BACKGROUND: Previous studies have not resolved the importance of several potential risk factors for the development of childhood atopy, airway hyperresponsiveness, and wheezing, which would allow the rational selection of interventions to reduce morbidity from asthma. Risk factors for these disorders were examined in a birth cohort of 1037 New Zealand children. METHODS: Responses to questions on respiratory symptoms and measurements of lung function and airway responsiveness were obtained every two to three years throughout childhood and adolescence, with over 85% cohort retention at age 18 years. Atopy was determined by skin prick tests at age 13 years. Relations between parental and neonatal factors, the development of atopy, and features of asthma were determined by comparison of proportions and logistic regression. RESULTS: Male sex was a significant independent predictor for atopy, airway hyper-responsiveness, hay fever, and asthma. A positive family history, especially maternal, of asthma strongly predicted childhood atopy, airway hyperresponsiveness, asthma, and hay fever. Maternal smoking in the last trimester was correlated with the onset of childhood asthma by the age of 1 year. Birth in the winter season increased the risk of sensitisation to cats. Among those with a parental history of asthma or hay fever, birth in autumn and winter also increased the risk of sensitisation to house dust mites. The number of siblings, position in the family, socioeconomic status, and birth weight were not consistently predictive of any characteristic of asthma. CONCLUSIONS: Male sex, parental atopy, and maternal smoking during pregnancy are risk factors for asthma in young children. Children born in winter exhibit a greater prevalence of sensitisation to cats and house dust mites. These data suggest possible areas for intervention in children at risk because of parental atopy.
Rationale: The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before age 3 yr and active wheeze at age 6 yr: never wheezers (n = 425), transient early wheezers (n = 164), persistent wheezers (n = 113), and late-onset wheezers (n = 124).
Objective: We sought to determine the prognosis for these phenotypes, with reference to lung function and symptoms, through adolescence.
Methods: Current wheeze was assessed by questionnaire, lung function was measured by conventional spirometry, and atopy was determined by skin prick tests.
Results: The prevalence of atopy and wheeze by age 16 yr was similar for never and transient wheezers and for persistent and late-onset wheezers. Both transient early, and persistent wheezers had significantly lower FEF25–75 (–259 ml/s, p < 0.001, and –260 ml/s, p = 0.001, respectively), FEV1 (–75 ml, p = 0.02, and –87 ml, p = 0.03, respectively), and FEV1:FVC ratio (–1.9%, p = 0.002, and –2.5%, p = 0.001, respectively) through age 16 yr compared with never wheezers. Late-onset wheezers had levels of lung function similar to those of never wheezers through age 16 yr. There was no significant change in lung function among subjects with any of the four phenotypes, relative to their peers, from age 6 to 16 yr.
Conclusion: Patterns of wheezing prevalence and levels of lung function are established by age 6 yr and do not appear to change significantly by age 16 yr in children who start having asthmalike symptoms during the preschool years.
adolescent; preschool child; respiratory function tests
Tobacco smoke and genetic susceptibility are risk factors for asthma and wheezing. The aim of this study was to investigate whether there is a combined effect of interleukin-13 gene (IL13) polymorphisms and tobacco smoke on persistent childhood wheezing and asthma.
In the Isle of Wight birth cohort (UK, 1989–1999), five IL13 single nucleotide polymorphisms (SNPs): rs1800925 (-1112C/T), rs2066960, rs1295686, rs20541 (R130Q) and rs1295685 were genotyped. Parents were asked whether their children had wheezed in the last 12 months at ages 1, 2, 4 and 10 years. Children who reported wheeze in the first 4 years of life and also had wheezing at age 10 were classified as early-onset persistent wheeze phenotype; non-wheezers never wheezed up to age 10. Persistent asthma was defined as having a diagnosis of asthma both during the first four years of life and at age 10. Logistic regression methods were used to analyze data on 791 children with complete information. Potential confounders were gender, birth weight, duration of breast feeding, and household cat or dog present during pregnancy.
