Medical therapy of feline asthma (Proceedings)

Feline asthma consists of an inflammatory disorder of the lower respiratory system of cats that results in bronchoconstriction and limited airflow to the lungs. Successful therapy of this condition starts with appropriate management of the animal environment and the selection of therapeutic combinations that safely address the long-term and short term needs of the animal. Over the last few years, newer products and routes of administration have allowed to increase safety and efficacy of drug management practices. This report will review some of the newer agents and management practices.

Objectives of the presentation

• To review the basic pathophysiology of feline asthma.

• To discuss environmental management issues.

• To discuss the pharmacologic basis of medical treatment.

• To evaluate current treatment approaches.

Key pathophysiologic points

• The major signs of feline asthma include recurrent episodes of cough and dyspnea resulting from bronchoconstriction.

• Although the pathophysiology of feline asthma is not completely understood, it is presumed to originate as a type I hypersensitivity reaction. Inhaled allergens react with immunoglobulin E (IgE) that is bound to previously sensitized mast cells. This stimulates the degranulation of mast cells and the sudden release of inflammatory mediators (histamine, serotonin, cytokines, etc) locally. These mediate the vasodilatation, vascular leakage and smooth muscle spasm that characterizes the initial response phase,  as well as the vascular permeability, neutrophil and eosinophil attraction and the bronchial spasm that characterize the asthma attack.

Relevant therapeutic points

• Asthma in cats is believed to have an important allergic/inflammatory component1,2. Likely allergens include dust, cigarette smoke, mildew and mold, parasitic proteins, pollen, cat litter, and possibly household chemicals. Although there is no conclusive proof of an allergic etiology in cats, some studies suggest that allergen avoidance contribute significantly to control this condition3,4. While exact determination of the causing allergen/s may be a difficult task, many can be easily eliminated. These include cigarette smoke, mildew and mold and household chemicals. Other potential allergens such as pollen or dust may require the use of air purifiers. Clay cat litter often needs to be replaced with pine or silicone, preferably unscented.

• Although it has been suggested that dietary hypersensitivity may be related to feline asthma, there is no scientific evidence supporting such point.

• Although the acute clinical signs (cough and dyspnea) are related to bronchial constriction, treatment with bronchodilators alone, without addressing the underlying inflammatory process, is not likely succeed in the long run.

• Treatment directed to decrease the inflammatory component of the disease while addressing occasional flare-ups constitute the most appropriate strategy.

• Decision to treat can be based on both frequency and severity of symptoms. Orientative guidelines have been proposed5:

• Moderate symptoms occur less than once weekly in untreated patients:

• Treat patients with bronchodilators to correct the acute episodes.

• Moderate symptoms occur more than once weekly in untreated patients:

• Treat with an oral corticosteroid, e.g. prednisolone 1-2 mg/kg q12h PO for 5-7 days.

• If signs frequency decreases, slowly taper the dose over the next 2-3 months.

• Treat with bronchodilators as needed for acute exacerbations.

• Alternatively:

• Treat with an oral corticosteroid, e.g. prednisolone 1 mg/kg q12h PO for 5 days and then q24h for 5 more days.

• Treat with one 100 µg fluticasone puff q12h

• If after 10 days of combined oral/inhaled therapy signs improve, the cat can be weaned off the oral prednisolone.

• Treat with bronchodilators as needed for acute exacerbations.

Drugs, dosages and indications

• Corticosteroids

• Among other actions, corticosteroids inhibit cytokine gene expression, stabilize cell membranes, and decrease the production of inflammatory mediators.

• They represent the most effective long-term treatment therapy for asthma in humans6.

• Long-term treatment with oral and parenteral corticosteroids causes serious adverse effects including, among others, hyperadrenocorticism, diabetes mellitus, immunosuppression, weight gain, and suppression of the hypothalamic-pituitary-adrenal (HPA) axis.

• Inhaled steroids have a reduced potential for side effects and toxicity, although adrenal suppression may occur7.

• Current standards of corticosteroid use dictate that the dose should be titrated to the lowest level that effectively controls clinical signs or results in normal thoracic radiographs. However, cats may still have subclinical inflammation that can lead to airway remodeling4,8. We may then wonder whether we should evaluate symptoms or radiographs to make effective treatment decisions, or if cytologic evaluation from bronchoalveolar lavage (BAL) samples should be used instead.

