FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Immun Inflamm Dis / Immunomodulatory asthma therapy in the equine animal model: ...
Immunity, inflammation and disease2019; 7(3); 130-149; doi: 10.1002/iid3.252

Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect.

Abstract: Equine asthma represents a naturally occurring animal model for human allergic neutrophilic asthma. Inhalative nanoparticle-bound cytosine-phosphate-guanosine (CpG-GNP) immunotherapy, independent of specific allergens, has already shown promising clinical and immunological results in previous studies and offers the possibility to treat the underlying cause of the disease. This study analyses the relationship between dose and response, and evaluates a possible long-term effect. In the prospective, randomised, double-blind clinical field study, 29 horses suffering from equine asthma received 10 inhalation treatments with either 187.5 µg CpG-GNP (CpG single dose [CpGsd]; n = 11), 375 µg CpG-GNP double dose (CpG double dose [CpGdd]; n = 9) (q48h for 20 days) or 1600 µg beclomethasone (n = 9) (q24h for 10 days). Each horse was examined three times: before the treatment (I), immediately after the 10 inhalations (II), and 8 weeks after the final inhalation (III). The three groups were compared according to clinical and laboratory parameters. The study examined the sustainability of the long-term effect of the treatment after 8 weeks, as well as the tolerability of the formula as a double dose. The CpGsd resulted in a significant improvement in 82% of the parameters, the CpGdd in 72%. In the long-term evaluation, the CpGsd showed a significant improvement in 100% of the parameters in comparison to the initial values, the CpGdd in 67%. On the immunological level, the bronchoalveolar lavage revealed a significant reduction of IL-4, IL-8, and interferon-γ. Both CpG groups displayed significant improvements in clinical and laboratory parameters, especially regarding the long-term effect of CpGsd. Doubling the CpG dose did not result in any improvement in comparison to the original single dose. On the immunological level, an anti-inflammatory, as well as an immunomodulatory effect, apart from a Th2-dominated immune response, could be observed. This immunomodulatory inhalation treatment could indicate a new possibility for human allergic asthma therapy.
© 2019 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
Get Full Text
Publication Date: 2019-05-29 PubMed ID: 31141308PubMed Central: PMC6688086DOI: 10.1002/iid3.252Google 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
  • Randomized Controlled Trial
  • Veterinary
  • 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 study explores the effects and long-term benefits of a nanoparticle-bound immunotherapy on horses suffering from equine asthma, which serves as an animal model for human allergic asthma. Surprisingly, increasing the dose of the treatment did not yield better results, and the single dose therapy successfully improved asthmatic symptoms in horses and reduced certain inflammation markers.

Study Overview

  • The research utilises equine asthma – a condition in horses that closely resembles human allergic asthma – as an animal model to test an immunotherapy treatment.
  • The treatment being tested involves inhalable nanoparticles bound with cytosine-phosphate-guanosine (CpG-GNP), which has already shown promising results in treating the root cause of equine asthma.
  • The primary goals of the study were to assess the relationship between the dosage of CpG-GNP and its effectiveness, and to observe any potential long-term effects of the treatment.
  • The study was designed as a prospective, randomised, double-blind clinical field trial, conducted on 29 horses.

Methodology and Findings

  • The horses were randomly split into three groups. Two groups received different doses of CpG-GNP (group 1: single dose, group 2: double dose), while the third group was treated beclomethasone, a standard medication for asthma.
  • The horses were evaluated before treatment, immediately after treatment and 8 weeks after treatment, and the three groups were compared based on clinical and laboratory parameters.
  • The single dose CpG-GNP group presented a significant improvement in 82% of monitored parameters, versus 72% in the double dose group. The long-term follow-up showed an even more remarkable result: 100% improvement in the single dose CpG-GNP group, versus 67% in the double dose group.
  • The bronchoalveolar lavage results indicated a significant reduction in several inflammatory cytokines (IL-4, IL-8, and interferon-γ).