Maternal smoking during pregnancy was associated with early-onset persistent wheeze (OR 2.93, p < 0.0001); polymorphisms in IL13 were not (OR 1.15, p = 0.60 for the common haplotype pair). However, the effect of maternal smoking during pregnancy was stronger in children with the common IL13 haplotype pair compared to those without it (OR 5.58 and OR 1.29, respectively; p for interaction = 0.014). Single SNP analysis revealed a similar statistical significance for rs20541 (p for interaction = 0.02). Comparable results were observed for persistent childhood asthma (p for interaction = 0.03).
This is the first report that shows a combined effect of in utero exposure to smoking and IL13 on asthma phenotypes in childhood. The results emphasize that genetic studies need to take environmental exposures into account, since they may explain contradictory findings.
Despite the identical immunological mechanisms activating the release of mediators and consecutive symptoms in immediate-type allergy, there is still a clear clinical difference between female and male allergic patients. Even though the risk of being allergic is greater for boys in childhood, almost from adolescence onwards it seems to be a clear disadvantage to be a woman as far as atopic disorders are concerned. Asthma, food allergies and anaphylaxis are more frequently diagnosed in females. In turn, asthma and hay fever are associated with irregular menstruation. Pointing towards a role of sex hormones, an association of asthma and intake of contraceptives, and a risk for asthma exacerbations during pregnancy have been observed. Moreover, peri- and postmenopausal women were reported to increasingly suffer from asthma, wheeze and hay fever, being even enhanced by hormone replacement therapy. This may be on account of the recently identified oestradiol-receptor-dependent mast-cell activation. As a paradox of nature, women may even become hypersensitive against their own sex hormones, resulting in positive reactivity upon intradermal injection of oestrogen or progesterone. More importantly, this specific hypersensitivity is associated with recurrent miscarriages. Even though there is a striking gender-specific bias in IgE-mediated allergic diseases, public awareness of this fact still remains minimal today.
allergy; gender; hormone allergy; mast cell; oestrogen
prevalence of asthma and allergic diseases in children and young adults
is inversely associated with family size. It has been suggested that
more frequent exposure to infections in a large family group,
particularly those spread by the faecal-oral route, may protect against
atopic diseases, although not all published data support this
hypothesis. Whether similar considerations apply to adult onset wheeze
is unknown. The relationship between adult onset wheezing and atopy
measured in adulthood and childhood exposure to a range of infections
METHODS—A nested case
control study of participants in a 30 year follow up survey was
conducted. Questionnaire data on childhood infections had been obtained
in a 1964 survey. In 1995 a further questionnaire on respiratory
symptoms and other risk factors for wheezing illness was administered,
total IgE, skin and RAST tests were performed, and serum was stored. In
1999 serological tests for hepatitis A,
Helicobacter pylori, and
Toxoplasma gondii were performed on the
stored samples. Information from the 1964 questionnaires was available
for 97 cases and 208 controls and serological tests were obtained for
85 cases and 190 controls. The potential risk factors were examined for
all cases, those who reported doctor diagnosed asthma, those who
described persistent cough and phlegm with wheeze, and subjects
stratified by atopic status.
structure was similar in cases and controls. In univariate analysis of
all cases, childhood infections reported by parents as acquired either
before or after the age of three years did not influence case:control
or atopic status. Seropositivity was also similar for all cases and
controls, but cases in the subgroup with chronic cough and phlegm were
more likely to be seropositive for hepatitis A and
H pylori. Seropositivity was unrelated to
atopic status. In multivariate analyses both the effect of having two
or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring
measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were
significantly related to a lower risk of doctor diagnosed asthma.
well characterised subjects, exposure to infections as measured by
parental reports obtained at age 10-14 years and by serological tests
obtained in adulthood did not influence the development of wheezing
symptoms or atopic status in adulthood. However, early exposure to
measles and family size may be associated with a lower risk of adult
onset doctor diagnosed asthma.
Rationale: Aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood.
Objective: To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing.
Methods: A total of 285 children at high risk for allergic disease and asthma were followed prospectively from birth. The timing and etiology of viral respiratory wheezing illnesses were determined, and aeroallergen sensitization was assessed annually for the first 6 years of life. The relationships between these events were assessed using a longitudinal multistate Markov model.
