Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study

Abstract

Purpose: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients.

Methods: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO.

Results: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence.

Conclusions: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

Keywords: Pseudomonas aeruginosa; Blood eosinophil count; Bronchiectasis; Fractional exhaled nitric oxide; Immunoglobulin E; Type 2 biomarkers.

Fig. 1

A overlap of baseline positivity of three clinical used biomarkers, BEC ≥ 300 cells/uL, FeNO ≥ 25 ppb, total IgE ≥ 75 kU/L in the bronchiectasis cohort (n = 130). B–D the correlation between BEC, FeNO and serum total IgE in the bronchiectasis cohort. Spearman’s test assessed correlations between quantitative variables. BEC blood eosinophil counts, FeNO fractional exhaled nitric oxide, IgE immunoglobulin E

Fig. 2

The correlations between Type 2 biomarkers, inflammatory markers, and immunological profiles with the severity scores in bronchiectasis. Spearman’s test assessed correlations between quantitative variables. The presence of asterisks indicates the level of statistical significance, with (*) denoting p < 0.05, (**) indicating p < 0.01, and (***) representing p < 0.001. The direction of the correlations is represented by the position of the markers: above the zero line for positive correlations and below for negative correlations. BAL bronchoalveolar lavage, BEC blood eosinophil counts, BSI bronchiectasis severity index, CRP C reactive protein, E-FACED exacerbation, forced expiratory volume in 1 s (FEV₁), age, chronic colonization by Pseudomonas aeruginosa, radiological extension and dyspnea, FeNO fractional exhaled nitric oxide, IgE immunoglobulin E, IL-1β interleukin [IL]-1beta, IL-6 interleukin[IL]-6, IL-8 interleukin [IL]-8, MCP-1 monocyte chemoattractant protein-1, NLR neutrophil–lymphocyte ratio, TNF-α tumor necrosis factor-alpha

Fig. 3

Kaplan–Meier curves illustrate the risk of moderate or severe exacerbations in bronchiectasis patients, stratified by: A BEC levels ≥ 300 cells/μL or < 300 cells/μL, B FeNO levels ≥ 25 ppb or < 25 ppb, C serum total IgE levels ≥ 75 kU/L or < 75 kU/L, and D combined BEC and FeNO into four subgroup levels. BEC blood eosinophil counts, IgE immunoglobulin E, FeNO fractional exhaled nitric oxide

Fig. 4

Type 2 biomarkers and airway cytokines in exacerbation and non-exacerbation groups of bronchiectasis patients. IL-6 interleukin-6, IL-8 interleukin-8, IL-1β interleukin-1 beta, TNF-α tumor necrosis factor-alpha, BEC blood eosinophil count, IgE immunoglobulin E, FeNO fractional exhaled nitric oxide

Fig. 5

Receiver operating characteristic (ROC) curve and area under the curve (AUC) with 95% confidence intervals (CIs) for clinical variables and biomarkers predictive of future exacerbations. BAL bronchoalveolar lavage, BSI bronchiectasis severity index, IL-6 interleukin[IL]-6, IL-8 interleukin [IL]-8, IL-1β interleukin [IL]-1beta, mMRC modified Medical Research Council, NLR neutrophil–lymphocyte ratio, TNF-α tumor necrosis factor-alpha, E-FACED exacerbation, forced expiratory volume in 1 s (FEV₁), age, chronic colonization by Pseudomonas aeruginosa, radiological extension and dyspnea