Editorial Type:
Respiratory System

Evaluation of biomarkers in bronchoalveolar lavage fluid for discrimination between asthma and chronic bronchitis in cats

Laura A. Nafe Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Search for other papers by Laura A. Nafe in
Current site
Google Scholar
PubMed Close
 DVM
,
Amy E. DeClue Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Search for other papers by Amy E. DeClue in
Current site
Google Scholar
PubMed Close
 DVM, MS
,
Tekla M. Lee-Fowler Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Search for other papers by Tekla M. Lee-Fowler in
Current site
Google Scholar
PubMed Close
 DVM
,
Jason M. Eberhardt Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Search for other papers by Jason M. Eberhardt in
Current site
Google Scholar
PubMed Close
 DVM
, and
Carol R. Reinero Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Search for other papers by Carol R. Reinero in
Current site
Google Scholar
PubMed Close
 DVM, PhD
DOI:
https://doi.org/10.2460/ajvr.71.5.583
Volume/Issue:
Volume 71: Issue 5
Online Publication Date:
01 May 2010
Restricted access
Sign In Reprints and Permissions Purchase Article

Abstract

Objective—To compare concentrations of interleukin (IL)-4, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and total nitric oxide (NO) metabolites in bronchoalveolar lavage fluid (BALF) for discrimination between asthma and chronic bronchitis in cats.

Animals—97 cats.

Procedures—Cats screened with cytologic examination of BALF included 13 client-owned cats with naturally developing asthma, 8 client-owned cats with chronic bronchitis, 23 research cats with experimentally induced asthma, 33 research cats with experimentally induced nonseptic suppurative inflammation of the airways, and 20 healthy control cats. Banked unconcentrated BALF supernatant samples were assayed for concentrations of IL-4, IFN-γ, TNF-α, and total NO metabolites.

Results—Concentrations of IL-4 and IFN-γ in BALF were less than the limits of detection for most cats, precluding statistical analysis. No significant differences were detected among groups for TNF-α concentrations. Concentrations of total NO metabolites were significantly higher in cats with clinical chronic bronchitis, compared with research cats with nonseptic suppurative inflammation or research cats with asthma.

Conclusions and Clinical Relevance—There were no significant differences in tested biomarkers between cats with asthma and healthy control cats. None of the measured cytokines or NO metabolites were useful for discriminating between cats with naturally developing asthma and those with chronic bronchitis.

Abstract

Objective—To compare concentrations of interleukin (IL)-4, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and total nitric oxide (NO) metabolites in bronchoalveolar lavage fluid (BALF) for discrimination between asthma and chronic bronchitis in cats.

Animals—97 cats.

Procedures—Cats screened with cytologic examination of BALF included 13 client-owned cats with naturally developing asthma, 8 client-owned cats with chronic bronchitis, 23 research cats with experimentally induced asthma, 33 research cats with experimentally induced nonseptic suppurative inflammation of the airways, and 20 healthy control cats. Banked unconcentrated BALF supernatant samples were assayed for concentrations of IL-4, IFN-γ, TNF-α, and total NO metabolites.

Results—Concentrations of IL-4 and IFN-γ in BALF were less than the limits of detection for most cats, precluding statistical analysis. No significant differences were detected among groups for TNF-α concentrations. Concentrations of total NO metabolites were significantly higher in cats with clinical chronic bronchitis, compared with research cats with nonseptic suppurative inflammation or research cats with asthma.

Conclusions and Clinical Relevance—There were no significant differences in tested biomarkers between cats with asthma and healthy control cats. None of the measured cytokines or NO metabolites were useful for discriminating between cats with naturally developing asthma and those with chronic bronchitis.

Contributor Notes

Presented in part at the 18th Annual European College of Veterinary Internal Medicine Congress, Ghent, Belgium, September 2006.

The authors thank Matt Haight, Hong Liu, Rachael Cohen, and Drs. Chee-Hoon Chang, Carol Haak, and Claire Sharp for technical support.

Address correspondence to Dr. Reinero (reineroc@missouri.edu).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 May 2010
  • 1.

