PLeural Effusion and Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusions

The PLEASE study is a single centre prospective study of 150 patients with symptomatic pleural effusions that require therapeutic drainage. The study aims to identify key factors that underlie breathlessness in pleural effusion patients and develop predictors of improvement in breathlessness following effusion drainage. Participants will undergo evaluation pre- and post-effusion drainage to assess functional impairment at rest and during exercise, respiratory and other physiological responses and respiratory muscle mechanics. Study Measurements include: 1. Baseline assessment (1.5 hours): All participants will be interviewed and examined prior to pleural drainage i) Patient data – Demographics, comorbidities (e.g. COPD, heart disease), underlying cancer (type, stage and treatment, etc.) and relevant clinical data including cardio-pulmonary status (respiratory rate, heart rate, blood pressure and oxygen saturation by pulse oximetry) will be recorded. ii) Pleural effusion characteristics – This will include the etiology of the effusion (if known) and the details of any prior pleural procedures. iii) Measurement of breathlessness - Breathlessness will be assessed using three instruments; a) Visual Analogue Scale b) Dyspnea-12 Questionnaire and c) Modified Borg 0-10 scale. The VAS score is a validated measure of breathlessness in malignant pleural effusion and has been used in clinical trials involving MPE cohorts. The participant places a mark on the 100mm vertical scale to indicate the severity of their breathlessness. A score of 0mm indicates the most severe breathlessness. The Dyspnea-12 Questionnaire has demonstrated validity and reliability in COPD, asthma, interstitial lung disease and pulmonary arterial hypertension. It consists of 12 questions with physical and affective components. Each question is scored 0-3 points, with a total maximum score of 36 points indicating the most severe level of dyspnoea. The modified Borg scale 0-10 scale will be used to assess exertional dyspnoea evoked during the six-minute walk test. iv) Measurement of functional capacity - Functional exercise capacity will be assessed using the 6-minute walk test. The distance walked, (i.e. 6MWD) will be expressed as an absolute distance (m) and as a percentage of the patient’s predicted 6MWD derived from a reference equation developed locally in healthy individuals. v) Measurements of lung physiology: Detailed lung function including spirometry, lung volumes and gas transfer measurements will be performed as per the American Thoracic Society recommendations, provided that there are no contra-indications. vii) Measurements of diaphragmatic morphology and function: Pleural ultrasound will be employed to assess diaphragm i) shape - normal (domed), flattened or inverted; and ii) movement - the zone of apposition (Zapp) of the diaphragm at the costo-phrenic angle will be measured. viii) Radiological assessment of size of effusion: Effusions will be graded based on their radiographic appearance into five categories (where 0 = no effusion, and 5 = >75% of hemithorax). The presence of other radiographic abnormalities (eg. presence of mediastinal shift, trapped lung and fluid loculations) will also be recorded. 2. Pleural Drainage (1 hour): The fluid will be removed at a controlled rate to ensure patient safety as per international clinical guidelines. Data collected at the time of pleural drainage will include: i) Total volume and duration of pleural fluid drainage. ii) Measurements of pleural pressure using a digital manometer [Compass, Mirador Biomedical, Inc, Seattle, USA] - In a subgroup of patients, end-inspiratory and end-expiratory pleural pressure measurements will be recorded at opening pressure, after every 100mL of drainage up to 1000mLs and at closing pressure. iii) Pleural fluid macroscopic appearance and biochemical analysis (e.g. pleural fluid pH and levels of protein, lactate dehydrogenase and glucose). 3. Repeat Testing (1.5 hours): The pre-drainage tests will be repeated between 24 and 36 hours after completion of drainage. 4. Follow up: Participants will be reviewed in the outpatient clinic 2 weeks after completing the testing. Data collected at this time point will only include any adverse events that may occur following the testing period. There will be no further scheduled study follow up visits following this. The pre- and post-drainage parameters will be collected and compared to identify the key factors and mechanisms that correlate with symptom improvement. The pleural drainage procedure will be performed as part of standard clinical care and is not an intervention of the study.