Transient Wheeze Research Articles

Longitudinal transcriptional immune profiles and persistent wheezing in moderate-to-late preterm infants.

Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing. A convenience sample of a multicenter birth cohort (SAREPREM) of moderate-late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression. Seventy-six children were included in the study; 33 were classified as non-wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non-wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers. Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late-preterm infants.

Maternal exposure to smoking and wheezing phenotypes in children: a cohort study of the Japan Environment and Children’s Study

BackgroundPrevious studies have shown that prenatal maternal smoking and maternal secondhand smoke exposure during pregnancy were associated with an increased risk of wheezing and asthma development. However, few studies have examined the influence of different sources of tobacco exposure in different perinatal timeframes (preconception, prenatal, and postnatal) on wheezing phenotypes in children. Using national survey data from Japan, we investigated the effects of exposure to tobacco smoke during pregnancy on wheezing phenotypes in children before the age of 3 years.MethodsPregnant women who lived in the 15 regional centers in the Japan Environment and Children’s Study were recruited. We obtained information on prenatal and postnatal exposure to active and secondhand smoke (SHS) and wheeze development up to 3 years of age. Multiple logistic regression analysis was performed to determine the association between tobacco smoke exposure and wheezing phenotypes in children.ResultsWe analyzed 73,057 singleton births and identified four longitudinal wheezing phenotypes: never wheezing; early transient wheezing (wheezing by age 1 year but not thereafter); late-onset wheezing (wheezing by age 2–3 years but not beforehand); and persistent wheezing. Maternal smoking during pregnancy was significantly associated with early transient and persistent wheezing in children compared with no maternal smoking [early transient wheezing: 1–10 cigarettes per day, adjusted odds ratio (aOR) 1.43, 95% confidence interval (CI) 1.23–1.66; ≥ 11 cigarettes per day, aOR 1.67, 95% CI 1.27–2.20; persistent wheezing: 1–10 cigarettes per day, aOR 1.64, 95% CI 1.37–1.97; ≥ 11 cigarettes per day, aOR 2.32, 95% CI 1.70–3.19]. Smoking cessation even before pregnancy was also significantly associated with increased risk of early transient wheezing, late-onset wheezing, and persistent wheezing in children. Moreover, maternal exposure to SHS during pregnancy was significantly associated with increased risk of early transient and persistent wheezing compared with no such exposure.ConclusionsMaternal smoking before and throughout pregnancy was associated with wheeze development in children up to 3 years of age. It appears that smoking is detrimental compared to never smoking, regardless of whether individuals quit smoking before or after becoming aware of the pregnancy.

Early-life nasal microbiota dynamics relate to longitudinal respiratory phenotypes in urban children

Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described. Our aim was to determine whether distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures. Microbiota profiling was performed using 16S ribosomal RNA-based sequencing of nasal samples collected at age 12 months (n= 120) or age 36 months (n= 142) and paired house dust samples collected at 3 months (12-month, n= 73; 36-month, n= 90) from all 4 centers in the Urban Environment and Childhood Asthma (URECA) cohort. In these high-risk urban children, nasal microbiota increased in diversity between ages 12 and 36 months (ß= 2.04; P= .006). Age-related changes in microbiota evenness differed significantly by respiratory phenotypes (interaction P= .0007), increasing most in the transient wheeze group. At age 12 months, respiratory illness (R2= 0.055; P= .0001) and dominant bacterial genus (R2= 0.59; P= .0001) explained variance in nasal microbiota composition, and enrichment of Moraxella and Haemophilus members was associated with both transient and high-wheeze respiratory phenotypes. By age 36months, nasal microbiota was significantly associated with respiratory phenotypes (R2= 0.019; P= .0376), and Moraxella-dominated microbiota was associated specifically with atopy-associated phenotypes. Analysis of paired house dust and nasal samples indicated that 12 month olds with low wheeze and atopy incidence exhibited the largest number of shared bacterial taxa with their environment. Nasal microbiota development over the course of early childhood and composition at age 3 years are associated with longitudinal respiratory phenotypes. These data provide evidence supporting an early-life window of airway microbiota development that is influenced by environmental microbial exposures in infancy and associates with wheeze- and atopy-associated respiratory phenotypes through age 7 years.

