FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of veterinary internal medicine2021; 35(4); 2026-2034; doi: 10.1111/jvim.16159

Bronchial angiogenesis in horses with severe asthma and its response to corticosteroids.

Abstract: Severe asthma in horses is characterized by structural changes that thicken the lower airway wall, a change that is only partially reversible by current treatments. Increased vascularization contributes to the thickening of the bronchial wall in humans with asthma and is considered a potential new therapeutic target. Objective: To determine the presence of angiogenesis in the bronchi of severely asthmatic horses, and if present, to evaluate its reversibility by treatment with corticosteroids. Methods: Study 1: Bronchial samples from asthmatic horses in exacerbation (7), in remission (7), and aged-matched healthy horses. Study 2: Endobronchial biopsy samples from asthmatic horses in exacerbation (6) and healthy horses (6) before and after treatment with dexamethasone. Methods: Blinded, randomized controlled study. Immunohistochemistry was performed using collagen IV as a marker for vascular basement membranes. Number of vessels, vascular area, and mean vessel size in the bronchial lamina propria were measured by histomorphometry. Reversibility of vascular changes in Study 2 was assessed after 2 weeks of treatment with dexamethasone. Results: The number of vessels and vascular area were increased in the airway walls of asthmatic horses in exacerbation (P = .01 and P = .02, respectively) and in remission (P = .02 and P = .04, respectively) when compared to controls. In Study 2, the differences observed between groups disappeared after 2 weeks of treatment with corticosteroids because of the increased number of vessels in healthy horses. Conclusions: Angiogenesis contributes to thickening of the airway wall in asthmatic horses and was not reversed by a 2-week treatment with corticosteroids.
© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Get Full Text
Publication Date: 2021-05-28 PubMed ID: 34048095PubMed Central: PMC8295704DOI: 10.1111/jvim.16159Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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.

The article discusses a study on the role of angiogenesis in severe asthma for horses and whether corticosteroids can reverse it. The research shows an increase in bronchial vascularization in horses with asthma, which doesn’t appear to be reversed by a 2-week corticosteroids treatment.

Research Objective and Methods

  • The main purpose of this research was to determine whether angiogenesis (the formation of new blood vessels) occurs in the bronchi of horses with severe asthma. If it is present, the researchers aimed to study whether it could be reversed by corticosteroid treatment.
  • The study was divided into two parts. The first involved bronchial samples from horses with asthma in varying conditions: exacerbation, remission, and healthy matched controls. In the second, bronchial biopsy samples from asthmatic and healthy horses were taken before and after administering the corticosteroid dexamethasone.
  • The methodology was a blinded, randomized controlled study. Immunohistochemistry, a method that visually detects specific components in tissue samples, was utilized with the use of collagen IV as a marker for vascular basement membranes.
  • Researchers observed and measured the number of blood vessels, vascular area, and average size of vessels present in the bronchial lamina propria, a layer of loose connective tissues beneath the epithelium, by histomorphometry, a method to collect quantitative data from histological samples.

Research Findings

  • The result indicated a significant increase in the number of blood vessels and vascular area in the bronchial tissues of asthmatic horses during both exacerbation and remission compared to healthy controls.
  • In the second part of the study, after 2 weeks of corticosteroid treatment, the differences in the number of vessels between asthmatic and healthy horses disappeared, mainly due to an increase in vessels in the healthy horses.

Conclusion

  • The findings confirmed that angiogenesis is a contributing factor to thickening of the bronchial wall in asthmatic horses.
  • Despite the increased number of vessels in healthy horses after corticosteroid treatment, the study concluded that the vascular changes in asthmatic horses are not reversed by a 2-week treatment with corticosteroids. Therefore, the treatment might not be an effective measure against angiogenesis associated with asthma in horses.

Cite This Article

APA
Millares-Ramirez EM, Lavoie JP. (2021). Bronchial angiogenesis in horses with severe asthma and its response to corticosteroids. J Vet Intern Med, 35(4), 2026-2034. https://doi.org/10.1111/jvim.16159

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 35
Issue: 4
Pages: 2026-2034

Researcher Affiliations

Millares-Ramirez, Esther M
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Q, Canada.
Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Q, Canada.

