Systematic review of worldwide variations of the prevalence of wheezing symptoms in children

Background: Considerable variation in the prevalence of childhood asthma and its symptoms (wheezing) has been observed in previous studies and there is evidence that the prevalence has been increasing over time. Methods: We have systematically reviewed the reported prevalence and time trends of wheezing symptoms among children, worldwide and within the same country over time. All studies comprising more than 1000 persons and meeting certain other quality criteria published over a 16-year period, between January 1990 and December 2005, are reported and a comparison of ISAAC (International Study of Asthma and Allergies in Childhood) and non-ISAAC studies is made, in part as a way of expanding the power to examine time trends (the older studies tend to be non-ISAAC), but also to examine possible methodological differences between ISAAC and non-ISAAC questions. Results: A wide range of current prevalence of wheeze was observed between and within countries over time. The UK had the highest recorded prevalence of 32.2% in children aged 13–14 in 1994–5 and Ethiopia had the lowest prevalence, 1.7% in children aged 10–19 in 1996. All studies in Australia and the UK were compared using multiple logistic regression. ISAAC phase I and III studies reported significantly higher prevalence of current wheeze (OR = 1.638) compared with non-ISAAC studies, after adjusting for various other factors (country, survey year, age of child, parental vs child response to the survey). Australia showed a significantly higher prevalence of current wheezing (OR = 1.343) compared with the UK, there was a significant increase in the prevalence odds ratio per survey year (2.5% per year), a significant decrease per age of child (0.7% per year), and a significantly higher response in current wheezing if the response was self-completed by the child (OR = 1.290). These factors, when explored separately for ISAAC and non-ISAAC studies, showed very different results. In ISAAC studies, or non-ISAAC studies using ISAAC questions, there was a significant decrease in current wheezing prevalence over time (2.5% per year). In non-ISAAC studies, which tend to cover an earlier period, there was a significant increase (2.6% per year) in current wheezing prevalence over time. This is very likely to be a result of prevalence of wheezing increasing from the 1970s up to the early 1990s, but decreasing since then. Conclusion: The UK has the highest recorded prevalence of wheezing and Ethiopia the lowest. Prevalence of wheezing in Australia and the UK has increased from the 1970s up to the early 1990s, but decreased since then and ISAAC studies report significantly higher prevalences than non-ISAAC studies.

Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing

Background Serum eosinophilic cationic protein (ECP) concentrations may be useful noninvasive markers of airways inflammation in atopic asthma. However, the usefulness of serum ECP measurement for the prediction of airways inflammation in children with a history of wheezing is unknown.

Risk factors for recurrent wheezing in infants

Introduction: wheezing is one of the most common respiratory symptoms in childhood. Regardless of the cause, it is a reason to seek medical care in emergency rooms, especially if there is recurrence of episodes. Very common in childhood, recurrent wheezing has its first episodes in the first year of life. We sought to examine the risk factors for recurrent wheezing in infants in the first year of life. Methods: this is a cross-sectional quantitative study in which a standardized questionnaire of the International Study of Wheezing in Infants, translated and validated in Brazil, consisting of objective questions, applied 40 mothers were enrolled in two Family Health units. Results: the risk factors found were: smoking during pregnancy, family history of asthma, rhinitis and allergic dermatitis, the presence of at least one pet in the home at the time of birth and age at first cold less than or equal to three months of life. No significant relationships were found between males and wheezing, exclusive breastfeeding or numbers of colds in the first year of life. Conclusion: our findings are different from those reported in the literature.

Prevalence and risk factors associated with wheezing in the first year of life

Objective: to investigate the prevalence and risk factors associated with wheezing in infants in the first year of life.Methods: this was a cross-sectional study, in which a validated questionnaire (Estudio Internacional de Sibilancias en Lactantes - International Study of Wheezing in Infants - EISL) was applied to parents of infants aged between 12 and 15 months treated in 26 of 85 primary health care units in the period between 2006 and 2007. The dependent variable, wheezing, was defined using the following standards: occasional (up to two episodes of wheezing) and recurrent (three or more episodes of wheezing). The independent variables were shown using frequency distribution to compare the groups. Measures of association were based on odds ratio (OR) with a confidence interval of 95% (95% CI), using bivariate analysis, followed by multivariate analysis (adjusted OR [aOR]).Results: a total of 1,029 (37.7%) infants had wheezing episodes in the first 12 months of life; of these, 16.2% had recurrent wheezing. Risk factors for wheezing were family history of asthma (OR = 2.12; 95% CI: 1.76-2.54) and six or more episodes of colds (OR = 2.38; 95% CI: 1.91-2.97) and pneumonia (OR = 3.02; 95% CI: 2.43-3.76). For recurrent wheezing, risk factors were: familial asthma (aOR = 1.73; 95% CI: 1.22-2.46); early onset wheezing (aOR = 1.83; 95% CI: 1.75-3.75); nocturnal symptoms (aOR = 2.56; 95% CI: 1.75-3.75), and more than six colds (aOR = 2.07; 95% CI 1.43-.00).Conclusion: the main risk factors associated with wheezing in Fortaleza were respiratory infections and family history of asthma. Knowing the risk factors for this disease should be a priority for public health, in order to develop control and treatment strategies. (C) 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Prevalence of recurrent wheezing and its risk factors

