Airway Hyperresponsiveness, but Not Bronchoalveolar Inflammatory Cytokines Profiles, Is Modified at the Subclinical Onset of Severe Equine Asthma.
Abstract: Airway hyperresponsiveness (AHR) and inflammation are both observed in human and equine asthma. The aim of this study was to assess the timeline and relationship of both features at the subclinical onset of severe equine asthma (SEA). First, the repeatability of the pulmonary function test (PFT) using impulse oscillometry system, and the methacholine bronchoprovocation test (BPT) were assessed at a 1-day interval on six SEA horses in clinical remission and six control horses. Then, clinical and ancillary tests were performed before and after a 1-week low-dust environmental challenge, including weighted clinical score, respiratory endoscopy, bronchoalveolar fluid cytology, PFT, and BPT. Both PFT and BPT showed acceptable repeatability. No test allowed SEA horses in clinical remission to be distinguished from control, unlike in human patients. Because of the low-dust environment, no significant difference was observed in the results of clinical and conventional ancillary examinations after the challenge. However, SEA horses showed increased AHR after the environmental challenge. At that stage, no signs of inflammation or changes in pro-inflammatory cytokines profiles (quantification and gene expression) were observed, suggesting AHR is present at an earlier stage of equine asthma than airway inflammation. This feature indicates SEA could present in a different disease pathway than neutrophilic human asthma.
Publication Date: 2023-08-01 PubMed ID: 37570294PubMed Central: PMC10417247DOI: 10.3390/ani13152485Google 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.
- Journal Article
- Airway Disease
- Asthma
- Bronchoalveolar Lavage
- Clinical Examination
- Clinical Findings
- Clinical Pathology
- Clinical Study
- Cytokines
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Disease Management
- Disease Treatment
- Equine Diseases
- Equine Health
- Equine Science
- Inflammation
- Respiratory Disease
- Veterinary Medicine
- Veterinary Research
- Veterinary Science
Summary
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This experimental study investigates how airway hyperresponsiveness (AHR) and inflammation corresponds with the early onset of severe equine asthma (SEA). The researchers found that while SEA horses showed increased AHR after being exposed to a low-dust environment for a week, there were no corresponding signs of inflammation. This suggests that AHR could be an early symptom of equine asthma, and that SEA might follow a different disease pathway from human neutrophilic asthma.
Objective and Methodology of the Study
- The aim of this study was to investigate the interplay between AHR and inflammation at the early stages of severe equine asthma (SEA). In particular, the researchers wanted to understand the temporal relationship between these two symptoms.
- Twelve horses were used in this experiment: six with SEA in clinical remission and six healthy controls. The researchers first tested the reliability of two diagnostic methods over a one-day interval: the pulmonary function test (PFT) and the methacholine bronchoprovocation test (BPT).
- After the initial tests, the horses were exposed to a low-dust environmental challenge for a week. Before and after this challenge, multiple tests were performed to assess the horses’ clinical condition and to examine cell compositions, PFT, and BPT results.
Findings of the Study
- The PFT and BPT diagnostic methods produced consistent results over time.
- Before the environmental challenge, the SEA horses in clinical remission couldn’t be differentiated from the control horses based on these tests.
- Following the one-week challenge in a low dust environment, there wasn’t any significant difference in the conditions of the horses.
- However, the SEA horses exhibited increased AHR after the challenge, an important indicator that their condition had worsened.
- Paradoxically, there were neither signs of inflammation nor changes in pro-inflammatory cytokines observed in the affected horses.
Implications of the Study
- This study suggests that AHR occurs before inflammation in cases of equine asthma, challenging previous presumptions about the progression of the illness.
- The lack of inflammation in the SEA horses after the challenge implies that these horses may follow a different disease pathway from human neutrophilic asthma.
- The findings could have implications in the diagnosis and early detection of SEA. By monitoring AHR, it might be possible to identify the disease before the onset of inflammation, potentially allowing for a more effective intervention.
Cite This Article
APA
Frippiat T, Art T, Tosi I.
(2023).
Airway Hyperresponsiveness, but Not Bronchoalveolar Inflammatory Cytokines Profiles, Is Modified at the Subclinical Onset of Severe Equine Asthma.
Animals (Basel), 13(15), 2485.
https://doi.org/10.3390/ani13152485 Publication
Researcher Affiliations
- Equine Sports Medicine Centre, FARAH Research Centre, Faculty of Veterinary Medicine, University of Liu00e8ge, 4000 Liege, Belgium.
- Sportpaardenarts-Equine Sports Medicine, 1250AD Laren, The Netherlands.
- Equine Sports Medicine Centre, FARAH Research Centre, Faculty of Veterinary Medicine, University of Liu00e8ge, 4000 Liege, Belgium.
