Retrospective analysis of incidence, clinical features, potential risk factors, and prognostic indicators for aspiration pneumonia in three brachycephalic dog breeds

Hannah P. Darcy Department of Clinical Sciences and Services, Queen Mother Hospital for Animals, University of London, North Mymms, Hatfield, AL9 7TA, England.

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Karen Humm Department of Clinical Sciences and Services, Queen Mother Hospital for Animals, University of London, North Mymms, Hatfield, AL9 7TA, England.

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Gert ter Haar Department of Clinical Sciences and Services, Queen Mother Hospital for Animals, University of London, North Mymms, Hatfield, AL9 7TA, England.

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Abstract

OBJECTIVE To investigate incidence, clinical features, potential risk factors, and prognostic indicators for aspiration pneumonia in Pugs, French Bulldogs, and Bulldogs.

DESIGN Retrospective, observational study.

ANIMALS 41 brachycephalic dogs with aspiration pneumonia.

PROCEDURES Medical records of a veterinary referral hospital were retrospectively searched to identify Pugs, French Bulldogs, and Bulldogs treated for aspiration pneumonia between 2006 and 2015. Signalment, clinical data, and outcomes were recorded. Variables of interest were analyzed for statistical associations with outcome. Incidence of aspiration pneumonia for the population of interest was compared with that for all other dog breeds and for the general hospital population of dogs during the study.

RESULTS 41 of 2,141 (1.91%) dogs of the selected brachycephalic breeds and 396 of 80,137 (0.49%) dogs overall had a diagnosis of aspiration pneumonia. Relative risk of the disease in the population of interest was 3.77 times that for all other breeds. Median age at disease onset was greater for Pugs (83 months) than for French Bulldogs (8 months) and Bulldogs (6 months). History of gastrointestinal signs was the most commonly observed preidentified risk factor (27/41 [66%]) in these breeds. Neurologic disease was significantly more common in Pugs than in French Bulldogs and Bulldogs. On univariate analysis, increased age, male sex, obtundation, hypoalbuminemia, azotemia, and high liver enzyme activities were associated with nonsurvival; on logistic regression, increased age was associated with nonsurvival.

CONCLUSIONS AND CLINICAL RELEVANCE Age at onset and presence of other risk factors for aspiration pneumonia may vary among brachycephalic dog breeds. Prospective studies are needed to determine common risk factors and prognostic indicators for aspiration pneumonia in the larger population of brachycephalic dogs.

Abstract

OBJECTIVE To investigate incidence, clinical features, potential risk factors, and prognostic indicators for aspiration pneumonia in Pugs, French Bulldogs, and Bulldogs.

DESIGN Retrospective, observational study.

ANIMALS 41 brachycephalic dogs with aspiration pneumonia.

PROCEDURES Medical records of a veterinary referral hospital were retrospectively searched to identify Pugs, French Bulldogs, and Bulldogs treated for aspiration pneumonia between 2006 and 2015. Signalment, clinical data, and outcomes were recorded. Variables of interest were analyzed for statistical associations with outcome. Incidence of aspiration pneumonia for the population of interest was compared with that for all other dog breeds and for the general hospital population of dogs during the study.

RESULTS 41 of 2,141 (1.91%) dogs of the selected brachycephalic breeds and 396 of 80,137 (0.49%) dogs overall had a diagnosis of aspiration pneumonia. Relative risk of the disease in the population of interest was 3.77 times that for all other breeds. Median age at disease onset was greater for Pugs (83 months) than for French Bulldogs (8 months) and Bulldogs (6 months). History of gastrointestinal signs was the most commonly observed preidentified risk factor (27/41 [66%]) in these breeds. Neurologic disease was significantly more common in Pugs than in French Bulldogs and Bulldogs. On univariate analysis, increased age, male sex, obtundation, hypoalbuminemia, azotemia, and high liver enzyme activities were associated with nonsurvival; on logistic regression, increased age was associated with nonsurvival.

CONCLUSIONS AND CLINICAL RELEVANCE Age at onset and presence of other risk factors for aspiration pneumonia may vary among brachycephalic dog breeds. Prospective studies are needed to determine common risk factors and prognostic indicators for aspiration pneumonia in the larger population of brachycephalic dogs.

Aspiration pneumonia is recognized as the final stage in a progression of inflammation arising from inhalation of oral or gastric contents.1 Damage to the pulmonary parenchyma initiated by acidic2 or particulate matter leaves the tissue vulnerable to colonization by bacteria from the oropharynx.3 Reported risk factors for aspiration pneumonia in veterinary patients include vomiting or regurgitation, esophageal or gastric dysmotility, gastric sphincter incompetence, pyloric outflow obstruction, laryngeal disease, and reduced mentation.4–7 Previous veterinary studies7–9 have shown an association between aspiration pneumonia and large dog breeds, with brachycephalic breeds specifically described as not overrepresented. This is surprising, given that brachycephalic breeds are known to have a number of features that have been identified as risk factors for aspiration pneumonia.10 Endoscopic evaluation of brachycephalic dogs with upper respiratory tract disease revealed a high prevalence (71/73 [97%]) of gastrointestinal abnormalities,11 including gastroesophageal reflux, hiatal hernias, and pyloric stenosis.11,12 The high prevalence of obstructive airway syndrome in these breeds10 is also likely to increase the risk of aspiration; upper airway obstruction results in marked negative pressures exerted over the thoracic contents, increasing the incidence of reflux and damaging the larynx. People with OSA are known to be at increased risk of aspirating oral contents,13 and OSA is a condition for which Bulldogs have been used in research.14 Given the high prevalence of risk factors in brachycephalic dog breeds, it has been postulated that dogs with this type of conformation are at risk for aspiration pneumonia.15,16 Although brachycephalic breeds are often grouped together, anatomic features, including the severity of brachycephalic index,10 can vary, and this could lead to differing predispositions to and risk factors for aspiration pneumonia.

