Atopic dermatitis in a high-risk cohort: natural history, associated allergic outcomes, and risk factors.

BACKGROUND: Atopic dermatitis (AD) is commonly associated with asthma and other atopic disorders in childhood. OBJECTIVE: To evaluate the natural history of AD and its association with other allergic outcomes in a high-risk cohort through the age of 7 years. METHODS: A total of 373 high-risk infants, who had undergone a randomized controlled trial with intervention measures for primary prevention of asthma applied during the first year of life, were assessed for asthma, AD, and allergic sensitization at 1, 2, and 7 years. RESULTS: The multifaceted intervention program did not reduce AD despite reducing the prevalence of asthma significantly. Sixty-two children (16.6%) had AD during the first 2 years (early-onset AD); of these, 26 continue to have AD at the age of 7 years (persistent), whereas 36 no longer had the disease (nonpersistent) at the age of 7 years. Twenty-three children (6.2%) developed AD only after the age of 2 years (late-onset AD). Early-onset AD, persistent or nonpersistent, was associated with increased risk of allergic sensitization to food allergens within the first 2 years of life and asthma diagnosis at year 7. However, only persistent AD was associated with an increased risk of other atopic diseases and allergic sensitization to food and aeroallergens at year 7. Late-onset AD was not associated with atopic diseases or allergic sensitization at year 7 with the exception of Alternaria alternans. CONCLUSION: In this cohort of infants at high risk of asthma, early-onset persistent AD, which was highly associated with atopic sensitization, increased the risk of atopic diseases in later childhood and thus appears to be part of the atopic march.

Association between endotoxin and mite allergen exposure with asthma and specific sensitization at age 7 in high-risk children.

The role of endotoxin and house dust mite allergen (HDM) in allergen sensitization and asthma is unclear. The timeframe of exposure and asthma assessment appears critical. We aimed to determine, in children at 7 yr of age, the association between current exposure to endotoxin and HDM and risks of recurrent wheeze, paediatric allergist diagnosed asthma and allergen sensitization. Three hundred and eighty children who had an increased risk of asthma because of family background were assessed at age 7 yr by a questionnaire-standardized interview, allergen skin testing and clinical examination by a paediatric allergist. Dust samples were collected from their homes and analysed for levels of endotoxin and HDM (Der p 1 and Der f 1). Levels of endotoxin in dust samples were associated with protection from paediatric allergist diagnosed asthma with inhaled steroid use (OR 0.69, 95% CI 0.53-0.91) and specific sensitization to dog allergen (OR 0.68, 95% CI 0.51-0.90) at the age of 7 yr; both endotoxin and HDM were associated with decreased risk of sensitization to dog allergen. In high-risk children at age 7, endotoxin levels were associated with decreased sensitization to dog, as well as with decreased asthma.

Indoor allergen exposure, sensitization, and development of asthma in a high-risk birth cohort.

Contradictory findings have been observed for the association of house dust mite (HDM), cat, and dog allergen exposure with sensitization and asthma. We sought to determine the relationship between exposures to these allergens, at various points during early childhood, and specific sensitization and asthma at age 7 in a high-risk birth cohort. As part of a multi-faceted Canadian intervention program for the primary prevention of asthma in high-risk infants, children were assessed by pediatric allergists at age 7 for asthma and underwent allergy skin prick testing. House dust samples were analyzed for HDM, cat, and dog allergen levels at several time points during years 1 and 7 of life. Multiple logistic regression analyses were carried out for the combined cohort and separately for the control and intervention groups. Exposure to a higher level of HDM allergen in year 1 or year 7 was associated with a higher risk of year 7 sensitization to HDM but not asthma. Exposure to higher levels of cat allergen in year 1 or year 7 did not affect the risk of year 7 sensitization to cat or asthma. Dog ownership, or exposure to higher levels of dog allergen in year 1 or year 7, did not affect the risk of year 7 sensitization to dog; however, year 7 dog allergen exposure (intervention group only) or ownership was associated with increased year 7 asthma risk. Our findings suggest that in high-risk children, there are allergen-specific associations of exposure with sensitization and with asthma; early life-elevated HDM exposure was associated with risk of sensitization but not asthma while the opposite was true for dog exposure.