Objective: analyze the prevalence of recurrent wheezing and its risk factors. Method: systematic literature review, guided by the research question “what is the prevalence of recurrent wheezing and its risk factors?”. The search was performed in the databases MedLine and LILACS, in April and May 2013. The inclusion criteria were: scientific study, fully available, published between 2002 and 2013, with free access. Results: wheezing presents a higher prevalence in developing countries, possibly due to poor socioeconomic conditions. Among its risk factors, we find heredity, mother’s education level, attendance of day nursery, smoking during pregnancy, breastfeeding for < 3 months, animals in the household of children, among others. Conclusion: in Latin America, the prevalence of wheezing shows to be high and the use of non-standardized instruments hampers its treatment.

Wheezing in infants: frequency, clinical characteristics and treatment

Objective: To estimate the frequency and describe the clinical characteristics and respective treatments of previous history of wheezing. Methods: Infants aged 6-23 months with upper respiratory tract complaints and reporting previous wheezing were followed-up retrospectively. Data were registered on a validated standardized form. Results: Out of 451 infants, 164 (36.4%; 95%CI: 31.9-41.0) had a report of prior history of wheezing, 148 (32.8%; 95%CI: 28.5-37.4) during the first year of life. The mean age at the first episode of wheezing was 5.3 +/- 3.9 months. Among those who had had their first episode before 12 months of age, 38.5% reported 3 to 6 episodes and 14.2% > 6 episodes. Mean age at first episode was lower for those with a >= 3 episodes in comparison with those with <= 2 episodes (3.2 +/- 2.7 vs. 5.7 +/- 2.5 months, p < 0.001). Conclusion: One third of the infants reported wheezing during the first year of life. The earlier the first episode occurs, the more frequently wheezing recurs.

Leukocytes from wheezing infants release lower amounts of IL-12 and IFN-gamma compared to non-wheezing infants

Objective This study investigated environmental endotoxin exposure during early life, sensitization to aeroallergens, the production of cytokines by LPS-stimulated leukocytes, and the development of a wheezing phenotype in a prospective cohort of infants with high risk of developing allergic diseases. Materials and Methods Eighty-four infants were followed from birth until 30 months of age. We assessed endotoxin concentration in house dust of their homes during the first 6 months of life. At age 30 months they were clinically evaluated to determine the development of wheezing and other clinical events, were skin prick tested, and had blood samples collected for the evaluation of cytokine release by LPS-stimulated peripheral blood mononuclear cells (PBMC). Results The level of endotoxin exposure during early life was not associated with development of a wheezing phenotype. On the other hand a higher incidence of respiratory infections occurred among recurrent wheezing (RW) infants. PBMC from RW children exposed to higher levels of environmental endotoxin (above 50?EU/mg) released less Interleukin (IL)-12p70 and IFN-? compared to the non-RW group. TNF-a, IL-10, IL-4, IL-5, and IL17 production by LPS-stimulated PBMC from RW and non-RW children was equivalent in both groups of environmental endotoxin exposure. Conclusion In this prospective cohort of infants with high risk of developing allergic diseases we observed that RW and non-RW children were exposed to similar levels of endotoxin early in life. LPS-stimulated PBMC from RW infants exposed to higher levels of endotoxin released significantly less IL-12 and IFN-? compared to non-RW infants. Pediatr Pulmonol. 2012. 47:10541060. (C) 2012 Wiley Periodicals, Inc.