Measurements and Main Results: Children who were sensitized to aeroallergens had greater risk of developing viral wheeze than nonsensitized children (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.2–3.1). Allergic sensitization led to an increased risk of wheezing illnesses caused by human rhinovirus (HRV) but not respiratory syncytial virus. The absolute risk of sensitized children developing viral wheeze was greatest at 1 year of age; however, the relative risk was consistently increased at every age assessed. In contrast, viral wheeze did not lead to increased risk of subsequent allergic sensitization (HR, 0.76; 95% CI, 0.50–1.1).
Conclusions: Prospective, repeated characterization of a birth cohort demonstrated that allergic sensitization precedes HRV wheezing and that the converse is not true. This sequential relationship and the plausible mechanisms by which allergic sensitization can lead to more severe HRV-induced lower respiratory illnesses support a causal role for allergic sensitization in this developmental pathway. Therefore, therapeutics aimed at preventing allergic sensitization may modify virus-induced wheezing and the development of asthma.
virus; wheezing; allergic sensitization; RSV; human rhinovirus
Rationale: Virus-induced wheezing episodes in infancy often precede the development of asthma. Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood.
Objectives: To define the relationship between specific viral illnesses and early childhood asthma development.
Methods: A total of 259 children were followed prospectively from birth to 6 years of age. The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage, culture, and multiplex reverse transcriptase–polymerase chain reaction. The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed.
Measurements and Main Results: Viral etiologies were identified in 90% of wheezing illnesses. From birth to age 3 years, wheezing with respiratory syncytial virus (RSV) (odds ratio [OR], 2.6), rhinovirus (RV) (OR, 9.8), or both RV and RSV (OR , 10) was associated with increased asthma risk at age 6 years. In Year 1, both RV wheezing (OR, 2.8) and aeroallergen sensitization (OR, 3.6) independently increased asthma risk at age 6 years. By age 3 years, wheezing with RV (OR, 25.6) was more strongly associated with asthma at age 6 years than aeroallergen sensitization (OR, 3.4). Nearly 90% (26 of 30) of children who wheezed with RV in Year 3 had asthma at 6 years of age.
Conclusions: Among outpatient viral wheezing illnesses in infancy and early childhood, those caused by RV infections are the most significant predictors of the subsequent development of asthma at age 6 years in a high-risk birth cohort.
rhinovirus; respiratory syncytial virus; wheezing; asthma; allergic sensitization
Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals.
Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV1), mid forced expiratory flow (FEF25-75)) and bronchial responsiveness were made at 7–9 years of age.
Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV1 per μmol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV1 per μmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes.
The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.
Background: In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood.
Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses (never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13 971 (50%) children.
Results: The mean (SD) TCB score was 9.4 (4.1), range 0–30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood (adjusted odds ratio (OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) (adjusted OR 2.3 (95% CI 1.2 to 4.4)).
Conclusion: These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood.
A cohort of 67 babies at risk of developing atopic disorders was followed up prospectively for 11 years. Clinical assessment and skin prick allergen sensitivity testing were performed annually over the first five years. At 11 years the cohort was restudied, symptoms were assessed by questionnaire, and bronchial reactivity (BHR) to histamine was measured. On the basis of skin testing, 35 children were atopic and 32 remained non-atopic. The expression of atopy increased with age. The lifetime prevalence of eczema, wheeze, and hay fever were 46%, 63%, and 56% respectively. The yearly period prevalence of hay fever increased with age, that of eczema declined, while that for wheeze showed a bimodal distribution with a peak before the age of 2 years and a gradual increase thereafter. Of the 21 children who wheezed before their second birthday, most never wheezed again and did not show BHR at 11 years. Of the 21 children whose first wheezing was after 2 years of age, 17 were still wheezing at 11 years and 12 showed BHR. Of the children who wheezed before 2 years of age, 10 were or became atopic, compared with 20 of the 23 children who wheezed at 11 years. These findings suggest that childhood asthma is a heterogeneous condition with atopy being strongly associated with the persistence of wheeze.