Conclusions and Implications

  • The researchers concluded that the CpG-GNP treatment led to major improvements in clinical and laboratory parameters, particularly in regards to its long-term effects.
  • Interestingly, doubling the dose did not result in increased efficacy relative to the original single dose.
  • The treatment demonstrated an anti-inflammatory and immunomodulatory response, attenuating an otherwise predominantly Th2-immune response, which characterizes allergic asthma.
  • This innovative immunomodulatory treatment paves the way for potential new approaches in treating human allergic asthma.

Cite This Article

APA
Klier J, Bartl C, Geuder S, Geh KJ, Reese S, Goehring LS, Winter G, Gehlen H. (2019). Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect. Immun Inflamm Dis, 7(3), 130-149. https://doi.org/10.1002/iid3.252

Publication

Immunity, inflammation and disease
ISSN: 2050-4527
NlmUniqueID: 101635460
Country: England
Language: English
Volume: 7
Issue: 3
Pages: 130-149

Researcher Affiliations

Klier, John
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
Bartl, Carolin
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
  • Department of Veterinary Medicine, Equine Clinic, Surgery and Radiology, Free University of Berlin, Berlin, Germany.
Geuder, Sabine
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
Geh, Katharina J
  • Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Munich, Germany.
Reese, Sven
  • Department of Veterinary Medicine, Equine Clinic, Surgery and Radiology, Free University of Berlin, Berlin, Germany.
Goehring, Lutz S
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
Winter, Gerhard
  • Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Munich, Germany.
Gehlen, Heidrun
  • Department of Veterinary Medicine, Equine Clinic, Surgery and Radiology, Free University of Berlin, Berlin, Germany.

MeSH Terms

  • Administration, Inhalation
  • Animals
  • Asthma / immunology
  • Asthma / therapy
  • Asthma / veterinary
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dinucleoside Phosphates / administration & dosage
  • Dinucleoside Phosphates / immunology
  • Dinucleoside Phosphates / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Horse Diseases / immunology
  • Horse Diseases / therapy
  • Horses
  • Humans
  • Immunomodulation / immunology
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / immunology
  • Oligodeoxyribonucleotides / therapeutic use
  • Prospective Studies
  • Treatment Outcome

Conflict of Interest Statement

The authors declare no competing financial interests. The study was conducted at the Equine Clinic, Centre for Clinical Veterinary Medicine, LMU Munich, Germany. Part of the lab work was performed by CB and JK in the lab of the Institute for Animal Welfare, Ethology, Animal Hygiene and Animal Husbandry, Faculty of Veterinary Medicine, Department of Veterinary Science, Ludwig‐Maximilians‐University, Munich. An abstract of this study was presented in part at the 2016 British Equine Veterinary Association (BEVA) Congress, Birmingham, England.