Properdin in childhood and its association with wheezing and atopy

Properdin, a serum glycoprotein, is an important component of innate immunity, the only known positive regulator of complement, acting as an initiation point for alternative pathway activation. As an X-linked protein, we hypothesized that properdin may play a modulatory role in the pathogenesis of viral wheeze in children, which tends to be more common and more severe in boys. We aimed to determine properdin levels in a community-based paediatric sample, and to assess whether levels of properdin were associated with childhood wheeze phenotypes and atopy. We studied 137 school-children aged 8-12 yrs, a nested sample from a cohort study. Properdin was measured by a commercial enzyme-linked immunoabsorbant assay. We assessed wheeze by questionnaire, validated it by a nurse-led interview and performed skin prick tests and a methacholine challenge in all children. Forty children (29%) reported current wheeze. Serum properdin levels ranged between 18 and 40 microg/ml. Properdin was not associated with age, gender, atopy, bronchial responsiveness, current wheeze (neither the viral wheeze nor multiple-trigger wheeze phenotype) or severity of wheeze, but was slightly lower in south Asian (median 21.8 microg/ml) compared with white children (23.3 microg/ml; p = 0.006). Our data make it unlikely that properdin deficiency is common in healthy children or that levels of properdin are a major risk factor for wheeze or atopy.

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

A disease model for wheezing disorders in preschool children based on clinicians' perceptions

BACKGROUND: Wheezing disorders in childhood vary widely in clinical presentation and disease course. During the last years, several ways to classify wheezing children into different disease phenotypes have been proposed and are increasingly used for clinical guidance, but validation of these hypothetical entities is difficult. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to develop a testable disease model which reflects the full spectrum of wheezing illness in preschool children. We performed a qualitative study among a panel of 7 experienced clinicians from 4 European countries working in primary, secondary and tertiary paediatric care. In a series of questionnaire surveys and structured discussions, we found a general consensus that preschool wheezing disorders consist of several phenotypes, with a great heterogeneity of specific disease concepts between clinicians. Initially, 24 disease entities were described among the 7 physicians. In structured discussions, these could be narrowed down to three entities which were linked to proposed mechanisms: a) allergic wheeze, b) non-allergic wheeze due to structural airway narrowing and c) non-allergic wheeze due to increased immune response to viral infections. This disease model will serve to create an artificial dataset that allows the validation of data-driven multidimensional methods, such as cluster analysis, which have been proposed for identification of wheezing phenotypes in children. CONCLUSIONS/SIGNIFICANCE: While there appears to be wide agreement among clinicians that wheezing disorders consist of several diseases, there is less agreement regarding their number and nature. A great diversity of disease concepts exist but a unified phenotype classification reflecting underlying disease mechanisms is lacking. We propose a disease model which may help guide future research so that proposed mechanisms are measured at the right time and their role in disease heterogeneity can be studied.

Classification and pharmacological treatment of preschool wheezing: changes since 2008.

Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.

Analysis of Phenotypic Variation in Childhood Wheezing Disorders

Recurrent wheezing or asthma is a common problem in children that has increased considerably in prevalence in the past few decades. The causes and underlying mechanisms are poorly understood and it is thought that a numb er of distinct diseases causing similar symptoms are involved. Due to the lack of a biologically founded classification system, children are classified according to their observed disease related features (symptoms, signs, measurements) into phenotypes. The objectives of this PhD project were a) to develop tools for analysing phenotypic variation of a disease, and b) to examine phenotypic variability of wheezing among children by applying these tools to existing epidemiological data. A combination of graphical methods (multivariate co rrespondence analysis) and statistical models (latent variables models) was used. In a first phase, a model for discrete variability (latent class model) was applied to data on symptoms and measurements from an epidemiological study to identify distinct phenotypes of wheezing. In a second phase, the modelling framework was expanded to include continuous variability (e.g. along a severity gradient) and combinations of discrete and continuo us variability (factor models and factor mixture models). The third phase focused on validating the methods using simulation studies. The main body of this thesis consists of 5 articles (3 published, 1 submitted and 1 to be submitted) including applications, methodological contributions and a review. The main findings and contributions were: 1) The application of a latent class model to epidemiological data (symptoms and physiological measurements) yielded plausible pheno types of wheezing with distinguishing characteristics that have previously been used as phenotype defining characteristics. 2) A method was proposed for including responses to conditional questions (e.g. questions on severity or triggers of wheezing are asked only to children with wheeze) in multivariate modelling.ii 3) A panel of clinicians was set up to agree on a plausible model for wheezing diseases. The model can be used to generate datasets for testing the modelling approach. 4) A critical review of methods for defining and validating phenotypes of wheeze in children was conducted. 5) The simulation studies showed that a parsimonious parameterisation of the models is required to identify the true underlying structure of the data. The developed approach can deal with some challenges of real-life cohort data such as variables of mixed mode (continuous and categorical), missing data and conditional questions. If carefully applied, the approach can be used to identify whether the underlying phenotypic variation is discrete (classes), continuous (factors) or a combination of these. These methods could help improve precision of research into causes and mechanisms and contribute to the development of a new classification of wheezing disorders in children and other diseases which are difficult to classify.