Coughing and wheezing cats: Diagnosis and treatment of feline asthma (Proceedings)

Lower respiratory tract disease produces typical clinical signs in cats, including chronic cough and wheeze as well as dyspnea that may have a sudden onset.1 Owners may report an increase in respiratory rate (>30-40 breaths per minute), increased expiratory effort and lethargy. Clinical signs may be mild to severe and may be chronic or intermittent.

Differential diagnoses include heartworm disease2-3 , viral, bacterial or fungal infection, inhaled foreign body, cardiac disease, thoracic disease, neoplasia, and pulmonary parasites (ascarids, lungworms, lung flukes). Essentially, a diagnosis of feline asthma is a diagnosis of exclusion. Diagnosis involves a thorough history and physical examination as well as a minimum database (complete blood count, serum chemistries, urinalysis, and retrovirus serology). Other diagnostic tests for feline lower airway disease include thoracic radiographs, bronchoscopy and/or bronchoalveolar lavage with cytology and culture, feline heartworm serology, and fecal analysis. The most common radiographic abnormalities in cats with bronchial disease are bronchial and interstitial patterns, pulmonary hyperinflation and hyperlucency, aerophagia, and pulmonary soft tissue opacities.1,4

Feline Asthma

Feline asthma is one of a spectrum of conditions under the umbrella of chronic lower airway disease or bronchopulmonary disease that also includes chronic bronchitis. Feline asthma may also be called allergic airway disease or allergic bronchitis. There are important similarities between feline asthma and human asthma, and limited evidence suggests that some environmental allergens can cause disease in both cats and humans.5

Since feline asthma is characterized by airway inflammation and bronchoconstriction, therapy is aimed at reversing these changes. There are many treatments for feline asthma, including some experimental modalities borrowed from human medicine. Many of these treatments have not been well evaluated in the cat.

Treatment of Lower Airway Disease Patients with Acute Clinical Signs

Patients in acute respiratory distress may be unstable and should be examined and treated with great care. Some drugs may cause a temporary increase in heart and respiratory rate. When using combination drug therapy, be aware of the risk of arrhythmia in stressed, hypoxic cats. Some very anxious and stressed dyspneic cats may benefit from mild sedation with a low dose of acepromazine (0.05 mg/kg, IM, SQ).

First line therapy:

     • Supplemental oxygen: Preferably using an oxygen cage

     • Bronchodilators: Best via nebulizer or metered dose inhaler as the effects are seen within 5 minutes (versus 15-30 minutes by injection); give 2-4 puffs of inhaled drugs such as albuterol every 20 minutes; repeat injectable drugs in 15 minutes if required

     • Short-acting corticosteroid: Intravenous dexamethasone or prednisolone sodium succinate; may take 3-6 hours for maximum effect; useful in cats on chronic oral bronchodilator therapy to reverse down-regulation of airway β-adrenergic receptors causing drug tolerance

Second line therapy:

     • Anticholinergics: Atropine, glycopyrrolate; block vagal input causing bronchoconstriction and decrease bronchial secretions; not useful for long term therapy as these drugs will cause increased viscosity of airway mucus

Third line therapy:

     • Epinephrine: α- and β-agonist, can reverse bronchoconstriction; may cause arrhythmia

Treatment of Chronic Lower Airway Disease

Corticosteroids are the cornerstone of treatment for feline asthma as control of inflammation leads to clinical control.6 Inflammation exists even in the absence of clinical signs. Treatments can be combined to create tailored regimes. In general, the simpler and easier the treatment regime is, the more likely owner compliance will be achieved.

Feline asthma patients should be re-evaluated every 3 to 6 months and owners should be instructed to alert the veterinarian promptly if respiratory distress develops or the cat's clinical signs worsen.

Oral Therapy

     • Antibiotic therapy: Not usually indicated for treatment of feline asthma. However, Mycoplasma has been isolated from the airways of 25% of cats with lower airway disease, while it is not found in the airways of clinically healthy cats.7 It may be reasonable to treat feline asthma patients for Mycoplasma with doxycycline for 14 days if they do not respond to corticosteroid treatment within 5-7 days.

