Feline Asthma – part 1
Germán Santamarina Pernas, DVM, PhD
Asthma may be defined as an obstructive, reversible disease that affects the lower respiratory tract. It is characterized by bronchial hyper-reaction that causes a reduction in the bronchial diameter and an excessive mucous secretion which results in a variety of signs, including coughing, wheezing and respiratory distress. It is a rare condition in the animal kingdom that has only been described with these characteristics in the feline and human species (1).
First recognised in 1906 (2), asthma is one of the most common lung diseases in cats with considerable morbidity and eventual mortality. This respiratory condition has been given various names: lower airway feline disease, allergic feline asthma, allergic acute bronchitis, immune-mediated lower respiratory tract disease and feline bronchial disease. In any case, it must be clear that feline asthma is caused by an exaggerated immune reaction towards an inhaled allergen that generates specific chemical and structural changes in the tracheobronchial tree. Clinically, feline asthma is evidenced by the relatively variable presence of coughing, wheezing, exercise intolerance and respiratory distress that can settle spontaneously or in response to medical treatment (1,3,4).
This article aims at reviewing current knowledge on the pathophysiology of asthma in cats, recognizing the most frequent clinical signs and available diagnostic methods, and addressing a practical approach for the treatment and management of these cases.
Pathophysiology and pathogenesis
As with human asthma, the pathophysiology of feline asthma is not completely understood. However, recent research with experimental antigen-induced inflammatory bronchial disease models has helped to better characterize the mechanisms of this condition (5). Asthma is a predisposition to chronic airway inflammation with reversible bronchoconstriction episodes. There are three basic pathogenic events associated with feline asthma: immune response alteration, adrenergic-cholinergic system imbalance, and increased mucous production.
Immune response alteration: T lymphocytes, mast cells and eosinophil interaction
An allergic Type I hypersensitivity reaction is probably the reason for feline asthma, as is the case with human asthma. In cats with asthma, exposure to airborne allergens that would be harmless to normal cats stimulates the production of allergenic-specific IgE antibodies. The process starts when the dendritic cells of the respiratory tract in the asthmatic patient take the antigenic particle and then migrate to the lymphatic nodes to present the novel substance to the T1 helper lymphocytes (TH1 cells). Interaction between TH1 cells and T2 helper lymphocytes (TH2 cells) induces cellular differentiation of B lymphocytes to produce specific IgE against the antigen. These IgE antibodies will then blend with mast cells and basophils in the respiratory mucous layer making them more sensitive towards a future exposure to the same antigen (1,3,4).
If re-exposure to the allergen occurs, the IgE on the surface of the sensitised mast cells attaches to the allergen, triggering a reaction that acutely releases preformed mediators, mainly histamine and serotonin. Histamine is a vasoactive amine that, when joined to other mediators, is believed to contribute to mucous secretion, increase capillary permeability and promote granulocyte chemotaxis. It has recently been demonstrated that serotonin is a primary mediator in feline mast cells which contributes to smooth muscle contraction. This mediator is not present in human, horse and dog respiratory airways. During an acute asthmatic episode in cats, the release of serotonin from mast cells provokes a sudden contraction of smooth muscles in the bronchi (1,3). For a long time, it had been assumed that the histamine released from feline mast cells was the chemical that caused the acute bronchoconstriction. This presumption has recently changed because of the finding that nebulised histamine in the cat’s airways has unpredictable effects that can vary from one individual to another. In fact, histamine can have no effect at all, or can unleash bronchoconstriction, or can even dilate a cat’s airways (1).
Activated mast cells also have the ability to release other mediators: eosinophilic chemotactic factor, interleukins 1, 2, 3, 4 and 5, granulocyte and macrophage colony stimulating factors, interferon γ, tumor necrosis factor α, prostaglandins, thromboxane A2 and leukotrienes. Interleukin-5 promotes eosinopoiesis in the bone marrow, increasing the release of mature eosinophils into the bloodstream. Moreover, interleukin-3 also promotes the differentiation of multiple eosinophil precursors. These granulocytes enter the inflammation site in the airways via the influence of several chemokines and cytokines, mainly eosinophilic chemotactic factor, leucotriens and a product of histamine degradation called imidazole-acetic acid. The survival of eosinophils is increased because of the action of interleukin-5 and granulocyte and macrophage colony stimulating factors released from the mast cells. The activated eosinophils also release inflammatory mediators, particularly the main basic protein from the eosinophil, which renders damage to the airways permanent (1,4,6).
Adrenergic-cholinergic system imbalance
Inappropriate contraction of bronchial smooth muscle is directly associated with inflammation, modifying the sympathetic-parasympathetic balance of the bronchial tree. The adrenergic system acts on the airways via β2-adrenergic receptors whose stimulation increases the production of cAMP causing bronchodilation and a reduction in mucous production. Cholinergic stimulation is opposed to β2-adrenergic action by means of the generation of cGMP causing respiratory smooth muscle to contract (bronchoconstriction), increasing mucous production and provoking vasodilation. TH2 cells and eosinophil activity contribute to the imbalance of adrenergic-cholinergic systems of the respiratory tract. This imbalance is responsible for the typical severe hyper-reaction in feline asthma that makes an asthmatic cat prone to acute narrowing of airways with only low levels of antigen stimulation (4).
