The heterogeneity of systemic inflammation in bronchiectasis

Area of Science:

• Pulmonology
• Immunology
• Biomarker Discovery

Background:

• Systemic inflammation in bronchiectasis is not well understood concerning its causes and severity.
• Investigating molecular inflammation patterns may help classify bronchiectasis by etiology and severity.

Purpose of the Study:

• To explore the relationship between systemic inflammatory protein patterns, bronchiectasis etiology, and disease severity.
• To identify potential biomarkers for assessing bronchiectasis severity and outcomes.

Main Methods:

• Assayed blood concentrations of 31 proteins in 90 bronchiectasis patients (derivation cohort).
• Utilized Principal Component Analysis (PCA) to analyze marker relationships with etiology and severity.
• Validated key findings in two independent patient cohorts (97 and 79 patients).

Main Results:

• Significant heterogeneity in protein concentrations observed across the patient population.
• Increasing bronchiectasis severity correlated with elevated fibrinogen levels (validated across cohorts).
• Higher fibrinogen associated with poorer lung function, Pseudomonas colonization, and reduced health status.
• Primary immunodeficiency patients exhibited exaggerated Interleukin-17 (IL-17) responses compared to other etiologies (validated).
• IL-17 demonstrated potential in discriminating primary immunodeficiency from other bronchiectasis causes.

Conclusions:

• Bronchiectasis exhibits diverse systemic inflammatory protein profiles, not fully explained by etiology or severity alone.
• More severe bronchiectasis is linked to heightened acute-phase responses.
• Plasma fibrinogen emerges as a promising biomarker for bronchiectasis severity, Pseudomonas colonization, and health status.