A One Health review of aerodigestive disease in dogs

Abstract This review article seeks to define and describe aerodigestive disease in dogs, and review current and emerging methods of diagnostic evaluation. Aspiration of gastric contents into the respiratory tract is associated with the development and progression of numerous respiratory diseases in humans. In veterinary medicine the term “aspiration” is considered synonymous with “aspiration pneumonia” which, while frequently encountered, does not accurately reflect the breadth of aspiration associated respiratory syndromes (AARS). In the clinical veterinary literature, the effect of alimentary dysfunction on respiratory disease and vice versa (aerodigestive disease) is rarely investigated despite evidence in the human literature, animal models, and some studies and case reports linking alimentary and respiratory disease in small animals. Current methods of investigating aerodigestive diseases in veterinary patients are limited by inadeqate sensitivity or specificity, potential for bias, cost, and availability. This necessitates investigations into advanced diagnostics to identify potentially underrecognized animals with AARS. Additionally, similarities in anatomy, physiology, and several disorders between dogs and humans, make experimental and naturally occurring canine models of AARS integral to translational research. Thus, evaluating dogs with aerodigestive disease might represent an area of substantial clinical relevance in human as well as veterinary medicine.

obstructive pulmonary disease (COPD). [3][4][5][6][7] Uncontrolled AeroD including gastroesophageal reflux disease (GERD), and its extraesophageal manifestation, extraesophageal reflux disease (EERD), contribute to diminished lung function, morbidity, and increased treatment costs. 8 While treatment of AeroD improves prognosis in people, obvious clinical signs of alimentary disease might be absent, making identification diagnostically challenging. 2,3,9,10 Though historically focused on aspiration pneumonia, AeroD in dogs encompasses a wide variety of disorders (Table 1) which will be further discussed in this review. 2,14,23,[76][77][78][79] As in people, in some cases treatment for alimentary diseases improves prognosis, for example, in dogs undergoing surgical correction of brachycephalic obstructive airway syndrome (BOAS). 80 Additionally, the challenges in diagnosing AeroD in people are mirrored in dogs presenting without obvious alimentary clinical signs (ie, occult disease). 2 Increasing clinical awareness of AeroD in dogs and a multimodal clinical approach are necessary for identification and optimal treatment.

| MECHANISMS OF AIRWAY PROTECTION
Aerodigestive diseases often represent failures of airway protection.

| Normal swallowing
Normal swallowing is an important means of airway protection, with dysphagia being an important risk factor for aspiration-associated respiratory syndromes (AARS). 81,114 A swallow is classically divided into 3 sequential phases. 87,115 The oral/preparatory phase is largely voluntary and responsible for the accumulation of a formed food bolus within the vallecullae which is bordered by the soft palate, elevated epiglottis and base of the tongue ( Figure 2). 82,87 The pharyngeal swallow phase might occur spontaneously (reflexive swallow) or be associated with feeding behavior. 81,96 A pharyngeal swallow triggers the esophageal phase by initiating primary esophageal peristalsis. Esophageal peristalsis, either primary or secondary, conducts the bolus into the stomach through an open lower esophageal sphincter (LES) followed by LES closure with transient hypertonicity to prevent reflux. 87 2.2 | Respiratory swallow coordination "gate keeping" "Gatekeeping" refers to the centrally mediated partnership that ensures that respiration and swallowing do not occur simultaneously. 83 Alterations in breath-swallow coordination are documented in people with dysphagia and chronic respiratory disease linking disordered swallow and respiratory coordination with increased risk of AARS. 82,83,116,117 An additional means of breath-swallow coordination is swallow-apnea. 82 Multiple swallows in series prolongs swallowapnea. 118 This places increased stress on patients with respiratory disease and is associated with disordered coordination of respiration and swallow. 83,116 This might increase risk of aspiration in patients with existing respiratory disease contributing to disease exacerbations. 116 T A B L E 1 Aerodigestive diseases in dogs.

