The Wheezing Cat: Lower Respiratory Disease

Clinical Signs

Clinical signs of lower airway disease most commonly include coughing with or without periodic respiratory distress. Audible wheezes and prolonged expiration or an expiratory push may be appreciated. Upper airway diseases should result in prolonged inspiratory phase, by contrast. Cats are usually 1 year to about 9 or 10 years when first affected. Kittens with cough should be evaluated for an underlying disease such as parasitic migration or for another cause such as nasopharyngeal polyp. Older cats, while they will continue to have asthma throughout their lives should not develop asthma for the first time as geriatrics. Any time asthma is suspected in an old cat, a complete evaluation should be performed, as a distinct underlying condition is much more likely present.

Some cats have a syndrome more consistent with asthma, reversible bronchoconstriction in response to inhaled allergens. Other cats are more similar to chronic bronchitis with cough, excessive mucous and bronchial thickening. Still others are difficult to distinguish. The underlying cause is often unknown and the role of viral respiratory infections, a common cause of asthma in genetically susceptible infants, is unclear. Some cats are affected seasonally and others year round. Certain cats appear sensitive to environmental contaminants such as dusty cat litter, tobacco smoke or aerosol fragrances. Secondary spontaneous pneumothorax has been reported. Clinical signs of affected cats include cough, wheeze and respiratory distress.

Thoracic radiology is the main source of diagnosis. Affected cats have a bronchial or bronchointerstitial pattern. Hyperinflation due to air trapping and right middle lung lobe collapse from a mucous plug may occur.

Baseline work up is usually unremarkable. In endemic areas, heartworm antigen and antibody testing and Baermann fecal for lungworms is indicated. Bronchoalveolar lavage appears unable to distinguish between chronic bronchitis and asthma but is useful to evaluate for other causes such as neoplasia or infection.

Pre-oxygenate for 10 minutes, intubate using a sterile tube. Infuse 3-6 mls of sterile saline into the tube and collect for cytology.

Acute Signs

Acute therapy includes supplemental oxygen therapy, glucocorticoids and bronchodilators. Cats with lower airway disease should improve with in 4-6 hours. In acute situations 2-4 mg/cat of dexamethasone IV. 5-10 mg/cat prednisolone may be needed foe a period of time. As bronchoconstriction is common, albuterol 1-2 puffs every 6 hours or terbutaline (0.01 mg/kg SQ) is often helpful.

The distinction between cardiac and respiratory distress may be difficult. Rapid assessment by ECG is ideal, however the cardiac biomarker NT pro-BNP may be helpful to exclude a diagnosis of heart disease. Pulmonary infection is not common in cats but must be excluded before commencing corticosteroid therapy.

Chronic

Chronic therapy is aimed at removal of any identifiable triggers and glucocorticoids. Inhaled corticosteroids reduce the risk of systemic effects but require administration via face mask and spacer. (Aerokat, Trudell Medical, London and Ontario).Typically oral glucocorticoids precede inhaled therapy and are given simultaneously for a period followed by tapering of oral form.

Several drugs have been shown to be of no help: cyproheptadine, cetirizine, zafirlukast, and maropitant.

Fluticasone is the inhaled corticosteroid most commonly used. Dosage is not certain. This author starts fluticasone at 110mcg/cat twice daily. Combination products such fluticasone with the long-acting bronchodilator salmeterol improved efficacy in one study. For cats who do not respond well to oral corticosteroids, the inhaled form is unlikely to be helpful. Cyclosporine has been described as helpful (10 mg/kg PO q 12 hours) with improvement in airway hyperresponsiveness and amelioration of cytologic inflammation. It is a potent immunosuppressive so blood levels should be monitored as well as potential for pathogens to gain a foothold with an impaired immune system. Doxycycline or Azithromycin is prescribed if infection is suspected, but this is uncommon.

Future therapeutic options are promising including rush immunotherapy which has been effective in research cats. Masitinib and fish oil may be useful after further research. Stem cell therapy research is ongoing for long-term disease control.

Improving Indoor Air Quality

Key elements of improved air quality are source control, adequate ventilation (especially in shower, laundry, and cooking areas), maintaining relative humidity between 30–50%, changing air filters on a regular basis, and air duct cleaning as needed. To limit dust accumulation, use a quality vacuum with a high-efficiency filter weekly. Water leaks should be promptly repaired, and after any flooding, areas should be thoroughly cleaned and dried. If materials cannot be dried promptly, they should be replaced. CO monitors should be installed in the home. All gas appliances should be properly functioning or inspected and adequately cleaned and repaired. Gas stoves and heaters should be vented to the outside of the home. Owners should be reminded that gas ranges should never be used as a heat source. Smoke detectors, along with the enforcement of improved building codes, are effective in reducing fire-related deaths. Owners should be cautioned about so-called air purifiers that use ionization as a means of "clearing the air" but actually increase indoor ozone concentrations, at times to levels well in excess of that considered safe. Kerosene heaters should be used only as indicated by the manufacturer's instructions, and should be refueled outdoors using specially manufactured low-sulfur fuel. Cars, lawn mowers, etc., should never be left running inside a garage or shed, especially if the space is ever used to house a pet.

