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E MATERIAL AND METHODS
E Study design, recruitment criteria and clinical assessment
From birth till the second birthday we evaluated symptoms reported by the family doctors
and/or pediatricians in the six months prior to consultation. Doctors were instructed to use
the following definitions:
”Wheeze” was defined as 3 episodes, lasting for at least three days, of wheeze evaluated by
auscultation and/or the presence of a wheezy sound during breathing and/or prolonged
expiration, presence of dyspnoe and/or cough.
“Eczema” was defined as a more than six weeks lasting itchy, scaly rash, with or without
surinfection, in or outside the for atopic dermatitis characteristic localizations.
“Rhinitis/rhinoconjunctivitis” was diagnosed if 2 out of 3 criteria were present: sneeze (>3X in
a row), nasal blockage or nasal discharge during at least 2 weeks outside an infectious
period (with or without eye symptoms: itchy, teary eyes and/or red conjunctivae, with or
without itch in ears and/or throat).
Food reactions were defined as eczema, localized or generalized urticaria, respiratory
symptoms, gastro-intestinal symptoms, angio-oedema or collapse in association with food
intake, with or without failure to thrive.
At the age of 6 years the symptoms over the past 12 months were recalled independently of
the symptoms at young age, except for anaphylaxis which was defined as in (1): in that case
the presence of any event during the last four years was noted.
The Fraction exhaled Nitric Oxide (FeNO) measured at age 6 years (at a flow rate of 50
ml/sec) was measured with a NIOX Flex chemiluminiscence analyser (Nossegem, Belgium).
Lung function parameters (FEV1 as % predicted (FEV1%) based on age, sex and height)
were also studied at age 6.
E RESULTS
E Clinical patterns and FENO levels in healthy and early (n=17) allergic children
As shown in figure E1, up to 80 percent of early allergic children suffered from chronic
eczema during the first half year of life. This proportion declined during the second year of
life, but rose again to the same level at the age of six years. A substantial proportion of the
six year old early allergic children suffered from seasonal allergic eczema. Almost one in five
at the age of 12 months presented with wheeze, and at age six, more than 70% of them had
(had) recurrent wheeze symptoms during the last year. The proportion with
rhinoconjunctivitis in the early allergic children reached around 60% at the age of six years.
Gastro-intestinal complaints and urticaria peaked at 18 and 24 months respectively and
declined later on. Strikingly, 2 out of 17 early allergic children had at least one episode of
well-defined anaphylaxis between age 2 and 6. In contrast, the main symptom in non-allergic
children was eczema, although the incidence was below 10% (data not shown)
We studied FENO levels at age 6 years (figure E2). Early allergic children had significantly
higher FENO levels at the age of 6 years than healthy children. Not surprisingly, FENO levels
were highest in children with diagnosed asthma, treated either by short acting beta-2agonists or by montelukast (figure E2). FEV1% values (data not shown) were comparable
between all groups.
E Sensitization patterns in early allergic children
Table E1: Numbers of allergic children sensitized to specific allergens
A.
early allergic children
(N=17)
Sensitized to
At 12 months
At 24 months
At 6 years
Egg
10
3
2
Potato
4
1
0
Cow’s milk
5
3
1
Peanut
0
2
1
Nuts
0
1
1
House dust mite
4
7
16
Birch pollen
0
1
7
Grass pollen
0
0
8
Alternaria
0
0
2
Animal dander*
Cat: 1
Cat: 2
Cat: 6
Dog: 7
Rabbit: 2
Horse: 2
B. late allergic children
(N=10)
Sensitized to
At 12 months
At 24 months
At 6 years
Cow’s milk
0
0
1
Peanut
0
0
1
House dust mite
0
0
5
Birch pollen
0
0
2
Grass pollen
0
0
6
Alternaria
0
0
1
Animal dander*
0
0
Cat: 1
Dog: 2
*all these children with animal dander allergy are multisensitized and among other also sensitized to
HDM
Legends to figures
Figure E1: Clinical symptoms in early allergic children
Cohort children were clinically assessed at the age of 6, 12, 18 and 24 months as well as at
6 years. “Early” (E-A) allergic children were defined as symptomatic with relevant
sensitization “before age 2 years”. Non-allergic children (N-A) had no sensitizations between
birth and age 6 years. Their symptoms were recalled at each visit as explained in material
and methods, and the proportions of early allergic children suffering from the indicated
clinical symptoms are represented. GI: gastro-intestinal; other: urticaria, angio-oedema or
oral allergy syndrome.
Figure E2: FENO levels
FENO levels in early allergic and healthy children were measured at the age of 6 years. N-A=
non allergic; E-A= early allergic. Analysis was done in 41 and 11 children respectively due to
missing values by technical reasons. Closed symbols represent infants suffering from
wheeze, open symbols infants without bronchial complaints. Dotted arrows indicate infants
treated with daily Montelukast, full arrows indicate infants treated with daily inhaled
corticosteroids.
Bibliography
E1.
de Swert LF, Bullens D, Raes M, Dermaux A. Anaphylaxis in referred pediatric
patients: demographic and clinical features, triggers, and therapeutic approach. Eur J
Pediatr. 2008;167:1251-61.