Lower respiratory disease in cats (Proceedings)

Approach to the Cat with Lower Respiratory Tract Disease

If the cat is presented for labored breathing questions should be directed to assist in differentiating upper from lower respiratory disease as some owners perceive stertorous breathing in a cat with upper respiratory disease as a form of labored breathing. This could be misleading to a clinician. Does the cat have a history of coughing? Cats with airway diseases such as asthma or bronchitis often times will have historical coughing versus cats with respiratory distress from congestive heart failure which commonly do not cough. Character of the cough should be discerned: is the cough dry or does it appear productive which can be quite difficult to evaluate in a cat. The clinician should discuss with the owner whether the cat's chest wall is moving more than normal (faster or larger chest excursions) and if the patient is tiring more than usual. Many of our feline patients are indoor only and are not required to perform much physical activity and many outdoor cats are not supervised thus making an assessment of exercise intolerance somewhat difficult. Additionally information regarding timing, frequency, onset, and duration of clinical signs should be acquired from the owner. The owner should be questioned as to the cats overall health. Has the cat shown other signs of systemic illness such as lethargy, inappetence, vomiting. Cats with pneumonia or pyothorax may show signs of systemic illness. The animal's environment, access to the outdoors (possibility of trauma), access to other cats (potential for cat-fighting) and any change in environment in respect to onset of clinical signs should be obtained. The cat's vaccination status and retroviral status are important as well as travel history.

Even before approaching the cat an attempt should be made to observe the animal paying close attention to its respiratory pattern. A normal cat breathing at rest shows minimal movement of the chest wall. When breathing becomes labored the ribs are pulled caudally and laterally by the diaphragm and the chest wall muscles and the abdomen moves slightly outward. Flaring of the nostrils, open-mouth breathing or contraction of abdominal muscles indicates severe labored breathing.

Certain breathing patterns can be associated with disease at a specific location in the respiratory tract. Short and shallow respirations with small tidal volumes are indicative of stiff non-compliant lungs or restricted expansion of the lungs from pleural or thoracic wall disease. Prolonged deep inspirations may be more associated with laryngeal, pharyngeal, or cervical tracheal disease. Prolonged expirations and inspirations are more compatible with a fixed obstruction. Narrowing of small airways has a more profound effect on expiration than inspiration and clinically appears as an expiratory or abdominal push. Animal in severe distress may assume an orthopneic position.

After observing the animal a complete physical examination may be performed. The animal's overall body condition should be noted. Mucous membranes should be checked for pallor, cyanosis indicating the immediate need for oxygen therapy. Assessment of the upper airway should be made and tracheal and thoracic cavity palpation performed. Normal breath sounds include soft low-pitched airway sound most often appreciated on inspiration; in cats it may be difficult to appreciate normal sounds. Lungs should be ausculted for increased sound, crackles and wheezes. Wheezes are primarily classified according to pitch (high vs low) and timing (inspiratory vs expiratory); they are generated by airway narrowing, stenosis, or obstruction. Crackles are typically produced by a delayed opening of small airways attributable to an abnormal fluid-air interface (pneumonia, pulmonary edema, bronchitis). Muffled lung sounds and heart sounds may be indicative of pleural effusive disease (pyothorax, chylothorax), pneumothorax, hernia, or mass. (Miller, CJ, Vet Clin Small Anim, 2007, 861-878)

Diagnostic Testing

Patients with lower respiratory disease often have hematological and biochemical profiles that are unremarkable or show non-specific change but are important to uncover any systemic or metabolic diseases that might be affecting the respiratory system. Hematologic abnormalities might include a polycythemia from chronic hypoxia, leukocytosis with infections, eosinophillia with asthma or parasitic infections, basophillia with heartworm disease. Cats with unknown FeLV or FIV status should have serology performed.

Thoracic radiography is a valuable tool for investigating respiratory disease; however diagnostic information is limited by poor technique, poor patient cooperation, and inherently low sensitivity and specificity. Three (left and right lateral and ventro-dorsal) radiographic views are recommended and the importance of sedation in a stressed or uncooperative cat cannot be over-emphasized. Although diagnostic specificity may be low and rarely can a clinician form a definitive diagnosis based on radiographs alone, thoracic radiography is very useful in aiding in development and narrowing of a working differential list.

