Pathophysiology of Brachycephalic Airway Syndrome

David Cook 

ANZCVS Resident’ Forum 

Surgery Chapter 2013

PRIMARY ABNORMALITIES 1 

Shortened maxilla – 

bony structures 

reduced in length 

without relative 

reduction in soft 

tissue length 

Linked to multiple 

single nucleotide 

polymorphisms in 

the Cfa1 gene 

Bannasch 2010

PRIMARY ABNORMALITIES 2 

Stenotic Nares 

Elongated Soft Palate 

Thickened as well as elongated 

Caudally displaced nasopharyngeal 

turbinates 

Redundant pharyngeal mucosal tissue 

Hypoplastic trachea

ABNORMALITIES OF GAS FLOW 1 

Anatomic abnormalities lead to increased 

upper airway resistance compared to meso 

and dolicocephalic animals 

Turbulent flow of gas is more likely 

Dogs and cats prefer to breathe through 

the nose 

Resistance is reduced with mouth 

breathing but there is loss of nasal function 

(humidification, filtration of particulate 

material, reduced olfactory function)


Increased resistance and turbulent flow 

(rather than laminar flow) increase the 

amount of driving pressure required to 

move gas 

Increased driving pressure requires 

increased work by respiratory muscles


Respiratory disease is often associated with 

reduced airway diameter 

Upper airway obstruction 

Dynamic lower airway disease 

Fluid or exudate accumulation 

These changes lead to 

○ Increased resistance to flow 

○ Increase in driving pressure necessary to generate the 

breath 

○ Increased likelihood of turbulent flow 

○ Increased work of breathing 

Exaggerated breathing efforts can also lead to high 

gas flows which increase the likelihood of turbulent 

flow and work of breathing

LAMINAR GAS FLOW EQUATION 

Increased resistance to airflow is caused by a 

decrease in airway radius described by 

Poiseulle’s Law – Q = πΔPr 4 /8ηl 

Q = flow rate 

ΔP = pressure difference between the ends of the 

airway 

r = radius of airway 

η = viscosity of gas (eta) 

l = length of airway 

Resistance to laminar flow is directly related to 

the length of the tube and the viscosity of the 

fluid, and is inversely related to the radius of the 

tube 4

TURBULENT GAS FLOW 

Mathematical equations not easily used 

Turbulent flow occurs when there is a 

disruption of orderly laminar flow à occurs at 

airway bifurcations and branches and with 

partial airway obstructions (abrupt changes in 

airway diameter) as well as at high flow rates 

Turbulent flow can return to laminar if there is 

long enough distance 

Resistance to turbulent flow is directly related 

to the density of the fluid and is inversely 

related to the tube radius 5 

This is a non linear relationship

REYNOLDS NUMBER 

Predicts laminar or turbulent flow 

Laminar flow 4000

ENERGY REQUIRED FOR 

BREATHING 

Change in pressure required 

Laminar flow 

ΔP ≈ Q x R 

Turbulent flow 

ΔP ≈ Q 2 X R 

Where ΔP represents the required effort of 

breathing and is close to the difference 

between atmospheric pressure and 

intrapleural pressure (= transpulmonary 

pressure)

AIRWAY RESISTANCE IN NORMAL 

DOGS 

Inspiration 

79% nasal 

6% laryngeal 

15% small airway 

Expiration 

74% nasal 

3% laryngeal 

23% small airway

UPPER AIRWAY RESISTANCE IN 

BAS DOGS 

Experimentally, clinically affected 

bulldogs have 6 x the upper airway 

resistance of laboratory beagles, and 5 x 

the upper airway resistance of mildly/ 

non clinically affected bulldogs 

Weistner AJVR 2007

CHRONIC CHANGES TO AIRWAY 

RESISTANCE (4 m experimental) 

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Partial bilateral obstruction leads to large 

increase in airway resistance 

Also leads to large decrease in intrapleural 

pressure reflecting increased inspiratory effort 

Ohnishi Laryngoscope 1971 (81:712)

