Bronchiectasis in severe asthma is associated with eosinophilic airway inflammation and activation

Abstract

Background: Bronchiectasis is a common comorbidity in severe asthma; causative pathogenic mechanisms are not fully understood but may differ from other causes of bronchiectasis. The role of eosinophilic airway inflammation, a classic feature of asthma predominantly driven by IL-5 and IL-13, in bronchiectasis is unclear, but association with disruption of the airway epithelium through eosinophil degranulation and increased mucus production is plausible.

Objective: We sought to describe the prevalence of bronchiectasis in an unselected population of patients with severe asthma, and the association with the airway eosinophilic inflammation and activation.

Methods: All patients with severe asthma according to European Respiratory Society/American Thoracic Society criteria (high-dose inhaled corticosteroids/oral corticosteroids), attending 4 respiratory clinics over a 1-year period, were included. All patients underwent high-resolution computed tomography and induced sputum was collected and analyzed for a cell differential count, free eosinophilic granules, and airway messenger RNA expression of T2 inflammatory pathways.

Results: Bronchiectasis was present in 31% (34 of 108) of patients with severe asthma, and half (52%) of these patients had airway eosinophilia whereas only 16% of patients without bronchiectasis had airway eosinophilia. Patients with bronchiectasis had a significantly higher sputum eosinophil count (5.3 vs 0.8; P = .001) as well as more extensive eosinophil degranulation, compared with those without bronchiectasis (13% vs 2%; P = .05), suggesting a higher degree of eosinophil activation. Pairwise analyses identified significantly higher messenger RNA expression of Charcot-Leyden crystal galectin in patients with bronchiectasis (P = .02).

Conclusions: Bronchiectasis in severe asthma was associated with eosinophilic airway inflammation and eosinophilic degranulation as well as messenger RNA expression of Charcot-Leyden crystal galectin.

Keywords: Severe asthma; airway inflammation; bronchiectasis; eosinophil activation; eosinophil degranulation; eosinophils; free eosinophil granules; messenger RNA.

Fig 1

Flowchart visualizing the number of patients available for analyses of bronchiectasis and airway inflammation. HRCT, High-resolution computed tomography; mRNA, messenger RNA.

Fig 2

Associations between bronchiectasis and inflammatory phenotype in sputum: Eosinophilic (eosinophils ≥3% and neutrophils <61%), neutrophilic (eosinophils <3% and neutrophils ≥61%), mixed granulocytic (eosinophils ≥3% and neutrophils ≥61%), and paucigranulocytic (eosinophils <3% and neutrophils <61%). ns, Nonsignificant. Significance levels: ∗P = .0002 (χ²), ∗∗P = .02 (Fisher exact test), ∗∗∗P = .02 (χ²).

Fig 3

Heatmaps illustrating differences in gene expression based on (A) the presence of airway eosinophilia and bronchiectasis, (B) eosinophil degranulation across all patients, and (C) eosinophil degranulation in patients with bronchiectasis. Gene expression is presented as mean fold abundance in mean gene expression relative to the mean of a healthy control group. A fold abundance of more than 1 equals a relative increase compared with the mean in healthy control group, whereas fold abundance less than 1 equals a relative decrease.