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Frontiers in immunology2022; 13; 921077; doi: 10.3389/fimmu.2022.921077

Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity.

Abstract: Asthma encompasses a spectrum of heterogenous immune-mediated respiratory disorders sharing a similar clinical pattern characterized by cough, wheeze and exercise intolerance. In horses, equine asthma can be subdivided into severe or moderate asthma according to clinical symptoms and the extent of airway neutrophilic inflammation. While severe asthmatic horses are characterized by an elevated neutrophilic inflammation of the lower airways, cough, dyspnea at rest and high mucus secretion, horses with moderate asthma show a milder neutrophilic inflammation, exhibit intolerance to exercise but no labored breathing at rest. Yet, the physiopathology of different phenotypes of equine asthma remains poorly understood and there is a need to elucidate the underlying mechanisms tailoring those phenotypes in order to improve clinical management and elaborate novel therapeutic strategies. In this study, we sought to quantify the presence of neutrophil extracellular traps (NETs) in bronchoalveolar lavage fluids (BALF) of moderate or severe asthmatic horses and healthy controls, and assessed whether NETs correlated with disease severity. To this end, we evaluated the amounts of NETs by measuring cell-free DNA and MPO-DNA complexes in BALF supernatants or by quantifying NETs release by BALF cells by confocal microscopy. We were able to unequivocally identify elevated NETs levels in BALF of severe asthmatic horses as compared to healthy controls or moderate asthmatic horses. Moreover, we provided evidence that BALF NETs release was a specific feature seen in severe equine asthma, as opposed to moderate asthma, and correlated with disease severity. Finally, we showed that NETs could act as a predictive factor for severe equine asthma. Our study thus uniquely identifies NETs in BALF of severe asthmatic horses using three distinct methods and supports the idea that moderate and severe equine asthma do not rely on strictly similar pathophysiological mechanisms. Our data also suggest that NETs represent a relevant biomarker, a putative driver and a potential therapeutic target in severe asthma disease.
Publication Date: 2022-07-13 PubMed ID: 35911691PubMed Central: PMC9326094DOI: 10.3389/fimmu.2022.921077Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research looks at equine asthma and specifically the presence and potential role of neutrophil extracellular traps (NETs) in the bronchoalveolar lavage fluids (BALF) of horses with severe asthma. The authors conclude that NETs levels are elevated in severe cases, suggesting different underlying mechanisms for moderate and severe asthma, and that NETs could serve as a useful biomarker and potential therapeutic target.

Background

  • The paper starts by describing asthma as a variety of immune-mediated disorders affecting the respiratory system, symptoms of which include wheezing, exercise intolerance, and coughing.
  • Equine asthma – asthma in horses – is divided into two categories: severe and moderate, based on the degree of airway neutrophilic inflammation and clinical symptoms.
  • Severe equine asthma is marked by high neutrophilic inflammation in the lower airways, an abundance of mucus secretion, and symptoms such as labored breathing and coughing. In contrast, moderate asthma is characterized by milder inflammation and exercise intolerance, but no laborious breathing while resting.
  • Despite this categorization, the mechanisms driving the differences in these asthma phenotypes remain unclear, representing a gap in understanding which the study aims to address.

Study purpose and methods

  • The research aims to quantify the presence of Neutrophil extracellular traps (NETs) in the bronchoalveolar lavage fluid (BALF) of horses with moderate or severe asthma, as well as in healthy horses.
  • More importantly, the study aims to determine if the level of NETs correlates with the severity of the asthma.
  • To achieve this, the researchers measured cell-free DNA and MPO-DNA complexes in the BALF supernatants and assessed the release of NETs from BALF cells using confocal microscopy.

Findings

  • The research reports that there is a noticeable increase in NETs levels in the BALF of horses with severe asthma compared to healthy horses and those showing signs of moderate asthma.
  • This rise in NETs only appears in cases of severe equine asthma, indicating that it could correlate with disease severity.
  • Beyond this, the study suggests NETs could potentially be a predictive indicator of severe equine asthma.

Conclusions and suggestions for further research

  • Research here suggests that moderate and severe equine asthma has different underlying pathophysiological mechanisms.
  • With the detection of elevated NETs in the BALF of severely asthmatic horses, NETs could be seen as an important biomarker, a potential driver of the disease, and a possible target for treatment in severe asthmatic conditions.
  • However, further research is needed to confirm these observations and to expand our understanding of these NETs in the pathophysiology of equine asthma.

Cite This Article

APA
Janssen P, Tosi I, Hego A, Maréchal P, Marichal T, Radermecker C. (2022). Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity. Front Immunol, 13, 921077. https://doi.org/10.3389/fimmu.2022.921077

Publication

ISSN: 1664-3224
NlmUniqueID: 101560960
Country: Switzerland
Language: English
Volume: 13
Pages: 921077

Researcher Affiliations

Janssen, Pierre
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.
Tosi, Irene
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.
Hego, Alexandre
  • In Vitro Imaging Platform, GIGA Institute, Liège University, Liège, Belgium.
Maréchal, Pauline
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
Marichal, Thomas
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.
Radermecker, Coraline
  • Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
  • Faculty of Veterinary Medicine, Liège University, Liège, Belgium.

MeSH Terms

  • Animals
  • Asthma / pathology
  • Asthma / veterinary
  • Bronchoalveolar Lavage Fluid
  • Cough / pathology
  • Cough / veterinary
  • Extracellular Traps
  • Horses
  • Inflammation / pathology
  • Inflammation / veterinary
  • Neutrophils / pathology
  • Patient Acuity

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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