WORK OF BREATHING 

Energy is required to overcome frictional 

resistance to gas flow through airways, and 

elastic recoil of lungs/chest wall 

Normal lung under resting respiratory effort – 

all work is done by inspiratory muscles à 

exhalation achieved through potential 

energy stored in expanded elastic tissues of 

lung and chest wall 

Resp muscle oxygen consumption is less 

than 2% of the total metabolic rate 

Airway narrowing increases he work of 

breathing necessary to overcome airway 

resistance

RESPIRATORY STRATEGY OF BAS 

DOGS 1 

Prolonged inspiratory phase with 

increased flow rate 

Markedly increased expiratory flow rate 

reflecting increased muscle effort 

Reduced or absent respiratory pause 

Increased respiratory rate 

Change in measured respiratory 

parameters reflects fixed and dynamic 

components of upper resp obstruction

RESPIRATORY STRATEGY OF BAS 

DOGS 2 

BAS dogs without clinical signs display 

respiratory patterns similar to normal 

dogs with experimental upper resp 

obstruction 

Similar changes demonstrated with 

Plethysmography - Bernaerts 2010 Vet J 

Tidal Flow Volume Loops – Amis 1986 AJVR

WHAT IS PLETHYSMOGRAPHY 

Pressure measured in box to 

calculate changes in volume 

over time 

RR 

Est tidal volume/kg (TV/BW) 

Est minute vol/kg (MV/BW) 

Inspiratory and expiratory times 

(Ti, Te) 

Relaxations time (= time at 

which 65% of tidal vol exhaled) 

(RT) 

Peak inspiratory and expiratory 

pseudoflows per KG (PIF or 

PEF/BW) 

Enhanced pause (unitless index 

of airflow limitation or 

bronchoconstriction) à 

calculated by Penh = (PEF/PIF) 

x ((Te – RT)/RT) 

Hoffman 2007

ABNORMALITIES DESCRIBED BY 

PLETHYSMOGRAPHY 

Te/Ti, PIF/BW, and RT are significantly 

lower / prolonged) compared to normal dogs 

PEF/BW, PEF/PIF, Penh and Pause were 

significantly higher / prolonged compared to 

normal dogs 

1 day post operative changes 

○ Only significant change was decrease in PEF/PIF 

value 

○ Compared to normal dogs, PEF/PIF, Penh and 

pause remained significantly increased in 

brachycephalic dogs however Te/Ti, RT, PIF/BW 

and PEF/BW were not statistically significantly 

different

Bernaerts 2010 Vet J

ARTERIAL BLOOD GAS 

ABNORMALITIES 1 

Significantly lower PaO 2 (86 vs 100) 

Significantly higher 

PaCO 2 (36 vs 32) 

PCV (48 vs 44) 

Arterial blood pressure (oscillometric mean 

123, systolic 178 and diastolic 95) 

Horeau JVIM 2012

BLOOG GAS ABNORMALITIES 2 

Most abnormalities should be compensated for by 

peripheral chemoreflex via central control of respiratory 

patterns in normal animals 

In particular CO 2 diffusion is unlikely to be limited at 

high respiratory rates as long as alveolar ventilation is 

adequate 

Peripheral chemoreflex also stimulates sympathetic 

drive – increase blood pressure in response to 

hypoxaemia and hypercapnia 

Habituation – change to set points 

Humans with sleep apnoea are predisposed to 

hypertension via activation of RAAS and the 

sympathetic nervous system. Changes are linked to 

obesity 

PCV increase may be compensatory for chronic 

hypoxia or reflect RAAS activation

BLOOD GAS ABNORMALITIES 3 

Slawuta 2011 

PaO 2 = 73 

PaCO 2 = 52 

More extreme changes relative to 

Horeau’s study 

Population of French Bulldogs 

Significant improvement in values 

following alarplasty (PaO2 = 82, PaCO 2 

= 49)

CYTOKINE ABNORMALITIES 1 

Rancan 2013 

Measured pro and anti inflammatory 

cytokines in normal and BAS dogs (with 

and without clinical signs) 