Может ли компонентная аллергодиагностика помочь в установлении траектории формирования «атопического марша»?

Recently, the atopic march (AM) is no longer considered a clear and sequential development of successive allergic diseases, such as atopic dermatitis (AD), asthma, and allergic rhinitis (AR). Recent studies have shown that associations between allergic disorders in children are much more complex, and there may be different variants of AM trajectories. Previously, eight classes of AM were described: (1) no allergic disorders, (2) AM, (3) AD and transient wheeze, (4) AD with later-onset rhinitis, (5) transient wheeze and later-onset rhinitis, (6) transient wheeze only, (7) eczema only, and (8) rhinitis only. 48.3% of children exhibit specific types of sequential development of allergic disorders, but only 7% exhibit profiles resembling ‘classic' AM. The aim of this article was to analyze AM trajectories in real clinical practice in children and to discuss the role of component resolved diagnosis (CRD) in the analysis of AM. The article presents anamnestic patient data and CRD results using a multiplex panel. The literature shows that AM classes do not always match the actual clinical presentation of a patient, indicating the presence of previously unreported AM trajectories. Molecular allergy diagnostics can identify true and cross-sensitization in complex clinical cases, allowing for consideration of the causes of established sensitization and conceptualization of clinical symptoms and individual AM trajectory. It is important to ensure that sensitization to true allergens is established and clinically verified. The analysis of anamnestic data can make it difficult to understand the sequence of allergic disease development. However, CRD significantly facilitates diagnostic search by allowing consideration of the order of sensitization and clinical manifestations. This can help predict the possible severity of allergic reactions to established allergens. KEYWORDS: atopic march, atopic dermatitis, allergic rhinitis, asthma, children, component resolved diagnosis, respiratory allergens. FOR CITATION: Lepeshkova T.S., Andronova E.V. Can component resolved diagnosis help establish "atopic march" trajectory? Russian Medical Inquiry. 2024;8(3):163–170 (in Russ.). DOI: 10.32364/2587-6821-2024-8-3-7.

Predictors of persistent asthma among preschooler wheezers: a retrospective case series study

BackgroundEarly childhood wheezing can evolve to different asthma phenotypes. Prediction of persistent asthma during the preschool years has proven challenging. Through this study, we aimed to identify predictors of persistent asthma in preschooler wheezers.MethodsThis was a retrospective case series study over 10 years. Patient data from 98 infants diagnosed with infantile asthma were obtained from their medical records. A multivariate logistic regression model was developed to determine predictors of persistent asthma in preschooler wheezers.ResultsThe sex ratio was 1.72. The mean age at the first episode of wheezing was 7 ± 3.17 months. The mean age at diagnosis was 14.82 ± 4.28. Asthma was well controlled in 71 cases (72.44%) and partly controlled in 27 cases (27.56%). Two groups were identified: transient wheezers (61.33%) and persistent wheezers beyond the age of 5 years old (38.77%). The average age for wheezing disappearance was 24.28 ± 4.1 months.Four predictive factors for persistent asthma were identified: familial atopy (adjusted odds ratio [OR] 4.76; 95% confidence interval [CI] 2.52–12.45; p < 0.001), passive smoking (adjusted OR 5.98; 95% CI 2.48–13.64; p < 0.001), poor control of asthma (adjusted OR 5.23; 95% CI 2.47–14.76; p 0.0013), and aerosensitization (adjusted OR 7.38; 95%CI 3.87–17.84; p < 0.001).ConclusionsThe main predictors for persistent asthma among preschooler wheezers were aerosensitization, family history of atopy, early exposure to passive smoking, and poor control of asthma. The detection of such factors allows for earlier diagnosis and targeted prevention strategies.

