Non-Invasive Monitoring: Pulmonary Pharmacokinetics and Pharmacodynamic Biomarkers Using Exhaled Particles

Exhaled particles are microscopic droplets generated, among other processes, when small airways reopen and are released with exhaled air. They contain components of ELF and can therefore serve as a non-invasive sample source for investigations of the pulmonary compartment.

Depending on the research question and analytical feasibility, exhaled particles can be used to quantify suitable drugs, analyze biochemical components, and conduct exploratory biomarker investigations. Particle number and size distribution can also provide information about processes in the small airways.

Epithelial lining fluid (ELF) is the thin liquid layer on the surface of the airways and alveoli. It is in direct contact with drugs administered by inhalation or orally and is therefore relevant for investigating local drug concentrations and biological processes in the lung.

The best-established application to date is the investigation of local drug concentrations following inhaled administration. The method may also be relevant for comparing local and systemic exposure and for exploratory biomarker and airway-related research questions. Suitability must be assessed individually for each project.

Not as a general rule. Bronchoscopy enables more extensive and spatially targeted sampling but is invasive and therefore more burdensome for patients. For suitable research questions, exhaled particles can provide a non-invasive complement or alternative, particularly when repeated sampling is planned.

Measurements are performed in collected exhaled-particle samples that contain components of ELF. A clinical proof-of-principle study showed that salbutamol could be quantified in these samples after inhaled administration and that a concentration–time profile could be derived. Whether this is possible for another drug depends, among other factors, on dose, particle yield, sample volume, and the analytical limit of detection.

Sampling is non-invasive and can generally be repeated, enabling serial measurements within a clinical study. The number and timing of samples are defined according to the pharmacokinetic research question and study design.

Yes. In a clinical proof-of-principle study involving six healthy participants, salbutamol was administered by inhalation or orally. Following inhaled administration, a pharmacokinetic profile was obtained from exhaled-particle samples in five of the six participants. The study demonstrates general feasibility but does not replace project-specific assessment for other drugs and study designs.