FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Vet Intern Med / Severe asthma in horsed is associated with increased airway ...
Journal of veterinary internal medicine2023; doi: 10.1111/jvim.16941

Severe asthma in horsed is associated with increased airway innervation.

Abstract: Altered innervation structure and function contribute to airway hyperresponsiveness in human asthma, yet the role of innervation in airflow limitation in asthma in horses remains unknown. Objective: To characterize peribronchial innervation in horses with asthma. We hypothesized that airway innervation increases in horses with asthma compared with controls. Methods: Formalin-fixed lung samples from 8 horses with severe asthma and 8 healthy horses from the Equine Respiratory Tissue Biobank. Ante-mortem lung function was recorded. Methods: Blinded case-control study. Immunohistochemistry was performed using rabbit anti-s100 antibody as a neuronal marker for myelinating and non-myelinating Schwann cells. The number and cumulative area of nerves in the peribronchial region and associated with airway smooth muscle were recorded using histomorphometry and corrected for airway size. Results: Both the number (median [IQR]: 1.87 × 10 nerves/μm [1.28 × 10 ]) and the cumulative nerve area (CNA; 1.03 × 10 CNA/μm [1.57 × 10 ]) were higher in the peribronchial region of horses with asthma compared with controls (5.17 × 10 nerves/μm [3.76 × 10 ], 4.14 × 10 CNA/μm [2.54 × 10 ], Mann-Whitney, P = .01). The number of nerves within or lining airway smooth muscle was significantly higher in horses with asthma (4.47 × 10 nerves/μm [5.75 × 10 ]) compared with controls (2.26 × 10 nerves/μm [1.16 × 10 ], Mann-Whitney, P = .03). Conclusions: Asthma in horses is associated with greater airway innervation, possibly contributing to airway smooth muscle remodeling and exacerbating severity of the disease.
© 2023 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: 2023-12-06 PubMed ID: 38054207DOI: 10.1111/jvim.16941Google 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.

This research explores the connection between the structure of airway innervation and severity of asthma in horses. The study found that horses with asthma have significantly greater airway innervation than healthy ones, which could potentially contribute to the severity of the disease.

Objective of the Study

The primary objective of the research was to investigate peribronchial innervation in horses suffering from asthma. The researchers hypothesized that there are increases in airway innervation among asthmatic horses in comparison to healthy ones.

Methodology

  • The research used lung samples from 8 horses afflicted by severe asthma and 8 healthy horses, these samples were obtained from the Equine Respiratory Tissue Biobank.
  • The study further recorded the ante-mortem lung function of these horses.
  • The lung samples were formalin-fixed and a blinded case-control study was conducted.
  • An immunohistochemistry procedure was carried out using rabbit anti-s100 antibody as a neuronal marker. This marker identifies the presence of myelinating and non-myelinating Schwann cells.
  • The number and cumulative area of nerves specifically in the peribronchial region and associated with airway smooth muscle were determined through histomorphometry and then corrected for airway size.

Results

  • The findings suggested that both the number and cumulative nerve area were higher in the peribronchial region of horses with asthma compared to healthy controls. The number of nerves within or lining airway smooth muscle was also significantly higher in asthmatic horses.
  • Data indicated that airway innervation is greater in horses with asthma, a factor that may contribute to the remodeling of airway smooth muscle, which exacerbates the severity of the disease.

Conclusion

The research concluded that asthma in horses correlates with increased airway innervation. This increased innervation can potentially cause greater severity in the disease by increasing the remodeling of airway smooth muscle. This finding could play a crucial role in developing new strategies for managing asthma in horses.

Cite This Article

APA
Leduc L, Leclère M, Gauthier LG, Marcil O, Lavoie JP. (2023). Severe asthma in horsed is associated with increased airway innervation. J Vet Intern Med. https://doi.org/10.1111/jvim.16941

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English

Researcher Affiliations

Leduc, Laurence
  • Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Q, Canada.
Leclère, Mathilde
  • Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Q, Canada.
Gauthier, Laurie Girardot
  • Collège André Grasset, Montréal, Q, Canada.
Marcil, Olivier
  • Collège André Grasset, Montréal, Q, Canada.
Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, Q, Canada.

