Dynamic Upper Airway Obstruction Secondary to Severe Feline Asthma

Introduction

The upper airway consists of the nasal cavity, oral cavity, laryngeal and pharyngeal regions, and proximal trachea.¹ Resistance within the upper airway decreases during inspiration, permitting passive breathing.¹ In humans, the pharynx accounts for a negligible amount of airway resistance, whereas the larynx accounts for 25–30% of the total resistance at rest and an even greater amount during exercise when the respiratory rate exceeds 60 breaths/min.¹ In small animals, the pharynx, larynx, and nasal cavity accounts for ∼ 60% of the upper airway resistance.² In an effort to decrease airway resistance, animals breathe through their mouths, bypassing the resistance within the nasal cavities.^1,2

Upper airway patency is a delicate balance between forces promoting collapse (negative pressure of inspiration and extraluminal positive pressure from the soft tissues surrounding the upper airways) and those maintaining patency (contracture of the pharyngeal dilator muscles, including the intrinsic laryngeal muscles).² When this balance is disrupted, extrathoracic upper airway collapse ensues, resulting in variable degrees of respiratory distress.² This phenomenon has been reported in animals with brachycephalic airway syndrome and humans with bronchial obstruction.^3–5

This report describes a case of dynamic upper airway obstruction secondary to bronchial asthma that required aggressive medical therapy and a temporary tracheostomy to successfully manage. To the authors’ knowledge, this is the first report of upper airway obstruction secondary to feline asthma in veterinary medicine. This case highlights the importance of aggressive medical therapy and recognition of this uncommon secondary sequelae of a common disease that could require surgical intervention.

Case Report

A 2 yr old castrated male domestic shorthair weighing 6 kg presented to its primary veterinarian after 24 hr of nonproductive coughing, gagging, and increased respiratory effort. The cat had a history of intermittent coughing since it was a kitten, with no reported episodes of respiratory distress. The cat was fully vaccinated, negative for both the feline leukemia and feline immunodeficiency viruses, and lived both indoors and outdoors. The owner reported no respiratory abnormalities in the littermates that lived in the same household. A lateral thoracic radiograph, reviewed by a board-certified veterinary radiologist, showed no cardiovascular, pulmonary, or tracheal abnormalities. Amoxicillin^a (23.8 mg/kg per os [PO] q 12 hr) was prescribed for a suspected upper respiratory tract infection. The amoxicillin was discontinued after three doses because no improvement was noted by the owner and the cat vomited after each dose.

The following day, the cat presented to a referral emergency facility due to an increased respiratory effort, coughing, vomiting, and voice change. Referred inspiratory and expiratory upper airway sounds and bradycardia (heart rate was 100 beats/min) were ausculted. No polyps were detected on an otoscopic examination, and the remainder of his physical exam was unremarkable. A 6-lead electrocardiogram showed a sinus bradyarrhythmia (heart rate was 70 beats/min). Thoracic radiographs, reviewed by a board-certified veterinary radiologist, showed a very mild cardiomegaly with normal vasculature and a mild diffuse interstitial pattern with a mild bronchial pattern in the caudodorsal lung fields. Differential diagnoses at that time included asthma, parasitism (Dirofilaria immitis [D. immitis] and Aelurostrongylus abstrusus [A. abstrusus]), and infectious bronchitis.

Abnormalities on the complete blood cell count revealed a mature neutrophilia (10.7 × 10³/μL; reference range, 2.1–10.1 × 10³/μL) and eosinophilia (2.1 × 10³/μL; reference range, 0.0–1.9 × 10³/μL). The serum biochemical analysis was unremarkable. No laryngeal abnormalities were noted on sedated oral examination performed under propofol^b titration (6.67 mg/kg IV), but the left tonsil was subjectively larger than the right. Aspirates of the left tonsil were not obtained. Following sedation, the cat had significant respiratory distress with inspiratory stridor and was placed in an oxygen cage (fraction of inspired O₂ was 40%). The cat’s respiratory distress resolved within 1 hr and he was transferred to another referral emergency facility for nasal computed tomography (CT) and rhinoscopy to further characterize the inspiratory stridor. One dose of terbutaline^c (0.01 mg/kg subcutaneously) and prednisolone^d (0.85 mg/kg PO) were administered prior to transfer.

