Q: Please update me on common respiratory diseases in cats.
Drs. Carol Norris Reinero, Leah A. Cohn and Ray Dillon gave excellent lectures on common respiratory diseases in cats at the 2009 American College of Veterinary Internal Medicine Forum in Montreal, Canada. Some relevant points are provided below.
Dr. Carol Norris Reinero of the University of Missouri defines asthma as a chronic inflammatory disorder of the lower airways that also has airway hyper-responsiveness and airflow limitation (leading to clinical respiratory signs) as well as airway remodeling as prominent features. Genetics and environmental exposures are thought to play important roles in asthma development.
Asthma in cats has been suggested to be related to dietary hypersensitivity. With the waxing and waning signs that normally occur with this disease in many cats, it might appear that a change of diet could alter clinical signs. However, no scientific evidence supports a dietary causation of feline allergic airway disease.
Allergic asthma is typically associated with an eosinophilic inflammatory response. However, the presence of a peripheral eosinophilia has not been correlated with the degree of airway eosinophilia. Normal thoracic radiographs have been reported in up to 23 percent of asthmatic cases. A characteristic bronchial or bronchointerstitial pattern can be seen with other respiratory diseases in cats, including chronic bronchitis, heartworm-associated respiratory disease and lungworm infection (Aelurostrongylus abstrusus). There is ongoing debate on what should be considered a reference range for the various cell types in bronchoalveolar lavage fluid and how to best discriminate feline asthma from feline chronic bronchitis, but eosinophilic airway inflammation supports a diagnosis of feline asthma (especially once parasitic diseases have been ruled out).
Feline asthma is routinely treated with injectable or oral glucocorticoids. In healthy cats, inhaled glucocorticoids have minimal systemic effects on the adaptive immune system, although they can still suppress the hypothalamic-pituitary-adrenocortical axis. Inhaled glucocorticoids have reduced eosinophilic airway inflammation in experimental feline asthma. It is commonly accepted that glucocorticoids effectively control lower airway inflammation and should be titrated to the lowest effective dose to control clinical signs of disease. Bronchodilators are important in the medical management of asthma. Albuterol (also called salbutamol in Europe), a short-acting beta2 agonist, is frequently given by metered dose inhalation using a spacer in cats. Chronic use of inhalant racemic albuterol induces neutrophilic airway inflammation de novo in healthy cats and exacerbates eosinophilic airway inflammation in experimentally asthmatic cats (the so-called beta agonist paradox). Thus, inhalant racemic albuterol should be used as rescue therapy and not as monotherapy for daily treatment.
If an underlying allergic trigger can be identified as a cause for asthma, allergen avoidance or allergen-specific immunotherapy can be tried. It is challenging to identify clinically relevant allergens in cats, as the timing and amount of allergen exposure, different numbers and types of allergens, concurrent medications and other environmental factors may influence test results. Both intradermal skin testing and serum allergen-specific IgE determination can be used; in experimentally asthmatic cats with known/controlled aeroallergen exposure, the former is sensitive and the latter (by the high affinity Fc epsilon receptor-based ELISA) is highly specific. Abbreviated protocols for allergen-specific immunotherapy called rush immunotherapy (RIT) have shown great promise in experimental feline asthma. Ongoing studies are focusing on cross-protection with RIT using one allergen unrelated to the allergen used for experimental sensitization and challenge.
Dr. Leah A. Cohn of the University of Missouri indicates that natural influenza virus infections and experimental infections can be transmitted by direct inoculation of the virus parenterally or through the respiratory tract in domestic cats. It is thought that initial viral replication occurs in the respiratory and gastrointestinal tract with subsequent viremia. Some cats can remain well despite infection; these cats most likely have exposure to lesser viral loads. In those with greater exposure, extensive pulmonary damage and multifocal organ hemorrhage and necrosis are responsible for death. Neurologic signs including ataxia and seizures in naturally infected cats likely result from nonsuppurative encephalitis. More common signs are nonspecific and include fever, depression, third eyelid prolapse, conjunctivitis, increased respiratory effort, nasal discharge and icterus. Sometimes, sudden death is observed within days of infection.
More causes to consider
There are more likely causes for an acute onset of respiratory signs in cats (e.g., herpesvirus, calicivirus, bacterial pneumonia), but veterinarians should be vigilant to the possibility of influenza infection. Viral isolation or RT-PCR from oropharyngeal or rectal swabs or necropsy specimens is the typical method of confirmation. Immunohistochemistry can be used on infected organs. Serologic diagnosis using hemagglutination inhibition is also possible. Treatment would be largely supportive.
Chronic rhinosinusitis in cats is a common and frustrating condition. Often, veterinarians reach for antibiotics to treat this condition without pursuing a specific diagnosis in a belief that all or nearly all rhinosinusitis is the result of persistent or recurrent viral infection with secondary bacterial infection. However, many nonviral disease conditions may result in similar clinical signs of chronic nasal discharge, including nasal neoplasia (carcinoma and lymphoma), inflammatory rhinitis, mycotic rhinitis (e.g., cryptococcosis, aspergillosis), dental disease, nasal polyps and foreign bodies.
