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Home / Equine Research Bank / BMC Vet Res / The amount of hyaluronic acid and airway remodelling increas...
BMC veterinary research2024; 20(1); 273; doi: 10.1186/s12917-024-04136-2

The amount of hyaluronic acid and airway remodelling increase with the severity of inflammation in neutrophilic equine asthma.

Abstract: Equine asthma (EA) is a chronic lower airway inflammation that leads to structural and functional changes. Hyaluronic acid (HA) has crucial functions in the extracellular matrix homeostasis and inflammatory mediator activity. HA concentration in the lungs increases in several human airway diseases. However, its associations with naturally occurring EA and airway remodelling have not been previously studied. Our aim was to investigate the association of equine neutrophilic airway inflammation (NAI) severity, airway remodelling, and HA concentration in horses with naturally occurring EA. We hypothesised that HA concentration and airway remodelling would increase with the severity of NAI. HA concentrations of bronchoalveolar lavage fluid supernatant (SUP) and plasma of 27 neutrophilic EA horses, and 28 control horses were measured. Additionally, remodelling and HA staining intensity were assessed from endobronchial biopsies from 10 moderate NAI horses, 5 severe NAI horses, and 15 control horses. Results: The HA concentration in SUP was higher in EA horses compared to controls (p = 0.007). Plasma HA concentrations were not different between the groups. In the endobronchial biopsies, moderate NAI horses showed epithelial hyperplasia and inflammatory cell infiltrate, while severe NAI horses also showed fibrosis and desquamation of the epithelium. The degree of remodelling was higher in severe NAI compared to moderate NAI (p = 0.048) and controls (p = 0.016). Intense HA staining was observed in bronchial cell membranes, basement membranes, and connective tissue without significant differences between the groups. Conclusions: The release of HA to the airway lumen increases in naturally occurring neutrophilic EA without clear changes in its tissue distribution, and significant airway remodelling only develops in severe NAI.
© 2024. The Author(s).
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Publication Date: 2024-06-25 PubMed ID: 38918797PubMed Central: PMC11197223DOI: 10.1186/s12917-024-04136-2Google Scholar: Lookup
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  • Journal Article

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 investigates the connection between hyaluronic acid levels, airway remodelling, and the severity of equine neutrophilic airway inflammation in horses with naturally occurring equine asthma.

Research Objective

  • The main aim of this study was to investigate the relationship between the severity of equine neutrophilic airway inflammation (NAI), airway remodelling, and concentrations of hyaluronic acid (HA) in horses suffering from a chronic lung condition termed equine asthma (EA).
  • The researchers hypothesized that the increase in the severity of neutrophilic inflammation would lead to an increase in HA concentration and airway remodelling.

Methods

  • A total of 55 horses were included in the study: 27 with neutrophilic EA and 28 non-asthmatic control horses.
  • The researchers measured HA concentrations in the bronchoalveolar lavage fluid supernatant (SUP) and the plasma of all horses. They compared the results between the two groups.
  • In addition, they evaluated airway remodelling and HA staining intensity in endobronchial biopsies taken from the lungs of 10 moderate NAI horses, 5 severe NAI horses and 15 control horses.

Findings

  • The study revealed that the HA concentration in bronchoalveolar lavage fluid supernatant was significantly higher in EA horses compared to the control group.
  • However, there were no significant differences in HA levels in plasma across all groups.
  • It was also found that horses with severe NAI exhibited epithelial hyperplasia, inflammatory cell infiltration, fibrosis, and desquamation of the epithelium – indicators of airway remodelling – whereas those with moderate NAI only showed signs of epithelial hyperplasia and inflammatory cell infiltration.
  • The degree of airway remodelling was significantly higher in horses with severe NAI compared to those with moderate NAI and those in the control group.
  • Intense HA staining was observed in bronchial cell membranes, basement membranes and connective tissue across all groups, suggesting that there are no significant differences in tissue distribution of HA between them.

Conclusion

  • The study confirmed that the release of HA in the airways of horses with naturally occurring neutrophilic equine asthma increases, but without clear changes in its tissue distribution.
  • Significant airway remodelling was evident only in horses with severe neutrophilic inflammation.

