Understanding and treating feline asthma (Proceedings)

Feline asthma arises from a heterogeneous and poorly characterized group of conditions of the bronchi. "Asthma" is technically caused by reversible bronchospasm (sudden constriction of the smooth muscle of the small bronchi), which is triggered by an underlying inflammatory process. Inflammation in the airway may be brief and transient, or may be a chronic ongoing process. Bronchial inflammation occurs in numerous species, and is mediated by neutrophils, monocytes/macrophages, eosinophils, mast cells and lymphocytes, IgE, histamine, PAF, leukotrienes, prostaglandins, interleukins and TNF. Cats with asthma, like people, seem to have hyper-responsiveness of the airway smooth muscle, and a given stimulus or degree of inflammation leads to a greater degree of bronchospasm in asthmatic cats than it does in normal cats. Clinical signs include coughing and dyspnea, caused by inflammation and bronchospasm.

Chronic inflammation and narrowing of the small bronchi can lead to a number of serious changes in the lung. The lesions in the small bronchi primarily affect expiration. Since the negative pressure exerted by the lung parenchyma on the small bronchi during inspiration tends to "stent" the airways open, inhalation can occur normally. When exhalation occurs, however, the small bronchi tend to collapse because they are narrowed and weakened by inflammation. Early closure of small bronchi during exhalation results in air trapping in the lung and an expiratory respiratory distress. Clinically, lung overdistention with air can be recognized by the presence of over-inflated lungs and a flattened diaphragm on thoracic radiographs. As the lungs become overdistended, emphysema (breakdown of alveolar septal walls) can develop at the periphery of the lungs, leading to decreased alveolar surface area for gas exchange. Persistent mucous plugs in narrowed airways may lead to the development of absorbtive atelectasis (manifested as an alveolar pattern) as the lung collapses distal to the obstructive airway. The right middle lung lobe is particularly susceptible to collapse in asthmatic cats.

Do we know why cats have hyper-responsive airways?

Acute and/or chronic inflammation of bronchi occurs in numerous species: canine chronic bronchitis, equine 'heaves", feline asthma/bronchitis and human asthma/bronchitis. Interestingly, smooth muscle hyper-reactivity to inflammation does not occur in all species. It is well documented in cats, horses, and humans, but does not appear to occur in dogs. The reasons for this lack of bronchospasm in the smooth muscle of canine airways are not well understood. One theory involves differences in the innervation of the airway smooth muscle between species. In all species, the airways are innervated by parasympathetic cholinergic pathways which mediate bronchoconstriction, and by sympathetic adrenergic pathways which mediate bronchodilation. Most species also have miscellaneous pathways including tachykinin-containing nerves, rapidly and slowly adapting receptors, and unmyelinated C fibers. In addition, cats, horses and people (but not dogs) have a non-adrenergic vagal inhibitory pathway (NANC) which causes bronchodilation, for which vasoactive intestinal peptide (VIP) and nitric oxide appear to be the mediators. NANC appears to be a remnant of a primitive inhibitory nervous system, which is present in both the GI and the respiratory tracts. In humans, absence of GI NANC leads to loss of inhibition and spasm of GI smooth muscle (Hirschsprung's disease). It is possible that a defect in the NANC system in the feline respiratory tract could result in the hyper-reactive airways we see in feline asthma. Since NANC does not appear to exist in the canine respiratory tract, this could explain the absence of a parallel disease in the dog.

Clinical signs of feline asthma

Classical acute feline asthma is often an eosinophilic inflammatory disorder. These cats have marked acute bronchoconstriction and inflammation that may be triggered by specific allergens. They can present with acute and severe dyspnea. In these cases, once the acute phase has passed and bronchospasm resolves, the animal can return to perfectly normal function, and thoracic radiographs taken after resolution of the crisis will be normal. Clinical signs in these cats are primarily caused by bronchospasm, with an additional contribution from the inflammation. Other cats have more chronic inflammation of the bronchi with infiltrates of inflammatory cells (including neutrophils, eosinophils, or macrophages) that surround the bronchi. Accompanying the inflammatory cells, there is hyperemia and edema of the bronchial mucosa, increased numbers of goblet cells, and increased secretion of mucus. In these cats, a chronic cough is often recognized because the inflammation is ongoing. Intermittent reversible exacerbations of disease may occur, but the underlying inflammatory disease seems to persist between each exacerbation. Thus, thoracic radiographs obtained between incidences of respiratory distress may show varying amounts of peribronchial inflammation.

