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

INTRODUCTION AND AIM: 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. MATERIAL AND METHOD: 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. RESULTS AND CONCLUSION: 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.

The implication of infection with respiratory syncytial virus in pediatric recurrent wheezing and asthma: knowledge expanded post-COVID-19 era.

BACKGROUND: Respiratory syncytial virus (RSV) infection has been identified to serve as the primary cause of acute lower respiratory infectious diseases in children under the age of one and a significant risk factor for the emergence and development of pediatric recurrent wheezing and asthma, though the exact mechanism is still unknown. METHODS AND RESULTS: In this study, we discuss the key routes that lead to recurrent wheezing and bronchial asthma following RSV infection. It is interesting to note that following the coronavirus disease 2019 (COVID-19) epidemic, the prevalence of RSV changes significantly. This presents us with a rare opportunity to better understand the associated mechanism for RSV infection, its effects on the respiratory system, and the immunological response to RSV following the COVID-19 epidemic. To better understand the associated mechanisms in the occurrence and progression of pediatric asthma, we thoroughly described how the RSV infection directly destroys the physical barrier of airway epithelial tissue, promotes inflammatory responses, enhances airway hyper-responsiveness, and ultimately causes the airway remodeling. More critically, extensive discussion was also conducted regarding the potential impact of RSV infection on host pulmonary immune response. CONCLUSION: In conclusion, this study offers a comprehensive perspective to better understand how the RSV infection interacts in the control of the host's pulmonary immune system, causing recurrent wheezing and the development of asthma, and it sheds fresh light on potential avenues for pharmaceutical therapy in the future.

Predictors of recurrent wheezing in late preterm infants.

INTRODUCTION: Premature infants have an increased risk of respiratory morbidity, including the development of recurrent wheezing. We sought to determine perinatal factors in late preterm infants associated with an increased risk of recurrent wheezing in the first 3 years of life. METHODS: A retrospective chart review of infants born between 32 and 36 weeks gestational age at a tertiary hospital from 2013 to 2016 was performed. Infants with any co-morbid medical conditions were excluded. Recurrent wheezing was identified by two or more visit diagnoses for reactive airway disease, wheezing-associated respiratory infection, wheezing, or asthma during the first 3 years of life. Those with recurrent wheezing were compared to matched preterm infants who did not develop wheezing. RESULTS: Three hundred and fourteen late preterm infants were included in this study; 210 infants developed recurrent wheezing while 104 did not. Gender, sex, and race were comparable between both groups. Development of wheezing was associated with positive family history of asthma (p = .014), receiving antibiotics during the neonatal period (p < .001), requiring continuous positive airway pressure for <24 h (p = .019), and receiving supplemental oxygen during the newborn period (p = .023). CONCLUSION: This study retrospectively identified risk factors associated with development of wheezing in late preterm infants. Prospective studies are needed to determine whether these factors will predict recurrent wheeze in this patient population.

Congenital Lobar Emphysema in Children: Case Series.

Recurrent wheezing is very common in infants. When these symptoms appear early without a free interval, a pulmonary malformation should be investigated. Congenital lobar emphysema is a rare abnormality of the lower respiratory tract. Here, we report a case series of six cases of congenital lobar emphysema between 2015 and 2023. Clinical and radiological data were collected according to an operating sheet previously established in our pediatric pneumo-allergology unit. They all had recurrent wheezing and dyspnea. Chest radiography and chest CT were consistent with the diagnosis of congenital lobar emphysema. All patients had lobectomy without complications.

Clinical manifestations of respiratory syncytial virus infection and the risk of wheezing and recurrent wheezing illness: a systematic review and meta-analysis.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infants is a global health priority. We aimed to investigate the common manifestations of RSV infection by age group and human development index (HDI) level and to assess its association with the development of wheezing and recurrent wheezing illness. METHODS: We searched the literature published between January 1, 2010 and June 2, 2022 in seven databases. Outcomes included common manifestations and long-term respiratory outcomes of RSV infection in children. Random- and fixed-effect models were used to estimate the effect size and their 95% confidence intervals. Subgroup analysis was conducted by age and HDI levels. This review was registered in PROSPERO (CRD42022379401). RESULTS: The meta-analysis included 47 studies. The top five manifestations were cough (92%), nasal congestion (58%), rhinorrhea (53%), shortness of breath (50%), and dyspnea (47%). The clinical symptoms were most severe in infants. In our analysis, compared to very high and high HDI countries, fewer studies in medium HDI countries reported related manifestations, and no study in low HDI countries reported that. The RSV-infected infants were more likely to develop wheezing than the non-infected infants [odds ratio (OR), 3.12; 95% CI, 2.59-3.76] and had a higher risk of developing wheezing illnesses after recovery (OR, 2.60; 95% CI, 2.51-2.70). CONCLUSIONS: Cough and shortness of breath are common manifestations of RSV infection. More attention should be given to infants and areas with low HDI levels. The current findings confirm an association between RSV infection and wheezing or recurrent wheezing illness.

