Asthma (Proceedings)

What disease(s) are we really talking about?

Although feline asthma is among the most commonly diagnosed respiratory conditions in cats, there is still a lot of confusion about how to define or classify this condition or how to differentiate it from other lower respiratory tract problems.

In recent years a number of different terms have been proposed to help classify disorders of the lower respiratory tract of cats. In many cases, these are still very general terms that primarily describe localization (e.g. bronchi) or relevant diagnostic test results (e.g. inflammatory cells in an airway wash). In other cases, there has been an attempt to describe the etiology (e.g. allergy) or make distinctions based on clinical signs (e.g. bronchitis when cough is predominant, asthma when reduced airflow or dyspnea). From this larger discussion of terminology it has been suggested, and largely accepted, that feline non-infectious lower airway (or bronchial) diseases can be divided into two general categories of chronic bronchitis and asthma.

There seems to be general agreement that a diagnosis of asthma should imply certain characteristic features including: 1) chronicity with variable and recurrent clinical signs, 2) reduction in airflow, 3) bronchial hyperresponsiveness, 4) increased mucous production, 5) lower airway inflammation, and 6) lack of a specific infectious etiology. Some authors also remain adamant that asthma in cats has allergic basis and is associated with spontaneous bronchoconstriction, unlike other lower airway inflammatory diseases. Overall, however, there is currently no widely accepted, standardized specific criterion for making a specific diagnosis of feline asthma (as opposed to chronic bronchitis).

From a practical standpoint, there is so much overlap in the clinical and diagnostic features of feline asthma and feline chronic bronchitis that distinguishing the two conditions in a clinical setting can be quite challenging. For an individual veterinarian, cat, or client it may also not make that much difference given our current level of understanding of the two conditions and currently available therapeutic options.

Pathophysiology

Numerous factor have been implicated in the development of asthma in humans, including allergies, environmental irritant substances/pollutants, exercise, stress, and medications. Almost all of these factors have also been reported to cause lower respiratory tract disease in cats, but in general, feline asthma has been considered to be an allergic condition, while respiratory problems secondary to the other factors are often classified as separate conditions.

Cases of true allergic disease, or asthma, likely represent type I hypersensitivity reactions. Initiation of the process occurs when potential allergens are inhaled, taken up and processed by dendritic cells in the airways, and then presented in conjunction with MHC II molecules to naïve CD4+ lymphocytes. In susceptible individuals, when these lymphocytes are activated in the presence of appropriate co-stimulatory molecules, the immune response is polarized towards a Th2 response. The cytokines produced by this (especially IL4, IL5, and IL13) orchestrate an inflammatory response in which allergen-specific IgE is produced and eosinophils, basophils, and mast cells all become involved. When the cat is re-exposed to the allergen, IgE bound to mast cells becomes cross-linked and results in degranulation, leading to further exacerbation of the inflammatory cascade.

Tissue responses and injury resulting from degranulation of mast cells and eosinophils include smooth muscle contraction, increased vascular permeability, edema, damage to / sloughing of the protective epithelial lining of the airways, enhanced local neural responsiveness. Long term changes can include epithelial metaplasia and proliferation, hyperplasia of mucous glands with excess mucous production, impaired mucociliary clearance, hypertrophy and hyperplasia of smooth muscle, fibrosis, and emphysematous changes in the pulmonary parenchyma.

In non-allergic bronchitis, similar tissue injury can be seen as a result of the oxidative damage caused by neutrophilic inflammation.

Clinical presentation

Cats of any age can develop bronchial diseases, but the condition is most often diagnosed in young to middle-aged cats. There is no recognized sex predilection. Many cats are overweight, but it is not clear if there is any direct cause or effect relationship with the disease (e.g. less activity due to the disease, greater respiratory effort and airway pressures due to weight).

Classic clinical signs can range from chronic cough, lethargy, exercise intolerance, or loud breathing, to tachypnea, labored breathing with increased expiratory effort, or episodes of acute respiratory distress. Coughing may be seemingly random, associated with specific environmental stimuli, or relatively persistent. Observation of breathing patterns may reveal normal breathing between acute episodes. During periods of acute asthma attacks, some cats may only demonstrate tachypnea, but often careful observation will also reveal an increase in the time and effort of the expiratory phase of breathing or an end-expiratory push/grunt. If episodes are typical short and self limiting, it can be useful to have clients obtain a video recording of the episode.

Thoracic auscultation may not reveal any abnormalities in some cats, especially if the patient is between episodes and observed to be breathing normally. However, many cats do have "harsh" lung sounds, wheezes (typically expiratory), or crackles (inspiratory).

Diagnostic testing

Since there are no standardized criteria for making a diagnosis of feline asthma or bronchitis, it is essentially always a presumptive diagnosis based on the exclusion of other likely differentials. In addition, as will be covered in the next section, one of the mainstays of therapy is long-term corticosteroids which has some obvious potential drawbacks and should only be administered after careful consideration of the risk/benefit to the patient.

There are therefore two main aims to any diagnostic plan for these conditions: 1) to rule out other potential causes of the clinical signs (especially those that with a significantly different prognosis, or with different treatments) and 2) to accumulate supportive evidence for the presumptive diagnosis and gather as much information as possible about the specific underlying pathologic changes in the patient.

