Chronic upper respiratory disease in cats (Proceedings)

Anatomy and Physiology

The nasal cavity is defined as part of the upper respiratory tract that extends from the nares to the choanae. The choanae is the caudal most part of the nasal cavity that communicates with the nasopharynx. The nasal cavity is surrounded by bone and divided in half by a cartilaginous and boney septum. A scroll-like turbinate system, the nasal conchae, is generously supplied by blood vessels and nerves and acts to increase the surface area of the nasal passages. The large surface area is important for filtration, humidification, and warming of inspired air. These actions serve to prevent particulate matter from entering the lower airways and protect the lower airways from cold and dry air.

The nasal conchae/turbinates can be divided into dorsal, ventral and ethmoidal nasal conchae or turbinates. The ethmoidal turbinates fill the caudal nasal cavity and are made up of outgrowths of the ethmoid bone covered with mucosa. A specialized olfactory area is located in the region of the ethmoidal turbinates and ventral nasal conchae. Specialized neuroepithelium covering these turbinates gives rise to the olfactory nerves, which transmit information to the brain through the cribriform plate. The location and proximity of the caudal nasal cavity and cribriform plate to the brain make extreme caution necessary when performing nasal flushes, biopsy, or surgery. Cats have a highly developed sense of olfaction that has a role in protective behavior and appetite. In cats with severe nasal disease anorexia may result from an inability to smell food. The meatuses are air passageways that occupy the space between the nasal turbinates and include the dorsal, middle, ventral, and common. The ventral meatus is the largest and leads into the choanal region. The common meatus unites the dorsal, middle and ventral meatus and is found on either side of the septum. The paranasal sinuses in the cat include the frontal and sphenoid sinuses. They are of questionable function in the normal animal.

Most of the airways including the nasal passages and nasopharynx are covered by a mucociliary transport system. This consists of ciliated pseudo-columnar epithelium, the respiratory epithelium, which contains abundant serous and mucus glands. The epithelium is covered by a mucus layer that is secreted by the serous and mucus glands. The mucus layer is made up of two parts: an outer viscous layer and an inner watery layer. The cilia of the respiratory epithelium are embedded in the more watery layer. When large particles such as dust, pollen, and bacteria are breathed in they are trapped in the viscous mucus layer. The cilia then beat in a direction toward the pharynx to carry the viscous outer mucus layer with the trapped particles to be swallowed. The production of local secretory IgA by epithelial cells also play a role in the defense mechanism of the upper respiratory tract. The ultimate cleaning procedure for the nasal cavity is the sneeze, which starts with a rapid inspiration followed by an involuntary, sudden, violent, and audible expulsion of air through the nose and mouth. This reflex occurs after stimulation of the sensory receptors in the nasal mucosa.

The nasal passages of healthy cats are normally colonized by a variety of gram positive and gram-negative aerobic or facultative commensal bacteria.2 Less is known about the normal flora of the nasopharynx of cats.

The feline nasopharynx has well-defined anatomic boundaries. It is located above the soft palate and bordered rostrally by the nasal choanae. The caudal border of the nasopharynx is defined by the intrapharyngeal ostium with demarcations of the caudal border of the soft palate and the palatopharyngeal arches. It sits at the crossroads to the entrances to the lower respiratory tract and upper gastrointestinal tract and has close anatomic relation to the caudal nasal cavity, nasofrontal openings, and pharyngeal openings of the Eustachian tubes. Since these structures are in such close proximity disease in the upper respiratory tract may be widespread leading to complications in adjoining areas. It has been reported that 34% of cats with CT evidence of nasopharyngeal disease had signs of bulla effusion. 65% of cats in the same previous study that were evaluated for chronic upper respiratory disease had CT evidence of soft-tissue opacity within the paranasal sinuses.

The larynx has three main functions: acts as a conduit for air, protects the lower airway from aspiration during deglutition, vocalization.

