Recurrent Wheezing In Children Research Articles

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...

ANALYSIS OF THE RISK OF RECURRENT WHEEZING IN CHILDREN WITH BRONCHIOLITIS BASED ON THE WEIBULL MATHEMATICAL MODEL

Given the frequency of recurrent wheezing (up to 50 % of cases) in young children during the first year after bronchiolitis, the assessment of the prognostic value of diagnostic biological markers of bronchiolitis requires special attention.According to modern concepts, mast cells, eosinophils, play a significant role in the pathogenesis of bronchiolitis, with degranulation of which the release of cationic proteins (eosinophilic cationic protein (ECP), eosinophil-derived neurotoxin (EDN)) and molecular mediators, namely vascular cell adhesion molecule-1 (VCAM-1), which is a regulator of leukocyte adhesion and transendothelial migration. That is why VCAM-1, ECP and EDN are discussed as important prognostic markers in assessing the risk of recurrent wheezing in children with bronchiolitis.The aim of the study. To analyze the risk factors for recurrent wheezing in children with bronchiolitis, considering allergic history, the influence of external factors (passive smoking, place of residence), levels of VCAM-1, ECP, EDN in the blood serum.Material and Methods. This article is a part of the research work of the Department of Paediatrics No. 1 of Vinnytsia National Medical University named after M.I. Pyrohov on the topic "Optimization of diagnosis and treatment of somatic pathology in children", state registration No. 0115U007075.A clinical examination of 67 infants was carried out. The main group consisted of 34 children with bronchiolitis without a complicated allergic history. The comparison group consisted of 33 children with bronchiolitis who had a burdened allergic history. The average age of the children in the main group was 8.4±1.6 months, and 6.2±1.4 months in the comparison group. The analytical component of the study was based on parametric survival models (Weibull and generalized Gamma models). The analysis of Weibull models was performed in the statistical packages of analytical system R for Mac OS X FAQ, Version 3.1.0 2014-04-10, R. app 1.64 based on the Mac OS X 10.9 platform, 64-bit Intel Core i7 architecture.The study was approved by the Commission on Biomedical Ethics for compliance with the moral and legal rules for conducting medical research at Vinnytsia National Medical University named after M.I. Pyrohov. It was established that the research does not contradict the basic bioethical norms and meets the principles of compliance with the basic provisions of the GCP (1996), the Council of Europe Convention on Human Rights and Biomedicine (04.04.1997), WMA Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (1964-2008) and Order of the Ministry of Health of Ukraine No. 690 of 23.09.2009 (as amended by Order of the Ministry of Health of Ukraine No. 523 of 12.07.2012). All patients were informed about the purpose and possible consequences of the research procedures. All patients signed an informed written consent to participate in the study prior to the procedure.Results of the study. The risks of recurrent wheezing in children with bronchiolitis according to the Weibull model were allergic history ( β=1,996) mixed feeding, and to an even greater extent artificial feeding ( β=7,832 and β=8,337). High serum levels of ECP β=5,03, EDN β=0,182 and VCAM-1 β=0,0254 are reliable markers of increased risk of recurrent wheezing in children with bronchiolitis. Living in rural areas ( β=-5,8) significantly reduces the risk of recurrent wheezing in children with bronchiolitis compared to children living in urban areas β=0.0162).Conclusions. 1. The levels of VCAM-1, ECP and EDN in the blood serum were recognized as reliable markers for the prognosis of recurrent vesicitis in children with bronchiolitis. The level of EDN ≤ 7 ng/ml in the blood serum is a prognostic marker for the risk of recurrent wheezing in children with bronchiolitis.2. The hypothesis that artificial feeding in children with bronchiolitis with a complicated allergic history confirms and significantly increases the risk of recurrent vesicitis in children with bronchiolitis. The hypothesis about the role of passive smoking exposure in a significant increase in the risk of recurrent wheezing in children with bronchiolitis was confirmed only for patients with EDN levels not exceeding 7 ng/ml in the blood serum.

Wheezing in preschool children: New perspective.