     • Corticosteroids: Appropriate for long-term oral therapy but must monitor for adverse effects, especially diabetes mellitus. The dose should be tapered carefully, with many cats achieving alternate or every third day therapy in the long term. Repository corticosteroid injections are more likely to cause adverse effects and cats may become refractory to corticosteroid treatment more readily with this approach. In general, repository corticosteroids should be reserved for very fractious cats or non-compliant owners. Frequency of administration should be not more often than every 2 months.

     • Bronchodilators:

          o Methylxanthines: Weak bronchodilators, narrow therapeutic window; adverse effects include vomiting and diarrhea, hyperactivity, muscle tremors. Oral aminophylline is not recommended as adverse effects are common. Only the sustained-release forms of theophylline produced by Inwood Laboratories should be used in cats (Theocap ER 19 mg/kg, q24h; Theochron ER 15 mg/kg, q24h)8

          o β-agonists: Effective bronchodilators, primary side effects are tachycardia and hypertension, β2-agonists have fewer cardiac side effects (e.g. terbutaline)

Inhalant Therapy

The administration of inhaled steroids and bronchodilators via metered dose inhalers (MDIs) has revolutionized treatment of feline asthma.9-10 Using a nebulized radiopharmaceutical, it has been shown that inhaled medications can be distributed to the lower airways in cats.11 With use of inhaled medications, systemic side effects can be effectively minimized or eliminated.12

In cats with moderate to severe asthma, oral corticosteroids are recommended for the first few weeks of therapy, and the dose can be tapered as the cat responds to the inhaled medications. If a patient is being switched from oral therapy to inhaled therapy, the transition should occur over a period of at least one week. Some severely asthmatic cats require every second day oral corticosteroid dosing concurrent with inhaled medications, although up to 80% of cats can be maintained on inhaled corticosteroids alone.13

Each inhaler delivers a set dose per actuation ("puff") and contains a fixed number of doses. MDIs require slow, deep inhalation on the part of the patient. This type of inspiration is not possible for infants and animals, so a spacer and mask must be used. Spacers decrease the amount of drug deposited in the oropharynx.

A spacer and facemask is available for veterinary patients (AeroKat?, Trudell Medical International). The spacer and mask must be applied to the cat's face before the MDI is actuated. The spacer has an indicator valve (Flow-Vu indicator) that makes it easier for the owner to tell when the cat takes a breath. This is a superior system for use with cats as it has been optimized for the smaller feline tidal volume.

The most commonly used inhaled corticosteroid is fluticasone, but others are sometimes available (e.g. beclomethasone) and may be less expensive (although potentially less effective). Fluticasone has the longest half-life of the available inhalant corticosteroids, is the most potent, and the least likely to be absorbed systemically. A corticosteroid inhaler used twice daily should be the cornerstone of therapy. A typical starting dose is 1-2 puffs twice daily using 44 mcg fluticasone.12

Recent evidence suggests it may be difficult to determine optimal corticosteroid dosing based on clinical signs. In humans, resolution of clinical signs is known to be a poor predictor of the degree of airway inflammation. In a small study of 9 cats with asthma receiving prednisolone for 3 weeks or more, all cats had resolution of clinical signs. However, only 3 of the cats had resolution of airway inflammation based on bronchoalveolar lavage fluid analysis.14

Inhalers containing bronchodilators are also widely used and are inexpensive. Albuterol (salbutamol) is a short acting β2-agonist that relaxes smooth muscle and increases airflow within five minutes of administration. The effect of albuterol will last four to six hours. A bronchodilator inhaler may be used two to four times daily initially, but for most patients, they should be reserved for occasional use in acute bronchoconstriction to avoid development of tolerance. It has also been demonstrated that long term use of inhaled albuterol may exacerbate inflammation.15 Patients with mild intermittent disease may be treated with a bronchodilator alone on an as-needed basis.

Inhaled medications are more expensive than oral medications, and a certain cost is associated with purchase of the spacer and mask. However, for cats that are difficult to medicate orally and for owners who wish to minimize long-term effects of oral corticosteroids, MDIs are a good choice. Most cats readily learn to tolerate the spacer and mask after some initial training. Owners must be carefully instructed on care and use of the spacer, mask and MDI.