History and Clinical Signs

The medical history of a cat with nasal disease is generally clear-cut because the signs of disease – discharge, sneezing, epistaxis – are obvious to the owner. Additional inquiries should be made as to the timing, frequency, onset, and duration of clinical signs; the cat's lifestyle and travel history; general condition, appetite, activity, endurance; prior therapies and efficacy of such treatments. If nasal discharge is the predominant signs questions should be asked as to determine if the discharge is unilateral (right or left nostril) or bilateral. The nasal discharge should be characterized (watery, mucoid, pus, blood) and its frequency noted such as discharge only noted when sneezing occurs or modest versus frequent epistaxis. If sneezing is noted duration, timing, and frequency should be ascertained. An owner should be questioned as to the presence of pain. Additionally, is there increased respiratory noise? Stertor is a soft snoring, rustling, or sniffing sound that is synchronous with inspiration, expiration, or both. Narrowing of the nasal passages or nasopharyngeal obstruction can increase the velocity of airflow causing stertor. Gagging or vomiting may be a signs of a nasopharyngeal mass. Stridor is a wheeze or whistling sound usually heard on inspiration that reflects changes in the larynx. Change in voice should be questioned indicating a possible laryngeal disease. Owners may complain of respiratory distress/dyspnea, as cats with nasal obstruction tend to avoid mouth breathing almost to the point of suffocation.

Physical Examination

The cat should be closely examined for evidence of facial deformity. Palpation of the nose and retropulsion of the globes should be included. The eyes should be examined for epiphora or exophthalmia. Under quiet conditions the clinician should listen carefully for stertor especially with the mouth closed. Airflow can be assessed by watching movement of a small fluff of cotton held in front of each nostril or for the presence of condensation on a glass slide. The area of the nostrils should be examined for discharge or crusts and epithelial lesions. The mouth should be carefully inspected with the roof of the mouth (ventral wall of the nasal passages) palpated if possible. Oral or lingual ulcers and any pain on opening the mouth should be noted. The teeth may be inspected at the same time. Lymph nodes should be carefully palpated. A fundic examination should be performed.

Diagnostic Evaluation

A complete blood count, serum chemistry panel, and urinalysis will provide information on the cat's overall health, but will not likely yield specific information as to the cause of the upper respiratory disease. Thoracic radiographs may be indicated especially for older cats in which neoplasia may be more likely. Microscopic examination of nasal discharge may assist in determining a fungal etiology to upper airway disease such as in nasal Cryptococcus in cats. Cryptococcal antigen titers are very sensitive and specific for a diagnosis of nasal crytococcal infection.

Special Diagnostic Procedures

Additional special diagnostic procedures for cats with upper airway disease requires general anesthesia: skull radiography, computed tomography (CT), rhinoscopy for evaluation of foreign bodies for biopsy and bacterial/fungal cultures and virus isolation/PCR on nasal biopsy specimens or nasal flush fluid, nasopharyngoscopy, and, laryngoscopy, and less commonly performed for upper airway disease, magnetic resonance imaging. Demko et al showed that advanced diagnostic testing such as imaging studies and biopsy can increase the likely-hood of achieving an etiologic diagnosis of chronic nasal discharge. However even when invasive or expensive diagnostic testing is performed, an etiology for chronic nasal discharge may be identifiable in less than half of all cases - classifying most as having idiopathic disease.

Skull radiography consisting of dorsoventral and lateral projections may be of limited value in examining the nose and nasal sinuses in the cat due to superimposition of structures. Additional projections such as the craniocaudal, open-mouth projections, or radiographs with intra-oral film may be required. Cats should be placed under general anesthesia to achieve perfect positioning for these views to increased diagnostic value. In referral practices CT is replacing skull radiography due to its superior image quality and diagnostic capabilities. Because the images with CT represent slices there is decreased summation of tissues and superimposition of structures. Sheonborn et al. showed that CT was more sensitive that radiographs in localizing disease and determining extent of disease. Procedural time is decreased with CT as well. Contrast agents can be given with CT to help define normal from abnormal tissues and facilitate vessel recognition.

Laryngeal function can be evaluated at the time of anesthesia induction and with the patient under anesthesia evaluation for laryngeal masses can be performed as well as biopsy of laryngeal masses. Biopsy can be performed using (cup-pinch) biopsy forceps. It is important to carefully monitor a patient during recover from anesthesia when laryngeal disease is diagnosed, being ready to re-intubate the cat or even perform a tracheotomy. The nasopharynx can be evaluated with the use of a spay hook to pull the soft palate rostrally and a dental mirror to facilitate examination. Using a flexible endoscope to retroflex into the nasopharyngeal cavity can provide for an excellent examination of that space. Rhinoscopy can be performed in an anesthetized cat with a rigid or flexible endoscope. Rigid endoscopes provide for better image quality than the very small flexible scopes. Rhinoscopy can be used to evaluate for foreign bodies, nasal turbinate quality, nasal masses, parasites, and to facilitate nasal biopsy. It has been shown that rhinoscopic lesions do not always reflect the severity of histpathologic changes and as such biopsy is recommended at the time of rhinoscopy. Rhinoscopy can also be performed with the use of an otoscope with a strong light source. Due to the narrow nasal passages of the cat, rhinoscopy can be challenging and visualization limited. When nasal biopsies or nasal flushing is performed, tracheal intubation is necessary. The back of the cat's mouth should be packed off as well with gauze sponges (remember to count), or Kling to absorb blood and fluid.