LEVELS OF IL-4 AND Γ- INTERFERON IN CHILDREN’S BLOOD SERUM AS PREDICTORS OF ASTHMA FORMATION

Introduction. The prevalence of asthma continues to increase every year. Asthma is the leading chronic disease. Infl ammation,both acute and chronic, is closely related to the action of cytokines (pro- and anti-infl ammatory). T-helper 2 lymphocytesrelease IL-4, which triggers the production of immunoglobulin E (IgE) antibodies, which set the stage for allergy and activateinfl ammatory cells. The regulators of this process are T helper-1 lymphocytes, which produce cytokines (IFN-gamma) thatsuppress Th-2 activity. Disturbances in the ratio of Th-1/Th-2 lymphocyte clones are a subject of debate in the early detectionof asthma and the prediction of the development of this disease.The aim of the study was to evaluate the levels of IL-4 and γ-interferon in the blood serum of children with transient wheezeand asthma..Material and methods. 121 children were included in the study. The patients were divided into groups: group 1 – childrenwith transient wheezing (TW) (n = 81), group 2 – children with doctor- diagnosed asthma (DDA) (n = 15), group 3 – healthychildren (n = 25).IL-4 and γ-interferon in blood serum were analyzed by ELISA using commercial kits (human IL-4 and human γ-interferon“Vector Best- Ukraine”). Data were analyzed using Statsoft Statistica version 8 (Tulsa, OK) and the MedCalc version 17.2statistical program.The planned clinical trials were conducted after obtaining the approval of the local ethics committee (date: February 1, 2015;number: 2015/01) and were conducted in accordance with the principles of the Declaration of Helsinki, as amended in October 2013.This article was conducted within the framework of the Department of Pediatrics No. 2 of Kharkiv National MedicalUniversity «Medical and biological aspects of adaptation of children with somatic pathology to modern conditions. Predictionof asthma control in children taking into account infl ammatory markers and the state of the airway barrier of the lungs» (stateregistration number 0120U102471).Results. It was found that in children of the fi rst and second groups, in the midst of clinical manifestations of wheezing, IL-4levels signifi cantly increased and serum γ-interferon levels decreased. The highest levels of IL-4 and the lowest levels of serumγ-interferon were found in patients with DDA.Serum levels of IL-4 above 15.33 pg/mL and γ-interferon below 98.62 pg/mL in children with wheezing episodes may beconsidered as a possible indicator of asthma development.Conclusions. Serum IL-4 and γ-interferon are involved in the regulation of allergic infl ammatory processes in the body.A statistically signifi cant increase in IL-4 levels and a decrease in γ-interferon levels in the blood serum of patients with asthmais likely to indicate the development of a chronic form of infl ammation.

The ADEM2 project: early pathogenic mechanisms of preschool wheeze and a randomised controlled trial assessing the gain in health and cost-effectiveness by application of the breath test for the diagnosis of asthma in wheezing preschool children

BackgroundThe prevalence of asthma-like symptoms in preschool children is high. Despite numerous efforts, there still is no clinically available diagnostic tool to discriminate asthmatic children from children with transient wheeze at preschool age. This leads to potential overtreatment of children outgrowing their symptoms, and to potential undertreatment of children who turn out to have asthma. Our research group developed a breath test (using GC-tof–MS for VOC-analysis in exhaled breath) that is able to predict a diagnosis of asthma at preschool age. The ADEM2 study assesses the improvement in health gain and costs of care with the application of this breath test in wheezing preschool children.MethodsThis study is a combination of a multi-centre, parallel group, two arm, randomised controlled trial and a multi-centre longitudinal observational cohort study. The preschool children randomised into the treatment arm of the RCT receive a probability diagnosis (and corresponding treatment recommendations) of either asthma or transient wheeze based on the exhaled breath test. Children in the usual care arm do not receive a probability diagnosis. Participants are longitudinally followed up until the age of 6 years. The primary outcome is disease control after 1 and 2 years of follow-up. Participants of the RCT, together with a group of healthy preschool children, also contribute to the parallel observational cohort study developed to assess the validity of alternative VOC-sensing techniques and to explore numerous other potential discriminating biological parameters (such as allergic sensitisation, immunological markers, epigenetics, transcriptomics, microbiomics) and the subsequent identification of underlying disease pathways and relation to the discriminative VOCs in exhaled breath.DiscussionThe potential societal and clinical impact of the diagnostic tool for wheezing preschool children is substantial. By means of the breath test, it will become possible to deliver customized and high qualitative care to the large group of vulnerable preschool children with asthma-like symptoms. By applying a multi-omics approach to an extensive set of biological parameters we aim to explore (new) pathogenic mechanisms in the early development of asthma, creating potentially interesting targets for the development of new therapies.Trial registrationNetherlands Trial Register, NL7336, Date registered 11–10-2018.