Differential diagnosis of coughing in cats

• Feline asthma

• Chronic bronchitis

• Bronchiectasis

• Emphysema

• Parasitic infestation

• Aspirated foreign bodies

• Chronic bronchopneumonia

• Pulmonary fungal infections (Cryptococcosis)

• Pulmonary Toxoplasmosis

• Cranial mediastinal masses

• Heartworms (Dirofilaria immitis)

Diagnostic testing for cats suspected to have asthma/bronchitis

Cats presenting with signs consistent with feline asthma or bronchitis require some diagnostic testing to confirm the diagnosis and direct therapy. If the cat presents in a respiratory crisis caused by bronchospasm, diagnostic testing to confirm the diagnosis should be postponed till after the cat has been stabilized. Emergency stabilization may include treatment with bronchodilators administered parenterally or by inhalation, and/or anti-inflammatory doses of glucocorticoids administered parenterally.

Physical examination

On auscultation, wheezes may be heard indicating narrowing of small airways, sometimes crackles are ausculted representing the sound of small airways snapping open and closing. The heart should sound normal on auscultation in an uncomplicated case of feline asthma.

Blood tests

Most of these patients deserve a basic clinical workup including a complete blood count, chemistry panel, urinalysis, and heartworm testing. The intent is to determine the presence of organic or systemic disease that may be contributing to chronic cough. Testing for Feline Leukemia Virus and Feline Immunodeficiency Virus may be indicated.

Radiographs

Thoracic radiographs are vital in evaluation of cats suspected to have asthma. Typically, radiographs are normal or have a peribronchial pattern. The lungs may be hyperinflated, evidenced by a flattened diaphragm and an increased distance between the caudal border of the heart and the diaphragm. Although atelectasis can occur because of occlusion of small airways in cats with asthma, the finding of alveolar disease should prompt consideration of other disorders such as bronchopneumonia, neoplasia, or congestive heart failure. Bronchiectasis can be evident as a cylindrical dilation of bronchi as they extend to the periphery of the lung lobes, rather than their usual tapering. Masses may be evident in lung lobes or compressing the airways. Radio-opaque foreign bodies may be seen. Lastly, intraluminal masses, abscesses, parasitic nodules or foreign bodies may be outlined by the negative contrast of air in the major airways.

Fecal flotation for parasites

In areas where lungworms are endemic, a Baermann preparation should be performed to detect the presence of lungworm larvae in the stool. It must be remembered that lungworm larvae may not be present in the stool, as their numbers may be low or they may be intermittently shed. Usually fecal samples are evaluated three days in a row, and if there is a strong suspicion of the presence of lungworms, anthelminthic therapy may be initiated even if the results are negative.

Cultures and respiratory cytology

When a bronchoscope is not available, diagnostic samples may be obtained by endotracheal washing. Because of the inherent risks associated with anesthesia and increased tracheal and bronchial inflammation, this technique should be used cautiously in cats with feline asthma. When available, bacterial and fungal cultures from the airway may be diagnostic if bronchopneumonia or bronchiectasis is present, but should not be over-interpreted in the presence of chronic bronchitis. Although positive bacterial cultures are obtained in some patients with chronic airway disease, the bacteria may be colonizing the inflamed airway rather than primary pathogenic agents. Cytologic samples may show evidence of toxoplasma tachyzoites, fungal yeast forms, or lungworm larvae, and they occasionally reveal neoplastic cells. The type of inflammatory cell can also provide useful information, for example the presence of a predominant population of eosinophils in tracheal wash fluid.

Other

Congestive heart failure is a common cause of chronic coughing in dogs, but is unlikely to cause coughing in cats. However, congestive heart failure is a common cause of dyspnea in cats, and is therefore an important differential for feline asthma. Heart disease may require evaluation with echocardiography and electrocardiography.