Effects and safety of hypertonic saline combined with airway clearance in non-hospitalized children with recurrent wheezing.

Background: The International Study of Wheezing in Infants defines recurrent wheezing as the presence of three or more medically documented episodes of wheezing within one year. To date, there is no evidence on the use of hypertonic saline (HS) combined with airway clearance techniques (ACT) for children with recurrent wheezing treated in an outpatient setting. Therefore, this is the first study to explore the use of such interventions in infants with recurrent wheezing. Objectives: To evaluate the effects and safety of a three-month protocol including HS and ACT for non-hospitalized infants with recurrent wheezing. Methods: Randomized, double-blind, controlled trial, including outpatient infants with recurrent wheezing. Children were randomized to either 3% HS or 0.9% saline groups and were treated with bronchodilator and nebulized with the respective solutions before ACT. The primary outcome was the Wang score. Secondary outcomes included the number of hospitalizations and respiratory crisis, need for rescue medication, and school absences. All variables were measured during the three previous months from inclusion and during intervention period. The study protocol was registered at ClinicalTrials.gov (NCT04331496) on March, 31, 2020. Results: Forty children were included. Regarding immediate effects, significant differences (p<0.001) were found for time, but not for group or interaction (group × time), in all outcome variables (increase in SpO2, decrease in heart and respiratory rate, wheezing episodes, retraction, and Wang score). Comparing the previous three months with the study period, there were significant differences in both groups for the severity of crisis (p<0.001) and medication steps (p=0.002). Conclusion: A three-month protocol including HS and ACT for outpatient infants with recurrent wheezing was safe and reduced morbidity. No differences were found between the use of HS and 0.9% saline.

Risk factors for recurrent wheezing after bronchiolitis.

BACKGROUND: This study aimed to determine whether there was an association between certain factors in patients with bronchiolitis and recurrent wheezing in childhood. METHOD: In 2021 we tracked children hospitalized for bronchiolitis at Chengdu Women's and Children's Central Hospital in 2017. The patients were classified into recurrent wheezing group (RWG) and non-recurrent wheezing group (NRWG). Possible risk factors including maternal age, school-age siblings, allergic history, atopic dermatitis, allergic rhinitis, atopic family history, severity of the condition, duration of hospitalization, nasopharyngeal secretions culture, blood eosinophil counts, FeNO and skin prick test were compared between the two groups. Continuous variables were analyzed by independent sample t-test for normal distribution and Mann-Whitney U-test for non-normal distribution. Categorical variables were tested using chi-square tests. Multifactor analysis was conducted by stepwise logistics regression analysis. RESULTS: In total 167 participants were included, of which 26 and 141 were in RWG and NRWG respectively. In RWG children represented higher maternal age (P = 0.02) and greater probability of allergic history, atopic dermatitis, allergic rhinitis, atopic family history (odds ratio [OR] = 4.0,3.7, 7.8, 10.9 respectively, P < 0.01). However, school-age siblings, severity of the condition, duration of hospitalization, blood eosinophil counts, fractional exhaled nitric oxide and skin prick test results seemed unrelated to recurrent wheezing. In the subgroup analysis of nasopharyngeal secretion culture, there were more Moraxella catarrhalis-positive in RWG(P = 0.043). Atopic dermatitis, allergic rhinitis and atopic family history were identified as independent risk factors for recurrent wheezing. CONCLUSION: Some children with bronchiolitis will develop recurrent wheezing, and the risk factors are allergic history, Moraxella catarrhalis infection or colonization, atopic dermatitis, allergic rhinitis and atopic family history; the latter three are independent risk factors.

Dysregulation of iron homeostasis in airways associated with persistent preschool wheezing.