On presentation to the second emergency facility, the cat had a moderate respiratory effort and inspiratory stridor with intermittent wheezes and episodes of open-mouth breathing. The cat was placed in a supplemental oxygen cage (the fraction of inspired O₂ was 40%), and his respiratory pattern normalized within 1 hr. After 1 hr, the cat’s heart rate was 200 beats/min, the respiratory rate was 16 breaths/min, and the rectal temperature was 38°C. Referred upper airway sounds with inspiratory stridor were ausculted over all lung fields. No abnormalities were noted on either cardiac auscultation or tracheal palpation, and the remainder of the physical exam was unremarkable. Overnight, the cat remained stable in the oxygen cage. No additional medications were administered because the cat had already been administered terbutaline and prednisolone for the presumed inflammatory airway disease. Approximately 8 hr later, the patient became vocal, vomited twice, and had an episode of severe inspiratory respiratory distress. The cat was administered dolasetron^e (0.5 mg/kg IV q 24 hr), intramuscular terbutaline (0.01 mg/kg q 12 hr), albuterol^f (2 puffs^g q 8 hr), fluticasone^h (2 puffs q 12 hr), and dexamethasoneⁱ (0.13 mg/kg IV q 12 hr). The cat’s respiratory distress did not improve.

The cat was intubated following a IV bolus of fentanyl^j (1.5 μg/kg) and maintained on isoflurane^k. Normal laryngeal function, with no evidence of edema, was noted, and a lateral cervical radiograph was unremarkable. Nasal CT, performed to characterize the cat’s stridor, showed a small volume of isodense, noncontrast-enhancing dependent fluid (possibly mucous) surrounding the nasal turbinates in the caudal aspect of the nasal cavity. No anatomic abnormalities were identified.

A tracheoscopy, rhinoscopic biopsies, and an endotracheal wash were also performed. No gross abnormalities were noted on tracheoscopy, and there was no evidence of tracheal collapse. A gastroduodenoscopy was subsequently performed, and biopsies were obtained because the cat continued to vomit despite discontinuation of the amoxicillin.

Dexamethasone (0.13 mg/kg IV) was administered prior to extubation to reduce upper and lower airway inflammation. The cat’s laryngeal function was evaluated by a surgeon at the time of recovery from the general anesthetic (following extubation), and appropriate abduction of the laryngeal cartilages was noted. The cat was recovered in an oxygen cage and was eupneic for 9 hr before having another episode of open-mouth breathing, together with raspy inspiratory upper airway sounds and wheezes. An additional dose of dexamethasone and albuterol were administered with minimal improvement. The cat was then mildly sedated with IV butorphanol^l (0.08 mg/kg) and his respiratory distress resolved.

The cat was prescribed doxycycline^m (5 mg/kg IV q 12 hr) for possible Mycoplasma spp. infection, and the dexamethasone was increased to 0.27 mg/kg IV q 12 hr. A significantly higher dose of dexamethasone was chosen due to the degree of respiratory distress and presumed airway inflammation. An occult heartworm testⁿ was antibody positive and antigen negative, suggestive of exposure to D. immitis. An echocardiogram was recommended based on the cat’s mild cardiomegaly and possible heartworm infection, but the owners declined because feline heartworm disease was low on the list of differential diagnoses. Over the next 24 hr, the cat was treated medically with albuterol, dexamethasone, fluticasone, terbutaline, and doxycycline at the doses prescribed above, pending the laboratory results.

Rhinoscopic biopsies showed minimal neutrophilic rhinitis. The endotracheal wash cytology showed mucoid, neutrophilic, lymphocytic, and eosinophilic inflammation with goblet cell hyperplasia and low numbers of hemosiderophages consistent with feline asthma. No growth was noted on the aerobic culture of the endotracheal fluid. Gastric mucosal biopsies showed a mild epithelial hyperplasia, and duodenal biopsies showed minimal to mild lymphoplasmacytic duodenitis. Polymerase chain reaction (PCR) for Mycoplasma spp.^o was requested on the endotracheal fluid, and a fecal sample for was submitted for Baermann fecal sedimentation evaluation^p.