The objective of the study reported here was to retrospectively evaluate the incidence of aspiration pneumonia in brachycephalic dogs of 3 breeds (Pugs, French Bulldogs, and Bulldogs [per the American Kennel Club designation]17) and to assess clinical features, potential risk factors, treatment, and prognostic indicators for the disease in these dogs. These 3 breeds were selected on the basis of investigations by Packer et al,10 which indicated that Pugs, Bulldogs, and French Bulldogs were the breeds at greatest risk of having BOAS. We additionally aimed to assess whether variation exists in the degree of risk and nature of clinical features of aspiration pneumonia among the 3 selected breeds. We hypothesized that the incidence of aspiration pneumonia would be greater for these brachycephalic dogs than for the general population of dogs evaluated at our referral hospital during the > 8-year study period.

Materials and Methods

Case selection and medical records review

A computerized search of patient records at the Queen Mother Hospital for Animals was conducted to identify patients with a diagnosis of aspiration pneumonia between November 1, 2006, and July 31, 2015. The following criteria had to be met for the initial record identification: diagnostic imaging evidence of a pulmonary infiltrate that had a distribution consistent with aspiration, report of acute onset or exacerbation of respiratory disease, and no cause identified for the pulmonary infiltrate other than aspiration. Records were excluded from further consideration if evaluation revealed data consistent with an alternative etiopathogenesis for pulmonary findings (eg, cardiac disease or foreign body inhalation) or if they were deemed incomplete.

Records of patients with aspiration pneumonia were then searched to identify dogs of 3 brachycephalic breeds: Pugs, French Bulldogs, and Bulldogs. Records for these dogs were individually assessed for variables of interest including signalment; presence of specific, previously identified risk factors for aspiration pneumonia in dogs (gastrointestinal signs, neurologic disease, and recent general anesthesia [ie, ≤ 14 days prior to diagnosis])5; clinical signs; diagnostic imaging findings; clinicopathologic data (CBC, biochemical analysis, and blood gas analysis results); cytologic and culture results for airway (fluid or swab) samples; treatments provided; and outcome. Culture isolates were tested by conventional laboratory methods, with intermediate susceptibility to tested antimicrobials classified as nonsusceptible for study purposes. Patients that survived to discharge from the hospital and those that died or were euthanized during hospitalization were classified as survivors and nonsurvivors, respectively. The incidence of aspiration pneumonia in the 3 breeds of interest was calculated by dividing the number of newly diagnosed cases of aspiration pneumonia in Pugs, French Bulldogs, and Bulldogs by the total number of these breeds evaluated at the hospital within the study period. Incidence data for aspiration pneumonia in dogs of all other breeds and in the overall population of dogs evaluated at our facility during the study period were similarly calculated for comparison purposes. Each dog was included in the study only once.

Statistical analysis

Statistical analysis was performed with a commercially available statistical software package.a Normally and nonnormally distributed numeric data were reported as mean ± SD or median and range, respectively. The relative risk of aspiration pneumonia was calculated with 95% CI for dogs of the 3 selected brachycephalic breeds, compared with the risk for dogs of all other breeds evaluated at the same hospital during the study period. The χ2 and Fisher exact tests were used to assess association between categorical variables, with the latter used when cell values were < 5. The Fisher exact test was also used to assess potential associations between individual variables of interest (related to signalment, clinical history, examination findings, and treatment) in the selected brachycephalic breeds and survival; values significantly (P < 0.05) associated with this outcome were entered into a logistic regression analysis with backward elimination performed to investigate negative prognostic factors for aspiration pneumonia. Values of P < 0.05 were considered significant.

Results

Incidence of aspiration pneumonia and associations with signalment

There were 80,137 dogs evaluated at the authors' facility during the study period; 396 (0.49%) had a diagnosis of aspiration pneumonia. Of 2,141 Pugs, French Bulldogs, and Bulldogs examined during the same period (2.67% of the total canine caseload), 41 (1.91%; 5 Pugs, 11 French Bulldogs, and 25 Bulldogs) had a diagnosis of aspiration pneumonia. The incidence of aspiration pneumonia in all other breeds was 355 of 77,996 (0.46%). The risk of aspiration pneumonia in the 3 selected brachycephalic breeds was significantly (P < 0.001) higher than in all other dog breeds (relative risk, 3.77; 95% CI, 2.74 to 5.19).

Bulldogs were more commonly evaluated during the study period (1,006/2,141 [47.0%]) than were Pugs (685 [32.0%]) and French Bulldogs (450 [21.0%]), and dogs of this breed were also more commonly identified as having aspiration pneumonia (25/41 [61%]) than were Pugs (5 [12%]) and French Bulldogs 11 [27%]). The odds of a diagnosis of aspiration pneumonia among French Bulldogs and Bulldogs were significantly (P < 0.001 for both comparisons) greater than for the general canine population of the hospital (OR, 4.93 [95% CI, 3.30 to 7.30] and 4.73 [95% CI, 2.62 to 8.55], respectively). The odds of this diagnosis for Pugs did not differ significantly (P = 0.407) from those for the general canine population (OR, 1.44; 95% CI, 0.59 to 3.49). No significant (P = 1.0) difference in this variable was detected for Bulldogs, compared with French Bulldogs (OR, 1.04; 95% CI, 0.52 to 2.10), but bulldog breeds (Bulldogs and French Bulldogs) had a significantly (P < 0.01) higher risk of developing aspiration pneumonia than did Pugs (OR, 3.30; 95% CI, 1.30 to 8.37).

Among dogs of the 3 selected breeds with aspiration pneumonia, males were overrepresented (28/41 [68%]), and most affected males (22/28 [79%]) and affected females (9/13) were sexually intact. The median age of all 41 dogs in this group was 7 months (range, 2 to 163 months). Bulldogs and French Bulldogs typically had a diagnosis of aspiration pneumonia prior to 1 year of age (median ages, 6 and 8 months, respectively). Pugs were significantly (P < 0.001) older (median age, 83 months) than French Bulldogs and Bulldogs at the time of the initial examination.

