Allergic asthma and chronic bronchitis are inflammatory diseases affecting the lower airways of cats. In the veterinary literature, the terminology used to describe these 2 conditions is confusing and includes bronchial asthma, asthmatic bronchitis, allergic bronchitis, feline asthma syndrome, chronic bronchitis, chronic asthmatic bronchitis, chronic bronchitis with emphysema, idiopathic small airway disease, feline obstructive lung disease, feline lower airway disease, and feline bronchial disease.1–5 It is postulated that asthma in cats is allergic in etiology and is similar to human allergic asthma, caused by a Th2-lymphocyte-driven hypersensitivity reaction to inhaled aeroallergens.2,6,7 Cytokines produced by Th2 cells lead to eosinophilic airway inflammation, airway hyperreactivity, and airway remodeling (permanent architectural changes of the lung); these immunopathologic changes have been characterized in cats on the basis of allergens identified in client-owned cats with naturally developing asthma.6 The cause of chronic bronchitis is less well understood and is thought to be secondary to a previous insult (eg, infection or inhaled irritants) that damages the airways. Chronic bronchitis is characterized cytologically by inflammation with nondegenerate neutrophils.8 Because chronic allergic asthma can damage the airways, leading to variable neutrophilic inflammation, there is also overlap between these diseases (termed chronic asthmatic bronchitis).5
It is difficult to discriminate between asthma and chronic bronchitis on the basis of clinical signs alone because both can induce coughing and wheezing. Although asthma can also be associated with episodic respiratory distress that is at least in part reversible with bronchodilators, not all asthmatic cats have clinically important bronchospasm. Additionally, in rare instances, cats with chronic bronchitis may progress to development of emphysema and have expiratory distress minimally responsive to bronchodilators. Diagnostic tests used in practice to attempt to differentiate these conditions include thoracic radiography and cytologic analysis of BALF. Thoracic radiography may reveal normal findings in as many as 23% of cats,1 and other radiographic abnormalities (eg, bronchial and bronchointerstitial patterns) are frequently found in cats with asthma and those with chronic bronchitis.3 Results of cytologic examination of BALF are also problematic in discriminating between these diseases because the types of inflammatory cells are affected by the timing of exposure to aeroallergens or other inhaled irritants, concurrent secondary bacterial infections, and effects of immunosuppressive drugs or diseases.
Biomarkers—endogenously synthesized biochemical compounds used in the diagnosis, management, and prognostication of disease—have not yet been evaluated in cats with naturally occurring lower airway disease. Because of the difficulty of discriminating asthma from chronic bronchitis in cats via traditional diagnostic tests, it is worthwhile to evaluate the use of inflammatory mediators as potential biomarkers. In humans with asthma, increases in concentrations of IL-4, TNF-α, and NO metabolites or exhaled NO have been found, prompting interest into further investigation of the role of these inflammatory mediators in asthma in cats.9–11 Conversely, other studies11,12 have found that the Th1 cytokine IFN-γ is reduced in naturally developing and experimental asthma and therefore contributes to the Th2-Th1 imbalance characteristic of allergic disease. Although TNF-α has been implicated in the pathogenesis of chronic bronchitis13 and increased exhaled NO in humans with chronic bronchitis,14 it is not clear if there are differences in the magnitude of increase of these mediators in BALF between humans with asthma and those with chronic bronchitis. The purpose of the study reported here was to compare concentrations of IL-4, TNF-γ, TNF-α, and total NO metabolites in BALF supernatant of cats with naturally developing clinical asthma (CLIN ASM group), cats with naturally developing chronic bronchitis (CLIN CB group), research cats with experimentally induced allergic asthma (EXP ASM group), research cats with experimentally induced nonseptic suppurative inflammation (RES SUPP group), and healthy control cats (control group). We hypothesized that cats with allergic asthma (clinical and experimental) would have increased IL-4 concentrations and an increased ratio of IL-4 to TNF-γ, compared with cats with naturally occurring chronic bronchitis, research cats with nonseptic suppurative inflammation, and healthy control cats. Additionally, we expected cats with inflammatory airway disease (RES SUPP, EXP ASM, CLIN ASM, and CLIN CB groups) to have higher concentrations of TNF-α and NO metabolites than cats in the control group.
Bronchoalveolar lavage fluid
Naturally developing clinical asthma
Naturally developing chronic bronchitis
Experimentally induced asthma
Research cats with experimentally induced nonseptic suppuractive inflammation
Tumor necrosis factor
Fujinon EB 110, Wayne, NJ.
Tri-State Hospital Supply Corp, Howell, Mich.
BioRad Laboratories, Hercules, Calif.
R&D Systems, Minneapolis, Minn.
Savant SPP11V SpeedVac, Thermo Electron Corp, Waltham, Mass.
Gibco, Invitrogen Corp, Auckland, New Zealand.
Sigma-Aldrich, St Louis, Mo.
Benton Dickinson & Co, Franklin Lakes, NJ.
Fischer Scientific International, Pittsburgh, Pa.
Animal Health Diagnostic Center, Cornell University, Ithaca, NY.
Cayman Chemical nitrate/nitrite assay kit, Cayman Chemical Co, Ann Arbor, Mich.
Amicon Ultra, Millipore Corp, Billerica, Mass.
SigmaStat, Systat Software Inc, San Jose, Calif.
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