The effects of tobacco smoke exposure on respiratory health in school-aged children

The effects of tobacco smoke exposure on the respiratory health of school-aged children relate to persisting effects of exposure to tobacco smoke during pregnancy and early infancy, passive exposure to environmental tobacco smoke in the home and elsewhere, and active smoking during later childhood. Much of the current evidence comes from cross-sectional and longitudinal observational studies and suggests that, for asthma and pulmonary function outcomes, the strongest associations are with smoke exposure in pregnancy and early childhood, although independent effects of later exposure are reported. Exposure in later childhood to environmental tobacco smoke is associated with increased respiratory symptoms, although for some of these, the effect appears to diminish with increasing age of the child. There is currently a paucity of evidence on the long-term adverse respiratory consequences of active smoking by children and adolescents, but such evidence there is suggests that these may be substantial.     

Linking COPD epidemiology with pediatric asthma care: Implications for the patient and the physician

What are the implications of a lower than expected forced expiratory volume in one second (FEV1) in childhood on respiratory health later in adulthood? Lung function is known to track with age, and there is evidence from recent epidemiologic studies that impaired lung function early in life is associated with later chronic airflow limitation, or even chronic obstructive pulmonary disease, COPD. This risk seems particularly strong in subjects with persistent and severe forms of childhood asthma. Can we translate findings from longitudinal cohort studies to individual risk predictions and preventive guidelines in our pediatric care? In this review, we discuss the clinical implementations of recent epidemiological respiratory studies and the importance of preserved lung health across the life course. Also, we evaluate available clinical tools, primarily lung function measures, and profiles of risk factors, including biomarkers, that may help identifying children at risk of chronic airway disease in adulthood. We conclude that translating population level results to the individual patient in the pediatric care setting is not straight forward, and that there is a need for studies specifically designed to evaluate performance of prediction of risk profiles for long‐term sequelae of childhood asthma and lung function impairment.     

Wheezing requiring hospitalization in early childhood: Predictive factors for asthma in a six-year follow-up

Although asthma is common after wheezing in early childhood, the risk factors for and the prevention of later asthma are poorly understood. During the present follow-up study, a range of possible predictive factors for school-age asthma was evaluated. The study group consisted of 82 children hospitalized for wheezing at age < 2 years in 1992–93. The baseline data were collected on entry to the study. In 1999, the children were re-examined at the median age of 7.2 years. A structured questionnaire was applied to chart the symptoms suggestive of asthma, and the children were examined clinically. An exercise challenge test, as well as skin prick tests (SPT) to common inhalant allergens, was performed. Asthma was present in 33 (40%) children, 30 (91%) having continuous medication for asthma. The significant asthma-predictive factors, present on entry to the study, were blood eosinophilia (p = 0.0008), atopic dermatitis (p = 0.0089), elevated total serum immunoglobulin E (IgE) (p = 0.0452), and a history of earlier episodes of wheezing in infancy (p = 0.0468). SPT positivity in early childhood was also associated with school-age asthma (p = 0.002). In contrast, respiratory syncytial virus (RSV) identification during the index episode of wheezing played a minor role as a predictive factor for asthma. In conclusion, if hospitalization for wheezing occurs in infancy, more than every third child will suffer from asthma at early school age; the risk is significantly increased with recurrent wheezing in infancy and the development of allergic manifestations.     

The association between respiratory syncytial virus infection and the development of childhood asthma: a systematic review of the literature

BACKGROUND: The relation between early respiratory syncytial virus (RSV) infection and later emergence of episodes of wheezing/asthma remains a subject of debate. We carried out a systematic review of studies of the association between RSV infection in the first 36 months of life and the subsequent development of asthma/bronchial hyperreactivity. METHODS: A literature search for original studies on RSV respiratory infection published in English or Spanish over the last 21 years was conducted in the bibliographic databases Medline, Embase, and Indice Médico Espa?ol, and in the Cochrane library. Articles were included if they described original studies of confirmed RSV infection in children under 3 years of age, and had defined outcome variables. The methodologic quality of articles included in the review was evaluated according to the Hadorn criteria. RESULTS: The review included 12 original articles that respond to the research question. The studies evaluated showed that RSV lower respiratory tract infection is associated with an increased risk for subsequent development of asthma/recurrent wheezing, and that this association becomes progressively smaller with increasing age. CONCLUSION: On the basis of this systematic review of the literature, it can be concluded that a significant association exists between RSV infection in childhood and the long-term development of subsequent episodes of recurrent wheezing or asthma. However, the methodologic quality of the articles evaluated is limited, and hence additional studies are needed, ideally, with specific therapeutic interventions aimed at reducing RSV replication.     