Heartworm Disease

In endemic areas, indoor and outdoor cats are at similar risk for infection. The infective L3 stage larva enters the cat through a bite wound, molts to L4 and L5 stages and migrates to the pulmonary arteries as immature adults 70-90 days after infection. Once infected, the cat’s natural resistance results in a short period of microfilaremia. The clinical worm burden is also lower in cats, from 1 to 9 worms, than in dogs. The average time for infective larvae to develop into circulating microfilariae in experimental feline infections is about 8 months. Thus, microfilaremia is uncommon (<20%), inconsistent, and transient in cats, and very low numbers are usually produced. The comparable development period in dogs is 5-6.5 months.

There is high mortality of L5 as they arrive in the distal pulmonary arteries in the cat. High mortality of immature adult heartworms is associated with intense pulmonary bronchial and parenchymal response called Heartworm-Associated Respiratory Disease (HARD). Residual pulmonary pathology related to HARD persists even after immature heartworms die. Thus many heartworm infections may be misdiagnosed as feline asthma.

Heartworm disease in cats is characterized by pulmonary eosiniphilic bronchial and interstitial reaction associated with immature adults (3-6 months after infection) chronic lung changes associated with mature adult heartworms (6 months – 4 years) and acute respiratory distress associated with the death of worms at any age.

Lesions associated with HARD are initiated by immature larvae as early as 70 to 90 days after infection. The lesions in HARD are characterized by peribronchial fibrosis, intertstitial myofibroblasts and fibrosis of alveolar struts. Muscular hypertrophy, villous endarteritis and adventitial cellular infiltrates are common findings in all pulmonary arteries, although caudal arteries are most commonly seen radiographically. Infiltrative interstitial lung disease, reduced clearance of mucous and inflammatory debris are the hallmark of this lung disease as opposed to increased bronchiolar wall reactivity as proposed in asthma models.

Wolbachia are gram-negative bacteria belonging to the order Rickettsia that reside within the body of D. immitis and appear within 2 months of exposure to infective larvae. The release of bacteria following worm death has shown to cause upregulation of proinflammatory cytokines, neutrophil recruitment and an increase in specific immunoglobulins, although the role of this intracellular bacteria alone in the pathogenesis of feline heartworm is unclear.

Clinical signs often include coughing or vomiting most commonly associated with immature heartworms arriving in the lungs or death of adult heartworms. The initial arrival of L5 in the distal pulmonary arteries induces diffuse pulmonary infiltrates and often eosinophilic pneumonitis. Clinical signs associated with acute phase subside as the worms mature but lesions remain even in cats who clear infection.

Most infected cats will be asymptomatic during most of infection. Adult heartworm death, even as little as one, may induce acute, potentially fatal disease with acute circulatory collapse or severe respiratory distress. Anorexia and lethargy may be the only presenting complaints. Coughing or intermittent vomiting may occur. The vomiting appears unrelated to eating. Inflammatory mediators and stimulation of the chemoreceptor trigger zone are postulated as the cause.

Positive antibody result indicates infection with L3 which has moulted to L4 and lived at least 2-3 months. Adult heartworms may or may not develop from this infection. ELISA antigen testing is specific for glycoproteins associated mainly with reproductive tract of fully mature female worms, making false-negative results common. Cats presenting with HARD from immature adults will be antigen negative as will those with low worm numbers. Eosinophilic cytology from BAL will be most intense 3-6 months after migration and is intermittent. Thoracic radiology is helpful but not specific. Aelurostrongylus and roundworm infection are the most common pulmonary infections to mimic heartworm radiologic signs.

Year round heartworm prevention prevents both patent infection and HARD. When cats were infected with L3 heartworms experimentally and treated with selamectin monthly commencing 28 days later did not develop adult worms but did seroconvert to antibody-positive status. Another study demonstrated that cats pretreated with selamectin 32 and 2 days before L3 infection did not develop HARD or seroconvert to antibody positive. The role of Wolbachia remains to be illuminated. Heartworm in cats is often confused with lungworm, roundworm, bronchitis, asthma, or in many cases overlooked.

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