Cite This Article

APA
Höglund N, Rossi H, Javela HM, Oikari S, Nieminen P, Mustonen AM, Airas N, Kärjä V, Mykkänen A. (2024). The amount of hyaluronic acid and airway remodelling increase with the severity of inflammation in neutrophilic equine asthma. BMC Vet Res, 20(1), 273. https://doi.org/10.1186/s12917-024-04136-2

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 20
Issue: 1
Pages: 273
PII: 273

Researcher Affiliations

Höglund, Nina
  • Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, FI-00014, Finland. nina.m.hoglund@helsinki.fi.
Rossi, Heini
  • Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, FI-00014, Finland.
Javela, Hanna-Maaria
  • Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, FI-00014, Finland.
Oikari, Sanna
  • Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, FI-70211, Finland.
Nieminen, Petteri
  • Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, FI-70211, Finland.
Mustonen, Anne-Mari
  • Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, FI-70211, Finland.
  • Department of Environmental and Biological Sciences, Faculty of Science, Forestry and Technology, University of Eastern Finland, Joensuu, FI-80101, Finland.
Airas, Niina
  • Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, FI-00014, Finland.
Kärjä, Vesa
  • Department of Clinical Pathology, Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, FI-70210, Finland.
Mykkänen, Anna
  • Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, FI-00014, Finland.

MeSH Terms

  • Animals
  • Horses
  • Hyaluronic Acid / blood
  • Asthma / veterinary
  • Asthma / pathology
  • Horse Diseases / pathology
  • Airway Remodeling
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Female
  • Male
  • Neutrophils
  • Inflammation / veterinary
  • Inflammation / pathology
  • Severity of Illness Index

Conflict of Interest Statement

The authors declare no competing interests.

