Bronchial disease

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Thoracic radiograph of a cat with bacterial bronchopneumonia (lateral view). Widespread patchy areas of alveolar pulmonary infiltrate and diffuse bronchial pattern
Granulocytic bronchoalveolar lavage cytology from a cat with chronic bronchial disease. The differential count in this cat was characterised by 82% eosinophils (normal <25%). Courtesy August, JR (2006)[1]

Bronchial disease is a common respiratory ailment of cats at all ages, and in all breeds, seen usually as asthma or chronic bronchitis[2][3].

Bronchial disease is an obstructive airway disease which occurs as a consequence of chronic inflammatory disease of the pulmonary airways. The mainstay of therapy for inflammatory airway disease is the administration of glucocorticoids[4]. Pneumonia is sometimes seen in advanced cases or with acute bacterial infections from numerous bacterial species.

Cause

Although the etiology of many cases of feline bronchial disease are unknown, it can be simulated by antigenic or allergic responses which cause activation of CD4+ lymphocytes and initiation of a Th2 immune response[5].

Activation of lymphocytes toward Th2 immunity results in induction of specific cytokines that are protective against parasitic infection or are associated with type 1 hypersensitivity. In comparison, Th1 adaptive immunity is characterised by increased interferon-gamma and macrophage activating factor, and this arm of the immune system protects against bacterial or viral organisms. Th2 immunity is characterised by classically by production of IL-4, IL-5 and IL13, and IL-5 is particularly important in differentiation and maturation of eosinophils. Degranulation of feline eosinophils results in elaboration of major basic proteins, myeloperoxidase, and ribonucleases, and these are responsible for damage and destruction of the epithelial lining of airways. Sloughing of pneumocytes exposes sensory and irritant nerve endings to increased types and concentrations of allergens or irritants. Cytokines also may cause increased release of neurotransmitters, and thus inflammatory damage can enhance neural responsiveness. In cats with primarily neutrophilic inflammation, similar toxic damage to airways occurs, followed by the resultant repair process. Recent investigations into the pathophysiology of asthma in several species indicate that inflammation can cause oxidative stress and nitration of proteins, which perpetuate airway injury and proliferative responses.

In cats, the characteristic changes which appear histologically include metaplasia and proliferation of airway epithelium, hyperplasia of mucous glands with production of excess mucus, hypertrophy and hyperplasia of airway smooth muscle and distal emphysematous changes in the pulmonary parenchyma.

In human beings, infiltration of airway smooth muscle cells is being recognised as a specific finding in asthma versus eosinophilic bronchitis and may be responsible for the induction of airway hyperresponsiveness and subsequent airway remodelling. Hyperresponsiveness of airway smooth muscle cells results in airway constriction in response to nonspecific stimuli such as airway irritants, allergens, parasites, or viral particles. Reversible airway constriction is a primary component of the acute asthmatic form of inflammatory airway disease, and this is a feature in some cats with bronchial disease. With chronic and uncontrolled lower airway disease, airway remodelling results in smaller diameter of airways, increased airway resistance, and fixed airway obstruction, and thus some cats display irreversible bronchial changes and expiratory airflow obstruction.

Feline bronchial disease shares many clinical and histological characteristics with human asthma and recurrent airway obstruction (RAO) in horses, although human asthma is associated with eosinophilic airway inflammation, whereas neutrophils predominate in the equine condition. Disease may result from allergic stimulation, hyperresponsiveness to parasitic or fungal elements, or airway irritation associated with inhalation of gastric acid, heavy metals, or particulate matter. Clinical signs may be exacerbated in dirty, dusty or polluted environments, or in association with upper respiratory tract infections in cats. Although genetic influences in the development of asthma have been established in human medicine, this has not been investigated in cats. Despite many similarities in this condition across species, certain differences also are noted. For example, leukotrienes are implicated in the pathogenesis of certain forms of human asthma; however, leukotriene metabolites are not increased in bronchial fluid or urine of cats with experimentally induced allergic airway inflammation.

Clinical signs

Clinical signs of feline bronchial disease include chronic cough, lethargy, exercise intolerance, loud breathing, rapid or laboured respirations, and acute respiratory distress. These signs may be acute in origin or may be chronic, non-progressive problems. The cough associated with lower airway inflammation typically is harsh and associated with active abdominal effort. Owners may believe that the cough represents an attempt to remove a hairball, or they may suspect that a foreign object is stuck in the throat. Coughing can be intermittent or present only during exposure to certain environmental stimuli, or it may be relatively constant. Determining the association of cough with specific trigger events can be an important part of the effort to control clinical signs.

