Diagnostic value of exhaled nitric oxide in childhood asthma and allergy.

Fractional exhaled nitric oxide (FE(NO) ) has been proposed as a diagnostic test of asthma. We aimed to investigate in a population based birth cohort of children the usefulness of FE(NO) as a diagnostic tool. The 10-yr follow up of the Environment and Childhood Asthma Study in Oslo included 616 children representative of the prospective birth cohort. Both FE(NO) (single breath technique) and skin prick test (SPT) were measured in 331, limited at the time by equipment availability. Structural parental interview, spirometry, methacholine challenge and exercise test were performed. FE(NO) was significantly elevated in children with current asthma (geometric mean 9.6 (95% confidence interval (CI) (6.9, 13.4) p.p.b.) compared with healthy children (5.8 (5.4, 6.3) p.p.b.; p < 0.001). FE(NO) was highest among children with current allergic asthma (asthma and positive SPT) (14.0 (8.9, 22.1) p.p.b.), whereas children with non-allergic asthma (6.1 (4.0, 9.2) p.p.b.) had comparable FE(NO) levels to healthy children (p = 0.99). Allergic sensitization was most closely associated with FE(NO) . A FE(NO) cut-off value of 20.4 p.p.b. had a high specificity (0.97), but a low sensitivity (0.41) and a Positive Likelihood Ratio of 16.1 for current allergic asthma. In the present childhood population-based study, high FE(NO) levels were closely associated with current allergic asthma and not with current asthma without allergic sensitization. Estimating the individual predictive probability of having asthma by use of FE(NO,) improves the diagnostic utility of the test.

Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score.

BACKGROUND: Allergic sensitisation increases the risk for asthma development. In this prospective birth cohort (Environment and Childhood Asthma) study, we hypothesized that combining quantitative measures of IgE antibodies (Sigma-IgE) and Severity score of obstructive airways disease (OAD) at 2 years of age (Severity score) is superior to predict current asthma (CA) at 10 years than either measure alone. Secondarily, we assessed if gender modified the prediction of CA. METHODS: A follow-up study at 10 years of age was performed in 371 2-year-old children with recurrent (n = 219) or no (n = 152) bronchial obstruction with available serum analysed for Sigma-IgE to common food and inhalant allergens through a panel test, Phadiatop Infant) (Phadia, Uppsala, Sweden). Clinical variables included allergic sensitisation and exercise testing to characterise children with CA vs not CA at 10 years and the Severity score (0-12, 0 indicating no OAD) was used to assess risk modification. RESULTS: Severity score alone explained 24% (Nagelkerke R(2) = 0.24) of the variation in CA, whereas Sigma-IgE explained only 6% (R(2) = 0.06). Combining the two increased the explanatory capacity to R(2) = 0.30. Gender interacted significantly with Sigma-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Sigma-IgE for CA at 10 years was significant in boys only. CONCLUSION: Combining Sigma-IgE to inhalant allergens and Severity score at 2 years was superior to predict asthma at 10 years than either alone. Severity score predicted CA in both genders, whereas Sigma-IgE significantly predicted CA in boys only.

Do allergic families avoid keeping furry pets?

UNLABELLED: Studies addressing the relationship between pet keeping and development of asthma and allergies may be influenced by pet avoidance in families with a history of allergic disease. Following a cohort of 1019 children in Oslo till 10 years of age, we studied the association of pet keeping with socio-economic factors and allergic disease in the family. A family history of asthma and rhinoconjunctivitis was not significantly associated with pet ownership at birth or with pet removal by 10 years. Acquiring cats and dogs was less likely if the child had allergic rhinoconjunctivitis, whereas no association was seen with asthma (in any family member). Single parenthood increased the likelihood of acquiring a cat, smoking parents more often had cats or dogs, and having older siblings was associated with keeping dogs and other furry pets. Among 319 families reporting pet avoidance, 70% never had pets, 8% had given up pets, and 22% avoided a particular type of pet only. Twenty-four per cent of the parents failed to retrospectively report pet keeping during the child's first year of life. Overall, allergic rhinitis, but not asthma was associated with actual pet avoidance, whereas the strongest predictors for keeping pets were found to be socio-economic factors. PRACTICAL IMPLICATIONS: Allergic disease in a child most often does not lead to the removal of the family's furry pet. Pet avoidance is associated with allergic symptoms, but not asthma. Socio-economic factors like parental education, single parenthood and smoking affects the families' decisions on pet keeping, including the type of pets the families will avoid or acquire. The large recall error demonstrated points to the need for prospective data regarding pet keeping.