Persistent Asthma at School Age: Associated Factors in Preschool Children with Asthma.

Most patients with childhood asthma present their first symptoms at preschool age. Identifying modifiable risks and protective factors at an early age may help develop asthma prevention and control strategies. This study aimed to identify factors at preschool age that are associated with persistent asthma at school age. This retrospective observational study included preschool children with asthma from 2015 to 2020 at a university hospital in Southern Thailand. In total, 189 eligible participants (70.9% boys; median age, 7.6 [6.7, 8.5] years) were included. Wheeze characteristics included early transient wheeze, persistent wheeze, and late-onset wheeze that accounted for 55%, 27.5%, and 19.5% of the patients, respectively. Approximately 20% of the participants had persistent asthma. Breastfeeding was a protective factor (odds ratio [OR] 0.4 [0.2, 0.9], p = 0.04). The modifiable risk factors were siblings living in the same household (OR 2.6 [1.1, 6.2], p = 0.02) and residence in an industrial area (OR 3.8 [1.4, 10.5], p = 0.009). Additionally, presence of allergic rhinitis was associated with an increased risk of persistent asthma at school age (OR 3.6 [1.6, 8.2], p = 0.002). Early therapeutic interventions targeting modifiable factors provide a window of opportunity to prevent persistent asthma at school age.

Comparison of parent reported physician diagnosed asthma and general practitioner registration

Objective To compare parent reported physician diagnosed asthma from questionnaires for epidemiological purposes, to general practitioner (GP) recorded childhood asthma. Methods This study was embedded in the KOALA Birth Cohort Study with regular follow-up by ISAAC core questions on asthma in 2834 children in two different recruitment groups, with ‘conventional’ lifestyles or ‘alternative’ lifestyles. At age 11–13 years these data were linked to data extracted from GP records. We compared parent reported physician diagnosed asthma, asthma medication use, and current asthma with GP recorded asthma diagnosis and medication. Two different combinations of questions were used to define current asthma (i.e. ISAAC and MeDALL based definition). Results Among 958 children with information provided both by the parents and GPs, 98 children (10.2%) had parent reported physician diagnosed asthma, 115 children (12.0%) had a GP recorded asthma diagnosis (Cohen’s kappa 0.49; 95% CI 0.40 to 0.57). Discrepant cases showed that asthma symptoms at an early age led to different labeling between parents and GP. The agreement between ISAAC based definition and MeDALL based definition was excellent (Cohen’s kappa 0.82; 95% CI 0.74 to 0.88). Conclusion Parent reported physician diagnosed asthma and GP recorded childhood asthma had only moderate agreement, and is possibly influenced by labeling early transient wheeze as asthma diagnosis. It is important that parent reported physician diagnosed asthma is combined with additional questions such as current asthma symptoms and asthma medication use, as used in ISAAC or MeDALL based current asthma, in order to obtain reliable information for epidemiological research.

Transient low IgG4 levels cause recurrent wheezing requiring multiple hospitalizations in infancy.