Some cats with respiratory disease exhibit exercise intolerance or lethargy. Reduced play activity or panting or open-mouth breathing after light exercise could be clues to underlying airway disease. Interestingly, some owners of cats with bronchial disease complain of loud respirations or detection of wheezing sounds from their cat. Cats may be observed to breathe more rapidly than expected or to exhibit difficulty breathing. These signs may be chronic or intermittent in nature.

A subset of cats develops acute bronchoconstriction and displays episodes of respiratory distress, persistent tachypnoea, cyanosis or collapse. Some of these cats may have a previous history of cough or laboured respirations, whereas others previously were considered healthy.

Cats with airway disease generally are young to middle age and mostly present with tachypnoea as the primary presenting sign, with or without prolonged expiration or an expiratory / abdominal push. This respiratory manoeuvre is an indication of lower airway narrowing or obstruction and increased expiratory effort. Cats with chronic airway disease that have substantial airway and parenchymal remodelling may display a barrel-chested appearance and decreased thoracic compressibility because of over-inflation and emphysema.

Cough is a common feature of feline bronchial disease, and detection of a cough in the cat that presents with respiratory distress or tachypnoea is a major clue to the presence of underlying inflammatory airway disease. Affected cats show variable degrees of tracheal sensitivity following palpation. Caution is advised during palpation of the trachea to avoid excessive stress for the cat.

Auscultation of the respiratory tract reveals harsh lung sounds, inspiratory crackles, or expiratory wheezes in 65% of cats; however, the absence of such sounds does not rule out inflammatory airway disease because cats can appear normal between episodes. Tracheal auscultation may reveal gurgling sounds resulting from the presence of excess secretions; however, stridor is not anticipated in a cat with lower airway disease.

Diagnosis

Inflammatory bronchial disease should be considered a diagnosis of exclusion. Bronchial disease is considered highly likely when chronic cough or acute onset of respiratory distress is found in a young to middle-aged cat. Because idiopathic inflammatory airway disease generally requires long-term management with corticosteroids and/or bronchodilators, diagnostic efforts are aimed at ruling out infectious etiologies and primary causes of airway inflammation.

The minimum database rarely contributes to the diagnosis of feline airway disease; however, the presence of eosinophils is suggestive of asthma in a cat with relevant clinical signs. Asthma has been reported as one of the top causes of peripheral eosinophilia in cats; although many affected cats display neutrophilia resulting from chronic inflammation. In cats with peripheral neutrophilia, ruling out lower respiratory tract infection is particularly important because this has been a consistent finding in two recent studies.

Although airway parasites and heartworm disease are identified uncommonly in cats, complete diagnostic testing for these conditions is wise to rule out a primary cause of airway inflammation. Faecal floatation is performed to detect the double-operculated egg of Capillaria aerophila (also known as Eucoleus aerophilus), whereas a Baermann test is used to detect larval stages of Aelurostrongylus abstrusus.

Tests for heartworm disease should be considered in some cats presenting with cough, particularly when vomiting also is in the history, or when the cat is from an area in which feline heartworm disease has been identified. Detection of large pulmonary arteries on thoracic radiographs is definite indication that heartworm disease should be ruled out; concurrent pulmonary infiltrates may or may not be present. Heartworm disease can be diagnosed by the appearance of parallel lines in the pulmonary artery or right heart with echocardiography. A positive heartworm antigen test is a highly specific test and is indicative of heartworm disease. The ELISA antigen test detects the presence of a protein that originates from the female heartworm's reproductive tract. This test typically becomes positive 5 to 7 months after infection. However, the test can be negative because of low worm burden or presence of only male heartworm, and therefore this is more of a diagnostic test than a screening test. The heartworm antibody test for cats detects exposure to the developing larvae of heartworm and therefore is a reasonable screening test for exposure. Antibodies are found approximately 2 to 3 months after infection; however, a cat with heartworm infection may be antibody-negative occasionally. In addition, the antibody test

There are 3 basic radiographic pulmonary patterns:


Lung Pattern Hallmark Radiographic Sign
Alveolar Air Bronchogram
Interstitial Loss of visualization of vessels
Bronchial Donuts/Train Tracks