Thoracic ultrasound is best used subsequent to thoracic radiography to define the location of a lesion. It is most useful when evaluating cardiac or mediastinal masses, consolidated or collapsed lung lobes, pleural effusion, thoracic wall masses, or looking for diaphragmatic hernias. It can assist with fine needle aspirates or biopsy of masses and aspiration of fluid for cytology or histopathology. Structures within the lung that are surrounded by aerated lung are not accessible with ultrasound.

Thoracic CT may detect more subtle changes, smaller masses within the thoracic cavity not detected by radiographs. It may be a useful tool in surgical planning for removal of masses (i.e. mediastinal masses). CT angiography has been used in veterinary medicine to detect PTE. (Miller, CJ, Vet Clin Small Anim, 2007, 861-878)

Endotracheal washes can be performed in cats with evidence of airway disease to obtain fluid samples for culture and cytology. Bronchoalveolar lavage may be performed with or without bronchoscopic guidance and is indicated to obtain samples from cats with alveolar or interstitial lung disease. Complications associated with endotracheal washes and BAL (with/without bronchoscopy) include anesthetic complications, hypoxia, pneumothorax, and death. (McCullough S et.al. Clin Tech in Small Anim Pract 1999, 220-226; Andreasen CV, Vet Clin Small Anim 2003, 69-88) In one study evaluating bronchoscopic BAL in cats a complication rate of 38% was encountered and 6% of cats were euthanized or died after the procedure. (Johnson LR et.al. JVIM 2007, 219-225.)

Aspirate samples of lung may be obtained as well. This can be done with ultrasonographic guidance for lung masses, mediastinal masses, pleural effusion or without ultrasound guidance, using radiographs to identify the location of the mass or area of most fluid. Lung aspirates may be performed in cats with diffuse interstitial or nodular interstitial disease such as may be seen with pulmonary lymphoma or pulmonary histoplasmosis, however the risk of pneumothorax is greater than with aspirate of a peripheral lung mass. CT guidance can be used to perform trans-thoracic aspirates as well.

Lung biopsy can be considered in disease processes for which airway washes and bronchoscopy do not provide a definitive answer.

Pulse oximeters are commonly used to continuously and noninvasively measure the oxygen saturation of hemoglobin. They are used to determine the need for oxygen administration and to monitor the patient that is being given oxygen supplementation. The usefulness of pulse oximetry is limited by patient cooperation in the non-anesthetized cat making it less reliable than arterial blood gas analysis. Arterial blood gas measurement allows direct assessment of gas exchange and is the most definitive assessment of overall pulmonary function. An arterial blood sample is very challenging to obtain from a cat, unfortunately. The femoral artery is the only accessible artery large enough to obtain an adequate sample. When PCO2 rises (>55-60 mmHg), PO2 decreases (<60 mmHg), or there is risk of fatigue mechanical ventilation is recommended.

Feline Asthma

Feline asthma is one of the most common causes of lower respiratory tract disease in the cat. It is caused by altered immunosensitivity of the respiratory tract/hyperrepsonsiveness to inhaled allergens leading to inflammation, bronchospasm, and abnormal mucous production that can lead to mucus plugs. Clinical signs include coughing, wheezing, tachypnea, orthopnea, open mouth breathing, and expiratory dyspnea. Patients often have a history of paroxysmal coughing that may be associated with episodes of respiratory distress. Cats often appear normal between events.

The presentation of the acute asthmatic patient may be similar to other disease processes, especially cardiogenic shock. Physical examination findings may help to differentiate between a cat with primary cardiac disease and primary pulmonary disease. Patients with cardiogenic shock are frequently hypothermic secondary to reduced cardiac output and subsequent reduced tissue perfusion, whereas feline asthmatic patients typically have a normal body temperature. Thoracic auscultation of an asthmatic cat often reveals expiratory wheezes and coughing is a frequent complaint of owners of asthmatic cats; conversely, cats with cardiomyopathy rarely cough. The presence of a heart murmur should not be used as the sole factor to differentiate between primary cardiac and pulmonary disease.

When presented with the acute asthmatic patient (respiratory distress) measures should be taken to stabilize the patient with minimal handling. These patients are critically ill and are at risk of respiratory arrest even with minimal handling. Oxygen supplementation should be given while performing a triage examination. A single attempt at catheter placement may be tried and bronchodilators and corticosteroids via IV or IM injection or inhalation may be administered. Many of these cats are extremely stressed and sedatives such as butorphanol and acepromazine should be considered. A "crash cart" should be accessible in case intubation and mechanical ventilation are necessary. The animal may then be placed in an oxygen cage if available for observation.