| Basal and response mechanisms
Basal and response mechanisms are barriers to aspiration which are present independent of and dependent on chemical and mechanical stimulation, respectively. Examples of basal and response mechanisms include the upper and lower esophageal sphincters (UES and LES), and primary and secondary peristalsis, respectively. 83,106 A summary of airway protective mechanisms including the basal and response mechanisms are provided in Table 4.

| Signalment
Aerodigestive diseases can occur in dogs of any age and breed. However, brachycephalic dogs might be considered predisposed, develop AeroD at a younger age, or might have more severe clinical signs related to AeroD compared to nonbrachycephalic dogs. 2 Additionally, the static nature of radiographs limit the ability of the modality to detect and evaluate functional and dynamic processes inclusive of dysphagia, reflux, and repetitive microaspiration. 2,15,[121][122][123][124][125] This is supported by recent studies in dogs with respiratory clinical signs with AeroD documented using videofluoroscopic swallow studies (VFSS) that had normal thoracic radiographs. 2,15,119 Laryngeal and pharyngeal stimulation, reflux, and occult aspiration triggering cough might be missed by thoracic radiography. 14,126 Further, thoracic radiographs might miss or underestimate the severity of pulmonary pathology. Computed tomography (CT) provides superior resolution and lesion localization compared to thoracic radiographs for many AeroD. 23 and digestive enzymes that have the potential to cause damage when the pH is relatively neutral. 28,140,141 Though further studies are needed, nonacidic reflux is reported in dogs and has the potential to contribute disease. 138,[141][142][143] Diagnostics requiring anesthesia impart increased risk of aspiration events because of decreased airway protective mechanisms.
In human studies endoscopy identified abnormalities in less than 50% of patients with known disease (eg, nonerosive reflux disease). 144 Studies utilizing high resolution manometry (HRM) and pH probes have made significant contributions to our understanding of pharyngeal and esophageal motility and GERD. HRM is feasible in both awake or sedated dogs, with esophageal pressure profiles being successfully collected for both liquid and solid food boluses. 145 HRM studies also demonstrated increased LES resting pressures after oral administration of cisapride but not metoclopramide compared to placebo. 146 Ambulatory pH monitors are utilized to determine response to acid suppression and to evaluate the association between GER events and respiratory clinical signs in healthy dogs. 128,143,147 There is a poor association between GER and respiratory clinical signs. However, as noted above, this method detects only acidic reflux and cannot distinguish between Hiatal hernia (type 1 and type 2) 50 Gastric dilatation and volvulus (GDV) 70 Esophagitis 71 Paraneoplastic syndromes 72 Pituitary dwarfism 73 T A B L E 4 A summary of airway protective mechanisms.

Airway protective mechanisms
Normal swallowing Coordinated conduction and clearance of food material and or secretions from the upper aerodigestive tract into the stomach 81 Respiratory swallow coordination Gatekeeping Centrally mediated coordination between respiration and swallowing to prevent both occurring simultaneously 82,83 Respiratory phase coordination The phase of the respiratory cycle during which a swallow is triggered. This is variable across species [82][83][84][85][86] Swallow apnea Interruption of airflow corresponding to pharyngeal swallow 82,83 Basal mechanisms Lower esophageal sphincter (LES) High pressure zone comprised of circumferential smooth muscle at the esophageal gastric junction (EGJ), external pressure from the diaphragm, rugal folds, and angle of entry of esophagus into the stomach 87,88 Barrier to gastric contents entering aerodigestive tract (ie, esophagus) In nonanesthetized dogs the basal pressure of the LES is approximately 30 mmHg though this varies with consciousness and body position (eg, reduced during sleep and anesthesia) 89 Upper esophageal sphincter (UES) Barrier between the upper airway and the esophagus. Tonic closure of the cricopharyngeus muscle prevents aerophagia during quiet breathing and orad movement of esophageal contents into the pharynx following pharyngeal swallow 90 Residual volumes (pharynx and esophagus) The finite volume of material the pharynx and esophagus have the capacity to contain before overflow into the airways and pharynx, respectively 83,91 Mucociliary apparatus System comprised of ciliated epithelial cells and associated mucus layer that traps and clears aspirated material, as well as providing a biological and chemical barrier against injury 92 Innate immunity Antimicrobial defense mechanism involving leukocytes and epithelial cells lining the alveoli and conducting airways 93

