Respiratory variables and related questions
The other respiratory variables were: “In the last 12 months, has your child’s chest sounded
wheezy during or after exercise?”(wheeze if exercise), “In the last 12 months, has your child’s
chest sounded wheezy when he or she had not recently taken exercise?” (wheeze if no
exercise), “In the last 12 months, has your child had wheezing or whistling in the chest when
he/she had a cold or flu?” (wheeze with a cold), “In the past 12 months, has your child had
wheezing or whistling in the chest when he/she had no cold or flu?” (wheeze if no cold), “In
the last 12 months, has your child had a dry cough at night, apart from a cough associated
with a cold or chest infection?” (dry cough at night), “In the last 12 months, has your child
usually seemed congested in the chest or coughed up phlegm with colds?” (coughed up
phlegm with colds), “In the last 12 months, has your child usually seemed congested in the
chest or coughed up phlegm when he/she did not have a cold?”(coughed up phlegm without
colds), “Does your child seem congested in the chest or chough up phlegm on most days (4 or
more days a week) for as much as 3 months of the year?”(coughed up phlegm frequently),
“Has your child woken up with shortness of breath at any time of his or her life?” (ever
woken with shortness of breath), “Has your child woken up with tightness of the chest at any
time of his or her life?” (ever woken with tightness of the chest). All items were coded binary
with 0 indicating “no” and 1 “yes”.
Bronchial hyperresponsiveness (BHR)
Spirometry was performed according to ATS criteria (1). At least two spirograms were
recorded, and the higher of two reproducible measurements (with less than 5% variation) of
forced expiratory volume in one second (FEV1) was recorded as baseline value. The predicted
values of FEV1 in percent (FEV1%) as descriptor of lung function were calculated based on
age, weight (except Albania and the United Kingdom) and height stratified for sex and centre
by linear regression models. High FEV1 indicates good lung function.
As described elsewhere in detail2,3 bronchial hyperresponsiveness (BHR) was assessed
using de Vilbiss nebuliser by further measurements of FEV1 after inhalation of nebulised
hyperosmolar saline (4.5 %) for increasing time periods (0.5, 1, 2, 4, and 8 minutes)4FEV1
was measured 1 min after the end of each inhalation period and the next challenge was
performed after 3 min wash-out time. If the FEV1 fell 10-15 % below the baseline value, the
previous exposure time was repeated. If after two repetitions the fall of FEV1 was still
between 10% and 15%, the exposure time was also doubled. Bronchial challenge was stopped
if either the FEV1 had fallen by 15% or more or the total inhalation period of 15.5 min had
been reached. In children with a baseline FEV1 of <75% of predicted value, no bronchial
challenge was performed and an inhaled bronchodilator was administered. Children were
considered BHR-positive if FEV1 had fallen by 15% compared to baseline, or increased by
25% or more after administration of a bronchodilator.
Allergic Sensitization
SPT were performed on 3781 children using six common aeroallergens: D. pteronyssinus, D.
farinae, cat hair, Alternariatenuis, mixed tree and grass pollen (ALK, Hørsholm, Denmark).
At least one positive reaction (wheal size ≥ 3mm after subtraction of the negative control) was
defined as a positive SPT. The magnitude (size) of the skin prick test reaction was described
as the sum of the mean diameters (after substraction of negative control) for all six allergens.
Allergen-specific IgE
Allergen-specific
IgE
antibodies
to
a
mix
of
common
inhalant
allergens
(Dermatophagoidespteronyssinus, D. farinae, birch, timothy, mugwort, cat, dog, horse,
Cladosporium, olive pollen and Parietaria) were measured by Phadiatop® (Phadia AB,
Uppsala, Sweden) in one central laboratory (8). A positive allergen-specific IgE test was
defined as  0.35 kUA/L. Cut-off levels of 0.7 and 3.5 kUA/L were also tested.14
Total IgE
The serum concentrations of IgE were determined in the same laboratories as sIgE by
ImmunoCAP™ Total IgE (Phadia AB, Uppsala, Sweden) according to the manufacturer’s
instructions. The lower detection limit was 2 kU/L.