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Background: Primary prevention of food allergy by early introduction of allergenic foods seems promising. We aimed to determine whether early food introduction or the application of regular skin emollients in infants from a general population reduced the risk of food allergy. Methods: This 2 × 2 factorial, cluster-randomised trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine 18-week ultrasound examination were cluster-randomised at birth to the following groups: (1) no intervention group; (2) the skin intervention group (skin emollients; bath additives and facial cream; from age 2 weeks to

BACKGROUND Improved quality of life (QoL) after oral immunotherapy (OIT) in peanut allergic children is often reported by their parents, while the child's perspective is less clear. OBJECTIVE We aimed to explore whether 2 years of OIT improved QoL in children with peanut allergy and to identify factors influencing change in QoL. METHODS In the open-labeled TAKE-AWAY peanut OIT trial including children with anaphylaxis to peanuts, 57 were randomized to OIT and 20 to observation. The Pediatric Quality of Life Inventory Version 4.0 was completed by parents and children at enrollment (Y0 ), after 1 year (end of updosing; Y1 ) and after 2 years (Y2 ) of OIT. Minimally clinically important difference (MCID) is ≥5.3. Perceived treatment burden was recorded by visual analogue scales, including adverse events (AEs). An open food challenge (OFC) was performed at Y2 . RESULTS At Y2 , 18 children had discontinued OIT and 2 of 39 OIT children refused OFC, while 35 of 37 were desensitized to 7500 mg peanut protein. From Y0 to Y2, the mean change (95% confidence intervals) in QoL was 4.4 (0.5, 8.3) among child self-reports and twice as large among parental proxy reports (9.3 [4.3, 14.3]; both P

Background There are limited data on the feasibility, efficacy and safety of high-dose oral immunotherapy (OIT) in children highly allergic to peanuts. Objective In children highly allergic to peanut, we primarily aimed to determine the feasibility of reaching the maximum maintenance dose (MMD) of 5000 mg peanut protein or, alternatively, a lower individual maintenance dose (IMD), by OIT up-dosing. Secondarily, we aimed to identify adverse events (AEs) and determine factors associated with reaching a maintenance dose. Methods The TAKE-AWAY peanut OIT trial enrolled 77 children 5-15 years old, with a positive oral peanut challenge. Fifty-seven were randomized to OIT with biweekly dose step-up until reaching MMD or IMD and 20 to observation only. Demographic and biological characteristics, AEs, medication and protocol deviations were explored for associations with reaching maintenance dose. Results All children had anaphylaxis defined by objective symptoms in minimum two organ systems during baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5% discontinued OIT. During up-dosing, 19.4% experienced anaphylaxis. Not reaching the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and social reasons (6.7%). Increased peanut s-IgG4 /s-IgE ratio (OR [95% CI]: 1.02 [1.00, 1.04]) was associated with reaching MMD. Conclusion Although 75.5% of children with peanut anaphylaxis reached a maintenance dose of 0.25-5 g, only 21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of anaphylaxis, limited the feasibility of reaching MMD.

Summary Background Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. Methods This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Ostfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov , NCT02449850 . Findings 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI –0·3 to 6·5) for skin intervention and 1·0% (–2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. Interpretation Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. Funding The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vardalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council—the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare—FORTE, Oslo University Hospital, the University of Oslo, and Ostfold Hospital Trust.

Objective An inverse effect of Helicobacter pylori (H. pylori) on the occurrence of asthma is debated and early acquisition of H. pylori may be important. We analyzed sera from 197 children from Environment and Childhood Asthma (ECA) study in Oslo for Helicobacter pylori (H. pylori) at 2 and 10 years, and symptoms and signs of asthma at 16 years of age. Results While 16.4% of children who were H. pylori negative at 2 and 10 years had current asthma at 16 years, none of the 12 children who were H. pylori positive at 2 years of age had asthma at the age of 16 years, regardless of H. pylori status at 10 years. This trend for less current asthma in children who were H. pylori positive at 2 years compared to persistent or transient negative status at 10 years was not statistically significant, probably due to low number of H. pylori positive children at 2 years of age. Acquisition of H. pylori in school age did not appear to influence the risk of current asthma. Much larger prospective studies are probably required to document whether or not early H. pylori infection may be involved in the risk of asthma development in later childhood.

