• airway inflammation;
  • bronchial hyperresponsiveness;
  • child;
  • follow-up studies;
  • food allergy


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 (FENO) 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 FENO 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 FENO, 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 FENO 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 FENO, 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 FENO and BHR at school age. Very early exposure to CM was associated with less BHR.

Cite this as: L. P. Malmberg, K. M. Saarinen, A. S. Pelkonen, E. Savilahti and M. J. Mäkelä, Clinical & Experimental Allergy, 2010 (40) 1491–1497.