BACKGROUND: Currently, there are no reliable clinical tools available to identify persistent asthma symptoms among preschool children with recurrent wheezing. We investigated iron homeostasis in the airways of preschoolers with recurrent wheezing and assessed whether iron homeostasis-related indices may reliably predict persistent wheezing. METHODS: Iron levels and mRNA expression levels of iron homeostasis molecules were examined in bronchoalveolar lavage samples from 89 preschoolers with recurrent wheezing and 56 controls, with a 12-month follow-up conducted. Risk factors for persistent wheezing were identified using least absolute shrinkage and selection operator and multivariate logistic regression. The addition of predictive values of iron indices to the modified Asthma Predictive Index (mAPI) or clinical predictors was determined using area under receiver operating characteristic curves (AUC). RESULTS: Preschoolers with recurrent wheezing had reduced iron levels in their airways, associated with significantly decreased expression of iron export molecule SLC40A1 and increased expression of iron intake factor TFR1 and iron storage factors FTH and FTL. Risk factors for persistent wheezing included mAPI positivity, iron predictors (lower expression of SLC40A1 and higher expression of FTL), and clinical predictors (aeroallergen sensitivity, shorter breastfeeding duration, and earlier age of first wheezing episode). The addition of information on iron predictors significantly enhanced the power of clinical predictors (AUC: 84%, increase of 12%) and mAPI (AUC: 81%, increase of 14%). CONCLUSIONS: Iron homeostasis is altered in the airways of preschoolers with recurrent wheezing. Adding information on iron-related indices to clinical information significantly improves accurate prediction of persistent wheezing in preschool-aged children.

Serum bilirubin is associated with a reduced risk of subsequent recurrent wheezing following acute respiratory syncytial virus bronchiolitis.

BACKGROUND: Bilirubin is a potent antioxidant and anti-inflammatory molecule that has been shown to ameliorate airway inflammation. We aimed to study whether serum bilirubin is protective and can predict the development of subsequent recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis. METHODS: The medical records of 188 infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were retrospectively reviewed. Our main outcome of interest was the development of subsequent recurrent wheezing by the age of 3 years. Each infant's serum bilirubin concentration was extracted from their blood biochemical results. RESULTS: Seventy-one (37.8%) infants developed recurrent wheezing by the age of 3 and 117 (62.2%) did not. The serum total bilirubin, unconjugated bilirubin, and conjugated bilirubin levels at hospital admission were lower in infants who developed recurrent wheezing as compared to those who did not (p ＜ 0.001). The area under the receiver-operating characteristic curve of serum total bilirubin, unconjugated bilirubin, and conjugated bilirubin for the prediction of subsequent recurrent wheezing were 0.71 (95% confidence interval [CI], 0.64-0.78), 0.70 (95% CI, 0.63-0.78), and 0.67 (95% CI, 0.59-0.75), respectively. Higher admission serum total bilirubin levels were independently associated with a lower risk of development of subsequent recurrent wheezing (adjusted OR 0.17, p ＜ 0.001). CONCLUSION: During the first episode of severe RSV bronchiolitis in infants <6 months of age, moderately higher levels of serum bilirubin are associated with a reduced risk of developing subsequent recurrent wheezing by 3 years of age.

Recurrent wheezing phenotypes after severe bronchiolitis and progression to asthma.

Background: Recurrent wheezing, a common diagnosis after severe bronchiolitis, has multiple phenotypes of uncertain relation to childhood asthma. Objective: Among infants hospitalized for bronchiolitis, we investigated the relation of three 2020 recurrent wheezing phenotypes by age 4 years to asthma by age 6 years. Methods: In a 17-center cohort study of infants hospitalized with bronchiolitis, we investigated the National Heart, Lung, and Blood Institute (NHLBI) 2020-defined recurrent wheezing phenotype and 2 additional phenotypes based on this definition: multitrigger and severe. As a sensitivity analysis, we examined the NHLBI 2007 recurrent wheezing phenotype. We calculated the proportion of study subjects who developed asthma by age 6 years and used multivariable logistic regression to examine characteristics associated with the highest-risk 2020 phenotype. Results: Of 921 infants, 632 (69%) developed NHLBI 2020 recurrent wheezing, 734 (80%) developed multitrigger wheezing, and 165 (18%) developed severe wheezing by age 4 years; in addition, 296 (32%) developed NHLBI 2007-defined recurrent wheezing by age 3 years. Of 862 children with sufficient data (94%), 239 (28%) developed asthma by age 6 years. The proportions of children who progressed to asthma were as follows: 33% of those with NHLBI 2020-defined wheezing, 33% of those with multitrigger wheezing, 54% of those with severe wheezing, and 52% of those with NHLBI 2007-defined recurrent wheezing. The children with the severe phenotype who developed asthma had the associated characteristics preterm birth, child eczema, maternal asthma, and non-respiratory syncytial virus infection. Conclusion: Most infants with severe bronchiolitis developed the NHLBI 2020-defined recurrent wheezing phenotype by age 4 years. Depending on the phenotype, 33% to 54% will develop asthma by age 6 years. Future research will examine whether earlier treatment of high-risk phenotypes will improve wheezing symptoms and potentially prevent childhood asthma. (J Allergy Clin Immunol Global 2023;2:84-7.).

