Neutrophil-derived biomarkers in bronchiectasis: identifying a common therapeutic target

Abstract

Bronchiectasis is a chronic respiratory disease that can lead to a substantial decline in lung function, ultimately leading to a significantly increased risk of morbidity and mortality. Despite the increasing global impact of bronchiectasis, no specific (or licensed) treatment for the disease currently exists, with most available therapies, though beneficial, focusing on symptom management and infection control. In part, the lack of specific treatments for bronchiectasis may be due to a lack of established biomarkers for the disease. Because bronchiectasis varies so widely in its clinical presentation and can be caused by various aetiologies, the establishment of validated biomarkers has proven challenging. However, identifying key biomarkers in bronchiectasis is crucial to developing appropriate diagnosis and management plans, as well as to measuring effective responses to treatment. While there is a multitude of potential biomarkers in bronchiectasis, almost all instances of bronchiectasis are underpinned by chronic neutrophilic inflammation. The imbalance in neutrophil serine proteases (NSPs) and their endogenous inhibitors has been strongly linked to the lung destruction, mucosal-related defects, infection and worsening of clinical outcomes that are frequently observed in bronchiectasis. In this review, we discuss the various biomarkers linked to bronchiectasis, with a specific focus on NSPs as the most validated biomarkers in bronchiectasis, given their marked role in the pathogenesis of the disease. Lastly, we touch on potential therapeutic approaches aimed at reducing NSP activity in bronchiectasis, showing that, to date, indirect NSP inhibition appears to be the strategy that most effectively addresses chronic neutrophilic inflammation in bronchiectasis.