Children with asthma may be less physically active than their healthy peers. We aimed to investigate whether perceived exercise limitation (EL) was associated with lung function or bronchial hyper-responsiveness (BHR), socioeconomic factors, prenatal smoking, overweight, allergic disease, asthma severity, or physical activity (PA).The 302 children with asthma from the 10-year examination of the Environment and Childhood Asthma birth cohort study underwent a clinical examination including perceived EL (structured interview of child and parent(s)), measure of overweight (body mass index by sex and age passing through 25 kg/mIn the final model explaining 30.1%, asthma severity score (OR: 1.49, (1.32, 1.67)) and overweight (OR: 2.35 (1.14, 4.82)) only were significantly associated with perceived EL. Excluding asthma severity and allergic disease, severe BHR (OR: 2.82 (1.38, 5.76)) or maximal reduction in FEVPerceived EL in children with asthma was independently associated with asthma severity and overweight, the latter doubling the probability of perceived EL irrespectively of asthma severity, allergy status, socioeconomic factors, prenatal smoking, or PA.

BACKGROUND Peanut allergy necessitates dietary restrictions, preferably individualized by determining reactivity threshold through an oral food challenge (OFC). However, risk of systemic reactions often precludes OFC in children with severe peanut allergy. OBJECTIVE We aimed to determine whether clinical and/or immunological characteristics were associated with reactivity threshold in children with anaphylaxis to peanut and secondarily, to investigate whether these characteristics were associated with severity of the allergic reaction during OFC. METHODS A double-blinded placebo-controlled food challenge (DBPCFC) with peanut was performed in 96 5- to 15-year-old children with a history of severe allergic reactions to peanut and/or sensitization to peanut (skin prick test [SPT] ≥3 mm or specific immunoglobulin E [s-IgE] ≥0.35 kUA/L). Investigations preceding the DBPCFC included a structured interview, SPT, lung function measurements, serological immunology assessment (IgE, IgG and IgG4 ), basophil activation test (BAT) and conjunctival allergen provocation test (CAPT). International standards were used to define anaphylaxis and grade the allergic reaction during OFC. RESULTS During DBPCFC, all 96 children (median age 9.3, range 5.1-15.2) reacted with anaphylaxis (moderate objective symptoms from at least two organ systems). Basophil activation (CD63+ basophils ≥15%), peanut SPT and the ratio of peanut s-IgE/total IgE were significantly associated with reactivity threshold and lowest observed adverse events level (LOAEL) (all P < .04). Basophil activation best predicted very low threshold level (

Background: High-molecular-weight phthalates in indoor dust have been associated with asthma in children, but few studies have evaluated phthalate biomarkers in association with respiratory outcomes. Objectives: We explored the association between urinary concentrations of phthalate metabolites and current asthma. Methods: In a cross-sectional analysis, 11 metabolites of 8 phthalates [including four metabolites of di(2-ethylhexyl) phthalate] were measured in one first morning void collected from 2001 through 2004 from 623 10-year-old Norwegian children. Logistic regression models controlling for urine specific gravity, sex, parental asthma, and income were used to estimate associations between current asthma and phthalate metabolite concentrations by quartiles or as log10-transformed variables. Results: Current asthma was associated with both mono(carboxyoctyl) phthalate (MCOP) and mono(carboxynonyl) phthalate (MCNP), although the association was limited to those in the highest quartile of these chemicals. The adjusted odds ratio (aOR) for current asthma was 1.9 (95% CI: 1.0, 3.3) for the highest MCOP quartile compared with the lowest quartile, and 1.3 (95% CI: 0.98, 1.7) for an interquartile-range increase. The aOR for current asthma was 2.2 (95% CI: 1.2, 4.0) for the highest MCNP quartile and 1.3 (95% CI: 1.0, 1.7) for an interquartile-range increase. The other phthalate metabolites were not associated with current asthma. Conclusions: Current asthma was associated with the highest quartiles of MCOP and MCNP, metabolites of two high molecular weight phthalates, diisononyl phthalate and diisodecyl phthalate, respectively. Given the short biological half-life of the phthalates and the cross-sectional design, our findings should be interpreted cautiously.

Aim: We investigated whether paracetamol exposure in pregnancy and until 6 months of age was associated with allergic disease in school children. Methods: In a prospective birth cohort study in Oslo, 1016 children included at birth were re-investigated at 10 years. Paracetamol exposure in pregnancy and until 6 months of age was registered. Outcomes at 10 years included current asthma, a history of asthma, allergic sensitization and allergic rhinitis. Results: Maternal paracetamol use in the first trimester increased the risk for allergic rhinitis at 10 years OR (odds ratio) (95%CI) 2.30 (1.06, 4.97) in boys and girls. Paracetamol use until 6 months in girls increased the risk for allergic sensitization OR 2.20 (1.15, 4.22) and a history of asthma OR 2.20 (1.13, 4.30). The ORs for allergic sensitization and history of asthma in girls remained unchanged adjusting for upper or lower airway infections during the first 6 months of life. Conclusion: Paracetamol exposure in pregnancy was associated with allergic rhinitis, but not with asthma or allergic sensitization at 10 years of age. Paracetamol used until 6 months of age was associated with allergic sensitization and having a history of asthma in girls at 10 years of age, even considering concomitant airway infections.

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.

Early intervention with inhaled corticosteroid (ICS) treatment for lung function development in childhood is debated. In view of lung function at birth, we aimed to assess if early use of ICS influenced lung function at 10 yrs of age. A 10-yr follow-up study of 614/802 children (mean age 10.9 +/- 0.9 yrs) with lung function measurements at birth in the Environment and Childhood Asthma study in Oslo included information on ICS treatment (124 with history of asthma) obtained at 2 and 10 yrs by parental interviews. Main outcomes at 10 yrs were the best values (% predicted and Z-scores) of forced expiratory volume in 1 s (FEV(1)) and mid-expiratory flow. The main explanatory factors were never, past or current use of ICS and Z-scores of the tidal flow-volume ratio t(PTEF)/t(E) [time to peak expiratory flow (t(PTEF)) and total expiratory time (t(E))] at birth. ICS treatment, reported by 11.9% of children in the population sample and 71.6% with current asthma, did not significantly influence lung function from birth to 10 yrs. The best values (and Z-scores) of FEV(1), and mid-expiratory flow were similar (p > 0.1) in subjects receiving ICS during and after 0-3 yrs of age, after 3 yrs only or currently compared with steroid naive children. Almost half of the change in lung function 0-10 yrs was explained by gender, a history of asthma and t(PTEF)/t(E) at birth. ICS treatment for asthma, reported in every eighth child by age 10 yrs, did not significantly improve lung function from birth to 10 yrs.

Background: The HLA (human leukocyte antigen) class II genes DQB1 and DRB1 and the Tumor Necrosis Factor α 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.

The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p < 0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr.

Summary Background Several candidate genes have been implicated in the etiology of asthma, including the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Mutations in the CFTR gene result in derangements of mucociliary clearance. Homozygotes for CFTR mutations develop cystic fibrosis (CF), a disorder characterized mainly by lung and pancreas disease. Objective To investigate whether there was an increased frequency of CFTR mutations in asthma patients. Methods Seven hundred and three subjects aged 10–11 years from the environment and childhood asthma (ECA) study were included in the present study. Possible associations between asthma, reduced lung function, bronchial hyperresponsiveness (BHR), and increased or decreased nitrogen oxide (NO) levels (based on structural parental interview, spirometry, PD 20 methacholine challenge test and exhaled NO measurements), and the five most common CFTR mutations in Norway (ΔF508, R117H, R117C, 4005+2T→C, 394delTT), the modulating polymorphisms IVS8(TG) m T n and the IVS8-5T were investigated. Results No association were found between asthma, reduced lung function, BHR or exhaled NO levels and CF heterozygosity. However, the IVS8(TG) 11 T 7 haplotype was associated with normal lung function. Conclusions Our results do not support the hypothesis that CFTR mutations or polymorphisms play a role in the pathogenesis of asthma in children. However, the distribution of Tn(TG)m haplotypes differed between individuals with reduced lung function and individuals with normal lung function.

Childhood asthma phenotypes reflecting underlying developmental mechanisms are sought, with little information on asthma phenotypes based on allergic comorbidities.We asked whether lung function trajectories from birth to 16 years were associated with asthma phenotypes with comorbid allergic rhinitis and atopic dermatitis.Lung function (given as z scores) was measured at birth in 329 subjects in the "Environment and Childhood Asthma" birth cohort study in Oslo by using tidal flow volume loops, and at 10 and 16 years by using spirometry. Asthma phenotypes were classified on the basis of recurrent bronchial obstruction at 0 to 2 years, and asthma from the 2- to 10-year and 10- to 16-year intervals, and by combining asthma, atopic dermatitis, and/or allergic rhinitis from 10 to 16 years, stratifying for allergic sensitization. The reference group included 231 subjects without recurrent bronchial obstruction or asthma.Lung function trajectories differed significantly for asthma comorbidity phenotypes for FEV1, forced expiratory flow at 25% to 75% of forced vital capacity, and FEV1/forced vital capacity (all P.0001). Significant lung function impairment was observed from birth through 16 years among subjects with asthma, atopic dermatitis, and allergic rhinitis. Lung function trajectories in subjects with asthma at 10 to 16 years or asthma in remission differed significantly for all 3 spirometric values compared with the trajectories in those who never had asthma (P.0001), but not between asthma groups. Allergic sensitization was not significantly associated with asthma phenotype lung function trajectories.The trajectory consisting of impaired lung function from birth throughout childhood in children with asthma, atopic dermatitis, and allergic rhinitis appears less likely to be driven by allergic sensitization, and may imply disease onset in utero, with clinical presentation later in childhood.

Plasma levels of calprotectin correlate with disease activity and clinical assessments of arthritis in various rheumatic diseases, and high levels have been demonstrated in the synovial fluid of patients with rheumatoid arthritis. However, the role of calprotectin in rheumatic inflammation is unclear. The purpose of the present study was to investigate potential intra-articular effects of calprotectin. Calprotectin was injected into joints of healthy male Lewis rats and into joints of rats in the latency period before onset of avridine-induced arthritis. In addition, a group of animals had IgG antibodies to rat calprotectin injected into joints before onset of avridine-induced arthritis. Injection of 0.2 or 10 micrograms calprotectin into the ankles of healthy male Lewis rats resulted in histologically minor and reversible inflammatory changes, but without any circulating antibodies to calprotectin. Furthermore, animals with 40 micrograms calprotectin injected into ankles before the expected onset of avridine-induced arthritis had lower scores for cellular infiltration than were seen in control joints. This difference did not quite reach statistical significance in the two-sided test used. However, the induced arthritis increased in joints injected with IgG antibodies to calprotectin. These findings may indicate that increased local concentrations of calprotectin are partially protective against avridine-induced arthritis. In contrast, reduced local concentrations appear to exacerbate the severity of arthritis. Calprotectin may thus be involved in the regulation of inflammatory processes in joints.

We investigated whether paracetamol exposure in pregnancy and until 6 months of age was associated with allergic disease in school children.In a prospective birth cohort study in Oslo, 1016 children included at birth were re-investigated at 10 years. Paracetamol exposure in pregnancy and until 6 months of age was registered. Outcomes at 10 years included current asthma, a history of asthma, allergic sensitization and allergic rhinitis.Maternal paracetamol use in the first trimester increased the risk for allergic rhinitis at 10 years OR (odds ratio) (95%CI) 2.30 (1.06, 4.97) in boys and girls. Paracetamol use until 6 months in girls increased the risk for allergic sensitization OR 2.20 (1.15, 4.22) and a history of asthma OR 2.20 (1.13, 4.30). The ORs for allergic sensitization and history of asthma in girls remained unchanged adjusting for upper or lower airway infections during the first 6 months of life.Paracetamol exposure in pregnancy was associated with allergic rhinitis, but not with asthma or allergic sensitization at 10 years of age. Paracetamol used until 6 months of age was associated with allergic sensitization and having a history of asthma in girls at 10 years of age, even considering concomitant airway infections.

Sachs-Olsen C, Lodrup Carlsen KC, Mowinckel P, Haland G, Devulapalli CS, Munthe-Kaas MC, Carlsen K-H. Diagnostic value of exhaled nitric oxide in childhood asthma and allergy. Pediatr Allergy Immunol 2010: 21: e213–e221. © 2010 John Wiley & Sons A/S Fractional exhaled nitric oxide (FENO) has been proposed as a diagnostic test of asthma. We aimed to investigate in a population based birth cohort of children the usefulness of FENO 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 FENO (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. FENO 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

To cite this article: Lodrup Carlsen KC, Soderstrom L, Mowinckel P, Haland G, Pettersen M, Munthe Kaas MC, Devulapalli CS, Buchmann M, Ahlstedt S, Carlsen K-H. Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score. Allergy 2010; 65: 1134–1140. Abstract 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 (Σ-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 Σ-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 R2 = 0.24) of the variation in CA, whereas Σ-IgE explained only 6% (R2 = 0.06). Combining the two increased the explanatory capacity to R2 = 0.30. Gender interacted significantly with Σ-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Σ-IgE for CA at 10 years was significant in boys only. Conclusion: Combining Σ-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 Σ-IgE significantly predicted CA in boys only.

Summary Background Divergent results have been reported regarding early life exposure to indoor environmental agents and the risk of asthma and allergic sensitization later in life. Objective To assess whether early exposure to indoor allergens, β(1,3)-glucans and endotoxin modifies the risk of allergic diseases at 10 years of age. Methods The concentrations of mite, cat and dog allergens, endotoxin and β(1,3)-glucans were determined in dust from the homes of 260 two-year-old children with lung function measured at birth (tidal flow volume loops) in the Environment and Childhood Asthma study in Oslo. At 10 years, the health status was assessed in a follow-up study including a structured interview of the parents and an extended clinical examination. Results Cat and dog keeping at 2 years of age was reported in 6.5% and 5.5% of the families, respectively. Mite allergens were detected in only 4/260 dust samples. The adjusted odds ratio for asthma at age 10 was 1.20 (95% confidence interval: 1.01–1.43) and 1.22 (1.02–1.46) for bronchial hyperresponsiveness (BHR) per 10 μg/g dust increase in cat allergen exposure at 2 years of age. No association was seen with allergic sensitization. Moreover, endotoxin and β(1,3)-glucan exposure did not modify the risk of asthma or allergic sensitization. None of the measured environmental factors were associated with lung function at 10 years of age or a relative change in lung function from birth. Conclusion In a community with a low prevalence of pet keeping and low mite allergen levels, exposure to cat allergens early in life increased the risk of late childhood asthma and BHR, but not the risk of allergic sensitization. No risk modification was seen for dog allergens, endotoxin and β(1,3)-glucans. Cite this as: R. J. Bertelsen, K. C. Lodrup CarlsenK.-H. Carlsen, B. Granum, G. Doekes, G. Haland, P. Mowinckel and M. Lovik, Clinical & Experimental Allergy, 2010 (40) 307– 316.

The causal relationship between lower respiratory tract infections (LRIs) in early life and reduced lung function later in childhood is unsettled. Therefore, we assessed whether LRIs the first 2 yr of life influenced lung function development from birth to school age. In the prospective Oslo birth cohort, 'the Environment and Childhood Asthma (ECA) study' lung function was measured at birth in 802 infants by tidal flow volume loops and in 664 infants by passive respiratory mechanics and half yearly questionnaires, including LRI questions, were completed until 2 yr of age. The present study includes 607 children with information about LRIs the first 2 yr of life and successfully forced expiratory flow (FEF) volume measurements at the 10-yr follow-up assessment. At 10 yr of age, FEF at 50% of forced vital capacity (FEF(50)) (mean 95% confidence interval) was reduced in children with at least one bronchiolitis (85.0, 80.6-89.5, p = 0.020) or bronchitis (86.2, 82.6-89.8, p = 0.030) or > or =3 LRIs (83.4, 78.1-88.8, p = 0.017) when compared with no LRIs (90.6, 88.8-92.5) by 2 yr of life. The effects were significant in girls only when stratifying for gender. Among girls with later bronchiolitis compliance of the respiratory system (3.64, 3.17-4.10 vs. 4.18, 3.98-4.37, p = 0.031) and the ratio of time to peak tidal expiratory flow to total expiratory time (t(PTEF)/t(E)) measured at birth was significantly reduced (0. 26, 0.23-0.29 vs. 0.32, 0.30-0.33, p = 0.005) when compared with children with no LRIs. Change in lung function from birth (by t(PTEF)/t(E)) to 10 yr of age was not significantly associated with LRIs the first 2 yr of life, and LRIs by 2 yr of life were not significantly associated with lung function at 10 yr of age in regression analyses including lung function at birth and other possible predictors of lung function at 10 yr. In our study, LRIs during the first 2 yr of life did not impair lung function development from birth until 10 yr 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 (⩾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 (PD 20 metacholine 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.

The aim of the study was to assess if lung function at birth predicts lung function at 2 yr and secondly, if lung function development was influenced by the common phenotypes of recurrent bronchial obstruction (rBO) or atopic eczema (AE) by 2 yr. Lung function was assessed at birth (n = 802) and at 2 yr within the prospective birth cohort study 'the Environment and Childhood Asthma Study' in Oslo. The 135 children with lung function measured at birth by tidal flow volume (TFV) loops and passive respiratory mechanics, who were included in a nested case-control study were reinvestigated at 2 yr with clinical examination, TFV loops (n = 90) (mean age 26.6 (3.7 s.d.) months), skin prick test and parental interview. Children were categorized into quartiles (lower, middle two, upper) according to time to peak tidal expiratory flow/total expiratory time (t(PTEF)/t(E)) at birth as well as clinical phenotype based on the presence of rBO and/or AE (ever) by 2 yr. The observed reduction in mean t(PTEF)/t(E) from birth to 2 yr within the quartiles, were not significantly different after controlling for 'regression to the mean'. t(PTEF)/t(E) at birth correlated significantly with t(PTEF)/t(E) at 2 yr, (r = 0.475, p0.001). Children with both rBO and AE by 2 yr had significantly lower t(PTEF)/t(E) at 2 yr (p = 0.002) and at birth (p = 0.027), compared with children with no rBO or AE. Clinical phenotype at 2 yr did not influence the change in t(PTEF)/t(E) from birth to 2 yr. This study demonstrates a clear tracking of lung function from birth, not influenced by rBO or AE by 2 yr.

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 ≥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

SummaryBackgroundIt is debated whether early treatment with inhaled corticosteroids (ICS) can change the natural course of childhood asthma.AimTo assess if ICS treatment before 2 years of age in children with obstructive airways disease reduces current asthma at 10 years of age.MethodsChildren with (n = 233) and without (n = 219) recurrent (r) bronchial obstruction (BO) attending clinical examination at 2 years of age in the birth cohort Environment and Childhood Asthma study in Oslo, were reinvestigated at 10 years of age. Current asthma (CA) at 10 years was defined as asthma with either symptoms and/or asthma treatment during the last year, and/or ⩾10% fall in forced expired volume in 1s after standardized treadmill run. The risk of CA was assessed by logistic regression and propensity modelling (including gender, parental atopy and severity score at 2 years) in children with rBO who received ICS or not by 2 years.ResultsCA was found in 97 children, more often among rBO children with (56.9%) and without ICS treatment (30.8%) compared to no-BO children (5.5%) (p