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.

Children at the Risk of Recurrent Wheezing: A Matched Case-Control Study in a Tertiary Care Center.

Introduction Wheezing is a common symptom in early childhood. Recurrent wheezing is defined as more than three episodes of wheezing in the past year. Many studies have been conducted to delineate the risk factors for recurrent wheezing and to predict which of these children will progress to asthma. Most studies about risk factors and the clinicodemographic profile of children with recurrent wheeze have been carried out in developed nations. Data in developing countries may differ. This study was carried out to identify risk factors associated with recurrent wheezing in children in a tertiary care center. Materials and methods It was a retrospective, matched case-control study conducted over a period of two years (July 2019 to July 2021). Records of children aged one month to 12 years who came to pediatric OPD or were admitted to a pediatric ward with a history of recurrent wheezing were included in the study. Cases with uncontrolled recurrent wheezing diagnosed by examination with an unreliable history and those with a global developmental delay were excluded from the study. The study involved the hospital records of 60 children. Of these, 30 were recurrent wheezers, and 30 were non-wheezers (controls). Data were collected with detailed proformas from case histories and examination sheets. The proforma had several known and suspected risk factors associated with wheezes. Each risk factor was studied and compared with the control group. The risk factors included in this study were male gender, not exclusively breastfed, history of bottle feeding, exposure to vehicles; exposure to pollen; exposure to animals; using an agarbatti or dhoop, passive smoking, or playing with a soft toy. Data were entered in an Excel sheet, and appropriate statistical analyses were done. Results The male-to-female ratio was 2:1. Out of the number of cases, 73.33% were younger than six years; 56.66% of cases were not exclusively breastfed, and 43.33% were exclusively breastfed for six months; 20% of the cases were bottle-fed, and 40% of the controls were bottle-fed. The percentage of cases exposed to vehicle smoke was 26.66%, while 20% of cases had exposure to pollen and 16% of controls were exposed to pollen. 30% of cases were exposed to animals, and 23% of controls were exposed to animals. With regard to passive smoking, 16.66% of cases were exposed to passive smoking, and 20% of controls were not exposed to passive smoking. Out of the study group, 26.66% of the children played with soft toys. Of all these risk factors, a significant difference between cases and controls was found in only one factor: not being exclusively breastfed for six months. All other risk factors showed no significant difference between cases and controls. Conclusion The present study concluded that the significant risk factor that was associated with recurrent wheezing was "not exclusively breastfeeding." The other factors studied that were suspected to be associated with recurrent wheezing cannot be ruled out entirely due to the relatively small size of the sample and the need to be studied further in detail.

An analysis of risk factors associated with recurrent wheezing in the pediatric population.

BACKGROUND: Recurrent wheezing is a common clinical problem in early childhood, which is associated with significant morbidity. There is no international consensus on the management and prevention of recurrent wheezing; therefore, identifying the risk factors associated with recurrent wheezing is crucial to prevent episodes of wheezing in young children. METHODS: In this retrospective study, we collected the data of 24,737 patients who were admitted to our hospital between 27th April 2012 and 11th September 2019. After screening for patients with wheezing, we identified 8572 patients with a primary diagnosis of pneumonia with wheezing. Patients' clinical data were collected from the hospital medical records. Patients were stratified for age in the groups of < 6 months, 6-12 months, and > 12 months. RESULTS: Among the 8569 pediatric pneumonia patients with wheezing, there were 343 patients with recurrent wheezing. Most enrolled patients were under 6 months of age (45.17%) and had a normal birth weight (86.95%). Winter was the most common onset season for the first episode of wheezing, while spring was the most common season for the second episode of wheezing for those with recurrent wheezing. The univariate and multivariate logistic regression analysis for the risk factor associated with recurrent wheezing showed that male gender, past history of respiratory and cardiovascular diseases, low birth weight, development of severe pneumonia, and PICU admission were significantly associated with recurrent wheezing. CONCLUSION: Male gender, past history of respiratory and cardiovascular diseases, low birth weight, severe pneumonia, and PICU admission are independent risk factors of recurrent wheezing in the pediatric population.

