Treating feline bronchial disease

Q: What is the standard of care for cats diagnosed with bronchitis or asthma?

A: Dr. Philip Padrid gave an excellent lecture entitled "Inhaled steroids to treat feline lower-airway disease: 300 cases 1995-2007" at last year's American College of Veterinary Internal Medicine (ACVIM) Forum in San Antonio. Here are some relevant points from it:

Chronic bronchial disease in cats occurs most commonly as chronic bronchitis and asthma. Chronic bronchitis is defined as an inflammatory disorder of the lower airways that causes a daily cough, for which other causes of cough (including heartworm disease, pneumonia, lungworms and neoplasia) have been excluded. Asthma is more loosely defined as a disorder of the lower airways that causes airflow limitation, which may resolve spontaneously or in response to medical treatment.

Airflow limitation generally is the result of some combination of airway inflammation, accumulated airway mucus and airway smooth-muscle contraction. The signs of asthma can be dramatic, including acute wheezing and respiratory distress. Sometimes, however, the only sign of asthma-induced airflow limitation is a daily cough.

Definitive diagnosis of asthma usually is based on specific pulmonary function studies that require a cat's cooperation. Because both disorders, bronchitis and asthma, can cause a daily cough as the only clinical sign, there are many times when it is not possible to distinguish bronchitis from asthma in the cat. Nevertheless, the diagnosis, prognosis and treatment options for both diseases overlap with great frequency.

Inhaled medications

Inhaled corticosteroids and broncho-dilators have been formally recommended to treat cats with bronchial asthma since at least 1993. Since then, a number of articles have demonstrated the clinical effectiveness of fluticasone for treatment of cats with allergic rhinitis, bronchitis and asthma. There have been no controlled published studies to determine the optimal dose or interval for use of fluticasone in cats.

Aerosol administration of the medications to cats relies on delivery of drugs to the distal airways, which in turn depends on the size of the aerosol particles and various respiratory parameters, such as tidal volume and inspiratory flow rate. Recent published studies in cats have demonstrated that passive inhalation through a mask and spacer combination is an effective method of delivering sufficient medication to be clinically effective.

Drugs for inhalation typically come in a rectangular-metered dose inhaler (MDI) or a round "disk" form. At present, only the MDI form is practical for use in cats. Recently, the propellants used for these medications have changed. The efficacy of the medication delivered by the newer propellant has not been affected.

The most effective means of using an MDI involves coordination between inhalation and actuation of the device, something that is not reliable in most infants, small children or animals. For this reason, an alternative involves the use of a spacer device and a mask specifically designed for cats. A small, aerosol-holding chamber is attached to an MDI on one end and a face mask on the other. The spacer is approximately the size of the inner cardboard roll used with toilet paper. The MDI supplies precise doses of the aerosol drug, and the holding chamber contains the aerosol so it can be inhaled when cats inspire. The mask is designed to cover the cat's nose.

The designers of one popular spacer have shown that a holding chamber with a length of 11 cm and a diameter of >3.5 cm delivered almost all of a therapeutically "ideal" aerosol (i.e., aerosol of equivalent aerodynamic diameter <2.8 mcg) produced by an MDI, and in some cases delivery was enhanced because of evaporation of large, suspended particles.

The choice of spacer is relevant because cats have a tidal volume of between 5 ml and 10 ml inspired air per pound of body weight.

Using these spacer devices, cats will inhale the majority of drug propelled into the spacer by breathing seven to 10 times through the spacer-mask combination after actuation of the MDI.

It is important to teach the owner to observe the cat actually breathing, because cats initially may hold their breath when introduced to this form of treatment.

The procedure is not time-consuming, but it can be helpful to acclimate the cat to the mask. When administering inhalation therapy, the MDI is first shaken to open an internal valve within the canister, and then it is attached to the spacer. The mask attached to the other end of the spacer is placed snuggly on the animal's nose or muzzle, and the MDI is pressed to release the medication into the spacer.

Fluticasone propionate

The primary signs of chronic bronchial disease include cough and wheeze, and these signs are frequently the result of some degree of airway smooth muscle contraction. In clinical practice, it usually is difficult to distinguish between chronic bronchitis and asthma in coughing cats. It is tempting to treat coughing cats with suspected bronchial disease by using only bronchodilators to relax the airway smooth muscle contraction. Although this is a central method of treatment when acute signs develop, it is critically important to understand that asthmatic and bronchitic airways show evidence of chronic ongoing inflammation whether the cat is symptomatic or not. Therefore, treatment strategies are most successful if they are directed toward decreasing the underlying inflammatory component of the disease in addition to addressing the acute clinical signs of cough, wheeze and increased respiratory effort.

Long-term corticosteroids

The most effective long-term treatment of chronic non-infectious bronchial disease is systemically administered corticosteroids. This class of drugs is most likely to suppress airway inflammation, a process orchestrated by a network of proteins (cytokines) that act on circulating and structural airway cells. An important effect of steroids is to inhibit the synthesis of genes for cytokines that are important in generating airway inflammation.

The side effects of systemic steroid medications given for long periods are undesirable. Fortunately, inhaled steroids have become available that do not cause systemic side effects, and this therapeutic approach has greatly enhanced our ability to treat cats with bronchial disease.