Once stabilized, a complete physical examination should be performed. Thoracic radiography is indicated. The typical lung pattern seen in an asthmatic cat is a diffuse bronchiolar to bronchointerstitial pattern, although a variety of interstitial, bronchial, and alveolar infiltrates may be seen. The lungs are often hyperinflated and the diaphragm is often flattened indicating alveolar air-trapping. Excessive mucous production and obstruction of larger airways can cause alveolar infiltrates, consolidating lesions, or atelectasis. The right middle lung lobe is the most common area for atelectasis. The severity of radiographic pattern may not match the degree of respiratory compromise in an asthmatic cat and normal thoracic radiographs do not rule out the diagnosis of bronchial disease. Normal radiographs have been reported in up to 23% of asthmatic cats.(Adamama-Moraitou KK et.al. J Feline Med Surg 2004 227) Some asthmatic cats may have a peripheral eosinophillia; however lack of or presence of an eosinophillia does not rule in or out asthma. In a stable cat an endotracheal wash or BAL may be performed, although no specific cytological findings from these procedures are pathognomonic for feline asthma/bronchial disease. One study indicated that normal cats could have a mean eosinophil count of up to 18% in BAL fluid.(Padrid PA, et.al. Am J Vet Res 1992 1300) Cytology of wash/lavage samples generally reveal increased mucous with inflammatory cells, the primary cell types being eosinophils, neutrophils, and macrophages. Bacteria may be visualized. Aerobic and Mycoplasma culture and antibiotic susceptibility should be performed. Cats with eosinophillic cytology should be assessed for dirofilarisis with an antibody and antigen test if from endemic areas, fecal sedimentation of feces for Aleurostrongylus, and Paragonimus particularly if the cat is indoor-outdoor and from parasite endemic areas. Broad-spectrum antibiotics (doxycycline 5 mg/kg PO BID followed by 6 mls H2O) are usually administered while awaiting tests and empiric deworming may be considered as well.

Therapy for the asthmatic cat generally revolves around the use of corticosteroids to minimized inflammation and bronchodilators. Prednisolone or prednisone (5-10 mg PO BID) is administered and tapered slowly over 2-3 months to 0.5 mg/kg PO every other day if clinical signs do not recur) and an albuterol inhalant (0.9 mg/actuation, 2 puffs BID for 1 week only in severe cases, or as needed in the acute setting for all cats). Inhalant albuterol, when administered to humans, produces significant bronchodilation within 15 minutes and lasts for 3-6 hours. Albuterol is a beta 2-antagonist. The most commonly prescribed form is racemic albuterol composed of a 1:1 mixture of an R-enantiomer and an S-enantiomer. The R-enantiomer has bronchodilatory and anti-inflammatory properties whereas the S form is associated with increased airway hyperreactivity and pro-inflammatory effects. In a prospective study of 6 healthy cats presented at the 26th Annual ACVIM Forum it was shown via BAL fluid cytology of healthy cats treated with the R,S albuterol and S-albuterol had significantly higher nucleated cell numbers (inflammatory cells) than those healthy cats treated with R-albuterol. The results of this study question the use of inhalant albuterol (R,S-albuterol) in the chronic management of feline lower airway disease. (Reinero CN Proceedings 26th ACVIM Forum 2008) If an inhalant medication is not tolerated by the cat theophylline or terbutaline may be considered. Terbutaline should be avoided in cats with cardiac disease or diseases that may contribute to hypertension such as renal disease or hyperthyroidism. Inhalant glucocorticoids work nicely in many asthmatic patients if tolerated. I will use Fluticasone Propionate (Flovent 220μg (250μ Canadian), 2 puffs twice daily, then tapered slowly to 1 puff every other day or every third day). Flovent comes in three strengths 44μg, 110μg, and 220μg. There is evidence that many cats 44μg q 12 hours is sufficient for reducing airway eosinophillia. (Cohn AL J Feline Med Surg 2010 91) Fluticasone is a large molecule and acts topically within the airway mucosa. It has poor absorption across gut epithelia and may as well across airway mucosa, which could explain why clinical effects of fluticasone usually do not occur for 1-2 weeks. During the first 1-2 weeks of fluticasone therapy, oral glucocorticoids should be administered. Repositol steroids should only be used as a last resort. In addition to administration of medications, environmental modifications are important. It is recommended that if the owner not use any room or carpet deodorizers, scented detergents fabric softeners. There should be no cigarette smoking allowed around the cat and an air filtration system may be considered. It is important when presented with an asthmatic/bronchial disease cat in acute crisis that owners be questioned as to recent changes in detergents, deodorizers, or even cat litter as these things could precipitate an asthmatic crisis and should be avoided.