Network analyses of upper and lower airway transcriptomes identify shared mechanisms among children with recurrent wheezing and school-age asthma.

Background: Predicting which preschool children with recurrent wheezing (RW) will develop school-age asthma (SA) is difficult, highlighting the critical need to clarify the pathogenesis of RW and the mechanistic relationship between RW and SA. Despite shared environmental exposures and genetic determinants, RW and SA are usually studied in isolation. Based on network analysis of nasal and tracheal transcriptomes, we aimed to identify convergent transcriptomic mechanisms in RW and SA. Methods: RNA-sequencing data from nasal and tracheal brushing samples were acquired from the Gene Expression Omnibus. Combined with single-cell transcriptome data, cell deconvolution was used to infer the composition of 18 cellular components within the airway. Consensus weighted gene co-expression network analysis was performed to identify consensus modules closely related to both RW and SA. Shared pathways underlying consensus modules between RW and SA were explored by enrichment analysis. Hub genes between RW and SA were identified using machine learning strategies and validated using external datasets and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the potential value of hub genes in defining RW subsets was determined using nasal and tracheal transcriptome data. Results: Co-expression network analysis revealed similarities in the transcriptional networks of RW and SA in the upper and lower airways. Cell deconvolution analysis revealed an increase in mast cell fraction but decrease in club cell fraction in both RW and SA airways compared to controls. Consensus network analysis identified two consensus modules highly associated with both RW and SA. Enrichment analysis of the two consensus modules indicated that fatty acid metabolism-related pathways were shared key signals between RW and SA. Furthermore, machine learning strategies identified five hub genes, i.e., CST1, CST2, CST4, POSTN, and NRTK2, with the up-regulated hub genes in RW and SA validated using three independent external datasets and qRT-PCR. The gene signatures of the five hub genes could potentially be used to determine type 2 (T2)-high and T2-low subsets in preschoolers with RW. Conclusions: These findings improve our understanding of the molecular pathogenesis of RW and provide a rationale for future exploration of the mechanistic relationship between RW and SA.

Parental Mental Health and Childhood Respiratory Outcomes in a Severe Bronchiolitis Cohort.

Parental mental health conditions appear to contribute to the development of childhood respiratory illness. We investigated the relationship between parental mental health and childhood respiratory illness using data from a 17-center prospective cohort study of infants hospitalized with bronchiolitis between 2011 and 2014 (n = 921). Among 779 (84.6%) participants with self-reported parental mental health history data, 184 (23.6%) had parental history of depression and 155 (19.9%) had anxiety. Multivariable analyses found that both parental history of depression (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.01-1.99) and anxiety (HR 1.28, 95% CI 1.08-1.52) were associated with an increased risk of recurrent wheezing by age 3 years. However, only parental history of anxiety was associated with asthma by age 5 years (odds ratio 1.79, 95% CI 1.25-2.55). Further research on exposure severity, other early life stressors, and effective methods of parental psychosocial support is needed to develop targeted risk factor prevention strategies to reduce the burden of childhood respiratory illness.

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

BACKGROUND: Severe 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. METHODS: Observational, 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. RESULTS: A 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). CONCLUSIONS: Our 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.

Association of adenotonsillectomy with wheezing episodes in childhood: A secondary analysis of the Childhood Adenotonsillectomy Trial.