Disparate geographic prevalences of asthma, allergic rhinoconjunctivitis and atopic eczema among adolescents in five Canadian cities.

To assess concordance of prevalence rates of asthma, allergic rhinoconjunctivitis and atopic eczema symptoms among adolescents in five Canadian cities. The International Study of Asthma and Allergies in Childhood Phase 3 written questionnaires were answered by 8334 adolescents aged 13 to 14 in Vancouver, Saskatoon, Winnipeg, Hamilton and Halifax, Canada. Prevalence rates of current symptoms ranged from 13.7-33.0% for wheezing, 14.6-22.6% for allergic rhinoconjunctivitis and 8.2-10.4% for atopic eczema. Using Hamilton as reference, the prevalence of wheezing was significantly higher in Halifax (OR = 1.58; 95% CI 1.36-1.84) and Saskatoon (1.27; 1.07-1.50) and significantly lower in Vancouver (0.51; 0.44-0.59). In contrast, allergic rhinoconjunctivitis was significantly more prevalent in Winnipeg (1.39; 1.16-1.68) and Halifax (1.36; 1.14-1.61) and trended lower in Saskatoon (0.81; 0.66-1.00). Atopic eczema was significantly more prevalent in Winnipeg (1.31; 1.01-1.69) and Vancouver (1.28; 1.04-1.58). Multivariable logistic regression analyses showed the region of residence, being born in Canada, recent use of acetaminophen and heavy exposure to traffic exhaust were significantly associated with all three allergic conditions, while obesity and having two or more smokers at home was only associated with increased risk for wheezing. Chinese ethnicity decreased that risk. Among five Canadian centres, the highest prevalence rates of allergic rhinoconjunctivitis or atopic eczema were not observed in the same regions as the highest prevalence rates of wheezing. This disparity in regional variations in the prevalence rates suggests dissimilar risk factors for the development or expression of wheezing (asthma), allergic rhinoconjunctivitis and atopic eczema.

Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort.

There is considerable interest in identifying children at high risk for developing atopic diseases for primary prevention. This study evaluates risk factors for detectable cord blood IgE and assesses CB-IgE in predicting asthma and other IgE-mediated allergic diseases in children at high risk because of family history. Cord blood was obtained as part of a randomized controlled trial assessing the efficacy of an intervention program in the primary prevention of IgE-mediated allergic diseases. CB-IgE was measured and the degree to which this was associated with perinatal risk factors was assessed. The cohort was then evaluated for atopic disorders at 7 yrs of age to assess the predictive value of CB-IgE. Fifty-five (19.3%) of infants had detectable CB-IgE (>/=0.5 kU/l). Maternal atopy and birth in winter months were risk factors associated with detectable CB-IgE. CB-IgE was found to be significantly associated with allergic sensitization (OR 2.22; 95% CI 1.11, 4.41) and recurrent wheeze at 7 yrs (OR 2.51, 95% CI 1.09, 5.76) but not with other outcomes. CB-IgE may be a useful measure for identifying children at high risk of atopic diseases for the purpose of primary prevention.

Early environmental determinants of asthma risk in a high-risk birth cohort.

Environmental exposures during early life have been suggested to have the greatest impact on childhood asthma. Our aim was to evaluate the risk factors associated with asthma at age 7 yr in a high-risk cohort that participated in a randomized controlled study on the primary prevention of asthma. Indoor exposures were characterized before birth and at 2 weeks, 4, 8, 12, 18, and 24 months after birth and again at 7 yr. Nasal scrapings for respiratory viruses were done at the same intervals during the first 2 yr. At age 7, the children were assessed by a pediatric allergist and had allergy skin tests. Logistic regression analysis was undertaken to evaluate the effect of exposures on asthma for the entire cohort with adjustment for group allocation. In addition to the lower risk of asthma in the intervention group, we found a higher prevalence of asthma at age 7 for males, those having a positive history of asthma in mother, father, or older siblings, for children residing in Winnipeg and for atopic subjects. Upon adjustment for intervention group assignment and baseline factors, significant environmental risk factors during year 1 included dog ownership and respiratory syncytial viral infection detected at 12 months while maternal smoking was protective. Dog ownership was a significant risk factor in year 2, but highly correlated with dog ownership in year 1. Indoor environmental exposures during year 7 were not associated with asthma at age 7. Maternal smoking at year 7 was associated with a reduced risk of asthma at 7 yr. Early-life exposures were more important determinants than those in later years. A 'window of opportunity' exists for intervention measures to be applied.