Monitoring therapy efficacy is usually undertaken in veterinary medicine by observing for resolution of clinical signs and observing for thoracic radiographic resolution; however it has been shown in human medicine that resolution of clinical signs are poor predictor of airway inflammation and up to 23% of cats with lower airway disease have normal radiographs. (Adamama-Moraitou KK et.al. J Feline Med Surg 2004 227) It is not completely known if airway inflammation is adequately suppressed in dogs or cats with inflammatory bronchial disease in clinical or radiographic remission. There is preliminary evidence in cats that improvement in clinical signs is a poor indicator of airway inflammation (Reinero CV, Proceedings 28th ACVIM Forum, 2010) Persistent inflammation, even subclinical inflammation can have a negative impact on long-term pulmonary function. Airway inflammation leads to structural changes referred to as airway remodeling: thickening of the basement membrane, bronchial smooth muscle hypertrophy, goblet cell hyperplasia, submucosal gland hypertrophy, airway wall thickening, loss of alveolar-bronchial attachments, angiogenesis, and fibrosis. This leads to airway narrowing, mucous plug formation, airway hypersensitivity, decreased immune defenses, altered gas exchange, and an overall loss of function. The structural changes are permanent thus prevention is key. As such, more invasive diagnostic testing such as repeat BAL may be indicated in the monitoring of these patients. (Reinero CV, Proceedings 26th ACVIM Forum 2008) Many patients require life-long therapy. It is recommended that a recheck wash approximately 1 month after discontinuation of medications be performed to evaluate for subclinical inflammation. Allergy testing and immunotherapy may play a role in treatment of feline asthma. (Halliwell RE J Am Animal Hosp Assoc 1997 282; Lee-Fowler TM et.al. Vet Immunol Immunopath 2009 49). Supplementation with omega-3 fatty acids may also be of benefit.

Parasitic Disease

Parasites that can lead to cough and dyspnea in cats include Toxocara cati, Toxoplasma gondii, Aleurostrongylus abstrusus, Eucoleus aerophilia, and Paragonimus kellicoti. Aleurostrongylus abstrusus is a metastrongyloidae parasite that has an indirect life cycle with rodents as the intermediate host. Thoracic radiographs show a bronchial pattern with alveolar infiltrates and some increased interstitial densities. Ivermectin (0.4 mg/kg SQ once) is very effective. Fenbendazole (25 mg/kg PO daily for 5 days then repeated in 5 days) can be used as an alternative. Glucocorticoids are recommended (1-2 mg/kg PO daily) as eosinophillic pneumonitis occurs with these agents. Thoracic radiographs may worsen after treatment.

Paragonimus kellicoti is a trematode parasite found in pulmonary cysts in cats and other mammals. Animals at risk of infection are those that live in the southern, midwestern, and Great Lakes regions of the United States. Hemoptysis occurs occasionally with Paragonimus and pneumothorax is rare. Thoracic radiographs may reveal interstitial nodules in cats usually within the caudodorsal lung fields. Sedimentation techniques are superior to fecal flotation for demonstration of Paragonimus. The eggs are large and operculated and may occasionally be found in phlegm. Praziquantel (25 mg/kg PO q 8 hr for three days) or Fenbendazole (50 mg/kg PO q 24 hr for 10 days) may be used for treatment.

Eucoleus aerophilia, previously Capillaria aerophilia, is a nematode parasite. Adults reside primarily in the trachea and bronchi. They deposit eggs, which are coughed up, swallowed, and shed in the feces. Most animals are asymptomatic. Cough is the most commonly clinical sign in animals that are clinical for the disease. Radiographic features include, as for most parasitic diseases, peribronchiolar infiltrates, interstitial patterns that can have a nodular feature, and occasionally alveolar pattern. Diagnosis is made by detection of ova is respiratory washes and fecal flotation, although intermittent shedding can cause false results and multiple fecal flotations are recommended. The ova have an operculum at the end and are similar in appearance to Trichuris vulpis. Administration of fenbendazole (25-50 mg/kg PO q 12 hr for 14 days) is recommended for treatment. (Lappin MR Proceedings 26th ACVIM Forum 2008)

It is difficult to prove respiratory cough due to migrating Toxocara cati; however demonstration of eggs in the feces of coughing kittens supports a presumptive diagnosis. There is no effective treatment for the migrating phase of the parasite.