BACKGROUND: Observational studies suggest that asthma/wheezing improves after adenotonsillectomy (AT). However, there is a paucity of randomized clinical trial (RCT) specifically studying the effects of AT in asthma/wheezing. Therefore, we conducted a post-hoc analysis of the Childhood Adenotonsillectomy Trial (CHAT), the largest RCT of AT in children with obstructive sleep apnea (OSA) to test the hypothesis that AT would result in fewer wheezing episodes. METHODS: In the CHAT study, 464 children with OSA, aged 5-9 years, were randomized to early AT (n = 226) or watchful waiting with supportive care (WWSC) (n = 227). For this post-hoc analysis, children were categorized as having "any wheezing" versus "no wheezing" at baseline and at 7 months of follow-up. A multivariate analysis was conducted to evaluate the association between "any wheezing" at follow-up and treatment group after controlling for several potential confounders. RESULTS: Children in the "any wheezing" group were predominantly black, had more allergic rhinitis, eczema, second-hand smoke exposure, body mass index, apnea-hypopnea index (AHI), and had lower maternal education and family income than those in the "no wheezing group." In the AT arm, the prevalence of wheezing significantly decreased from baseline to follow-up (at 7 months of the intervention) (47% vs. 21.6%, p < 0.001); while in the WWSC arms did not change (45.2% vs. 43.1%, p = 0.67). In the multivariate analysis, second-hand smoke exposure, wheezing at baseline, and belong to WWSC arm (odds ratio: 3.65 [2.16-6.19]) increase the risk of wheezing at follow-up. CONCLUSION: This study demonstrated that AT decreased the risk of wheezing at 7 months of follow-up.

The Use of Bacterial Lysate for the Prevention of Wheezing Episodes in Preschool Children: A Cost-Utility Analysis.

BACKGROUND: Although increasing recent evidence has shown the efficacy of bacterial lysate therapy for the prevention of wheezing episodes and asthma exacerbations in pediatric patients, evidence of its cost-effectiveness in preschool patients is scarce. OBJECTIVES: To evaluate the cost-utility of bacterial lysate therapy as an add-on to standard care of preschool children with recurrent wheezing. METHODS: To achieve the objectives of the study, we used a Markov simulation model with 3 mutually exclusive nonabsorbent states (regular Markov chain). Effectiveness parameters were obtained from a recent systematic review of the literature with meta-analyses (5 randomized controlled trials, 433 children). Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national health care system in Colombia. The main outcome of the model was quality-adjusted life-years. To assess the robustness of the model's results, we performed deterministic and probabilistic sensitivity analysis. RESULTS: Compared with standard care, bacterial lysate add-on therapy to standard care was associated with lower overall treatment costs (US $694.03 vs $830.71 average cost per patient) and the greatest gain in QALYs (0.9211 vs 0.9154 QALYs on average per patient), thus showing dominance. CONCLUSIONS: In Colombia, compared with standard care, bacterial lysate add-on therapy to standard care for treating preschool children with recurrent wheezing is a dominant strategy because it showed a greater gain in QALYs at lower total treatment costs.

Establishment and validation of a model for predicting recurrent wheezing in children with bronchiolitis / 中国医师进修杂志

Objective:To analyze the risk factors of recurrent wheezing in children with bronchiolitis and to construct a predictive model.Methods:Prospective research methods was used. One hundred and eighty children with bronchiolitis who were treated in Hefei Eighth People's Hospital from February 2017 to February 2019 were selected as the study subjects, and the included children were separated into a modeling group (126 cases) and a validation group (54 cases) according to 7∶3. The children were followed up for 3 years, and then the modeling group was divided into wheezing group (48 cases) and no wheezing group (78 cases) according to whether the children had recurrent wheezing. The Hosmer-Lemeshow fitting curve and receiver operating characteristic (ROC) curve were drawn to evaluate the validity and accuracy of the constructed prediction model.Results:Multivariate Logistic regression analysis showed that artificial feeding ( OR = 8.838, 95% CI 2.601 to 30.027), family history of allergies ( OR = 6.709, 95% CI 1.825 to 24.665), underlying diseases ( OR = 8.114, 95% CI 1.638 to 40.184), and higher IgE level ( OR = 1.020, 95% CI 1.012 to 1.029) were the independent risk factors for recurrent wheezing in children with bronchiolitis ( P<0.05). The area under the curve of the modeling group was 0.917 (95% CI 0.855 to 0.959), and the sensitivity and specificity were 83.33% and 85.90%, respectively; the area under the curve of the validation group was 0.911 (95% CI 0.847 to 0.954), and the sensitivity and specificity were 89.58% and 79.49%, respectively. Conclusions:Artificial feeding, family history of allergies, underlying diseases, and higher IgE level are the independent risk factors for recurrent wheezing in children with bronchiolitis. The constructed prediction model has good accuracy and validity, and can be used as an effective tool for clinical prediction of recurrent wheezing in children with bronchiolitis.