All BAS dogs had elevated TNF α 

IL – 17A increased in markedly affected 

BAS dogs – in humans thought to 

contribute to subeptihelial fibrosis and 

airway remodelling in asthma

CYTOKINE ABNORMALITIES 2 

NO increased in severely affected dogs, 

trend to increase in other BAS dogs 

IL-10 (anti inflammatory cytokine) – 

significantly higher in BAS dogs – in 

humans used as marker of pulmonary 

disease therapy in COPD

ACUTE PHASE PROTEINS 1 

Planellas 2012 

C reactive protein, haptoglobin, cardiac 

troponin I levels measured in 50 BAS 

dogs 

Link between sleep apnoea in people 

and increased rate of CV complications 

Patients had concurrent ECG

ACUTE PHASE PROTEINS 2 

47% of dogs had increased CTn I (100% 

english bulldogs, 55% French Bulldogs) 

14% CRP, 22% Hb 

Dogs with everted laryngeal saccules had 

increased resp scores and sig increase in CRP 

Correlation between severity of GI signs and 

CTnI levels 

CTnI sensitive marker of acute myocardial 

injury but is non specific – can increase (in 

humans) with tachycardia and inadequate 

oxygen supply, pulmonary hypertension, 

systemic hypertension, acute exacerbations of 

COPD, strenuous endurance exercise

CONCURRENT CARDIAC DISEASE 

Affected breeds pre disposed to heart 

disease 

CKCS – acquired valvular disease 

Bulldogs – Pulmonic stenosis 

Theory (Monnet in Slatter, 2003) of 

pulmonary hypertension secondary to 

reflex pulmonary perfusion changes 

under chronic hypoxic conditions 

eventually leading to cor pulmonale and 

right sided heart failure

STENOTIC NARES 1 

Axial deviation of the dorso lateral nasal 

cartilage and associated mucosa and 

epithelium 

Leads to upper respiratory obstruction in 

affected breeds 

Theorised to lead to secondary changes 

Can be treated at a young age (Pink 

2006)

STENOTIC NARES

STENOTIC NARES 2 

Wiestner 2007 

Brachycephalic dogs showing clinical 

signs of upper resp obstruction have 6x 

the resistance of laboratory beagles 

BAS dogs not showing CSx have 2x the 

resistance of lab beagles 

Slawuta 2011 showed significant 

improvement in PaO 2 following surgical 

correction

SOFT PALATE 

Soft palate arises from the caudal 

margin of the hard palate and extends 

aborally 

Considered elongated if the tip of the 

soft palate extends more than 1-3mm 

distal to the most rostral aspect of the 

epiglottis

ELONGATED SOFT PALATE

SOFT PALATE PHYSIOLOGY 

Sensory component as part of swallowing 

reflex (CN V) 

Closure of intrapharyngeal region to 

prevent nasopharyngeal reflux 

Levator palatini and palatopharyngeus mm 

elevate palate and draw caudal palate, 

palatopharyngeal arches and caudal 

pharynx together to close nasopharynx 

Elongated palate causes stertor and stridor 

which are audible vibrational effects

SOFT PALATE CHANGES 1 

Pichetto 2011 found that Brachycephalic 

dogs with few or no clinical signs had 

histological abnormalities of the palate 

Epithelial hyperplasia (worse on oral side) 

Oedema (lamina propria, worse aborally) 

Fibrosis, abnormal collagen fibre orientation 

Mucous gland hyperplasia and increased mucin 

production 

Muscular portion did not extend to aboral tip 

Changes to muscle fibres consistent with 

chronic trauma

SOFT PALATE CHANGES 2 

Grand 2011 found 

that soft palate 

thickness increased 

with severity of 

clinical signs based 

on a CT 

measurement and 

clinical score

NASOPHARYNGEAL TURBINATES 

Caudally displaced nasopharyngeal 

turbinates identified by endoscopy or CT 

Varying degrees reported 

Ginn 2011 20% of dogs with BAS (11/52) 

○ 82% of these were pugs 

Bernaerts 2010 – 1 English bulldog (1/11) 