Presence of previously identified risk factors for aspiration pneumonia

Gastrointestinal signs were the most commonly observed previously identified risk factor for aspiration pneumonia among the 3 breeds of interest (27/41 [66%] overall; 4 Pugs, 9 French Bulldogs, and 14 Bulldogs). The signs were considered acute in 16 and chronic in 11 animals. Vomiting and regurgitating were the only reported gastrointestinal signs in these patients, and investigation and treatment of respiratory disease generally took precedence over investigating gastrointestinal signs further. Neurologic disease was present in 4 of the 41 (10%) dogs (3 Pugs and 1 Bulldog) and included necrotizing meningoencephalitis (n = 1), suspected intracranial neoplasia (1), and seizure activity (2). Neurologic disease was significantly (P = 0.003) more common in Pugs than in Bulldogs and French Bulldogs. A recent history of general anesthesia was found for 4 (10%) of the 41 dogs (2 Bulldogs and 2 French Bulldogs). Three of these anesthetic episodes occurred ≤ 24 hours prior to the evaluation for respiratory disease; the reasons for anesthesia included cesarean section, ventriculoperitoneal shunt placement and surgical treatment for BOAS, and surgery for a prolapsed gland of the membrana nictitans. The fourth anesthetic procedure was for a dog that underwent surgical treatment for BOAS 4 days prior to development of respiratory signs. Nine of the 41 affected dogs had no history of exposure for any of the previously reported risk factors. A large proportion of Bulldogs with aspiration pneumonia (8/25 [32%]) had no previously reported risk factor exposure; however, this proportion did not differ significantly (P = 0.067) from that for the other 2 breeds combined (1/16 [6.3%]).

Physical examination, diagnostic imaging, and clinicopathologic findings

Dyspnea was the most commonly reported clinical sign on initial examination of Pugs, French Bulldogs, and Bulldogs with aspiration pneumonia (35/41 [85%]), followed by tachypnea (33/41 [80%]). Median values for physiologic variables in this population were as follows: rectal temperature, 38.3°C (100.9°F; range, 37.6° to 40.2°C [99.7° to 104.4°F]); heart rate, 104 beats/min (range, 60 to 200 beats/min); and respiratory rate, 44 breaths/min (range, 20 to 116 breaths/min), with panting reported for 3 dogs. Only 11 of 41 (27%) patients had a high body temperature (> 39.2°C [102.6°F]6) at this examination. Abnormal sounds on lung field auscultation were reported in 31 of 41 (76%) patients, with pulmonary crackles most commonly recorded (14/41 [4%]). Nasal discharge was present in 7 of 41 (17%) dogs. Other common clinical signs included coughing (24 [59%]), lethargy (18 [44%]), and reduced appetite (8 [20%]).

Thirty-five of the 41 dogs underwent radiography, and 7 underwent thoracic CT, including 1 dog examined by both imaging methods. Alveolar infiltrate was the most commonly reported lung field pattern seen (24/41 [59%)], with bronchointerstitial infiltrate reported in 9 (22%). The right middle lung lobe was most commonly affected (21/41 [51%]), followed by the right cranial (17 [41%]), left cranial (13 [32%]), left caudal (5 [12%]), right caudal (4 [10%]), and accessory (3 [7%]) lobes. Location was unspecified in 9 of 41 (22%) dogs. The number of affected lung lobes ranged from 1 (14/41 [34%]) to 5 (1 [2%]), with 13 (32%) dogs having > 2 lobes affected and 6 (15%) described as having diffuse infiltrates. No association was identified between the number of affected lung lobes and survival (P = 0.16).

The CBC, serum biochemical evaluation, and blood gas analysis results for affected dogs in the population of interest were deemed nonspecific. Abnormalities included neutrophilia (16/41 [39%]), hyperphosphatemia (10/29 [34%]), hypercalcemia (7/29 [24%]) and hypoalbuminemia (7/29 [24%]). Hyperphosphatemia and hypercalcemia were considered physiologic in all instances, as all dogs were < 12 months of age. Seven of 34 (21%) dogs had values within the respective reference ranges on CBC, and 17 of 29 (59%) dogs had values within the respective reference ranges on serum biochemical examination. Samples were collected from the respiratory tract for 16 of the 41 (39%) dogs. Of these, 8 dogs underwent endoscopically guided bronchoalveolar lavage, 7 had an endotracheal wash, and 1 had the sample obtained by a swab introduced through an endotracheal tube. Cytologic examination revealed neutrophilia in the airway for 13 of 16 dogs, with intracellular bacteria detected in 6 of 16. Bacterial culture results were positive for 11 of 16 samples. The most commonly isolated pathogens were Pasteurella spp, followed by Escherichia coli, Staphylococcus spp, and Bordetella bronchiseptica; 7 of 11 specimens yielded growth of multiple organisms (Table 1). The greatest proportions of tested isolates were susceptible to enrofloxacin (23/23 [100%]) and marbofloxacin (3/3), followed by imipenem (11/12) and amoxicillin-clavulanic acid (20/23 [87%]). The smallest proportion of isolates (1/22 [5%]) was susceptible to clindamycin.

Table 1—

Antimicrobial susceptibility of isolates obtained by culture of samples from the respiratory tracts in 11 of 41 Pugs, French Bulldogs, and Bulldogs with aspiration pneumonia.

  Antimicrobial (proportion of isolates susceptible)
IsolateNo. of affected dogsENRAMCCEVCFXCEPCLNOTCTMSIMIMRB
Pasteurella spp66/66/66/66/64/60/66/65/66/6NA
Escherichia coli44/43/43/43/42/40/42/44/44/44/4
Staphylococcus spp44/44/44/44/44/41/42/42/4NANA
Bordetella bronchiseptica33/33/30/30/30/30/33/30/3NA3/3
Pseudomonas aeruginosa22/20/20/20/20/20/20/20/21/22/2
Mycoplasma spp22/22/20/20/20/20/22/20/2NANA
Coliforms11/11/11/11/10/10/11/11/1NANA
Klebsiella sp11/11/11/11/11/1NA1/11/1NANA

Values represent the proportion of isolates that were deemed susceptible to the antimicrobial by standard laboratory methods. Samples were obtained for 16 dogs by bronchiolar lavage (n = 8), endotracheal wash (7), or tracheal swabbing (1), and culture results were negative for 5 dogs. Seven of 11 specimens yielded multiple isolates.