Sibilancia recurrente en pediatría

Introducción: los episodios de obstrucción bronquial a temprana edad constituyen un problema frecuente en pediatría. Se realizó un estudio descriptivo, longitudinal, retrospectivo. Objetivo: caracterizar el comportamiento de la sibilancia recurrente en los niños menores de 5 años pertenecientes al municipio Bayamo, del Hospital Provincial Pediátrico Docente "General Milanés "en el año 2019. Métodos: la muestra fue de 63 pacientes y se estudiaron las variables edad, sexo, lactancia materna, ingresos previos, procedencia, género de vida y posibles factores de riesgo. El análisis estadístico se realizó a través de las estimaciones de las frecuencias absolutas y relativas. Resultados: predominaron los niños de 1 a 5 años con 52 casos (82.6%) y el sexo masculino, 29 de ellos pertenecieron a este grupo etáreo ( 80.6%); los ingresos previos de menos de 3 días en 37 casos (66.1%) y 56 casos no recibieron lactancia materna exclusiva, 37 de ellos representó el 66.1%; 44 casos tuvieron un género de vida malo ( 69.8%) y de los 43 casos que procedían de la zona urbana 28 pertenecían a ese género de vida(65.1%); los antecedentes patológicos familiares de alergia o asma y la atopia fueron los más significativos con 63 y 52 casos(100 y 82.5%) respectivamente. Conclusiones: se comprobó que la edad de 1 a 5 años, el sexo masculino, los ingresos de menos de tres días, sin lactancia materna , el género de vida malo, la procedencia urbana fueron los que predominaron en el estudio, así como los antecedentes patológicos familiares y la atopia como factores de riesgo que exacerbaron la enfermedad.

Introduction: episodes of bronchial obstruction at an early age are a frequent problem in pediatrics. A descriptive, longitudinal, retrospective study was conducted. Objective: to characterize the behavior of recurrent wheezing in children under 5 years of age belonging to the Bayamo municipality, of the "General Milanés" Teaching Pediatric Provincial Hospital in 2019. Methods: the sample consisted of 63 patients and the variables age, sex, breastfeeding, previous income, origin, gender of life and possible risk factors were studied. Statistical analysis was performed through estimates of absolute and relative frequencies. Results: there was a predominance of children aged 1 to 5 years with 52 cases (82.6%) and males, 29 of them belonged to this age group (80.6%); previous admissions of less than 3 days in 37 cases (66.1%) and 56 cases did not receive exclusive breastfeeding, 37 of them accounted for 66.1%; 44 cases had a bad lifestyle (69.8%) and of the 43 cases that came from the urban area, 28 belonged to that kind of life (65.1%); Family pathological history of allergy or asthma and atopy were the most significant wit. Conclusions: it was found that age from 1 to 5 years, male sex, income of less than three days, without breastfeeding, poor lifestyle, urban origin were those that predominated in the study, as well as family pathological history and atopy as risk factors that exacerbated the disease.

Introdução: episódios de obstrução brônquica em idade precoce são um problema frequente em pediatria. Trata-se de um estudo descritivo, longitudinal e retrospectivo. Objetivo: caracterizar o comportamento da sibilância recorrente em crianças menores de 5 anos pertencentes ao município de Bayamo, do Hospital Provincial Pediátrico Universitário "General Milanés", em 2019. Métodos: a amostra foi composta por 63 pacientes e estudadas as variáveis idade, sexo, aleitamento materno, renda prévia, procedência, sexo de vida e possíveis fatores de risco. A análise estatística foi realizada por meio de estimativas de frequências absolutas e relativas. Resultados: houve predomínio de crianças de 1 a 5 anos com 52 casos (82,6%) e do sexo masculino, sendo que 29 deles pertenciam a essa faixa etária (80,6%); internações anteriores inferiores a 3 dias em 37 casos (66,1%) e 56 casos não receberam aleitamento materno exclusivo, sendo que 37 deles corresponderam a 66,1%; 44 casos tinham estilo de vida ruim (69,8%) e dos 43 casos provenientes da zona urbana, 28 pertenciam a esse tipo de vida (65,1%); História anatomopatológica familiar de alergia ou asma e atopia foram as mais significativas, com 63 e 52 casos (100 e 82,5%), respectivamente. Conclusões: verificou-se que idade de 1 a 5 anos, sexo masculino, renda inferior a três dias, ausência de aleitamento materno, estilo de vida ruim, origem urbana foram os que predominaram no estudo, assim como história patológica familiar e atopia como fatores de risco que exacerbaram a doença.