Understanding the role of neutrophil enzymes in a type of asthma with low inflammation

ISRCTN	ISRCTN18205231
DOI	https://doi.org/10.1186/ISRCTN18205231
Integrated Research Application System (IRAS)	361386
Sponsor	Asthma + Lung UK
Funder	NHS Tayside

Submission date: 11/12/2025
Registration date: 28/04/2026
Last edited: 18/05/2026

Recruitment status: Not yet recruiting
Overall study status: Ongoing
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Asthma is a common long-term condition that affects the airways and makes breathing difficult. While many people with asthma respond well to standard treatments, about one in ten have a form called type 2-low asthma. This type is particularly hard to treat, as current medicines such as inhaled steroids and biologic therapies are often ineffective. People with type 2-low asthma tend to have more hospital visits, more severe attacks, and a poorer quality of life. A possible reason for this form of asthma is the presence of higher numbers of a type of immune cell called neutrophils in the airways. When activated, neutrophils release proteins including neutrophil elastase that can damage the airway lining and worsen inflammation. Recent research in other lung diseases has shown that medicines which block neutrophil activity may help reduce flare-ups. However, these treatments have not yet been studied in people with type 2-low asthma. This project will investigate whether neutrophil proteins, particularly neutrophil elastase, are increased in people with type 2-low asthma compared to those with other types of asthma.

Who can participate?
Patients with moderate-to-severe asthma from NHS Tayside.

What does the study involve?
Participants will be asked to provide sputum (phlegm) samples, undergo lung function tests, and complete questionnaires about their symptoms and quality of life. The aim is to identify a specific “neutrophilic” form of asthma that may benefit from future treatments targeting neutrophil activity. If successful, this study will provide the foundation for a clinical trial of new medicines, with the ultimate goal of improving symptom control, reducing asthma attacks, and enhance quality of life for those with type 2-low asthma.

What are the possible benefits and risks of participating?
Participants are not expected to benefit directly from taking part. However, their participation may help improve understanding of asthma, particularly the type 2-low phenotype, and could contribute to improved treatments and clinical outcomes in the future.

In terms of risk, sputum induction may cause coughing and temporary discomfort. There is also a potential risk to confidentiality. To minimise these risks, sputum samples can be collected using a nebuliser with hypertonic saline and strong safeguards are in place to ensure that all participant data are kept secure.

Where is the study run from?
Ninewells Hospital & Medical School, UK.

When is the study starting and how long is it expected to run for?
July 2026 to October 2027.

Who is funding the study?
NHS Tayside, UK.

Who is the main contact?
Dr Rory Chan, r.chan@dundee.ac.uk

Contact information

Dr Rory Chan
Principal investigator, Scientific, Public

Ninewells Hospital & Medical School
Dundee
DD1 9SY
United Kingdom

Phone	+44 01382383920
Email	r.chan@dundee.ac.uk

Study information

Primary study design	Observational
Observational study design	Cross sectional study
Participant information sheet	48658_PIS_v2_22Aug2025.pdf
Scientific title	Characterising neutrophil serine protease activity in type 2 low asthma
Study objectives	To determine whether sputum neutrophil elastase activity is increased in patients with T2-low asthma compared to T2-high asthma. To compare other neutrophil-derived proteins (proteinase-3, cathepsin-G, azurocidin-1, neutrophil extracellular trap markers) in patients with T2-low asthma versus T2-high asthma. To assess relationships between neutrophil protease activity and clinical outcomes such as symptom control, lung function, quality of life, and exacerbation history.
Ethics approval(s)	Approved 05/05/2026, West of Scotland REC 4 (1055 Great Western Road, Glasgow, G12 0XH, United Kingdom; -; ggc.wosrec4@nhs.scot), ref: 26/WS/0059
Health condition(s) or problem(s) studied	Type 2 inflammatory asthma
Intervention	This is an observational study, which means it will not be testing a new drug or treatment. Instead, the study will carefully study people with asthma to better understand what is happening in their lungs. The study plans to recruit 120 adults with moderate-to-severe asthma from NHS Tayside. Each patient attending the specialist asthma clinic in Ninewells hospital will be asked whether they would like to participate in this study. At this clinic visit, participants will: Provide a sputum (phlegm) sample by coughing into a container. This allows us to measure proteins released by neutrophils, such as neutrophil elastase. Complete breathing tests (such as spirometry and oscillometry) to measure lung function. Answer short questionnaires about their asthma symptoms and quality of life. Provide a small blood sample to measure markers of inflammation. Afterwards, researchers will analyse the samples in the laboratory. The results will be compared between patients with type 2-low asthma and those with type 2-high asthma. The researchers expect to identify a group of patients with high neutrophil activity who may represent a distinct type of asthma.
Intervention type	Other
Primary outcome measure(s)	Sputum neutrophil elastase activity, via the concentration of neutrophil elastase in induced sputum in patients with T2-low asthma compared with patients with T2-high asthma measured using a kinetic fluorescence-based neutrophil serine protease activity assay at a single time point
Key secondary outcome measure(s)	Neutrophil-derived proteins (proteinase-3, cathepsin-G, azurocidin-1, and neutrophil extracellular trap markers) concentration levels in induced sputum in patients with T2-low asthma compared with patients with T2-high asthma measured using laboratory assays of neutrophil serine protease activity, azurocidin-1, and neutrophil extracellular trap formation at a single time point
Completion date	01/10/2027