In recent years the understanding about the mechanism of development of wheezing in children has improved and various management strategies were tried by different researchers. A search was made in PubMed by putting search term ‘Recurrent Wheezing in Children Diagnosis and Management’ and ‘Recurrent Wheezing in Children’. The respiratory syncytial virus induced bronchiolitis and rhinovirus infection in preschool children may lead to recurrent wheezing in preschool children. In infant immune system is immature and depends mainly on TLR ligation and maternal derived antibodies. Anti-inflammatory cytokines such as IL-10 and TGF beta are more common. RSV NS1 and NS2 proteins target RLR and TLR 3 dependent signaling and suppress the cellular response to RSV replication .This can lead to Th2 like response leading to asthma and allergy. CDHR3 acts as receptor in rhinovirus C infection. RV infection causes increase in IL 25 and IL 33 both induce Th2 type of immunity by increasing IL5 and IL 13 Daily Inhaled Corticosteroids (ICS) have been found useful in preventing exacerbations. Evidence is inconclusive about intermittent inhaled corticosteroids, intermittent montelukast and daily montelukast in recurrent wheezing. Azithromycin started early may decrease duration of wheezing episode. About intravenous magnesium sulfate and hypertonic saline evidence is inconclusive. Vitamin D supplementation in preterm babies for 6 months and avoidance of cow’s milk for first three days of life may be useful in prevention of recurrent wheezing in preschool children.

Wheezing Phenotypes in Preschoolers

The incidence of wheezing is very high during the first years of life. Up to 25-30% of the infants have at least one episode of wheezing. The diagnostic approache should start with the differentiation between congenital or inherited wheezing, and subsequently the diagnosis of acute, chronic or recurrent wheezing (RW). In children with RW or chronic wheezing the somatic development is relevant. If the child presents a good nutritional status and a good general state, the most frequent diagnosis would be asthma. In children with failure to thrive the investigation plan will start with cystic fibrosis and gastroesophageal reflux. There are two major classification of RW in children: according to symptoms and to the clinical course. Wheezing phenotypes based on symptoms are: 1) episodic wheezing, in which the duration of symptoms is short, without any symptoms between episodes, and they associate other sings of viral infection; and 2) wheezing with multiple triggers (beside infections they present wheezing during exercise, or after allergen exposure, or during emotional changes). According to clinical course there are three main RW phenotypes: 1) transient wheezing with early onset, during infancy; 2) persistent wheezing with the onset during the first 3 years of life and persistence of symptoms after 6 years, and 3) RW with late onset, after the age of 3 years. The last two may be related to atopy. In these children we use the Asthma Predictive Index (API) to identify the future patients with asthma that require lonf term therapy.

The Role of Vitamin D Deficiency in Children With Recurrent Wheezing-Clinical Significance.

Recurrent wheezing (RW) in infancy is one of the most frequent reasons for parents to consult health care providers and creates a significant global burden. Clinical course of RW is difficult to predict, also which infants will progress to asthma, since no valid biomarkers have been established. Identification of those infants with RW who are at risk of further recurrences and/or severe acute respiratory tract infection (ARTI) could help pediatricians to improve their therapeutic decisions. Increasing research interest is focused on the extra-skeletal actions of vitamin D (VD) and the clinical impact of VD insufficiency/deficiency. As VD deficiency could be a risk factor for causing RW in children, measurement of their serum level of 25-hydroxycholecalciferol [25(OH)D] is recommended. In the case of deficiency, VD administration is recommended in age-appropriate doses for at least 6 weeks, until achievement of normal blood 25(OH)D level, followed by supplementation as long as exposure to sun is inadequate. Higher doses of VD given in an attempt to prevent asthma development appear to be of no additional benefit. In children with severe ARTI, VD level is recommended to be assess.

Predictors of Persistent and Recurrent Wheeze in Children in The Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (M-PAACH) Cohort

Predictors of Persistent and Recurrent Wheeze in Children in The Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (M-PAACH) Cohort

Impact of Parental Asthma, Prenatal Maternal Asthma Control, and Vitamin D Status on Risk of Asthma and Recurrent Wheeze in 3-Year-Old Children

