Consensus Statements Flashcards
With reference to asthma, what is the typical age distribution for mild (IAD) versus severe (RAO)?
RAO 7 yrs plus
IAD any age
Is equine asthma a disease continuum in which horse with IAD should be expected to progress to RAO?
No, although they may be at higher risk.
What are the typical characteristics of racehorses with IAD?
Coughing, increased tracheal mucous and high bacterial counts
List features of the IAD phenotype of asthma that can be used for diagnosis of this condition.
- Poor performance with or without chronic coughing
- Airway mucous grade >2/5 for racehorses >3/5 for sports horses
- BALF neutrophilia, eosinophils and or metachromatic cells
- If PFT available evidence of pulmonary dysfunction seen as lower airway obstruction, hyperresponsiveness, or impaired blood gas exchange
- Exclusion of systemic diseases that could result in these signs.
Are abnormalities on thoracic auscultation expected in horses with IAD?
Usually not but subtle wheezes and increased breath sounds may be heard, particularly with rebreathing examinations.
Which features indicate and increased risk of later development of RAO?
- Occasional cough
- Nasal discharge
List potential contents of the respirable fraction in a stable
- Organic and inorganic particles including
- Fungi
-Moulds - Endotoxins
- Beta-D-Glucan
- Ultrafine particles
- Microorganisms
- Vegetative material
- Inorganic dusts
- Noxious gases
What does the presence of increased eosinophils and mast cells along with Th-2 cytokines such as IL-4 and IL-5 in BALF suggest?
A role for aero allergens
True or false: predominance of metachromatic cells indicates airway hyperreactivity and presence of increased neutrophils has been associated with cough and tracheal mucous?
True
True or false: BALF neutrophilia occurs more commonly in young horses whereas airway eosinophilia has been associated with Coughing?
False. Eosinophilia is more common in young horses (<5yrs) whereas neutrophilia is more often in older horses and associated with coughing.
Which inflammatory mediators are associated with an innate immune response and BALF neutrophilia compared with those suggesting involvement of the adaptive immune system and mast cells?
Increased expression of genes encoding for TNF-a, IL-1B and IFN-y have been linked to luminal neutrophilia and suggest activation of the innate immune response and Th-1 polarisation may be involved in the pathognesis. Likewise mRNA expression of IL-17 and IL-23 have been linked with increased neutrophils while increased IL-4 and IL-5 with the matocytic form supporting implication of the adaptive immune response including Th-2 polarisation.
True or false: there is no conclusive evidence about the relationship between bacterial and viral infections and IAD.
True
What volume of fluid is administered for BAL and what cut off values are proposed for diagnosis of IAD versus RAO?
250-500mL 0.9% NaCl
IAD: neut <5%, eosinophils <1%, metachromatics <2%.
Total nucleated cell count <530 cells/uL
RAO: >25% neutrophils.
True or false: Tracheal mucous score was positively associated with neutrophil percentage but negatively correlated with mast cell percentage
True, by some authors.
True or false: doubling the infusate volume (ie using 500ml instead of the more commonly used 250mL) requires doubling the cut off values?
True. If using 500mL infusate the cut off for IAD neutrophil percent becomes 10% instead of 5%.
True or false: tracheal wash cytology has been correlated well to poor performance.
False. There is a lack of association between TW cytology and poor performance.
Gas exchange is impaired during exercise in horses with IAD, and more sensitive lung function tests such as forced expiration and impulse oscillometry indicate that horses with IAD have detectable airway obstruction. Airway hyperresponsiveness is a prominent feature of IAD, in particular with which cell types?
Increased eosinophils and mast cells.
The development of bronchoconstriction, airway hyperresponsiveness and cough are likely the airways response to what?
Inhaled irritants
How might IAD be differentiated from RAO?
- Severity of exercise intolerance
- Evidence of increased respiratory effort at rest in RAO only
- Severity of airway neutrophilia and mucous.
There is weaker evidence for a role of bacterial bronchitis (Strep zoo, S. pneumoniae) as an aetiological factor in IAD in which horses more commonly?
Typically young horses and those that have recently entered training.
