Background: Host and environment early-life risk factors are known to be associated with the evolvement of subsequent wheeze in childhood. They include sex, maternal atopy, viral infections, and pollutants, however their individual relative contribution is small. We hypothesized that the dynamic interactions of these determining risk factors with an infantŽs developing respiratory system are the dominant factor for the subsequent wheeze.

Methods: We used data from the Basel-Bern Infant Lung Development (BILD) and the Protection Against Allergy STUdy in Rural Environments (PASTURE) prospective birth cohorts. We made week-by-week correlations of the determining factors with cumulative symptom scores (CSS), which showed temporal changes during infancy. The complex dynamic interaction between the host and environment factors and the CSS resulted in a dynamic host?environment correlation network. We quantified this in a simple descriptor, trajectory function G(t).

Results: Using a standard logistic regression classification G(t) was able to distinguish between the group of infants with subsequent wheezing disorders at 2-6 years when compared to the healthy group (AUC 0.85 in BILD and 0.99 in PASTURE). Furthermore, in PASTURE, G(t) also showed clear differences between the groups of infants from a farming and non-farming environment (AUC of 0.78).

Conclusions: In comparison to individual risk factors, our results illustrate that the dynamic host?environment correlation network properties have a better discriminative ability for identifying the group of infants with subsequent wheeze. Results from this study are consistent with the hypothesis stated by the 2018 Lancet Commission on Asthma.