Severe asthma in childhood: assessed in 10 year olds in a birth cohort study.

BACKGROUND: Limited information is available regarding the prevalence of severe asthma in children. The present study aimed at investigating the prevalence of severe asthma in an urban child population; secondarily evaluating the applicability of the chosen definition by clinical characteristics. METHODS: Children enrolled in the prospective birth cohort; the Environment and Childhood Asthma Study in Oslo; were reinvestigated at the age of 10 years (n = 1019). A representative population based cohort of 616 children [mean age 10.9 (SD 0.9) years] with lung function measurements at birth was used for prevalence estimates, whereas all 1019 children (154 with current asthma) attending the 10-year follow-up were included for verification of the definition of severe asthma. Clinical investigations included spirometry, tests of bronchial hyperresponsiveness, skin prick tests and exhaled nitric oxide. Severe asthma was defined as poorly controlled asthma despite treatment with > or = 800 microg budesonide or equivalent; assessed by a detailed structured interview. RESULTS: The population point prevalence at age 10 years of current severe asthma was 0.5% (three of 616) and among children with current asthma 4.5% (three of 67). The 10/154 children identified as suffering from severe asthma more often had severe bronchial hyperresponsiveness (PD(20) methacholine <1 micromol) (60%vs 22%, P = 0.015), lower median forced expiratory volume in 1 s/forced vital capacity ratio (93%vs 99%, P = 0.04) and higher body mass index (mean BMI 22.3 vs 18.3, P < 0.001) than nonsevere current asthmatics. CONCLUSIONS: The prevalence of severe asthma was 0.5% in all 10-year olds, and 4.5% among current asthmatics. The severe asthma definition applied in this study is supported by results of clinical investigations.

Severity of obstructive airways disease by age 2 years predicts asthma at 10 years of age.

BACKGROUND: Predicting school-age asthma from obstructive airways disease (OAD) in early life is difficult, even when parental and children's atopic manifestations are taken into consideration. OBJECTIVE: To assess if the severity of OAD in the first 2 years of life predicts asthma at 10 years of age. METHODS: From a nested case control study within the Environment and Childhood Asthma study, 233 2-year-old subjects with recurrent (> or = 2 episodes) bronchial obstruction (rBO+) and 216 subjects without bronchial obstruction (rBO-) underwent clinical examination, parental interview, treadmill test and metacholine bronchial hyperresponsiveness (BHR) measurement at 10 years. A severity score at 2 years was calculated by frequency, persistence of bronchial obstruction and hospital admissions because of OAD. MAIN OUTCOMES: Current asthma at 10 years (asthma with symptoms and/or asthma medication during the past year and/or positive treadmill test). Secondary outcome was metacholine BHR at 10 years. RESULTS: Compared with rBO- subjects, adjusted odds ratio (95% CI) of current asthma among rBO+ was 7.9 (4.1, 15.3), and among rBO+ with a severity score of > 5, 20.2 (9.9, 41.3). In receiver operated characteristic analysis, positive and negative predictive values demonstrated the applicability and value of the score, with an optimal cut-off at severity score 5. Children with severity score > 5 had severe BHR more often (PD20 metacholine < 1 micromol) than children with a lower or 0 score (p = 0.0041). CONCLUSION: Using a simple scoring system, a high severity score of OAD by 2 years of age is a strong risk factor for, and may predict, current asthma at 10 years of age.

HLA Dr-Dq haplotypes and the TNFA-308 polymorphism: associations with asthma and allergy.