- Equine Sports Medicine Centre, FARAH Research Centre, Faculty of Veterinary Medicine, University of Liu00e8ge, 4000 Liege, Belgium.
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 65 references
- Couu00ebtil LL, Cardwell JM, Gerber V, Lavoie JP, Lu00e9guillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
- Kaur R, Chupp G. Phenotypes and endotypes of adult asthma: Moving toward precision medicine.. J Allergy Clin Immunol 2019 Jul;144(1):1-12.
- Lowell FC. Observations on heaves. An asthma-like syndrome in the horse. 1964.. Allergy Proc 1990 May-Jun;11(3):149-50; discussion 147-8.
- Kaup FJ, Drommer W, Damsch S, Deegen E. Ultrastructural findings in horses with chronic obstructive pulmonary disease (COPD). II: Pathomorphological changes of the terminal airways and the alveolar region.. Equine Vet J 1990 Sep;22(5):349-55.
- Herszberg B, Ramos-Barbu00f3n D, Tamaoka M, Martin JG, Lavoie JP. Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling.. J Allergy Clin Immunol 2006 Aug;118(2):382-8.
- Naylor JM, Clark EG, Clayton HM. Chronic obstructive pulmonary disease: Usefulness of clinical signs, bronchoalveolar lavage, and lung biopsy as diagnostic and prognostic aids.. Can Vet J 1992 Sep;33(9):591-8.
- Fairbairn SM, Page CP, Lees P, Cunningham FM. Early neutrophil but not eosinophil or platelet recruitment to the lungs of allergic horses following antigen exposure.. Clin Exp Allergy 1993 Oct;23(10):821-8.
- McGorum BC, Dixon PM, Halliwell RE. Responses of horses affected with chronic obstructive pulmonary disease to inhalation challenges with mould antigens.. Equine Vet J 1993 Jul;25(4):261-7.
- Joubert P, Cordeau ME, Boyer A, Silversides DW, Lavoie JP. Cytokine expression by peripheral blood neutrophils from heaves-affected horses before and after allergen challenge.. Vet J 2008 Nov;178(2):227-32.
- Tesarowski DB, Viel L, McDonell WN. Pulmonary function measurements during repeated environmental challenge of horses with recurrent airway obstruction (heaves).. Am J Vet Res 1996 Aug;57(8):1214-9.
- Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
- Thomas SJ, de Solis CN, Coleman MC. Case-Control Study of Risk Factors for Equine Asthma in Texas.. J Equine Vet Sci 2021 Aug;103:103644.
- Couu00ebtil LL, Ward MP. Analysis of risk factors for recurrent airway obstruction in North American horses: 1,444 cases (1990-1999).. J Am Vet Med Assoc 2003 Dec 1;223(11):1645-50.
- Vandenput S, Duvivier DH, Votion D, Art T, Lekeux P. Environmental control to maintain stabled COPD horses in clinical remission: effects on pulmonary function.. Equine Vet J 1998 Mar;30(2):93-6.
- Derksen FJ, Robinson NE, Armstrong PJ, Stick JA, Slocombe RF. Airway reactivity in ponies with recurrent airway obstruction (heaves).. J Appl Physiol (1985) 1985 Feb;58(2):598-604.
- Armstrong PJ, Derksen FJ, Slocombe RF, Robinson NE. Airway responses to aerosolized methacholine and citric acid in ponies with recurrent airway obstruction (heaves).. Am Rev Respir Dis 1986 Mar;133(3):357-61.
- Hargreave FE, Ryan G, Thomson NC, O'Byrne PM, Latimer K, Juniper EF, Dolovich J. Bronchial responsiveness to histamine or methacholine in asthma: measurement and clinical significance.. J Allergy Clin Immunol 1981 Nov;68(5):347-55.
- Beckett WS, Marenberg ME, Pace PE. Repeated methacholine challenge produces tolerance in normal but not in asthmatic subjects.. Chest 1992 Sep;102(3):775-9.
- Singh S. Bronchial challenge test in patients with a history suggestive of bronchial asthma with normal spirometric studies.. Med J Armed Forces India 2021 Jan;77(1):82-85.
- Klein HJ, Deegen E. Histamine inhalation provocation test: method to identify nonspecific airway reactivity in equids.. Am J Vet Res 1986 Aug;47(8):1796-800.
- Doucet MY, Vrins AA, Ford-Hutchinson AW. Histamine inhalation challenge in normal horses and in horses with small airway disease.. Can J Vet Res 1991 Jul;55(3):285-93.
- Vandenput S, Votion D, Duvivier DH, Van Erck E, Anciaux N, Art T, Lekeux P. Effect of a set stabled environmental control on pulmonary function and airway reactivity of COPD affected horses.. Vet J 1998 Mar;155(2):189-95.
- Miller RL, Grayson MH, Strothman K. Advances in asthma: New understandings of asthma's natural history, risk factors, underlying mechanisms, and clinical management.. J Allergy Clin Immunol 2021 Dec;148(6):1430-1441.