Specific Diseases of the Nasal Cavity and Nasopharynx

Common Causes of Chronic Sneeze, Noisy Breathing, Nasal Discharge (clear, cloudy, green/yellow, +/-blood tinged)

     • Allergy (?)

     • Nasal mass (neoplasia, polyp)

     • Idiopathic chronic rhinosinusitis

     • Nasal foreign body

     • Nasal parasites

     • Congenital disease (oropharyngeal clefts, choanal atresia)

     • Nasopharyngeal abscess

     • Epistaxis

     • Systemic disease

     • Local disease

     • Neoplaisa

     • Fungal infection (Cryptococcus)

     • Secondary bacterial infection

     • Viral rhinitis

     • Tooth root abscess

     • Environmental irritants

     • Stenotic nares (brachycephalic cats)

     • Uncommon causes

     • Nasopharyngeal stenosis

Allergic Rhinitis

Allergic rhinitis is presumed to occur as in humans, but confirmation of the diagnosis (IgE based rhinitis) has yet to be demonstrated. It is usually ruled out with the empiric use of antihistamines. Hydroxizine may have the greatest efficacy in feline patients. Chronic cases may respond better to oral steroids or inhaled steroids such as fluticasone.

Mass

The two most common nasal tumors in cats are carcinoma and lymphoma. Both are treated with radiation therapy; chemotherapy may be recommended in conjunction with radiation therapy for lymphoma. Nasal polyps occur in the nasal cavity of cats. Clinical signs are suggestive of obstructive rhinitis. Bilateral obstruction may be caused by bilateral nasal polyps or a unilateral polyp that extends into the nasopharynx. Polyps consist of focal accumulation of edema fluid, hyperplasia of the submucosal connective tissue and variable inflammatory infiltrate (eosinophils, plasma cells, and lymphocytes). Diagnosis of nasal mass is usually made by CT and rhinoscopy. Rhinoscopy alone may be adequate for diagnosis of a nasal mass, especially for that of a nasal polyp. Complete removal of a nasal polyp is difficult and requires removal of all structures in the nasal cavity. Nasopharyngeal polyps most likely originate from the middle ear. They are composed of inflammatory granulation tissue covered with respiratory epithelium. Polyps arising in the middle ear cavity may extend by a stalk down the Eustachian tube into the nasopharynx, remain in the middle ear cavity, or migrate through the tympanic membrane into the horizontal ear canal. Clinical signs of affected cats include stertorous respiration, occasional sneezing, nasal discharge, dysphagia, weight loss, Horner's syndrome, head tilt, otic discharge, and pawing at the ears. If the polyp is large enough to cause intermittent laryngeal obstruction respiratory stridor and syncope may occur. It is the most common nasopharyngeal disease of younger cats and accounts for almost one third of all feline nasopharyngeal diseases. No sex or breed predilection exists; although nasopharyngeal polyps are most commonly found in younger cats (mean 3 years: range 4 months to 6.1 years; median age 24 months), this disease should also be included in the differential diagnosis for older cats. It is unknown why nasopharyngeal polyps occur, but it does not seem likely that the polyps are a manifestation of chronic viral (FCV or FHV) infections. With the use of PCR testing, no evidence of persistence of feline herpesvirus-1 or feline calicivirus was found in polyps of 21 cats. Definitive diagnosis is made by direct visualization of the nasopharyngeal mass and histopathology. Quite often, nasopharyngeal polyps can be discovered with digital palpation of the soft palate. Diagnostic imaging (skull radiographs and CT) is not necessary for the diagnosis but can provide valuable information toward the extent of the mass and possible middle ear involvement. Treatment depends on clinical presentation and extent of disease. If evidence of concurrent middle ear involvement is seen, a ventral bulla osteotomy is indicated. If the disease appears to be limited to the nasopharynx, then traction avulsion to remove the polyp at its stalk is usually attempted. The high rate of reoccurrence with this disease (33%) has led to the suggestion that ventral bulla osteotomy should be performed on all cats with nasopharyngeal polyps.