Grant Funding

  • PJT-148807 / CIHR

References

This article includes 56 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):301-308.
    doi: 10.2746/042516407x180129google scholar: lookup
  2. Couetil L, Cardwell JM, Leguillette R. Equine asthma: current understanding and future directions.. Front Vet Sci 2020;7:450.
    doi: 10.3389/fvets.2020.00450google scholar: lookup
  3. Robinson NE, Chairperson W. International workshop on equine chronic airway disease Michigan State University 16-18 June 2000.. Equine Vet J 2001;33(1):5-19.
    doi: 10.2746/042516401776767412google scholar: lookup
  4. Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011;16(7):1027-1046.
    doi: 10.1111/j.1440-1843.2011.02033.xgoogle scholar: lookup
  5. Leclere M, Lavoie-Lamoureux A, Joubert P. Corticosteroids and antigen avoidance decrease airway smooth muscle mass in an equine asthma model.. Am J Respir Cell Mol Biol 2012;47(5):589-596.
    doi: 10.1165/rcmb.2011-0363ocgoogle scholar: lookup
  6. Polverino M, Polverino F, Fasolino M, Andò F, Alfieri A, De Blasio F. Anatomy and neuro-pathophysiology of the cough reflex arc.. Multidiscip Respir Med 2012;7(1):5.
    doi: 10.1186/2049-6958-7-5google scholar: lookup
  7. Canning BJ, Woo A, Mazzone SB. Neuronal modulation of airway and vascular tone and their influence on nonspecific airways responsiveness in asthma.. J Allergy 2012;2012:1-7.
    doi: 10.1155/2012/108149google scholar: lookup
  8. Lommatzsch M. Airway hyperresponsiveness: new insights into the pathogenesis.. Semin Respir Crit Care Med 2012;33(6):579-587.
    doi: 10.1055/s-0032-1325617google scholar: lookup
  9. Verhein KC, Fryer AD, Jacoby DB. Neural control of airway inflammation.. Curr Allergy Asthma Rep 2009;9(6):484-490.
    doi: 10.1007/s11882-009-0071-9google scholar: lookup
  10. Kistemaker LEM, Prakash YS. Airway innervation and plasticity in asthma.. Physiology (Bethesda) 2019;34(4):283-298.
    doi: 10.1152/physiol.00050.2018google scholar: lookup
  11. Belvisi MG. Airway sensory innervation as a target for novel therapies: an outdated concept?. Curr Opin Pharmacol 2003;3(3):239-243.
    doi: 10.1016/s1471-4892(03)00048-1google scholar: lookup
  12. Kistemaker LEM, Bos ST, Mudde WM. Muscarinic M3 receptors contribute to allergen-induced airway remodeling in mice.. Am J Respir Cell Mol Biol 2014;50(4):690-698.
    doi: 10.1165/rcmb.2013-0220ocgoogle scholar: lookup
  13. Kistemaker LEM, Gosens R. Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling.. Trends Pharmacol Sci 2015;36(3):164-171.
    doi: 10.1016/j.tips.2014.11.005google scholar: lookup
  14. Liu R, Song J, Li H. Treatment of canine asthma by high selective vagotomy.. J Thorac Cardiovasc Surg 2014;148(2):683-689.
    doi: 10.1016/j.jtcvs.2013.12.041google scholar: lookup
  15. Ollerenshaw SL, Jarvis D, Sullivan CE, Woolcock AJ. Substance P immunoreactive nerves in airways from asthmatics and nonasthmatics.. Eur Respir J 1991;4(6):673-682.
  16. Mazzone SB, Undem BJ. Vagal afferent innervation of the airways in health and disease.. Physiol Rev 2016;96(3):975-1024.
    doi: 10.1152/physrev.00039.2015google scholar: lookup
  17. Matera MG, Amorena M, Lucisano A. Innervation of equine airways.. Pulm Pharmacol Ther 2002;15(6):503-511.
    doi: 10.1006/pupt.2002.0390google scholar: lookup
  18. Herszberg B, Ramos-Barbón 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):382-388.
    doi: 10.1016/j.jaci.2006.03.044google scholar: lookup
  19. Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner É, 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):181-187.
    doi: 10.1165/rcmb.2010-0300ocgoogle scholar: lookup
  20. Ceriotti S, Bullone M, Leclere M, Ferrucci F, Lavoie JP. Severe asthma is associated with a remodeling of the pulmonary arteries in horses.. PloS One 2020;15(10):e0239561.
    doi: 10.1371/journal.pone.0239561google scholar: lookup
