Evidence map›Paper›PMID 39467608›Full record

ReviewThe European respiratory journal2025

Targeting neutrophil serine proteases in bronchiectasis.

James D Chalmers, Marcus A Mall, Sanjay H Chotirmall, Anne E O'Donnell, Patrick A Flume, Naoki Hasegawa, Felix C Ringshausen, Henrik Watz, Jin-Fu Xu, Michal Shteinberg and 1 more

Abstract readReview
In one paragraph

Review in The European respiratory journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  4. The frequent exacerbator phenotype in bronchiectasis revisited: data from EMBARC registry.American journal of respiratory and critical care medicine · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

James D ChalmersDivision of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK.
Marcus A MallDepartment of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany marcus.mall@charite.de.ORCID https://orcid.org/0000-0002-4057-2199
Sanjay H ChotirmallLee Kong Chian School of Medicine, Nanyang Technological University, Singapore.ORCID https://orcid.org/0000-0003-0417-7607
Anne E O'DonnellGeorgetown University Medical Center, Washington, DC, USA.
Patrick A FlumeMedical University of South Carolina, Charleston, SC, USA.
Naoki HasegawaDepartment of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
Felix C RingshausenDepartment of Respiratory Medicine and Infectious Diseases, Hannover Medical School (MHH), Hannover, Germany.ORCID https://orcid.org/0000-0001-9084-4968
Henrik WatzVelocity Clinical Research Grosshansdorf, formerly Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research Grosshansdorf (DZL), Grosshansdorf, Germany.
Jin-Fu XuDepartment of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, China.ORCID https://orcid.org/0000-0002-8039-8973
Michal ShteinbergCarmel Medical Center, Haifa, Israel.ORCID https://orcid.org/0000-0002-0432-3398
Pamela J McShaneUniversity of Texas Health Science Center at Tyler, Tyler, TX, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur. Despite the defined role of prolonged, high levels of NSPs in bronchiectasis, no drug that controls neutrophilic inflammation is licensed for the treatment of bronchiectasis. Previous methods of suppressing neutrophilic inflammation (such as direct inhibition of NE) have not been successful; however, an emerging therapy designed to address neutrophil-mediated pathology, inhibition of the cysteine protease cathepsin C (CatC, also known as dipeptidyl peptidase 1), is a promising approach to ameliorate neutrophilic inflammation, since this may reduce the activity of all NSPs implicated in bronchiectasis pathogenesis, and not just NE. Current data suggest that CatC inhibition may effectively restore the protease-antiprotease balance in bronchiectasis and improve disease outcomes as a result. Clinical trials for CatC inhibitors in bronchiectasis have reported positive phase III results. In this narrative review, we discuss the role of high NSP activity in bronchiectasis, and how this feature drives the associated morbidity and mortality seen in bronchiectasis. This review discusses therapeutic approaches aimed at treating neutrophilic inflammation in the bronchiectasis lung, summarising clinical trial outcomes and highlighting the need for more treatment strategies that effectively address chronic neutrophilic inflammation in bronchiectasis.

Indexed as

BronchiectasisCathepsin CNeutrophilsSerine ProteasesAnimalsHumansInflammationLeukocyte ElastaseCathepsin CLeukocyte ElastaseSerine Proteases

Identifiers

PMID39467608
PMCPMC11694565

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.