To examine the relationship between parental asthma, maternal asthma control during pregnancy, and vitamin D status on risk of asthma or recurrent wheeze in children at 3 years of age.This was a secondary analysis of the Vitamin D Antenatal Asthma Reduction Trial, a randomized, double-blind, placebo-controlled clinical trial of vitamin D supplementation versus placebo in pregnant women to prevent recurrent wheeze and asthma in their offspring. Data consisted of 806 women and their partners and infants, with data from birth up to 3 years of age. The mother or father was required to have a physician diagnosis of asthma or atopy.The primary outcome was the first occurrence of the infant’s asthma or recurrent wheeze in the first 3 years of life, determined by parental report. The main risk variables included (1) parental asthma status, (2) maternal asthma control, and (3) insufficient vitamin D status in cord blood. Subject characteristics were compared using a t test, χ2 test, or Fisher’s exact test, and outcomes were analyzed using the log-rank trend test, Kaplan-Meier method, and Weibull univariable regression models.A total of 218 children had asthma and/or recurrent wheeze by 3 years. The highest risk was seen among children whose parents both had asthma, as compared with parents that did not have asthma (adjusted hazard ratio [aHR]: 2.3; 95% CI: 1.35–3.84), and had an aHR of 1.70 if only the mother had asthma (95% CI: 1.17–2.40). Children born to mothers with uncontrolled asthma had a higher risk of asthma compared with children born to mothers with controlled asthma (aHR: 1.60; 95% CI: 1.02–2.54). Cord blood vitamin D level was lower among infants with asthma and/or recurrent wheeze by the age of 3 years compared with those who did not (mean difference of 5.43 ng/mL; 95% CI: 2.20–8.60).This study found that maternal asthma is a risk factor for early childhood asthma and wheeze. This risk was further increased if both parents had asthma or if there was a lack of maternal asthma control during pregnancy. In addition, cord blood vitamin D sufficiency at delivery reduced the risk of asthma and/or recurrent wheeze by 3 years.This study provides additional information about the impact of paternal asthma and the mother’s asthma control on the risk of asthma and/or recurrent wheeze in offspring. Limitations include participant report of data and the potential lack of generalizability to nonatopic populations. Strengths include the large sample size and cohort study design. Maternal asthma control should be monitored during pregnancy not only for maternal health but also for the possibility of reducing the risk of asthma or recurrent wheeze in the child. Vitamin D deficiency is another potential risk factor, and there are ongoing studies in which researchers are evaluating the effects of supplemental vitamin D on development of allergic disorders.

Correspondence: Association of Serum Vitamin D Levels and Recurrent Wheezing in Children

Correspondence: Association of Serum Vitamin D Levels and Recurrent Wheezing in Children

Association of Serum Vitamin D Levels and Recurrent Wheezing in Children

Association of Serum Vitamin D Levels and Recurrent Wheezing in Children

Tekrarlayan Hışıltılı Çocuklarda Etiyolojik Değerlendirme

Tekrarlayan Hışıltılı Çocuklarda Etiyolojik Değerlendirme

Cellular and humoral immunity of virus-induced asthma

Asthma inception is associated with respiratory viral infection, especially infection with respiratory syncytial virus (RSV) and/or human rhinovirus (HRV), in the vast majority of cases. However, the reason why RSV and HRV induce the majority of bronchiolitis cases during early childhood and why only a small percentage of children with RSV- and HRV-induced bronchiolitis later develop asthma remains unclear. A genetic association study has revealed the important interaction between viral illness and genetic variants in patients with asthma. Severe RSV- and HRV-induced bronchiolitis may be associated with a deficiency in the innate immune response to RSV and HRV. RSV and HRV infections in infants with deficient innate immune response and the dysfunction of regulatory T cells are considered to be a risk factor for the development of asthma. Sensitization to aeroallergens, beginning in the first year of life, consistently predisposes children to HRV-induced wheezing illnesses, but the converse is not true. Some evidence of virus specificity exists, in that allergic sensitization specifically increased the risk of wheezing in individuals infected with HRV, but not RSV. Administration of Palivizumab, a humanized monoclonal antibody that targets the A antigenic site of the Fusion-protein of RSV, decreases the risk of hospitalization in high-risk infants and the risk of recurrent of wheezing. However, palivizumab did not have any effect on subsequent recurrent wheezing in children with a family history of atopy. These findings suggest that infection with RSV and infection with HRV might predispose individuals to recurrent wheezing through an atopy-independent and an atopy-dependent mechanism, respectively. Respiratory virus-induced wheezing illnesses may encompass multiple sub-phenotypes that relate to asthma in different ways.

478 Post-Bronchiolitis Recurrent Wheezing in Children Under 2 Years of Age - A Clinical Epidemiological Study

ObjectivesThe research involved tracing some causality relationships among acute bronchiolitis, post-bronchiolitis recurrent wheezing and/or the atopic field.Material and methodThe study group was made up of 118 cases of acute bronchiolitis...

Recurrent wheeze in children with Down syndrome: is it asthma?

To compare the prevalence of current wheeze in children with Down syndrome (DS), their siblings, and nonrelated population controls. This was a case-control study in which the International Study of Asthma and Allergy in Childhood questionnaire for respiratory symptoms was completed by parents for 130 children with DS, 167 of their siblings, and for 119 age- and sex-matched control subjects from the general population. Both wheeze ever and wheeze during the last 12 months was more commonly reported in DS than in their siblings or controls. The relative risk (RR) of current wheeze in DS was 2.8 (95% CI, 1.42-5.51) compared with siblings, and 2.75 (95% CI, 1.28-5.88) compared with controls. A doctor's diagnosis of asthma was found in 3.1% in children with DS, in 4.2% in siblings and in 6.7% in controls. During 4-years follow-up, the diagnosis of asthma could not be confirmed in the 24 DS children with current wheeze, and atopy was found in none of them. Wheeze is common in children with DS. This is likely to be related to the factors specific for DS and probably unrelated to asthma.