MeSH Terms

  • Adrenal Cortex Hormones / therapeutic use
  • Animals
  • Asthma / drug therapy
  • Asthma / veterinary
  • Bronchi
  • Bronchoscopy / veterinary
  • Horse Diseases / drug therapy
  • Horses
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / veterinary

Grant Funding

  • PJT-148807 / CIHR
  • PJT-148807 / CIHR

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 47 references
  1. Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
    pmc: PMC4913592pubmed: 26806374doi: 10.1111/jvim.13824google scholar: lookup
  2. Pirie RS, Couëtil LL, Robinson NE, Lavoie JP. Equine asthma: An appropriate, translational and comprehendible terminology?. Equine Vet J 2016 Jul;48(4):403-5.
    pubmed: 27292020doi: 10.1111/evj.12586google scholar: lookup
  3. Pirie RS. Recurrent airway obstruction: a review.. Equine Vet J 2014 May;46(3):276-88.
    pubmed: 24164473doi: 10.1111/evj.12204google scholar: lookup
  4. Bullone M, Lavoie JP. Asthma "of horses and men"--how can equine heaves help us better understand human asthma immunopathology and its functional consequences?. Mol Immunol 2015 Jul;66(1):97-105.
    pubmed: 25547716doi: 10.1016/j.molimm.2014.12.005google scholar: lookup
  5. Bullone M, Lavoie JP. The equine asthma model of airway remodeling: from a veterinary to a human perspective.. Cell Tissue Res 2020 May;380(2):223-236.
    pubmed: 31713728doi: 10.1007/s00441-019-03117-4google scholar: lookup
  6. Robinson NE, Derksen FJ, Olszewski MA, Buechner-Maxwell VA. The pathogenesis of chronic obstructive pulmonary disease of horses.. Br Vet J 1996 May;152(3):283-306.
    pubmed: 8762605doi: 10.1016/s0007-1935(96)80101-1google scholar: lookup
  7. Bullone M, Beauchamp G, Godbout M, Martin JG, Lavoie JP. Endobronchial Ultrasound Reliably Quantifies Airway Smooth Muscle Remodeling in an Equine Asthma Model.. PLoS One 2015;10(9):e0136284.
    pmc: PMC4562526pubmed: 26348727doi: 10.1371/journal.pone.0136284google scholar: lookup
  8. Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, David F, Martin JG, Lavoie JP. Effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma.. Am J Respir Cell Mol Biol 2011 Jul;45(1):181-7.
    pubmed: 20935189doi: 10.1165/rcmb.2010-0300ocgoogle scholar: lookup
  9. Setlakwe EL, Lemos KR, Lavoie-Lamoureux A, Duguay JD, Lavoie JP. Airway collagen and elastic fiber content correlates with lung function in equine heaves.. Am J Physiol Lung Cell Mol Physiol 2014 Aug 1;307(3):L252-60.
    pubmed: 24879055doi: 10.1152/ajplung.00019.2014google scholar: lookup
  10. Zanini A, Chetta A, Imperatori AS, Spanevello A, Olivieri D. The role of the bronchial microvasculature in the airway remodelling in asthma and COPD.. Respir Res 2010 Sep 29;11(1):132.
    pmc: PMC2955663pubmed: 20920222doi: 10.1186/1465-9921-11-132google scholar: lookup
  11. Li X, Wilson JW. Increased vascularity of the bronchial mucosa in mild asthma.. Am J Respir Crit Care Med 1997 Jul;156(1):229-33.
    pubmed: 9230753doi: 10.1164/ajrccm.156.1.9607066google scholar: lookup
  12. Kumar SD, Emery MJ, Atkins ND, Danta I, Wanner A. Airway mucosal blood flow in bronchial asthma.. Am J Respir Crit Care Med 1998 Jul;158(1):153-6.
    pubmed: 9655722doi: 10.1164/ajrccm.158.1.9712141google scholar: lookup
  13. Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G, Couture C, Martin JG, Lavoie JP. Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model.. Am J Respir Cell Mol Biol 2012 Nov;47(5):589-96.
    pubmed: 22721832doi: 10.1165/rcmb.2011-0363ocgoogle scholar: lookup
  14. Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP. Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma.. Sci Rep 2017 Aug 18;7(1):8843.
    pmc: PMC5562887pubmed: 28821845doi: 10.1038/s41598-017-09414-8google scholar: lookup
  15. Charan NB, Baile EM, Paré PD. Bronchial vascular congestion and angiogenesis.. Eur Respir J 1997 May;10(5):1173-80.
    pubmed: 9163664doi: 10.1183/09031936.97.10051173google scholar: lookup
  16. Jackson JR, Seed MP, Kircher CH, Willoughby DA, Winkler JD. The codependence of angiogenesis and chronic inflammation.. FASEB J 1997 May;11(6):457-65.
    pubmed: 9194526
