New determinants of exacerbations and uncontrolled course of severe asthma in obese patients

Objective. To study asthma control parameters and exacerbations characteristics in obese patients, as well as their associations with intestinal endotoxin (ET), fecal zonulin levels, along with clinical, laboratory and instrumental findings in this patient cohort. Materials and methods. The study included 143 individuals: 98 patients with asthma and obesity (Group 1 – mild asthma, (n = 47), Group 2 – severe asthma, (n = 51)) and 45 obese patients without asthma. All the patients underwent a comprehensive standard examination. Specific methods of study included measurements of intestinal endotoxin, fecal zonulin, and IgA levels. The IBM SPSS Statistics 26.0 software package was used for statistical analysis. A p-value of 0.05 was considered statistically significant. Results. New additional markers of uncontrolled asthma course in obese patients were identified: an intestinal endotoxin (ET) level ≥1.965 EU/ml (p = 0,034) and a fecal zonulin level ≥89.6 ng/ml (p 0,001). Asthma control in obese patients (as assessed by ACT-test) had statistically significant inverse associations with body mass index (BMI) (p 0.001), waist circumference (WC) (p 0.001), hip circumference (HC) (p = 0.001), the WC/HC ratio (p = 0.034), intestinal ET level (p 0.001), fecal zonulin level (p 0.001), and the number of metabolic syndrome (MS) components (p 0.001). Direct correlations were observed with forced vital capacity (FVC) (p 0.001) and forced expiratory level (FEV1) (p 0.001). In patients of Group 2 (severe asthma), statistically significant negative correlations were found between the presence of exacerbations, increased exacerbation frequency (2 or more per year), use of systemic glucocorticosteroids (SGCs) during exacerbations, and such parameters as AСT score (p = 0.008; p = 0.004; p 0.001), IgA level (p 0.001; p = 0.005; p 0.001), FVC (p = 0.003; p = 0.018; p 0.001), FEV1 (p 0.001; p = 0.001; p 0.001). Positive correlations were found with BMI (p 0.001), intestinal ET (p 0.001; p = 0.002; p 0.001) and fecal zonulin (p 0.001; p = 0.002; p 0.001). The number of MS components was positively correlated with both an increased frequency of asthma exacerbations (p = 0.034) and the need for SGCs to manage exacerbations (p = 0.006). Conclusions. Fecal zonulin and intestinal ET levels can be considered as additional markers for the risk of uncontrolled asthma in obese patients. An increase in these indicators is associated with the presence, frequency and severity of exacerbations.