Comparative analysis of the asthma phenotypes with and without exercise induced bronchoconstriction in school age children (results of cluster analysis)

Abstract

Well known association between bronchial asthma (BA) and exercise induced bronchoconstriction (EIB) was revealed long ago, but the exact mechanisms of this association are not fully defined. Patients with persistent moderate and severe BA were included in alternative clinical groups: in particular, 30 children with EIB BA phenotype and 30 patients without EIB BA were examined. EIB was diagnosed in case of the presence of bronchospasm after exercise in the patient’s history and spirometric index of bronchospasm after a dosed physical activity of at least 15%. According to the main characteristics (sex, age and place of residence) the groups were comparable. Hierarchical probabilistic approach and cluster analysis (CA) with the K-means method were used for statistical analysis. While analyzing the clinical and paraclinical characteristics of the phenotypes of BA with and without EIB in school-age children, it was found that a severe variant of the disease, allergic burden only after father's pedigree, the total number of points of clinical manifestations of exacerbation of BA higher than 15 before treatment, complaints of chest tightness during the last exacerbation, higher than 4% eosinophil count and more than 1.0 G/l absolute T lymphocyte content in the peripheral blood, and the need for constant use of short-acting beta-agonists in the remission period statistically significantly increased the chances of diagnosing BA with EIB. The bronchial lability index more than 25% most significantly increased the chances of detecting the BA phenotype with EIB, this diagnostic marker was characterized by significant reproducibility and validity (80%), while bronchial nonspecific hyperresponsiveness test to histamine (PC20H) of inhalation less than 0.8 mg/ml histamine concentration, which caused 20% FEV1 fall, also most significantly increased the chances of diagnosing of BA with EIB in children of school age. CA of a whole cohort of patients indicated a significant clinical similarity of BA phenotypes with and without EIB in children, because the first and second clusters were formed of 56% and 44% and 43% and 57% of children with phenotypes with and without EIB correspondingly. Thus, the results of CA of the cohort of pediatric patients with alternative phenotypes of the disease due to exercise induced bronchoconstriction showed a significant similarity between two clinical subclusters and the difference existed mainly due to markers of atopic reactivity.