Lower airway disease Flashcards
How is pleural fluid formed?
Pleural fluid is the interstitial fluid of the parietal pleura. A pressure gradient driving its formation exists because the parietal pleura is supplied by the systemic circulation and because the pressure of the pleural space is more negative than that of the subpleural interstitium.
Describe the pathophysiological mechanisms leading to increased pleural fluid production.
Fluid production in the pleural space increases if any of the following occurs:
1) elevation of the hydrostatic pressure gradient (CHF, portal hypertension)
2) a decrease in the colloid osmotic pressures (hypoproteinaemia)
3) an increased permeability of the capillary vessels (infection, malignancy, inflammation)
4) decreased removal of fluid because of impaired lymphatic drainage or obstruction (neoplasia) or infiltration of the pleura or parenchyma (neoplasia)
Also, excessive amounts of peritoneal fluid may accumulate in the pleural cavity as the fluid moves through diaphragmatic defects or through diaphragmatic lymphatics.
List important diagnostic tests to consider in horses with pleural effusion.
1) physical and rectal examination
2) CBC & Biochemistry
3) Cardiac evaluation
4) thoracic and abdo u/s
5) abdominocentesis
6) transtracheal aspirate (if infectious agents suspected)
+/- (depending on nature of effusion and geographic location of horse)
7) Coggins test (AGID)
8) titers against Coccidioides immitis, Cryptococcus neoformans, Mycoplasma felis
What are the most common diagnoses associated with the development of pleural effusion?
Bacterial pneumonia or lung abscesses
What are some other diagnoses associated with the development of pleural effusion?
1) thoracic neoplasia eg. lymphoma (most common), fibrosarcoma, gastric or oesophageal SCC, hepatoblastoma, haemangiosarcoma, melanoma, mesothelioma, metastatic mammary or ovarian adenocarcinoma
2) thoracic trauma
3) pericarditis
4) peritonitis
5) viral, mycoplasmal, fungal infections
6) CHF
7) liver disease
8) diaphragmatic herniation
9) hypoproteinaemia
10) EIA
11) pulmonary granulomata
12) damage of the thoracic duct
How could you differentiate between some of the causes of pleural effusion?
Cytologic and microbiological evaluation of pleural fluid
- identify neoplastic cells or fungal elements
- transudate (protein <25g/L; few cells): CHF, liver fibrosis, hypoalbuminaemia, early neoplastic processes
- modified transudate (low NCC; moderate to high protein >25g/L): neoplasia + many other disorders
- exudate (high NCC; protein > 30g/L): infectious and intraabdominal diseases
- can distinguish septic effusions from nonseptic effusions by biochemical analysis of pleural fluid
- septic: pH <7.2, glucose < 40mg/dL, lactate dehydrogenase > 1000IU/L
- chylous: milky white-pale pink, TG > simultaneously measured serum
Describe the features of Acute respiratory distress syndrome (ARDS)
A syndrome of lung injury characterised by:
- alveolar damage
- high-permeability pulmonary oedema
- respiratory failure
According to the 2016 Consensus Statement, define the IAD phenotype based on clinical presentation and dx tests.
Clinical presentation:
- any age but more common in young horses
- clinical signs include poor performance (non-respiratory causes should be ruled out if this is only clinical sign) and chronic (>3 weeks), occasional coughing.
Diagnostic confirmation:
- endoscopy revealing excess tracheol-bronchial mucus (>2/5 for racehorses; >3/5 for sports/pleasure horses). Rule out other causes of poor perfromance
OR
- BAL cytology characterised by mild increases in neutrophils, eosinophils and/or metachromatic cells
- further confirmed for research purposes by documenting pulmonary dysfunction based on evidence of lower airway obstruction, airway hyperresponsiveness or impaired blood gas exchange
Exclusion criteria:
- evidenced of systemic signs of infection (anorexia, lethargy, haematologic abnormalities compatible with infection)
- increased respiratory effort at rest (heaves)
Summarise the pathogenesis of IAD and reported risk factors
- dysregulation of the inflammatory cell homeostasis in the airway lumen leading to clinical signs of variable severity
- variety of aetiological agents might be involved - relative contribution to the development of IAD varies among different populations of horses based on:
- environmental conditions they are exposed to during and after training
- feeding
- housing
- season
- preventive medicine practices
- differences in distribution of infectious agents
- varying genetic influences
- activation of innate immune system and Th-1 polarization often involved in pathogenesis of IAD and most likely drive the luminal neutrophilia
- implication of adaptive immune response, including Th-2 type polarization in some IAD phenotypes
- non-infectious agents central to development of IAD
- high burdens of aerosolised particles and gases eg stabling is a risk factor
- exposure to cold, dry environments may predispose to pathogenesis of BAL neutrophilia in some horses with IAD
- contribution of infectious agents uncertain - difficult to determine if bacterial infections contribute to increased mucus or if bacterial colonization occurs as a consequence of impaired mucus clearance
- role of viral infection in IAD is controversial
What are the different phenotypes of IAD?
- some associated with specific inflammatory cells in BAL:
- metachromatic cells - associated with airway hyperreactivity and subclinical pulmonary obstruction
- neutrophilic IAD - more often associated with cough and presence of tracheal mucus
- BAL eosinophilia more common in younger horses (< 5yo)
- BAL neutrophilia more frequently diagnosed in older horses (> 7yo)
How is IAD diagnosed?
The diagnosis of IAD (mild-moderate equine asthma) is based on:
1) presence of clinical signs of lower airway disease (poor performance, cough)
2) documentation of lower airway inflammation based on excess mucus on endoscopy, BAL cytology or abnormal lung function
3) exclusion of severe equine asthma (RAO/heaves) as well as infectious and other respiratory diseases
Describe the mucus scoring system used to quantify mucus accumulation in the trachea
Grade 0 - no visible mucus
Grade 1 - single to multiple small blobs of mucus
Grade 2 - larger but nonconfluent blobs
Grade 3 - confluent or stream forming mucus
Grade 4 - pool forming mucus
Grade 5 - profuse amounts of mucus
Describe the findings on BAL fluid cytology on horses with IAD
- mild to moderate increase in neutrophil, eosinophil and /or mast cell percentages
- > 10% neutrophils
- > 5% mast cells
- > 5% eosinophils
- importance of BAL cytology should be interpreted in light of history, clinical exam and endoscopic findings
- NB. TW cytology not considered an appropriate alternative to BAL cytology for diagnostic confirmation or characterisation of IAD
What are the main differences between RAO and IAD?
- lack of laboured breathing at rest permits differentiation of IAD from RAO
- severe exercise intolerance in RAO
- combination of pronounced BAL neutrophilia (> 25%) and tracheal mucus accumulation (grades >2/5) in RAO