Grand 2011 – none reported 

Oechtering 2007 – abstract ‘up to 100%’ – CT 

study described rostral and caudal abnormalities 

with ‘crude and abnormal branching of lamellae’

Ginn 2008

HYPOPLASTIC TRACHEA 1 

Congenital abnormality in which the ends 

of the tracheal cartilage rings overlap 

Lumen is rigid and narrow with reduced or 

absent dorsal tracheal membrane 

Theoretically may complicate BAS due to 

increased resistance to flow (laminar flow is 

proportional to radius 4 ) 

Multiple studies have found no worsening 

of prognosis with surgery when hypoplastic 

trachea is present (Riecks 2007, Lorison 

1997, Coyne 1992))

Clarke 2011


Ratio for measurement of tracheal diameter 

radiographically is a ratio between the 

diameter of the tracheal lumen and the 

distance between the mid body of the first 

thoracic verterbae and the middle of the 

manubrium of the sternum 

Normal ranges 

Normal dogs > 20% 

Brachycephalic dogs > 16% 

Bulldogs 12.7%


Pink 2006 reported histological changes 

from the trachea of 1 bulldog post 

mortem 

Loss of ciliated epithelium 

Mucosal hypertrophy 

Mucous gland necrosis 

Marked mononuclear infiltrate 

Submucosal fibrosis


Improvement in tracheal diameter ratio 

has been documented in group of 6 

bulldogs admitted for 

bronchopneumonia (Clarke 2011) 

Bulldogs puppies improved from 0.07 to 

0.14 (significant) 

Non brachycephalic control puppies with 

bronchopneumonia improved from 0.14 

to 0.17 (no significant)


Infectious agents cultured from these 

puppies were mixed 

5 cases supported aspiration pneumonia 

3 cases had bordetella sp

SECONDARY CHANGES 

Acquired pharyngeal muscular dysfunction 

Everted Tonsils 

Everted laryngeal saccules 

Laryngeal collapse 

Dynamic lower airway disease 

Structural and inflammatory gastrointestinal 

changes 

Aspiration pneumonia/pulmonary oedema 

(complications)

PHARYNGEAL CHANGES 1 

In humans, palatine muscles contract to 

stiffen upper airways in response to 

increasingly negative upper airway 

pressures and hypoxic hypercapnia à 

palatine contraction helps to partition 

airflow


Bulldogs studied in a human sleep 

apnoea model were found to have 

fibrosis of pharyngeal dilator muscles, 

abnormal muscle fibre morphology and 

increased proportions of Type II fibres 

MRI studies found that pharyngeal 

muscles relax then undergo 

spontaneous vigorous contraction when 

the patient becomes hypoxic


Rat models suggest increased fatigue 

ability of pharyngeal muscles under 

hypoxic conditions 

Brachycephalic dogs are likely to have 

reduced ability to moderate pharyngeal 

tone when they are fatigued particularly 

a reduced ability to dilate the pharynx 

during inspiration 

This is likely to increase resistance and 

increase the risk of turbulent flow

EVERTED TONSILS 

Described in up to 56% of cases (Fasanella 

2010) 

Lymphoid hyperplasia – mild/moderate 

Infiltrate of neutrophils or eosinophils 

common 

Stimulated by turbulent airflow, increased 

negative pressure of inspiration and 

antigenic stimulation related to 

regurgitation 

Contribute to narrowing of airway and risk 

of turbulent flow when panting

LARYNGEAL SACCULES 1 

Saccule = mucosal lining of lateral laryngeal ventricle 

(between vestibular and vocal folds) à place with 

least structural resilience in laryngeal wall 

Historical first stage of Laryngeal collapse (Leonard 

1960) 

Considered separate condition to laryngeal collapse 

by Torrez and Hunt 2006 

Hypothesis is that saccules evert in response to 

chronic negative airway pressure 

Reported incidence mostly in the range of 55-65% in 

larger case series (Poncet, Torrez, Riecks, 

Fasanella)