References

This article includes 83 references
  1. Bracher V, von Fellenberg R, Winder CN, Gruenig G, Hermann M, Kraehenmann A. An investigation of the incidence of chronic obstructive pulmonary disease (COPD) in random populations of Swiss horses.. Equine Vet J 1991 Mar;23(2):136-41.
    pubmed: 2044507doi: 10.1111/j.2042-3306.1991.tb02738.xgoogle scholar: lookup
  2. Hotchkiss JW, Reid SW, 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 Jul;39(4):301-8.
    pubmed: 17722720doi: 10.2746/042516407x180129google scholar: lookup
  3. Ainsworth DM, Cheetham J. Disorders of the respiratory system. Equine Internal Medicine 3 St. Louis, USA: Saunders Elsevier; 2010.
  4. 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
  5. Robinson NE. Recurrent airway obstruction (Heaves). Equine Respiratory Disease Ithaca, New York: International Veterinary Information Service; 2001.
  6. 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
  7. Gerber V, Tessier C, Marti E. Genetics of upper and lower airway diseases in the horse.. Equine Vet J 2015 Jul;47(4):390-7.
    pubmed: 24773614doi: 10.1111/evj.12289google scholar: lookup
  8. Gerber V, Baleri D, Klukowska-Rötzler J, Swinburne JE, Dolf G. Mixed inheritance of equine recurrent airway obstruction.. J Vet Intern Med 2009 May-Jun;23(3):626-30.
    pubmed: 19645845doi: 10.1111/j.1939-1676.2009.0292.xgoogle scholar: lookup
  9. Brazil TJ, Dagleish MP, McGorum BC, Dixon PM, Haslett C, Chilvers ER. Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation.. Clin Exp Allergy 2005 Jul;35(7):854-65.
    pubmed: 16008670doi: 10.1111/j.1365-2222.2005.02231.xgoogle scholar: lookup
  10. Dubuc J, Lavoie JP. Airway wall eosinophilia is not a feature of equine heaves.. Vet J 2014 Nov;202(2):387-9.
    pubmed: 25239297doi: 10.1016/j.tvjl.2014.08.020google scholar: lookup
  11. Davis E, Rush BR. Equine recurrent airway obstruction: pathogenesis, diagnosis, and patient management.. Vet Clin North Am Equine Pract 2002 Dec;18(3):453-67, vi.
    pubmed: 12516928doi: 10.1016/s0749-0739(02)00026-3google scholar: lookup
  12. 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
  13. Kündig TM, Klimek L, Schendzielorz P, Renner WA, Senti G, Bachmann MF. Is The Allergen Really Needed in Allergy Immunotherapy?. Curr Treat Options Allergy 2015;2(1):72-82.
    pmc: PMC4335088pubmed: 25722959doi: 10.1007/s40521-014-0038-5google scholar: lookup
  14. Senti G, Johansen P, Haug S, Bull C, Gottschaller C, Müller P, Pfister T, Maurer P, Bachmann MF, Graf N, Kündig TM. Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial.. Clin Exp Allergy 2009 Apr;39(4):562-70.
    pubmed: 19226280doi: 10.1111/j.1365-2222.2008.03191.xgoogle scholar: lookup
  15. Klier J, Fuchs S, May A, Schillinger U, Plank C, Winter G, Coester C, Gehlen H. A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.. Pharm Res 2012 Jun;29(6):1650-7.
    pubmed: 22302522doi: 10.1007/s11095-012-0686-8google scholar: lookup
  16. Klier J, Lehmann B, Fuchs S, Reese S, Hirschmann A, Coester C, Winter G, Gehlen H. Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.. J Vet Intern Med 2015 Jan;29(1):286-93.
    pmc: PMC4858074pubmed: 25619520doi: 10.1111/jvim.12524google scholar: lookup
  17. Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells.. Immunology 2006 Apr;117(4):433-42.
    pmc: PMC1782242pubmed: 16556256doi: 10.1111/j.1365-2567.2006.02321.xgoogle scholar: lookup
  18. Schneberger D, Caldwell S, Suri SS, Singh B. Expression of toll-like receptor 9 in horse lungs.. Anat Rec (Hoboken) 2009 Jul;292(7):1068-77.
    pubmed: 19548205doi: 10.1002/ar.20927google scholar: lookup
  19. Zwiorek K, Bourquin C, Battiany J, Winter G, Endres S, Hartmann G, Coester C. Delivery by cationic gelatin nanoparticles strongly increases the immunostimulatory effects of CpG oligonucleotides.. Pharm Res 2008 Mar;25(3):551-62.
    pubmed: 17912489doi: 10.1007/s11095-007-9410-5google scholar: lookup