The reduction in asthma symptoms and bronchial hyperresponsiveness in adolescence is not well understood. Nor can the differences in asthma prevalence and severity between the sexes, which reverse at puberty, be explained. It has been suggested that the improvement in asthma during adolescence may result from diminished clinical and immunological responsiveness directly related to hormonal changes and that the effect of age on the prevalence of asthma in each sex may relate to differences in hormonal status, potentially influencing airway size, inflammation, and smooth muscle and vascular functions. However, few comprehensive studies are available. In summary, all wheezing is not asthma. Non-asthmatic wheezing illnesses may in part be attributable to anatomical abnormalities of the lung (transient early wheezing, premature birth). Little is known about the genetic and environmental determinants of childhood asthma, and factors related to the development of atopic sensitisation, such as exposure to allergens, infectious diseases, or tobacco smoke early in life, and dietary habits may be important, whereas the relevance of air pollution remains to be established. Unfortunately, we still do not know how to prevent the manifestation of childhood asthma.
Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma.
rhinovirus; virus; allergy; asthma; inflammation
Obesity and asthma have increased in westernised countries. Maternal obesity may increase childhood asthma risk. If this relation is causal it may be mediated through factors associated with maternal adiposity, such as fetal development, pregnancy complications or infant adiposity. We investigated the relationships of maternal BMI and fat mass with childhood wheeze and examined the influences of infant weight gain and childhood obesity.
Maternal pre-pregnancy BMI and estimated fat mass (from skinfold thicknesses) were related to asthma, wheeze and atopy in 940 children. Transient or persistent/late wheeze was classified using questionnaire data collected at ages 6, 12, 24 and 36 months and 6 years. At 6 years, skin prick testing was conducted and exhaled nitric oxide and spirometry measured. Infant adiposity gain was calculated from skinfold thickness at birth and 6 months.
Greater maternal BMI and fat mass were associated with increased childhood wheeze (RR 1.08 per 5 kg m−2, p=0.006; RR 1.09 per 10 kg, p=0.003); these reflected associations with transient wheeze (RR 1.11, p=0.003; RR 1.13, p=0.002, respectively) but not with persistent wheeze or asthma. Infant adiposity gain was associated with persistent wheeze but not significantly. Adjusting for infant adiposity gain or BMI at 3 or 6 years did not reduce the association between maternal adiposity and transient wheeze. Maternal adiposity was not associated with offspring atopy, exhaled nitric oxide, or spirometry.
Greater maternal adiposity is associated with transient wheeze but not asthma or atopy, suggesting effects upon airway structure/function but not allergic predisposition.
adiposity; body mass index; obesity; asthma; allergic sensitisation
BACKGROUND: There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood. METHOD: In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined. RESULTS: Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p < 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity). CONCLUSIONS: Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.
Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood.
To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life.
Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2–3 months.
Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2–3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1–3.7; P = 0.03 in a multivariate analysis.
Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life.
childhood asthma; indoor allergens; mouse allergen
To assess the influence of dietary patterns on the prevalence of wheezing in the child and adolescent population in Northeastern Brazil. This is a cross-sectional study of male and female students, 6–12 years old, from the public elementary schools of São Francisco do Conde, Bahia, Northeastern Brazil. The report of wheezing in the past 12 months was collected using a questionnaire from the International Study of Asthma and Allergies in Childhood Program phase III, adapted to Portuguese. Consumption patterns were derived from principal component analysis based on the frequency of consumption of 97 food items by the food frequency questionnaire. We also obtained the anthropometric status, level of physical activity, pubertal development, and socioeconomic information, for each participant. Multivariate logistic regression analyses were used to assess the associations of interest. Of the children surveyed, 10.6% reported having wheezing. We identified 2 dietary patterns named Western and Prudent. We found a positive statistically significant association of the Western pattern with wheeze (odds ratio=1.77, 95% confidence interval: 1.10–2.84) after adjustment for total energy intake and controlling for potential confounders. The results showed that the Western dietary pattern was associated with wheezing. Our result is according with previous findings reported in several other studies.