To investigate whether the immunoglobulin G (IgG4) subclass is associated with recurrent wheezing and/or asthma in infants. From April 2015 to March 2016, 77 infants under 3 years old who attended our hospital were enrolled in four groups (Group 1, controls; Group 2, infants with recurrent wheezing and multiple hospitalizations despite starting inhaled corticosteroids [ICS]; Group 3, infants with recurrent wheezing and without hospitalization after starting ICS; Group 4, allergic infants without wheezing). The relationship between IgG subclasses, especially IgG4, and recurrent wheezing resistant to ICS and requiring multiple hospitalizations in infants was examined. The serum IgG, IgM, IgA, IgG1, IgG2, and IgG3 levels did not differ significantly among the four groups. The IgG4 level in Group 2 infants (3.1 ± 0.2 mg/dl) was significantly lower than in Groups 1,3, and 4 (9.9 ± 8.0, 8.4 ± 6.1, and 23.4 ± 18.0 mg/dl). Of the 16 infants in Group 2, 10 could be followed to age 6 years. Nine of them had no recurrent wheezing at 6 years without medication. In addition, their IgG4 levels at age 6 years (16.1 ± 7.1 mg/dl) were significantly increased from those in infancy (3.0 ± 0.1 mg/dl). A transient low IgG4 level in infancy might cause recurrent wheezing and/or asthmatic symptoms in infants, and it may be one of the types of early transient wheezing.

Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study

Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood. In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years. Wheeze data were collected at 8 time points from 3 months to 5 years of age. We used group-based trajectory models to derive wheeze trajectories among 3154 children. Associations with risk factors and clinical outcomes were analyzed by weighted regression models. We identified 4 trajectories: a never/infrequent trajectory, transient wheeze, intermediate-onset (preschool) wheeze, and persistent wheeze. Higher body mass index was a common risk factor for all wheeze trajectories compared with that in the never/infrequent group. The unique predictors for specific wheeze trajectories included male sex, lower respiratory tract infections, and day care attendance for transient wheeze; paternal history of asthma, atopic sensitization, and child genetic risk score of asthma for intermediate wheeze; and maternal asthma for persistent wheeze. Blood eosinophil counts were higher in children with the intermediate wheeze trajectory than in those children with the other trajectories at the ages of 1 and 5 years. All wheeze trajectories were associated with decreased lung function and increased risk of asthma at age 5 years. We identified 4 distinct trajectories in children from 3 months to 5 years of age, reflecting different phenotypes of early childhood wheeze. These trajectories were characterized by different biologic and physiologic traits and risk factors.

Modifiable environmental factors predispose term infants to bronchiolitis but bronchiolitis itself predisposes to respiratory sequelae

Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections. The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalizationfor bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort,who never had bronchiolitis. We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma. Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]:0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthmaby 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test. Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma.

Dietary strategies for the prevention of asthma in children.

This review summarizes information relating to dietary intake during pregnancy, lactation and early life that may prevent childhood asthma. This review also summarizes how future studies may be improved. Recent findings from observational studies suggest that eating according to certain dietary patterns during pregnancy, such as the dietary inflammatory index, Mediterranean diet and Maternal diet index, may reduce asthma and or wheeze in the child. Vitamin D supplementation with higher doses than recommended during pregnancy may be associated with reduced early transient childhood wheezing in the offspring. Higher levels of omega-3 fatty acids in breast milk may be protective against childhood asthma. Breastfeeding infants has been shown to offer many benefits to mother and child but a direct relationship between breastfeeding and the development of asthma has not been established. During childhood, infants and children may need to reduce their intake of advanced glycation end products, increase their food intake according to the traditional Mediterranean diet and increase the diversity of foods eaten. Current evidence provides limited suggestions regarding dietary changes for preventing early transient childhood wheezing. In order to harmonize methods for future data collection and reporting, it is important to harmonize relevant definitions and other important factors. The aim of the considerations described here is to enable a better comparison of future studies and provide better guidance to patients and families.

Childhood wheezing phenotypes and their association to perinatal factors: a longitudinal study.

