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Equine veterinary journal2021; 54(5); 865-874; doi: 10.1111/evj.13514

Airway smooth muscle remodelling in mild and moderate equine asthma.

Abstract: Airway smooth muscle remodelling in severe equine asthma includes both thickening of airway smooth muscle, resulting from hyperplasia and hypertrophy, and changes in contractility. However, airway smooth muscle changes have not been studied in milder forms of the disease. Objective: To investigate bronchial smooth muscle remodelling in horses with mild and moderate asthma (MEA). Methods: Retrospective case-control study. Methods: The endobronchial biopsies from 18 horses with MEA referred to the Equine Hospital of the Université de Montréal and from seven healthy age-matched control horses were studied. The diagnosis was based on clinical signs and bronchoalveolar lavage fluid cytology. Airway smooth muscle cell proliferation was measured by quantifying the expression of the proliferating cell nuclear antigen (PCNA) using immunohistochemistry and histomorphometry. The expression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform, an hypercontractile protein, was assessed by RT-qPCR. Results: Expression of the (+)insert SMMHC isoform in airway smooth muscle was approximately 1.5 times greater in horses with MEA compared with controls (P = .02, mean difference 0.01). Although there were no differences between groups in the proliferation of airway smooth muscle cells (P = .4) or myocyte density (P = .3, mean difference -0.6), the percentage of proliferating myocytes was correlated to pulmonary neutrophilia in horses with neutrophilic inflammation (P = .01, r = .80) and to the expression of the (+)insert SMMHC isoform in asthmatic horses (P = .03, r = .66). Conclusions: Small cohorts of horses were studied, and conclusions are limited to the central airways. Conclusions: These results confirm the presence of bronchial smooth muscle remodelling in mild forms of equine asthma and pave the way for the development of biomarkers to measure asthma progression and response to therapy.
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Publication Date: 2021-10-19 PubMed ID: 34529300DOI: 10.1111/evj.13514Google Scholar: Lookup
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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 research article investigates the condition of airway smooth muscle in horses with milder forms of asthma, revealing notable changes in muscle structure and contractility that are similar to those seen in severe equine asthma. The findings could provide potential biomarkers to gauge the progression of asthma and the effectiveness of treatment.

Objectives and Methodology

  • The aim of this study was to examine alterations in bronchial smooth muscle in horses suffering from mild and moderate cases of asthma. This was done through a retrospective case-control study.
  • The case study was conducted involving 18 horses with Mild and Moderate Equine Asthma (MEA) referred to the Equine Hospital of Université de Montréal, and seven healthy horses of the same age were taken as a control group.
  • The diagnosis was decided based on the symptoms and bronchoalveolar lavage fluid cytology.
  • To analyze airway muscle cell proliferation, the research team quantified the expression of the proliferating cell nuclear antigen (PCNA) through immunohistochemistry and histomorphometry.
  • The expression of the hypercontractile protein called (+)insert smooth muscle myosin heavy chain (SMMHC) isoform was evaluated using RT-qPCR.

Results

  • According to the results of this study, airway smooth muscle expression of the (+)insert SMMHC isoform was found to be approximately 1.5 times higher in MEA horses in comparison to the control group.
  • No significant difference was noticed between the groups in terms of airway smooth muscle cell proliferation or myocyte density.
  • However, in horses with neutrophilic inflammation, there was a correlation established between the number of proliferating myocytes and pulmonary neutrophilia.
  • Moreover, an association was also found between the expression of the (+)insert SMMHC isoform and the number of proliferating myocytes in asthmatic horses.

Conclusions

  • The study was only conducted on a small group of horses, and the conclusions drawn were tailored mainly to central airways.
  • Nevertheless, the study was successful in confirming the occurrence of bronchial smooth muscle remodeling in horses with milder forms of asthma.
  • The findings could influence the development of biomarkers to assess the progression of asthma and the response of these horses to therapy.

Cite This Article

APA
Dupuis-Dowd F, Lavoie JP. (2021). Airway smooth muscle remodelling in mild and moderate equine asthma. Equine Vet J, 54(5), 865-874. https://doi.org/10.1111/evj.13514

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 5
Pages: 865-874

Researcher Affiliations

Dupuis-Dowd, Florence
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Québec, Canada.