Radiographs play an important role in documenting airway disease and excluding other causes of cough; however, normal thoracic radiographs do not exclude idiopathic airway disease as a cause for clinical signs in affected cats. The classic finding in cats with airway disease is peribronchial infiltrates; lung hyperinflation, flattening of the diaphragm, increased space between the diaphragm and heart, or aerophagia also may be seen. Some cats may display only a mild interstitial pattern, and lobar collapse (primarily of the right middle lung lobe) or focal alveolar infiltrates can be seen in some cats because of mucous plugging of large airways with secondary atelectasis. Alveolar infiltrates generally are presumed to indicate pneumonia; however, they are not pathognomonic. A bronchial pattern was reported in 40% of cats with lower respiratory tract infection, and 36% had bronchoalveolar infiltrates in a recent study. Therefore peribronchial radiographic changes should not be considered pathognomonic for idiopathic feline bronchial disease.

In the stable patient, airway fluid analysis is recommended to exclude primary causes of cough and airway inflammation. A transoral tracheal wash or bronchoscopy can be used to collect fluid. Pretreatment with terbutaline (0.01 mg/kg SQ) for 12 - 24 hrs before the procedure may improve the safety of the procedure by initiating bronchodilation before anaesthesia. For a transoral tracheal wash, the cat is sedated for intubation with a sterile endotracheal tube. A sterile, 5- to 7-French polypropylene or red rubber catheter is passed to the level of the carina (approximately at the fourth intercostal space), and 3 to 5 ml of warmed, sterile saline are injected and then aspirated. Retrieval of 0.5 to 1.0 ml is sufficient for cytological analysis and culture. For bronchoscopy, a small endoscope (preferably 2.5 to 3.8 mm outer diameter) is safest to use and easiest to manipulate within the airways of cats. The cat is anaesthetised with intravenous agents (e.g. propofol) and oxygen supplementation is supplied through jet ventilation or with an oxygen cannula passed down the trachea. The endoscope is passed through the trachea and all airways are examined. Cats with bronchial disease typically have viscid secretions within airways. Cats usually do not display mucosal hyperemia as do dogs with bronchitis; however, the epithelial surface may appear irregular, granular or nodular.

Before obtaining bronchoalveolar lavage (BAL) fluid for culture and cytology, the endoscope is removed from the airway, the biopsy channel is rinsed, and the outer surface is wiped free of contamination. BAL is performed by wedging the endoscope gently in a small airway, instilling a 3 ml to 10 ml aliquot of warmed sterile saline, and retrieving the fluid by gentle aspiration. If insufficient fluid is obtained, a second aliquot is instilled at the same site. The presence of foam within the fluid indicates that it contains surfactant and therefore has been in contact with the alveolar surface.

Cats with idiopathic lower respiratory tract inflammation can have primarily neutrophilic or eosinophilic cytology. The significance of the primary cellular infiltrate currently is unknown, and it appears that more cats have primary neutrophilic inflammation than eosinophilic inflammation. Light growth of bacteria from the lower airways of cats with and without bronchial disease is common, occurring in approximately 75% of healthy or bronchitic cats. True infection typically is associated with systemic signs of illness, degenerative or septic airway cytology, and a positive response to antimicrobial therapy.

The role of Mycoplasma spp infection in respiratory disease remains controversial. It has been isolated from tracheobronchial lavage with various types of lower respiratory disease, but not from bronchoalveolar lavage samples of healthy cats. Aerobic and Mycoplasma cultures always should be performed in cats with cough or tachypnoea, because Mycoplasma species are a common finding in cats with lower respiratory tract infections and because of the possibility that Mycoplasma species may worsen airway hyperreactivity.

Pulmonary function tests to evaluate airway resistance and lung compliance or flow-volume relationships can be performed at certain referral institutions. Many cats with bronchial disease exhibit higher airway resistance than healthy cats because of relative bronchoconstriction. Administration of terbutaline decreases resistance in some affected cats, indicating partial reversibility of smooth muscle contraction. Cats with bronchial disease also exhibit airway hyperresponsiveness to a nonspecific aerosol stimulant, as evidenced by a reduction in the dosage of methacholine required to increase airway resistance. Whole body plethysmography (in a sealed and calibrated plexiglass box) recently has been proposed as a method to document airway hyperreactivity in awake, spontaneously breathing cats by measurement of box pressure signals and calculation of enhanced pause, a variable that correlates with airway resistance.