  20. Klier J, May A, Fuchs S, Schillinger U, Plank C, Winter G, Gehlen H, Coester C. Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles.. Vet Immunol Immunopathol 2011 Nov 15;144(1-2):79-87.
    pubmed: 21831455doi: 10.1016/j.vetimm.2011.07.009google scholar: lookup
  21. Geh KJ, Hubert M, Winter G. Optimisation of one-step desolvation and scale-up of gelatine nanoparticle production.. J Microencapsul 2016 Nov;33(7):595-604.
    pubmed: 27556342doi: 10.1080/02652048.2016.1228706google scholar: lookup
  22. Klier J, Geis S, Steuer J, Geh K, Reese S, Fuchs S, Mueller RS, Winter G, Gehlen H. A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma-affected horses, an animal model.. Immun Inflamm Dis 2018 Mar;6(1):81-96.
    pmc: PMC5818452pubmed: 29094511doi: 10.1002/iid3.198google scholar: lookup
  23. Mutwiri GK, Nichani AK, Babiuk S, Babiuk LA. Strategies for enhancing the immunostimulatory effects of CpG oligodeoxynucleotides.. J Control Release 2004 May 31;97(1):1-17.
    pubmed: 15147800doi: 10.1016/j.jconrel.2004.02.022google scholar: lookup
  24. Rush BR, Raub ES, Thomsen MM, Davis EG, Matson CJ, Hakala JE. Pulmonary function and adrenal gland suppression with incremental doses of aerosolized beclomethasone dipropionate in horses with recurrent airway obstruction.. J Am Vet Med Assoc 2000 Aug 1;217(3):359-64.
    pubmed: 10935040doi: 10.2460/javma.2000.217.359google scholar: lookup
  25. Gerber V, King M, Schneider DA, Robinson NE. Tracheobronchial mucus viscoelasticity during environmental challenge in horses with recurrent airway obstruction.. Equine Vet J 2000 Sep;32(5):411-7.
    pubmed: 11037263doi: 10.2746/042516400777591183google scholar: lookup
  26. Grabner A. Arterielle blutgasanalyse. Klinische Labordiagnostik in der Tiermedizin 6 Stuttgart: Schattauer; 2005:pp. 429‐430.
  27. Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses.. Vet Immunol Immunopathol 2009 Feb 15;127(3-4):242-8.
    pubmed: 19027964doi: 10.1016/j.vetimm.2008.10.313google scholar: lookup
  28. Kleiber C, McGorum BC, Horohov DW, Pirie RS, Zurbriggen A, Straub R. Cytokine profiles of peripheral blood and airway CD4 and CD8 T lymphocytes in horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2005 Mar 10;104(1-2):91-7.
    pubmed: 15661334doi: 10.1016/j.vetimm.2004.10.002google scholar: lookup
  29. Miltenyi S, Müller W, Weichel W, Radbruch A. High gradient magnetic cell separation with MACS.. Cytometry 1990;11(2):231-8.
    pubmed: 1690625doi: 10.1002/cyto.990110203google scholar: lookup
  30. Horohov DW, Beadle RE, Mouch S, Pourciau SS. Temporal regulation of cytokine mRNA expression in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2005 Oct 18;108(1-2):237-45.
    pubmed: 16098607doi: 10.1016/j.vetimm.2005.07.013google scholar: lookup
  31. Soboll Hussey G, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 2011 Feb 7;42(1):23.
    pmc: PMC3045331pubmed: 21314906doi: 10.1186/1297-9716-42-23google scholar: lookup
  32. El Abbas S, Frellstedt L, Art T. Characterization of T‐helper lymphocytes in peripheral bloos and broncho‐alveolar lavage of healthy horses and in horses with recurrent airway obstruction. Proceedings of the 2nd Scientific Meeting of the Faculty of Veterinary Medicine 2012 Liege, Belgium.
  33. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.. Anal Biochem 1987 Apr;162(1):156-9.
    pubmed: 2440339doi: 10.1006/abio.1987.9999google scholar: lookup
  34. Nakagawa S, Cuthill IC. Effect size, confidence interval and statistical significance: a practical guide for biologists.. Biol Rev Camb Philos Soc 2007 Nov;82(4):591-605.
    pubmed: 17944619doi: 10.1111/j.1469-185x.2007.00027.xgoogle scholar: lookup
  35. Farrokhi S, Abbasirad N, Movahed A, Khazaei HA, Pishjoo M, Rezaei N. TLR9-based immunotherapy for the treatment of allergic diseases.. Immunotherapy 2017 Mar;9(4):339-346.
    pubmed: 28303762doi: 10.2217/imt-2016-0104google scholar: lookup
  36. Niedermaier G, Gehlen H. Möglichkeiten der Inhalationstherapie zur Behandlung der chronisch obstruktiven Bronchitis des Pferdes. Pferdeheilkunde 2009;25:327‐332.
