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.

Risk of Wheezing Attacks in Infants With Transient Tachypnea Newborns

Background: The most common reason of respiratory distress in the newborn is transient tachypnea of the newborn (TTN). There are some reports saying that TTN is associated with increased frequencies of wheezing attacks. Objectives: The aims of this study were to determine the risk factors associated with TTN and to determine the association between TTN and the development of wheezing syndromes in early life. Materials and Methods: In a historical cohort study, we recorded the characteristics of 70 infants born at the Shohadaye Kargar Hospital in Yazd between March 2005 and March 2009 and who were hospitalized because of TTN in the neonatal intensive-care unit. We called their parents at least four years after the infants were discharged from the hospital and asked about any wheezing attacks. Seventy other infants with no health problems during the newborn period were included in the study as the control group. Results: The rate of wheezing attacks in newborns with TTN was more than patients with no TTN diagnosis (P = 0.014). TTN was found to be an independent risk factor for later wheezing attacks (relative risk [RR] = 2.8). Conclusions: The most obvious finding of this study was that TTN was an independent risk factor for wheezing attacks. So long-term medical care is suggested for these patients who may be at risk, because TTN may not be as transient as has been previously thought.

Sibilância em crianças e adolescentes vizinhos a uma indústria petroquímica no Rio Grande do Norte, Brasil

OBJETIVO: Verificar a associação entre relato de sibilância em crianças e adolescentes e o local de residência em relação à dispersão dos poluentes atmosféricos emitidos pelo Pólo Petroquímico (PPQ) de Guamaré (RN). MÉTODOS: Estudo transversal de relato de sibilância em crianças e adolescentes de 0 a 14 anos de idade, residentes no entorno do PPQ de Guamaré, em 2006. Foi utilizado o questionário padronizado do International Study of Asthma and Allergies in Childhood, acrescido de questões relativas ao tabagismo, renda, moradia e escolaridade. Concentrações diárias de PM10, PM2,5, carbono grafítico, SO2, NO2, O3, benzeno, tolueno e xilenos foram medidas em uma estação de monitoramento fixa. As comunidades residentes na área de influência das emissões do PPQ foram classificadas, segundo a direção preferencial dos ventos, em expostas e de referência. RESULTADOS: Participaram do estudo 209 crianças e adolescentes. As concentrações médias diárias dos poluentes monitorados mantiveram-se abaixo dos limites estabelecidos nos padrões de qualidade do ar. A prevalência de sibilos nos últimos 12 meses foi de 27,3%. Associações estatisticamente significantes com sibilos nos últimos 12 meses foram verificadas mesmo após ajustamentos para comunidades expostas [razão de chances (odds ratio, ORajust) = 2,01; intervalo de confiança de 95% (IC95%) 1,01-4,01], gênero masculino (ORajust = 2,50; IC95% 1,21-5,18) e idade de 0 a 6 anos (ORajust = 5,00; IC95% 2,41-10,39). CONCLUSÃO: Mesmo em baixas concentrações de poluentes atmosféricos, a ocorrência de sintomas respiratórios em crianças e adolescentes nas comunidades no entorno de um PPQ esteve associada a residência na direção preferencial dos ventos, mostrando-se mais vulnerável o grupo de pré-escolares do gênero masculino.

Poluição da queima de cana e sintomas respiratórios em escolares de Monte Aprazível, SP

OBJETIVO: Estimar a prevalência de sintomas respiratórios e analisar fatores associados, bem como medidas de pico de fluxo expiratório em escolares. MÉTODOS: Estudo descritivo transversal com escolares de dez a 14 anos de Monte Aprazível, SP. Foram aplicados questionários sobre sintomas de asma e de rinite do protocolo International Study of Asthma and Allergies in Childhood, questões sociodemográficas, fatores predisponentes e antecedentes pessoais e familiares. Foram realizadas medidas repetidas do pico de fluxo expiratório nas crianças e dos níveis de concentração de material particulado (MP2,5) e de black carbon. RESULTADOS: A prevalência de sintomas de asma foi de 11% e de 33,2% de rinite; 10,6% apresentaram mais de quatro crises de sibilos nos últimos 12 meses. Antecedentes familiares para bronquite e rinite associaram-se à presença de asma (p = 0,002 e p < 0,001) e de rinite atuais (p < 0,001 e p < 0,001, respectivamente). Para rinite, houve associação com presença de mofo ou rachadura na casa (p = 0,009). Houve maior freqüência de rinite nos meses de junho a outubro, período de safra da cana de açúcar. Prevalência diária de pico de fluxo expiratório abaixo de 20% da mediana de medidas na criança foi maior em dias com maior concentração de MP2,5. CONCLUSÕES: A prevalência de sintomas de asma está abaixo e a de rinite está acima da média nacional. Ainda que dentro dos níveis aceitáveis, a poluição nos períodos de queima da palha da cana-de-açúcar pode contribuir para a exacerbação de episódios de asma e de rinite.