Phenotypes of childhood asthma: are they real?

It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long-term outcome. Classical attempts to define phenotypes have been one-dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi-dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term 'phenotype' causing much circular debate. If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children.

Maternal dietary pattern during pregnancy is not associated with recurrent wheeze in children

The rise in asthma prevalence over the last few decades may be a result of changes in prenatal or early-life environment, including maternal diet during pregnancy. Previous studies have found associations between individual foods or nutrients consumed during pregnancy and asthma or wheeze in children, but these may be confounded by overall dietary pattern. To determine whether overall maternal dietary pattern during pregnancy is associated with recurrent wheeze in children. A total of 1376 mother-infant pairs from Project Viva, a longitudinal prebirth cohort, who had responses for food frequency questionnaires in the first and second trimester and outcome data at 3 years of age were included. Multivariable logistic regression was used to look at associations between dietary pattern and the primary outcome of recurrent wheeze at 3 years. Overall dietary pattern was examined by using Mediterranean diet score, Alternate Healthy Eating Index modified for pregnancy (AHEI-P), and principal components analysis to look at Western and Prudent diets. None of these dietary patterns was associated with the primary outcome of recurrent wheeze in children in either the crude or the multivariable model (multivariable model, odds ratio per 1-point increase in Mediterranean diet, 0.98 [95% CI, 0.89-1.08]; AHEI-P, 1.07 [0.87-1.30]; Prudent, 1.02 [0.83-1.26]; Western, 0.98 [0.81-1.19]). Overall dietary pattern during pregnancy is not associated with recurrent wheeze in this cohort. Maternal intake of individual nutrients may be more important determinants of offspring wheeze-associated illness than is dietary pattern.

High Incidence of Recurrent Wheeze in Children With Down Syndrome With and Without Previous Respiratory Syncytial Virus Lower Respiratory Tract Infection

Respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) is associated with the subsequent development of recurrent wheeze. In a recent study, we found a high incidence (9.9%) of hospitalization for RSV-induced LRTI among children with Down syndrome (DS), indicating DS as a new risk factor for RSV-induced LRTI. In the current study we aimed to investigate the development of long-term airway morbidity in children with DS after hospitalization for RSV-induced LRTI. A combined retrospective cohort and prospective birth cohort of children with DS with a history of hospitalization for RSV-induced LRTI was studied (n = 53). Three control populations were included: children with DS without hospitalization for RSV-induced LRTI (n = 110), children without DS but with hospitalization for RSV-induced LRTI (n = 48), and healthy siblings of the previous 3 groups mentioned (n = 49). The primary outcome was physician-diagnosed wheeze up to 2 years of age. The incidence of physician-diagnosed recurrent wheeze in children with DS with a history of hospitalization for RSV-induced LRTI was 36%. Unexpectedly, up to 30% of children with DS without a history of RSV-induced LRTI had physician-diagnosed recurrent wheeze (no significant difference). In children without DS physician-diagnosed wheeze was found more frequently in children hospitalized for RSV-induced LRTI than healthy controls (31% vs. 8%, P = 0.004). In this combined retrospective/prospective cohort study RSV-induced LRTI did not significantly contribute to the risk of recurrent wheeze in children with DS. An unexpected finding was that recurrent wheeze was very common among children with DS.

Polymorphisms in inflammation genes, tobacco smoke and furred pets and wheeze in children

Persistent wheeze in childhood is associated with airway inflammation. The present study investigated relationships between polymorphisms in inflammatory genes, exposure to tobacco smoke and furred pets and risk of recurrent wheeze in children. Within a birth cohort of 101,042 children we identified 1111 eighteen month old cases with recurrent wheeze and 735 wheeze-free controls among 11942 children recruited in the Copenhagen area. Polymorphisms in IL-4R, IL-8, IL-13, SPINK5, and CD14 were genotyped. Interviews at gestational wks 12 and 30, and at age 6 and 18 months included questions on number of episodes with wheeze (18 months), exposure to tobacco smoke and pet-keeping. Recurrent wheeze was defined as at least four episodes of wheeze before the child was 18 months old. There was a statistically significant association between the IL-13 Arg144Gln polymorphism and risk of recurrent wheeze (p = 0.01). Furthermore, there was a statistically significant interaction between this polymorphism and exposure to tobacco smoke during pregnancy, though this was probably a chance finding. There were no other statistically significant effects of the polymorphisms or interactions with exposure to tobacco smoke in relation to the risk of recurrent wheeze. Polymorphisms in IL-8 affected the association between pet-keeping and risk of wheeze. Polymorphisms in inflammation genes might affect the association between environmental exposures and risk of recurrent wheeze in early childhood.