Tidal breathing flow volume loops (TBFVL) are used commonly to evaluate pulmonary function in noncompliant human paediatric patients and also have been used to investigate respiratory flow characteristics in cats with bronchial disease. This procedure provides a measure of expiratory and inspiratory flows and volumes during normal respiration in awake, unsedated cats. The cats breathes through a facemask attached to a pneumotachograph and pulmonary mechanics analyser. Pressure measured at the pneumotachograph is proportional to flow through the mask, and signals are integrated over time to determine volume at each cycle of respiration. TBFVLs in cats clinically affected by bronchial disease exhibit defects in expiratory flow consistent with bronchoconstriction, which supports the presence of airflow obstruction in these cats. Significant findings in cats with bronchial disease included increased expiratory:inspiratory time ratio, decreased peak expiratory flow rate, and decreased tidal breathing expiratory volume.

Differential diagnosis

The primary differential diagnosis to consider are those that cause cough and those that result in tachypnoea or laboured respirations. Cough may be an indication of parasitic pneumonia (secondary to lungworms Aelurostrongylus abstrusus or Eucoleus aerophilus) or could be suggestive of heartworm disease. Cats with heartworm infection can have concurrent vomiting in the history and also may have a heart murmur. Cough can be a sign of an airway foreign body, and this may or may not be obvious on thoracic radiographs. Cough and abnormal respiratory rate or effort also are associated with lower respiratory tract infection caused by bacterial or Mycoplasma infection. Fungal pneumonia is less likely to result in cough in cats.

Tachypnoea and laboured respirations can be indicative of inflammatory airway disease but also may be consistent with upper airway obstruction, cardiac disease, pyothorax, chylothorax and pulmonary inflammation or pneumonia. Tachypnoea resulting from upper airway disease (laryngeal mass or paralysis) is associated with inspiratory effort and stridor. Cardiac disease with pulmonary oedema would be supported by concurrent detection of a heart murmur or gallop rhythm; however, some cats with heart disease lack auscultatory abnormalities. An important distinction between cats with lung versus heart disease is the presence of a cough, because cats with congestive heart failure typically do not cough. Pleural effusion resulting from cardiac disease or other causes also can result in tachypnoea. The physical examination finding of absent lung sounds ventrally would be typical in those cases, whereas increased lung sounds are expected in bronchial disease. Tachypnoea also is found in cats with infectious or atypical pneumonia. In cats with infectious causes of pneumonia, systemic and naso-ocular signs also are common, although fever is detected in less than 20% of cases.

Treatment

Diagnostic tests should be kept to a minimum initially for the cat presenting with signs of acute bronchoconstriction such as cyanosis, tachypnoea, and open-mouth or abdominal breathing. Stabilisation can be achieved by providing an oxygen-enriched environment and using parenteral administration of a β2 agonist such as terbutaline. This drug alleviates bronchoconstriction by opposing smooth muscle contraction and is effective in cats with airway disease that have reversible airway constriction. It is an effective bronchodilator with few cardiac side effects, it is a relatively safe drug, and it is easy to administer subcutaneously, or intravenously at 0.01 mg/kg. An additional dose can be administered after 30 mins if insufficient response is noted.

Epinephrine, a sympathomimetic agent, is a potent bronchodilator but should be used only when cardiac disease has been excluded from the differential diagnosis list because alpha and β1-adrenergic stimulation can result in adverse side effects of cardiac arrhythmias, vasoconstriction, and systemic hypertension. Aminophylline is a weak bronchodilator and its use in an emergency situation may not be justified because other drugs are more likely to be effective. Also, intravenous aminophylline injection can be associated with anaphylaxis, and intramuscular or subcutaneous routes of administration cause pain on injection.

Respiratory rate and effort should be monitored visually in the first hour of observation to determine a therapeutic response. If the cat does not respond to terbutaline, use of a short-acting corticosteroid (dexamethasone-sodium phosphate or Solu-delta-cortef at standard doses) often results in rapid alleviation of clinical signs caused by inflammatory airway disease. Use of corticosteroids affects further diagnostic testing because these drugs decrease migration of inflammatory cells into the airway; however, corticosteroids may be required to stabilise the animal. If the cat fails to respond to these measures, causes for respiratory distress other than idiopathic bronchial disease should be investigated.