Treatment of bronchitic or asthmatic cats begins with signs that occur more than once weekly (without medication) and includes prednisolone, 1 to 2 mg/kg orally every 12 hours for five to seven days.

At this point, the majority of newly diagnosed cats have greatly diminished signs. The dose of steroids is then tapered slowly, over at least two to three months. This approach is much more effective than giving low doses of prednisone for short periods and in response to acute flare-ups.

Cats with signs that occur less than once weekly (without medication) generally are not considered to have chronic active inflammatory airways. These cats may be safely treated with bronchodilators when needed.

Some cats are effectively and safely managed by administration of low-dose, alternative-day corticosteroids. However, most cats with chronic bronchial disease continue to wheeze/cough when treated in this conservative manner. For cats with a good response to higher doses of consistently administered systemic corticosteroids, inhaled corticosteroid therapy should be encouraged as an alternative to reduce adverse effects.

The most commonly used inhaled corticosteroid is fluticasone propionate, a synthetic corticosteroid with an 18-fold higher affinity for the corticosteroid receptor when compared to dexamethasone. Binding of the steroid to this receptor results in a new molecular complex that leads to up or down regulation of the gene and its products. Fluticasone, like other corticosteroids, acts to inhibit mast cells, eosinophils, lymphocytes, neutrophils and macrophages involved in the generation and exacerbation of allergic airway inflammation by transcriptional regulation of these target genes. Preformed and newly secreted mediators including histamine, eicosanoids, leukotrienes and multiple cytokines are inhibited as well.

Fluticasone is a large molecule and acts topically within the airway mucosa. Because there is delayed absorption across mucosal epithelium, there is minimal oral systemic bioavailability. Plasma levels do not predict therapeutic effects. This explains the lack of systemic side effects. Optimal clinical effects, therefore, may not occur for one to two weeks.

The drug usually comes in three strengths: 44 mcg, 110 mcg and 220 mcg per actuation. The 44-mcg dosing twice daily does not consistently result in acceptable clinical responses. For cats with mild to moderate disease, 110 mcg given twice daily frequently results in clinical responses equivalent to that achieved by administration of 5 mg oral doses of prednisone given BID. Cats with more serious disease may require 220 mcg inhaled BID. Administration of fluticasone more than twice daily has not resulted in clinical benefit.

Albuterol sulfate

The use of bronchodilators, including albuterol, is based on the assumption that clinically significant bronchoconstriction is evident. Cats develop naturally occurring and clinically significant bronchoconstriction that in severe cases can be life-threatening. Bronchodilator drugs can be beneficial to these cats. These drugs are classified generally as beta-receptor agonists, methylxanthine derivatives, or anti-cholinergics.

Albuterol is a selective beta2-receptor agonist that produces relaxation of the smooth muscle found principally in bronchial, vascular and uterine tissues. The exact mechanism by which activation of beta2 (beta-2) receptors results in smooth-muscle relaxation is not totally understood, but it likely involves intracellular cAMP induced suppression of the kinase controlling myosin and actin interaction.

At usual doses, albuterol has little effect on beta1 (beta-1) receptors; hence, direct cardiostimulatory effects are minimal. However, albuterol should always be used with care in cats that may have increased sensitivity to adrenergic agents — in particular, cats with pre-existing cardiac disease, diabetes mellitus, hyper-thyroidism, hypertension or seizure disorders.

All beta-2 agonists may lower plasma potassium; hence, it may be prudent to monitor serum potassium levels in at-risk cats receiving long-term albuterol therapy. In clinical practice, it is uncommon to find beta-2 agonist associated hypokalemia in cats.

When albuterol is used with other sympathomimetics, the risk of adverse cardiovascular effects increase, as does its concurrent use with digoxin, tricyclic antidepressants and monoamine oxidase inhibitors. These potential effects are more likely in cats with pre-existing cardiac disease, especially hypertrophic cardiomyo-pathy. Use with various inhalation anesthetics may predispose the cats to ventricular arrhythmias.

Albuterol is available as a tablet, syrup and is contained in various inhalants. The inhaled form comes as a single-strength, 17-gram metered dose inhaler and delivers 90 mcg per actuation of the device.

The pharmacokinetic profile of albuterol in cats has not been reported. When administered by inhalation, albuterol produces significant bronchodilation within 15 minutes that lasts three to four hours. It is well absorbed orally and may have bronchodilatory effects for up to eight hours. Anecdotal experience with this drug in clinical practice suggests a similar pharmacokinetic profile in cats. Albuterol can be used once daily prior to administering fluticasone or as needed for acute coughing and wheezing. In emergency cases, albuterol can be used every 30 minutes for up to four to six hours without serious side effects.

Albuterol undergoes extensive hepatic metabolism. After oral administration, 58 percent to 78 percent of the dose is excreted in the urine over 24 hours, with 60 percent in an inactive form.

Rarely, adverse effects include mild skeletal muscle tremors and restlessness, which generally subside in two to three days.

The use of inhaled medications to treat asthma and bronchitis is considered the standard of care in cats with chronic bronchial disease. This approach avoids many of the side effects previously seen in cats treated with systemic medications.

Dr. Hoskins is owner of Docu-Tech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: jdhoskins@mindspring.com.