Background: The aetiology of bronchiectasis (BE) is complex and may be idiopathic in nature, post-infectious or associated with specific conditions, such as COPD and primary immunodeficiency (PID). Heterogeneity of BE may be underpinned by variable contributions of neutrophilic and eosinophilic inflammation, impaired mucociliary clearance, and defective immune responses.

Objectives: To better understand the complex pathway interaction networks underlying BE, we explored disease-specific protein abundance profiles in sputa of patients with bronchiectasis, COPD and PID using a non-targeted proteomics approach.

Methods: Sputa from healthy controls (15) and subjects with BE (16), COPD (14) or PID (12) were collected. The fluid phase was analysed by LC-MS/MS using a data-independent acquisition mode to identify differences in the relative protein abundance between the groups. Pathway analysis was performed to deepen the understanding of the heterogeneity in the underlying gene ontology networks.

Results: We identified over 1,200 proteins in sputum across all samples in the four groups. We found common and specific gene ontologies in the disease groups. BE patients showed the largest number of differentially expressed proteins compared to healthy controls, as reflected in a high number of activated canonical pathways. Activation of acute phase response signalling was seen in all groups, leukocyte extravasation signalling was specific to BE and COPD patients, while glucose metabolism was specific to BE patients. 

Conclusion: Sputum proteomic analysis offers a powerful tool to explore a broad set of proteins in the airway lumen and improve our understanding of the disease pathophysiology.