Human neutrophil elastase (HNE) is a key mediator of tissue remodeling and inflammation. An excess of HNE activity has been implicated in the pathogenesis of inflammatory pulmonary diseases like bronchiectasis (BE) and COPD. HNE inhibitors could potentially restore the protease/anti-protease balance in these diseases providing a new therapeutic target.
In order to assess, whether biomarkers could support clinical evaluation of this new treatment concept, a multicenter biomarker study was conducted in BE patients and healthy controls: A sputum induction and processing protocol was implemented at three study sites and collected sputum was analyzed for neutrophil cell count, HNE activity, IL-8 and other markers with a 2 week interval over six weeks. In addition, the elastin degradation product desmosine was analyzed in urine.
First results from 15 patients and 5 healthy controls indicate that, based on sputum HNE activity, BE patients could be divided into HNE(low) and HNE(high) groups (>10-fold difference), whereas healthy volunteers were always found to be HNE(low). Furthermore, high sputum HNE activity often coincides with other markers of inflammation (neutrophil cell count, IL-8). Those markers may guide patient selection and contribute to identifying BE patients eligible to treatment with a novel HNE inhibitor, which is currently in clinical development.
In summary, Biomarker evaluation in BE patients revealed that significant HNE activity in sputum could be detected and might be used for stratification of patients for HNE inhibitor treatment.