Differentiate IAD from parasitic infections and EIPH from IAD?
The eosinophilic inflammation in BALF from horses with parasitic pneumonitis or eosinophilic pneumonia is usually more severe.
EIPH usually causes macrophagiv bronchiolitis and fibrosis and the haemorrhage is almost exclusively from the caudodorsal lung fields.
True or false: some studies have shown an additive effect on clinical signs, airway neutrophilia and inflammatory cytokines in horses with RAO when combining corticosteroid Tx with measures to improve air quality.
True
List medications for systemic and inhaled treatment of asthma
Systemic:
- Dex 0.05mg/kg SID
- Pred 1.2-2.2mg/kg SID
- Aminophylline 6-12mg/kg BID
- Clenbuterol 0.8-3.2ug/kg BID
- Pentoxifylline 35mg/kg BID
- Omega 3 fatty acids 1.5g DHA SID
Inhaled puffers:
- Beclomethasone 1-8ug/kg BID
- Fluticasone 1-6ug/kg BID
- Albuterol 1-2ug/kg q1-3h
- Ipratropium bromide 0.2-0.4ug/kg q812h
- Dex nebuliser 5mg diluted 1:1 in saline q12-24h
Inhaled nanoparticles of cytosine phosphate-guanosine oligonucleotides have been shown to decreased neutrophil percentage in TW and mucous secretions as well as improve lung function and clinical signs in horses with RAO - what is the mechanism behind this response?
Inducing a Th-2/Th-1 shift.
As bronchoconstriction has not been shown to be clinically significant in horses with IAD at rest and not well studied during exercise, what would be an additional benefit of clenbuterol?
Increasing mucociliary clearance
What feeding and managements changes should be implemented for horses with IAD?
- Feed complete pelleted diet or haulage.
- Soak hay (decreases dust by 60%)
- Switch to wood shaving bedding
- Feed from the ground to reduce respirable dust
List clinical signs of EIPH
Reported clinical signs:
- Blood in the airways and possibly nares
- Poor performance
- Epistaxis
- Abnormalities on U/S or rads
- Coughing
- Increased respiratory rate (no evidence)
- Respiratory distress or behaviour change (no evidence)
Consensus findings: Very low quality evidence of consistent clinical abnormalities in horses with EIPH with the exception of epistaxis after exercise.
Some horses with EIPH have changes detectable on radiography. Many horses have minimal to undetectable changes and some horses without a history of EIPH can have marked abnormalities. Where are the abnormalities typically identified radiographically?
Cauo-dorsal lung fields.
Does EIPH affect blood-gas exchange?
There is very low quality evidence of an adverse effect of EIPH on arterial oxygen tension, and similarly of higher blood lactate concentrations in horses with EIPH.
Is EIPH a cause of sudden death?
EIPH was considered to have contributed to sudden death during or shortly after racing in 50 of 143 horses for which a cause of death was identified - it may be secondary to other causes of sudden death such as heart failure. It is considered low quality evidence that EIPH is causally associated with sudden death, and there was no evidence of increased risk of sudden death in horses with EIPH.
Does EIPH shorten race careers?
There is moderate quality evidence that EIPH grade 1-3 is not associated with a shorter race career but that grade 4 is associated with a shorter race career.
Is EIPH associated with airway inflammation?
There is low quality evidence that EIPH leads to inflammation in either the pulmonary parenchyma or airways. During intense exercise horses are more likely to bleed into areas that are inflamed, however there is very low quality evidence that inflammation causes EIPH.
Does EIPH result in lesions in the lungs and if so what sort of lesions may be seen?
EIPH can result in both microscopic and gross lesions in the dorso-caudal lung fields bilaterally. Lesions may consist of pleural discolouration secondary to haemosiderin accumulation and this may be accompanied by pleural and septal fibrosis and angiogenesis. Extensive remodelling of small pulmonary veins characterised mainly by accumulation of adventitial collagen and smooth muscle hyperplasia with decreased luminal diameter.
Microscopically in recently exercise horses breaks in the capillary endothelium and basement membrane, interstitial and alveolar accumulations of erythrocytes and interstitial oedema consistent with capillary stress failure may be seen.