Prevalence of asthma among Chinese adolescents living in Canada and in China.

BACKGROUND: Studies of the prevalence of asthma among migrating populations may help in identifying environmental risk factors. METHODS: We analyzed data from Vancouver, Canada, and from Guangzhou, Beijing and Hong Kong, China, collected during phase 3 of the International Study of Asthma and Allergies in Childhood. We subdivided the Vancouver adolescents according to whether they were Chinese immigrants to Canada, Canadian-born Chinese or Canadian-born non-Chinese. We compared the prevalence of asthma and wheezing among Chinese adolescents born in Canada, Chinese adolescents who had immigrated to Canada and Chinese adolescents living in China. RESULTS: Of 7794 Chinese adolescents who met the inclusion criteria, 3058 were from Guangzhou, 2824 were from Beijing, and 1912 were from Hong Kong. Of 2235 adolescents in Vancouver, Canada, 475 were Chinese immigrants, 617 were Canadian-born Chinese, and 1143 were Canadian-born non-Chinese. The prevalence of current wheezing among boys ranged from 5.9% in Guangzhou to 11.2% in Canadian-born Chinese adolescents. For girls, the range was 4.3% in Guangzhou to 9.8% in Canadian-born Chinese adolescents. The prevalence of ever having had asthma ranged from 6.6% to 16.6% for boys and from 2.9% to 15.0% for girls. Prevalence gradients persisted after adjustment for other environmental variables (odds ratios for ever having had asthma among Canadian-born Chinese compared with native Chinese in Guangzhou: 2.72 [95% confidence interval 1.75-4.23] for boys and 5.50 [95% confidence interval 3.21-9.44] for girls; p < 0.001 for both). Among Chinese adolescents living in Vancouver, the prevalence of ever wheezing increased with duration of residence, from 14.5% among those living in Canada for less than 7 years to 20.9% among those living their entire life in Canada. The same pattern was observed for the prevalence of ever having had asthma, from 7.7% to 15.9%. INTERPRETATION: Asthma symptoms in Chinese adolescents were lowest among residents of mainland China, were greater for those in Hong Kong and those who had immigrated to Canada, and were highest among those born in Canada. These findings suggest that environmental factors and duration of exposure influence asthma prevalence.

Relationship of early childhood viral exposures to respiratory symptoms, onset of possible asthma and atopy in high risk children: the Canadian Asthma Primary Prevention Study.

The contribution of respiratory viral infections to the onset of asthma and atopy is controversial. In "high risk" children (n = 455) born into asthmatic/atopic families, we determined the relationship of exposures to common respiratory viruses and concomitant respiratory symptoms, and to subsequent possible asthma and atopy at ages 1 and 2 years. Frozen nasal specimens, obtained when children were 2 weeks, 4, 8, and 12 months old, underwent reverse transcription-polymerase chain reaction (RT-PCR) testing for parainfluenza virus (PIV), respiratory syncytial virus (RSV), and picornavirus (rhinovirus/enterovirus). Odds ratios of viral RT-PCR results to respiratory symptoms ("cold," rhinitis, cough, wheezing) and to possible asthma or atopy at 1 and 2 years of age were calculated. Positive viral RT-PCR was associated with increased odds of "cold" and cough; PIV and picornavirus were associated with rhinitis, and RSV was associated with wheezing. PIV was associated with increased odds of atopy at 1 year of age in the control group; PIV and RSV were associated with possible asthma at 2 years of age. We conclude that in high-risk children, viral exposures documented by RT-PCR are associated with respiratory symptoms, and exposures to PIV and RSV during the first year of life are associated with the initial onset of possible asthma.

A comparison of the relative growth velocities with budesonide and fluticasone propionate in children with asthma.