References

This article includes 41 references
  1. Couëtil L, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory airway disease of horses — revised consensus statement.. J Vet Intern Med 2016;30:503–15.
    doi: 10.1111/jvim.13824pmc: PMC4913592pubmed: 26806374google scholar: lookup
  2. Bullone M, Lavoie JP. The equine asthma model of airway remodeling: from a veterinary to a human perspective.. Cell Tissue Res 2020;380:223–36.
    doi: 10.1007/s00441-019-03117-4pubmed: 31713728google scholar: lookup
  3. Bullone M, Chevigny M, Allano M, Martin J, Lavoie JP. Technical and physiological determinants of airway smooth muscle mass in endobronchial biopsy samples of asthmatic horses.. J Appl Physiol 2014;117:806–15.
    doi: 10.1152/japplphysiol.00468.2014pubmed: 25103978google scholar: lookup
  4. Bullone M, Hélie P, Joubert P, Lavoie JP. Development of a semiquantitative histological score for the diagnosis of heaves using endobronchial biopsy specimens in horses.. J Vet Intern Med 2016;30:1739–46.
    doi: 10.1111/jvim.14556pmc: PMC5032871pubmed: 27527123google scholar: lookup
  5. Dupuis-Dowd F, Lavoie JP. Airway smooth muscle remodeling in mild and moderate equine asthma.. Equine Vet J 2022;54:865–74.
    doi: 10.1111/evj.13514pubmed: 34529300google scholar: lookup
  6. Bessonnat A, Hélie P, Grimes C, Lavoie JP. Airway remodeling in horses with mild and moderate asthma.. J Vet Intern Med 2022;36:285–91.
    doi: 10.1111/jvim.16333pmc: PMC8783337pubmed: 34877706google scholar: lookup
  7. Allegra L, Patrona SD, Petrigni G. Hyaluronic acid.. In: Lever R, Mulloy B, Page C, editors. Heparin - a century of progress. Berlin, Heidelberg: Springer; 2012. pp. 386–97.
  8. Vasvani S, Kulkarni P, Rawtani D. Hyaluronic acid: a review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies.. Int J Biol Macromol 2020;151:1012–29.
    doi: 10.1016/j.ijbiomac.2019.11.066pubmed: 31715233google scholar: lookup
  9. Isnard N, Legeais JM, Renard G, Robert L. Effect of hyaluronan on MMP expression and activation.. Cell Biol Int 2001;25:735–9.
    doi: 10.1006/cbir.2001.0759pubmed: 11482897google scholar: lookup
  10. Weigel PH, Hascall VC, Tammi M. Hyaluronan synthases.. J Biol Chem 1997;272:13997–4000.
    doi: 10.1074/jbc.272.22.13997pubmed: 9206724google scholar: lookup
  11. Bousquet J, Chanez P, Lacoste J, Enander I, Venge P, Peterson C. Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma.. J Allergy Clin Immunol 1991;88:649–60.
    doi: 10.1016/0091-6749(91)90159-Lpubmed: 1918730google scholar: lookup
  12. Liang J, Jiang D, Jung Y, Xie T, Ingram J, Church T. Role of hyaluronan and hyaluronan-binding proteins in human asthma.. J Allergy Clin Immunol 2011;128:403–11.
    doi: 10.1016/j.jaci.2011.04.006pmc: PMC3149736pubmed: 21570715google scholar: lookup
  13. Söderberg M, Bjermer L, Hällgren R, Lundgren R. Increased hyaluronan (hyaluronic acid) levels in bronchoalveolar lavage fluid after histamine inhalation.. Int Arch Allergy Immunol 1989;88:373–6.
    doi: 10.1159/000234719pubmed: 2722257google scholar: lookup
  14. Vignola AM, Chanez P, Campbell AM, Souques F, Lebel B, Enander I. Airway inflammation in mild intermittent and in persistent asthma.. Am J Respir Crit Care Med 1998;157:403–9.
    doi: 10.1164/ajrccm.157.2.96-08040pubmed: 9476850google scholar: lookup
  15. Cheng G, Swaidani S, Sharma M, Lauer M, Hascall V, Aronica M. Hyaluronan deposition and correlation with inflammation in a murine ovalbumin model of asthma.. Matrix Biol 2011;30:126–34.
    doi: 10.1016/j.matbio.2010.12.003pmc: PMC3099436pubmed: 21251977google scholar: lookup
  16. Souza-Fernandes AB, Pelosi P, Rocco PR. Bench-to-bedside review: the role of glycosaminoglycans in respiratory disease.. Crit Care 2006;10:237.
    doi: 10.1186/cc5069pmc: PMC1794443pubmed: 17118216google scholar: lookup
  17. Carro LM, Martínez-García MA. Use of hyaluronic acid (HA) in chronic airway diseases.. Cells 2020;9:2210.
    doi: 10.3390/cells9102210pmc: PMC7601363pubmed: 33003557google scholar: lookup
  18. Klagas I, Goulet S, Karakiulakis G, Zhong J, Baraket M, Black JL. Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD.. Eur Respir J 2009;34:616–28.
    doi: 10.1183/09031936.00070808pubmed: 19282346google scholar: lookup
  19. Tulamo RM, Maisi P. Hyaluronate concentration in tracheal lavage fluid from clinically normal horses and horses with chronic obstructive pulmonary disease.. Am J Vet Res 1997;58:729–32.
    doi: 10.2460/ajvr.1997.58.07.729pubmed: 9215448google scholar: lookup
  20. Couëtil L, Hawkins J. Diagnostic tests and therapeutic procedures.. In: Couëtil L, Hawkins J, editors. Respiratory diseases of the horse: a problem-oriented approach to diagnosis & management. London: Manson Publishing Ltd; 2013. pp. 56–8.
  21. Gerber V, Straub R, Marti E, Hauptman J, Herholz C, King M. Endoscopic scoring of mucus quantity and quality: observer and horse variance and relationship to inflammation, mucus viscoelasticity and volume.. Equine Vet J 2004;36:576–82.
    doi: 10.2746/0425164044864525pubmed: 15581321google scholar: lookup