Anti-inflammatory agents

Inflammation is believed responsible for the pathogenesis of feline bronchial disease, and corticosteroids are effective in emergency therapy and in chronic management of this disease. Corticosteroids reduce inflammation by inhibition of phospholipase A, the enzyme responsible for the initial metabolism of arachidonic acid into inflammatory mediators. Corticosteroids also decrease migration of inflammatory cells into the airway, thereby decreasing the concentration of granulocyte products such as major basic protein and other eosinophil-derived products.

The duration and dose of corticosteroid therapy depend on the degree and chronicity of respiratory embarrassment in the cat, the severity of the pulmonary infiltrate, and the severity of the pulmonary infiltrate, and the severity of inflammation on cytology. An individualised approach to anti-inflammatory treatment is required for each case. Initially, prednisolone should be administered at 1mg/kg PO q 12 hr for 5 to 10 days, and the dosage decreased to 0.5 mg/kg PO q 12 hr for 5 to 10 days if a good therapeutic response is seen. If the patient remains relatively free of respiratory signs, the dosage may be decreased over time to once-daily or every-other-day treatment. Recurrent episodes of coughing or respiratory distress necessitate a return to the original dosage. Repeat diagnostic testing also may be indicated. Cats are relatively resistant to the side effects of corticosteroids; however, an attempt should be made to achieve the lowest dose of the drug that will control signs. Approximately one half to two thirds of cats require lifelong medication.

Cats that cannot be medicated orally can be treated with intramuscular injection of a repositol corticosteroid (methylprednisolone acetate at 10 to 20 mg IM every 2 to 8 weeks); however, this method provides only sporadic control of airway inflammation. Alternately, inhaled treatment can be prescribed. Both corticosteroids and bronchodilators are readily available from human pharmacies as metered dose inhalers (MDIs). Administration of inhaled medication requires use of an MDI attached to a spacer with facemask. The spacer device causes generation of an aerosol cloud from the MDI that separates large particles from smaller particles, creating 1 to 7 micron particles that will deposit in airways during tidal respiration. In healthy cats, nebulisation of a product administered via spacer and facemask resulted in adequate pulmonary deposition.

Various preparations of antiinflammatory and bronchodilator medications are available for aerosol therapy via MDIs. The most commonly recommended steroid is Flovent (fluticasone propionate), which is available as an MDI containing 120 doses. Three strengths of drug are available; 220 μg/dose, 110 μg/dose, and 44 μg/dose. The 110-μg dose is used most commonly. The MDI must be shaken well before actuation and must be attached to the spacer before the dose is ejected. Typically, the MDI is actuated once per treatment, and the cat inhales 8 to 10 breaths (10 seconds) to deposit drug in the airways. Some of the sid effects note in human medicine include adrenal suppression with long-term and high-dose use, thinning of the skin, and perioral dermatitis or infection (particularly with candidiasis). These complications have note been noted in veterinary patients.

In cats with moderate to severe clinical manifestations of disease, standard doses of oral steroids generally are recommended during the first several weeks of inhaled therapy, and the oral dose then can be tapered downward depending on the clinical response.

For bronchodilation, an inhaler containing a β-agonist (Proventil or generic) can be given. The MDI contains 200 doses of 90 μg/dose or 108 μg/dose. When both bronchodilators and steroids are given by inhalation, the bronchodilator is administered first, and the second drug can be given after 5 to 10 minutes.

Inhaled medications are more expensive than oral medications, but they may result in improved owner compliance, particularly when cats are difficult to medicate orally and chronic therapy is required. Many owners find that cats tolerate inhalation therapy readily, although problems may be encountered. Some cats may be frightened by actuation of the MDI , although they often become habituated to the sound with training. In an acute asthmatic attack, tolerance of the small facemask can be variable until the cat has learned to accept the device. An additional concern may be the competence of the drug delivery because owners lack ability to deploy device correctly, or because of the failure of the device to induce deposition of aerosol into constricted airways. It is unclear whether this is a concern in treatment of cats. Finally, breath holding by the cat can be a reason for treatment failure.