AMC = Amoxicillin-clavulanic acid. CEP = Cephalexin. CEV = Cefovecin. CFX = Cefuroxime. CLN = Clindamycin. ENR = Enrofloxacin. IMI = Imipenem. MRB = Marbofloxacin. NA = Not assessed. OTC = Oxytetracycline. TMS = Trimethoprim-sulfamethoxazole.

Treatment

Most (39/41 [95%]) affected dogs in the population of interest received antimicrobials. One of the 2 dogs with no record of antimicrobial administration was euthanized, and the other survived to hospital discharge. For 16 of these 39 patients, antimicrobial administration was guided by culture and susceptibility testing of airway samples. Of the 39 dogs that were treated with antimicrobials, 26 (67%) received 1 drug and 13 (33%) received > 1 drug; amoxicillin-clavulanic acid (31/39 [79°%]) and enrofloxacin (10 [26°%]) were most frequently prescribed. The median duration of antimicrobial administration was 22 days (range, 5 to 42 days), with a mean of 22 days. The overall rate of survival to hospital discharge for dogs that received potentiated amoxicillin as a sole agent (16/21 [76%]) did not differ significantly (P = 0.30) from that for dogs that received a fluoroquinolone alone (3/3). Similarly, no significant (P = 0.93) difference in survival rates was found between patients treated with potentiated amoxicillin (25/31 [81%] versus fluoroquinolones in any combination (9/11 [82%]). Additionally, no difference in survival rates was detected between patients that received 1 versus 2 antimicrobials (20/25 [80%] and 11/14 [79%], respectively; P = 0.78). The most common empirical antimicrobial treatment prescribed for patients that had not undergone airway sampling was potentiated amoxicillin (administered as the sole agent in 17/25 [68%] dogs and in combination with ≥ 1 other antimicrobial in 4 [16%]).

Other treatments included oxygen therapy (23/41 [56%] affected dogs), with (n = 5) or without (18) mechanical ventilation. The median duration of oxygen therapy was 24 hours (range, 2 to 192 hours). Fourteen of the 41 (34%) dogs were administered gastrointestinal medications, including omeprazole (n = 11), metoclopramide (5), maropitant (1), and sucralfate (1), alone or in combination.

Outcome

The overall survival rate among Pugs, French Bulldogs, and Bulldogs with aspiration pneumonia was 32 of 41 (78%). Bulldogs and French Bulldogs had highly similar survival rates (21/25 and 9/11, respectively). The survival rate of Pugs (2/5) appeared lower, but did not differ significantly (P = 0.07) from that for the other 2 breeds combined. Seven of 9 nonsurvivors were euthanized (all because of poor prognosis), and 2 died during hospitalization.

Factors related to signalment, clinical signs, common clinicopathologic changes, and treatment modalities were individually assessed for association with survival (Table 2). Most variables that met the significance criterion at the univariate level were entered into a logistic regression analysis to assess negative prognostic factors for aspiration pneumonia for the 3 breeds of interest; hypoalbuminemia and azotemia were excluded owing to incomplete data sets. When backward elimination was performed, age at the time of initial examination was the only factor found to be a negative prognostic indicator, with older animals having a greater likelihood of nonsurvival (OR, 1.043; 95% CI, 1.014 to 1.072; P = 0.004).

Table 2—

Results of univariate analysis (Fisher exact test) for association between suspected negative prognostic factors and survival to hospital discharge for the same 41 dogs as in Table 1.

FactorP value
Signalment 
  Pug breed (vs French Bulldog or Bulldog)0.065
  Age on initial examination*0.004
  Male (vs female)0.017
  Neutered (yes vs no)0.190
Clinical history (yes vs no) 
  Gastrointestinal signs1.000
  Neurologic disease0.030
  General anesthesia < 7 days before evaluation0.559
Examination findings (present vs absent) 
  Obtundation0.006
  No. of lung lobes affected0.693
  Hypoalbuminemia0.018
  Azotemia0.008
  High liver enzyme activity0.018
Treatment (yes vs no) 
  Oxygen therapy1.000
  Nebulization0.401
  Coupage0.410
  Gastrointestinal drug administration0.692
  IV fluid administration0.031

Values of P < 0.05 were considered significant.

Measured as a continuous variable.

Indicates ALT above the reference range (13 to 88 U/L) in 4 dogs or ALT and ALP above the reference ranges (19 to 285 U/L for ALP) in 3 dogs.

Discussion

In the present study, we investigated the incidence and characteristics of aspiration pneumonia in Pugs, French Bulldogs, and Bulldogs. These 3 breeds were selected for study because they have consistent brachycephalic conformation10 with substantial facial shortening. The finding that these dogs had a significantly (P < 0.001) greater risk of aspiration pneumonia, compared with dogs of all other breeds examined at our hospital during the study period, was in contrast to those of previous studies of dogs3,7 or dogs and cats8 with aspiration pneumonia, in which no predisposition to the disease was identified for brachycephalic breeds, and large-breed dogs appeared more commonly affected than small and medium-sized dogs.5 However, several conditions identified as risk factors for aspiration pneumonia, including hiatal hernia, pyloric stenosis, pyloric mucosal hyperplasia, retention of gastric contents, and gastroesophageal reflux,12 are commonly found in brachycephalic dogs.1,7 Additionally, in people with obstructive airway syndrome, negative pressures exerted over the thoracic contents13,18,19 are associated with an increased risk of aspiration resulting from laryngeal and pharyngeal damage20–22 and an increased risk of regurgitation and aspiration of oral contents.12,23

Interestingly, Pugs had a significantly (P < 0.01) lower risk of developing aspiration pneumonia than French Bulldogs or Bulldogs in our study. A study10 that investigated relationships between craniofacial morphology and respiratory function in dogs revealed that Pugs had the greatest brachycephalic index (corresponding to the highest degree of facial shortening) among the breeds enrolled, and this was associated with an increased risk of BOAS.10 Thus, the results for Pugs in the present study did not appear to support that the conformational changes alone in brachycephalic dogs increase aspiration pneumonia risk. It is possible that other anatomic variations are greater determinants of this risk than external facial conformation. Neck circumference, for example, has been positively associated with OSA in people.22,24,25 Other possible differences in respiratory anatomy among dog breeds include the degree of nasopharyngeal turbinate protrusion, pharyngeal or laryngeal hypoplasia and collapse, soft palate length, and tracheal hypoplasia.11 These factors may further increase airway resistance and disturb normal airflow. The present study did not investigate possible relationships between BOAS score or neck circumference and aspiration pneumonia, as these data were not documented in hospital records.

