Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma

Abstract

Rationale: The relationship between airway inflammation and obesity in severe asthma is poorly understood.

Objectives: We sought to determine the relationship between sputum mediator profiles and the distribution of eosinophilic inflammation and obesity in people with severe asthma.

Methods: Clinical parameters and eight mediators in sputum were assessed in 131 subjects with severe asthma from a single center categorized into lean, overweight, and obese groups defined by their body mass index. In an independent group of people with severe asthma (n = 45) and healthy control subjects (n = 19) eosinophilic inflammation was enumerated in bronchial submucosa, blood, and sputum and related to their body mass index.

Measurements and main results: Sputum IL-5 geometric mean (95% confidence interval) (pg/ml) was elevated in the obese (1.8 [1.2-2.6]) compared with overweight (1.1 [0.8-1.3]; P = 0.025) and lean (0.9 [0.6-1.2]; P = 0.018) subjects with asthma and was correlated with body mass index (r = 0.29; P < 0.001). There was no relationship among body mass index, the sputum cell count, or other sputum mediators. In the bronchoscopy group the submucosal eosinophil number in the subjects with asthma was correlated with body mass index (Spearman rank correlation, rs = 0.38; P = 0.013) and the median (interquartile range) number of submucosal eosinophils was increased in obese (19.4 [11.8-31.2]) (cells per square millimeter) versus lean subjects (8.2 [5.4-14.6]) (P = 0.006). There was no significant association between sputum or peripheral blood eosinophil counts and body mass index.

Conclusions: Sputum IL-5 and submucosal eosinophils, but not sputum eosinophils, are elevated in obese people with severe asthma. Whether specific antieosinophilic therapy is beneficial, or improved diet and lifestyle in obese asthma has antiinflammatory effects beyond weight reduction, requires further study.

Figure 1.

The relationship of sputum IL-5 and obesity in severe asthma. (a) Subjects are classified by their body mass index (BMI) (kg/m²) into lean (<24.9); overweight (≥25–29.9); and obese (≥30). The bar represents the geometric mean sputum IL-5 concentration (pg/ml). P value across the groups (ANOVA) is given above the solid line. For pairwise comparisons, P values are given above the line with markings at each end (unpaired t tests for exact P values, when Tukey’s post hoc test P < 0.05). (b) Correlation between sputum IL-5 and BMI.

Figure 2.

Bronchial submucosal eosinophil count in subjects with severe asthma stratified by body mass index. (a) Photomicrograph of a bronchial biopsy from an obese subject with severe asthma showing isotype control (left) and major basic protein-stained eosinophils (right) (original magnification, ×200). (b) Subjects with asthma are classified by their body mass index (kg/m²) into lean (<24.9), overweight (≥25–29.9), and obese (≥30) and compared with healthy control subjects. The horizontal bar is the median. Open symbols denote subjects with sputum eosinophilia less than 3%; closed symbols denote subjects with sputum eosinophilia greater than or equal to 3%. P values for across and between group comparisons are as shown.

Figure 3.

Peripheral blood eosinophil count in subjects with severe asthma stratified by body mass index. Subjects with asthma are classified by their body mass index (kg/m²) into lean (<24.9), overweight (≥25–29.9), and obese (≥30) and compared with healthy control subjects. The horizontal bar is the median. Open symbols denote subjects with sputum eosinophilia less than 3%; closed symbols denote subjects with sputum eosinophilia greater than or equal to 3%. P values for across and between group comparisons are as shown.

Figure 4.

Sputum eosinophil count in subjects with severe asthma stratified by body mass index. Subjects with asthma are classified by their body mass index (kg/m²) into lean (<24.9), overweight (≥25–29.9), and obese (≥30) and compared with healthy control subjects. The horizontal bar is the median. Open symbols denote subjects with sputum eosinophilia less than 3%; closed symbols denote subjects with sputum eosinophilia greater than or equal to 3%. P values for across and between group comparisons are as shown.