Neutrophil elastase in bronchiectasis

Abstract

The role of neutrophil elastase (NE) is poorly understood in bronchiectasis because of the lack of preclinical data and so most of the assumptions made about NE inhibitor potential benefit is based on data from CF. In this context, NE seems to be a predictor of long-term clinical outcomes and a possible target of treatment. In order to better evaluate the role of NE in bronchiectasis, a systematic search of scientific evidence was performed.Two investigators independently performed the search on PubMed and included studies published up to May 15, 2017 according to predefined criteria. A final pool of 31 studies was included in the systematic review, with a total of 2679 patients. For each paper data of interest were extracted and reported in table.In this review sputum NE has proved useful as an inflammatory marker both in stable state bronchiectasis and during exacerbations and local or systemic antibiotic treatment. NE has also been associated with risk of exacerbation, time to next exacerbation and all-cause mortality. This study reviews also the role of NE as a specific target of treatment in bronchiectasis. Inhibition of NE is at a very early stage and future interventional studies should evaluate safety and efficacy for new molecules and formulations.

α1-Antitrypsin deficiency and chronic respiratory disorders

“…Bronchiectasis has also been associated with AATD, with the mechanistic link of incompletely opposed neutrophil elastase activity [25]. There is concrete evidence of a direct impact of neutrophil elastase on bronchiectasis disease progression through effects on ciliated epithelium, mucus production, emphysema development and inactivation of the immune response [26]. However, whether bronchiectasis comes from a primary mechanism of the disease or is the result of recurrent respiratory infection is still matter of debate [27].…”

Pathophysiology, causes and genetics of paediatric and adult bronchiectasis

“…The predominant immune cells seen histologically in bronchiectasis are: (i) neutrophils (principally in the airway lumen), supporting a role for neutrophil‐derived proteases (found in high levels in sputum from bronchiectasis patients) in driving bronchial wall damage; (ii) macrophages; and (iii) lymphocytes (predominantly CD4+ cells). Recent work has implicated IL‐17‐secreting lymphocytes (Th17 cells and NK cells) in driving neutrophil recruitment as well as mucus hypersecretion.…”

A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation

“…The test is semi-quantitative and shows a good correlation with neutrophil elastase activity measured by immunoassay. Neutrophil elastase activity is an established biomarker of bronchiectasis as well as being associated with risk of exacerbations, airway infection status and lung function decline in other conditions such as cystic fibrosis [16]. Implementation of sputum biomarkers into clinical practice are limited by the requirement to process sputum via centrifugation and the design of traditional assays for neutrophil elastase, which are typically based on the cleavage of chromogenic substrates.…”

“…Neutrophil elastase activity is a leading candidate for a bronchiectasis biomarker [13]. The relationship between sputum neutrophil elastase activity and airway infection has been known for more than two decades and studies demonstrate that neutrophil elastase may directly impact on bronchiectasis disease progression through effects of ciliated epithelium, mucus production, emphysema development and inactivation of the immune response [14][15][16]. A systematic review of clinical studies in bronchiectasis identified 31 studies and found that higher neutrophil elastase activity in sputum was associated with sputum colour, P. aeruginosa infection, airway bacterial load, disease severity, forced expiratory volume in 1 s (FEV1) symptoms and long-term risk of exacerbations and lung function decline [16].…”

“…Therefore, neutrophil elastase has been tested and validated as a biomarker across multiple studies [13,[16][17][18]. However, it has not been implemented into clinical practice, in part due to the difficulty of standardising sputum processing and performing ELISA or chromogenic assays in clinical laboratories.…”