  22. Smith BL, Aguilera-Tejero E, Tyler WS. Endoscopic anatomy and map of the equine bronchial tree.. Equine Vet J 1994;26:283–90.
    doi: 10.1111/j.2042-3306.1994.tb04388.xpubmed: 8575395google scholar: lookup
  23. Mustonen A-M, Lehmonen N, Oikari S, Capra J, Raekallio M, Mykkänen A. Counts of hyaluronic acid-containing extracellular vesicles decrease in naturally occurring equine osteoarthritis.. Sci Rep 2022;12:17550.
    doi: 10.1038/s41598-022-21398-8pmc: PMC9585069pubmed: 36266410google scholar: lookup
  24. Tammi RH, Tammi MI, Hascall VC, Hogg M, Pasonen S, MacCallum DK. A preformed basal lamina alters the metabolism and distribution of hyaluronan in epidermal keratinocyte organotypic cultures grown on collagen matrices.. Histochem Cell Biol 2000;113:265–77.
    doi: 10.1007/s004180000128pubmed: 10857478google scholar: lookup
  25. Mustonen A-M, Nieminen P, Joukainen A, Jaroma A, Kääriäinen T, Kröger H. First in vivo detection and characterization of hyaluronan-coated extracellular vesicles in human synovial fluid.. J Orthop Res 2016;34:1960–8.
    doi: 10.1002/jor.23212pubmed: 26919117google scholar: lookup
  26. Hallgren R, Samuelsson T, Laurent T, Modig J. Accumulation of Hyaluronan (hyaluronic acid) in the lung in adult respiratory distress syndrome.. Am Rev Respir Dis 1989;139:682–7.
    doi: 10.1164/ajrccm/139.3.682pubmed: 2923370google scholar: lookup
  27. Larsson K, Eklund A, Malmberg P, Bjermer L, Lundgren R, Belin L. Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis.. Chest 1992;101:109–14.
    doi: 10.1378/chest.101.1.109pubmed: 1309495google scholar: lookup
  28. Bergström C, Eklund A, Sköld M, Tornling G. Bronchoalveolar lavage findings in firefighters.. Am J Ind Med 1997;32:332–6.
    doi: 10.1002/(SICI)1097-0274(199710)32:4<332::AID-AJIM2>3.0.CO;2-Wpubmed: 9258385google scholar: lookup
  29. Ernst G, Jancic C, Auteri S, Rodriguez Moncalvo J, Galindez F, Grynblat P. Increased levels of hyaluronic acid in bronchoalveolar lavage from patients with interstitial lung diseases, relationship with lung function and inflammatory cells recruitment.. Mod Res Inflamm 2014;3:27–36.
    doi: 10.4236/mri.2014.32004google scholar: lookup
  30. Litwiniuk M, Krejner A, Speyrer MS, Gauto AR, Grzela T. Hyaluronic acid in inflammation and tissue regeneration.. Wounds 2016;28:78–88.
    pubmed: 26978861
  31. Lauer ME, Majors AK, Comhair S, Ruple LM, Matuska B, Subramanian A. Hyaluronan and its heavy chain modification in asthma severity and experimental asthma exacerbation.. J Biol Chem 2015;290:23124–34.
    doi: 10.1074/jbc.M115.663823pmc: PMC4645592pubmed: 26209637google scholar: lookup
  32. Bond S, Léguillette R, Richard EA, Couëtil L, Lavoie JP, Martin JG. Equine asthma: integrative biologic relevance of a recently proposed nomenclature.. J Vet Intern Med 2018;32:2088–98.
    doi: 10.1111/jvim.15302pmc: PMC6271326pubmed: 30294851google scholar: lookup
  33. Powell JD, Horton MR. Threat matrix: low-molecular-weight hyaluronan (HA) as a danger signal.. Immunol Res 2005;31:207–18.
    doi: 10.1385/IR:31:3:207pubmed: 15888912google scholar: lookup
  34. Turino GM, Cantor JO. Hyaluronan in respiratory injury and repair.. Am J Respir Crit Care Med 2003;167:1169–75.
    doi: 10.1164/rccm.200205-449PPpubmed: 12714341google scholar: lookup
  35. Weigel PH, DeAngelis PL. Hyaluronan synthases: a decade-plus of novel glycosyltransferases.. J Biol Chem 2007;282:36777–81.
    doi: 10.1074/jbc.R700036200pubmed: 17981795google scholar: lookup
  36. Galdi F, Pedone C, McGee CA, George M, Rice AB, Hussain SS. Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study.. Respir Res 2021;22:30.
    doi: 10.1186/s12931-020-01610-xpmc: PMC7847749pubmed: 33517896google scholar: lookup
  37. Esposito AJ, Bhatraju PK, Stapleton RD, Wurfel MM, Mikacenic C. Hyaluronic acid is associated with organ dysfunction in acute respiratory distress syndrome.. Crit Care 2017;21:304.
    doi: 10.1186/s13054-017-1895-7pmc: PMC5729515pubmed: 29237497google scholar: lookup
  38. Lazaar AL, Panettieri RA. Airway smooth muscle: a modulator of airway remodeling in asthma.. Allergy Clin Immunol 2005;116:488–95.
    doi: 10.1016/j.jaci.2005.06.030pubmed: 16159613google scholar: lookup
  39. Lee G, Beeler-Marfisi J, Viel L, Piché É, Kang H, Sears W. Bronchial brush cytology, endobronchial biopsy, and SALSA immunohistochemistry in severe equine asthma.. Vet Pathol 2022;59:100–11.
    doi: 10.1177/03009858211048635pmc: PMC8679176pubmed: 34903109google scholar: lookup
  40. Niedzwiedz A, Mordak R, Jaworski Z, Nicpon J. Utility of the histological examination of the bronchial mucosa in the diagnosis of severe equine asthma syndrome in horses.. J Equine Vet Sci 2018;67:44–9.
    doi: 10.1016/j.jevs.2018.02.028google scholar: lookup
  41. Rossi H, Koho N, Ilves M, Rajamäki M, Mykkänen A. Expression of extracellular matrix metalloproteinase inducer and matrix metalloproteinase-2 and – 9 in horses with chronic airway inflammation.. Am J Vet Res 2017;78:1329–37.
    doi: 10.2460/ajvr.78.11.1329pubmed: 29076374google scholar: lookup

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