- Coeshott C, Ohnemus C, Pilyavskaya A, Ross S, Wieczorek M, Kroona H, Leimer AH, Cheronis J. Converting enzyme-independent release of tumor necrosis factor alpha and IL-1beta from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3.. Proc Natl Acad Sci U S A 1999 May 25;96(11):6261-6.
- Osei ET, Brandsma CA, Timens W, Heijink IH, Hackett TL. Current perspectives on the role of interleukin-1 signalling in the pathogenesis of asthma and COPD.. Eur Respir J 2020 Feb;55(2).
- Niessen NM, Gibson PG, Simpson JL, Scott HA, Baines KJ, Fricker M. Airway monocyte modulation relates to tumour necrosis factor dysregulation in neutrophilic asthma.. ERJ Open Res 2021 Jul;7(3).
- Johnson VJ, Yucesoy B, Luster MI. Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma.. J Allergy Clin Immunol 2005 Oct;116(4):851-8.
- Mitchell C, Provost K, Niu N, Homer R, Cohn L. IFN-u03b3 acts on the airway epithelium to inhibit local and systemic pathology in allergic airway disease.. J Immunol 2011 Oct 1;187(7):3815-20.
- Figueiredo CA, Rodrigues LC, Alcantara-Neves NM, Cooper PJ, Amorim LD, Silva NB, Cruz AA, Barreto ML. Does IFN-u03b3 play a role on the pathogenesis of non-atopic asthma in Latin America children?. Allergy Asthma Clin Immunol 2012 Dec 19;8(1):18.
- Ordou00f1ez CL, Shaughnessy TE, Matthay MA, Fahy JV. Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance.. Am J Respir Crit Care Med 2000 Apr;161(4 Pt 1):1185-90.
- Franchini M, Gill U, von Fellenberg R, Bracher VD. Interleukin-8 concentration and neutrophil chemotactic activity in bronchoalveolar lavage fluid of horses with chronic obstructive pulmonary disease following exposure to hay.. Am J Vet Res 2000 Nov;61(11):1369-74.
- Ainsworth DM, Gru00fcnig G, Matychak MB, Young J, Wagner B, Erb HN, Antczak DF. Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2003 Nov 15;96(1-2):83-91.
- Montgomery JB, Husulak ML, Kosolofski H, Dos Santos S, Burgess H, Meachem MD. Tumor necrosis factor-alpha protein concentrations in bronchoalveolar lavage fluid from healthy horses and horses with severe equine asthma.. Vet Immunol Immunopathol 2018 Aug;202:70-73.
- Giguu00e8re 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.
- Perkins GA, Viel L, Wagner B, Hoffman A, Erb HN, Ainsworth DM. Histamine bronchoprovocation does not affect bronchoalveolar lavage fluid cytology, gene expression and protein concentrations of IL-4, IL-8 and IFN-gamma.. Vet Immunol Immunopathol 2008 Dec 15;126(3-4):230-5.
- Pirie RS, Mueller HW, Engel O, Albrecht B, von Salis-Soglio M. Inhaled ciclesonide is efficacious and well tolerated in the treatment of severe equine asthma in a large prospective European clinical trial.. Equine Vet J 2021 Nov;53(6):1094-1104.
- Beeler-Marfisi J, Clark ME, Wen X, Sears W, Huber L, Ackerley C, Viel L, Bienzle D. Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide, and silica microspheres in horses.. Am J Vet Res 2010 Jun;71(6):682-9.
- Lavoie JP, Bullone M, Rodrigues N, Germim P, Albrecht B, von Salis-Soglio M. Effect of different doses of inhaled ciclesonide on lung function, clinical signs related to airflow limitation and serum cortisol levels in horses with experimentally induced mild to severe airway obstruction.. Equine Vet J 2019 Nov;51(6):779-786.
- 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.
- Koch C, Straub R, Ramseyer A, Widmer A, Robinson NE, Gerber V. Endoscopic scoring of the tracheal septum in horses and its clinical relevance for the evaluation of lower airway health in horses.. Equine Vet J 2007 Mar;39(2):107-12.
- Hoffman AM. Bronchoalveolar lavage: sampling technique and guidelines for cytologic preparation and interpretation.. Vet Clin North Am Equine Pract 2008 Aug;24(2):423-35, vii-viii.
- van Erck E, Votion D, Art T, Lekeux P. Measurement of respiratory function by impulse oscillometry in horses.. Equine Vet J 2004 Jan;36(1):21-8.
- van Erck E, Votion DM, Kirschvink N, Art T, Lekeux P. Use of the impulse oscillometry system for testing pulmonary function during methacholine bronchoprovocation in horses.. Am J Vet Res 2003 Nov;64(11):1414-20.