Response mechanisms
Volume clearance

Reflexive pharyngeal swallow (RPS)
Removes debris and residue from the pharynx and promotes clearance of refluxate from the esophagus by triggering primary esophageal peristalsis 94,95 Protective against spill-over of oral contents during the oral/preparatory phase of swallowing, and orad movement of esophageal and gastric contents (eg, extraesophageal reflux (EER) and esophageal-oropharyngeal reflux (EOR)) 94,96,97 RPS is not preceded by an oral/preparatory phase 94 A higher threshold to trigger a RPS is considered a risk factor to aspiration in elderly people 96,98 Primary esophageal peristalsis Esophageal clearance triggered by pharyngeal swallow. 99 Conducts swallowed bolus toward the stomach. Retained material incompletely cleared by primary peristalsis may be cleared by subsequent secondary esophageal peristalsis

Secondary esophageal peristalsis
Vagally mediated reflex triggered by esophageal distension and not preceded by a pharyngeal swallow 100,101 Removes retained volume in the esophagus following primary peristalsis, or in response to refluxed material from the stomach 100,101 UES pressure

Magnitude
The pressure of the UES is dependent on arousal, body position, and the degree, location, and rate of esophageal distention, as well as the distending material (gas vs liquid, acidic vs nonacidic) 90

| Videofluoroscopic swallow studies
Observation of feeding behavior, particularly by VFSS, is critical to localizing disease in dogs with dysphagia. 120 Videofluoroscopic swallow studies are the criterion standard for evaluation of dysphagia in dogs. 148 Historically, these have been performed with dogs held in lateral recumbency and force-feeding, limiting use because of unacceptable risks of aspiration. A recent alternative which, by allowing unrestrained freefeeding, reduces risk of aspiration to what would be expected from feeding at home. 148 Natural feeding position, physiologic bolus sizes, and standardized food items with rheological properties (ie, material properties reflecting flow and deformation; eg, viscosity) objectively consistent with commercially available products, further increases the physiologic relevance of VFSS in dogs. 148 Objective metrics in VFSS help identify dogs with pharyngeal weakness, cricopharyngeal achalasia and dyssynchrony, esophageal weakness, reflux, and lower esophageal sphincter achalasia-like syndrome (LES-AS). 2,52,148 In people, VFSS using an objective 8-point scale of laryngeal penetration and aspiration (P-A) has been used to evaluate airway protection. A score of ≥3 is considered abnormal and is predictive of ARRS in children and adults. 149-152 A 7-point scoring system is validated in animals (Table 5). 153 The application of this system helped identify an Response mechanisms

Pharyngeal-laryngeal adduction reflex
Brief closure of the larynx in response to stimulation of the pharynx. This response is absent in patients that aspirate before pharyngeal swallow 108,109 Laryngeal adductor reflex Adduction of the larynx in response to laryngeal stimulation [109][110][111] Particulate clearing Cough Airway protective mechanism triggered by chemical or mechanical stimulation of the pharynx, larynx, trachea, and bronchi 29,112,113 Throat clear (TC) Airway protective mechanism that differs from cough through the absence of an inhalation phase. Associated with stimulation of the upper respiratory tract (pharynx, larynx, cervical trachea) 112,113 F I G U R E 1 (A-C) A still VFSS image from a 13-year-old MC Boston Terrier diagnosed with cricopharyngeal achalasia after being evaluated for chronic cough and mucopurulent nasal discharge. (A) The dog is freely consuming a kibble consistency. Kibble is seen above the soft palate following pharyngeal swallow demonstrating nasopharyngeal reflux (white arrow). (B) The dog is freely consuming a liquid consistency. A hypertrophied cricopharyngeus muscle (Cr) demonstrates a classic "thumbprint" pattern. Macroaspiration is observed with material entering the cervical trachea (arrowhead). (C) An image from a retroflexed choanal examination of the nasopharynx identified a foreign body (carrot; black arrow). A 1 cm size marker is denoted by the asterisk (*). The image from the choanal examination was provided by Dr. Vientos-Plotts, University of Missouri.
incidence of P-A of 39% in dogs undergoing VFSS as well as risk factors for P-A including pharyngeal weakness. 119