Initial stabilization

Cats that present with severe dyspnea associated with bronchospasm require aggressive but careful management. They should be immediately placed in an oxygen cage, and manipulated as little as possible to minimize stress, maximize oxygen delivery, and minimize oxygen consumption. Observation of the cat while it is resting in oxygen allows determination of the respiratory pattern. Classically, cats with asthma have expiratory dyspnea with increased abdominal effort on exhalation. Clinically, however, almost any respiratory pattern may be recognized.

Drug therapy

If there is a high index of suspicion of an asthmatic crisis, there are two main therapeutic aims. First, acute bronchodilation must be achieved, and secondly, the inflammation that is the underlying cause of the bronchoconstriction must be addressed. It is important that drugs not be given orally to the dyspneic patient.

Bronchodilators

We have found that the 2 agonists, particularly terbutaline (0.01 mg/kg IV or IM) are particularly helpful in management of cats presenting in an asthmatic crisis. Bronchodilators such as aminophylline can be considered, but are often less effective and must be diluted in large volumes for parenteral administration. In patients that fail to respond to terbutaline, epinephrine (0.5-0.75 ml of a 1:10,000 solution can be given IM or SQ) can be used in an aggressive attempt to achieve bronchodilation by its effects. Before administration of a parenteral bronchodilator, the cat should be carefully evaluated to confirm that there is no evidence of heart disease. Parenteral administration of a beta agonist to a cat with hypertrophic cardiomyopathy could result in worsening of dyspnea and tachycardia, with progression of congestive heart failure. If a murmur or gallop rhythm is detected on physical examination, then this category of drugs should be avoided, and instead corticosteroids become the most important therapeutic modality. Bronchodilators can be a useful part of long term therapy if corticosteroids are contraindicated, or if the cat is refractory to steroids. They require oral administration up to three times daily, compared to once daily, or even every other day, for steroids. Recognizing that inflammation is the underlying cause of bronchospasm, it is recommended that cats should not receive bronchodilators alone (without corticosteroids) for asthma therapy.

Corticosteroids

Anti-inflammatory to immunosuppressive doses of short-acting corticosteroids should also be administered to counteract the underlying inflammation that is resulting in bronchoconstriction. Dexamethasone (0.2-1 mg/kg IV or IM) is our drug of choice because of its low cost and easy availability. By addressing the underlying inflammatory process, corticosteroids decrease edema, minimize mucus production, and minimize the subsequent bronchospasm. Steroids are well tolerated by most cats, and do not cause many of the unwelcome side-effects that are recognized in dogs and people. Although corticosteroids have been implicated as an acute cause of increased intravascular volume which can precipitate progression to congestive heart failure, a single dose of steroids does not seem to cause clinical problems in the dyspneic cat, and if there is concern then a low dose of furosemide can be administered concurrently. The dose of corticosteroids is variable, depending on the condition and requirements of the individual cat. Following stabilization of the crisis, oral administration of prednisolone has been the mainstay of therapy for many years. Most clinicians begin with a fairly high dose (Prednisone 1-2 mg/kg PO BID), and rapidly taper to a low maintenance dose. Cats should be maintained on the minimum dose that controls their disease. Many cats can be completely weaned from steroids, with resumption of therapy when their disease recurs. Some cats require life-long therapy to control clinical signs.

Aerosolization of drugs in crisis management

Both bronchodilators (albuterol) and corticosteroids (fluticasone) can be administered by inhalation. However, they may not effectively be distributed to all parts of the lower respiratory tract if the patient is dyspneic, and the mask may not be tolerated by all dyspneic cats. Thus, aerosol administration should not be used instead of parenteral drug therapy, but rather as an adjunct in addition to parenteral drugs. If there is concern about possible cardiomyopathy, the use of inhaled albuterol may be a good option for bronchodilation that avoids systemic drug levels. Similarly, aerosolization of fluticasone may represent a good option if corticosteroids are contraindicated, eg in a diabetic cat.

Follow-up

Most cats with asthma respond well to rest, oxygen supplementation, and parenteral treatment with a 2 agonist and corticosteroids, and are significantly improved within about 30 minutes of drug administration. Cats that fail to respond to this therapy and remain dyspneic should be evaluated for other disorders such as pleural effusion, pneumothorax or heart disease. Severely dyspneic cats may require anesthesia and intubation in order to perform diagnostic tests.

References available on request