    Adamama-Moraitou KK, Patsikas MN, Koutinas AF. Feline lower airway disease: a retrospective study of 22 naturally occurring cases from Greece. J Feline Med Surg 2004;6:227–233.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Corcoran BM, Foster DJ, Fuentes VL. Feline asthma syndrome: a retrospective study of the clinical presentation in 29 cats. J Small Anim Pract 1995;36:481–488.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Foster SF, Allan GS, Martin P, et alTwenty-five cases of feline bronchial disease (1995–2000). J Feline Med Surg 2004;6:181–188.

  • 4.

    Moriello KA, Stepien RL, Henik RA, et alPilot study: prevalence of positive aeroallergen reactions in 10 cats with small-airway disease without concurrent skin disease. Vet Dermatol 2007;18:94–100.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Moise NS, Wiedenkeller D, Yeager AE, et alClinical, radiographic, and bronchial cytologic features of cats with bronchial disease: 65 cases (1980–1986). J Am Vet Med Assoc 1989;194:1467–1473.

    • Search Google Scholar
    • Export Citation
  • 6.

    Norris Reinero CR, Decile KC, Berghaus RD, et alAn experimental model of allergic asthma in cats sensitized to house dust mite or Bermuda grass allergen. Int Arch Allergy Immunol 2004;135:117–131.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Prost C. Treatment of feline asthma with allergen avoidance and specific immunotherapy: experience with 20 cats. Rev Fr Allergol Immunol Clin 2008;48:409–413.

    • Search Google Scholar
    • Export Citation
  • 8.

    Kirschvink N, Leemans J, Delvaux F, et alInhaled fluticasone reduces bronchial responsiveness and airway inflammation in cats with mild chronic bronchitis. J Feline Med Surg 2006;8:45–54.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Brightling C, Berry M, Amrani Y. Targeting TNF-alpha: a novel therapeutic approach for asthma. J Allergy Clin Immunol 2008;121:5–10.

  • 10.

    Jang AS, Choi IS, Lee S, et alNitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects. Clin Exp Allergy 1999;29:1136–1142.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Shahid SK, Kharitonov SA, Wilson NM, et alIncreased interleukin-4 and decreased interferon-gamma in exhaled breath condensate of children with asthma. Am J Respir Crit Care Med 2002;165:1290–1293.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Koch M, Witzenrath M, Reuter C, et alRole of local pulmonary IFN-gamma expression in murine allergic airway inflammation. Am J Respir Cell Mol Biol 2006;35:211–219.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Mukhopadhyay S, Hoidal JR, Mukherjee TK. Role of TNFalpha in pulmonary pathophysiology. Respir Res 2006;7:125.

  • 14.

    Delen FM, Sippel JM, Osborne ML, et alIncreased exhaled nitric oxide in chronic bronchitis: comparison with asthma and COPD. Chest 2000;117:695–701.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Dye JA, McKiernan BC, Rozanski EA, et alBronchopulmonary disease in the cat: historical, physical, radiographic, clinicopathologic, and pulmonary functional evaluation of 24 affected and 15 healthy cats. J Vet Intern Med 1996;10:385–400.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Baarsch MJ, Wannemuehler MJ, Molitor TW, et alDetection of tumor necrosis factor alpha from porcine alveolar macrophages using an L929 fibroblast bioassay. J Immunol Methods 1991;140:15–22.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    DeClue AE, Cohn LA, Lechner ES, et alEffects of subanesthetic doses of ketamine on hemodynamic and immunologic variables in dogs with experimentally induced endotoxemia. Am J Vet Res 2008;69:228–232.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Dargaville PA, South M, Vervaart P, et alValidity of markers of dilution in small volume lung lavage. Am J Respir Crit Care Med 1999;160:778–784.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 2008;8:183–192.

  • 20.

    Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 2008;118:3546–3556.

  • 21.

    Cohn L, Herrick C, Niu N, et alIL-4 promotes airway eosinophilia by suppressing IFN-gamma production: defining a novel role for IFN-gamma in the regulation of allergic airway inflammation. J Immunol 2001;166:2760–2767.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Reinero CR, Byerly JR, Berghaus RD, et alRush immunotherapy in an experimental model of feline allergic asthma. Vet Immunol Immunopathol 2006;110:141–153.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Reinero CR, Cohn LA, Delgado C, et alAdjuvanted rush immunotherapy using CpG oligodeoxynucleotides in experimental feline allergic asthma. Vet Immunol Immunopathol 2008;121:241–250.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Larche M. Immunoregulation by targeting T cells in the treatment of allergy and asthma. Curr Opin Immunol 2006;18:745–750.

