in children with treatment-refractory, recurrent wheeze (n=616). MethodsChildren underwent BAL to examine viral nucleic acid sequences, bacterial cultures, granulocyte counts, and phlebotomy for both general and type-2 inflammatory markers. ResultsDespite the absence of cold symptoms, RV was the most common pathogen detected (30%), and when present, was accompanied by BAL granulocytosis in 75% of children. Compared to children with no BAL pathogens (n=341), those with RV alone (n=127) had greater (p < 0.05) isolated neutrophilia (43% versus 16%), mixed eosinophils and neutrophils (26% versus 11%), and less pauci-granulocytic (27% versus 61%) BAL. Children with RV alone furthermore had biomarkers of active infection with higher total blood neutrophils and serum c-reactive protein (CRP), but no differences in blood eosinophils or total IgE. With advancing age, the log odds of BAL RV alone were lower, 0.82 [0.76-0.88, p < 0.001], but higher, 1.58 [1.01-2.51, p = 0.04], with high-dose daily corticosteroid treatment. ConclusionsChildren with severe recurrent wheeze often (22%) have a silent syndrome of lung RV infection with granulocytic bronchoalveolitis and elevated systemic markers of inflammation. The syndrome is less prevalent by school age, and not informed by markers of type-2 inflammation. We speculate that dysregulated mucosal innate antiviral immunity is a responsible mechanism.

Relationships between lung function, allergy, and wheezing in urban children

BackgroundAllergic sensitization and low lung function in early childhood are risk factors for subsequent wheezing and asthma. However, it is unclear how allergic sensitization impacts lung function over time. ObjectiveTo test whether allergy influences lung function and whether these factors synergistically increase the risk of continued wheezing in childhood. MethodsWe analyzed longitudinal measurements of lung function (spirometry, impulse oscillometry) and allergic sensitization (aeroallergen skin tests, serum allergen-specific IgE) throughout early childhood in the Urban Environmental and Childhood Asthma study which included high-risk urban children living in disadvantaged neighborhoods. Intraclass correlation coefficients (ICC) were calculated to assess lung function stability. Cluster analysis identified low, medium, and high allergy trajectories, which were compared to lung function and wheezing episodes in linear regression models. A variable selection model assessed predictors at age 5 for continued wheezing through age 12. ResultsLung function adjusted for growth was stable (ICC 0.5–0.7) from ages 5–12 years and unrelated to allergy trajectory. Lung function and allergic sensitization were associated with wheezing episodes in an additive fashion. In children with asthma, measuring lung function at age 5 added little to the medical history for predicting future wheezing episodes through age 12. ConclusionIn high-risk urban children, age-related trajectories of allergic sensitization were not associated with lung function development, however, both indicators were related to continued wheezing. These results underscore the importance of understanding early life factors that negatively impact lung development and suggest that treating allergic sensitization may not alter lung function development in early to mid-childhood.

Proportional of wheezing events in asthmatic children post-vaccination of annual flu vaccine

