title: Cow's milk allergy as a predictor of bronchial hyperresponsiveness and airway inflammation at school age.
abstract: BACKGROUND
  Cow's milk allergy (CMA) has been found to be associated with an increased incidence of asthma at school age. However, prospective population-based studies of CMA and the development of airway inflammation and bronchial hyperresponsivess (BHR) are lacking.
  
  
  OBJECTIVE
  The aims of this study was to evaluate CMA as a risk factor for BHR and airway inflammation presented later in childhood.
  
  
  METHODS
  We followed prospectively 118 children with CMA and invited them to a clinical visit at a mean age of 8.6 years including the measurement of exhaled nitric oxide (FE(NO) ) and bronchial challenge with histamine. Ninety-four patients and 80 control subjects from the same cohort participated.
  
  
  RESULTS
  At school age, children with a history of CMA had higher FE(NO) levels (P=0.0009) and more pronounced responsiveness to histamine (P=0.027) than their controls. Stratified analysis showed a significant difference only in IgE-positive CMA. Multinomial logistic regression analysis showed that IgE-positive CMA [odds ratio (OR) 3.51; 95% confidence intervals (CI) 1.56-7.90; P=0.002] and a history of wheeze during the first year of life (OR 2.81; 95% CI 1.16-6.84; P=0.023) were independent explanatory factors for increased FE(NO) , and IgE-positive CMA (OR 3.37; 95% CI 1.03-10.97; P=0.044) and parental smoking (OR 3.41; 95% CI 1.14-10.22; P=0.028) for increased BHR, whereas for IgE-negative CMA, no associations with FE(NO) or BHR were found. In the CMA group, those exposed to CM very early at the maternity hospital, had less BHR (P=0.002).
  
  
  CONCLUSIONS
  Compared with their controls, children with a history of IgE-positive CMA show signs of airway inflammation, expressed as higher FE(NO) , and more pronounced bronchial responsiveness to histamine at school age. In contrast to IgE-negative CMA, IgE-positive CMA is a significant predictor of increased FE(NO) and BHR at school age. Very early exposure to CM was associated with less BHR.
authors.affiliation: Department of Allergy, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland. pekka.malmberg@hus.fi
authors.forename: L P
authors.initials: LP
authors.lastname: Malmberg
authors.forename: K M
authors.initials: KM
authors.lastname: Saarinen
authors.forename: A S
authors.initials: AS
authors.lastname: Pelkonen
authors.forename: E
authors.initials: E
authors.lastname: Savilahti
authors.forename: M J
authors.initials: MJ
authors.lastname: Mäkelä
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000150:complications* / Q000276:immunology; D001985:Bronchial Provocation Tests; D002417:Cattle; D002648:Child; D045853:Exhalation; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008892:Milk / Q000276:immunology; D016269:Milk Hypersensitivity / Q000150:complications* / Q000276:immunology; D009569:Nitric Oxide / Q000032:analysis; D011014:Pneumonia / Q000150:complications* / Q000276:immunology; D012129:Respiratory Function Tests; D012307:Risk Factors; D012882:Skin Tests
chemical_list: D009569:Nitric Oxide; D007073:Immunoglobulin E