Symptoms, but not a biomarker response to inhaled corticosteroids, predict asthma in preschool children with recurrent wheeze.

BACKGROUND: A reliable asthma diagnosis is challenging in preschool wheezing children. As inhaled corticosteroids (ICS) are more effective in asthmatics than in children with transient wheeze, an ICS response might be helpful in early asthma diagnosis. METHODS: 175 children (aged two-four years) with recurrent wheeze received 200 µg Beclomethasone extra-fine daily for eight weeks. Changes in Exhaled Breath Condensate (EBC) biomarkers (pH, interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, IFN-γ, sICAM, and CCL-11), Fractional exhaled Nitric Oxide (FeNO), airway resistance, and symptoms were assessed. At six years of age a child was diagnosed as transient wheezer or asthmatic. Adjusted logistic regression analysis was performed with multiple testing correction. RESULTS: 106 transient wheezers and 64 asthmatics were analysed at six years of age. Neither changes in EBC biomarkers, nor FeNO, airway resistance, or symptoms during ICS trial at preschool age were related to asthma diagnosis at six years of age. However, asthmatics had more airway symptoms before the start of the ICS trial than transient wheezers (P < 0.01). DISCUSSION: Although symptom score in preschool wheezing children at baseline was associated with asthma at six years of age, EBC biomarkers, airway resistance, or symptom response to ICS at preschool age could not predict asthma diagnosis at six years of age.

Can exhaled inflammatory markers predict a steroid response in wheezing preschool children?

BACKGROUND: The efficacy of inhaled corticosteroids (ICS) varies among wheezing preschool children. Currently, it is not possible to predict which fraction of wheezing children will benefit from an ICS treatment. OBJECTIVE: We explored whether fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC) can predict an ICS response in preschool wheezers. METHODS: An 8-week ICS study (registered at Clinicaltrial.gov: NCT 00422747; 200 µg; beclomethasone extra-fine daily) was performed in 93 wheezing children (age range 2.0-4.4 years). At baseline, FeNO was determined off-line. EBC was collected using a closed glass-condenser. The acidity of EBC was determined and other EBC markers [interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, soluble intercellular adhesion molecule, interferon-γ, eotaxin] were measured using a multiplex immunoassay. The change in airway resistance (Rint) and symptom score following ICS treatment was related to atopy (positive Phadiatop Infant test), FeNO and EBC markers. RESULTS: Airway resistance and symptoms mildly improved after ICS treatment [median (IQR): 1.4 (1.2-1.7) to 1.3 (1.1-1.5) kPa s/L, symptom score: 26 (23-28) to 28 (24-29), P < 0.01, respectively]. Only IL-10 and atopy had limited predictive value regarding a change in symptoms [ß (SE) =-0.13 (0.07), P = 0.08, ß (SE) = 2.05 (1.17), P = 0.08, respectively]. CONCLUSIONS AND CLINICAL RELEVANCE: We did not find convincing evidence that FeNO and EBC markers could predict an ICS response in preschool wheezers. Recommendations for future studies on this topic are given.