Multiple gestational and early life factors have been described as the variables that increase the risk for each phenotype of infantile wheezing. Our objective was to study the evolution of wheezing in a cohort of children followed up to 9-10 years of age and its relationship with different perinatal risk factors. A longitudinal study was made on the evolution of wheezing, over time, in 1164 children from Salamanca (Spain) included in the International Study of Wheezing in Infants, when the children were 12 months old. They were classified into three phenotypes: transient early wheezing (last episode before 3 years of age), early persistent wheezing (start before 3 years age and persisting thereafter), and late-onset wheezing (first episode after 3 years of age). Univariate and multivariable analyses were performed to establish associations between the different phenotypes and perinatal factors. Data were obtained corresponding to a total of 531 children. Of these, 169 (31.8%) had experienced transient early wheezing, 100 (18.8%) early persistent wheezing, 28 (5.3%) late-onset wheezing, and 234 (44.1%) had never experienced wheezing. Cesarean delivery, early exposure to infections, the presence of atopic eczema, and a smoking father were associated with transient early wheezing. Early persistent wheezing was associated with a family history of allergy, smoking, and obstetric diseases. Exclusive breastfeeding was identified as a protective factor in both transient and persistent early wheezing. Late-onset wheezing was associated with the male gender and with maternal history of rhinitis and eczema. Wheezing phenotypes were associated with different risk perinatal factors. Knowledge in the field is essential in order to influence the modifiable factors.

Identifying wheezing phenotypes in a pediatric Turkish cohort

Objective Characterization of wheezing phenotypes in children might help to identify the underlying mechanisms through which asthma occurs. In our study, we aimed to describe wheezing phenotypes in Turkish children and to identify risk factors according to phenotypes. Methods 651 wheezy children were evaluated and 5 wheezing phenotypes were described according to age of onset, atopy and persistence at 6 years of age and risk factors were identified. Results Distribution of wheezing phenotypes was transient early wheeze (TEW)(34.9%) non-atopic wheeze (NAW) (18%), atopic wheeze (AW) (22.3%), intermediate onset wheeze (IOW) (11.1%), late onset wheeze (LOW) (11.7%). LOW, AW, and IOW were associated with, father’s, sibling’s and family’s atopy (p:0.001) whereas LOW and AW were associated with mother’s asthma and atopy as well as family’s asthma (p < 0.05). Atopic dermatitis and allergic rhinitis were common of patients with LOW, AW, and IOW (p < 0.05). İnfection was the major trigger for TEW and NAW whereas multiple triggers were common of AW, LOW, and IOW. Allergens were mostly associated with AW, IOW and LOW. Aeroallergen-specific IgE positivity was mostly with AW, IOW, and LOW phenotype. Skin prick tests showed multiple allergen sensitivity in IOW, LOW groups and mostly single allergen in AW phenotype. Modified asthma predictive index (mAPI) positivity was high in all groups except TEW and NAW. Conclusions With this study we classified five wheeze phenotypes and found that atopy and family’s atopy history, maternal asthma were strongly associated with AW, LOW, and IOW phenotypes which were usually effected by allergens or multiple triggers.

A model of perinatal stress and childhood wheezing: ELSPAC-CZ cohort.

Prenatal origins of wheezing are not fully understood. This study develops a model of mechanisms linking perinatal stress exposure to wheeze phenotypes in children. Data were obtained from 1880 mother-child dyads participating in ELSPAC-CZ birth cohort. Wheeze phenotypes assessed between birth and age 7 years included "never wheeze," "early-onset transient (EOT) wheeze," "early-onset persistent (EOP) wheeze," and "late-onset (LO) wheeze." Prenatal and postnatal stress exposures were assessed in mid-pregnancy and 6 months after delivery, respectively, using an inventory of 42 life events. In adjusted models, children in the highest tercile (high) versus lowest tercile (low) for prenatal life events had a 38% higher risk of EOT wheeze (relative risk ratio [RRR] = 1.38; 95% confidence interval [CI] = 1.01-1.88; p = .041) and 50% higher risk of LO wheeze (RRR = 1.50; 95% CI = 1.00-2.25; p = .047). High versus low exposure to postnatal life events predicted a 60% increase in relative risk of EOT wheeze (RRR = 1.60; 95% CI = 1.17-2.19; p = .003) and medium versus low exposure was related to an 85% increase in relative risk of EOP wheeze (RRR = 1.85; 95% CI = 1.16-2.95; p = .010). Lower respiratory tract infections and postpartum depression partially mediated between postnatal life events and any wheeze (indirect effects 1.06, 95% CI = 1.02-1.09, p = .003 and odds ratio [OR] = 1.08, 95% CI = 1.02-1.15, p = .012, respectively), while postnatal events mediate for prenatal events (indirect effect OR = 1.11; 95% CI = 1.03-1.18; p = .005). Exposures to prenatal and postnatal life events are risk factors for the development of wheezing. Prenatal stress contributes to wheeze directly and also through postnatal life events, respiratory infections, and maternal depression.