  21. Derksen FJ, Robinson NE, Slocombe RF. Ovalbumin-induced lung disease in the pony: role of vagal mechanisms.. J Appl Physiol Respir Environ Exerc Physiol 1982;53(3):719-725.
    doi: 10.1152/jappl.1982.53.3.719google scholar: lookup
  22. Olszewski MA, Zhang XY, Robinson NE. Pre- and postjunctional effects of inflammatory mediators in horse airways.. Am J Physiol - Lung Cell Mol Physiol 1999;277(2):L327-L333.
    doi: 10.1152/ajplung.1999.277.2.l327google scholar: lookup
  23. Pujol R, Girard CA, Richard H. Synovial nerve fiber density decreases with naturally-occurring osteoarthritis in horses.. Osteoarthr Cartil 2018;26(10):1379-1388.
    doi: 10.1016/j.joca.2018.06.006google scholar: lookup
  24. Gundersen HJG, Bendtsen TF, Korbo L. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis.. APMIS 1988;96(1-6):379-394.
    doi: 10.1111/j.1699-0463.1988.tb05320.xgoogle scholar: lookup
  25. Bankhead P, Loughrey MB, Fernández JA. QuPath: open source software for digital pathology image analysis.. Sci Rep 2017;7(1):16878.
    doi: 10.1038/s41598-017-17204-5google scholar: lookup
  26. James AL, Hogg JC, Dunn LA, Paré PD. The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening.. Am Rev Respir Dis 1988;138(1):136-139.
    doi: 10.1164/ajrccm.138.1.136google scholar: lookup
  27. Millares-Ramirez EM, Lavoie JP. Bronchial angiogenesis in horses with severe asthma and its response to corticosteroids.. J Vet Intern Med 2021;35(4):2026-2034.
    doi: 10.1111/jvim.16159google scholar: lookup
  28. Canning BJ. Reflex regulation of airway smooth muscle tone.. J Appl Physiol 2006;101(3):971-985.
    doi: 10.1152/japplphysiol.00313.2006google scholar: lookup
  29. de Lagarde M, Rodrigues N, Chevigny M, Beauchamp G, Albrecht B, Lavoie JP. N-butylscopolammonium bromide causes fewer side effects than atropine when assessing bronchoconstriction reversibility in horses with heaves.. Equine Vet J 2014;46(4):474-478.
    doi: 10.1111/evj.12229google scholar: lookup
  30. Couetil L, Hammer J, Miskovic Feutz M, Nogradi N, Perez-Moreno C, Ivester K. Effects of N-butylscopolammonium bromide on lung function in horses with recurrent airway obstruction.. J Vet Intern Med 2012;26(6):1433-1438.
    doi: 10.1111/j.1939-1676.2012.00992.xgoogle scholar: lookup
  31. Santing RE, Pasman Y, Olymulder C, Roffel AF, Meurs H, Zaagsma J. Contribution of a cholinergic reflex mechanism to allergen-induced bronchial hyperreactivity in permanently instrumented, unrestrained Guinea-pigs.. Br J Pharmacol 1995;114(2):414-418.
  32. Lutz W, Sułkowski WJ. Vagus nerve participates in regulation of the airways: inflammatory response and hyperreactivity induced by occupational asthmogens.. Int J Occup Med Environ Health 2004;17(4):417-431.
  33. McAlexander MA, Gavett SH, Kollarik M, Undem BJ. Vagotomy reverses established allergen-induced airway hyperreactivity to methacholine in the mouse.. Respir Physiol Neurobiol 2015;212-214:20-24.
    doi: 10.1016/j.resp.2015.03.007google scholar: lookup
  34. 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.
    doi: 10.1371/journal.pone.0136284google scholar: lookup
  35. Sparrow MP, Lamb JP. Ontogeny of airway smooth muscle: structure, innervation, myogenesis and function in the fetal lung.. Respir Physiol Neurobiol 2003;137(2-3):361-372.
    doi: 10.1016/s1569-9048(03)00159-9google scholar: lookup
  36. Damon DH. Sympathetic innervation promotes vascular smooth muscle differentiation.. Am J Physiol Heart Circ Physiol 2005;288(6):H2785-H2791.
    doi: 10.1152/ajpheart.00354.2004google scholar: lookup
  37. Gosens R, Bos IST, Zaagsma J, Meurs H. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling.. Am J Respir Crit Care Med 2005;171(10):1096-1102.
    doi: 10.1164/rccm.200409-1249ocgoogle scholar: lookup
  38. Ohta S, Oda N, Yokoe T. Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma.. Clin Exp Allergy 2010;40(8):1266-1275.
    doi: 10.1111/j.1365-2222.2010.03478.xgoogle scholar: lookup