On day three of hospitalization, the cat became distressed (vocalizing with episodes of open-mouth breathing and increased inspiratory effort) and was sedated with acepromazine^q (0.01 mg/kg IV). Minimal improvement was noted. The cat became cyanotic and was intubated following the administration of propofol (3.3 mg/kg IV). Additional doses of albuterol (3 puffs via the endotracheal tube), intramuscular terbutaline (0.06 mg/kg), IV dexamethasone (0.27 mg/kg), and IV butorphanol (0.08 mg/kg) were administered to decrease airway inflammation and to sedate the cat. Once intubated, the cat’s respiratory effort normalized. Ventilatory support was not required. One hr later, the cat extubated himself. The cat’s respiratory effort immediately increased and severe inspiratory stridor was noted. The cat was reintubated, and an emergency tracheostomy was performed using a standard technique to alleviate the cat’s suspected upper airway obstruction.6 A 3.0 mm tracheostomy tube^r was placed, and cefazolin^s (25 mg/kg IV q 8 hr) was as administered because the procedure was not performed in a sterile surgical suite. Tracheostomy nebulization and suctioning treatments were instituted as standard of care. Within 6 hr, the patient was breathing comfortably in the O₂ cage (fraction of inspired oxygen of 40%) and he began eating for the first time since being hospitalized.

On day four of hospitalization, the supplemental oxygen was discontinued and fenbendazole^t (50 mg/kg PO q 24 hr) was prescribed for possible lungworm infection pending the results of the Baermann fecal sedimentation examination. On day five of hospitalization, the cat began to cough and wheeze during restraint. The tracheostomy tube was suctioned, and he was placed in supplemental oxygen until his respiratory pattern normalized. After an additional dose of albuterol and fluticasone, the tracheostomy tube was removed because it appeared to be occluded with mucous. The cat continued to breathe comfortably without the tracheostomy tube and was removed from the O₂ cage 5 hr later.

On day six of hospitalization, the cat was transitioned to oral medications. He was prescribed terbutaline^u (0.1 mg/kg PO q 12 hr), doxycycline^v (5 mg/kg PO q 12 hr), cephalexin^w (21.7 mg/kg PO q 12 hr), and prednisone^x (1.67 mg/kg PO q 12 hr). The albuterol (2 puffs q 8 hr) and fluticasone (2 puffs q 12 hr) were continued. No further episodes of respiratory distress or stridor occurred after removal of the tracheostomy tube.

The cat was discharged from the hospital on day seven of hospitalization with an 8 wk tapering course of prednisone (1.67 mg/kg PO q 12 hr for 3 days, 1.25 mg/kg PO q 12 hr for 7 days, 0.83 mg/kg PO q 12 hr for 7 days, 0.83 mg/kg PO q 24 hr for 3 wk, and 0.83 mg/kg PO q 48 hr for 3 wk), albuterol (2 puffs q 12 hr for 5 days, then 2 puffs q 24 hr), fluticasone (2 puffs q 12 hr), doxycycline (5 mg/kg PO q 12 hr for 10 days), fenbendazole (50 mg/kg PO q 24 hr for 10 days), terbutaline (0.1 mg/kg PO q 12 hr for 5 days), and cephalexin (21.7 mg/kg PO q 12 hr for 7 days). The results of the Mycoplasma spp. PCR and Baermann fecal sedimentation examination were both negative, but the owners were advised to complete the prescribed doxycycline and fenbendazole in case of falsely negative test results. A minimal amount of subcutaneous emphysema was noted around the tracheostomy site at the time of discharge. Despite prior documentation, no bradyarrhythmias were documented during this period of hospitalization.

A follow-up examination was performed 5 days after discharge. The cat’s respiratory rate was 32 breaths/min. Intermittent wheezes were ausculted, and the owner had described audible upper airway sounds when restrained at home. The tracheostomy site had healed, and the skin edges were apposed. A large amount of subcutaneous emphysema was palpable over the cervical region, extending down the forelimbs and over the dorsum. The emphysema was presumed to be the result of the cat continuing to breathe through an incompletely healed trachea even though the skin had closed.