MeSH Terms

  • Airway Remodeling
  • Animals
  • Asthma / drug therapy
  • Asthma / veterinary
  • Case-Control Studies
  • Horse Diseases / pathology
  • Horses
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Hyperplasia / veterinary
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Protein Isoforms / metabolism
  • Protein Isoforms / therapeutic use
  • Retrospective Studies

Grant Funding

  • Universitu00e9 de Montru00e9al
  • Zoetis Canada
  • Fonds du Centenaire of the Universitu00e9 de Montru00e9al
  • PJT-148807 / CIHR
  • PJT-148807 / CIHR

References

This article includes 58 references
  1. Hotchkiss JW, Reid SWJ, Christley RM. A survey of horse owners in Great Britain regarding horses in their care. Part 2: risk factors for recurrent airway obstruction.. Equine Vet J 2007;39(4):301-8.
  2. Ivester KM, Couetil LL, Moore GE. An observational study of environmental exposures, airway cytology, and performance in racing thoroughbreds.. J Vet Intern Med 2018;32(5):1754-62.
  3. Secombe CJ, Lester GD, Robertson ID, Cullimore AM. Retrospective survey of bronchoalveolar lavage fluid cytology in Western Australian horses presented for evaluation of the respiratory tract: effect of season on relative cell percentages.. Aust Vet J 2015;93(5):152-6.
  4. Couëtil LL, Cardwell JM, Gerber V, Lavoie J-P, Léguillette R, Richard EA. Inflammatory airway disease of horses-revised consensus statement.. J Vet Intern Med 2016;30(2):503-15.
  5. Bond S, Leguillette R, Richard EA, Couetil L, Lavoie J-P, Martin JG. Equine asthma: integrative biologic relevance of a recently proposed nomenclature.. J Vet Intern Med 2018;32(6):2088-98.
  6. Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: from benchside to clinical practice.. Can Respir J 2010;17(4):e85-93.
  7. Hirota N, Martin JG. Mechanisms of airway remodeling.. Chest 2013;144(3):1026-32.
  8. Bullone M, Lavoie JP. The equine asthma model of airway remodeling: from a veterinary to a human perspective.. Cell Tissue Res 2020;380(2):223-36.
  9. Lambert RK, Wiggs BR, Kuwano K, Hogg JC, Pare PD. Functional significance of increased airway smooth muscle in asthma and COPD.. J Appl Physiol (1985) 1993;74(6):2771-81.
  10. Pepe C, Foley S, Shannon J, Lemiere C, Olivenstein R, Ernst P. Differences in airway remodeling between subjects with severe and moderate asthma.. J Allergy Clin Immunol 2005;116(3):544-9.
  11. James AL, Bai TR, Mauad T, Abramson MJ, Dolhnikoff M, McKay KO. Airway smooth muscle thickness in asthma is related to severity but not duration of asthma.. Eur Respir J 2009;34(5):1040-5.
  12. Herszberg B, Ramos-Barbon D, Tamaoka M, Martin JG, Lavoie JP. Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling.. J Allergy Clin Immunol 2006;118(2):382-8.
  13. Bara I, Ozier A, Tunon de Lara JM, Marthan R, Berger P. Pathophysiology of bronchial smooth muscle remodelling in asthma.. Eur Respir J 2010;36(5):1174-84.
  14. James AL, Elliot JG, Jones RL, Carroll ML, Mauad T, Bai TR. Airway smooth muscle hypertrophy and hyperplasia in asthma.. Am J Respir Crit Care Med 2012;185(10):1058-64.
  15. Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G. Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model.. Am J Respir Cell Mol Biol 2012;47(5):589-96.
  16. Bullone M, Vargas A, Elce Y, Martin JG, Lavoie JP. Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma.. Sci Rep 2017;7(1):8843.
  17. Woolcock AJ, Peat JK. Epidemiology of bronchial hyperresponsiveness.. Clin Rev Allergy 1989;7(3):245-56.
  18. Gil FR, Lauzon AM. Smooth muscle molecular mechanics in airway hyperresponsiveness and asthma.. Can J Physiol Pharmacol 2007;85(1):133-40.
  19. Jiang H, Rao K, Liu X, Halayko AJ, Liu G, Stephens NL. Early changes in airway smooth muscle hyperresponsiveness.. Can J Physiol Pharmacol 1994;72(11):1440-7.