  37. 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
  38. Vaughn JM, McConville JT, Burgess D, Peters JI, Johnston KP, Talbert RL, Williams RO 3rd. Single dose and multiple dose studies of itraconazole nanoparticles.. Eur J Pharm Biopharm 2006 Jun;63(2):95-102.
    pubmed: 16516450doi: 10.1016/j.ejpb.2006.01.006google scholar: lookup
  39. Zillies JC, Zwiorek K, Hoffmann F, Vollmar A, Anchordoquy TJ, Winter G, Coester C. Formulation development of freeze-dried oligonucleotide-loaded gelatin nanoparticles.. Eur J Pharm Biopharm 2008 Oct;70(2):514-21.
    pubmed: 18582569doi: 10.1016/j.ejpb.2008.04.026google scholar: lookup
  40. Geh KJ, Hubert M, Winter G. Progress in formulation development and sterilisation of freeze-dried oligodeoxynucleotide-loaded gelatine nanoparticles.. Eur J Pharm Biopharm 2018 Aug;129:10-20.
    pubmed: 29777773doi: 10.1016/j.ejpb.2018.05.016google scholar: lookup
  41. Rush BR, Raub ES, Rhoads WS, Flaminio MJ, Matson CJ, Hakala JE, Gillespie JR. Pulmonary function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone dipropionate and dexamethasone, respectively.. Am J Vet Res 1998 Aug;59(8):1039-43.
    pubmed: 9706210
  42. Dauvillier J, Felippe MJ, Lunn DP, Lavoie-Lamoureux A, Leclère M, Beauchamp G, Lavoie JP. Effect of long-term fluticasone treatment on immune function in horses with heaves.. J Vet Intern Med 2011 May-Jun;25(3):549-57.
    pubmed: 21488960doi: 10.1111/j.1939-1676.2011.0717.xgoogle scholar: lookup
  43. Robinson NE, Olszewski MA, Boehler D, Berney C, Hakala J, Matson C, Derksen FJ. Relationship between clinical signs and lung function in horses with recurrent airway obstruction (heaves) during a bronchodilator trial.. Equine Vet J 2000 Sep;32(5):393-400.
    pubmed: 11037260doi: 10.2746/042516400777591147google scholar: lookup
  44. 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 Mar-Apr;28(2):618-23.
    pmc: PMC4858023pubmed: 24417562doi: 10.1111/jvim.12279google scholar: lookup
  45. Rettmer H, Hoffman AM, Lanz S, Oertly M, Gerber V. Owner-reported coughing and nasal discharge are associated with clinical findings, arterial oxygen tension, mucus score and bronchoprovocation in horses with recurrent airway obstruction in a field setting.. Equine Vet J 2015 May;47(3):291-5.
    pubmed: 24761754doi: 10.1111/evj.12286google scholar: lookup
  46. Laumen E, Doherr MG, Gerber V. Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families.. Equine Vet J 2010 Mar;42(2):142-8.
    pubmed: 20156250doi: 10.2746/042516409x479586google scholar: lookup
  47. Deegen E, Klein H‐J. Interpleuraldruckmessungen und Bronchospasmolysetests mit einem transportablen Ösophagusdruckmeßgerät beim Pferd. Pferdeheilkunde 1987;3:213‐221.
  48. Dixon PM, Railton DI, McGorum BC. Equine pulmonary disease: a case control study of 300 referred cases. Part 2: Details of animals and of historical and clinical findings.. Equine Vet J 1995 Nov;27(6):422-7.
    pubmed: 8565938doi: 10.1111/j.2042-3306.1995.tb04422.xgoogle scholar: lookup
  49. Robinson NE, Berney C, Eberhart S, deFeijter-Rupp HL, Jefcoat AM, Cornelisse CJ, Gerber VM, Derksen FJ. Coughing, mucus accumulation, airway obstruction, and airway inflammation in control horses and horses affected with recurrent airway obstruction.. Am J Vet Res 2003 May;64(5):550-7.
    pubmed: 12755293doi: 10.2460/ajvr.2003.64.550google scholar: lookup
  50. Gerber V, Straub R, Marti E, Hauptman J, Herholz C, King M, Imhof A, Tahon L, Robinson NE. Endoscopic scoring of mucus quantity and quality: observer and horse variance and relationship to inflammation, mucus viscoelasticity and volume.. Equine Vet J 2004 Nov;36(7):576-82.
    pubmed: 15581321doi: 10.2746/0425164044864525google scholar: lookup
  51. Takeyama K, Dabbagh K, Jeong Shim J, Dao-Pick T, Ueki IF, Nadel JA. Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor: role of neutrophils.. J Immunol 2000 Feb 1;164(3):1546-52.