Idiopathic Chronic Rhinosinusitis

This disease process represents one of the most common causes of chronic upper respiratory disease in cat. The cause is unknown. It may have some relation to chronic FVH-1 or FCV carriers. Some have postulated that chronic idiopathic rhinosinusitis is a result of damage to the turbinates from previous URI infections allowing for chronic intermittent colonization and infection with environmental bacteria. A subset of cats with chronic idiopathic rhinosinusitis have a history of acute FVH-1 infection or FCV infection. Allergy has also been a proposed etiology or possibly an immune mediated disease. The disease can be seen in any age of cats and clinical signs may exist for years. Cats usually have a history of chronic intermittent or progressive sneezing, stertor, and nasal discharge. Nasal discharge is usually copious, mucopurulent, bilateral, and can occasionally contain blood. Significant destruction of turbinates may be seen on CT, which is associated with a worsening prognosis. It is diagnosed by exclusion of other causes of disease (i.e. foreign body, fungal infection, etc) and histopathologic findings of inflammatory infiltrate with lymphocytes and plasma cells primarily, eosinophils, or neutrophils and variable degree of turbinate lysis and remodeling. There can be considerable discordance between rhinoscopic changes and degree of inflammation on histopathology.

In general treatment is first undertaken with antibiotics (ideally based on culture of nasal flush or tissue culture) for approximately 4-6 weeks to clear a secondary bacterial component of the disease, following with steroid therapy. Inhalants may work well for this purpose (fluticasone, Flovent 220mcg metered dose, 2 puffs twice daily and wean, some cats may respond to lower concentration Flovent). Flovent usually takes approximately 1-2 weeks to reach maximal efficacy. During this time concurrent administration of oral steroid (prednisolone) may provide additional relief for the patient. Glucocorticoids may exacerbate infection and some cats respond poorly. Additional therapies that may be considered include antihistamines, L-lysine, NSAIDs (not concurrently with steroids), Little Noses saline drops, or Little Noses decongestant drops on a three-day on three-day off schedule to avoid rebound vasodilation. Famciclovir, an anti-viral, has been evaluated in a small number of cats and seems to be well tolerated with a positive impact on the cat's condition. Intermittent nasal suction and flushing (anesthesia usually required) may provide additional relief for the severely affected cat. The mucus produced by cats is rich in sialic acid giving feline mucus a distinctive thick, ropey texture. Most cats cannot sneeze forcefully enough through their narrowed passages to clear the discharge material. Response to therapy is quite variable. This can be a very frustrating disease for cat owners and practitioners.

Nasal Foreign Body

In cats, unlike dogs, nasal foreign bodies are mostly composed of plant material that lodges in the nasal cavity or above the soft palate after coughing or vomiting. Clinical signs may include sneezing, reverse sneezing, gagging, and repeated swallowing and may be acute or chronic. More chronically stertorous breathing and nasal discharge is seen. FBs may be recognized and removed with rhinoscopy, especially retroflex examination of the nasopharynx and choanae. Unless a foreign body is radio-opaque, imaging with radiographs or CT will not be helpful for identification. The nasal cavity should be copiously flushed from the anterior nares with saline, packing off the back of the mouth/pharyngeal region with gauze or Kling to trap the material. It may be difficult given the limited space to extract foreign with a flexible or rigid scope. Occasionally rhinotomy (dorsal or ventral approach) is needed to remove foreign material.

Fungal Infection

Cryptococcus species may cause rhinitis and/or nasopharyngitis and is the most common cause of fungal rhinitis in the cat. Lesions occur most commonly in the rostral nasal cavity. Cats may exhibit sneezing, epistaxis, and nasal discharges. In more chronic disease granulomatous lesions may be seen at the external nares and submandibular lymphadenopathy may be present. Infection can penetrate the bones overlying the nasal cavity leading to swelling of soft tissue over the bridge of the nose giving cats the characteristic "Roman nose". Less commonly the lesion may be present in the nasopharynx causing signs of upper airway obstruction without rostral nasal disease. Penetration of the cribriform plate can occur resulting in cryptococcal meningoencephalitis and optic neuritis (fundic examination!!) Cryptococcal granulomas can appear polypoid resembling nasal/nasopharyngeal polyps on gross observation necessitating that all lesions be submitted for histopathology. The cryptococcal antigen titer is very sensitive and specific for the diagnosis of cryptococcal infections. Itraconazole (may be more effective) or fluconazole may be used for the treatment of cryptococcal rhinitis. Treatment should extend 1-2 months past clinical resolution or until antigen titer is negative. Prognosis is good for recovery unless disease is disseminated, or there is CNS or ocular involvement. Other causes of fungal rhinitis in the cat include less commonly Aspergillus or Penicillium spp. Ocular involvement may be seen with nasal aspergillosis. Oral anti-fungal medications may be considered, clotrimazole nasal flush may have better efficacy for Aspergillus or Penicillium. Various other fungal organisms have been reported to infect the nasal cavities of cats.