Wheezy babies—wheezy adults? Review on long-term outcome until adulthood after early childhood wheezing

Population-based birth cohort studies have documented that about 30% of children suffer from wheezing during respiratory infection before their third birthday. Recurrent wheezing is common in early childhood, but most patients outgrow their symptoms by school age. However, recent long-term postbronchiolitis follow-up studies from Sweden and Finland have revealed that asthma is present in about 40% of young adults and over half of the cases are relapses after many symptom-free years.
In population studies, the principal predictors for later asthma have been parental asthma, recurrent wheezing, atopy and eosinophilia. In the Swedish postbronchiolitis study, atopic diathesis through the development of clinical atopy, and early passive smoking through bronchial hyper-reactivity or later active smoking led to adult asthma. The Finnish postbronchiolitis follow-up stressed early recurrence of wheezing, wheezing induced by less invasive viruses than respiratory syncytial virus (RSV), early-life atopy and eosinophilia and parental asthma as predictors for adult asthma.
Conclusion: The majority of wheezing infants and children outgrow their symptoms by school age, but based on recent long-term follow-up studies, asthma relapses are common in young adults. These studies have highlighted parental asthma, maternal smoking and wheezing induced by other viruses than RSV as predictive factors for later asthma.     

Wheezy babies--wheezy adults? Review on long-term outcome until adulthood after early childhood wheezing.

Population-based birth cohort studies have documented that about 30% of children suffer from wheezing during respiratory infection before their third birthday. Recurrent wheezing is common in early childhood, but most patients outgrow their symptoms by school age. However, recent long-term postbronchiolitis follow-up studies from Sweden and Finland have revealed that asthma is present in about 40% of young adults and over half of the cases are relapses after many symptom-free years. In population studies, the principal predictors for later asthma have been parental asthma, recurrent wheezing, atopy and eosinophilia. In the Swedish postbronchiolitis study, atopic diathesis through the development of clinical atopy, and early passive smoking through bronchial hyper-reactivity or later active smoking led to adult asthma. The Finnish postbronchiolitis follow-up stressed early recurrence of wheezing, wheezing induced by less invasive viruses than respiratory syncytial virus (RSV), early-life atopy and eosinophilia and parental asthma as predictors for adult asthma. CONCLUSION: The majority of wheezing infants and children outgrow their symptoms by school age, but based on recent long-term follow-up studies, asthma relapses are common in young adults. These studies have highlighted parental asthma, maternal smoking and wheezing induced by other viruses than RSV as predictive factors for later asthma.     

Analysis of epidemiological studies: facts and artifacts

Cohort studies have provided the foundation for much of our knowledge of childhood asthma. Four important lessons have been learned from these longitudinal studies: that asthma is a complex disease, encompassing many phenotypes; that it is linked to the development of the immune system and respiratory tract in the first years of life; that early life events strongly affect the development of asthma risk and that relationships between certain exposures and asthma risk are age dependent. The Tucson Children's Respiratory Study is used to exemplify these lessons and to illustrate the advantages of cohort studies in investigating a complex disease.     

Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: A prospective study of allergy‐prone children from birth to six years

Thomson JA, Widjaja C, Darmaputra AAP, Lowe A, Matheson MC, Bennett CM, Allen K, Abramson MJ, Hosking C, Hill D, Dharmage SC. Early childhood infections and immunisation and the development of allergic disease in particular asthma in a high‐risk cohort: a prospective study of allergy‐prone children from birth to six years.
Pediatr Allergy Immunol 2010: 21: 1076–1085.
© 2010 John Wiley & Sons A/S The role of early childhood infections and immunisation in the development of allergic diseases remains controversial. To examine these associations, six hundred and twenty infants with first‐degree relatives with allergic diseases were recruited into the Melbourne Atopy Cohort Study. Information on risk factors and outcomes was collected by interviewer administered questionnaire and was based on parental report and/or a physician’s diagnosis. Risk factors examined included early childhood infections (including gastroenteritis, otitis media and lower respiratory tract infections) and immunisations in the first 2 yr of life. Outcomes were current asthma, allergic rhinitis and eczema at 6 yr of age. Univariate and multivariate regression analysis were used to estimate relative risk (RR) and assess confounding. By 6 yr, 79% of the original cohort remained in the study. Those with at least three episodes of gastroenteritis showed an increased risk (crude RR 2.36, 95%CI 1.41 3.95; adjusted RR 2.03 95%CI 1.50 2.75) for the later development of asthma at age 6. Of the scheduled immunisations, Sabin immunisation in the second year had a reduced risk of asthma at 6 yr (crude RR 0.60, 95%CI 0.37 0.98; adjusted RR 0.63 95%CI 0.39 1.02). Combined diphtheria and tetanus (CDT) immunisation in the first year had an increased risk of asthma at 6 yr (RR 1.76, 95%CI 1.11 2.78; adjusted RR 1.88 95%CI 1.28 2.77). Recurrent gastroenteritis in early childhood is associated with a later risk of asthma. This may reflect a cause and effect relationship, or exposure to common risk factors. In contrast, Sabin immunisation in the second year is associated with a decreased risk of asthma in later childhood. CDT immunisation in the first year may be a risk factor for asthma, but the need for CDT immunisation may also be a marker of increased risk of asthma in later childhood.     