    pubmed: 10640773doi: 10.4049/jimmunol.164.3.1546google scholar: lookup
  52. Gerber V, Robinson NE, Venta RJ, Rawson J, Jefcoat AM, Hotchkiss JA. Mucin genes in horse airways: MUC5AC, but not MUC2, may play a role in recurrent airway obstruction.. Equine Vet J 2003 May;35(3):252-7.
    pubmed: 12755427doi: 10.2746/042516403776148291google scholar: lookup
  53. Herholz C, Straub R, Gerber V, Wampfler B, Lüthi S, Imhof A, Moens Y, Busato A. Relationship between clinical signs and pulmonary function estimated by the single breath diagram for CO(2) (SBD-CO(2)) in horses with chronic obstructive pulmonary disease.. Vet J 2002 Mar;163(2):187-95.
    pubmed: 12093194doi: 10.1053/tvjl.2001.0646google scholar: lookup
  54. Giguère S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.. Vet Immunol Immunopathol 2002 Mar;85(3-4):147-58.
    pubmed: 11943316doi: 10.1016/s0165-2427(01)00420-2google scholar: lookup
  55. Williamson KK, Davis MS. Evidence-based respiratory medicine in horses.. Vet Clin North Am Equine Pract 2007 Aug;23(2):215-27.
    pubmed: 17616311doi: 10.1016/j.cveq.2007.03.006google scholar: lookup
  56. Gerber V, Schott Ii HC, Robinson NE. Owner assessment in judging the efficacy of airway disease treatment.. Equine Vet J 2011 Mar;43(2):153-8.
    pubmed: 21592208doi: 10.1111/j.2042-3306.2010.00156.xgoogle scholar: lookup
  57. Ramseyer A, Gaillard C, Burger D, Straub R, Jost U, Boog C, Marti E, Gerber V. Effects of genetic and environmental factors on chronic lower airway disease in horses.. J Vet Intern Med 2007 Jan-Feb;21(1):149-56.
    pubmed: 17338163doi: 10.1892/0891-6640(2007)21[149:eogaef]2.0.co;2google scholar: lookup
  58. Cordeau ME, Joubert P, Dewachi O, Hamid Q, Lavoie JP. IL-4, IL-5 and IFN-gamma mRNA expression in pulmonary lymphocytes in equine heaves.. Vet Immunol Immunopathol 2004 Jan;97(1-2):87-96.
    pubmed: 14700540doi: 10.1016/j.vetimm.2003.08.013google scholar: lookup
  59. 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
  60. Robbin MG, Wagner B, Noronha LE, Antczak DF, de Mestre AM. Subpopulations of equine blood lymphocytes expressing regulatory T cell markers.. Vet Immunol Immunopathol 2011 Mar 15;140(1-2):90-101.
    pubmed: 21208665doi: 10.1016/j.vetimm.2010.11.020google scholar: lookup
  61. van Scott MR, Justice JP, Bradfield JF, Enright E, Sigounas A, Sur S. IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice.. Am J Physiol Lung Cell Mol Physiol 2000 Apr;278(4):L667-74.
    pubmed: 10749743doi: 10.1152/ajplung.2000.278.4.l667google scholar: lookup
  62. Shamji MH, Durham SR. Mechanisms of immunotherapy to aeroallergens.. Clin Exp Allergy 2011 Sep;41(9):1235-46.
    pubmed: 21762223doi: 10.1111/j.1365-2222.2011.03804.xgoogle scholar: lookup
  63. Moseman EA, Liang X, Dawson AJ, Panoskaltsis-Mortari A, Krieg AM, Liu YJ, Blazar BR, Chen W. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells.. J Immunol 2004 Oct 1;173(7):4433-42.
    pubmed: 15383574doi: 10.4049/jimmunol.173.7.4433google scholar: lookup
  64. Debrue M, Hamilton E, Joubert P, Lajoie-Kadoch S, Lavoie JP. Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2005 May 1;105(1-2):25-31.
    pubmed: 15797472doi: 10.1016/j.vetimm.2004.12.013google scholar: lookup
  65. Ainsworth DM, Matychak M, Reyner CL, Erb HN, Young JC. Effects of in vitro exposure to hay dust on the gene expression of chemokines and cell-surface receptors in primary bronchial epithelial cell cultures established from horses with chronic recurrent airway obstruction.. Am J Vet Res 2009 Mar;70(3):365-72.
    pubmed: 19254149doi: 10.2460/ajvr.70.3.365google scholar: lookup
  66. Lunn DP, Horohov DW. The equine immune system. Equine Internal Medicine 3 St. Louis, USA: Saunders Elsevier; 2010.
  67. Bohle B. CpG motifs as possible adjuvants for the treatment of allergic diseases.. Int Arch Allergy Immunol 2002 Nov;129(3):198-203.
    pubmed: 12444316doi: 10.1159/000066771google scholar: lookup