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	100 Years
Sex	All
Target sample size at registration	120
Key inclusion criteria	1. Patients aged ≥18 years old with GINA-defined moderate-to-severe asthma. 2. Taking a medium to high dose of ICS/LABA OR high dose ICS with another second line controller (BDP equivalent dose of ≥800µg) of step 4/5 GINA therapy. 3. Established diagnosis of persistent asthma ≥6 months according to GINA guidelines. 4. Ability to give informed consent. 5. Agreement for their GP to be made aware of study participation and to receive feedback as relevant to the participant’s wellbeing. 6. Able to understand the study procedures and the risks involved. 7. Good physical and mental status, determined on the basis of the medical history and a general clinical examination at screening.
Key exclusion criteria	1. Patients who are taking biologics for asthma. 2. Patients who are on maintenance oral corticosteroids. 3. Patients who have required a course of oral corticosteroids in the past month. 4. Any other respiratory diseases such as COPD and moderate to severe bronchiectasis which in the opinion of the investigator are clinically significant and may have an impact on the study outcomes. 5. Any disorder that is not stable in the opinion of the Investigator. 6. Patients unable or unwilling to consent. 7. Anyone who has had a recent chest infection or asthma exacerbation (within the past 4 weeks), as this may temporarily alter neutrophil levels in the sputum. 8. People currently taking part in another clinical trial involving investigational medicines or who have received such medicines within the past 3 months. 9. Individuals with severe comorbidities (such as uncontrolled heart disease, active cancer, or significant immunosuppression) where participation may pose additional risk.
Date of first enrolment	18/07/2026
Date of final enrolment	01/10/2027

Locations

Countries of recruitment

United Kingdom
Scotland

Study participating centre

Ninewells Hospital

Ninewells Avenue
Dundee
DD1 9SY
Scotland

Results and Publications

Individual participant data (IPD) Intention to share	No

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other files	version 2	30/01/2026	23/03/2026	No	No
Other files	version 3	28/01/2026	23/03/2026	No	No
Participant information sheet	version 2	22/08/2025	12/12/2025	No	Yes
Participant information sheet	version 5	20/02/2026	23/03/2026	No	Yes
Protocol file	version 6	20/02/2026	23/03/2026	No	No

Additional files

48658_PIS_v2_22Aug2025.pdf: Participant information sheet
48658_Characterising neutrophil serine protease activity in type 2 low asthma informative poster_v2_30Jan2026.pdf: Poster results
48658_PIS UK_v5_20Feb2026.pdf: Participant information sheet
48658_ICF UK_v3_28Jan2026.pdf: Other files
48658_Protocol_v6_20Feb2026.pdf: Protocol file

Editorial Notes

18/05/2026: Ethics approval added, and the date of first enrolment was changed from 01/04/2026 to 18/07/2026.
23/03/2026: Study’s existence confirmed by the Asthma + Lung UK.