To the authors’ knowledge, this is the first prospective clinical study of dogs suffering from BAOS that has evaluated the levels of several biomarkers [acute phase proteins (CRP, Hp) and cTnI] and the relation of them with clinical signs and anatomical features.
The English bulldog has snoring and fragmented sleep
 with mild hypoxemia and apneas only during rapid eye movement. English bulldog is the closest animal model for OSAS. Even if, UA obstructive disease in dogs is not equal to OSAS, important similarities exist. Some studies used brachycephalic dogs, as an animal model, to evaluate pharyngeal dilator muscular damages in UA obstructive disease, observing similar alterations to human patients with OSAS
The correlation between human OSAS, inflammation and cardiovascular disease is well established
[10, 13, 16]. The mechanism involved in the development of cardiovascular disease is attributed to increased sympathetic activity due to sleep deprivation and fragmentation, and repetitive hypoxemic events with significant arterial desaturation. These factors are believed to lead to an activation of pro-inflammatory cytokines. Even if OSAS and BAOS are different syndromes, this study tries to clear up a possible association of BAOS, inflammation and cardiovascular diseases.
The presence of digestive signs in dogs with BAOS has been described elsewhere
[3, 25–27]. The relationship between respiratory and digestive signs is due to the exaggerated repetitive variation of diaphragmatic pressure, present in patients with obstructive breathing, which causes gastroesophageal reflux and inflammation of the oropharyngeal areas that, in turn, worsen respiratory signs
[3, 27]. Poncet and others
[3, 27] found an association between the severity of respiratory and digestive signs in dogs with BAOS, which suggests that these signs are related. These authors also used endoscopy and histological studies to reveal the presence of lesions in the digestive tract of all dogs with BAOS. The majority of dogs with BAOS in the present study had digestive signs, but no association between the severity of digestive and respiratory signs was found. Even though the physiological relation of respiratory and digestive signs is clear, a correlation with severity of both signs is not always present. The results of the study indicate a correlation between the presence of digestive signs and high cTnI values, but authors did not find any plausible explanation for this association. Further studies should be performed in order to find the physiological reason of this correlation.
The most common anomalies present in dogs from the present study were stenotic nares and elongated soft palate, similar to findings described by previous studies
[16, 26, 28]. However, the prevalence of everted laryngeal saccules in dogs of the present study was lower that previously reported
[4, 6, 29]. Due to the prospective nature of this study, the presence of tracheal hypoplasia was evaluated in nearly all the cases included (96%) and was found in 14 dogs (29.1%). Tracheal hypoplasia is a concurrent finding in many patients with BAOS
[1–3, 5–7, 25, 30]. English bulldogs are more commonly affected by tracheal hypoplasia than other breeds, which could have biased our results
[1, 30, 31]. But, according other studies and our results, in the absence of concurrent pulmonary disease, tracheal hypoplasia is usually not associated with clinical signs
[31–33]. It may exacerbate the respiratory signs associated with BAOS because of increased resistance to airflow, but tracheal hypoplasia, according our results and other reports, is not associated with worse outcomes after surgical correction of BAOS
[1, 6, 31, 33, 34].
The presence of nasopharyngeal turbinates can be an important anatomic component of BAOS
, but in the present study it has not been evaluated in all dogs due to the multicentric nature of the study.
The innovative aspects of this work are the determination of different biomarkers in dogs with BAOS. The design of the study included a complete work-up to exclude other diseases that might affect the results of biomarker determination. In human medicine, high values of C-reactive protein (CRP) have been found in OSAS patients and have been associated with the severity of respiratory signs according to the apnea/hypopnea index
. The apnea/hypopnea index, obtained during polisomnography, is an important parameter for describing the severity of OSAS and describes the number of apneas or hypopneas per hour. Moreover levels of CRP, Hp and IL-6 in human patients with OSAS decreased after surgical or medical treatment
[16, 36]. A study performed with 17 brachycephalic dogs showed that some proinflammatory cytokines and nitric oxide are increased in brachycephalic dogs and also correlated with the severity of clinical signs
. Even though, in the present study few dogs had high values of CRP and Hp, and no correlation with the severity of respiratory signs was observed, with the exception of patients with everted laryngeal saccules. The presence of everted laryngeal saccules is considered a secondary change from airway obstruction, but can contribute to aggravate obstructive upper airway signs. A significant association has been found between the presence of everted laryngeal, severity of respiratory signs and CRP levels indicating that the presence of everted laryngeals can increase upper airway obstruction leading to severe respiratory signs and increase of inflammatory biomarkers. By contrast, the present results suggest that CRP and Hp determination, in general, do not offer valuable information in dogs with BAOS. Probably, in brachycephalic dogs, BAOS do not cause such an inflammatory status as OSAS in human patients. In human medicine, OSAS is diagnosed in adult patients and anatomical abnormalities are not the unique etiology of the syndrome. On the other hand, BAOS is diagnosed in young brachycephalic patients with upper airway abnormalities. Maybe those differences justify a less obvious systemic inflammatory response in dogs suffering from BAOS. Actually, a clinical grade system and upper airway examination can define BAOS in canine patients. Even though, an objective clinical test, such as apnea-hipopnea index, obtained during polisomnography and used to define human OSAS severity, could offer valuable information to better classify and understand BAOS. On the other hand, the respiratory functional assessment using barometric whole-body plethysmography in brachycephalic dogs could also be used to characterize the respiratory compromise in those dogs
. Due to the complexity of these tests, polisomnography and plethysmography were not available for our study.
Several authors suggested that cTnI determination in dogs is useful for identifying myocardial damage
[38, 39]. A large percentage of brachycephalic dogs (47.8%) had high levels of cTnI. It is interesting to note that all (100%) English bulldogs and 53.8% of French bulldog had high levels of cTnI. The hypothesis is that, as occurs in humans with OSAS, BAOS can induce surges in sympathetic activity, hypoxia and increased blood pressure that lead to myocardial damage.
All patients included in the study were submitted to a thorough physical examination, blood work, thoracic x-ray and an electrocardiogram, and no evidence of cardiac disease was found. However brachycephalic dogs may be predisposed to pulmonary hypertension, due to chronic hypoxia, and dogs with pulmonary hypertension can have increased concentrations of cTnI
. A limitation of the study due to its multicentric nature is that echocardiography was not performed in all dogs and therefore pulmonary hypertension and occult cardiac disease cannot be completely ruled out as a cause of increase cTnI in some dogs from this study. Even though, the evaluation of ECG (presence of arrhythmias and tachycardia) and vertebral heart score (VHS) was evaluated in relation to cTnI, CRP and Hp without obtaining any association. Moreover cTnI levels can vary with age and breed
[38, 41, 42] and canine reference intervals must be established for different age groups and breeds. This information should be added to future studies. Although further studies must clarify this condition, the results obtained from this study suggest that some patients with BAOS had hidden but biochemically detectable myocardial injury. Even though, it must be considered that repeated measurements of those biomarkers levels in each individual dog could have increased the robustness of the results. On the other hand, the lack of a control group is an important limitation of the study since could have helped to interpret the results. But it must be taken to account, that is very difficult to find brachycephalic dogs with a normal breathing pattern because nearly all of them have some degree of upper airway obstruction.