There have been no previous large, well-designed direct comparisons of the effects of fluticasone propionate (FP) and budesonide (BUD) on growth in children. This randomised, double-blind study compared the effects on growth of FP and BUD in children aged 6-9 years with persistent asthma. Following a 6-month run-in period (without inhaled corticosteroids), patients with normal growth velocity were randomised to 12 months' treatment with FP 100 micro g bd (n=114) or BUD 200 micro g bd (n=119). Growth velocity was determined by stadiometric height measurement. Lung function, asthma symptoms and use of relief medication were also assessed. Annualised mean growth velocity during run-in was comparable in the two groups (FP: 5.9 cm/yr; BUD: 6.0 cm/yr). During the treatment period, adjusted mean growth velocity was significantly higher in the FP than the BUD group (5.5 cm/yr vs 4.6 cm/yr; P<0.001). Asthma control improved similarly in both treatment groups. Bone mineral density and overnight urinary cortisol:creatinine ratios were similar in the two groups. Drug-related adverse events were reported among 3% of FP-treated children, compared with 2% for BUD. In conclusion, this study demonstrates that FP for childhood asthma has significantly less impact on childhood growth velocity than a therapeutically equivalent dose of BUD.

A modified vaccine reduces the rate of large injection site reactions to the preschool booster dose of diphtheria-tetanus-acellular pertussis vaccine: results of a randomized, controlled trial.

BACKGROUND: Large injection site reactions commonly follow booster doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccines at 4-6 years of age. A vaccine with lower diphtheria and pertussis dosage (Tdap) might be better tolerated for this dose. METHODS: We conducted a randomized, controlled, evaluator-blinded comparison of local reactions to DTaP.inactivated poliomyelitis vaccine (IPV) or Tdap booster vaccinations, in 4- to 5.5-year-old children. Reactions were assessed daily by parents and after 48 hours by study nurses. Serologic responses were measured before and 4 weeks after vaccination and examined in relation to large local reactions (>or=50 mm redness and/or swelling). RESULTS: 288 children were vaccinated, 145 with DTaP.IPV and 143 with Tdap, and after 48 hours examiners noted local redness >or= 50mm in 17.2 and 6.3%, respectively (P = 0.004). DTaP.IPV vaccinees initially experienced local pain (in 54%) which limited arm motion (in 37%), but symptoms largely resolved by 48 hours. Tdap vaccinees had fewer symptoms (pain in 20%, limited arm motion in 14%). Children with large reactions to DTaP.IPV more often than nonreactors had elevated preimmunization antibody concentrations to 1 or more of diphtheria, pertussis toxin or pertactin and elevated postimmunization antibody concentrations to all antigens except fimbriae. Booster responses to Tdap were reduced with the smaller antigen doses but were generally satisfactory. CONCLUSIONS: This preschool DTaP.IPV booster vaccination caused large local reactions in 1 in 5 children, with transient discomfort. With Tdap vaccine, such reactions were significantly fewer but not eliminated. A Tdap.IPV vaccine warrants study for routine use at 4-6 years of age.

Canadian Pediatric Asthma Consensus guidelines, 2003 (updated to December 2004): introduction.

BACKGROUND: Although guidelines for the diagnosis and management of asthma have been published over the last 15 years, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian asthma consensus report, important new studies, particularly in children, have highlighted the need to incorporate this new information into asthma guidelines. OBJECTIVES: To review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the Canadian Asthma Consensus Report, 1999 and its 2001 update with a major focus on pediatric issues. METHODS: Diagnosis of asthma in young children, prevention strategies, pharmacotherapy, inhalation devices, immunotherapy and asthma education were selected for review by small expert resource groups. In June 2003, the reviews were discussed at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published up to December 2004 were subsequently reviewed by the individual expert resource groups. RESULTS: This report evaluates early life prevention strategies and focuses on treatment of asthma in children. Emphasis is placed on the importance of an early diagnosis and prevention therapy, the benefits of additional therapy and the essential role of asthma education. CONCLUSION: We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This guide for asthma management is based on the best available published data and the opinion of health care professionals including asthma experts and educators.

Airway hyperresponsiveness to methacholine in 7-year-old children: sensitivity and specificity for pediatric allergist-diagnosed asthma.