  17. Walsh DA, Pearson CI. Angiogenesis in the pathogenesis of inflammatory joint and lung diseases.. Arthritis Res 2001;3(3):147-53.
    pmc: PMC128891pubmed: 11299055doi: 10.1186/ar292google scholar: lookup
  18. Huang H, Lavoie-Lamoureux A, Moran K, Lavoie JP. IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells.. Am J Physiol Lung Cell Mol Physiol 2007 May;292(5):L1147-54.
    pubmed: 17494951doi: 10.1152/ajplung.00294.2006google scholar: lookup
  19. Eldridge L, Wagner EM. Angiogenesis in the lung.. J Physiol 2019 Feb;597(4):1023-1032.
    pmc: PMC6376070pubmed: 30022479doi: 10.1113/jp275860google scholar: lookup
  20. Baluk P, Morikawa S, Haskell A, Mancuso M, McDonald DM. Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors.. Am J Pathol 2003 Nov;163(5):1801-15.
    pmc: PMC1892429pubmed: 14578181doi: 10.1016/s0002-9440(10)63540-7google scholar: lookup
  21. Felmeden DC, Blann AD, Lip GY. Angiogenesis: basic pathophysiology and implications for disease.. Eur Heart J 2003 Apr;24(7):586-603.
    pubmed: 12657217doi: 10.1016/s0195-668x(02)00635-8google scholar: lookup
  22. Ribatti D, Puxeddu I, Crivellato E, Nico B, Vacca A, Levi-Schaffer F. Angiogenesis in asthma.. Clin Exp Allergy 2009 Dec;39(12):1815-21.
    pubmed: 20085597doi: 10.1111/j.1365-2222.2009.03385.xgoogle scholar: lookup
  23. Salvato G. Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects.. Thorax 2001 Dec;56(12):902-6.
    pmc: PMC1745985pubmed: 11713351doi: 10.1136/thorax.56.12.902google scholar: lookup
  24. Herteman N, Bullone M, Lavoie JP. Endoscopic Evaluation of Angiogenesis in the Large Airways of Horses with Heaves Using Narrow Band Imaging.. J Vet Intern Med 2016 Mar-Apr;30(2):671-4.
    pmc: PMC4913588pubmed: 26926661doi: 10.1111/jvim.13890google scholar: lookup
  25. Jean D, Vrins A, Beauchamp G, Lavoie JP. Evaluation of variations in bronchoalveolar lavage fluid in horses with recurrent airway obstruction.. Am J Vet Res 2011 Jun;72(6):838-42.
    pubmed: 21627532doi: 10.2460/ajvr.72.6.838google scholar: lookup
  26. Jean D, Vrins A, Lavoie JP. Monthly, daily, and circadian variations of measurements of pulmonary mechanics in horses with chronic obstructive pulmonary disease.. Am J Vet Res 1999 Nov;60(11):1341-6.
    pubmed: 10566805
  27. Couëtil LL, Rosenthal FS, DeNicola DB, Chilcoat CD. Clinical signs, evaluation of bronchoalveolar lavage fluid, and assessment of pulmonary function in horses with inflammatory respiratory disease.. Am J Vet Res 2001 Apr;62(4):538-46.
    pubmed: 11327461doi: 10.2460/ajvr.2001.62.538google scholar: lookup
  28. Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP. Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma.. Respir Res 2017 Dec 12;18(1):207.
    pmc: PMC5727947pubmed: 29233147doi: 10.1186/s12931-017-0689-4google scholar: lookup
  29. Wang D, Stockard CR, Harkins L, Lott P, Salih C, Yuan K, Buchsbaum D, Hashim A, Zayzafoon M, Hardy RW, Hameed O, Grizzle W, Siegal GP. Immunohistochemistry in the evaluation of neovascularization in tumor xenografts.. Biotech Histochem 2008 Jun;83(3-4):179-89.
    pmc: PMC2651088pubmed: 18846440doi: 10.1080/10520290802451085google scholar: lookup
  30. Orsida BE, Li X, Hickey B, Thien F, Wilson JW, Walters EH. Vascularity in asthmatic airways: relation to inhaled steroid dose.. Thorax 1999 Apr;54(4):289-95.
    pmc: PMC1745476pubmed: 10092688doi: 10.1136/thx.54.4.289google scholar: lookup
  31. Naldini A, Carraro F. Role of inflammatory mediators in angiogenesis.. Curr Drug Targets Inflamm Allergy 2005 Feb;4(1):3-8.
    pubmed: 15720228doi: 10.2174/1568010053622830google scholar: lookup
  32. Barbato A, Turato G, Baraldo S, Bazzan E, Calabrese F, Panizzolo C, Zanin ME, Zuin R, Maestrelli P, Fabbri LM, Saetta M. Epithelial damage and angiogenesis in the airways of children with asthma.. Am J Respir Crit Care Med 2006 Nov 1;174(9):975-81.
    pubmed: 16917118doi: 10.1164/rccm.200602-189ocgoogle scholar: lookup
  33. Calzetta L, Rogliani P, Page C, Roncada P, Pistocchini E, Soggiu A, Piras C, Urbani A, Matera MG. Clinical effect of corticosteroids in asthma-affected horses: A quantitative synthesis.. Equine Vet J 2018 Sep;50(5):594-601.