Background: The common childhood chronic disease asthma causes hospitalisation and exacerbations due to respiratory tract viral infections like influenza. Due to uncertainty about the benefits and role of influenza vaccines in preventing asthma exacerbations, many children with asthma do not receive them, despite recommendations from organisations like the Canadian National Advisory Committee on Immunisation. There are two main types of influenza vaccines: intramuscular trivalent inactivated and intranasal cold-adapted, live attenuated. Both vaccines are highly immunogenic and induce an adequate immune response, but their clinical efficacy varies by season and age. Aim: The aim of this study was to investigate the occurrence of increased wheeze rates in stable asthmatic children who received the annual flu vaccine, compared to a control group of asthmatic children who did not receive the vaccine. Methods: A retrospective study at the Queen Rania Abdullah for Children Hospital in Amman, Jordan, examined the vaccination status of 200 asthmatic children aged 3-14. The study focused on recurrent wheezing episodes and the minimum 12-month period between the last annual flu vaccination and asthmatic exacerbation. The study excluded uncontrolled or partially controlled patients for the past 12 months. Data was collected from demographic information, vaccination history, and past wheezing episodes. The children were divided into two groups, one without the flu vaccine and the other with the flu vaccine. A comprehensive questionnaire was used to assess sociodemographic and disease-related factors. If children received the vaccination as per the National Vaccination Schedule, their vaccination status was considered complete. Results: A study of 200 asthmatic children in Jordan found that 35% did not receive a flu vaccine, placing them in Group I. 65% had received a flu vaccine in the previous year. Males had higher distribution rates in both flu-based groups, with a statistically insignificant positive correlation. Age categories showed similar distribution rates, with 21.0% for 3-6 years, 34.0% for 6-9 years, 37.5% for 9-12 years, and 7.5% for 12-15 years. No significant correlation was found between receiving the flu vaccine and wheezing rates in the last seasonal year. Frequent wheezing episodes were higher in experienced groups than in naïve groups.

Analysis of exhaled breath condensate in patients with asthma and recurrent wheezing

Wheezing is the most common clinical symptom of bronchial obstructive syndrome. The functions of pulmonary surfactant (PS) depend directly on the level of total phospholipids (TP). This can be used to assess the integrity of the cell membrane structure. Objective. To determine the level of total phospholipids and calcium in exhaled breath condensate in young children with recurrent wheezing and asthma. Materials and methods. The study included 77 patients divided into 3 groups. Group 1 included 30 patients (20 girls and 10 boys) with no more than 2 episodes of recurrent wheezing in their lifetime; Group 2 -10 patients (6 boys and 4 girls) with more than 3 episodes of recurrent wheezing, and 37 patients (15 girls, 22 boys) with asthma. The control group consisted of 20 conditionally healthy children (11 girls, 9 boys). All patients were aged from 3 months to 6 years. The determination of phospholipid levels and calcium (Ca) in the exhaled breath condensate was performed in dynamics - during the period of clinical manifestations and remission. Results. The level of phospholipids in the exhaled breath condensate was the highest in patients of all groups at the stage of clinical manifestations compared with the period of remission, while its lowest level was noted in the control group. During the peak of the disease, the level of Ca in the exhaled breath condensate was significantly lower compared to the period of remission. The control group had the highest level. Conclusions. The exhaled breath condensate's high level of phospholipids in the first days of the disease confirms cell damage in the presence of inflammation. Additionally, the exhaled breath condensate's Ca level is lowest during this period, possibly indicating its involvement in cell damage

Vitamin D supply, respiratory viral infections and persistent wheezing in children: how significant is the relationship?

The review discusses the multifaceted effect of vitamin D on antiviral immunity, induction of antimicrobial peptides, functional activity of immunocompetent cells, autophagy processes, clearance of viruses and viral fragments. The relationship between vitamin D and allergic inflammatory cells, its modulating and tolerogenic potential is considered. The inhibitory effect of vitamin D on eosinophils, mast cells, the production of pro-inflammatory and proallergic mediators, and the synthesis of IgE has been shown. The protective role of vitamin D in the development of remodeling and hyperresponsiveness of the respiratory tract has been established by reducing the number of goblet cells, mucus hypersecretion, and the expression of metalloproteinases. The effects of vitamin D on the replication of respiratory viruses and experimental resistance to them through the induction of antimicrobial peptides and other mechanisms have been demonstrated. Data from clinical studies on the preventive effect of vitamin D on the incidence of respiratory infections and episodes of persistent wheezing in children are presented. Children with respiratory syncytial infection and vitamin D deficiency were more likely to require respiratory support and mechanical ventilation. The preventive role of vitamin D in the development of obstructive bronchitis in children and severe bronchiolitis in infants has been shown. It has been established that normal levels of 25(OH)D in the mother significantly reduce the risk of developing bronchial obstruction in the child. Alternative data that do not support a protective effect of vitamin D on respiratory morbidity and wheezing in children are discussed. Further monitoring studies that take into account geographic location and analysis of the dose of cholecalciferol used to assess its preventive role in the development of wheezing and bronchial asthma in children are advisable.