AIMS—To determine whether maternal
smoking during pregnancy is a risk factor for reported wheeze in early
childhood that is independent of postnatal environmental tobacco smoke
(ETS) exposure and other known risk factors.
METHODS—A total of 8561 mothers and
infants completed questions about smoking during pregnancy, ETS
exposure, and the mother's recall of wheeze during early childhood.
RESULTS—A total of 1869 (21.8%)
children had reported wheeze between 18 and 30 months of age, and 3496 (40.8%) had reported wheeze in one or more of the three study periods
(birth to 6 months, 6-18 months, 18-30 months). The risk of wheeze
between 18 and 30 months of age was higher if the mother smoked during
pregnancy. This relation did not show a dose-response effect and
became less obvious after adjustment for the effects of other factors.
Average daily duration of ETS exposure reported at 6 months of age
showed a dose-response effect and conferred a similar risk of reported wheeze. Factors associated with early childhood wheeze had the following adjusted odds ratios: maternal history of asthma 2.03(1.74 to 2.37); preterm delivery 1.66 (1.30 to 2.13); male sex 1.42 (1.28 to
1.59); rented accommodation 1.29 (1.11 to 1.51); and each additional
child in household 1.13 (1.04 to 1.24).
CONCLUSIONS—Maternal smoking during
pregnancy may be a risk factor for reported wheeze during early
childhood that is independent of postnatal ETS exposure. For wheeze
between 18 and 30 months of age, light smoking during the third
trimester of pregnancy appears to confer the same risk as heavier smoking.
There is evidence from two meta-analyses that children born through caesarean section (C-section) may have an increased risk of developing asthma compared with those born through vaginal delivery.
To evaluate the association between mode of delivery and wheezing (current and persistent) in childhood and adolescence, in two birth cohort studies in Brazil.
The outcome variable was based on the International Study of Allergy and Asthma questionnaire, which collects information about wheezing within the 12 months before the interview. Persistent wheezing was defined when it was present in more than one follow-up at different ages, in the 1993 cohort. The questions were asked to mothers when children were aged 4 years (1993 and 2004 cohorts) and directly to cohort participants at 11 and 15 years (1993 cohort). Mode of delivery was collected by the research team of each cohort when children were born.
Response rates in the last follow-up visit of the 1993 and 2004 cohorts were 85% and 92%, respectively. The prevalence of current wheezing increased from 20% to 28% at 4 years from 1993 to 2004; at 11 and 15 years, the prevalence was around 14% and 12%, in the 1993 cohort. The proportion of C-sections increased from 30.5% to 45% between 1993 and 2004. In each cohort, the prevalence of current wheezing was similar among children born through vaginal and C-section. The risk for persistent wheezing in the 1993 cohort was higher among girls born through C-section than boys.
Despite the increase in the proportion of C-section in two cohorts in Southern Brazil, we found no evidence of an association between mode of delivery and the subsequent risk of wheezing. Among girls, although there was no statistical significance, the risk was higher for those born by C-section, especially regarding persistent wheezing.
adolescent; caesarean section; child; cohort studies; current wheezing; developing countries; epidemiology; persistent wheezing
Several population-based birth cohort studies documented that 30% of children suffer from wheezing during respiratory infections before their third birthday. Infants are prone to wheeze because of anatomic factors related to the lung and chest wall in addition to immunologic and molecular influences in comparison to older children. Viral infections lead to immunologic derangements that cause wheezing both in immunocompetent and immunodeficient infants. Anatomic causes of wheeze may be extrinsic or intrinsic to the airway. Not every wheeze is indicative of asthma but prediction of asthma in persistent wheezers is possible. Testing for allergy in these infants is worthwhile and can be of significant value in avoidable allergens. Treatment of an infant with wheezing depends on the underlying etiology. Response to bronchodilators is unpredictable and a trial of inhaled steroids may be warranted in a patient who has responded to multiple courses of oral steroids, has moderate to severe wheezing, or a significant history of atopy including food allergy or eczema. Ribavirin administered by aerosol, hyper-immune respiratory syncytial virus immunoglobulin (RSV IVIG), and intramuscular monoclonal antibody to an RSV protein have been used for RSV bronchiolitis in infants with congenital heart disease or chronic lung disease.
wheeze; viral infection; bronchiolitis; bronchospasm; infants
The causation of asthma is poorly understood. Risk factors for atopic and non-atopic asthma may be different. This study aimed to analyze the associations between markers of poverty, dirt and infections and wheezing in atopic and non-atopic children.