Virus infections,wheeze and asthma

Viral infections are the most frequent triggers of wheeze and asthma and yet their role in the development of symptoms remains controversial. Pre-existing airway abnormalities contribute to early virus-induced symptoms which usually remit in early childhood, whereas an interaction with airway inflammation causes exacerbations in asthma. However, the distinction between these two groups and the reason why some but not other children wheeze with viral infections is still debated. The effect of early infections on the developing immune system is also complex. The successful maturation of the T-cell response from a predominantly type 2 (atopic predisposition) at birth to a predominantly type 1 (optimal viral immunity) response, is influenced by genetic factors and the number of infections, as both are known to affect outcome. The relative parts played by predisposition and immunomodulation by early infections in later development of asthma are still controversial. These contentions are gradually being resolved by detailed prospective studies.     

Asthma symptoms in early childhood – what happens then?

Aim: To study the outcome in early adulthood for children with early asthma symptoms and to analyse the factors associated with current asthma. Methods: In a prospective study, we have re-investigated 89/101 children who were hospitalized before the age of two years due to wheezing. The children were investigated using a questionnaire and allergy and bronchial hyper-responsiveness tests at the age of 17-20 years and compared with age-matched controls. Results: In the cohort, 43% had had asthma symptoms in the preceding 12 months compared with 15% in the control group. The strongest risk factors for asthma were current allergy, bronchial hyper-responsiveness and female gender. Female gender and passive smoking in infancy were independent infantile risk factors. In addition to female gender, two pathways led to current asthma: an allergic pathway from family atopy via the development of allergy and another pathway from early passive smoking via hyper-responsiveness and active smoking.

Conclusion: In children with early wheezing disorder, current allergy, bronchial hyper-responsiveness and female gender were the strongest risk factors for asthma in early adulthood, while female gender and passive smoking in infancy were independent infantile risk factors. The effects of early passive smoking persist longer than previously reported.     

Psychopathology in Infancy

The first three years of life present unique challenges to the study of psychopathology. We highlight four of the issues in a selective review of the developmental psychopathology of early childhood, including lack of specificity of risk and outcome variables, measurement difficulties, rapid developmental changes and the centrality of the relationship context in early childhood. We also highlight issues relevant to conceptualizations of disorders of infancy, emphasizing especially the need for efforts to validate clinical disorders. We consider two major domains of infant development that we believe are especially relevant to a discussion of psychopathology, namely, regulation of emotion and infant caregiver attachment Discussions of these two domains of infant development and their psycho-pathological extremes allow us to consider conceptualizations of psychopathology from the dual perspectives of developmental psychopathology and clinical disorders. We conclude by suggesting a number of strategies to build upon previous research.     

Bronchopulmonary dysplasia: a review for the pediatrician

In this review we have attempted to introduce bronchopulmonary dysplasia as a new chronic lung disease of infancy and childhood. The major risk factors for this illness are preterm birth and the respiratory distress syndrome. The precise etiology of BPD is not understood but trauma from mechanical ventilation and toxicity from exposure to supplemental oxygen are thought to be important. Problems in diagnosis and diagnostic criteria have been discussed as have the details of the unfavorable pulmonary mechanics. We have mentioned some of our own practices in regard to a large and successful home oxygen therapy program. Suggestions have been made for establishing readiness for discharge and for follow-up of these children. Medical management of these patients presently suffers from a lack of prospective and controlled studies. Medical care draws heavily from experience with pediatric asthma. What is known about the long-term outcome of these children has been reviewed with an attempt to highlight controversies between published reports and underscore the need for further investigation. The greatest future success in this area would be the prevention of premature birth. Prior to this, we must await the completion of future controlled and prospective studies.     

Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth

Bønnelykke K, Pipper CB, Tavendale R, Palmer CNA, Bisgaard H. Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth.
Pediatr Allergy Immunol 2010: 21: 954–961.
© 2010 John Wiley & Sons A/S Copenhagen Prospective Study on Asthma in Childhood (COPSAC) was one of the discovery cohorts of the association between eczema and variants in the filaggrin coding gene (FLG). Here, we study the FLG‐associated risk of asthma symptoms in early life and describe the temporal relationship in the development of the different FLG‐associated atopic outcomes: asthma, sensitization and eczema, assessed longitudinally from birth. A high‐risk cohort of 411 children was assessed in a prospective clinical study from birth to school‐age. Asthma, acute severe asthma exacerbations, sensitization and eczema were diagnosed prospectively by the investigators. FLG variants R501X and Del4 were determined in 382 Caucasians. Filaggrin variants increased risk of developing recurrent wheeze, asthma and asthma exacerbations (hazard ratio 1.82 [1.06–3.12], p = 0.03), which was expressed within the first 1.5 yr of life. Children with filaggrin variants had a marked and persistent increase in acute severe asthma exacerbations from 1 yr of age (incidence ratio 2.40 [1.19–4.81], p = 0.01) and increased risk of asthma by age 5 (odds ratio 2.62 [1.12–6.11], p = 0.03). FLG variants increased the risk of eczema, manifesting fully in the first year of life (point prevalence ratio for age 0–5 was 1.75 [1.29–2.37]; p‐value = 0.0003) contrasting the increased risk of specific sensitization by age 4 (odds ratio 3.52 [1.72–7.25], p = 0.0007) but not age 1.5. This study describes a FLG‐associated pattern of atopic diseases characterized by the early onset of asthma symptoms and eczema and later development of sensitization. The association of filaggrin variants with asthma suggests skin barrier dysfunction as a novel, and potentially modifiable, mechanism driving early childhood asthma.     

Malaria infection does not appear to modify the risk of bronchiolitis early in life

BACKGROUND: The observation of an increased prevalence of allergic disorders coinciding with a decreasing frequency of infectious diseases in early childhood has led to the speculation that infections may prevent allergic sensitization. Information on the role of parasites in this context is limited. Bronchiolitis in infancy has been linked with asthmatic symptoms later in childhood, although the underlying cause of this association is unknown. METHODS: To test the hypothesis that early parasitic infections in infancy might prevent the development of allergic manifestations later in life, the effect of malaria infections during the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian children at 18 months of age. The study was conducted as part of an intervention trial of malaria chemoprophylaxis and/or iron supplementation for the prevention of malaria and anemia in infants. RESULTS: The incidence of bronchiolitis up to 18 months of age in the 675 children was 0.58 episode per child per year. The risk factors analysis was based on 470 children with complete data. There was no difference in the incidence of bronchiolitis between those who had received malaria chemoprophylaxis during the first year of life and those who had not. However, the proportion of children who had bronchiolitis was lower among those who had had malaria episodes than among those who had not (48% vs. 55%, P = 0.05). CONCLUSIONS: This study does not support the hypothesis that reduced exposure to parasites may modulate the development of bronchiolitis early in life.     

Natural History of Allergic Diseases in Children

Abstract. Questionnaire data from 1335 14-year-old children with a history of past or present asthma, allergic rhinitis or eczema were analysed regarding age at onset and cessation of symptoms. Incidence of asthma and eczema was highest during the first years of life. Early incidence of asthma was higher in boys than in girls but the sex ratio equalized gradually during childhood. Early incidence of eczema was equal between the sexes but the proportion of girls increased gradually with later age at onset. In 24 % of the children more than one symptom was found. Cessation of symptoms was common in asthma (55 %), in particular in those with early onset (74 %), but less common in eczema (34 %). Cessation of symptoms was less common in both diseases when associated with other allergic symptoms. Incidence of allergic rhinitis was fairly constant during childhood and cessation of symptoms was uncommon. A high risk of allergic airways disease was found after early eczema.     

