Confirmed wheezing in infancy as basis for molecular fingerprinting in the prediction of asthma.

Rationale - Young children with confirmed wheeze do already exhibit the major
histological features of asthma. There is increasing evidence that microbial
and biological characteristics can improve the phenotyping of infants at risk
of asthma. The aim of the present study is to use confirmed wheezing as the
basis for the application of modern molecular profiling in the prediction of
asthma in young children.

The objective of this study is to test our hypothesis:

Hypothesis - We postulate that the development of asthma in preschool children
can be captured during the first 2 years of life by a minimally invasive
*fingerprint* based on the combination of:
a) Confirmed wheezing by doctors confirmation and/or electronic trachea sound
recordings.
b) Molecular microbial assessment by (multiplex) PCR analysis in nasopharyngeal
aspirates and throat swabs.
c) Molecular pattern recognition by electronic nose of exhaled volatile organic
compounds.
d) Molecular profiling in peripheral blood by RNA-expression analysis, cytokine
measurements and multiplex antibody assays

Study design - 3-phase 6 years prospective follow-up study:
* Phase 1 (2 yrs duration): inclusion and baseline assessments in wheezy
infants and their healthy age-matched controls during the first 2 years of
life.
* Phase 2 (2 yrs duration): monitoring of respiratory symptoms by Asthma
Control Questionnaire.
* Phase 3 (2 yrs duration): outcome assessment of the children for the presence
of objective criteria for asthma at age 5.

- Blood sample: We use Emla creme to sedate the skin and reduce potential
infant discomfort. Nevertheless the drawing of blood can hurt and may cause a
small bruise. We draw a small volume of blood (5 ml) thus not overstressing the
child. Current guidelines (ERS and NHG) advise to draw a venous blood sample
for airborne-allergent specifig IgE when a child presents with respiratory
wheeze and a suspicion of allergy. We will communicate results to the treating
physician so they can adjust therapy accordingly.

- Nose and throat swab: Collection of the sample can cause a short unpleasant
sensation when the swab touches the mucosal lining.

- Asthma diagnostics: When the infants is sensitive to
methacholine it may become a bit short of breath. The lungfunction laborant
will closely monitor the child during the test.

- Time: Dependent on subgroup: confirmed wheeze(max 210 min), unconfirmed
wheeze (max 180 min) healthy control (max 180 min) rest cohort (30 min).