Cantatore 2012 reported histologic findings 

and endoscopic follow up following 

staphylectomy, alarplasty and resection of 

1 ventricle 

Histological findings 

Oedema 

Epithelial hyperplasia/keratosis 

Fibrosis 

Lymphatic dilation 

Inconsistent inflammatory cell population – 

where present lymphoplasmacytic/mast cells

Cantatore 2012


Surgical treatment of other BAS 

abnormalities did not lead to 

improvement in histologic characteristics 

of saccules resected 2-4 months later 

Photographs in paper give impression of 

increased size of saccules left in situ 

Patients showed improved clinical 

scores

LARYNGEAL COLLAPSE 

Stages of collapse described by Leonard – 

1 to 3 (saccules, cuneiform, corniculate) 

Progressive loss of structural integrity of 

cartilage leads to collapse and further 

contribution to airway obstruction 

Excluding stage 1 collapse most studies 

report 53-67% range 

Riecks 2007 reported 8.1% 

Pink 2006 reported laryngeal collapse from 

4.5m age

Stage 2 collapse – Tobias and 

Johnston Ch101

LARYNGEAL COLLAPSE 2 

Pink described histologic changes from 

1 Bulldog post mortem (arytenoid) 

Loss of normal ciliated epithelium 

Muscosal hypertrophy 

Abnormal mucosal glands show marked 

necrosis with marked mononuclear infiltrate 

Submucosal fibrosis

Pink 2006


Collapse of the arytenoid cartilages can 

occur without eversion of laryngeal 

saccules - unclear whether this is a 

manifestation of BAS or a separate 

condition with congenital axial 

displacement of cuneiform processes 

(Torrez 2006, Nelissen 2012) 

Laryngeal paralysis may also be a feature 

4/6 dogs in this study had a history of 

respiratory surgery and many were 

brachycephalic breeds (Nelissen 2012)


Presence of laryngeal collapse significantly 

increases the risk of post operative dyspnoea 

in some studies (White 2012) 

9/10 dogs with stage 3 collapse experienced 

post operative dyspnoea 

20% of stage 2 collapse 

Post operative dyspnoea in most larger BAS 

studies is in the range of 5-8% despite 

reported rates of laryngeal collapse of 55-65% 

Laryngeal collapse linked to multiple upper 

airway abnormalities (not identified in patients 

with elongated palate only e.g. CKCS Torrez 

2006)

DYNAMIC LOWER AIRWAY 

DISEASE 1 

Collapse of the left mainstem bronchus 

and particularly the left cranial bronchus 

documented in 70 – 87.5% of patients 

De Lorenzi 2009 35/40 BAS patients 

had abnormalities 

Of these, 84% were left sided 

Airways distal to the mainstem bronchi 

were typically normal 

Bernaerts 2010 reported 70%

De Lorenzi 2009


DISEASE 2 

Proposed a grading scheme for lower 

airway collapse 

Grade 1 – up to 30% reduction in diameter 

Grade 2 – 30-60% 

Grade 3 - >60% 

Each bronchus assigned individual score 

Laryngeal collapse correlated with more 

severe bronchial collapse 

Severity of collapse did not correlate with 

surgical outcome (telephone follow up)


DISEASE 3 

Increased upper airway resistance for 

both inspiration and expiration leads to 

recruitment of muscles 

Increases transpulmonary pressure 

under forced exhalation 

Increase pressure on structural support 

(cartilage) leads to weakening and 

collapse 

Juvenile cartilage more prone to 

deformation under stress


DISEASE 4 

Increased expiratory pressure gradient increases 

gas velocity 

Increased velocity leads to reduction in intraluminal 

pressure (Bernoulli effect) 

This leads to greater transpulmonary pressure 

gradient and increased propensity to collapse 

Collapse of airways causes disparity in lumen 

diameter which increases the risk of turbulent flow 

In people, left mainstem bronchus is more prone to 

collapse – thought to relate to increased length 

relative to right 

Collapsing left cranial bronchus may be linked to 

increased rates of lung lobe torsion in 

brachycephalic dogs in that lobe (pugs)

GASTRO INTESTINAL 1 

Poncet 2005 (and 2006) describe 

findings and long term outcomes of 

treatment (surgical and medical) 