In certain geographic regions, lung parasites account for a substantial proportion of respiratory disease in cats. Important parasitic respiratory pathogens include Paragonimus kellicotti, Aelurostrongylus abstrusus and Eucoleus aerophilus (previously known as Capillaria aerophilia). A common misconception holds that these parasites can be ruled out through fecal flotation. Pulmonary parasites are shed through the feces only on an intermittent basis. Immature pulmonary parasites (ova or larvae) must be expectorated and swallowed prior to fecal shedding. For this reason, shedding is only intermittent at best. Even when using the most sensitive, most appropriate fecal examination techniques, intermittent shedding means that infections may be missed from a single sample. Therefore, it is recommended that fresh feces be examined on at least three different occasions before ruling out lung parasites as a cause of respiratory disease. Alternatively, a course of anthelmintic sufficient for the treatment of lung parasites can be employed as a therapeutic trial.
Acute upper respiratory infections (URIs) are common in cats. Traditionally, amoxicillin has been used to treat these infections. It is inexpensive, safe and available in convenient dosage strengths, and it has activity against most gram-positive and anaerobic pathogens. Recently, many veterinarians have switched from these traditional treatments with amoxicillin or doxycycline to azithromycin. Azithromycin has a long tissue half-life in cats, allowing it to be dosed infrequently. The drug would be expected to be efficacious for treating mycoplasmosis as well as infection with many gram-positive and gram-negative organisms. Despite the fact that some infections would be predicted to not respond to amoxicillin based on in vitro culture results, there was no difference in outcome between cats treated with amoxicillin and those treated with azithromycin. Azithromycin remains a reasonable antimicrobial choice for treating URIs in cats. However, it is considerably more expensive than some more traditionally used medications and may not offer a substantial advantage in regard to treatment efficacy.
Veterinarians have been taught that pyothorax follows cat fight wounds. This seemed to fit with the predominance of infections caused by mixed bacterial populations of anaerobes and facultative anaerobes plus oral flora. Recently, it has been proposed that infections are more likely the sequelae of parapneumonic spread of infection after colonization and invasion of lung tissue by oropharyngeal flora related to upper respiratory infection.
Unfortunately, a variety of both bacterial and viral organisms can be found as normal flora in healthy cats, after recovery from infection of previously ill cats, or as pathogens involved in current infections. Simply finding an organism doesn't prove cause and effect. This is true even if the organism is a known pathogen, such as feline herpesvirus 1 (FHV-1). Cats infected with FHV-1 remain latently infected long after clinical recovery from any illness; cats previously vaccinated for FHV-1 may be infected but never develop any clinical illness yet remain latently infected. Therefore, FHV-1 may be identified in either healthy cats or in cats with upper respiratory signs due to some altogether different cause. To even make matters more complicated, commonly used assays such as PCR cannot distinguish naturally occurring virulent FHV-1 infection from modified-live vaccine strains.
A similar problem occurs in relation to calicivirus. Cats may be healthy carriers of the virus for prolonged periods. One of these carrier cats might easily develop upper respiratory signs for some reason completely independent of calicivirus infection and yet "test positive" for calicivirus.
Similar issues arise with bacterial infections. Most organisms that cause bacterial rhinitis as secondary, opportunistic pathogens are found as part of the normal nasal or oropharyngeal flora. Simply growing these organisms from nasal culture does not prove that they are the primary, or even a secondary, cause of nasal or upper respiratory signs. Veterinarians who wish to obtain nasal cultures should request anaerobic and Mycoplasma species culture since these types of pathogens may have relevance and are not detected by routine aerobic culture.
Dr. Ray Dillon of Auburn University indicates that the last 30 years have increased the basic understanding of heartworm disease in cats and emphasized the clinical importance of this disease. Several basic concepts have been confirmed by data collected in clinical practices, shelter cat populations and experimental studies:
> Cats develop bronchial disease as a consequence of immature adult heartworms that never become fully adult and initiate heartworm-associated respiratory disease (HARD), which can persist for 12 months after a single short-lived infection.
> Cats that get only immature adults that live for two to three months and cats that develop adult heartworms both develop HARD associated with the death of immature adults.
> Cats get immature heartworms as early as 75 to 90 days after infection, and immature heartworms die creating lung and arterial disease that persists for up to 12 months.
> Cats that develop lung disease from immature heartworms that have died may be antibody-positive for only a few months although the bronchial disease persists.
> Cats with only immature adult heartworms will be antigen-negative, and, echocardiographically, worms cannot be visualized although bronchial disease is evident radiographically.
> The bronchial disease of heartworms in cats has 1) a bronchial epithelium component, 2) a smooth muscle proliferation remodeling and 3) alteration of bronchial smooth muscle reactivity.
> Some cats do develop adult heartworms that may live for up to three or four years in the cats.
> After adult heartworms develop, the lung's inflammatory reaction is reduced in cats, and signs may be limited for long periods although radiographic bronchial patterns continue.
> The lung recovery from heartworm infections is not uniform in parenchymal distribution, leaving severely diseased parenchyma adjacent to relatively normal lung.
> The death of immature as well as adult heartworms may be associated with acute lung injury and severe type 1 cell injury of alveolar capillary beds.
> Some cats that develop mature adult heartworms demonstrate minimal clinical signs prior to acute crisis typically associated with adult worm death.
> Most cats that develop adult mature heartworms survive the infection as the worms die over the next two to four years.
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: