Monica Cheng Munthe-Kaas

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

Background:  The western worlds 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.

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 (⩾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 μmol) 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.

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.

A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma

Type 1 diabetes (T1D) and allergic asthma are immune-mediated diseases. Pattern recognition receptors are proteins expressed by cells in the immune system to identify microbial pathogens and endogenous ligands. Toll-like receptors (TLRs) and CD14 are members of this family and could represent a molecular link between microbial infections and immune-mediated diseases. Diverging hypotheses regarding whether there exists a common or inverse genetic etiology behind these immune-mediated diseases have been presented. We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the ‘Environment and Childhood Asthma’ study. Allele and haplotype frequencies were analyzed in relation to diseases and in addition transmission disequilibrium test analyses were performed in the family material. Both T1D and allergic asthma were significantly associated with the TLR2 rs3804100 T allele and further associated with the haplotype including this SNP, possibly representing a susceptibility locus common for the two diseases. Neither TLR4 nor CD14 were associated with T1D or allergic asthma.

Diagnostic value of exhaled nitric oxide in childhood asthma and allergy

Sachs‐Olsen C, Lødrup Carlsen KC, Mowinckel P, Håland 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

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 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.

Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s-ECP levels and related phenotypes

Background:  Eosinophil cationic protein (ECP) is a potent cytotoxic secretory protein with bactericidal and antiviral properties. ECP is released by activated eosinophils and regarded as a marker of eosinophilic inflammation. High levels of ECP have been reported in cases of active asthma and other allergic diseases. This study aimed to assess whether three single‐nucleotide polymorphisms (SNPs) in the ECP gene (RNASE3) on chromosome 14 q24–q31 or their haplotypes are associated with asthma, allergy, or related phenotypes.

Original article: Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s-ECP levels and related phenotypes

Background:  Eosinophil cationic protein (ECP) is a potent cytotoxic secretory protein with bactericidal and antiviral properties. ECP is released by activated eosinophils and regarded as a marker of eosinophilic inflammation. High levels of ECP have been reported in cases of active asthma and other allergic diseases. This study aimed to assess whether three single‐nucleotide polymorphisms (SNPs) in the ECP gene (RNASE3) on chromosome 14 q24–q31 or their haplotypes are associated with asthma, allergy, or related phenotypes.

Lung function at 10 yr is not impaired by early childhood lower respiratory tract infections

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 (FEF50) (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 ≥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 (tPTEF/tE) 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 tPTEF/tE) 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.

Pet keeping and tobacco exposure influence CD14 methylation in childhood.

Several CD14 gene–environment interactions in relation to the development of allergic diseases have been reported, but the underlying biological mechanisms are unclear. We recently showed that CD14 methylation increased during childhood, parallelling a decreased impact of CD14 polymorphisms on soluble CD14 levels. Here, we aim to explore whether environmental stimuli during childhood affects CD14 methylation, thereby providing a biological mechanism through which environment may modulate genetic effect.