  • 25.

    Romagnani S. The role of lymphocytes in allergic disease. J Allergy Clin Immunol 2000;105:399–408.

  • 26.

    Brusselle GG, Kips JC, Tavernier JH, et alAttenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy 1994;24:73–80.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Mueller R, Chanez P, Campbell AM, et alDifferent cytokine patterns in bronchial biopsies in asthma and chronic bronchitis. Respir Med 1996;90:79–85.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Broide DH, Paine MM, Firestein GS. Eosinophils express interleukin 5 and granulocyte macrophage-colony-stimulating factor mRNA at sites of allergic inflammation in asthmatics. J Clin Invest 1992;90:1414–1424.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev 1998;50:515–596.

  • 30.

    Hartl D, Griese M, Nicolai T, et alPulmonary chemokines and their receptors differentiate children with asthma and chronic cough. J Allergy Clin Immunol 2005;115:728–736.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Wong CK, Ho CY, Ko FW, et alProinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol 2001;125:177–183.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Marguet C, Dean TP, Warner JO. Soluble intercellular adhesion molecule-1 (sICAM-1) and interferon-gamma in bronchoalveolar lavage fluid from children with airway diseases. Am J Respir Crit Care Med 2000;162:1016–1022.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Kumar RK, Webb DC, Herbert C, et alInterferon-gamma as a possible target in chronic asthma. Inflamm Allergy Drug Targets 2006;5:253–256.

  • 34.

    Keatings VM, Collins PD, Scott DM, et alDifferences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996;153:530–534.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    Katsuki M. Neutrophil chemotactic activity in bronchoalveolar lavage fluid recovered from patients with diffuse panbronchiolitis. Kurume Med J 1996;43:279–287.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Dweik RA, Comhair SA, Gaston B, et alNO chemical events in the human airway during the immediate and late antigen-induced asthmatic response. Proc Natl Acad Sci U S A 2001;98:2622–2627.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    van der Vliet A, Eiserich JP, Shigenaga MK, et alReactive nitrogen species and tyrosine nitration in the respiratory tract: epiphenomena or a pathobiologic mechanism of disease? Am J Respir Crit Care Med 1999;160:1–9.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Kumar L, Rajput N, Majumdar S. Nitric oxide metabolites in induced sputum: a noninvasive marker of airway inflammation in asthma. Indian Pediatr 2005;42:329–337.

    • Search Google Scholar
    • Export Citation
  • 39.

    Payne DN. Nitric oxide in allergic airway inflammation. Curr Opin Allergy Clin Immunol 2003;3:133–137.

  • 40.

    Kharitonov SA, Barnes PJ. Nitric oxide in exhaled air is a new marker of airway inflammation. Monaldi Arch Chest Dis 1996;51:533–537.

  • 41.

    Liu MC, Proud D, Lichtenstein LM, et alEffects of prednisone on the cellular responses and release of cytokines and mediators after segmental allergen challenge of asthmatic subjects. J Allergy Clin Immunol 2001;108:29–38.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Reinero CR, Brownlee L, Decile KC, et alInhaled flunisolide suppresses the hypothalamic-pituitary-adrenocortical axis, but has minimal systemic immune effects in healthy cats. J Vet Intern Med 2006;20:57–64.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Herbert C, Hettiaratchi A, Webb DC, et alSuppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma. Clin Exp Allergy 2008;38:847–856.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Hawkins EC, DeNicola DB, Kuehn NF. Bronchoalveolar lavage in the evaluation of pulmonary disease in the dog and cat. State of the art. J Vet Intern Med 1990;4:267–274.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45.

    Jatakanon A, Uasuf C, Maziak W, et alNeutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 1999;160:1532–1539.

  • 46.

    Sampson AP. The role of eosinophils and neutrophils in inflammation. Clin Exp Allergy 2000;30(suppl 1):22–27.

Advertisement