Pulmonary disease in cats with Toxoplasma gondii is common. Pulmonary toxoplasmosis can be an acute, fulminate, and fatal disease. Physical examination can reflect the multisystem nature of the disease. Auscultation may reveal increased bronchial sounds or crackles and thoracic radiographic features include diffuse alveolar and interstitial disease. Diagnosis is supported by serology (increased IgM or increased IgG in an animal with compatible disease) and definitively may by demonstration of organisms in the tissue. Occasionally tachyzoites can be detected in BAL washings or lung aspirates of affected cats. Clindamycin (10-12 mg/kg PO BID for 4 weeks) may be effective for toxoplasmosis. (Green Infectious Diseases of the Dog and Cat 3rd ed. 754)

The incidence of heartworm disease, dirofilarisis, in cats in a given area is much lower ( 5%-10%) than that of dogs. Worm burdens in cats are usually low (1-2) but morbidity and mortality tends to be greater than in dogs. Dogs are the usual definitive host for Dirofilaria immitis; however the life cycle can also be completed in the cat. Cats are less easily infected with heartworms than dogs and there are fewer filaria in feline infections. The lifespan of the filaria are about half that in the dog (2-3 years). The cat does not serve well as the definitive host because of the low microfilaremias detected. Wolbachia, an endosymbiontic bacterium present in D. immitis, may play a role in the inflammatory reaction seen in cats with heartworm disease.

Feline heartworm infection can occur at any age and immunosuppression is not a prerequisite for infection. Indoor and outdoor cats are equally represented. Clinical signs in cats can vary widely in severity and are most commonly related to the respiratory system including chronic cough or intermittent dypsnea, and asymptomatic infection. Vomiting is also a relatively common finding but the pathogenisis is unknown. Bronchial disease can occur prior to the development of adult heartworms (HARD – heartworm associated respiratory disease). Diagnosis is made by using a combination of tests including serum antibody tests for screening followed by serum antigen tests. As cats generally have low worm burdens, may have immature or male only worm infections antigen tests, detecting antigen found in the female worm reproductive tract, are often negative. Antibody tests only document exposure and will be positive in cats with previous heartworm infections. The sensitivity of various heartworm antibody serology ranges from approximately 70%-90% and specificity from 77%-98%. Thoracic radiographs may demonstrate pulmonary arterial distension, tortuosity, and blunting. Occasionally worms can be detected by echocardiography. The infection in cats is self-limiting in approximately 2 years. Most cats should be managed symptomatically with glucocorticoids. Cats should be placed on preventative. Microfilaricides are not required and adulticides not recommended for cats. (Lappin MR Proceedings 26th ACVIM Forum 2008)

Pneumonia

Pneumonia is inflammation of the lung parenchyma and bronchopneumonia is pneumonia that has begun in the terminal bronchioles. Bacterial pneumonia is rarely a primary disease and occurs less commonly in cats than dogs. Occasionally Bordetella bronchiseptica or Mycoplasma spp will induce pneumonia due to their adverse affects on mucocillary clearance. Yersinia pestis can cause pneumonia in infected cats and is zoonotic (southwestern states). Toxoplasma gondii causes interstitial pneumonia. Most causes of bacterial bronchopneumonia are secondary to immunosuppressive diseases or previous inflammatory insults (viral infection, aspiration, inhalant irritants) aspiration and owners should be carefully questioned to potential exposure to other animals and clinical signs associated with immunosuppressive diseases or possibility of aspiration. (Lappin MR Proceedings 26th ACVIM Forum 2008)

Cats with pneumonia may be clinically ill. Common complaints include depression, anorexia, dyspnea, productive moist cough with a terminal retch, and exercise intolerance. Some cats with pneumonia will not cough. In one retrospective study it was reported that 36% of cats with pneumonia did not have clinical signs that were referable to the respiratory tract and 41% lacked clinical signs of systemic illness; 4/39 lacked either signs of respiratory disease or signs consistent with systemic manifestation of pneumonia. (Macdonald ES, et.al. JAVMA 2003 223 1142)