| Scintigraphy
Nuclear scintigraphy, which has been employed to measure mucociliary clearance in dogs, 154 is also capable of measuring reflux and cumulative small volume aspiration (ie, microaspiration). 10,155-157 It does not rely on pH, is noninvasive, and can be performed without anesthesia. [155][156][157][158][159] This technique is safe, having been used to evaluate pulmonary aspiration in fragile human infants. 155,158 In people, cough and laryngospasm were strongly correlated with positive reflux/ aspiration on scintigraphy. 158 Further, patients who were positive for reflux on scintigraphy had symptomatic response to surgical treatment. 158

| Biomarkers of reflux
Biomarkers are used to diagnose, prognosticate, and identify groups at risk for disease and have had a beneficial impact in companion animal medicine when used appropriately. 160 Biomarkers might advance our understanding of disease pathogenesis and allow objective investigation of efficacy of novel therapeutics in various diseases. Biomarkers have been used reliably to provide evidence of reflux and aspiration in people. 134,161,162 In dogs proteomic profiles differed between gastric fluid and the oropharynx, and the oropharyngeal proteome differed between healthy dogs, dogs with cough, and dogs with vomiting/regurgitation. 28  The link between nasal/nasopharyngeal disease and EER is underrecognized in dogs. 14 Risk of chronic rhinosinusitis is increased in people with GER. 180 Speculated mechanisms include a direct cytotoxic effect of refluxate contacting the nasal passages or an indirect mechanism of an autonomic nervous system reflex. 181,182 Clinical signs might include sneezing, reverse sneezing, nasal discharge, stertor, labored inspiratory efforts and gagging. Diagnostic evaluation includes physical examination, VFSS, imaging of the head (radiography, fluoroscopy, or CT) and endoscopy (anterograde and retrograde rhinoscopy).

| Laryngeal disease (paralysis, paresis, and collapse)
Laryngeal paralysis is a congenital or acquired disorder wherein the arytenoid cartilages fail to abduct on inspiration leading to an upper airway obstruction. 19 Laryngeal paresis is associated with weak but present abduction of the arytenoid cartilages and was previously thought to occur as the early stage of a progressive degenerative disease leading to laryngeal paralysis in older, large breed dogs. 183 Laryngeal dysfunction, including laryngeal paresis and laryngeal spasm might occur secondary to EER. 17,184 Laryngeal collapse is not a primary disorder but occurs secondary to chronic upper airway obstruction (eg, BOAS) that increases negative intraglottic luminal pressures.
There are 3 stages: (1) everted laryngeal saccules, (2) aryepiglottic collapse with medial deviation of cuneiform processes, and (3) collapse of corniculate processes. 19 Clinical signs of laryngeal disease depend on the degree of airway obstruction and typically include stridor, inspiratory respiratory distress, exercise intolerance, cyanosis, and collapse. 19 A voice change is frequently observed. 19 Clinical signs of respiratory disease might be exacerbated by heat or exercise/excitement. Abnormal functioning of pharyngeal and esophageal muscles might lead to increased risk of micro-or macroaspiration and could lead to gag and cough. 19,185 Diagnosis relies on signalment, physical examination, neurologic examination, CBC/biochemical profile/urinalysis/thyroid testing, cervical and thoracic radiography, and upper airway examination. 19

| Airway foreign bodies
Large airway obstruction from airway foreign body aspiration might present as respiratory emergencies because of obstruction of airflow.
Size of the dog, size and location of the foreign body, and any dynamic repositioning will dictate severity of clinical signs. 23,194 More commonly, airway foreign bodies move to smaller airways and might migrate into the pulmonary parenchyma or pleural cavity. 195

| Chronic bronchitis
Chronic bronchitis (CB) is defined as a clinical syndrome of chronic cough greater than 2 months in duration associated with neutrophilic airway inflammation and mucus hypersecretion. 197 Repetitive microaspiration has been associated with canine CB. 2,23,24 Additionally, respiratory dysbiosis (perturbations of the airway microbial communities) might in part be caused by microaspiration, with additional research needed to elucidate the role of microbes in triggering, exacerbating or perpetuating airway injury. 198 Diagnosis relies on history, physical examination, thoracic radiography, bronchoscopy, and airway lavage for cytology and culture.