No episodes of respiratory distress were noted while the prednisone was being tapered, and 1 mo after discharge, no wheezes or stridor were noted. The subcutaneous emphysema had improved and was only noted directly around the tracheostomy site. Resolution of the eosinophilia was also documented. Two mo after discharge, no subcutaneous emphysema persisted, and the cat was only receiving fluticasone (2 puffs q 12 hr). Selamectin^y (45 mg topically q 30 days) was prescribed at this time as heartworm prevention. Thoracic radiographs showed neither cardiovascular nor pulmonary abnormalities, and the owner reported normal behavior, activity level, and respiratory pattern at home. An occult heartworm test, performed 6 mo after discharge, was both antibody and antigen negative. No further episodes of coughing, respiratory distress, stridor, or wheezes were noted by the owner during the 14 mo follow-up period. The cat’s only treatment at the time of the last follow-up examination was fluticasone (2 puffs q 24 hr) and selamectin (45 mg topically q 30 days).

Discussion

Feline bronchial asthma can occur secondary to several etiologies, including allergic bronchitis of unknown etiology, parasitism (A. abstrusus or D. immitis), or infectious diseases. There is no gold standard test for the diagnosis of feline asthma in veterinary medicine, but diagnostics, including thoracic radiographs, analysis of either a bronchoalveolar lavage or endotracheal wash, Baermann fecal sedimentation examination, Mycoplasma spp. PCR, and heartworm testing can all help diagnose feline asthma.7 All of those tests were performed in this cat.

Baermann fecal sedimentation examination is the diagnostic test of choice for A. abstrusus, with a sensitivity of 84.6% and a specificity of 100%.⁸ This cat’s Baermann test was negative, but a complete course of fenbendazole was prescribed because the cat tolerated the medication and false negatives can occur. Based on the cat’s clinical improvement 36 hr prior to starting the fenbendazole, it is unlikely his pulmonary disease was secondary to A. abstrusus.

According to the American Heartworm Association, cats that test antibody positive and antigen negative were infected with heartworm larvae but do not necessarily have an active adult infection.⁹ Berdoulay et al. (2004) evaluated the sensitivity and specificity of various feline heartworm tests and reported that the one specific heartworm antibody test, which was performed in the cat described herein, had a significantly lower specificity than the other antibody tests.¹⁰ Therefore, it is possible this cat initially had a false positive antibody test. Thoracic radiographs can help increase the suspicion for heartworm disease if there is enlargement of the pulmonary arteries, which was not noted in this cat.⁹ Finally, immature and mature worms can be visualized on echocardiology.⁹ An echocardiogram was recommended but declined by the owner because heartworm disease was low on the list of differential diagnoses and the cat improved after the tracheostomy. Considering this cat seroconverted without adulticide therapy, either he was not truly been infected or he could have had a self-limited infection that contributed to his lower airway inflammation and peripheral eosinophilia.⁹

Cats with bronchial asthma commonly present for acute respiratory distress with clinical signs ranging from intermittent wheezes and coughing to life-threatening respiratory distress.⁷ These signs are due to a type I hypersensitivity reaction that results in reversible inflammation, smooth muscle contraction, bronchial hypertrophy, and bronchial wall edema.⁷ As noted by Poiseuille’s law, a reduction in airway diameter increases the work of breathing by increasing airway resistance.⁷ As the resistance increases, a greater negative intrathoracic pleural pressure is required to expand the lungs, resulting in a higher inspiratory negative upper airway pressure.² The negative pleural pressure generated can become so great that the cardia and part of the stomach are pulled into the thoracic cavity causing gastroesophageal reflux, which can cause upper airway edema and inflammation, further increasing airway resistance.¹¹ Eventually, the increase in upper airway resistance will overwhelm the factors maintaining patency causing collapse of the upper airways.^2,11