Respiratory Syncytial Virus (RSV) Burden in Infants in the Kingdom of Saudi Arabia and the Impact of All-Infant RSV Protection: A Modeling Study.

Respiratory syncytial virus (RSV) represents a considerable burden on the healthcare system and hospital resources. This study explored the impact of universal immunoprophylaxis with long-acting monoclonal antibody (nirsevimab) during infants' first RSV season on RSV-induced health events and related costs in the Kingdom of Saudi Arabia (KSA). The burden of RSV-induced health events and related costs under the current standard of practice (SoP) and the impact of universal immunoprophylaxis with nirsevimab was estimated using a static decision-analytic model in a cohort of infants experiencing their first RSV season in the KSA. The model estimated hospital admissions (including pediatric intensive care unit [PICU] admissions and mechanical ventilation [MV]), emergency room (ER) visits, primary care (PC) visits, long-term sequelae, and RSV mortality. The model estimated that under the current SoP, RSV results in 17,179-19,607hospitalizations (including 2932-3625 PICU and 172-525 MV admissions), 57,654-191,115 ER visits, 219,053-219,970 PC visits, 14 deaths, 12,884-14,705 cases of recurrent wheezing, and a total cost of SAR 480-619million. Universal nirsevimab immunoprophylaxis was estimated to avert 58% of hospitalizations (58% PICU admissions, 58% MV episodes), 53% of ER visits, 53% of PC visits, 58% of episodes of recurrent wheezing, 8 deaths, and result in savings of SAR 274-343million in total healthcare cost. Compared with current SoP, an nirsevimab immunoprophylaxis strategy in the KSA for all infants during their first RSV season was estimated to dramatically decrease healthcare resource use, and economic burden associated with RSV.

Vitamin D Level and Immune Modulation in Children with Recurrent Wheezing.

A direct causal relationship between vitamin D (vit D) deficiency and recurrent wheezing has not been proven. The present study investigated the role of vit D in enhancing the risk of asthma or recurrent wheezing by modifying the intensity of the inflammatory process. Forty children with wheezing presenting at the emergency service and sixteen healthy control subjects were included in the study. Children with wheezing were either in the first episode (20) or with recurrent wheezing (20). Children with chronic diseases, and other conditions that present with acute wheezing or that might influence the vit D level, were excluded. Blood samples were taken at presentation and 3-6 months later, to evaluate the serum levels of total IgE, vit D, IL-10 and IL-31. Statistical analysis was performed using the SPSS 25 program, with a significance level of p < 0.05. The vit D level was lower in patients with recurrent wheezing compared with those with a single episode and with the control group, and this increased with time. IL-10 was significantly higher in children with wheezing than in the control group, with the highest values in those with an acute episode of wheezing. IL-31 was higher in children with recurrent wheezing than in those with a first episode only at the initial point, while at the final time point it was lower. Low levels of vit D appear to be detected more frequently in recurrent wheezing than in simple wheezing. Immune modulation, as measured by Th2 status reflected by IL-10 and IL-31 levels, appears to depend on the wheezing phenotype and on the general health status.

Emergency management and asthma risk in young Medicaid-enrolled children with recurrent wheeze

Objectives To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma. Methods Retrospective cohort study of Medicaid-enrolled children 0–3 years old with an index ED visit for wheeze (e.g. bronchiolitis, reactive airway disease) from 2009 to 2013, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4 and 6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze. Results During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4 and 6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze. Conclusions Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies.

Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze

Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity as critical producers of type I interferons. pDCs also express the high-affinity IgE receptor through which type I interferon production may be negatively regulated. Whether antiviral function of pDCs is associated with recurrent episodes of wheeze in young children is not well understood. We sought to evaluate the phenotype and function of circulating pDCs in children with a longitudinally defined wheezing phenotype. We performed multiparameter flow cytometry on PBMCs from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDCs from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database. We observed a significant depletion of circulating pDCs inyoung children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the FcεRI on their pDCs. Based on transcriptomic analysis, pDCs from these individuals didnot mount a robust systemic antiviral response as observed inchildren who displayed a nonrecurrent wheezing phenotype. Our data suggest that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of high-affinity IgE receptor is increased and their function as major interferon producers is impaired during acute exacerbations of wheeze.

Clinical Impact of Serious Respiratory Disease in Children Under the Age of 2 Years During the 2021-2022 Bronchiolitis Season in England, Scotland, and Ireland.

Interventions introduced to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a widespread reduction in childhood infections. However, from spring 2021 onwards the United Kingdom and Ireland experienced an unusual out-of-season epidemic of respiratory disease. We conducted a prospective observational study (BronchStart), enrolling children 0-23 months of age presenting with bronchiolitis, lower respiratory tract infection, or first episode of wheeze to 59 emergency departments across England, Scotland, and Ireland from May 2021 to April 2022. We combined testing data with national admissions datasets to infer the impact of respiratory syncytial virus (RSV) disease. The BronchStart study collected data on 17 899 presentations for 17 164 children. Risk factors for admission and escalation of care included prematurity and congenital heart disease, but most admissions were for previously healthy term-born children. Of those aged 0-11 months who were admitted and tested for RSV, 1907 of 3912 (48.7%) tested positive. We estimate that every year in England and Scotland 28 561 (95% confidence interval, 27 637-29 486) infants are admitted with RSV infection. RSV infection was the main cause of hospitalizations in this cohort, but 51.3% of admissions in infants were not associated with the virus. The majority of admissions were in previously healthy term-born infants.

Clinical Results of a Randomized Placebo Controlled Trial of Inhaled Mometasone to Promote Reduction in Vaso-Occlusive Events (IMPROVE-II)

Introduction: A subset of patients living with sickle cell disease (SCD) who do not meet diagnostic criteria for asthma exhibit episodic cough or wheeze (ECW), and this is associated with higher rates of vaso-occlusive pain crisis and acute chest syndrome. ECW may be caused by pulmonary inflammation from SCD. In the former IMPROVE trial, 54 patients with SCD and ECW were randomized to receive 16 weeks of placebo or mometasone furoate, an inhaled corticosteroid used to treat pulmonary inflammation. Treatment with mometasone was associated with significant reductions in daily pain, markers of hemolysis, and soluble vascular cell adhesion molecule (sVCAM) (a biomarker of disease severity in SCD) compared to placebo. The IMPROVE-II trial evaluated whether treatment with mometasone over a longer period could improve clinical and biological endpoints in non-asthmatic patients with SCD and ECW. We report here the clinical outcomes from the IMPROVE-II trial. Methods: We conducted a randomized, placebo-controlled, single-center interventional trial. Patients with SCD without asthma were randomized to receive either mometasone furoate 220 mcg or placebo inhaled powder for 48 weeks followed by a 4-week wash out. Key inclusion criteria included age &amp;gt; 18 years with SCD genotype HbSS/HbSβ0 at stable baseline who endorsed ECW. Patients were excluded if they had &amp;gt;15 emergency department (ED) visits for vaso-occlusive pain crisis in the past 12 months or if other treatments for SCD (i.e. hydroxyurea, L-glutamine) were being titrated. The primary outcome was the change in soluble vascular cell adhesion molecule (sVCAM) level with treatment. Clinical outcomes included ED visits and hospitalizations for any reason, and health care visits for acute chest syndrome, pneumonia, stroke, or transient ischemic attack, as well as daily pain (self-report 1-10 scale), and 6 Minute Walk. Adaptive covariate randomization was used to balance covariates including hydroxyurea use (yes/no), age, and previous rate of ED use. Results: A total of 80 patients were randomized and 77 received study treatment; 40 were assigned to mometasone and 37 to placebo (Figure 1). There were no significant differences between treatment groups in patient demographics (Table 1). Treatment with mometasone was associated with higher rates of acute care visits for vaso-occlusive crisis (4 (2/19) vs 1 (1/3) /patient year (50%(25%/75%), p&amp;lt;0.001), hospitalization for acute chest syndrome (mean 0.2 vs 0.1/patient year, p=0.05) and ED utilization (2 (1/5) vs 2 (1/4) /patient year (50%(25%/75%), p0.01). Laboratory outcomes including sVCAM are not yet resulted. Adverse events that were reported by more than 5% of patients are listed in Table 1; there was no difference between rates of adverse (&amp;lt;5%) events between mometasone and placebo. There were no deaths during the study. Conclusions: In individuals with SCD and ECW who do not have asthma, long-term treatment with inhaled corticosteroids did not improve clinical outcomes and may be harmful as they were associated with higher rates of acute care visits for pain crisis, ED visits, and acute chest syndrome. Further analyses of biological endpoints and clinical laboratory data are needed to fully elucidate the effects of inhaled corticosteroids in SCD.

