# Point-of-Care Quantitation of Sputum Neutrophil Elastase Activity in Chronic Airway Disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $197,396

## Abstract

PROJECT SUMMARY
Cystic fibrosis (CF) is a debilitating, progressive lung disease that currently has no cure. With proper
management, patients can achieve good symptom control and quality of life. Exacerbations are acute episodes
of worsening of respiratory symptoms, often triggered by an infection. During exacerbations, excess neutrophil
elastase (NE) is released into the lung and causes irreversible damage to lung tissue. This enzyme can be
detected in sputum and therefore serves as a biomarker for acute exacerbations. We hypothesize that daily,
remote monitoring of this enzyme in CF patient sputum would result in more effective treatment and a reduction
in lung tissue damage. Therefore, the objective is to develop a portable, point-of-care assay that can be used by
CF patients to monitor NE activity in their sputum.
The testing platform will consist of a magnetic chip reader and a disposable biosensor chip that has been pre-
functionalized with NE-specific cleavable peptides attached to magnetic nanoparticles (MNPs). The peptides will
serve as linkers between the sensor surface and the MNPs. Cleavage of peptides by NE will release the MNP
resulting in a quantitative decrease in signal over time. The rate of peptide cleavage correlates with NE
abundance. Therefore, when NE increases in sputum, this device will notify clinicians that an acute exacerbation
is beginning.
The ability to detect and quantify NE activity will be determined by how well this enzyme can cleave surface
immobilized peptide substrates. Therefore, in Aim 1, we will use 96-well plate assays to evaluate different surface
chemistries for optimal attachment of the peptide. To facilitate efficient cleavage by NE, we will optimize the
density and length of the peptide substrate. Once optimized, the peptide substrate will be immobilized to the
magnetic sensor surface and the fluorescent reporter used in the 96-well plates will be replaced with MNPs. In
Aim 2, addition of either purified NE or patient sputum samples will result in cleavage of the peptide and a
decrease in magnetic resistance as the MNPs are released from the sensor surface. This wash-free protease
assay can be monitored in real-time enabling a “sample-to-answer” testing procedure that can be run by
untrained professionals. While our proposed research will focus on sputum from CF patients, this assay will be
suitable for use by patients with other chromic airway diseases, including Chronic Obstructive Pulmonary
Disease (COPD).

## Key facts

- **NIH application ID:** 10135061
- **Project number:** 5R21EB028485-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Drew Alexander Hall
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,396
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135061

## Citation

> US National Institutes of Health, RePORTER application 10135061, Point-of-Care Quantitation of Sputum Neutrophil Elastase Activity in Chronic Airway Disease (5R21EB028485-03). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10135061. Licensed CC0.

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