1445 children were recruited from a population-based cohort in Salvador, Brazil. Wheezing was assessed using the ISAAC questionnaire and atopy defined as allergen-specific IgE ≥0.70 kU/L. Relevant social factors, environmental exposures and serological markers for childhood infections were investigated as risk factors using multivariate multinomial logistic regression.
Common risk factors for wheezing in atopic and non-atopic children, respectively, were parental asthma and respiratory infection in early childhood. No other factor was associated with wheezing in atopic children. Factors associated with wheezing in non-atopics were low maternal educational level (OR 1.49, 95% CI 0.98-2.38), low frequency of room cleaning (OR 2.49, 95% CI 1.27-4.90), presence of rodents in the house (OR 1.48, 95% CI 1.06-2.09), and day care attendance (OR 1.52, 95% CI 1.01-2.29).
Non-atopic wheezing was associated with risk factors indicative of poverty, dirt and infections. Further research is required to more precisely define the mediating exposures and the mechanisms by which they may cause non-atopic wheeze.
Variation in exposure to polyunsaturated fatty acids (PUFAs) might influence the development of atopy, asthma, and wheeze. This study aimed to determine whether differences in PUFA concentrations in maternal plasma phosphatidylcholine are associated with the risk of childhood wheeze or atopy. For 865 term-born children, we measured phosphatidylcholine fatty acid composition in maternal plasma collected at 34 weeks' gestation. Wheezing was classified using questionnaires at 6, 12, 24, and 36 months and 6 years. At age of 6 years, the children underwent skin prick testing, fractional exhaled nitric oxide (FENO) measurement, and spirometry. Maternal n-6 fatty acids and the ratio of n-3 to n-6 fatty acids were not associated with childhood wheeze. However, higher maternal eicosapentaenoic acid, docosahexaenoic acid, and total n-3 fatty acids were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 0.69, resp. P = 0.01, 0.015, and 0.021, resp.). Maternal arachidonic acid was positively associated with FENO (P = 0.024). A higher ratio of linoleic acid to its unsaturated metabolic products was associated with reduced risk of skin sensitisation (RR 0.82, P = 0.013). These associations provide some support for the hypothesis that variation in exposure to n-6 and n-3 fatty acids during pregnancy influences the risk of childhood wheeze and atopy.
Wheezing is one of the most frequent complaints that lead to the use of medical resources in younger children. Generally, wheezing is caused by bronchiolitis and resolves spontaneously without recurrence, but sometimes, wheezing can progress into asthma. Early data on the natural history of childhood wheezing was mostly obtained from retrospective reviews of medical records or from questionnaires, which made it difficult to exclude biases. Now that many cohort studies are available, reviewing the results of birth cohort studies makes it possible to understand the natural course of early childhood wheezing and the risk factors for asthma. In this study, we have reviewed the various phenotypes of early childhood wheezing and their natural courses to help select the most appropriate management modalities for the different types of early childhood wheezing.
Asthma; Preschool child; Cohort studies; Infant; Wheezing
To examine the relation between pertussis vaccination and the prevalence of wheezing illnesses in young children.
Prospective cohort study.
Three former health districts comprising Avon Health Authority.
9444 of 14 138 children enrolled in the Avon longitudinal study of pregnancy and childhood and for whom data on wheezing symptoms, vaccination status, and 15 environmental and biological variables were available.