  68. Fonseca DE, Kline JN. Use of CpG oligonucleotides in treatment of asthma and allergic disease.. Adv Drug Deliv Rev 2009 Mar 28;61(3):256-62.
    pubmed: 19167442doi: 10.1016/j.addr.2008.12.007google scholar: lookup
  69. Umetsu DT, DeKruyff RH. The regulation of allergy and asthma.. Immunol Rev 2006 Aug;212:238-55.
    pubmed: 16903918doi: 10.1111/j.0105-2896.2006.00413.xgoogle scholar: lookup
  70. Hawrylowicz CM. Regulatory T cells and IL-10 in allergic inflammation.. J Exp Med 2005 Dec 5;202(11):1459-63.
    pmc: PMC2213335pubmed: 16330811doi: 10.1084/jem.20052211google scholar: lookup
  71. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses?. Int Immunol 2009 Oct;21(10):1105-11.
    pubmed: 19737784doi: 10.1093/intimm/dxp095google scholar: lookup
  72. Hamza E, Steinbach F, Marti E. CD4+CD25+ T cells expressing FoxP3 in Icelandic horses affected with insect bite hypersensitivity.. Vet Immunol Immunopathol 2012 Jul 15;148(1-2):139-44.
    pubmed: 21700344doi: 10.1016/j.vetimm.2011.05.033google scholar: lookup
  73. Vale-Pereira S, Todo-Bom A, Geraldes L, Schmidt-Weber C, Akdis CA, Mota-Pinto A. FoxP3, GATA-3 and T-bet expression in elderly asthma.. Clin Exp Allergy 2011 Apr;41(4):490-6.
    pubmed: 21114556doi: 10.1111/j.1365-2222.2010.03640.xgoogle scholar: lookup
  74. Desjardins I, Theoret C, Joubert P, Wagner B, Lavoie JP. Comparison of TGF-beta 1 concentrations in bronchoalveolar fluid of horses affected with heaves and of normal controls.. Vet Immunol Immunopathol 2004 Oct;101(3-4):133-41.
    pubmed: 15350743doi: 10.1016/j.vetimm.2004.03.008google scholar: lookup
  75. Kline JN. Eat dirt: CpG DNA and immunomodulation of asthma.. Proc Am Thorac Soc 2007 Jul;4(3):283-8.
    pmc: PMC2647631pubmed: 17607014doi: 10.1513/pats.200701-019awgoogle scholar: lookup
  76. Vollmer J, Krieg AM. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists.. Adv Drug Deliv Rev 2009 Mar 28;61(3):195-204.
    pubmed: 19211030doi: 10.1016/j.addr.2008.12.008google scholar: lookup
  77. Zißler U, Chaker A. Eine immunologische Schnittstelle. Deutsches Ärzteblatt ‐ Perspektiven der Pneumologie und Allergologie 2016;2:31‐32.
  78. Lazarevic V, Glimcher LH, Lord GM. T-bet: a bridge between innate and adaptive immunity.. Nat Rev Immunol 2013 Nov;13(11):777-89.
    pmc: PMC6290922pubmed: 24113868doi: 10.1038/nri3536google scholar: lookup
  79. Krug N, Hohlfeld JM, Kirsten AM, Kornmann O, Beeh KM, Kappeler D, Korn S, Ignatenko S, Timmer W, Rogon C, Zeitvogel J, Zhang N, Bille J, Homburg U, Turowska A, Bachert C, Werfel T, Buhl R, Renz J, Garn H, Renz H. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme.. N Engl J Med 2015 May 21;372(21):1987-95.
    pubmed: 25981191doi: 10.1056/nejmoa1411776google scholar: lookup
  80. Couëtil LL, Art T, de Moffarts B, Becker M, Mélotte D, Jaspar F, Bureau F, Lekeux P. DNA binding activity of transcription factors in bronchial cells of horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2006 Sep 15;113(1-2):11-20.
    pubmed: 16753225doi: 10.1016/j.vetimm.2006.03.020google scholar: lookup
  81. Hansen S, Baptiste KE, Fjeldborg J, Horohov DW. A review of the equine age-related changes in the immune system: comparisons between human and equine aging, with focus on lung-specific immune-aging.. Ageing Res Rev 2015 Mar;20:11-23.
    pubmed: 25497559doi: 10.1016/j.arr.2014.12.002google scholar: lookup
  82. Kehrli D, Jandova V, Fey K, Jahn P, Gerber V. Multiple hypersensitivities including recurrent airway obstruction, insect bite hypersensitivity, and urticaria in 2 warmblood horse populations.. J Vet Intern Med 2015 Jan;29(1):320-6.
    pmc: PMC4858110pubmed: 25270534doi: 10.1111/jvim.12473google scholar: lookup
  83. Cunningham FM, Dunkel B. Equine recurrent airway obstruction and insect bite hypersensitivity: understanding the diseases and uncovering possible new therapeutic approaches.. Vet J 2008 Sep;177(3):334-44.
    pubmed: 18023376doi: 10.1016/j.tvjl.2007.10.005google scholar: lookup