Alternate antiinflammatory drugs may be beneficial in some cats. In an experimental model of feline asthma, cyproheptadine, a serotonin-receptor blocker, attenuated airway constriction of isolated bronchial strips in vitro. Serotonin levels have not been measured in naturally occurring feline bronchial disease; however, some cats may benefit from administration of serotonin antagonists. Cyclosporine, an inhibitor of T lymphocyte activation, attenuates bronchoconstriction and airway remodelling in asthmatic human patients and in a feline model of airway hyperreactivity. Because cyclosporine absorption and distribution are extremely unpredictable, blood levels must be measured weekly until the desired trough level is achieved. The variable pharmacokinetics of cyclosporine and the potential toxicity of the drug make other agents more suitable for first-line therapy of feline bronchial disease; however, it could be considered for cases that are nonresponsive to standard therapy.

Bronchodilators

Bronchodilators can be helpful in emergency situations, in chronic management, and in control of exacerbations of disease in cats with bronchial disease. In some cases, bronchodilators allow a reduction in the dose of corticosteroids required to control clinical signs. This would be especially beneficial in cats afflicted with chronic recurrent bacterial infections, immunodeficiency, or diabetes mellitus. Individual cats show variable response to different classes of bronchodilators. If the drug used initially does not improve the cat's clinical condition, an alternate class of drugs should be employed. Adverse effects of bronchodilators include gastrointestinal upset, sinus tachycardia and hyperexcitability.

Administration of a β2 agonist results in bronchodilation from direct relaxation of airway smooth muscle. Terbutaline currently is the recommended adrenergic agents for cats. Intravenous terbutaline has been shown to reduce airway resistance acutely in cats with constricted airways, and pharmacokinetic studies have established the safety of the drug. The recommended dose is 0.01 mg/kg parenterally q 12hrs to q 6hrs or 0.625 mg PO q12hrs. Theoretically, down regulation of β-receptor density could occur with chronic use, resulting in decreased efficacy of the drug; however, this rarely is recognised clinically.

Theophylline (a methylxanthine) may provide some relief from clinical signs by preventing acute attacks of bronchoconstriction in predisposed cats, by suppressing inflammation, or by reducing the dose of corticosteroid required. Pharmacokinetics have not been established for sustained-release theophylline products currently on the market. Extrapolating from a dosage provided for dogs, extended-release theophylline can be administered at a dosage of 10 mg/kg PO in the evening.

Antibiotics should be prescribed based on culture and sensitivity and cytology results because airway infection may contribute to bronchial inflammation and hyperresponsiveness. If infection with Mycoplasma spp is suspected, a clinical trial of doxycycline (3 to 5 mg/kg PO q12hrs) can be prescribed while cultures are pending. If parasitic infection with Aelurostrongylus abstrusus is documented or suspected as a cause for airway inflammation, fenbendazole can be administered at 50mg /kg PO q 24 hrs for 10 days, or ivermectin can be used (300 μg/kg PO or SQ twice, 3 weeks apart).

Prevention

Feline airways are rich in sympathetic innervation, and β2-adrenergic activation is important in providing bronchodilation. Therefore β-blockers such as propanolol (a nonspecific beta blocker) and atenolol (primarily a β1-blocker) should be avoided if bronchial disease is suspected. Atropine, although it is a potent bronchodilator, should not be used chronically in bronchial disease, because it thickens bronchial secretions and encourages mucous plugging of airways.

Situations that might provoke bronchoconstriction should be avoided, particularly in cats that develop acute attacks of severe respiratory distress. Cigarette smoke, dusty litters, aerosol sprays, polluted environments, stressful situations, and exposure to upper respiratory viruses (e.g. herpes virus, calicivirus) can trigger clinical signs in susceptible cats.

References

  1. August, JR (2006) Consultations in Feline Internal Medicine, Vol 5. Elsevier Saunders, Philadelphia. pp:364
  2. Gadbois J et al (2009) Radiographic abnormalities in cats with feline bronchial disease and intra- and interobserver variability in radiographic interpretation: 40 cases (1999-2006). J Am Vet Med Assoc 234(3):367-375
  3. Venema, C & Patterson, C (2010) Feline asthma: What's new and where might clinical practise be heading? JFMS 12:681-692
  4. Cohn, LA et al (2010) Effects of fluticasone proprionate dosage in an experimental model of feline asthma. JFMS 12:91-96
  5. Cordeau, ME et al (2004) IL-4, IL-5 and IFN-gamma mRNA expression in pulmonary lymphocytes in equine heaves. Vet Immunol Immunopathol 97:87
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