Low gestational vitamin D level and childhood asthma are related to impaired lung function in high-risk children

Lung function impairment in early life often persists into adulthood. Therefore, identifying risk factors for low childhood lung function is crucial. We examined the effect of 25-hydroxyvitamin D (25[OH]D) level and childhood asthma phenotype on childhood lung function in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The 25(OH)D level was measured at set time points in mothers during pregnancy and in children during early life. On the basis of parental reports, children were categorized into 3 clinical phenotypes: asymptomatic/infrequent wheeze, early transient wheeze, and asthma at age 6 years. Lung function was assessed with impulse oscillometry at ages 4, 5, and 6 years and with spirometry at ages 5 and 6 years. A total of 570 mother-child pairs were included in this post hoc analysis. Mean gestational 25(OH)D-level quartiles were negatively associated with child respiratory resistance at 5 Hz (R5) from age 4 to 6 years (β, -0.021 kPa/L/s; 95% CI, -0.035 to -0.007; P= .003) and positively associated with FEV1 (β, 0.018 L; 95% CI, 0.005-0.031; P= .008) and forced vital capacity (β, 0.022 L; 95% CI, 0.009-0.036; P= .002) from age 5 to 6 years. Children with asthma at age 6 years had lower lung function from age 4 to 6 years than the asymptomatic/infrequent wheeze group (β, 0.065 kPa/L/s; 95% CI, 0.028 to 0.102; P< .001 for R5 and β, -0.063 L; 95% CI, -0.099 to -0.028; P< .001 for FEV1). Low gestational 25(OH)D level and childhood asthma are important risk factors for decreased lung function in early childhood.

Prevalência e fenótipos de sibilância na criança hospitalizada

Wheezing is quite common in childhood. Developed countries report prevalence between 20% and 30%, with high recurrence. The definition of phenotypes and the understanding of etiological factors are fundamental for prevention and treatment strategies. The aim of this study was to evaluate the prevalence and the main wheezing phenotypes in the hospitalized child. Descriptive observational study conducted in a public hospital on the outskirts of São Paulo in 2018. The medical records of children who were hospitalized in pediatric units with wheezing symptoms were excluded, and those whose parents did not consent and who had failures in the medical records were excluded. Approval of the research ethics committee No. 2,913,139. 787 children were hospitalized, 210 (26.7%) with wheezing symptoms. Eighty-six children were excluded, totaling a sample of 124 individuals. The average age was 2.8 ± 3.1 years and most were infants (51.2%). The phenotypes found were: transient wheezing (47.2%), non-atopic wheezing (37.4%) and persistent wheezing (15.4%). It was found that the prevalence of wheezing in 2018 was high and the main phenotypes were transient wheezing and nonatopic wheezing.

Variations of interleukin-1 receptor-associated kinase-4 encoding gene were not associated with post-bronchiolitis lung function.

Interleukin-1 receptor associated kinase-4 (IRAK4) encoded by the IRAK4 gene mediates signals of innate immunity. Single nucleotide polymorphisms (SNP) of the IRAK4 rs4251513 and rs4251520 were associated with an increased risk of early transient wheezing, when 94 SNPs were studied in 2007 Dutch and 7242 French children prospectively followed-up for eight years from birth (1).

Vitamin D Supplementation During Pregnancy and the Prevention of Childhood Asthma

(N Engl J Med. 2020;382:574–575) Asthma symptoms often first appear when children are preschool-age, and therefore many efforts to prevent asthma are aimed at the prenatal or early postnatal periods. During the preschool years, asthma symptoms and transient wheeze are nearly identical, so the outcomes of any intervention should be measured once children reach 5 or 6 years old.