The study has four main objectives. These are listed and further explained below:

1. To characterise mechanisms regulating phagocytosis and bacterial clearance in human AMs.

We will perform a series of test on Alveolar Macrophages (AMs), the primary immune cell resident to the human lungs. We will be taking samples of these cells through a procedure called a bronchoscopy then performing tests to show the exact mechanisms by which they can engulf (phagocytose) and clear foreign material such as bacteria from the lungs. 

2. To determine whether and how these mechanisms are disrupted by ageing and by critical illness.

We will be recruiting healthy adults from two separate age ranges, 18-30 and 60 or over. The purpose of this is to determine how their Alveolar Macrophages differ in function, and why. 

3. To define mechanisms by which inhaled GM-CSF alters human AM function.

We intend for every participant in the trial to receive 2 interventions. One will be a placebo, and the other will be inhaled GM-CSF. This will be performed in a blinded fashion so the research team are unaware which intervention has been delivered. On both occasions we will perform a bronchoscopy to obtain a sample of Alveolar Macrophages which will be studied by a number of laboratory assays. After the trial is complete, we will be able to use the data to determine if the GM-CSF did alter AM function and if so, how. 

4. To compare function/phenotype in primary human AMs with iPSC-derived AM-like cells and cell lines.

The final aspect of our study involves comparing AMs to cells that have been cultured outside of the body from stem cells. These cells have been specifically treated to appear and behave like Alveolar Macrophages. Our hope is that, if they are sufficiently similar in their action, it may provide an excellent model on which to trial new interventions in the future without the need for human participants.