True or false: EIPH can be considered progressive with respect to increasing load (ie increased race starts) but not age alone.
True, it is progressive and related to load of racing.
Is EIPH considered a heritable trait?
There is no evidence of heritability however it may be associated with pedigree.
What impact does EIPH have on racing performance?
In thoroughbreds, horses with no evidence or only grade 1 EIPH were more likely to win or finish in the first 3 positions. Horses with tracheobronchoscopic evidence of EIPH were associated with higher likelihood of having an inferior finishing position. There is also evidence that distance behind the winner is associated with increasing EIPH grade.
In standardbreds there is very low quality evidence that EIPH is not associated with finishing time in a race.
Is furosemide effective at reducing or preventing EIPH?
There is high quality evidece that furosemide (0.5-1mg/kg) administered IV 4 hours before strenuous exercise decreases the severity and incidence of EIPH.
What effect does furosemide have on pulmonary vascular pressure?
There is moderate evidence that furosemide decreases pulmonary arterial and pulmonary wedge pressures and hence pulmonary capillary and transmural pressure during intense exercise.
Are aminocaproic acid, bronchodilators, corticosteroids, NSAIDs, pentoxifylline or other treatments including nasal strips effective at reducing EIPH?
Evidence is of low quality but does not support an effective role of other products in preventing EIPH.
Is there evidence to support that furosemide enhances racing performance?
Yes there is evidence that it improves racing speed, finishing position and race earnings in both TB and SB racehorses, and may be associated (low quality evidence) with delayed onset fatigue and improved energetic cost of locomotion in horses on a treadmill.
True or false: the consensus statement strongly recommends that EIPH should be considered a disease and not a variably manifested normal result of strenuous exercise activity?
True.
True or false: The panel found that there is moderate quality evidence that moderate-severe EIPH is NOT associated with decreased athletic performance by TB racehorses?
False. They found that moderate-severe EIPH IS associated with decreased athletic capacity in TB racehorses.
True or false: The panel found no evidence of improved racing performance in TB and SB treated with furosemide?
False. They found high quality evidence for improved performance in TB and SB with treatment with furosemide.
True or false: With respect to S. equi equi younger horses exhibit more severe clinical signs with lymph node abscess formation and rupture whereas older horses are often less severely affected and recover more rapidly.
True
What are the first clinical signs typically seen with S. equi equi and at what stage after exposure do they occur?
Pyrexia with lethargy. 3-14 days after exposure. Pyrexia is persistent and may exceed 42C and may persist until lymph node abscesses rupture.
True or false: Squeezing the larynx will often cause marked pain, stridor, or gagging followed by coughing and endoscopically pharyngeal lymphoid hyperplasia and pharyngeal compression from enlarged lymph nodes may be seen in cases of S. equi equi
True
Which lymph nodes are commonly and less commonly involved with S. equi equi.
Submandibular and retropharyngeal commonly involved; parotid and cranial cervical occasionally involved.
What is the usual temporal relationship between infection and rupture of abscesses with S. equi equi?
Typically rupture between 7days and 4 weeks after infection - thick fibrous capsule.
In a horse that displays expulsion of large amounts of purulent discharge during coughing, eating or when the head is lowered what might you suspect?
Guttural pouch empyema. Approximately 50% of horses with guttural pouch empyema exhibit an intermittent unilateral nasal discharge and cough.
What is the pathogenesis of infection with S. equi equi?
The bacterium attaches to cells within the crypts of the lingual and palatine tonsils and to the follicular-associated epithelium of the pharyngeal and tubal tonsils. Ligands responsible for binding may include exposed surface proteins such as SzPSe. A few hours after infection the organism is difficult to detect on mucosal surfaces but is visible within epithelial cells and subepithelial tonsillar follicles. Thus, nasal or nasopharyngeal samples may be culture negative in early stages of infection. Translocation occurs in a few hours to the mandibular and retropharyngeal lymph nodes that drain the pharyngeal and tonsillar region. Complement-derived chemotactic factors attract large numbers of neutrophils although gross abscessation isn’t visible for 3-5 days.
