Search

Background: Early age at onset of atopy is associated with more severe asthma and increased airway responsiveness (AR); the underlying mechanism is unclear but may involve T cell responses., Objective: To test the hypothesis that enhanced T cell responses may be associated with early-onset atopy., Methods: In a longitudinal study, atopy was determined in infancy and at 6 and 11 years of age. Individuals were categorized as persistent infant-onset atopy (PIOA), early childhood-onset atopy (ECOA) and later childhood-onset atopy (LCOA). At 11 years of age, peripheral blood T cell cytokine responses, AR, exhaled nitric oxide (FE(NO)) and forced expiratory volume in 1 s were determined., Results: The age at onset of atopy was determined for 60 children, of whom 15 had PIOA, 24 had ECOA and 21 had LCOA. An additional 76 children who were never atopic were also included. T cell responses to house dust mite, including interleukin-5, -9, -10 and tumour necrosis factor alpha, were higher among children with PIA and ECOA, and lower in children with LCOA, P<0.05. In contrast, those children with LCOA or who were not atopic had the highest IL-10 response to PHA (P=0.014). Children with PIOA and ECOA, but not LCOA, had higher AR and FE(NO) compared with non-atopic children (P<0.05). The group with PIOA were more likely among the atopic children to be admitted to hospital for asthma (P<0.05) and also had lower %FEV(1) compared with non-atopic children (P=0.023)., Conclusions: Early age at sensitization is associated with enhanced T cell cytokine responses and indices of adverse asthma outcome. T cell cytokine responses might be programmed at the time of initial atopic sensitization.

Increased airway responsiveness (AR) is associated with asthma, but not all individuals with increased AR have asthma. The aim of this study was to identify factors, other than physician-diagnosed asthma (PDA), which are associated with increased AR. In a longitudinal study, data were collected on atopy and lower respiratory tract illness (LRTI) in infancy, and AR (expressed as dose-response slope (DRS)), atopy, tobacco-smoke exposure and PDA in childhood. At age 6 yrs, DRS was assessed in 102 children, of whom 22 (22%) had PDA; the corresponding figures at 11 yrs of age were 176 and 29 (15%). At age 6 yrs, DRS was significantly associated with PDA, current atopy and parental smoking (n = 83). At age 11 yrs, DRS was significantly associated with PDA, current atopy and LRTI in the first six months (n = 75). There was a significant positive interaction between atopy at age 12 months and PDA age 11 yrs. In conclusion, these data suggest that factors other than asthma or atopy may determine the level of airway responsiveness in children. In children with asthma, airway responsiveness may be influenced by the early onset of atopy. The current findings may explain the inconsistent relationship between airway responsiveness and asthma.

Background: We have previously reported a relationship between increased airway responsiveness (AR) in infancy and reduced childhood lung function., Objective: The current study aimed to determine whether the Arg16Gly polymorphism of the beta2 adrenoceptor (beta2AR) gene was important to this relationship., Methods: A cohort that initially numbered 253 individuals underwent assessments of AR and lung function aged 1 month, 6 and 11 years; genotyping for polymorphisms of the beta(2)AR was performed., Results: At 1 month of age, the genotype homozygous Arg16 (n=24) was associated with a mean increase in log dose-response slope (AR) of 0.27 [95% confidence interval (CI) 0.07, 0.49] compared with the genotype homozygous Gly16 (n=58), P=0.01. At 11 years of age, the genotype homozygous Arg16 (n=35) was associated with a mean reduction in the percentage of forced expiratory volume in 1 s of 5.3% [95% CI 0.3, 10.2] compared with the genotype homozygous Gly16 (n=65), P=0.03. There was no association between the Arg16Gly polymorphism and atopy or diagnosed asthma. However, nine of 69 individuals with the genotype homozygous Gly16 were admitted to hospital with asthma compared with five out of 111 individuals with the remaining genotypes (P<0.05)., Conclusion: The Arg16Gly polymorphism may be important to the association between increased AR in infancy and reduced lung function in childhood and may also be a determinant of asthma severity in children but not asthma per se.

Background: Exhaled nitric oxide (FE(NO)) is raised in asthmatic children, but there are inconsistencies in the relationship between FE(NO) and characteristics of asthma, including atopy, increased airway responsiveness (AR), and airway inflammation. The aim of this study was to investigate the relationship between FE(NO) and asthma, atopy, and increased AR in children., Methods: One hundred and fifty five children (79 boys) of mean age 11.5 years underwent an assessment that included FE(NO) measurements, spirometric tests, inhaled histamine challenge, and a skin prick test. Blood was collected for eosinophil count. Current and past asthma like symptoms were determined by questionnaire., Results: In multiple linear regression analyses FE(NO) was associated with atopy (p<0.001), level of AR (p = 0.005), blood eosinophil count (p = 0.007), and height (p = 0.002) but not with physician diagnosed asthma (p = 0.1) or reported wheeze in the last 12 months (p = 0.5). Separate regression models were conducted for atopic and non-atopic children and associations between FE(NO) and AR, blood eosinophils and height were only evident in atopic children. Exhaled NO was raised in children with a combination of atopy and increased AR independent of symptoms., Conclusion: Raised FE(NO) seems to be associated with an underlying mechanism linking atopy and AR but not necessarily respiratory symptoms.

Methods to test airway responsiveness to inhaled agonists in children were originally developed for use in adults, and agonist dosage regimens do not adequately correct for the size of the child. Because small children receive a higher dose relative to their body size than do large children, the age-related decline in airway responsiveness reported in many recent studies might reflect failure to adequately size-correct test dosages rather than a genuine physiological event. Until the administered doses of inhaled agonists can be satisfactorily size-corrected, tests of airway responsiveness in children should be regarded as qualitative rather than quantitative.

We have previously reported a relationship between increased airway responsiveness (AR) in infancy and reduced childhood lung function. The current study aimed to determine whether the Arg16Gly polymorphism of the β2 adrenoceptor (β2AR) gene was important to this relationship. A cohort that initially numbered 253 individuals underwent assessments of AR and lung function aged 1 month, 6 and 11 years; genotyping for polymorphisms of the β2AR was performed. At 1 month of age, the genotype homozygous Arg16 ( n=24) was associated with a mean increase in log dose–response slope (AR) of 0.27 [95% confidence interval (CI) 0.07, 0.49] compared with the genotype homozygous Gly16 ( n=58), P=0.01. At 11 years of age, the genotype homozygous Arg16 ( n=35) was associated with a mean reduction in the percentage of forced expiratory volume in 1 s of 5.3% [95% CI 0.3, 10.2] compared with the genotype homozygous Gly16 ( n=65), P=0.03. There was no association between the Arg16Gly polymorphism and atopy or diagnosed asthma. However, nine of 69 individuals with the genotype homozygous Gly16 were admitted to hospital with asthma compared with five out of 111 individuals with the remaining genotypes ( P<0.05). The Arg16Gly polymorphism may be important to the association between increased AR in infancy and reduced lung function in childhood and may also be a determinant of asthma severity in children but not asthma per se. [ABSTRACT FROM AUTHOR]