BACKGROUND: The HLA (human leukocyte antigen) class II genes DQB1 and DRB1 and the Tumor Necrosis Factor alpha gene (TNFA) within the HLA complex (chromosome 6p21) have been associated with asthma and allergy. Due to the strong linkage disequilibrium characterizing this complex and the multiple asthma/allergy expressions, we aimed to determine which of these genes were primarily involved in specific asthma/allergy traits. METHODS: The DRB1-DQB1 alleles and TNFA-308 polymorphism were genotyped in 959 children from the Environment and Childhood Asthma study and analyzed for possible associations with allergic and non-allergic asthma (with/without at least one positive skin prick test for allergens) and specific allergic sensitization, as well as bronchial hyperresponsiveness and total IgE, using both allele and extended haplotype analyses. RESULTS: Different genes within the HLA complex were associated with separate asthma and allergy traits. Nonallergic asthma was associated with both the TNFA-308A allele [Odds ratio (OR) 1.7 (1.3-2.3)] and DRB1 03 allele [OR 1.6(1-2.6)], but extended DRB1 03-TNFA-308 haplotype analysis suggested that the DRB1-DQB1 association was secondary to linkage disequilibrium with the TNFA-308 polymorphism. Allergies were associated with HLA class II alleles only; birch sensitization with DQB1 0603-DRB1 13 [OR 2.3 (1.4-4.0)] and mugwort sensitization with DQB1 0609-DRB1 13 [OR 7.1 (1.9-27.0)] and DQB1 0501-DRB1 01 [OR 2.0 (1.0-4.0)]. CONCLUSIONS: Our data suggests that asthma is not associated with DRB1 or DQB1 but rather TNFA or a gene(s) in linkage disequilibrium, while sensitization to specific allergens is associated with particular alleles at the DQ and/or DR loci. A novel association between DQB1 0603-DRB1 13 and birch allergy is identified.

Asthma in every fifth child in Oslo, Norway: a 10-year follow up of a birth cohort study.

BACKGROUND: The western world's increase in childhood asthma is suggested to level off. We aimed to investigate asthma prevalence in 10-year-old children within the prospective birth cohort Environment and Childhood Asthma (ECA) Study in Oslo established in 1992/1993. SUBJECTS AND METHODS: Six hundred and sixteen (77%) of 803 children (mean age 10.9 +/- 0.9 (SD) years) with lung function measurements at birth were reinvestigated at age 10 years. At birth they corresponded to the entire birth cohort (n = 3754) regarding gender, socio-demographic factors, parental allergic diseases, pet keeping and maternal smoking. Results from structured parental interview, spirometry, and skin prick test for inhalant and food allergens are presented. Asthma definition required minimum two positive criteria, (i) doctor's diagnosis of asthma, (ii) wheeze and/or chest tightness, (iii) use of anti-asthmatic treatment. Current asthma required asthma definition plus either (ii) and/or (iii) in the last 12 months, and/or > or = 10% fall in forced expired volume in 1 s after treadmill running. RESULTS: Lifetime prevalence of asthma was 20.2%; current asthma 11.1%, doctor diagnosis of asthma 16.1% and wheezes ever 30.3%. Allergic sensitization (29.3% overall) was more common among children with current (56.3%) compared to asymptomatic (last 12 months) (26.0%) or no asthma (27.6%) (P < 0.001). Boys more often than girls had current asthma (14.4 vs 7.1%, P = 0.004), wheeze ever (36.9 vs 22.5%, P = 0.002) and allergic sensitization (36.2 vs 22.1%, respectively, P < 0.001). CONCLUSION: Childhood asthma apparently continues to increase in Oslo, having affected every fifth 10-year-old child.

Effect of inhaled steroids on lung function in young children: a cohort study.

The objectives of the present study were to determine the use of inhaled corticosteroids (ICS) for treating recurrent bronchial obstruction (rBO) in young children up to 2 yrs of age and to assess possible modifying effects of ICS on lung function in young children with rBO. From an observational, noninterventional birth cohort of 3,754 newborn children (3,697 with complete questionnaire data by 2 yrs of age), 306 children with documented rBO by age 2 yrs (cases) were identified along with 306 matched controls. Two tidal flow/volume measurements were taken, one at presentation of disease (children were steroid naive) and one at 2 yrs of age (mean age 11.2 and 25.6 months, respectively), from: 21 cases who subsequently received ICS (ICS+); 33 who did not (ICS-); and in 15 controls. The mean +/- SD duration of ICS treatment was 10.3 +/- 6.5 months. The main outcomes were treatment with ICS and baseline ratio of time to peak expiratory flow/total expiratory time (tPTEF/tE). From the entire cohort, 77 children (2.1%) and 21% of children with rBO had received ICS by 2 yrs of age. Baseline tPTEF/tE was significantly lower at the first visit only in ICS+ as compared to ICS- subjects, as well as in ICS+ and ICS- as compared to controls. The mean difference in baseline tPTEF/tE from first to second visit was borderline statistically significant in the ICS+ group only and correlated significantly with duration of ICS treatment. The present observational cohort study demonstrated that one-fifth of young children with recurrent bronchial obstruction had received inhaled corticosteroids. Early inhaled corticosteroid treatment improved lung function by age 2 yrs, mostly in those with the longest duration of treatment.