Investigated the link between 

gastrointestinal pathology and severity 

of upper respiratory symptoms

Poncet 2005

GASTRO INTESTINAL 2 

Respiratory and gastrointestinal grading 

systems – 1 (mild) – 3 (severe) 

Population of mostly French and English 

Bulldogs 

Routine upper GI endoscopy (all) and 

biopsy (most) of gastric and duodenal 

mucosa 

Assessed mucosal pathology as mild, 

moderate or severe

GASTROINTESTINAL 3 

Oesophageal changes – 60% overall 

Tortuous/non linear oesophagus – 16% 

Gastroesophageal reflux like mucosal 

changes – 31% 

Atony of lower oesophageal sphincter – 38%


Stomach – 97.3% 

Mild – severe inflammatory changes (24% 

severe) – chronic, diffuse, follicular gastritis 

86% pyloric mucosal hyperplasia 

Hiatal hernia 4%


Duodenum 

Unable to evaluate duodenum in 7 cases 

(9.6%) due to inability to pass scope through 

pylorus (small, hyperplastic) 

Of the remaining 66, 53% had duodenal 

inflammation

Poncet 2005


2 dogs had no GI clinical signs, but still 

had inflammatory changes 

Significant relationship between severity 

of clinical signs (respiratory and GI) for 

French Bulldogs, males and heavy dogs 

(>13.8kg) 

Severe GI signs significantly associated 

with high body weight and English 

Bulldog breed


10 (19.6%) of the cases from the first study 

had follow up endoscopic exam following 

surgical therapy and medical therapy 

(omeprazole, cisapride, +/- sucralfate and 

prednisolone) 

7/10 had no Clinical signs 

3/10 were not completely improved 

All had a clear improvement in severity 

inflammatory changes 

Anatomic changes were static 

75% of dogs were off medical therapy long 

term (not segregated in results)

ASPIRATION PNEUMONIA 1 

Generally bacteria require favourable 

conditions to establish pneumonia 

(stomach contents, saliva) 

Severity depends on pH, tonicity, 

particulate size, volume, bacterial 

content 

Location is position and gravity 

dependent – right middle, right cranial, 

caudal portion of left cranial


Horeau 2011 described 15 brachycephalic 

dogs requiring mechanical ventilation. 

None were immediately post operative 

(most recent surgery 15m prior) 

27% were discharged from hospital, all 

were ventilated for impending respiratory 

fatigue (other groups were hypoxaemia 

PaO2 60) 

All dogs surviving to discharge had 

pneumonia at presentation 

Dogs having temporary tracheostomy more 

likely to be weaned


Bacterial pathogens 

Multiple pathogens common (up to 3) 

Population of pathogens changed with increasing 

time on the ventilator 

E coli, Enterococcus, Strep, Staph, others 

Dogs had increased ventilator settings 

(pressure, rate) in the face of bypass of upper 

airway obstruction à pulmonary compliance 

changes 

Historical discharge rate for pulmonary 

disease/hypoventilation 22% 

Lorison et al reported 5/6 Bulldogs who died 

post operatively had aspiration pneumonia


Aspiration pneumonia complicates 

brachycephalic airway syndrome by 

Fluid and exudate in airways causing 

narrowing and increasing resistance 

Reducing lung compliance, thereby further 

increasing effort required to breathe 

Obstruction and inflammation of alveoli 

leads to reduced area available for gas 

exchange

PULMONARY OEDEMA 

Pulmonary oedema can occur relating to 

upper respiratory obstruction 

Thought to be reactive pulmonary 

oedema with direct leakage of fluid from 

capillaries to alveoli – prognosis worse 

than cardiogenic/fluid overload 

pulmonary oedema

QUESTIONS 

What is the mechanism of systemic 

inflammatory changes and sympathetic 

nervous system activation 

Do BAS dogs have pulmonary 

parenchymal pathology influencing gas 

exchange 

What is the best way to measure the 

influence of surgery on the physiology of 

BAS dogs

Pathophysiology of Brachycephalic Airway Syndrome

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