Natural history of allergic diseases in children

Questionnaire data from 1335 14-year-old children with a history of past or present asthma, allergic rhinitis or eczema were analysed regarding age at onset and cessation of symptoms. Incidence of asthma and eczema was highest during the first years of life. Early incidence of asthma was higher in boys than in girls but the sex ratio equalized gradually during childhood. Early incidence of eczema was equal between the sexes but the proportion of girls increased gradually with later age at onset. In 24% of the children more than one symptom was found. Cessation of symptoms was common in asthma (55%), in particular in those with early onset (74%), but less common in eczema (34%). Cessation of symptoms was less common in both diseases when associated with other allergic symptoms. Incidence of allergic rhinitis was fairly constant during childhood and cessation of symptoms was uncommon. A high risk of allergic airways disease was found after early eczema.     

儿童哮喘与1岁以内使用抗菌药物的关系的Meta分析

目的评估生后1年内使用抗菌药物与儿童哮喘的关系。方法检索中国知网数据库、中国维普科技期刊数据库、万方数据库、Pub Med、EBSCO等中英文数据库关于儿童哮喘与其1岁以内使用抗菌药物的关系的前瞻性队列研究,采用Stata12.0软件,通过Meta分析方法探讨二者之间的关系。结果选取文献质量评分高并且调整了下呼吸道感染因素的效应值进行合并,共纳入8项研究。Meta分析结果显示,1岁以内抗菌药物的使用增加了儿童哮喘的风险(OR=1.14,95%CI:1.10~1.17,P0.05);1年内使用抗菌药物4次与使用0~1次相比哮喘风险增加(OR=1.28,95%CI:1.19~1.38,P0.05);高风险儿童(至少有1位直系亲属曾患有哮喘)使用抗菌药物罹患哮喘的风险与其他儿童相比增加(OR=1.47,95%CI:1.20~1.81,P0.05)。结论生后1年内使用抗菌药物增加儿童哮喘的风险;高风险儿童使用抗菌药物增加哮喘的风险;抗菌药物使用次数增加与哮喘风险增加有关,但具体的剂量关系有待进一步研究。     

Role of atopy in the natural history of wheeze and bronchial hyper-responsiveness in childhood

The role of atopy in the development of asthma has become increasingly recognised. We have been prospectively following a birth cohort of children of atopic parents to document the development of atopic disease. Our aim in this study was to document the natural history of BHR and wheeze at 10 years of age and to relate this to atopy. We reviewed 47 of our original cohort of 79 infants at 10 years of age and documented their clinical history of atopic disease and performed allergen skin prick tests and BHR to histamine. Thirty-three (70%) children wheezed at some time during their 10 years of life, with 13 commencing in infancy. Twenty-two children (47%) had current wheeze at 10 years of age. Wheeze in infancy was a poor predictor (RR 1.23, Cl₉₅ 0.66–2.23) of current wheeze while wheeze commencing after infancy was a good predictor (RR 2.89, Cl₉₅ 1.45–5.2). In contrast both atopy in infancy (RR 2.94, Cl₉₅ 1.92–4.53) and current atopy (RR 3.58, Cl₉₅ 1.43–9.03) were strong predictors of current wheeze. Analysis of BHR confirmed the importance of atopy in predicting its occurrence and severity. Sensitisation to D. pteronyssinus appeared to be the strongest predictor of both current wheeze and BHR. These observations confirm the importance of atopy in predicting outcome in children with asthma and suggest that wheezing in infancy and wheezing in later childhood may have different pathogenetic mechanisms.     

Origins of reactive airways disease in early life: do viral infections play a role?

There is mounting evidence suggesting that infection with respiratory syncytial virus (RSV) in early life increases the risk of developing reactive airway disease (RAD) later in childhood. A recent prospective study demonstrated that children hospitalized with RSV bronchiolitis in infancy face a significantly increased risk of recurrent wheezing and allergy at least until the age of 7 y that is independent of hereditary factors. Proposed mechanisms for this link include immune dysregulation, in which RSV-specific IgE or an imbalance between T-lymphocyte-dependent immune pathways may be involved, and abnormal neural control, in which the non-adrenergic, non-cholinergic pathways are altered by RSV infection. More recent studies suggest that immune and neural mechanisms may be linked and that post-RSV airway inflammation may be explained, at least in part, on the basis of these neuroimmune interactions.
Conclusion : Passive immunoprophylaxis may protect against persistent viral-induced inflammation of the respiratory tract, long-term changes in pulmonary function and increased frequency of RAD episodes.