Increased mucous production
An increase in mucous production is a key factor in the development of asthma, which definitely contributes to the morbidity and mortality of the disease. Goblet cells and submucosal gland cells are responsible for producing mucin in the airways. Mucin is a glucoprotein that represents the main ingredient of mucous in airways and the fundamental agent for its viscoelastic and adhesive properties. Several publications have documented severe hyperplasia and/or hypertrophy of mucous secreting cells in severe asthma cases, which represents airway remodelling (Figures 1, 2, 3). This situation leads to an increase in stored mucins and in mucins secreted in sputum. The functional aftermath of these changes include the increase in mucous production and narrowing of airways contributing to asthma aggravation.
Currently available data suggest that the action of TH2 cytokines (especially interleukin-13) plays a very important role in increasing mucous production by stimulating hyperplasia of Goblet cells in asthma cases (1, 4).
Due to the cellular infiltrate associated with chronic inflammation, airway oedema and excessive mucous secretion produce narrowing of the pulmonary tracts which impairs proper ventilation. In addition asthmatic cats can suffer from an acute narrowing of the airways due to constriction of bronchial smooth muscles leading to severe respiratory distress. Clinical signs such as coughing, wheezing and lethargy are the result of airflow restriction (1,4). Coughing can also be caused by stimulation of mechanoreceptors located in the inflamed and contracted smooth muscles of the airways. Complete blockage of a main bronchus may cause atelectasis in the corresponding lung lobe due to the inability of air to enter or leave the lungs (1,3,7).
Another typical characteristic of asthma in cats is expiratory dysfunction. The airway calibre is bigger during inspiration than during expiration. In this way a bronchial tube that is partially obstructed during inspiration can become totally blocked during expiration, leaving air trapped in the alveoli. This is why it becomes necessary to increase expiratory efforts to overcome the obstruction caused by bronchospasm and mucous excess. Under these circumstances, dramatic increase of intraluminal pressure may occur, and may even cause a permanent dilation of airways (bronchiectasis) and loss of elastic support structures (emphysema) (3,4,7).
COME BACK NEXT WEEK FOR THE SECOND HALF OF THIS ARTICLE... PRESENTATION, DIAGNOSIS & TREATMENT!
This article was kindly provided by Royal Canin, makers of a range of veterinary diets for dogs and cats. For the full range please visit www.RoyalCanin.co.uk or speak to your Veterinary Business Manager:
1. Padrid P. Asthma. In: August JR (ed). Consultations in feline internal medicine. Philadelphia: WB Saunders 2010; 447-458.
2. Hill JW. In: Jenkins WR (ed): The diseases of the cats. Diseases of the respiratory organs.. New York 1906; 11-22.
3. Bay JD, Johnson LR. Feline bronchial disease/asthma. In: King LG (ed). Textbook of respiratory disease in dogs and cats. Philadelphia: WB Saunders 2004; 388-396.
4. Byers ChG, Dhupa N. Feline bronchial asthma: pathophysiology and diagnosis. Compend Contin Educ Vet 2005; 27: 418-425.
5. Norris Reinero CR, Decile KC, Berghaus RD, et al. An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen. Int Arch Allergy Immunol 2004; 135:117-131.
6. Cohn LA. How to help the asthmatic cat breathe easy. Proceedings of the North American Veterinary Conference. Orlando, Florida 2007; 1267-1269.
7. Dye JA, McKiernan BC, Rozanski EA, et al. Bronchopulmonary 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.
8. Thébault A. Affections respiratoires chez le chat: diagnostic et traitement de l’asthme du chat. Point Vét 2004; 248: 26-30.
9. Foster SF, Martin P, Braddock JA, et al. A retrospective analysis of feline bronchoalveolar lavage cytology and microbiology (1995-2000). J Feline Med Surg 2004; 6:189-198
10. Johnson LR, Drazenovich TL. Flexible bronchoscopy and bronchoalveolar lavage in 68 cats (2001-2006). J Vet Intern Med 2007; 21: 219-25.
11. Byers ChG, Dhupa N. Feline bronchial asthma: treatment. Compend Contin Educ Vet 2005; 27: 426-431.
12. Padrid PA. Use of inhaled medications to treat respiratory diseases in dogs and cats. J Am Anim Hosp Assoc 2006; 42:165-169.
13. Cohn LA. Inhalant therapy: finding its place in small-animal practice. Vet Med 2009; 336-341.
14. Cohn LA, DeClue AE, Reinero CR. Endocrine and immunologic effects of inhaled fluticasone propionate in healthy dogs. J Vet Intern Med 2008; 22: 37-43.
15. Powell LL. Inhalation therapy. Proceedings of the North American Veterinary Conference. Orlando, Florida 2007; 220-221.
16. Reinero CR, Delgado C, Spinka C, et al. Enantiomer-specific effects of albuterol on airway inflammation in healthy and asthmatic cats. Int Arch Allergy Immunol 2009; 150: 43-50.
17. Padrid PA, Mitchell RW, Ndukwu IM, et al. Cyproheptadine-induced attenuation of type-I immediate-hypersensitivity reactions of airway smooth muscle from immune-sensitized cats. Am J Vet Res 1995; 56: 109-115.
18. Padrid PA, Cozzi P, Leff AR. Cyclosporine A inhibits airway reactivity and remodeling after chronic antigen challenge in cats. Am J Respir Crit Care Med 1996; 154: 1812-1818.
This article was previously published in 2011.