- Mazan MR, Hoffman AM, Manjerovic N. Comparison of forced oscillation with the conventional method for histamine bronchoprovocation testing in horses.. Am J Vet Res 1999 Feb;60(2):174-80.
- Lavoie JP, Cesarini C, Lavoie-Lamoureux A, Moran K, Lutz S, Picandet V, Jean D, Marcoux M. Bronchoalveolar lavage fluid cytology and cytokine messenger ribonucleic Acid expression of racehorses with exercise intolerance and lower airway inflammation.. J Vet Intern Med 2011 Mar-Apr;25(2):322-9.
- Bland JM, Altman DG. Measuring agreement in method comparison studies.. Stat Methods Med Res 1999 Jun;8(2):135-60.
- Nolen-Walston RD, Kuehn H, Boston RC, Mazan MR, Wilkins PA, Bruns S, Hoffman AM. Reproducibility of airway responsiveness in horses using flowmetric plethysmography and histamine bronchoprovocation.. J Vet Intern Med 2009 May-Jun;23(3):631-5.
- Dixon CE, Bedenice D, Mazan MR. Comparison of Flowmetric Plethysmography and Forced Oscillatory Mechanics to Measure Airway Hyperresponsiveness in Horses.. Front Vet Sci 2020;7:511023.
- 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.
- Miskovic M, Couu00ebtil LL, Thompson CA. Lung function and airway cytologic profiles in horses with recurrent airway obstruction maintained in low-dust environments.. J Vet Intern Med 2007 Sep-Oct;21(5):1060-6.
- van Den Toorn LM, Prins JB, Overbeek SE, Hoogsteden HC, de Jongste JC. Adolescents in clinical remission of atopic asthma have elevated exhaled nitric oxide levels and bronchial hyperresponsiveness.. Am J Respir Crit Care Med 2000 Sep;162(3 Pt 1):953-7.
- Giovannini M, Valli M, Ribuffo V, Melara R, Cappiello G, Businarolo E, Andreani A. Relationship between Methacholine Challenge Testing and exhaled nitric oxide in adult patients with suspected bronchial asthma.. Eur Ann Allergy Clin Immunol 2014 May;46(3):109-13.
- Wysocka B, Kluciu0144ski W. Usefulness of the assessment of discharge accumulation in the lower airways and tracheal septum thickening in the differential diagnosis of recurrent airway obstruction (RAO) and inflammatory airway disease (IAD) in the horse.. Pol J Vet Sci 2014;17(2):247-53.
- 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.
- Robinson N.E., Vet Med B., Wilson R. Airway Obstruction in the Horse. J. Equine Vet. Sci. 1989;9:155u2013160. doi: 10.1016/S0737-0806(89)80025-5.
- Fairbairn SM, Lees P, Page CP, Cunningham FM. Duration of antigen-induced hyperresponsiveness in horses with allergic respiratory disease and possible links with early airway obstruction.. J Vet Pharmacol Ther 1993 Dec;16(4):469-76.
- Cullimore AM, Secombe CJ, Lester GD, Robertson ID. Bronchoalveolar lavage fluid cytology and airway hyper-reactivity in clinically normal horses.. Aust Vet J 2018 Aug;96(8):291-296.
- Wichtel M, Gomez D, Burton S, Wichtel J, Hoffman A. Relationships between equine airway reactivity measured byu00a0flowmetric plethysmography and specific indicators of airway inflammation in horses with suspected inflammatory airway disease.. Equine Vet J 2016 Jul;48(4):466-71.
- Richard EA, Depecker M, Defontis M, Leleu C, Fortier G, Pitel PH, Couroucu00e9-Malblanc A. Cytokine concentrations in bronchoalveolar lavage fluid from horses with neutrophilic inflammatory airway disease.. J Vet Intern Med 2014 Nov-Dec;28(6):1838-44.
- Brusasco V, Crimi E, Pellegrino R. Airway hyperresponsiveness in asthma: not just a matter of airway inflammation.. Thorax 1998 Nov;53(11):992-8.
- Crimi E, Spanevello A, Neri M, Ind PW, Rossi GA, Brusasco V. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma.. Am J Respir Crit Care Med 1998 Jan;157(1):4-9.
- Brusasco V, Pellegrino R. Complexity of factors modulating airway narrowing in vivo: relevance to assessment of airway hyperresponsiveness.. J Appl Physiol (1985) 2003 Sep;95(3):1305-13.
- Boushey HA, Holtzman MJ, Sheller JR, Nadel JA. Bronchial hyperreactivity.. Am Rev Respir Dis 1980 Feb;121(2):389-413.
- Hare JE, Viel L. Pulmonary eosinophilia associated with increased airway responsiveness in young racing horses.. J Vet Intern Med 1998 May-Jun;12(3):163-70.
- Simu00f5es J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).