  20. Fredberg JJ, Inouye DS, Mijailovich SM, Butler JP. Perturbed equilibrium of myosin binding in airway smooth muscle and its implications in bronchospasm.. Am J Respir Crit Care Med 1999;159(3):959-67.
  21. Kelley CA, Takahashi M, Yu JH, Adelstein RS. An insert of seven amino acids confers functional differences between smooth muscle myosins from the intestines and vasculature.. J Biol Chem 1993;268(17):12848-54.
  22. Lauzon AM, Tyska MJ, Rovner AS, Freyzon Y, Warshaw DM, Trybus KM. A 7-amino-acid insert in the heavy chain nucleotide binding loop alters the kinetics of smooth muscle myosin in the laser trap.. J Muscle Res Cell Motil 1998;19(8):825-37.
  23. Low R, Léguillette R, Lauzon AM. (+)Insert smooth muscle myosin heavy chain (SM-B): from single molecule to human.. Int J Biochem Cell Biol 2006;38(11):1862-74.
  24. Leguillette R, Gil FR, Zitouni N, Lajoie-Kadoch S, Sobieszek A, Lauzon AM. (+)Insert smooth muscle myosin heavy chain (SM-B) isoform expression in human tissues.. Am J Physiol Cell Physiol 2005;289(5):C1277-85.
  25. Boivin R, Vargas A, Lefebvre-Lavoie J, Lauzon AM, Lavoie JP. Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways.. Thorax 2014;69(12):1113-9.
  26. Leclere M, Lavoie-Lamoureux A, Gelinas-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;45(1):181-7.
  27. Bessonnat A, Lavoie J-P. Évaluation du remodelage des voies respiratoires centrales de chevaux asthmatiques légers/modérés.. Montréal: Université de Montréal; 2018.
  28. ter Woort F, Caswell JL, Arroyo LG, Viel L. Histologic investigation of airway inflammation in postmortem lung samples from racehorses.. Am J Vet Res 2018;79(3):342-7.
  29. 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;72(6):838-42.
  30. Smith BL, Aguilera-Tejero E, Tyler WS, Jones JH, Hornof WJ, Pascoe JR. Endoscopic anatomy and map of the equine bronchial tree.. Equine Vet J 1994;26(4):283-90.
  31. Bullone M, Chevigny M, Allano M, Martin JG, Lavoie JP. Technical and physiological determinants of airway smooth muscle mass in endobronchial biopsy samples of asthmatic horses.. J Appl Physiol (1985) 2014;117(7):806-15.
  32. 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;307(3):L252-60.
  33. Hirota JA, Nguyen TT, Schaafsma D, Sharma P, Tran T. Airway smooth muscle in asthma: phenotype plasticity and function.. Pulm Pharmacol Ther 2009;22(5):370-8.
  34. Bullone M, Joubert P, Gagné A, Lavoie J-P, Hélie P. Bronchoalveolar lavage fluid neutrophilia is associated with the severity of pulmonary lesions during equine asthma exacerbations.. Equine Vet J 2018;50(5):609-15.
  35. Léguillette R, Laviolette M, Bergeron C, Zitouni N, Kogut P, Solway J. Myosin, transgelin, and myosin light chain kinase: expression and function in asthma.. Am J Respir Crit Care Med 2009;179(3):194-204.
  36. Xu X, Rijcken B, Schouten JP, Weiss ST. Airways responsiveness and development and remission of chronic respiratory symptoms in adults.. Lancet 1997;350(9089):1431-4.
  37. Mazan MR, Vin R, Hoffman AM. Radiographic scoring lacks predictive value in inflammatory airway disease.. Equine Vet J 2005;37(6):541-5.
  38. Leguillette R, Tohver T, Bond SL, Nicol JA, McDonald KJ. Effect of dexamethasone and fluticasone on airway hyperresponsiveness in horses with inflammatory airway disease.. J Vet Intern Med 2017;31(4):1193-201.
  39. DiSanto ME, Stein R, Chang S, Hypolite JA, Zheng Y, Zderic S. Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction.. Am J Physiol Cell Physiol 2003;285(6):C1397-410.
  40. Hassan M, Jo T, Risse P-A, Tolloczko B, Lemière C, Olivenstein R. Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma.. J Allergy Clin Immunol 2010;125(5):1037-45.e3.
  41. James AL, Noble PB, Drew SA, Mauad T, Bai TR, Abramson MJ. Airway smooth muscle proliferation and inflammation in asthma.. J Appl Physiol (1985) 2018;125(4):1090-6.