    pubmed: 29393535doi: 10.1111/evj.12815google scholar: lookup
  34. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
    pubmed: 21824219doi: 10.1111/j.1440-1843.2011.02033.xgoogle scholar: lookup
  35. Hoshino M, Takahashi M, Takai Y, Sim J, Aoike N. Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma.. Clin Exp Allergy 2001 May;31(5):722-30.
    pubmed: 11422131doi: 10.1046/j.1365-2222.2001.01071.xgoogle scholar: lookup
  36. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling.. Am J Respir Crit Care Med 2000 May;161(5):1720-45.
    pubmed: 10806180doi: 10.1164/ajrccm.161.5.9903102google scholar: lookup
  37. Feltis BN, Wignarajah D, Zheng L, Ward C, Reid D, Harding R, Walters EH. Increased vascular endothelial growth factor and receptors: relationship to angiogenesis in asthma.. Am J Respir Crit Care Med 2006 Jun 1;173(11):1201-7.
    pubmed: 16528018doi: 10.1164/rccm.200507-1105ocgoogle scholar: lookup
  38. Martidis A, Miller DG, Ciulla TA, Danis RP, Moorthy RS. Corticosteroids as an antiangiogenic agent for histoplasmosis-related subfoveal choroidal neovascularization.. J Ocul Pharmacol Ther 1999 Oct;15(5):425-8.
    pubmed: 10530703doi: 10.1089/jop.1999.15.425google scholar: lookup
  39. Small GR, Hadoke PW, Sharif I, Dover AR, Armour D, Kenyon CJ, Gray GA, Walker BR. Preventing local regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 enhances angiogenesis.. Proc Natl Acad Sci U S A 2005 Aug 23;102(34):12165-70.
    pmc: PMC1189304pubmed: 16093320doi: 10.1073/pnas.0500641102google scholar: lookup
  40. Morgan R, Keen J, Halligan D, O'Callaghan A, Andrew R, Livingstone D, Abernethie A, Maltese G, Walker B, Hadoke P. Species-specific regulation of angiogenesis by glucocorticoids reveals contrasting effects on inflammatory and angiogenic pathways.. PLoS One 2018;13(2):e0192746.
    pmc: PMC5813970pubmed: 29447208doi: 10.1371/journal.pone.0192746google scholar: lookup
  41. Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA. Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile.. Am J Respir Crit Care Med 2001 Oct 15;164(8 Pt 1):1410-3.
    pubmed: 11704587doi: 10.1164/ajrccm.164.8.2012091google scholar: lookup
  42. Oliver C, Jamur MC. Immunocytochemical methods and protocols.. Methods Mol Biol 2010;588:iv-v.
    pubmed: 20025087doi: 10.1007/978-1-59745-324-0google scholar: lookup
  43. Renshaw S. Immunohistochemistry and Immunocytochemistry: Essential Methods. 2nd ed. Chichester, West Sussex: Wiley Blackwell; 2017.
  44. Mayersbach HV. Principles and limitations of immunohistochemical methods.. J R Microsc Soc 1967;87(2):295-308.
    pubmed: 4866205
  45. Taylor CR, Levenson RM. Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment II.. Histopathology 2006 Oct;49(4):411-24.
    pubmed: 16978205doi: 10.1111/j.1365-2559.2006.02513.xgoogle scholar: lookup
  46. Pepper MS, Skobe M. Lymphatic endothelium: morphological, molecular and functional properties.. J Cell Biol 2003 Oct 27;163(2):209-13.
    pmc: PMC2173536pubmed: 14581448doi: 10.1083/jcb.200308082google scholar: lookup
  47. Soltani A, Wood-Baker R, Sohal SS, Muller HK, Reid D, Walters EH. Reticular Basement Membrane Vessels Are Increased in COPD Bronchial Mucosa by Both Factor VIII and Collagen IV Immunostaining and Are Hyperpermeable.. J Allergy (Cairo) 2012;2012:958383.
    pmc: PMC3303780pubmed: 22500190doi: 10.1155/2012/958383google scholar: lookup

Citations

This article has been cited 2 times.
  1. Leduc L, Leclère M, Gauthier LG, Marcil O, Lavoie JP. Severe asthma in horses is associated with increased airway innervation. J Vet Intern Med 2024 Jan-Feb;38(1):485-494.
    doi: 10.1111/jvim.16941pubmed: 38054207google scholar: lookup
  2. Kozłowska N, Wierzbicka M, Pawliński B, Domino M. Co-Occurrence of Severe Equine Asthma and Palatal Disorders in Privately Owned Pleasure Horses. Animals (Basel) 2023 Jun 12;13(12).
    doi: 10.3390/ani13121962pubmed: 37370472google scholar: lookup
Subscribe to our newsletter
Join 99,850 horse owners like you who receive our email updates on horse health and nutrition.