Managing allergic asthma in cats (Proceedings)

Feline allergic asthma, also called feline asthma, or feline lower airway disease, is often used to refer to a somewhat heterogeneous group of conditions affecting the lower airways of cats. Asthma is thought to be quite common in cats, with estimates suggesting that it affects 1-5% of the pet cat population. This lecture will review feline allergic asthma and its management by discussing predisposing factors, pathophysiology, history, physical examination findings, diagnostics, treatment and prognosis.

Definitions

Unfortunately there is no consensus definition for feline asthma in veterinary medicine and as such different authors use different terminology to describe feline lower airway diseases. Consequently it can be quite confusing when reviewing the literature.  The term asthma may suggest reversible bronchoconstriction, and predominantly eosinophilic inflammation. In contrast, chronic bronchitis may be associated with neutrophilic inflammation.

Predisposing factors for asthma in cats are thought to include living in the city (higher incidence than cats from more rural environments), smoking households (anecdotal), severe respiratory infection during kitten hood and environmental allergens (e.g. House dust mite, pollens etc.).

Pathophysiology

The mechanisms underlying the development of asthma in cats are postulated to be similar to those resulting in allergic asthma in humans, in which exposure to aeroallergens induces a preferential polarization of the immune response towards Th2 cytokine production (and suppression of the Th1 immune response). Th2 cytokines result in IgE production and eosinophilic inflammation & infiltration. This leads to the hallmark features of allergic asthma, namely airway inflammation, airway hyperreactivity; and airway remodeling. Mucus hypersecretion can also occur.

Signalment

Asthma is a young (to middle aged) cat disease. Old cats don't get new asthma, so asthma shouldn't be on your list of differential diagnoses for a 10 or 15 year old cat with a recent onset of cough. Female cats may be overrepresented and the Siamese breed is predisposed.

History

Asthmatic cats usually present with a history of chronic coughing. Many owners think that they are coughing up a hairball, and dismiss the cough until clinical signs worsen. Even those cats that present with an acute onset of respiratory distress (‘status asthmaticus', usually have a history of cough when the owner in questioned. Some cats have seasonal variation in the presence and severity of cough; presumably seasonal variation occurs for those cats allergic to outdoor allergens, vs. indoor allergens that are likely to be present year-round. Additionally, about 10-15% of cats are reported to vomit after coughing.

Physical examination may be normal in cats with chronic cough or can reveal moderate to severe respiratory distress (dyspnea and tachypnea) in cats presenting on an emergency basis. As with all lower airway diseases, cats with asthma have predominantly expiratory dyspnea. Thoracic auscultation may reveal pronounced crackles or wheezes. A wheeze may also be externally audible?

Diagnosis

The diagnostic approach depends a little on the severity of clinical signs at the time of presentation. Cats presenting with severe acute respiratory distress may be too unstable to safely undergo extensive diagnostic procedures, and as such, acute management may involve oxygen supplementation in an oxygen cage and a bronchodilator treatment trial (albuterol or terbutaline). A rapid, and near complete, resolution of clinical signs is suggestive of a diagnosis of feline allergic asthma. Confirmatory diagnostics include thoracic radiographs and lower airway cytology.

Abnormalities on thoracic radiographs that are consistent with allergic asthma include a generalized bronchial to bronchointerstitial pattern and hyperinflation (‘air trapping). Remember that a bronchial pattern is characterized by ‘doughnuts' and ‘tramlines'; and an interstitial pattern just reflects an increased opacity of the interstitium. Hyperinflation is often evidenced by flattening of the diaphragm, expanded lung fields and hyperlucent lungs. Occasionally cats with asthma will have collapse of the right middle lung lobe, and can even present with spontaneous pneumothorax or caudal rib fractures. Normal thoracic radiographs however do not rule out allergic asthma. Additionally thoracic radiographs are useful for excluding other causes of respiratory distress (e.g. CHF).

Obtaining samples for lower airway cytology is the only way to definitely diagnose lower airway disease. Lower airway samples can be obtained by a tracheal wash (TW) or bronchoalveolar lavage (BAL). In cats TW samples are obtained via an endotracheal approach (vs. in dogs when transtracheal samples are commonly used). BAL samples can be obtained bronchoscopically, but blind BALs are performed much more commonly. The procedure for a blind BAL is identical to that for a TW, except that for a BAL the sampling catheter must be advanced all the way in until it lodges in a bronchoalveolar unit.

Allergic asthma is characterized by predominantly eosinophilic airway inflammation (>~17% eosinophils); although other inflammatory cells may be present.

The technique that I use to obtain ‘blind' lower airway samples is as follows. Firstly I place an IV catheter, and pre-oxygenate the cat in an oxygen cage for ~5 minutes. I also usually pre-treat cats with a puff of albuterol (or an injection of terbutaline), so as to minimize airway reactivity associated with the procedure.

Anesthesia is induced with a rapidly acting agent IV. I prefer diazepam + ketamine, but others use midazolam + butorphanol, or propofol. The larynx is visualized with a laryngoscope (and lidocaine used to minimize laryngospasm PRN), and the trachea intubated with a sterile endotracheal tube. I do not usually inflate the cuff or secure the tube, since the procedure is so rapid. It is important to realize that anesthetizing a cat with severe lower airway disease to obtain airway cytology may exacerbate the respiratory status of the patient. As such, we will delay doing a BAL until clinical signs are improved with empiric treatment (oxygen and bronchodilators).

I use an 8Fr red rubber catheter as my lavage catheter and cut off the distal tip of the catheter (so that there are no longer fenestrations at the end); converting it to an open ended catheter. I make the cut with sterile scissors or a sterile scalpel blade while the tube is still inside its sterile plastic envelope. To ensure that the proximal end of the red rubber can be attached to a syringe to perform the lavage you either need to use a Christmas tree attachment, or cut off some of the proximal tip of the red rubber as well. An 8Fr red rubber catheter will comfortably fit down an ETT that is ³ 4mm, but a 5Fr red rubber is required for smaller ETTs. The proximal end of a 5Fr red rubber will attach to a syringe without adjustment.

I perform the lavage with the cat in lateral recumbence with the neck extended. With someone (an assistant) holding the cat's head, I put on sterile gloves and pass the red rubber catheter down the endotracheal tube, as far as it will go. You have to be careful so as not to traumatize the lung, so stop when you feel resistance. You can then inject sterile 0.9% saline; I usually use 10mL/lavage, injected with a 20mL syringe. When you first draw back on the syringe you should be sampling directly from a bronchoalveolar unit, and will get fluid that contains surfactant (foamy appearance).

As soon as fluid stops coming back you can then slowly withdraw the red rubber, while maintaining suction on the syringe.  You will lose your vacuum, and start to get air and fluid. I always have a sterile cup ready as well, as fluid may continue to drain out of the ETT following the lavage. If the sample is particularly productive (e.g. yields 5mL or more of fluid, that appears ‘chunky'), then I will stop. If I don't get a lot of fluid back, or it just looks like saline, then I will repeat the process another one or two times. The cat can be rotated to the other recumbence for a second sample.

Supplemental oxygen can be provided during the procedure with flow-by oxygen or attaching the ETT to an anesthesia machine and 100% oxygen.

Airway samples can be submitted for cytology and aerobic C&S. If you are doing in-house cytology in practice, the sample can be spun as for a urine sample. The supernatant is decanted and the pellet used for cytology.

Although cats rarely have pneumonia, culture is always recommended as some cats may have a secondary bacterial infection (particularly those with right middle lung lobe collapse). Additionally, mycoplasma infection is thought to play a role in triggering an asthmatic response in some cats.Additional diagnostics that are recommended include routine blood tests, a heartworm test and Baermann fecal to rule out other diseases.

A complete blood count and biochemistry profile should be performed when finances allow, for screening purposes. In most asthmatic cats these are usually normal, although a peripheral eosinophilia (> 1500 mL) may be present. FIV and FeLV testing are also recommended, especially in cats that live outdoors or in multicat households.

Heartworm testing should also be performed routinely in cats with signs of lower airway disease given the increasing recognition of feline heartworm associated respiratory disease (HARD). Heartworm antibodies can be detected on the feline 3-way snap test (along with FIV and FeLV). Unfortunately diagnosis of feline HWD may be challenging due to a small worm burden.

Cats with lower airway disease should also have a Baerman fecal performed, to evaluate for possible lung worm infection (Aelurostrongylus abstrusus); especially in young outdoor cats. Larvae may also be identified on TW/BAL. Regardless of the test result I routinely deworm with fenbendazole to cover lung worm (and other GI parasites that could potentially aberrantly migrate through the lung and precipitate inflammation).

Treatment of cats with allergic asthma involves the administration of glucocorticoids to reduce airway inflammation, and symptomatic control with bronchodilators. Additionally these cats are usually treated with fenbendazole (to cover lung worm) and heartworm prophylaxis (any of the monthly products for cats). Given the spectrum of clinical signs, therapy differs for acute crises vs. chronic management.Long-term therapy tends to reflect both the owner and the clinician's preferences.

Glucocorticoids are the mainstay of therapy for reducing airway inflammation and chronic therapy is recommended for cats that have clinical signs at least twice a week. Regardless of the type or route of corticosteroid used, the dose should be in the anti-inflammatory range. Options include oral prednisone/prednisolone, inhaled corticosteroids (e.g. Fluticasone, budesonide, others) and long-acting reposital preparations (e.g. Depo-MedrolÒ) .

When using oral prednisolone, an initial dose of 0.5-1mg/kg PO q 12 hours is recommended for the first 5-7 days (at least). Once clinical signs are well controlled, then you can start to taper the dose. Taper carefully and gradually (over 2-3 months) to a low SID or EOD dose, since clinical signs can recur if tapered too rapidly. As with the use of prednisone/prednisolone for any other disease, adverse effects can include PU/PD, polphagia and weight gain, alopecia, skin atrophy, poor wound healing and increased susceptibility to infection.

When using inhaled fluticasone, an initial dose of 110ug every 12 hours (using a metered dose inhaler and cat spacer) is recommended; however there is also evidence to suggest that 44ug q 12 hours may be effective. You can consider tapering to q 24 hours if there is no coughing for ~6 months, and potentially even stopping if there is no coughing with SID dosing.

The advantages of fluticasone (and other inhaled corticosteroids) are that they are minimally systemically absorbed and so potentially safer in cats with concurrent disease such as DM and HCM/CHF. Disadvantages include a delayed onset of action, unknown delivery to the lower airways, intolerance of inhaled route (by cat) and expense. Given that inhaled fluticasone takes about 10-14 days to be effective, it is not useful in a crisis; rather PO prednisolone must be administered concurrently for the first 3-4 weeks of therapy, and then tapered. If clinical signs of asthma were to recur on fluticasone therapy, it is recommended to start PO prednisolone is again.

The use of long-acting repository preparations such as Methylprednisolone acetate (Depo-MedrolÒ) is reserved for “bad cats” that cannot be pilled and will not tolerate inhaled medications but yet have bad clinical signs. It is dosed at 10-20mg/cat IM or SQ q 4-12 weeks, as needed to control clinical signs.

Bronchodilators are another common class of drugs used for the management of cats with allergic asthma. Options include b2-agonists and methylxanthines. Different bronchodilators should not be used concurrently in the same animal, as adverse effects will be compounded.

Inhaled albuterol is a very effective bronchodilator that is used for cats with an acute asthmatic crisis. A single dose of 90ug (administered via a MDI and spacer) will result in almost immediate clinical relief (within minutes); with maximal effect in 5-20 minutes of dosing. In addition, albuterol can be nebulized inside a closed cage (e.g. oxygen cage). Albuterol is NOT indicated for chronic use.

Terbutaline (0.01mg/kg IV or SQ) is also useful for rapid relief of clinical signs in an acute asthmatic crisis. It can also be dosed orally (0.1-0.2mg/kg PO q 8-12 hours) for chronic use in hard to control cats.

Adverse effects of b2-agonists include tachycardia, CNS stimulation, tremors and hypokalemia. These drugs should be used cautiously in cats with pre-existing DM, HCM, hypertension, hyperthyroidism or seizure disorders.

Methylxanthines are phosphodiesterase inhibitor bronchodilators that can be used chronically if needed, although tend to be used more often in dogs than cats (given variable efficacy in cats). Theophylline is available under various trade names (including Slo-bid and Theo-Dur) and a reliable generic product is made by Inwood laboratories. The recommended dose in cats in 20-25mg/kg PO q 24 hours in the evening.

Adverse effects of methylxanthines are similar to those of b2-agonists and include tachyarrhythmias, restlessness, CNS stimulation, increased gastric acid secretion and GI upset. It is also important to remember that theophylline should not be used concurrently with other drugs that require cytochrome p450 metabolism, as these will increase theophylline drug concentrations and increase the risk of side effects. Just a few such drugs that should not be used concurrently include enrofloxacin, clindamycin, erythromycin, cimetidine, and others.

Monitoring response to chronic therapy for cats with asthma may include monitoring clinical signs, repeated evaluation of BAL fluid, or barometric whole body plethysmography. Thoracic radiographs are not recommended for monitoring, since the severity of radiographic abnormalities does not correlate with clinical signs.

Specific treatment of status asthmaticus involves oxygen supplementation (usually in an oxygen cage), minimal handling / stress reduction and a dose of a b2-agonists bronchodilators (I prefer albuterol). In cats in which you have a high index of suspicion of asthma, an anti-inflammatory dose of Dex SP (e.g. 0.15mg/kg) should be given. A response to treatment is further supportive of a presumptive diagnosis of asthma. Lack of response should prompt you to re-consider your diagnosis.

A variety of novel treatments have also been assessed in cats with asthma, however thus far have failed as monotherapy. Such therapeutic failures for feline asthma include antihistamines (e.g. cetirizine), leukotriene receptor antagonists (e.g. zafirlukast) and cyproheptidine (which has antihistaminic, anticholinergic and antiserotonergic properties). Therapies undergoing evaluation as potential asthma treatments in people and cats include allergen specific immunotherapy, cyclosporine, anti-IL-5 monoclonal antibodies and omega-3 fatty acids.

Prognosis

Individual cats with asthma vary widely in their response to various therapies. That being said, the prognosis is usually good, although some cats have recurrent bouts and require frequent medications.