Cluster Analysis in Phenotyping Patients with Severe Bronchial Asthma

One in 10 patients with asthma suffers from severe asthma, which is characterized by the presence of several clinical phenotypes. The aim of the study is to identify the clinical phenotypes of patients with difficult-to-control and severe asthma based on cluster analysis. Materials and Methods : A cross-sectional study was conducted, including 200 patients with difficult-to-control asthma. Inclusion criteria: severe and difficult-to-control asthma, all patients received treatment according to the 4th-5th step of the provided guidelines (GINA); age over 18 years. Exclusion criteria: the presence of chronic obstructive pulmonary disease, active infectious diseases, including respiratory infections, oncological diseases, pregnancy. All patients underwent clinical and laboratory tests, and levels of leptin, adiponectin, IL-6, IL-8, IL-4, and TNF-α were measured. To phenotype patients with severe asthma, cluster analysis was performed. Statistical data processing was conducted using SPSS Statistics 20.0 and StatTech v. 4.7.2 (StatTech, Russia). Results : The study included 200 patients with difficult-to-control asthma, with a median age of 53.5 (39.0-59.25) years. As a result of the cluster analysis using the k-means method, 3 clusters were identified. Significant differences were found in BMI, eosinophil count, IgE levels, and leptin (p < 0.001 when comparing the 3 clusters). Differences were also found in the levels of pro-inflammatory cytokines, primarily IL-4 (p=0.003 for the 3 clusters), TNF-α, and IL-8 (p < 0.001 when comparing the 3 clusters). It was established that the development of hypereosinophilia in patients with difficult-to-control asthma may be mediated not only by the IL-4 level (1.326, 95 % CI 1.132-1.554), but also by TNF-α (OR 1.046, 95 % CI 1.022-1.07) and IL-8 (OR 1.054, 95 % CI 1.024-1.085). Conclusion : We identified 3 clusters of patients with difficult-to-control bronchial asthma based on the study of clinical, laboratory, and instrumental data. Each identified cluster is characterized by a specific combination of laboratory markers, which can be taken into account when further treating patients with this asthma phenotype.