• Oral steroids

• Prednisolone.

• Dosed at 1-2 mg/kg q12h initially for 7-14 days.

• Dose can be later tapered or entirely substituted by inhalant steroids.

• Prednisolone should be used instead of prednisone due to its better absorption profile.

• Inhaled steroids

• Fluticasone:

• Large molecule with poor systemic absorption from the lung.

• It acts locally in the airway mucosa, but the slow absorption prevents it from being fully effective until 1-2 weeks after treatment initiation.

• Minimal immunosuppressive effects, although it can still suppress the HPA7.

• Reduced eosinophilic airway inflammation in experimental feline asthma9.

• Dose not well established but typically used at 110-200 µg/puff q12h, depending on the severity of the symptoms.

• A study with 5 experimentally asthmatic cats did not find difference in efficacy between the 44 µg and 220 µg actuations in twice-a-day regimens10.

• Injectable steroids

• Methylprednisolone:

• Dose at 10-20 mg/cat IM once every 4-8 weeks.

• Side effects are more likely than with oral administration.

• It should only be used if the oral or oral/inhalation protocol are not practical.

• Bronchodilators

• Asthmatic cats typically develop bronchoconstriction, in some cases severe.

• Not indicated for chronic therapy but to treat acute exacerbations of asthmatic symptoms.

• Beta-agonists:

• Selective beta2-agonists are less prone to cardiovascular adverse effects.

• Albuterol:

• Administer when bronchoconstriction takes place (wheeze, noisy breathing).

• Short-acting beta-2 agonist administered orally or by inhalation.

• Administered via a metered-dose inhaler (MDI) with a spacer, similar to that used for small children. Inhalation form delivers 90 µg/puff with.

• Bronchial dilation takes place in 1-5 minutes. In severe cases it can be used every 30 minutes for up to 6 hr.

• Side effects are not common. Administer with caution in patients with underlying cardiac condition, hypertension, hyperthyroidism and diabetes mellitus.

• Terbutaline:

• Available as tablet, elixir, and SQ or IM injections.

• Reported parenteral dose is 0.01 mg/kg

• Reported oral dose is 0.1-0.2 mg/kg q8h

• Can be used as an alternative to inhaled albuterol to control acute respiratory symptoms.

• At home use by clients by the SQ route in emergency cases.

• Bronchodilation is observed within 15-30 minutes (50% decrease or more in respiratory rate)

• Cyproheptadine:

• Antiserotonin properties. Serotonin is one of the inflammatory mediators of asthma.

• Although it prevents antigen-induced respiratory smooth muscle constriction in vitro11, its clinical potential has not been fully demonstrated in vivo.

• While it might be indicated for symptomatic cats already receiving full doses of steroids and beta-2 agonists, further studies are needed to understand its usefulness.

• Leukotriene antagonists: Montelukast and zafirlukast.

• They antagonize the action of a type of leukotriene (cysteinyl leukotriene, cysLT) that is associated to asthma in certain human subpopulations.

• CysLT does not seem to differ between normal and asthmatic cats12.

• Although there are some anecdotal reports of efficacy of zafirlukast (1-2 mg/kg q12h) and montelukast (0.5-1 mg/kg q24h) in the treatment of feline asthma, more conclusive evidence is needed before these agents can be used regularly.

Table 1. Common drug and doses used in the treatment of feline asthma

Drug

Drug Class

Dose Regimen

Prednisolone

Corticosteroid

1-2 mg/kg q12h PO, 7-14 days

1 mg/kg/day PO, afterwards

Methylprednisolone

Corticosteroid (long-acting)

10-20 mg/cat IM every 4-8 wks

Fluticasone

Corticosteroid

110 µg/puff q12h by MDI

Range: (44-220 µg)

Albuterol

Beta2-agonist

90 µg/puff by MDI, as needed for acute control for up to 6 hr.

Terbutaline

Beta2-agonist

0.01 mg/kg SQ, as needed for control of acute symptoms

REFERENCES

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