  39. Drake MG, Scott GD, Blum ED. Eosinophils increase airway sensory nerve density in mice and in human asthma.. Sci Transl Med 2018;10(457):eaar8477.
    doi: 10.1126/scitranslmed.aar8477google scholar: lookup
  40. Drake MG, Lebold KM, Roth-Carter QR. Eosinophil and airway nerve interactions in asthma.. J Leukoc Biol 2018;104(1):61-67.
    doi: 10.1002/jlb.3mr1117-426rgoogle scholar: lookup
  41. Olszewski MA, Robinson NE, Derksen FJ. In vitro responses of equine small airways and lung parenchyma.. Respir Physiol 1997;109(2):167-176.
    doi: 10.1016/s0034-5687(97)00053-4google scholar: lookup
  42. Rydell-Törmänen K, Uller L, Erjefält JS. Allergic airway inflammation initiates long-term vascular remodeling of the pulmonary circulation.. Int Arch Allergy Immunol 2009;149(3):251-258.
    doi: 10.1159/000199721google scholar: lookup
  43. Lee J, Kang H. Hypoxia promotes vascular smooth muscle cell proliferation through microRNA-mediated suppression of cyclin-dependent kinase inhibitors.. Cell 2019;8(8):802.
    doi: 10.3390/cells8080802google scholar: lookup
  44. Crosswhite P, Sun Z. Molecular mechanisms of pulmonary arterial remodeling.. Mol Med 2014;20(1):191-201.
    doi: 10.2119/molmed.2013.00165google scholar: lookup
  45. Harkness LM, Kanabar V, Sharma HS, Westergren-Thorsson G, Larsson-Callerfelt AK. Pulmonary vascular changes in asthma and COPD.. Pulm Pharmacol Ther 2014;29(2):144-155.
    doi: 10.1016/j.pupt.2014.09.003google scholar: lookup
  46. Sloekers JCT, Herrler A, Hoogland G. Nerve fiber density differences in the temporal dura mater: an explanation for headache after temporal lobectomy? An anatomical study.. J Chem Neuroanat 2022;121:102082.
    doi: 10.1016/j.jchemneu.2022.102082google scholar: lookup
  47. Kawakami T, Ishihara M, Mihara M. Distribution density of intraepidermal nerve fibers in normal human skin.. J Dermatol 2001;28(2):63-70.
    doi: 10.1111/j.1346-8138.2001.tb00091.xgoogle scholar: lookup
  48. Fede C, Petrelli L, Pirri C. Innervation of human superficial fascia.. Front Neuroanat 2022;16:981426.
    doi: 10.3389/fnana.2022.981426google scholar: lookup
  49. Bradbury JM, Thompson RJ. Immunoassay of the neuronal and neuroendocrine marker PGP 9.5 in human tissues.. J Neurochem 1985;44(2):651-653.
    doi: 10.1111/j.1471-4159.1985.tb05461.xgoogle scholar: lookup
  50. Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J. PGP 9.5-a new marker for vertebrate neurons and neuroendocrine cells.. Brain Res 1983;278(1-2):224-228.
    doi: 10.1016/0006-8993(83)90241-xgoogle scholar: lookup
  51. 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.
    doi: 10.1038/s41598-017-09414-8google scholar: lookup
  52. Howarth PH, Springall DR, Redington AE, Djukanovic R, Holgate ST, Polak JM. Neuropeptide-containing nerves in endobronchial biopsies from asthmatic and nonasthmatic subjects.. Am J Respir Cell Mol Biol 1995;13(3):288-296.
    doi: 10.1165/ajrcmb.13.3.7654385google scholar: lookup
  53. Howarth PH, Djukanovic R, Wilson JW, Holgate ST, Springall DR, Polak JM. Mucosal nerves in endobronchial biopsies in asthma and non-asthma.. Int Arch Allergy Appl Immunol 1991;94(1-4):330-333.
    doi: 10.1159/000235396google scholar: lookup
  54. Chanez P, Springall D, Vignola AM. Bronchial mucosal immunoreactivity of sensory neuropeptides in severe airway diseases.. Am J Respir Crit Care Med 1998;158(3):985-990.
    doi: 10.1164/ajrccm.158.3.9608104google scholar: lookup
  55. Scott GD, Blum ED, Fryer AD, Jacoby DB. Tissue optical clearing, three-dimensional imaging, and computer morphometry in whole mouse lungs and human airways.. Am J Respir Cell Mol Biol 2014;51(1):43-55.
    doi: 10.1165/rcmb.2013-0284ocgoogle scholar: lookup
  56. West PW, Canning BJ, Merlo-Pich E, Woodcock AA, Smith JA. Morphologic characterization of nerves in whole-mount airway biopsies.. Am J Respir Crit Care Med 2015;192(1):30-39.
    doi: 10.1164/rccm.201412-2293ocgoogle scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.