Prevalência de asma e fatores de risco em escolares da cidade de São Paulo

OBJETIVO: Analisar a prevalência de asma e possíveis fatores de risco associados. MÉTODOS: Estudo transversal, integrante do International Study of Asthma and Allergies in Childhood. Participaram 561 escolares de seis a sete anos de idade, provenientes de 35 escolas públicas da cidade de São Paulo, escolhidas por sorteio, em 2002. A amostra incluiu 168 asmáticos e 393 não asmáticos, que responderam questionário constituído por 33 questões referentes a dados pessoais, familiares e ambientais. A associação entre asma e fatores de risco foi avaliada pela análise de regressão logística, considerando-se nível de significância estatística de 5%. RESULTADOS: Entre os escolares, 31,2% referiam sibilos nos 12 meses anteriores à entrevista. Os fatores de risco significativamente associados à asma foram: sexo masculino (OR=2,4;IC 95%: 1,4;4,2), mãe fumante no primeiro ano de vida (OR=2,0; IC 95%: 1,1;3,8), presença de eczema em locais característicos (OR=3,0; IC 95%:1,2; 7,6) e rinoconjuntivite (OR=2,4;IC 95%: 1,2; 4,8). CONCLUSÕES: A prevalência de asma na região estudada foi elevada e os fatores de risco relacionados foram: sexo masculino, sintomas de rinoconjuntivite no último ano, mãe fumante no primeiro ano de vida e presença de eczema em locais característicos.

Evaluation of thermal simulation of households in the metropolitan region of São Paulo, Brazil

Abstract This paper aims at assessing the performance of a program of thermal simulation (Arquitrop) in different households in the city of Sao Paulo, Brazil. The households were selected for the Wheezing Project which followed up children under 2 years old to monitor the occurrence of respiratory diseases. The results show that in all three study households there is a good approximation between the observed and the simulated indoor temperatures. It was also observed a fairly consistent and realistic behavior between the simulated indoor and the outdoor temperatures, describing the Arquitrop model as an efficient estimator and good representative of the thermal behavior of households in the city of Sao Paulo. The worst simulation is linked to the poorest type of construction. This may be explained by the bad quality of the construction, which the Architrop could not simulate adequately

Prevalence and Risk of Asthma Symptoms Among Firefighters in Sao Paulo, Brazil: A Population-Based Study

The firefighters are at increased risk of respiratory disease as a result of exposure to smoke and dust. The aim of this study was to determine the prevalence and risk associated with respiratory symptoms among city firefighters in Sao Paulo, Brazil. Methods A cross-sectional study utilizing the European Community Respiratory Health Survey (ECRHS) questionnaire was administered to firefighters and police officers, in order to evaluate their respiratory symptoms. Results Complete respiraton, data were obtained from 1,235 firefighters and 1,839 police officers. Among the firefighters, there were 55.5% never-smokers, 22.4% current smokers and 18.2% former smokers (P < 0.05). Among the police officers, there were 63.4%, 18.6%, and 9.6% who were never-smokers, current smokers and former smokers (P < 0.05), respectively. Compared to police, firefighters experienced an increase in wheezing [OR = 1.63 (95% CI: 1.43-1.87)], wheezing with breathlessness [OR = 1.34 (95% CI: 1.10-1.64)], wheezing without a cold [OR = 1.60 (95% CI: 1.32-1.95)], waking with tightness in the chest [OR = 1.20 (95% CI: 1.02-1.42)], and rhinitis [OR = 1.12 (95% CI: 1.03-1.22)]. The prevalence of adult-onset asthma in never-smokers was 9.3% and 6.7% for firefighters and police officers [OR = 1.23 (95% CI: 1.01-1.56)]. All independent association was observed between years employed, smoking, history of rhinitis, and work as a firefighter and respiratory, and nasal symptoms. We observed a high prevalence of asthma-like symptoms in firefighters who presented respiratory symptoms beginning immediately after firefighting. Conclusion These results suggest that the prevalence of respiratory symptoms and asthma in firefighters is higher than those in police officers. Work-as a firefighter, rhinitis and vears employed were risk factors for respiratory,symptoms of asthma. Am. J. Ind. Med. 52:261 269, 2009. (C) 2008 Wiley-Liss, Inc.

FREQUENCY OF HUMAN RHINOVIRUS SPECIES IN OUTPATIENT CHILDREN WITH ACUTE RESPIRATORY INFECTIONS AT PRIMARY CARE LEVEL IN BRAZIL

This study assessed the occurrence of human rhinovirus (HRV) species in outpatient children attending day-care in Sao Paulo, Brazil. HRV reverse transcriptase polymerase chain reaction and amplicon sequencing were done in 120 samples collected in 2008. HRV was detected in 27.5% of samples. HRV C was detected in 60.7% of wheezers, a frequency not different from that observed in nonwheezers (69.6%).