Alveolar Macrophage Immunometabolism study

Alveolar macrophages (AMs) are phagocytes that reside on the surface of the
lower respiratory tract, where they represent an initial line of leukocytic
antimicrobial defense. AMs showcase an extreme plasticity in immunological
functions, which is warranted by their localisation. AMs have the capability to
transition from anti-inflammatory housekeeping cells into central nodes of
immune activity during lung injury and infection. These functions are
relatively well described, however the immunometabolism behind this plasticity
remains enigmatic. Which metabolic changes facilitate this adaptive potential
is unknown. Can we define specific immunometabolic pathways that drive these
unique characteristics, also comparing this to blood-derived macrophages? We
will also investigate the direct microenvironment in which the AMs reside. We
aim to measure the composition of the lung microbiome, present in the
microenvironment, from remaining BAL fluid. Finally we will utilize lung
biopsies, Polarization Sensitive (PS-) Optical Cohorence Tomography (OCT) and
Confocal Laser Endomicroscopy to in vivo visualize the healthy alveolar
compartment and airway wall layers, being the direct boundaries of the
microenvironment.

We aim to analyze AMs of healthy volunteers using an integrative approach.
Combining functional and phenotypical analyses with -omics based techniques can
discover relationships across several cellular modalities, hereby providing an
integrative representation of the cell state. This study also aims to
investigate the composition and diversity of the lung microbiome in a healthy
state. Futhermore, the goal is to visualize the healthy alveolar compartment
and airway wall layers using (PS-) OCT and CLE and to compare the performance
of the current PS-OCT system with an upgraded version.

Observational study in healthy volunteers via bronchoscopy.

Participants might experience discomfort from the bronchoscopy and
venapuncture. We deem the possible gain of knowledge to outweigh the burden and
risks of this study. In depth understanding of the core mechanisms of AMs in a
healthy state is key to understand the pathophysiology of lung disease.
Participants will be thoroughly informed and financially compensated for their
time, effort and possible discomfort. The intervention is a standardized
procedure which is described in detail in this protocol. Extensive bronchoscopy
experience, including BAL and OCT/CLE is available within the Amsterdam UMC.
Bronchoscopy for the collection of bronchoalveolar lavage fluid, biopsies and
OCT/CLE images is in general a safe routine and research procedure. Both
adverse and serious adverse events resulting from this procedure are uncommon.
The participants will be given written instructions in the form of an
information leaflet on what to do in case of dyspnoea or fever. This same
leaflet is normally given to patients undergoing routine bronchoscopy in the
Amsterdam UMC.