  42. Woodruff PG, Dolganov GM, Ferrando RE, Donnelly S, Hays SR, Solberg OD. Hyperplasia of smooth muscle in mild to moderate asthma without changes in cell size or gene expression.. Am J Respir Crit Care Med 2004;169(9):1001-6.
  43. Naryzhny SN. Proliferating cell nuclear antigen: a proteomics view.. Cell Mol Life Sci 2008;65(23):3789-808.
  44. Johnson P, Roth M, Tamm M, Hughes M, Ge QI, King G. Airway smooth muscle cell proliferation is increased in asthma.. Am J Respir Crit Care Med 2001;164(3):474-7.
  45. Jones RL, Elliot JG, James AL. Estimating airway smooth muscle cell volume and number in airway sections. Sources of variability.. Am J Respir Cell Mol Biol 2014;50(2):246-52.
  46. Elliot JG, Jones RL, Abramson MJ, Green FH, Mauad T, McKay KO. Distribution of airway smooth muscle remodelling in asthma: relation to airway inflammation.. Respirology 2015;20(1):66-72.
  47. Jarjour NN, Erzurum SC, Bleecker ER, Calhoun WJ, Castro M, Comhair SAA. Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program.. Am J Respir Crit Care Med 2012;185(4):356-62.
  48. Grainge CL, Lau LCK, Ward JA, Dulay V, Lahiff G, Wilson S. Effect of bronchoconstriction on airway remodeling in asthma.. N Engl J Med 2011;364(21):2006-15.
  49. Gosens R, Grainge C. Bronchoconstriction and airway biology: potential impact and therapeutic opportunities.. Chest 2015;147(3):798-803.
  50. Prakash YS. Airway smooth muscle in airway reactivity and remodeling: what have we learned?. Am J Physiol Lung Cell Mol Physiol 2013;305(12):L912-33.
  51. Vargas A, Roux-Dalvai F, Droit A, Lavoie JP. Neutrophil-derived exosomes: a new mechanism contributing to airway smooth muscle remodeling.. Am J Respir Cell Mol Biol 2016;55(3):450-61.
  52. Benayoun L, Druilhe A, Dombret MC, Aubier M, Pretolani M. Airway structural alterations selectively associated with severe asthma.. Am J Respir Crit Care Med 2003;167(10):1360-8.
  53. Uberti B, Morán G. Role of neutrophils in equine asthma.. Anim Health Res Rev 2018;19(1):65-73.
  54. Jeffery P, Holgate S, Wenzel S, Endobronchial BW. Methods for the assessment of endobronchial biopsies in clinical research: application to studies of pathogenesis and the effects of treatment.. Am J Respir Crit Care Med 2003;168(6 Pt 2):S1-17.
  55. Woodruff PG, Innes AL. Quantitative morphology using bronchial biopsies.. Eur Respir Rev 2006;15(101):157-61.
  56. Martin JG, Duguet A, Eidelman DH. The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease.. Eur Respir J 2000;16(2):349-54.
  57. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D. Equine asthma: current understanding and future directions.. Front Vet Sci 2020;7:450.
  58. Bosshard S, Gerber V. Evaluation of coughing and nasal discharge as early indicators for an increased risk to develop equine recurrent airway obstruction (RAO).. J Vet Intern Med 2014;28(2):618-23.

Citations

This article has been cited 3 times.
  1. Lo Feudo CM, Ferrucci F, Bizzotto D, Dellacà R, Lavoie JP, Stucchi L. Differences in pulmonary function measured by oscillometry between horses with mild-moderate equine asthma and healthy controls. Equine Vet J 2025 May;57(3):619-628.
    doi: 10.1111/evj.14206pubmed: 39134475google scholar: lookup
  2. Höglund N, Rossi H, Javela HM, Oikari S, Nieminen P, Mustonen AM, Airas N, Kärjä V, Mykkänen A. The amount of hyaluronic acid and airway remodelling increase with the severity of inflammation in neutrophilic equine asthma. BMC Vet Res 2024 Jun 25;20(1):273.
    doi: 10.1186/s12917-024-04136-2pubmed: 38918797google scholar: lookup
  3. van den Brom-Spierenburg AJ, Mureșan AN, Westermann CM. Antimicrobial Prescription Behavior in Equine Asthma Cases: An International Survey. Animals (Basel) 2024 Jan 30;14(3).
    doi: 10.3390/ani14030457pubmed: 38338101google scholar: lookup
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