High Serum IgE is Associated with Risk of Severe Exacerbations Among Non-Eosinophilic Bronchiectasis

Purpose: Bronchiectasis has traditionally been characterized as a neutrophil-driven disease, yet emerging evidence suggested inflammatory heterogeneities. The prognostic significance of elevated serum immunoglobulin E (IgE) in patients without peripheral eosinophilia remains unclear. Methods: We conducted a multicenter prospective cohort study between 2017 and 2020 across 16 institutions in Taiwan. Individuals with bronchiectasis but without allergic bronchopulmonary aspergillosis were included. Patients were stratified by baseline absolute eosinophil count (cutoff 300 /uL) and serum IgE level (≤ 100, 100–500, > 500 IU/mL). The primary endpoint was severe exacerbations resulting in hospitalization at one year. Secondary endpoints included all-cause mortality, distribution of sputum pathogen, imaging pattern, and lung function. Results: A total of 579 individuals were enrolled. Nontuberculous mycobacteria (10.7%) and Pseudomonas aeruginosa (9.0%) were the most commonly isolated microorganisms in sputum. 493 patients (85.1%) were categorized as low-eosinophil bronchiectasis, and 41 (7.1%) presented serum IgE levels exceeding 500 IU/mL. The rate of hospitalization for acute exacerbation in such group was pronouncedly higher than in patients with lower IgE levels (9.8% vs. 0.9% and 2.3%; P = 0.009). In multivariate analysis, IgE exceeding 500 IU/mL was the strongest independent predictor of hospitalization (adjusted odds ratio, 7.38; 95% confidence interval, 2.40–22.7; P < 0.001). The association was particularly pronounced in female and patients with coexisting asthma. All-cause mortality did not differ significantly among IgE strata. Conclusion: Markedly elevated serum IgE independently predicted severe exacerbations resulting in hospitalization in patients with non-eosinophilic bronchiectasis, identifying a high-risk subgroup that may benefit from targeted immunomodulatory therapies.