Testing for differential diagnoses

While a minimum data base (serum chemistry, CBC, and urinalysis) is unlikely to contribute much to the diagnosis of inflammatory bronchial disease, it can be an important source of information about other potential diseases (i.e. a severe neutrophilia might raise concern for pneumonia or LRT infection) or provide evidence of other problems that would have to be taken into account when considering therapeutic options (i.e. diabetes, high liver enzymes, etc..)

Screening tests for airway parasites and heartworm are also commonly recommended, although the strength of the recommendation may vary depending upon risk factors (e.g. geography, history of preventative medications...). Testing for parasites typically involves performing both a fecal floatation and Baermann examination. Testing for heartworm disease in cats should include both antigen and antibody testing +/- echocardiography.

Thoracic radiographs are likely to be performed to help support the diagnosis of asthma or bronchitis, but also have a role in screening for other differentials. In general, there are almost no specific or pathognomonic patterns for most respiratory diseases, but certainly the presence of a single pulmonary nodule, generalized cardiomegaly, enlarged pulmonary vessels, pleural effusion, or any other abnormality that is not the "classic" bronchial/peribronchial pattern should prompt consideration of additional diagnostic testing.

Any airway sample collected to help establish a diagnosis should also be cultured to help rule out primary or secondary infections. I typically perform both general aerobic cultures and Mycoplasma spp cultures. Although the specific role of Mycoplasma spp. In feline inflammatory bronchial diseases remains unknown, I treat any symptomatic cat with a positive culture.

Supportive diagnostic testing

Finding of a peripheral eosinophilia, especially in a patient with compatible clinical signs and no evidence of parasitic infestation anywhere can help support the diagnosis. The absence of eosinophilia does not exclude the diagnosis.

The majority of cats with inflammatory bronchial disease will have a bronchial pattern on thoracic radiographs, often in association with evidence of pulmonary hyperinflation (flattened diaphragm, increased space between the heart and diaphragm). However, these changes are neither sensitive nor specific for non-infectious inflammatory bronchial disease. Other potential thoracic radiographic finding could include a mild interstitial pattern, right middle lobar collapse, or even a normal pulmonary appearance.

To achieve more than a presumptive diagnosis, analysis of an airway wash sample, or histopathology is required. Even with these tests, there can be a lot of overlap between the subsets of inflammatory bronchial disease, but there are a few key elements that can help with differentiation. When parasitic diseases have been ruled out, the finding of a mixed inflammatory population of cells with an increased percentage of eosinophils supports a diagnosis of asthma, whereas chronic bronchitis more typically has a predominant population of non-degenerate neutrophils. [This is not without some controversy however, as there is a wide variation in the reported ranges for eosinophil % in apparently healthy cats.]

There are an array of pulmonary function tests that are widely used in humans to assist in the diagnosis and management of asthma. These tests provide information about the restriction of airflow in asthma patients and can also be used to assess the results of provocation with allergic stimuli or response to certain therapeutic agents. Unfortunately, performing these tests is a bit more challenging in cats than in humans and they are generally only available on a limited basis at a few referral institutions.

Identification of specific allergens responsible for perpetuation of the condition is a common goal of diagnostic testing as it may provide opportunities for directed immunotherapy. Either intradermal skin testing (IDST) or serum allergen-specific IgE can be used, but based on one comparative study IDST appears to be the better test.

Therapeutic options

Emergency situations

Acute respiratory distress due to spontaneous bronchoconstriction can be a feature of feline asthma. Often the diagnosis is presumptive based on the clinical presentation of increased expiratory effort/time. In these cases, further confirmatory diagnostic testing should be kept to a minimum and initial efforts should be focused on stabilizing the patient. Stabilization is achieved by provision of a comfortable oxygen enriched environment and administration of a short acting bronchodilator. Injectible terbutaline is often the first choice (over inhaled medications) due to reliable dose delivery. If no response is seen, short acting corticosteroids can also be provided, but it should be remembered that these may interfere with later diagnostic testing.

Stable patients

Corticosteroids remain the mainstay of therapy for inflammatory bronchial diseases including asthma. In general, short acting medications (as opposed to depository injections) are preferred. The evidence for using these medications comes primarily from experimental and retrospective clinical studies. I typically start patients with oral prednisolone. If there are difficulties with administration, development of side effects, other concerns about long-term steroid use, or client preference for alternative routes of administration, then I will consider switching to inhalant steroid therapy.

Bronchodilators are also commonly used in treating feline asthma, but should not be considered appropriate as a long-term monotherapy as they have only limited effects (if any) on the underlying inflammation that exacerbates clinical signs and contributes to progression of the disease. In addition, there is some evidence that commonly used inhalant albuterol may actually exacerbate airway inflammation if administered chronically.

A form of allergen-specific immunotherapy called rush immunotherapy (RIT) has shown some promise in experimental settings. In cases where the sensitizing allergen is known or suspected based on testing, RIT protocols could be attempted.

There is currently no good evidence for the use of antihistamines or leukotriene inhibitors in cases of feline inflammatory bronchial disease. This does not exclude the possibility that certain individual cats or a currently unrecognized subset of feline patients might benefit from their use. I do not recommend these medications for my patients that this point, however.