Long-term airway morbidity following viral LRTI in early infancy: recurrent wheezing or asthma?

Episodes of lower respiratory illnesses (LRIs) in the first years of life have been associated with recurrent wheeze in studies of high-risk and community-based cohorts. Respiratory syncytial virus (RSV) is an agent especially associated with severe cases of bronchiolitis affecting young infants in winter months and has a typical seasonal pattern. Data from the Children's Respiratory Study from Arizona and a hospital-based Swedish study have been interpreted as evidence that severe RSV bronchiolitis is associated with a 30-40% likelihood of subsequent asthma. Other respiratory viruses, especially Rhinovirus, have been identified to be importantly associated with recurrent wheeze in children at risk for asthma. A case-control study of palivizumab given in the first year of life to preterm infants has shown a 50% reduction in the occurrence of recurrent wheeze even after controlling for potential confounding variables. Prospective trials with anti-viral strategies, including potential new vaccines, should give us better understanding of the role of viral infections in early life in the causation of childhood asthma.

Allergen and Endotoxin Exposure, Infection, and Breastfeeding in Early Life, and Recurrent Wheezing in Children: 48-month Follow-up of a Cohort Study

RATIONALE: Exposure to environmental factors early in life may have a critical role in subsequent development of sensitization and asthma.METHODS: One-hundred and four newborns were enrolled at birth in this cohort study. Children belonged to low-income families and were at high risk for asthma. Recurrent wheezing was defined as three or more wheezing episodes in the past year. Infection of the upper or lower respiratory tract requiring antibiotics was recorded. Dust samples were collected from bedding and floor of the infants' bedroom within six months after birth. Endotoxin content was determined by Limulus Amebocyte Lysate assay, and major allergens from mites, cockroach, cat, dog, mouse and rat were quantitated by ELISA in dust extracts. Serum IgE antibodies were quantitated by ImmunoCAP.RESULTS: At age 48 months, 35/98 (35.7%) children presented with recurrent wheezing. Multivariate analysis revealed that respiratory infection in the first 12 months of life was associated with recurrent wheezing, OR (95% CI) 3.94 (1.29-11.98), p = 0.016, whereas allergen exposure, exclusive breast feeding for at least four months, male gender, and high levels of exposure to endotoxin had no effect. Sensitization to D. pteronyssinus (CAP score≥2) was found in 25/90 (27%) children, with no association with recurrent wheezing.CONCLUSIONS: Respiratory infection in the first 12 months of life was associated with recurrent wheezing at age 4, whereas exposure to allergen and high levels of endotoxin in early life and exclusive breastfeeding for at least four months showed no effect in development of asthma. RATIONALE: Exposure to environmental factors early in life may have a critical role in subsequent development of sensitization and asthma. METHODS: One-hundred and four newborns were enrolled at birth in this cohort study. Children belonged to low-income families and were at high risk for asthma. Recurrent wheezing was defined as three or more wheezing episodes in the past year. Infection of the upper or lower respiratory tract requiring antibiotics was recorded. Dust samples were collected from bedding and floor of the infants' bedroom within six months after birth. Endotoxin content was determined by Limulus Amebocyte Lysate assay, and major allergens from mites, cockroach, cat, dog, mouse and rat were quantitated by ELISA in dust extracts. Serum IgE antibodies were quantitated by ImmunoCAP. RESULTS: At age 48 months, 35/98 (35.7%) children presented with recurrent wheezing. Multivariate analysis revealed that respiratory infection in the first 12 months of life was associated with recurrent wheezing, OR (95% CI) 3.94 (1.29-11.98), p = 0.016, whereas allergen exposure, exclusive breast feeding for at least four months, male gender, and high levels of exposure to endotoxin had no effect. Sensitization to D. pteronyssinus (CAP score≥2) was found in 25/90 (27%) children, with no association with recurrent wheezing. CONCLUSIONS: Respiratory infection in the first 12 months of life was associated with recurrent wheezing at age 4, whereas exposure to allergen and high levels of endotoxin in early life and exclusive breastfeeding for at least four months showed no effect in development of asthma.

Maternal Pre-Pregnancy Obesity is Associated with Recurrent Wheezing in Children

Maternal Pre-Pregnancy Obesity is Associated with Recurrent Wheezing in Children