BACKGROUND: The operating characteristics of PC(20) values used as cut-offs to define airway hyperresponsiveness, as it informs the diagnosis of asthma in children, are poorly understood. We examine data from a unique cohort to inform this concern. OBJECTIVE: Determine the sensitivity and specificity of incremental PC(20) cut-offs for allergist-diagnosed asthma. METHODS: Airway reactivity at age 7 was assessed in children within a birth cohort at high risk for asthma; PC(20) for methacholine was determined by standard technique including interpolation. The diagnosis of asthma was considered by the pediatric allergist without knowledge of the methacholine challenge results. Sensitivity and specificity were calculated using a cross-tabulation of asthma diagnosis with incremental PC(20) cut-off values, from 1.0 to 8.0 mg/ml, and plotted as receiver operator characteristic (ROC) curves. The "optimal" cut-off was defined as that PC(20) conferring maximal value for sensitivity plus specificity while the "balanced" cut-off was defined as that PC(20) at which sensitivity and specificity were most equal. RESULTS: 70/348 children (20.1%) were diagnosed with asthma. The optimal and balanced PC(20) cut-offs, both for all children and for females alone, were respectively 3 mg/ml (sensitivity 80.0%, specificity 49.1%) and 2 mg/ml (sensitivity 63.1%, specificity 64.7%). For males alone, the "optimal" and "balanced" PC(20) cut-offs were both 2 mg/ml. CONCLUSION: For this cohort of 7-year olds at high risk for asthma, methacholine challenge testing using a cut-off value of PC(20) 3 mg/ml conferred the maximal sum of specificity plus sensitivity. For contexts in which higher sensitivity or specificity is desired, other cut-offs may be preferred.

The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of age.

BACKGROUND: Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development. OBJECTIVE: The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age. METHODS: Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests. RESULTS: At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71). CONCLUSION: The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.

The Canadian asthma primary prevention study: outcomes at 2 years of age.

BACKGROUND: Avoidance of individual risk factors have not been successful in preventing the development of asthma. OBJECTIVE: We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants. METHODS: We identified 545 high-risk infants on the basis of an immediate family history of asthma. Families were randomized into intervention or control groups. Intervention measures included avoidance of house dust mite, pet allergen, and environmental tobacco smoke. Breast-feeding was encouraged with formula supplementation if necessary, and introduction of solid foods was delayed. RESULTS: At 2 years of age, 19.5% of the children had asthma, and 14.7% had atopy (positive skin test response to one or more common allergens). Significantly fewer children had asthma in the intervention group compared with in the control group (16.3% vs 23.0%), with 60% less persistent asthma at 2 years. There was a 90% reduction for recurrent wheeze in the intervention group compared with that seen in the control group. Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age. A positive skin test response, particularly to food, at 12 months predicted asthma at 2 years. There was no significant difference for atopy between the intervention and control groups, but daycare reduced atopy at 2 years. CONCLUSION: This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.

Effectiveness of and compliance to intervention measures in reducing house dust and cat allergen levels.

BACKGROUND: Allergic sensitization is a major risk factor in asthma. OBJECTIVE: To evaluate the effectiveness of and compliance to intervention measures in reducing levels of house-dust mite and cat allergen in the context of a randomized, controlled study in the primary prevention of asthma. METHODS: A total of 545 high-risk families were recruited prenatally and randomly assigned into the intervention group (n = 278) and the control group (n = 267). Intervention measures were instituted before birth of the infants and maintained for 12 months afterward in the intervention group and the control group received the usual care from their family physician. Dust samples were collected at six sites in the homes before birth and at specific intervals up to 24 months after birth for analysis of allergens. At 24 months, there were 244 families in the intervention group and 228 in the control group available for followup examination. RESULTS: House-dust mite avoidance measures, consisting of encasement of mattresses, pillows, and duvets, and hot-water washing of bedding were effective in reducing mite allergen in parents' mattresses to one-third from baseline, significantly lower than the control group, even at 24 months. The use of an acaricide did not reduce mite allergen levels in carpets and upholstered furniture. Seventeen intervention families gave up their cats but six families acquired a new one over a period of 24 months, similar to control families. Cat allergen levels decreased in all sites in the homes of those who removed the cat, similar in both groups. CONCLUSIONS: House-dust mite avoidance measures were effective in reducing house-dust mite allergen in mattresses, but not on floors. Reduction in cat allergen levels were evident for those families who got rid of their cats, but the advice to remove pets was not adhered to by most families.