Breakthrough in inhaled therapies: Drug concentrations in the human lung measurable for the first time

A research team from the Fraunhofer ITEM has, for the first time, demonstrated that drug concentrations in the human lung can be measured directly via particles in exhaled breath — a breakthrough with major implications for the targeted development and optimization of inhaled therapies. A completely new approach to measuring drug distribution in the lung has been published in the Journal of Aerosol Medicine and Pulmonary Drug Delivery (DOI: 10.1089/jamp.2024.0032).

In this clinical study, healthy volunteers received either an inhaled or oral dose of the bronchodilator salbutamol. Researchers then collected so-called exhaled breath particles (PEx) – tiny droplets released during exhalation when previously collapsed small airways reopen. The analysis showed that following inhalation, these particles provided clear pharmacokinetic profiles with significantly higher drug concentrations compared to samples taken from the nose or blood.

The study provides compelling proof of concept that PEx samples can be used to non-invasively measure drug levels directly within the epithelial lining fluid of the lungs – in a targeted and patient-friendly manner.

The publication builds on decades of scientific groundwork. As early as 2005, Prof. Dr. Jens Hohlfeld and Dr. Olaf Holz had highlighted the limitations of conventional exhaled breath condensate (EBC) analysis as part of a European Respiratory Society task force. Their core message at the time: to gain reliable insights into lung processes, particles in exhaled air must be specifically collected and thoroughly characterized, both physically and analytically. Two major research tracks evolved from this insight: one was a DFG-funded project focused on the physical characterization of exhaled aerosols, including experiments in microgravity. The other was the technical development of a device for collecting PEx particles – an effort spearheaded by Swedish researcher Prof. Anna-Carin Olin at the University of Gothenburg. This device, now commercially available under the name PExA, has now been used successfully for the first time in a pharmacokinetic study.

This study marks a milestone in the development of non-invasive methods to determine drug distribution in the lungs – a critical step toward improving the precision and effectiveness of inhaled treatments.

For this groundbreaking study, Prof. Dr. Jens Hohlfeld, Head of Airway Research at Fraunhofer ITEM, together with Dr. Olaf Holz, received the prestigious Willi Stahlhofen Award from the International Society for Aerosols in Medicine (ISAM).