| Bronchiectasis
Bronchiectasis is defined as irreversible dilation of airway walls because of cyclical inflammation, infection, and impairment of mucociliary function. 25,199 Aspiration is recognized as an important cause. 2,23,25 Cough nearly universally occurs, with tachypnea or labored respiration less frequently reported. 25 Bronchiectasis might be missed on survey radiography, but CT is highly sensitive. 25 Bronchoscopy can allow airway sampling, critical for documentation of inflammation and potentially infection. Dogs with bronchiectasis are at increased risk of bacterial infection. 200

| Diffuse aspiration bronchiolitis
Small airway diseases, affecting bronchioles <2 mm in diameter and lacking cartilage in their walls, have been described and classified in people and cats, 26,201 but are not well characterized in dogs. [202][203][204][205][206] Dogs have no pathognomonic respiratory clinical signs. There are many risk factors associated with small airway injury, with aspiration leading to a subtype of primary bronchiolar disease called diffuse aspiration bronchiolitis. 26 Survey radiography and respiratory cytology are incapable of diagnosing bronchiolar disorders, making CT and histopathology key diagnostics in dogs and cats with a risk factor for aspiration and other testing failing to provide an explanation for clinical signs. 26,201 Histologically, diffuse aspiration bronchiolitis is characterized by inflammation and a foreign body reaction in bronchioles. 26

| Aspiration pneumonia/pneumonitis
Inhalation of orophargyneal or gastrointestinal contents causes chemical, bacteriologic, and immunologic injury of the pulmonary parenchyma falling under the umbrella term "aspiration pneumonia" in dogs. 191 The type of inflammatory response following aspiration depends on the volume and composition of the aspirate, leading to aspiration pneumonia (with clinically impactful bacterial infection) or aspiration pneumonitis (chemical pneumonitis without clinically impactful bacterial infection). 27,207 In veterinary practice, the term aspiration pneumonia is used to encompass both syndromes as clinical signs and radiographic features are often overlapping. 27 Clinical signs can be systemic (eg, fever, lethargy) or local (eg, cough, tachypnea, labored respiration). The primary clinically relevant distinction between these 2 subtypes is whether antimicrobials are indicated for therapy. 27 While antimicrobial use is widespread in veterinary practice, there is increasing recognition that many cases of aspiration pneumonia in dogs lack clinically important infection. 27,208 In addition to identifying a predisposing factor for aspiration, clinical signs, radiographic features (dependent lung lobes with an interstitial or alveolar pattern), hematologic data (leukocytosis or leukopenia, band neutrophilia) and airway cytology and culture are useful for determining optimal treatment.

| Interstitial lung diseases
Interstitial lung diseases (ILDs) are a heterogenous group of diffuse parenchymal disorders associated with varying degrees of inflammation and fibrosis in absence of infection or neoplasia. 209 There are a variety of triggers of pulmonary injury, including aspiration, and fibrosis represents a final common pathway for many ILDs.
One subtype of fibrotic ILD in people called idiopathic pulmonary fibrosis (IPF) was suggested to be associated with GERD in a recent meta-analysis. 210 GERD is linked to progression of a variety of progressive fibrosing ILDs in people including IPF, hypersensitivity pneumonitis, connective tissue disease-ILD, cryptogenic organizing pneumonia and others. 211 In West Highland white terriers, a breed with familial pulmonary fibrosis, aspiration of gastroesophageal refluxate into the airways of affected dogs with silent repetitive microaspiration was documented by assessing for presence of bile acids in airway lavage. 24 Another ILD definitively linked to aspiration in dogs is exogenous lipid pneumonia which has been caused by inadvertent aspiration of mineral oil. 212 Clinical signs can include cough, tachypnea, rapid and shallow breathing, exercise intolerance, respiratory distress, and cyanosis. History, physical examination, radiography, CT, and airway cytology can rule out other disorders and make an ILD more likely; however, definitive diagnosis relies on histopathology.