The frequencies of gastrointestinal signs,1,5,6 neurologic disease,5,26 and a recent (ie, within 14 days) history of general anesthesia5,7 were investigated in the brachycephalic dogs with aspiration pneumonia in our study because these factors have previously been linked with the condition. Similar to findings in a previous study,6 gastrointestinal signs were the most commonly observed risk factor in the present study, with 4 of 5 Pugs, 9 of 11 French Bulldogs, and 14 of 25 Bulldogs with aspiration pneumonia having a known history of regurgitation or vomiting. Four of the 41 (10%) affected dogs had recently undergone general anesthesia, in line with previous reports, in which 12 of 88 (14%)6 to 20 of 125 (16%)5 dogs with aspiration pneumonia had undergone general anesthesia. Despite having an overall incidence of aspiration pneumonia no greater than that of the general hospital population of dogs, Pugs with this condition in our study had a high frequency of concomitant neurologic disease (3/5 dogs). Reduced consciousness increases the risk of aspiration for human patients,13 and we considered that the likely etiopathogenesis of aspiration in these Pugs was a combination of vomiting and reduced mentation. The incidences of neurologic conditions observed in affected dogs of the present study (seizure activity, necrotizing meningoencephalitis, and suspected intracranial neoplasia) increase with age.27,28 If neurologic disease is a key risk factor for aspiration pneumonia in Pugs, this could explain the significantly (P < 0.001) greater age of affected Pugs in our study (median, 83 months), compared with that of Bulldogs (6 months) and French Bulldogs (8 months), at the time of the examination.

There was no evidence of previously identified risk factors for aspiration pneumonia in 9 of the 41 (22%) affected dogs in the present study, a statistic not reported in previous studies of the condition in dogs. Lack of history of specific risk factor exposure could have been confounded by some events being unobserved or by a lack of recording of such events by the admitting clinician. However, it could also have suggested the presence of occult aspiration13 or other risk factors that were not explored in the study. Although this approach could have prevented identification of novel risk factors for aspiration pneumonia in the brachycephalic breeds studied, we were specifically interested in evaluating these patients for exposures previously associated with aspiration pneumonia in nonbrachycephalic dogs.1,5–7,9

Male dogs were more commonly represented than females in our study population (28 vs 13, respectively). Whether there is bias for one sex or the other in the general population of brachycephalic dogs is unknown; however, a predisposition for BOAS among males has been reported.29 A similar skew has been described in other studies3,5 of aspiration pneumonia in dogs. A study30 of mice with experimentally induced sepsis found an increased survival rate in females, which was hypothesized to be attributable to the protective effects of immunologic stimulation by estrogen. However, this was not supported by epidemiological investigations of sepsis in people.31 Most (31/41 [76%]) affected dogs in the population of interest for the present study were sexually intact; however, this could have been attributable to the young ages of most dogs at the time of examination and to clients' and practitioners' concerns regarding general anesthesia of brachycephalic dogs for elective procedures.

The median age of affected dogs in our population of interest was 7 months, and this differed substantially from the 7 to 8 years of age found in previous investigations.3,5,7 This suggested that risk factors for the condition in these brachycephalic dogs arise early in life, and this would support that conformational factors play a role in the etiopathogenesis of aspiration pneumonia, although as previously mentioned, the finding that Pugs were substantially older suggested that other anatomic factors or risk factors exist that are not conserved among brachycephalic breeds.

Notably, most (30/41 [73%]) study dogs were normothermic at the time of examination, and a fair proportion (10 [24%]) had apparently normal lung field auscultation, supporting previous findings.3,5 However, the proportion of dogs with tachypnea was greater than that reported elsewhere (33/41 [80%] vs 61/125 [49%]5). Identification of a pulmonary infiltrate in dependent lung lobes, particularly the right middle lobe, on diagnostic images is known to be associated with aspiration pneumonia in dogs.3,5 The right mainstem bronchus generally originates at a straighter angle from the carina than the left bronchus, with the bronchus for the right middle lobe branching ventrally,32,33 thus increasing the potential for aspirated fluid pooling in this lobe. The right middle lung lobe was most commonly affected (21/41 [51%]) in our patient population. Alveolar infiltrates predominated on imaging (24 [59%]), as would be expected; however, 9 (22%) patients had a predominantly bronchointerstitial infiltrate. Another study3 also found that interstitial patterns were fairly common in dogs with aspiration pneumonia (23/88 [26%]), and taken together, these findings suggest that patients with compatible signs and infiltrate distribution should not have aspiration pneumonia ruled out on the basis of an interstitial rather than alveolar pattern. Unfortunately, because of the retrospective nature of the present study, it was not possible to determine the timing of diagnostic imaging relative to development of clinical signs in many patients, and potential progression of patterns and distributions could not be assessed. Kogan et al6 found a worse prognosis for dogs with > 1 lung lobe affected, but our study found no association between the number of affected lung lobes and outcome.

Airway sampling was performed for only 16 of the 41 dogs with aspiration pneumonia in our study, with 25 of 41 (61%) dogs undergoing empirical antimicrobial treatment. The reasons for not submitting samples for culture and susceptibility testing were unknown in most cases but may have included financial constraints and concern over patient stability under general anesthesia. Culture and susceptibility results indicated that the identified isolates were most commonly susceptible to enrofloxacin, marbofloxacin, imipenem, amoxicillin-clavulanic acid, and oxytetracycline in vitro. As fluoroquinolones and imipenem are not considered first-line antimicrobial treatments,34 the use of potentiated amoxicillin (the most frequently prescribed antimicrobial in the study) for initial treatment seems appropriate, considering that the overall mean percentage of susceptible isolates in this study was 87%. No significant difference in survival rate was found between patients treated with potentiated amoxicillin (16/21 [76%]) and fluoroquinolones (3/3). This might have reflected discrepancies between in vitro and in vivo bacterial susceptibility to antimicrobials, where results in vivo can be affected by factors such as volume of distribution and tissue penetration. Single-agent versus dual-agent antimicrobial treatments also appeared to have no impact on survival rates, although the decision to use a multiagent approach in more severely affected patients could have confounded results.

The overall survival rate for affected dogs in the present study (32/41 [78%]) was similar to findings in previous investigations of dogs with aspiration pneumonia (102/125 [82%]5 and 68/88 [77%]6). Of the factors initially identified as negative prognostic indicators, age at the time of examination was the only independent predictor of outcome in logistic regression analysis, with increasing age associated with a greater likelihood of nonsurvival (P = 0.004). Lack of significant associations between the other variables assessed in this analysis (sex, neurologic disease, and obtundation at the time of examination) and outcome suggested a degree of dependency among some variables (eg, the previously described associations between age and neurologic disease27,28). The reason that sex was nonsignificant in the final analysis was unclear, although this may have been impacted by the small data set.

The retrospective nature of this study proved a primary limitation, with variability in range of diagnostic tests and treatment protocols. The inclusion criteria were selected with the intent to ensure an appropriate diagnosis of aspiration pneumonia; however, this can be difficult when no single standard test is used. Attempted methods of identifying aspiration pneumonia in human patients include presence of pepsin3,35 or lipid-filled macrophages3,36 in bronchiolar lavage fluid. Although the latter criterion may be of limited use because of the high numbers of lipid-laden macrophages present in the airway of healthy dogs, measurement of pepsin concentrations (once validated for canine patients) could serve as an ancillary test to confirm aspiration pneumonia. Obesity in is a known risk factor for OSA in people24; however, body condition score was inconsistently documented in the records of dogs in the present study. Results of 1 study37 suggest a minimal correlation between body weight and respiratory disease in brachycephalic dogs, but to the authors' knowledge, this has not been specifically examined in such dogs with aspiration pneumonia. No data were available regarding the facial conformation of each dog in the present study, and thus we could not assess whether there was a direct contribution of conformation to the risk of aspiration pneumonia. Including only Pugs, French Bulldogs, and Bulldogs in the present study ensured that all affected patients were brachycephalic; however, it is important to consider that the study excluded dogs of other brachycephalic breeds (eg, Pekingese and Boston Terriers), and thus the results may not necessarily be representative of the larger population of brachycephalic dogs.

The low number of dogs in the study population limited power for statistical analysis, which may have led to type II errors. For example, the small number of Pugs in the study may have affected some results such as mortality rates, although the association between neurologic disease and aspiration pneumonia in Pugs was significant.

Our results suggested that aspiration pneumonia should be considered a key differential diagnosis for respiratory disease in Pugs, French Bulldogs, and Bulldogs, even if the history appears devoid of obvious risk factors. Age at onset, and likely other risk factors for aspiration pneumonia, can vary among brachycephalic dog breeds, and a prospective study recruiting greater numbers of dogs from various breeds and assessing factors such as BOAS score, brachycephalic index, neck circumference, and body condition score could greatly increase our understanding of risk factors and prognostic indicators for aspiration pneumonia in these patients.

Acknowledgments

No external funding was provided for the study. The authors declare there were no conflicts of interest.

Presented in abstract form at the British Small Animal Veterinary Association Congress, Birmingham, England, April 2016.

The authors thank Dr. Yui-Mei Ruby Chang for reviewing the statistical analyses performed in the study.

ABBREVIATIONS

BOAS

Brachycephalic obstructive airway syndrome

CI

Confidence interval

OSA

Obstructive sleep apnea

Footnotes

a.

SPSS Statistics for Windows, version 22.0, IBM Corp, Armonk, NY.

References

  • 1. Schulze HM, Rahilly LJ. Aspiration pneumonia in dogs: pathophysiology, prevention and diagnosis. Compend Contin Educ Vet. 2012;34:E5.

  • 2. Cameron JL, Caldini P, Toung JK, et al. Aspiration pneumonia: physiologic data following experimental aspiration. Surgery 1972;72:238245.

    • Search Google Scholar
    • Export Citation
  • 3. Kogan DA, Johnson LR, Jandrey KE, et al. Clinical, clinicopathologic, and radiographic findings in dogs with aspiration pneumonia: 88 cases (2004–2006). J Am Vet Med Assoc 2008;233:17421747.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 2001;344:665671.

  • 5. Tart KM, Babski DM, Lee JA. Potential risks, prognostic indicators, and diagnostic and treatment modalities affecting survival in dogs with presumptive aspiration pneumonia: 125 cases (2005–2008). J Vet Emerg Crit Care (San Antonio) 2010;20:319329.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Kogan DA, Johnson LR, Sturges BK, et al. Etiology and clinical outcome in dogs with aspiration pneumonia: 88 cases (2004–2006). J Am Vet Med Assoc 2008;233:17481755.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Ovbey DH, Wilson DV, Bednarski RM, et al. Prevalence and risk factors for canine post anesthetic aspiration pneumonia (1999–2009): a multicenter study. Vet Anaesth Analg 2014;41:127136.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Epstein SE, Mellema MS, Hopper K. Airway microbial culture and susceptibility patterns in dogs and cats with respiratory disease of varying severity. J Vet Emerg Crit Care (San Antonio) 2010;20:587594.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Greenwell CM, Brain PH. Aspiration pneumonia in the Irish Wolfhound: a possible breed predisposition. J Small Anim Pract 2014;55:515520.

  • 10. Packer RM, Hendricks A, Tivers MS, et al. Impact of facial conformation on canine health: brachycephalic obstructive airway syndrome. PLoS One 2015;10:e0137496.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Poncet CM, Dupre GP, Freiche VG, et al. Prevalence of gastrointestinal tract lesions in 73 brachycephalic dogs with upper respiratory syndrome. J Small Anim Pract 2005;46:273279.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Poncet CM, Dupre GP, Freiche VG, et al. Long-term results of upper respiratory syndrome surgery and gastrointestinal tract medical treatment in 51 brachycephalic dogs. J Small Anim Pract 2006;47:137142.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Cardasis JJ, MacMahon H, Husain AN. The spectrum of lung disease due to chronic occult aspiration. Ann Am Thorac Soc 2014;11:865873.