Main outcome measures
Episodes of wheezing from birth to 6 months, 7-18 months, 19-30 months, and 31-42 months. These time periods were used to derive five categories of wheezing illness: early wheezing (not after 18 months); late onset wheezing (after 18 months); persistent wheezing (at every time period); recurrent wheezing (any combination of two or more episodes for each period); and intermittent wheezing (any combination of single episodes of reported wheezing). These categories were stratified according to parental self reported asthma or allergy.
Unadjusted comparisons of the defined wheezing illnesses in vaccinated and non-vaccinated children showed no significant association between pertussis vaccination and any of the wheezing outcomes regardless of stratification for parental asthma or allergy. Wheeze was more common in non-vaccinated children at 18 months, and there was a tendency for late onset wheezing to be associated with non-vaccination in children whose parents did not have asthma, but this was not significant. After adjustment for environmental and biological variables, logistic regression analyses showed no significant increased relative risk for any of the wheezing outcomes in vaccinated children: early wheezing (0.99, 95% confidence interval 0.80 to 1.23), late onset wheezing (0.85, 0.69 to 1.05), persistent wheezing (0.91, 0.47 to 1.79), recurrent wheezing (0.96, 0.72 to 1.26), and intermittent wheezing (1.06, 0.81 to 1.37).
No evidence was found that pertussis vaccination increases the risk of wheezing illnesses in young children. Further follow up of this population with objective measurement of allergy and bronchial responsiveness is planned to confirm these observations.
Key messagesPertussis vaccination has been proposed as a risk factor for the development of asthma and atopyThere was no evidence for increased wheezing illnesses in young children who were vaccinated against pertussis compared with non-vaccinated childrenFollow up studies of this population will help to further clarify the relation between early infections and vaccination and the development of atopic diseases, including asthmaLarge scale longitudinal studies beginning in pregnancy offer the opportunity to examine complex interactions between genetics and the environment in the cause of common childhood diseases
It is known that early childhood wheezing associated with sensitization to allergens, including food, has an increased risk of developing asthma later during school age. Gastroesophageal reflux (GER) is well known to be associated with asthma. The purpose of this study was to determine whether there is an association between silent GER and food sensitization in infants and young children with recurrent wheezing. Eighty-five infants or young children with recurrent wheezing, and no gastrointestinal symptoms, underwent 24 hr esophageal pH monitoring, as well as total serum IgE and specific IgE testing for eggs and milk. Among the 85 subjects, 48.2% had significant GER. There was no significant difference in the GER between atopic and non-atopic recurrent wheezers (41.7% and 50.8%, respectively). The sensitization rate to food (eggs or milk) was 12.2% and 20.5% in the GER and non-GER groups, respectively and showed no statistically significant difference between the two groups (P=0.34). In conclusion, about half of infants and young children with recurrent wheezing and no gastrointestinal symptoms have silent GER. The silent GER may not contribute to food sensitization in infants and young children with recurrent wheezing.
Recurrent Wheezer; Infant; Gastroesophageal Reflux; Food Antigen Sensitization
The prevalence of asthma in adolescents markedly varies between different localities as found by the International Study of Asthma and Allergies in Childhood (ISAAC) and this may be due to environmental factors. Although tobacco smoke exposure is related to an increase in the prevalence of asthma, there is lack of information on that respect in children from developing countries, where active tobacco smoking usually starts early in adolescence. This study was undertaken to assess the effect of tobacco smoking on the prevalence of asthma symptoms in a random sample of 4738 adolescents aged 13.4 ± 1.05 years who responded the ISAAC video questionnaires plus questions on tobacco smoking. The prevalence of tobacco smoking in the last 12 months was 16.2%, with significant female predominance. The persistent smokers had a significantly higher prevalence of asthma-like symptoms ever and in the last 12 months (wheezing, wheezing with exercise, nocturnal wheezing, severe wheezing, and dry nocturnal cough) than ex-smokers and nonsmokers. More than 27% of asthma symptoms in our adolescents are attributable to active tobacco consumption (population attributable risk). This study strongly suggests that potent and more effective campaigns against tobacco smoking should be implemented in developing countries, where active tobacco smoking is dramatically increasing in children.
asthma; prevalence; ISAAC; tobacco; video questionnaires