During inspiration, in nondiseased states, the transmural pressure across the upper airway decreases, promoting air to enter the respiratory tract.² This causes medial displacement of the soft tissues and dynamic upper airway collapse.² At rest, contracture of the laryngeal abductor muscles counteracts the pressure gradient across the upper airway preventing collapse.² With stress, exercise, or underlying pulmonary disease, additional work is required to breathe, which is noted by an increase in both respiratory rate and effort.¹² This results in a greater negative inspiratory pressure within the upper airways, exacerbating its collapse and further increasing the resistance and velocity of airflow.² That cycle continues until either complete obstruction of the upper airway occurs or the underlying etiology is effectively managed.^2,13

Fixed and dynamic upper airway obstructions have been extensively documented in canines, equines, felines and humans.^{1,3–5,13–22} Fixed obstructions, most commonly occur secondary to masses, strictures or external compression and affect both the inspiratory and expiratory phases of breathing.¹⁴ In animals, fixed obstructions are documented via direct visualization of the collapsed region during sedated oral examination, fluoroscopy, or videoendoscopy.^3,4,17 In contrast, dynamic lesions are difficult to definitively diagnose because they are transient in nature. In small animal veterinary medicine, dynamic lesions may be a diagnosis of exclusion.

In humans, asthma and upper airway obstructions are diagnosed with pulmonary function tests (e.g., spirometry) where the volume and flow of inhaled and exhaled air is measured, producing flow-volume and flow-time loops.^5,22 Forced vital capacity, the volume of air forcibly exhaled after a full inhalation, and forced expiratory volume in 1 sec can be measured via spirometry.¹⁸ A decrease in the ratio of forced expiratory volume in 1 sec to forced vital capacity is indicative of an obstructive bronchial disease.⁵ Flattening of the inspiratory limb of the maximal flow-volume loop is consistent with an extrathoracic upper airway obstruction.^5,16,18,23 Flow-volume loops can be performed in the nonanesthetized stable veterinary patient by placing a tight fitting mask over their mouth and nose; however, most animals with severe respiratory distress will not tolerate the restraint required to complete this test.¹² One limitation of this case report is that flow-volume loops were not performed while this patient was either awake or intubated, which could have further helped characterize the airway disease.

Studies have shown expiratory glottal collapse with inspiratory laryngeal contracture in humans with histamine-induced bronchoconstriction and exercise-induced asthma due to increased intrathoracic resistance.^18,21 Those studies also noted increased inspiratory resistance and glottal collapse when the respiratory rate was > 60 breaths/min.^20,22 A review of the human literature showed numerous reports of patients with coexisting bronchial asthma/exercise-induced asthma and functional upper airway obstruction either with or without vocal cord dysfunction.^5,16,18–20 In humans, it has been estimated that approximately 3–5% of all cases of intractable asthma are due to secondary dynamic upper airway dysfunction.¹⁹ Of those cases, several have required either emergency intubation or a temporary tracheostomy to relieve the patient’s respiratory distress.²⁰

This patient underwent several sedated oral examinations and advanced imaging that showed no evidence of fixed, anatomic upper airway abnormalities. This cat suffered from a dynamic, rather than fixed, inspiratory, upper airway obstruction that ultimately required a temporary tracheostomy. Given the fact that this cat responded to a temporary tracheostomy, his obstruction was likely rostral to the trachea. If the collapse had been either tracheal or bronchial in nature, fluoroscopy would have been useful in documenting the obstruction. The most likely cause of the upper airway obstruction was increased inspiratory resistance secondary to severe bronchoconstriction and a progressive increase in upper airway resistance that eventually resulted in upper airway collapse.

Conclusion

Severe bronchial asthma results in increased negative airway resistance that can causes a pressure gradient across the upper airway that can become so significant that the upper airway collapses. Clinically, one can see stridor progressing to complete upper airway obstruction, severe respiratory distress, and death. Diagnostics, including sedated oral examination, radiographs, tracheoscopy/bronchoscopy, and CT can be useful in characterizing the stridor, but additional diagnostics (fluoroscopy and flow-volume loops) or surgical intervention may be necessary to characterize the stridor. Clinicians should be aware of this uncommon sequelae of feline asthma because prompt recognition and treatment is necessary to alleviate the combined intra- and extrathoracic respiratory distress.