  • 14. Hendricks JC, Kline LR, Kovalski RJ, et al. The English Bulldog: a natural model of sleep-disordered breathing. J Appl Physiol (1985) 1987;63:13441350.

    • Search Google Scholar
    • Export Citation
  • 15. Packer RMA, Tivers MS. Strategies for the management and prevention of conformation-related respiratory disorders in brachycephalic dogs. Vet Med Res Rep 2015;6:219232.

    • Search Google Scholar
    • Export Citation
  • 16. Boveri S, Ryan TM. Successful short-term mechanical ventilation in a brachycephalic dog following aspiration pneumonia. Vet Rec Case Rep 2016;4:e000256.

    • Search Google Scholar
    • Export Citation
  • 17. American Kennel Club. Official standard of the Bulldog. Available at: images.akc.org/pdf/breeds/standards/Bulldog.pdf?_ga=2.39565667.1391350359.1515869654-329041318.1515869654. Accessed Feb 21, 2018.

    • Search Google Scholar
    • Export Citation
  • 18. Hoareau GL, Jourdan G, Mellema M, et al. Evaluation of arterial blood gases and arterial blood pressures in brachycephalic dogs. J Vet Intern Med 2012;26:897904.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Bernaerts F, Talavera J, Leemans J, et al. Description of original endoscopic findings and respiratory functional assessment using barometric whole-body plethysmography in dogs suffering from brachycephalic airway obstruction syndrome. Vet J 2010;183:95102.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Nachtigall I, Tafelski S, Rothbart A, et al. Gender-related outcome difference is related to course of sepsis on mixed ICUs: a prospective, observational clinical study. Crit Care 2011;15:R151.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Petrof BJ, Pack AI, Kelly AM, et al. Pharyngeal myopathy of loaded upper airway in dogs with sleep apnea. J Appl Physiol 1994;76:17461752.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Davies RJ, Stradling JR. The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apneoa syndrome. Eur Respir J 1990;3:509514.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Demeter P, Pap A. The relationship between gastroesophageal reflux disease and obstructive sleep apnea. J Gastroenterol 2004;39:815820.

  • 24. Katz I, Stradling J, Sljutsky AS, et al. Do patients with obstructive sleep apnea have thick necks? Am Rev Respir Dis 1990;141:12281231.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Hoffstein V, Mateika S. Differences in abdominal and neck circumferences in patients with and without obstructive sleep apnoea. Eur Respir J 1992;5:377381.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Fransson BA, Bagley RS, Gay JM, et al. Pneumonia after intracranial surgery in dogs. Vet Surg 2001;30:432439.

  • 27. Levine JM, Fosgate GT, Porter B, et al. Epidemiology of necrotizing meningoencephalitis in Pug dogs. J Vet Intern Med 2008;22:961968.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Song RB, Vite CH, Bradley CW, et al. Postmortem evaluation of 435 cases of intracranial neoplasia in dogs and relationship of neoplasm with breed, age, and body weight. J Vet Intern Med 2013;27:11431152.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Fasanella FJ, Shivley JM, Wardlaw JL, et al. Brachycephalic airway obstructive syndrome in dogs: 90 cases (1991–2008). J Am Vet Med Assoc 2010;237:10481051.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Zellweger R, Wichmann MW, Ayala A, et al. Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males. Crit Care Med 1997;25:106110.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Pietropaoli AP, Glance LG, Oakes D, et al. Gender differences in mortality in patients with severe sepsis or septic shock. Gend Med 2010;7:422437.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Amis TC, McKiernan BC. Systematic identification of endobronchial anatomy during bronchoscopy in the dog. Am J Vet Res 1986;47:26492657.

    • Search Google Scholar
    • Export Citation
  • 33. Eom K, Seong Y, Park H, et al. Radiographic and computed tomographic evaluation of experimentally induced lung aspiration sites in dogs. J Vet Sci 2006;7:397399.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Beco L, Guaguère E, Lorente Méndez C, et al. Suggested guidelines for using systemic antimicrobials in bacterial skin infection: part 2—antimicrobial choice, treatment regimens and compliance. Vet Rec 2013;172:156160.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Lee JS, Song JW, Wolters PJ, et al. Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 2012;39:352358.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Adams R, Ruffin R, Campbell D. The value of the lipid-laden macrophage index in the assessment of aspiration pneumonia. Aust N Z J Med 1997;27:550553.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. O'Neill DG, Jackson C, Guy JH, et al. Epidemiological associations between brachycephaly and upper respiratory tract disorders in dogs attending veterinary practices in England. Canine Genet Epidemiol 2015;2:10.

    • Crossref
    • Search Google Scholar
    • Export Citation

Contributor Notes

Address correspondence to Dr. Darcy (hdarcy@rvc.ac.uk).
  • 1. Schulze HM, Rahilly LJ. Aspiration pneumonia in dogs: pathophysiology, prevention and diagnosis. Compend Contin Educ Vet. 2012;34:E5.

  • 2. Cameron JL, Caldini P, Toung JK, et al. Aspiration pneumonia: physiologic data following experimental aspiration. Surgery 1972;72:238245.

    • Search Google Scholar
    • Export Citation
  • 3. Kogan DA, Johnson LR, Jandrey KE, et al. Clinical, clinicopathologic, and radiographic findings in dogs with aspiration pneumonia: 88 cases (2004–2006). J Am Vet Med Assoc 2008;233:17421747.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 2001;344:665671.

