Inflammatory markers in and the treatment of acute pre-school viral wheeze

Asthma in preschool children is characterised by recurrent viral cold triggered wheezy episodes (PVW) and in the majority may be phenotypically distinct from atopic asthma. In order to address this, I performed four interrelated studies on children (1-5 years) presenting to hospital with acute PVW, and 'normal' and 'atopic' controls. The study on eosinophil activation performed by analysing urinary (u) Eosinophil Protein X (EPX) showed that uEPX was increased in acute PVW compared to both controls, with no association between uEPX and IgE. uEPX fell on convalescence, but was not predictive of asthma symptoms two years later. The investigation on cysteinyl leukotrienes, using urinary (u) Leukotriene E4 (LTE4) showed for the first time, its relationship with wheeze and atopy. Elevated uLTE4 in acute PVW fell rapidly in recovery. uLTE4 correlated with IgE, and the fall in uLTE4 at recuperation was seen only in the high IgE subgroup. The neutrophil activation study was novel, and examined the expression of adhesion molecule L-selectin. In acute PVW this was reduced on systemic neutrophils and the soluble L-selectin in serum was increased compared to controls.;Children included in the clinical trial were allocated to a high- and low-primed stratum by measuring serum Eosinophil Cationic Protein and EPX, and randomised to receive parent-initiated prednisolone or placebo for the next PVW. 108 children were randomised to placebo and 109 to prednisolone. No difference in mean day- and night-time symptom score, salbutamol usage and need for hospitalisation was noted. Sub analysis within either eosinophil strata also was similar