Bacterial Rhinitis

Primary bacterial rhinitis is uncommon in cats and usually develops as a sequela to other primary nasal/nasopharyngeal diseases (viral rhinitis, foreign body, tumor, etc.) due to disruption of the normal mucociliary mucosal integrity. Bordetella bronchiseptica, Chlamydophilia felis, Mycoplasma spp, Staphylococcus spp, and Streptococcus spp may cause primary bacterial disease. Streptococcal and Staphylococcal species are commonly found as part of the normal nasal flora in addition to Pasteruella and a variety of anaerobic bacteria. Anaerobic species of bacteria, Mycoplasma spp., and a variety of potentially pathogenic organisms (Pasturella multocida, Eschericia coli, Streptococcus viridians, etc.) were more commonly detected (cultures from nasal flushing and tissue cultures) from cats with chronic rhinosinusitis when compared to control cats. Antibiotic therapy ideally should be based upon culture of nasal flush fluid or tissue. Doxycycline is the treatment of choice for Bordetella, Mycoplasma, Chlamdophilia. Azithromycin, a potentiated penicillin, or clindamycin are additional antibiotics that may be used empirically. This author rarely cultures nasal biopsy tissue or nasal flush fluid and never cultures nasal discharge. Bordetella vaccination may be considered for cats at a high risk of exposures.

Viral Rhinitis

Viral rhinitis is an important disease in cats. Clinical signs initially include paroxysmal sneezing, conjunctivitis, and serous ocular and nasal discharge. Approximately 5 days after the onset of sneezing the discharge may become mucopurulent and there may be ocular complications (corneal ulcers). The condition usually lasts for 2-3 weeks. FHV-1 and FCV are the most prevalent and virulent of the respiratory pathogens of cats and account for at least 80-90% of their upper respiratory infections. The use of modified live virus vaccine against the viruses has decreased mortality and morbidity but not eliminated the disease. These viruses can spread rapidly among kittens and the prevalence of chronically infected virus carriers is high, making elimination impossible. An estimated 80% of cats recovering from acute infection become chronic carriers. Treatment is generally supportive. In chronic, severe cases Famciclovir may be considered.

Viral infection, mainly FHV-1 complicated by secondary bacterial infection is commonly implicated as the underlying cause of chronic (signs > 2 mo) rhinosinusitis. However, a prospective study investigating the variety of organisms involved in chronic rhinosinusitis FHV-1 was detected via PCR from tissue biopsy or nasal flush in both control cats (no evidence of nasal disease) and cats with chronic rhinosinusitis of unknown cause.

Nasopharyngeal Stenosis

The normal caudal nasopharyngeal opening in the cat is approximately 5 mm in diameter. Occasionally scar tissue forms a membranous web above the soft palate resulting in a pin-hole sized aperture that obstructs flow through the naso-pharynx. Stenotic lesions can occasionally be imperforate. The lesion evident on nasopharyngeal retroflexion endoscopy and on CT (saggital images). Clinical signs of upper airway obstruction are more pronounced when cats sleep or eat. The stenosis may result from chronic infection, aspiration rhinitis, or may be congenital (choanal atresia). Treatment of nasopharyngeal stenosis includes conservative use of periodic antibiotics to address secondary bacterial infection, and nasal flushing. Surgical techniques have been described as well as balloon dilation, breaking down of the membranous web with the use of forceps. Placement of a nasopharyngeal stent may provide the least chance of recurrence.

Summary

Nasal/nasopharyngeal disease is common in cats. There are many causes; however in many (possibly > 1/2) a specific etiology cannot be identified and these cats are classified as having idiopathic chronic rhinosinusitis, which can be frustrating for owner and practitioner as treatment success may be poor. Advanced diagnostics (imaging with CT, rhinoscopy, biopsy, and culture) may increase chances of a definitive diagnosis and thus treatment success.

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