  • 5. Tart KM, Babski DM, Lee JA. Potential risks, prognostic indicators, and diagnostic and treatment modalities affecting survival in dogs with presumptive aspiration pneumonia: 125 cases (2005–2008). J Vet Emerg Crit Care (San Antonio) 2010;20:319329.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Kogan DA, Johnson LR, Sturges BK, et al. Etiology and clinical outcome in dogs with aspiration pneumonia: 88 cases (2004–2006). J Am Vet Med Assoc 2008;233:17481755.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Ovbey DH, Wilson DV, Bednarski RM, et al. Prevalence and risk factors for canine post anesthetic aspiration pneumonia (1999–2009): a multicenter study. Vet Anaesth Analg 2014;41:127136.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Epstein SE, Mellema MS, Hopper K. Airway microbial culture and susceptibility patterns in dogs and cats with respiratory disease of varying severity. J Vet Emerg Crit Care (San Antonio) 2010;20:587594.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Greenwell CM, Brain PH. Aspiration pneumonia in the Irish Wolfhound: a possible breed predisposition. J Small Anim Pract 2014;55:515520.

  • 10. Packer RM, Hendricks A, Tivers MS, et al. Impact of facial conformation on canine health: brachycephalic obstructive airway syndrome. PLoS One 2015;10:e0137496.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Poncet CM, Dupre GP, Freiche VG, et al. Prevalence of gastrointestinal tract lesions in 73 brachycephalic dogs with upper respiratory syndrome. J Small Anim Pract 2005;46:273279.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Poncet CM, Dupre GP, Freiche VG, et al. Long-term results of upper respiratory syndrome surgery and gastrointestinal tract medical treatment in 51 brachycephalic dogs. J Small Anim Pract 2006;47:137142.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Cardasis JJ, MacMahon H, Husain AN. The spectrum of lung disease due to chronic occult aspiration. Ann Am Thorac Soc 2014;11:865873.

  • 14. Hendricks JC, Kline LR, Kovalski RJ, et al. The English Bulldog: a natural model of sleep-disordered breathing. J Appl Physiol (1985) 1987;63:13441350.

    • Search Google Scholar
    • Export Citation
  • 15. Packer RMA, Tivers MS. Strategies for the management and prevention of conformation-related respiratory disorders in brachycephalic dogs. Vet Med Res Rep 2015;6:219232.

    • Search Google Scholar
    • Export Citation
  • 16. Boveri S, Ryan TM. Successful short-term mechanical ventilation in a brachycephalic dog following aspiration pneumonia. Vet Rec Case Rep 2016;4:e000256.

    • Search Google Scholar
    • Export Citation
  • 17. American Kennel Club. Official standard of the Bulldog. Available at: images.akc.org/pdf/breeds/standards/Bulldog.pdf?_ga=2.39565667.1391350359.1515869654-329041318.1515869654. Accessed Feb 21, 2018.

    • Search Google Scholar
    • Export Citation
  • 18. Hoareau GL, Jourdan G, Mellema M, et al. Evaluation of arterial blood gases and arterial blood pressures in brachycephalic dogs. J Vet Intern Med 2012;26:897904.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Bernaerts F, Talavera J, Leemans J, et al. Description of original endoscopic findings and respiratory functional assessment using barometric whole-body plethysmography in dogs suffering from brachycephalic airway obstruction syndrome. Vet J 2010;183:95102.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Nachtigall I, Tafelski S, Rothbart A, et al. Gender-related outcome difference is related to course of sepsis on mixed ICUs: a prospective, observational clinical study. Crit Care 2011;15:R151.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Petrof BJ, Pack AI, Kelly AM, et al. Pharyngeal myopathy of loaded upper airway in dogs with sleep apnea. J Appl Physiol 1994;76:17461752.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Davies RJ, Stradling JR. The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apneoa syndrome. Eur Respir J 1990;3:509514.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Demeter P, Pap A. The relationship between gastroesophageal reflux disease and obstructive sleep apnea. J Gastroenterol 2004;39:815820.

  • 24. Katz I, Stradling J, Sljutsky AS, et al. Do patients with obstructive sleep apnea have thick necks? Am Rev Respir Dis 1990;141:12281231.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Hoffstein V, Mateika S. Differences in abdominal and neck circumferences in patients with and without obstructive sleep apnoea. Eur Respir J 1992;5:377381.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Fransson BA, Bagley RS, Gay JM, et al. Pneumonia after intracranial surgery in dogs. Vet Surg 2001;30:432439.

  • 27. Levine JM, Fosgate GT, Porter B, et al. Epidemiology of necrotizing meningoencephalitis in Pug dogs. J Vet Intern Med 2008;22:961968.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Song RB, Vite CH, Bradley CW, et al. Postmortem evaluation of 435 cases of intracranial neoplasia in dogs and relationship of neoplasm with breed, age, and body weight. J Vet Intern Med 2013;27:11431152.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Fasanella FJ, Shivley JM, Wardlaw JL, et al. Brachycephalic airway obstructive syndrome in dogs: 90 cases (1991–2008). J Am Vet Med Assoc 2010;237:10481051.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Zellweger R, Wichmann MW, Ayala A, et al. Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males. Crit Care Med 1997;25:106110.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Pietropaoli AP, Glance LG, Oakes D, et al. Gender differences in mortality in patients with severe sepsis or septic shock. Gend Med 2010;7:422437.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Amis TC, McKiernan BC. Systematic identification of endobronchial anatomy during bronchoscopy in the dog. Am J Vet Res 1986;47:26492657.

    • Search Google Scholar
    • Export Citation
  • 33. Eom K, Seong Y, Park H, et al. Radiographic and computed tomographic evaluation of experimentally induced lung aspiration sites in dogs. J Vet Sci 2006;7:397399.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Beco L, Guaguère E, Lorente Méndez C, et al. Suggested guidelines for using systemic antimicrobials in bacterial skin infection: part 2—antimicrobial choice, treatment regimens and compliance. Vet Rec 2013;172:156160.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Lee JS, Song JW, Wolters PJ, et al. Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis. Eur Respir J 2012;39:352358.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Adams R, Ruffin R, Campbell D. The value of the lipid-laden macrophage index in the assessment of aspiration pneumonia. Aust N Z J Med 1997;27:550553.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37. O'Neill DG, Jackson C, Guy JH, et al. Epidemiological associations between brachycephaly and upper respiratory tract disorders in dogs attending veterinary practices in England. Canine Genet Epidemiol 2015;2:10.

    • Crossref
    • Search Google Scholar
    • Export Citation

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