Immunotherapy

Feline asthma is believed to be a type I hypersensitivity to aeroallergens. Immunotherapy, particularly allergen-specific rush immunotherapy, is undergoing evaluation for treatment of asthma in cats.16-17 Development of an effective protocol is necessary, as well as reliable methods to selection antigens. Intradermal skin testing and allergen-specific IgE determination via ELISA (Allercept™, Heska Laboratories) have been evaluated in an experimental asthma model. Both test methodologies are suitable for guiding selection of antigens for immunotherapy.18 However, a liquid phase enzymoimmunometric assay for IgE (VARL Liquid Gold, Veterinary Allergy Reference Laboratories) was unreliable and not recommended.18

Other Control Measures for Cats with Asthma

Certain measures can help reduce or prevent acute attacks, such as avoiding contact with cats showing signs of upper respiratory tract infection, and prevention or treatment of excess weight gain. Avoidance of known aerosol triggers may also be prudent, such as dusty or scented cat litter, air fresheners and room deodorizers, cleaning agents, fumigants, cigarette and wood fire smoke, etc. HEPA filters can help reduce aeroallergens. A few cats with asthma will respond favourably to a hypoallergenic diet, so a 4 to 8 week trial may be justified.

References

1. Foster S, Allan G, Martin P, et al. Twenty-five cases of feline bronchial disease (1995-2000). J Fel Med Surg 2004;6:181-188.

2. Atkins CE. Reassessing the definition of heartworm infection in cats. J Am Vet Med Assoc 2007;231:1338.

3. Browne LE, Carter TD, Levy JK, et al. Pulmonary arterial disease in cats seropositive for Dirofilaria immitis but lacking adult heartworms in the heart and lungs. Am J Vet Res 2005;66:1544-1549.

4. Gadbois J, d'Anjou M-A, Dunn M, et al. Radiographic abnormalities in cats with feline bronchial disease and intra- and interobserver variability in radiographic interpretation: 40 cases (1999-2006). Journal of the American Veterinary Medical Association 2009;234:367-375.

5. Reinero CR, DeClue AE, Rabinowitz P. Asthma in humans and cats: is there a common sensitivity to aeroallergens in shared environments? Environ Res 2009;109:634-640.

6. Padrid P. Feline asthma: diagnosis and treatment. Vet Clin North Am Sm Anim Pract 2000;30:1279-1293.

7. Randolph J, Moise N, Scarlett J, et al. Prevalence of mycoplasmal and ureaplasmal recovery from tracheobronchial lavages and of mycoplasmal recovery from pharyngeal swab specimens in cats with or without pulmonary disease. Am J Vet Res 1993;54:897-900.

8. Guenther-Yenke CL, McKiernan BC, Papich MG, et al. Pharmacokinetics of an extended-release theophylline product in cats. J Am Vet Med Assoc 2007;231:900-906.

9. Padrid P. Use of inhaled medications to treat respiratory diseases in dogs and cats. J Am Anim Hosp Assoc 2006;42:165-169.

10. Cohn LA. Inhalant therapy: finding its place in small-animal practice. Veterinary Medicine 2009;104:336-341.

11. Schulman RL, Crochik SS, Kneller SK, et al. Investigation of pulmonary deposition of a nebulized radiopharmaceutical agent in awake cats. Am J Vet Res 2004;65:806-809.

12. Cohn LA, DeClue AE, Cohen RL, et al. Effects of fluticasone propionate dosage in an experimental model of feline asthma. J Feline Med Surg 2010;12:91-96.

13. Padrid P. Inhaled steroids to treat feline lower airway disease: 300 cases 1995-2007. American College of Veterinary Internal Medicine Forum 2008;456-458.

14. Cocayne C, DeClue A, Reinero C. Subclinical airway inflammation despite oral corticosteroid therapy in cats with lower airway disease (abstract). J Vet Intern Med 2010;24:701.

15. 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.

16. Lee-Fowler TM, Cohn LA, DeClue AE, et al. Evaluation of subcutaneous versus mucosal (intranasal) allergen-specific rush immunotherapy in experimental feline asthma. Vet Immunol Immunopathol 2009;129:49-56.

17. Reinero CR, Cohn LA, Delgado C, et al. Adjuvanted rush immunotherapy using CpG oligodeoxynucleotides in experimental feline allergic asthma. Vet Immunol Immunopathol 2008;121:241-250.

18. Lee-Fowler TM, Cohn LA, Declue AE, et al. Comparison of intradermal skin testing (IDST) and serum allergen-specific IgE determination in an experimental model of feline asthma. Vet Immunol Immunopathol 2009;132:46-52.