Citations

This article has been cited 6 times.
  1. Klier J, Fuchs S, Winter G, Gehlen H. Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment.. Animals (Basel) 2022 Aug 16;12(16).
    doi: 10.3390/ani12162087pubmed: 36009677google scholar: lookup
  2. Khramtsov P, Burdina O, Lazarev S, Novokshonova A, Bochkova M, Timganova V, Kiselkov D, Minin A, Zamorina S, Rayev M. Modified Desolvation Method Enables Simple One-Step Synthesis of Gelatin Nanoparticles from Different Gelatin Types with Any Bloom Values.. Pharmaceutics 2021 Sep 22;13(10).
    doi: 10.3390/pharmaceutics13101537pubmed: 34683829google scholar: lookup
  3. Mainguy-Seers S, Lavoie JP. Glucocorticoid treatment in horses with asthma: A narrative review.. J Vet Intern Med 2021 Jul;35(4):2045-2057.
    doi: 10.1111/jvim.16189pubmed: 34085342google scholar: lookup
  4. Harman RM, Marx C, Van de Walle GR. Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy.. Front Cell Dev Biol 2021;9:654885.
    doi: 10.3389/fcell.2021.654885pubmed: 33869217google scholar: lookup
  5. Lönker NS, Fechner K, Wahed AAE. Horses as a Crucial Part of One Health.. Vet Sci 2020 Feb 29;7(1).
    doi: 10.3390/vetsci7010028pubmed: 32121327google scholar: lookup
  6. Sheats MK, Davis KU, Poole JA. Comparative Review of Asthma in Farmers and Horses.. Curr Allergy Asthma Rep 2019 Oct 10;19(11):50.
    doi: 10.1007/s11882-019-0882-2pubmed: 31599358google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.