Understanding the interactions between lung function and heart function in Chronic Obstructive Pulmonary Disease

Participants will attend three visits. The first two visits will be in the lung function laboratory at the Woolcock Institute of Medical Research. The third visit will be at the Specialist MRI Suite at Royal Prince Alfred Medical Centre. The three visits will be performed within a 4 week period and separated by at least one day. Visit 1: (2 hours) Participants will complete a questionnaire to quantify the state of their breathing symptoms and the effect of this on their daily activity. Participants will then perform a series of simple breathing tests administered by a trained respiratory physiologist: (1.5 hours in total) o Spirometry: This test is to determine how quickly your lungs can breathe air in and squeeze air out. You will need to suck and blow air as fast as you can and as forcefully as you can. o Body plethysmography: This test is used to calculate how big your lungs are. This test will involve sitting inside a glass box and taking panting breaths following by very big breaths. o Lung diffusing capacity: This test measures how well the air that you breathe is transported into your blood. We will also ask you take a big, quick breath of air containing a very small amount of carbon monoxide and a very small amount of nitrogen oxide. We will ask you to hold your breath for 10 seconds and then gently breathe all the air out of your lungs. o Forced oscillation technique (FOT): This test measures the stiffness of the airways. This machine sends different sound waves through the air, making the air feel ‘wobbly’. This test involves sitting and breathing normally on a mouthpiece. We will also ask you take a big, easy breath in and gently breathe all the air out of your lungs. o Multiple breath nitrogen washout test (MBNW): This test measure how evenly the air is distributed throughout your lungs. You will breathe into a mouthpiece, keeping the size of your breaths within a set range. During the test you will first breathe normal room air and then 100% oxygen for approximately 20 breaths. You will be asked to do this three times. o Bronchodilator test: This is to see how well your lungs respond to an inhaled bronchodilator, which is a medication that relaxes the muscle around the airways and is increase the amount of airway you can breathe out. To determine whether your airways opened up after the bronchodilator, we will ask you to repeat the spirometry and FOT tests in the same way that you performed them earlier. Visit 2: (2 hours) Participants will performing the following lung function tests, as described for visit 1; spirometry, body plethysmography and forced oscillation technique. A respiratory scientist will then place an elastic corset around the participant’s abdomen and chest, and the following lung function tests repeated; spirometry, body plethysmography, lung diffusing capacity, forced oscillation technique, multiple breath nitrogen washout and bronchodilator test. The elastic corset will be placed at the Xiphoid process (base of sternum) and tightness adjusted to reduce lung volume by 200-400mL, confirmed by body plethysmography. The elastic corset will be removed at the completion of the study visit. Several different sizes of the elastic corset will be used throughout the study with the size chosen for each participant based upon individual waist circumference. Each corset has a range of widths that it can accommodate so that the degree of compression can be individualised for each patient. As the main goal of the elastic corset is to reduce lung volume, the degree of compression is likely to differ between patients to induce the desired reduction in volume. Visit 3: (2 hours) Participants will begin by performing spirometry, as described for visit 1. Participants will wear noise-reducing headphones and lie on a table connected to a magnetic resonance image (MRI) scanner. The table will move into the MRI scanner and a cardiac MRI performed. During the test participants will be repeatedly asked to hold their breath for short periods (~10-15 seconds) whilst images of their heart are acquired. The cardiac MRI scan will take approximately 30min. After the first test a respiratory scientist will place the elastic corset around the participant’s abdomen and chest, and ask them to rest for 30min. The cardiac MRI scan will then be repeated with the participant wearing the elastic corset, which will again take approximately 30 min. The elastic corset will be removed at the completion of the study visit.