Physical examination may include fever. Thoracic auscultation may reveal crackles, wheezes and/or muffled lung sounds in case of consolidation or abscess. Increased tracheal sounds may be evident. Diagnostics should include CBC (evidence of inflammation), biochemical panel (detection of underlying immunosuppressive disease such as DM), urinalysis, thoracic radiographs (mixed alveolar, bronchial, interstitial pattern, right middle lung lobe is the most often affected with aspiration pneumonia), FeLV and FIV testing if status is unknown. If interstitial pneumonia is seen, T. gondii serology should be considered especially in the cat that has a history of hunting or eating raw meat. The esophagus can be evaluated on thoracic radiographs for evidence of megaesophagus that may predispose for aspiration and an esophagram considered if esophageal dysfunction (regurgitation) is suspected. If a cat has evidence of stridor, laryngeal function should be evaluation as laryngeal paralysis, although rare in cats, could predispose to aspiration. Endotracheal wash or BAL (+/- bronchoscopy) should be performed to obtain fluid for cytology and aerobic and Mycoplasma spp. culture and antibiotic susceptibility. Airway wash culture results should be interpreted with respect to cytology findings. Contamination of the sample with oropharyngeal organisms is not too uncommon. Bacterial culture is commonly positive in healthy cats as well. The presence of bacteria without inflammatory cells usually does not document pneumonia.

Therapy involves assuring that the patient is well hydrated. The mucociliary clearance apparatus works best in the well-hydrated animal. Cats that are compromised and unable to maintain hydration benefit from the administration of IV fluids. Airway hydration may be enhanced by nebulization or by placing the animal in a closed bathroom while running hot water through the shower. Antibiotic therapy should be based upon culture and susceptibility results. Broad-spectrum bactericidal antibiotics should be chosen empirically while awaiting results. Aminoglycosides can be nebulized. Septic cats should be administered parenteral antimicrobials. Antibiotics should be administered roughly for 6-8 weeks or for 2 weeks following resolution of radiographic evidence of disease. Oxygen therapy should be provided to the dyspneic patient. Passive physical therapy is recommended, gentle percussion if tolerated may be beneficial and mild play may be encouraged. Phosphodiesterase bronchodilators may be considered if resolution of disease is slow as they can improve mucociliary apparatus function and may strengthen muscles of respiration. Mucolytics such as acetylcysteine are generally not used during nebulization of cats due to bronchoconstriction. Thoracic radiographs should be reassessed 3-4 days after beginning therapy and every 2-3 weeks thereafter until resolution. If consolidated lung lobes are not beginning to inflate within a week to couple weeks therapy, especially if fever or other systemic signs are persistent, surgical exploration should be considered.

Histoplasmosis is the most common cause of fungal pneumonia in the cat. It is seen more commonly along the Mississippi, Missouri, and Ohio River valleys. Infection occurs primarily after inhalation of the organism. Cats are typically systemically ill. They are often febrile, tachpyneic, lethargic, and inappetent. Thoracic radiographs show a diffuse nodular interstitial pattern. Enlargement of hilar lymph nodes may be detected. Diagnosis can be made with transthoracic aspiration and cytology to identify the organism or via airway wash. Aspiration may have a higher diagnostic yield; however is associated with greater morbidity (pneumothorax). Adequate sedation is a must when performing lung aspiration. Histoplasma antigen serology (latex-agar agglutination test) is of low sensitivity and only confirms exposure. Recently antigen testing is available through Mira Vista diagnostics in Indianapolis, Indiana (www.miravistalabs.com).

Systemic antifungal medications are used for therapy. Itraconazole (5-10 mg/kg PO BID) may be most effective; however ketoconazole or fluconazole may be used as well. Many cats have worsening of clinical signs during the first couple weeks of therapy and low-dose anti-inflammatory corticosteroid therapy may be considered. Antifungal therapy is continued 4 weeks past resolution of radiographic signs of disease (usually months). Antifungal medications are quite expensive and itraconazole for a cat is typically about $200/month and duration of therapy long (6 mo or more). The azole medications are hepatotoxic and liver values should be checked 1-2 weeks and 3-4 weeks after starting therapy, then monthly. Cryptococcus is usually a pathogen of the upper-respiratory tract, namely the nose; however it can uncommonly cause pulmonary parenchymal disease. Blastomycosis and coccidiomycosis are uncommon in the cat, but both can cause respiratory disease in cats.