What factors of S. equi equi prevent phagocytosis?
Thought to be a combination of the hyaluronic acid capsule, anti-phagocytic SeM protein, H factor binding Se18.9, Mac protein and other undetermined antiphagocytic factors released by the organism.
What is the time progression to shedding with S. equi equi?
Nasal shedding usually begins 2-3 days after onset of fever and persists for 2-3 weeks in most animals, although up to 6 weeks post nasal discharge ceases is possible, or longer if guttural pouch or sinus colonisation occurs. Some asymptomatic horses will still shed.
Systemic and mucosal immune responses are evidence 2-3 weeks after infection and coincide with mucosal clearance.
What influence does the size of inoculum have on disease occurrence and severity with S. equi equi?
Lower numbers of bacteria are likely to be efficiently removed by the mucociliary clearance mechanisms.
Inocula of less than 10^6 CFU don’t consistently cause disease.
The larger the intranasal inoculum, the sohrter the incubation period and more severe the disease.
What percentage of horses develop convalescent immunity post S. equi equi?
Approximately 75% if not treated with antibiotics. However 20-25% of convalescent horses become susceptible to a second attack of the disease within several months.
True or false: It is appropriate to consider that all (strangles) recovered horses may be potentially infectious for at least 6 weeks after their purulent discharges have dried up.
True.
What is the survival of S. equi equi in the environment?
Fairly rapid death of the bacteria on fencing and in soil of 1-3 days. May remain viable in water for 4-6 weeks.
What are the pro’s and con’s of different testing strategies for S. equi equi and the temporal relevance of these?
- A needle aspirate from an enlarged or abscessed lymph node is the optimal sample for confirmation
- Moistened nasopharyngeal swabs (false negatives possible in early stages and with intermittent GP shedding), nasopharyngeal lavage (false negatives possible in early stages and with intermittent GP shedding), and guttural pouch lavage (best for detection of carriers; false negative may occur if lymph nodes have not yet ruptured into the pouch) may be useful however the bacteria will often not be isolated from these sites during the early stages of disease, so a negative doesn’t rule out disease.
- Washes have increased sensitivity compared to swabs.
What culture medium should be used for S. equi equi isolation?
Columbia CNA agar with 5% sheep or horse blood added.
True or false: Presence of other beta-haemolytic strep such as Strep zoo can complicate interpretation of cultures as zoocins produced bby Strep zoo will kill S. equi equi and so strangles abscesses that rupture quickly can become colonised and dominated by S. zoo
True.
During which periods is culture potentially unsuccessful or of low yield with S. equi equi?
During incubation, early clinical phases and when the bacterial count is low during convalescence - recovery can be as low as 40%.
S. equi equi may not be present on the mucosal until 24-48 hours after the onset of fever - what approach can be used to enable early recognition, isolation and limited transmission of disease?
Daily temperature monitoring
What genes do PCR look for when testing for S. equi equi?
- The antiphagocytic M protein of S. equi (SeM sequence)
- A superantigen-encoding gene seeI (qPCR)
Which antibodies does the S. equi equi ELISA test for and how quickly do they peak and return to normal?
Antigen A (N-terminal fragment of SEQ_2190 or Se75.3)
Antigen C (N-terminal fragment of SeM)
Peak titres are seen about 5 weeks after exposure and typically remain elevated for at least 6 months. This combined antigen A and C ELISA overcomes the problem of cross reactivity with Strep zoo and provides a similar sensitivity but greater specificity compared with the whole SeM antibody titre.
List different antibody responses and how these can be used to interpret risk for secondary complications with S. equi equi.
- Strong antibody response >1:3,200 may be at risk of developing purpura haemorrhagica
- Detection of recent infection evidenced by 4-fol increase in antibody titre in pared sera 10 days apart
- High titre >1:12,800 supports an existing diagnosis of purpura haemorrhagica or bastard strangles
- A vale of >1:3,200 would suggest vaccination is contraindicated due to increased risk of purpura haemorrhagica in these animals.
- Serologic values are not a measure of protection and also cannot be used to determine carrier status.