| Idiopathic cough
When a comprehensive diagnostic evaluation fails to identify an underlying structural, functional, infectious, inflammatory, fibrotic, or neoplastic disorder as an etiology of cough and when treatment of underlying causative factors is ineffective in controlling cough, it is termed "idiopathic" or unexplained cough. 213 Idiopathic cough must be discriminated from cases in which a thorough diagnostic evaluation and treatment trials have not been performed resulting in a lack of explanation for the cause of cough.
It is unclear if idiopathic cough in dogs bears similarities to chronic cough hypersensitivity syndrome in people, in which the initial cough trigger has disappeared but the cough reflex is enhanced. 29,214 Alternatively, because of the low index of suspicion and widespread inability to test for EER, laryngopharyngeal reflux (LPR; backflow of gastric contents into the laryngopharnyx), and repetitive microaspiration in dogs, it is possible that a subset of idiopathic canine cough is because of effects of reflux.

| Pharyngeal weakness
Pharyngeal weakness refers to impaired pharyngeal peristaltic activity in the absence of obstruction, improper timing of pharyngeal swallowing, or both. 215 Studies in dysphagic dogs identified pharyngeal weakness in 13% of cases reviewed by VFSS. 216 Pharyngeal weakness in dogs is the nonspecific consequence of neuromuscular diseases, 43,217 myopathies, 22,41 cranial nerve deficits, 35 infectious agents, 31,32 and long term negative pressure gradients 22,35 (Table 5). Brachycephalic dog models of OSA demonstrate architectural remodeling of the pharyngeal musculature leading to pharyngeal weakness, +/À collapse, and exacerbations of OSA and dysphagia. 22 Extraesophageal reflux disease in people is also thought to contribute to pharyngeal weakness through the development of a local myositis; however, comparable studies are missing in dogs. 218 Regardless of etiology, pharyngeal weakness is considered an independent risk factor for aspiration in dogs and people. 2,119,150,215 Pharyngeal weakness is most frequently diagnosed by VFSS. 44 An increased pharyngeal constriction ratio (PCR), the presence of residual contrast material in the pharynx following an appropriately timed pharyngeal swallow, or both are supportive of a diagnosis of pharyngeal weakness. 44,119 The timing of pharyngeal swallow is important to distinguish pharyngeal weakness from delayed opening of the upper esophageal sphincter (UES, that is, cricopharyngeal dyssynchrony). 44 High resolution manometry provides detailed information regarding both the pressure and timing of pharyngeal swallow; however, it is not widely available in veterinary medicine. 49

| Pharyngeal masses
Pharyngeal masses inclusive of abscesses, cysts, polyps, neoplasia, and sialoceles might all present with clinical signs associated with pharyngeal dysphagia. 46 A markedly elongated soft palate might also act as a pharyngeal "mass effect." Ventral cervical masses in dogs have also been reported to cause pharyngeal dysphagia. 47 These lesions disrupt normal pharyngeal swallow, increasing risk of impaired airway protection and AARS. 44 Dysphagia after surgery or radiation therapy affecting the ventral cervical area or oral cavity is common in humans. 219 A study in dogs undergoing definitive radiation therapy for thyroid carcinoma reported dysphagia as acute radiation side effect suggesting similar outcomes in dogs. 220 Videofluoroscopic swallow studies are the initial diagnostic of choice to assess dogs with suspected pharyngeal dysphagia. 44 Sedated or anesthetized oral examinations with or without sample collection are ultimately required for a diagnosis in most cases. Endoscopy, CT or both might also be necessary to evaluate extraluminal compressive masses, the extent of intraluminal disease, as well as metastasis.

| Cricopharyngeal achalasia and dyssynchrony
The cricopharyngeus muscle is the major muscular component of the UES. Absent or incomplete, or inappropriately timed opening (delayed opening or early closure) of the cricopharyngeus muscle reflect cricopharyngeal achalasia and dyssynchrony, respectively. A study in dysphagic dogs identified cricopharyngeal achalasia, dyssynchrony, or both, in 8% (n = 17) of evaluated dogs: 6 with asynchrony, 6 with achalasia, and 5 with both asynchrony and achalasia. 216 Both conditions result in impaired bolus clearance during pharyngeal swallow and high risk of aspiration of pharyngeal contents into the airways (Supplementary Video 1). 120,221 The underlying etiology in dogs is suspected to be a congenital focal neuropathy; however, acquired cases in older dogs have been reported including secondary to hypothyroidism. 48,222 In people, there is an association between acquired cricopharyngeal dyssynchrony and reflux disease (GERD and EERD).
These studies documented abnormalities in the timing of cricopharyngeal opening, with as many as 50% of dogs with GERD showing delayed opening or early closure of the cricopharyngeus muscle. 223,224 As for pharyngeal weakness, detection of cricopharyngeal achalasia and dyssynchrony is best achieved by HRM or VFSS with special attention paid to the PCR, timing of pharyngeal swallow, and the maximal diameter of the UES during bolus passage. 129,216,225

| Esophageal dysmotility
In people, ineffective esophageal peristalsis represents a heterogenous population of motility disorders often diagnosed by HRM. 226,227 In dogs, esophageal dysmotility is less well defined but generally refers to impaired esophageal motility resulting in accumulated swallowed boluses within the esophagus and or a prolonged esophageal transit time on VFSS. 2 Importantly, esophageal dysmotility might occur in the absence of overt megaesophagus. 2,52 Etiologies are suspected to be similar to those for megaesophagus and might actually precede esophageal dilation in these cases (Table 3). 228 In addition, esophageal dysmotility has been documented with esophagitis, geriatric onset laryngeal paralysis polyneuropathy (GOLPP), sliding hiatal hernia (sHH), esophageal diverticula, esophageal fistulas, and LES-AS. 13,15,52,58,71,216,229 Some breeds appear predisposed to esophageal dysmotility including the Bouvier and Chinese Shar Pei. 40,230 Several studies have also documented esophageal dysmotility alone or in combination with GERD and sHH in brachycephalic dogs of multiple breeds. 15,231 Mild esophageal dysmotility attributable to maturation of the neuromuscular system might be detected in juvenile dogs that might improve up to 1 year of age. 229 Defects in motility and esophageal clearance represent failures in airway protection. Esophago-oropharyngeal reflux (EOR) is associated with increased risk of pathologic laryngeal penetration and aspiration in dogs undergoing VFSS. 119 Concurrent laryngeal dysfunction compounds these risks. 58 In reflux esophagitis, a failure to effectively clear the refluxate from the esophagus might contribute to disease progression and the development of structural abnormalities such as esophageal strictures. 71 A VFSS is considered the diagnosis of choice in dogs to detect subtle and segmental abnormalities in esophageal motility. 216 Detailed information on esophageal motility might also be achieved by HRM; however, this is not routinely available in clinical practice. 131

| Megaesophagus
Megaesophagus describes the circumferential dilation of the esophagus (diffuse or segmental), with accompanying esophageal dysmotility. 232 Megaesophagus (ME) is a well-recognized cause of esophageal dysphagia in dogs and is considered an important risk factor for AARS. 207,232 Megaesophagus in dogs has been discussed extensively elsewhere but representative causes are presented in Table 2. Importantly, some dogs with presumed "idiopathic" ME have a functional obstruction of the lower esophageal sphincter (ie, LES-AS). 52 These dogs appear to respond to interventions targeting the LES including botulinum toxin injections, ballooning, and bougienage. 75 Sildenafil has also shown promise in managing clinical signs in dogs with congenital idiopathic ME. 233 Discrimination between ME and other causes of esophageal dilation (eg, aerophagia or sedation/anesthesia) is important to avoid inappropriate diagnosis and clinical decision making, including euthanasia. 232 A VFSS is necessary to identify LES-AS and discriminate ME from other forms of esophageal dilation. 52

| Esophagitis
Esophagitis refers to localized or diffuse inflammation of the esophageal mucosa. In most cases, this is the consequence of GER; however, focal injury because of esophageal foreign bodies (FB), medications (eg, doxycycline and clindamycin in cats) and eosinophilic esophagitis have also been reported. 74,[234][235][236] Conditions that increase the frequency of reflux events such as gastric hyperacidity, sHH, gastric hypomotility, anesthesia, and upper airway obstruction should be considered predisposing factors for esophagitis. 13,15,172,231,237,238 Severe esophagitis is associated with the development of esophageal strictures, necrosis, and diverticulum formation as well as aspiration pneumonia/pneumonitis, pneumothorax, and tracheal compression. 234 The decreased esophageal motility seen with esophagitis impairs the clearance of harmful gastric secretions introduced by reflux. 71 Further, studies using animal models of esophagitis demonstrated diminished strength and frequency of the esophago-laryngeal closure reflex (defined in Table 4), increasing risk of AARS. 239 The diagnosis of esophagitis is multimodal, involving, but not limited to, VFSS, endoscopy, biopsies (eg, eosinophilic esophagitis), treatment trials, and ambulatory pH monitoring. 71 Figure 1). 240  In human medicine, clinical signs of reflux are separated into "typical" and "atypical" forms. Typical reflux is associated with clinical signs of gastrointestinal disease (eg, heartburn and regurgitation). 244 People with atypical reflux present with exclusively respiratory clinical signs. 245 Gastroesophageal reflux in people has a prevalence of 50% in people with asthma, COPD, and chronic cough. 3,5-7 Extraesophageal reflux is implicated in chronic rhinosinusitis and chronic otitis media via eustachian tube. 246  Brachycephalic dogs however, were younger upon diagnosis and more likely to present in respiratory distress than their nonbrachycephalic counterparts. 15 Diagnosis of sHH has typically involved abdominal radiographs with or without abdominal compression, but this modality is poorly sensitive for detecting dynamic events such as reflux and accompanying esophageal dysmotility. 2,13,231 VFSS is superior to thoracic radiographs for detecting sHH in dogs. 15,231 5.14 | Structural diseases of the esophagus: strictures, persistent right aortic arch, diverticula Any impedance to esophageal clearance represents a risk factor for AARS. 23,207 A VFSS is helpful to identify a focal obstruction of the esophagus, such as those described above, as well as any accompanying AeroD (eg, esophageal dysmotility and reflux). 2 Care should be taken not to mistake normal esophageal redundancy in brachycephalic dogs for an esophageal diverticula. 231 Endoscopy is diagnostic and can be therapeutic for esophageal strictures. 253 A CT with or without an angiogram might be required for identification and surgical planning for vascular ring anomalies and esophageal diverticula. 251,252 Endoscopy aided thoracoscopic correction of persistent right aortic arch has also been reported in dogs. 254

| CONCLUSIONS
Aerodigestive disorders are the result of discordant respiration and swallowing. Despite a high prevalence for such disorders in dogs presenting for clinical signs of respiratory disease, the link between abnormalities of breathing and swallowing is likely underrecognized in clinical veterinary practice. Advanced diagnostic and monitoring tools including videofluoroscopic swallow studies, scintigraphy, biomarker analysis, and objective respiratory biometrics are needed to improve recognition and treatment of these dogs. Further, as both dogs and people have aerodigestive disorders, using a One Health approach will increase the opportunity for bidirectional advancement in research and its clinical application.

ACKNOWLEDGMENT
No funding was received for this study.

CONFLICT OF INTEREST DECLARATION
Authors declare no conflict of interest.

OFF-LABEL ANTIMICROBIAL DECLARATION
Authors declare no off-label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION
Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION
Authors declare human ethics approval was not needed for this study.