Urinary and exhaled biomarkers of exercise-induced bronchoconstriction in atopic asthmatic children

Abstract

Background: Exercise-induced bronchoconstriction (EIB) reflects poor asthma control. Assessing noninvasive biomarkers associated with EIB could help to monitor patients in the pediatric age.

Aims: To test exhaled and urinary biomarkers for assessing EIB in atopic asthmatic children.

Methods: In 45 atopic patients (11.1 ± 1.8 years, 25 males) we measured the fractional exhaled nitric oxide (FE_NO ), its alveolar (CaNO), and bronchial (J'awNO) components corrected for the trumpet shape of the airways and axial NO diffusion (TMAD), concentrations of urinary adenosine and 8-hydroxy-2'-deoxyguanosine (8-OxodG), blood eosinophils count, total immunoglobulin E , skin prick tests, and baseline spirometry before a treadmill exercise challenge. Forty healthy control subjects participated solely to baseline measurements.

Results: Patients yielded higher FE_NO and urinary adenosine concentrations than healthy controls. After the challenge, 18 patients (40%) had EIB; these patients had higher levels of CaNO, CaNO TMAD, and urinary adenosine than patients without EIB. Baseline spirometry, FE _NO , JawNO, JawNO TMAD, urinary 8-OxodG, allergy, and blood eosinophil counts were found similar in both groups. In multiple linear regression, the fall in FEV ₁ was explained by CaNO TMAD, urinary adenosine and blood eosinophil count, whereas the fall in FEF _25-75 was explained by CaNO TMAD and blood eosinophil count. Both CaNO TMAD ≥10.5 ppb and urinary adenosine ≥406 nmol/mmol Cr predicted a fall in FEV ₁ ≥10%, while only CaNO TMAD ≥10.5 ppb predicted a fall in FEF _25-75 ≥26%.

Conclusion: Concentrations of peripheral airway NO are complementary with urinary adenosine for assessing EIB and promising tools of asthma control in pediatric patients with the atopic phenotype.

Keywords: adenosine; allergy; asthma; eosinophils; guanosine; nitric oxide; pediatrics; treadmill test; urine.