Inflammatory related plasma proteins involved in acute preschool wheeze.

Preschool wheeze is a risk factor for asthma development. However, the molecular mechanism behind a wheezing episode is not well understood. Our aims were to assess the association of plasma proteins with acute preschool wheeze and to study the proteins with differential expression at the acute phase at revisit after 3months. Additionally, to investigate the relationship between protein expression and clinical parameters. We measured 92 inflammatory proteins in plasma and clinical parameters from 145 children during an episode of preschool wheeze (PW) and at the revisit after 3months (PW-R, n=113/145) and 101 healthy controls (HC) aged 6-48months in the GEWAC cohort using the antibody-mediated proximity extension-based assay (Olink Proteomics, Uppsala). Of the 74 analysed proteins, 52 were differentially expressed between PW and HC. The expression profiles of the top 10 proteins, Oncostatin M (OSM), IL-10, IL-6, Fibroblast growth factor 21 (FGF21), AXIN1, CXCL10, SIRT2, TNFSF11, Tumour necrosis factor β (TNF-β) and CASP8, could almost entirely separate PW from HC. Five out of 10 proteins were associated with intake of oral corticosteroids (OCS) 24h preceding blood sampling (OSM, CASP8, IL-10, TNF-β and CXCL10). No differences in protein expression were seen between PWs with or without OCS in comparison to HC. At the revisit after 3months, differential protein expressions were still seen between PW-R and HC for three (IL-10, SIRT2 and FGF21) of the 10 proteins. Our results contribute to unravelling potential immunopathological pathways shared between preschool wheeze and asthma.

From preschool wheezing to asthma: Environmental determinants.

Wheezing is common among preschool children, representing a group of highly heterogeneous conditions with varying natural history. Several phenotypes of wheezing have been proposed to facilitate the identification of young children who are at risk of subsequent development of asthma. Epidemiological and immunological studies across different populations have revealed the key role of environmental factors in influencing the progression from preschool wheezing to childhood asthma. Significant risk factors include severe respiratory infections, allergic sensitization, and exposure to tobacco smoke. In contrast, a farming/rural environment has been linked to asthma protection in both human and animal studies. Early and intense exposures to microorganisms and microbial metabolites have been demonstrated to alter host immune responses to allergens and viruses, thereby driving the trajectory away from wheezing illness and asthma. Ongoing clinical trials of candidate microbes and microbial products have shown promise in shaping the immune function to reduce episodes of viral-induced wheezing. Moreover, restoring immune training may be especially important for young children who had reduced microbial exposure due to pandemic restrictions. A comprehensive understanding of the role of modifiable environmental factors will pave the way for developing targeted prevention strategies for preschool wheezing and asthma.