Exhaled particles and small airways

Abstract

Background: Originally, studies on exhaled droplets explored properties of airborne transmission of infectious diseases. More recently, the interest focuses on properties of exhaled droplets as biomarkers, enabled by the development of technical equipment and methods for chemical analysis. Because exhaled droplets contain nonvolatile substances, particles is the physical designation. This review aims to outline the development in the area of exhaled particles, particularly regarding biomarkers and the connection with small airways, i e airways with an internal diameter < 2 mm.

Main body: Generation mechanisms, sites of origin, number concentrations of exhaled particles and the content of nonvolatile substances are studied. Exhaled particles range in diameter from 0.01 and 1000 μm depending on generation mechanism and site of origin. Airway reopening is one scientifically substantiated particle generation mechanism. During deep expirations, small airways close and the reopening process produces minute particles. When exhaled, these particles have a diameter of < 4 μm. A size discriminating sampling of particles < 4 μm and determination of the size distribution, allows exhaled particle mass to be estimated. The median mass is represented by particles in the size range of 0.7 to 1.0 μm. Half an hour of repeated deep expirations result in samples in the order of nanogram to microgram. The source of these samples is the respiratory tract ling fluid of small airways and consists of lipids and proteins, similarly to surfactant. Early clinical studies of e g chronic obstructive pulmonary disease and asthma, reported altered particle formation and particle composition.

Conclusion: The physical properties and content of exhaled particles generated by the airway reopening mechanism offers an exciting noninvasive way to obtain samples from the respiratory tract lining fluid of small airways. The biomarker potential is only at the beginning to be explored.

Keywords: Airway closure; Airway opening; Albumin; DPPC; Exhaled particles; POPC; Proteomics; SP-A; Small airways; Surfactant.

Fig. 1

The Expiratory Droplet Investigation System setup used by Morawska et al. [21]. Test participants exhaled into a particle- free wind tunnel. A fan maintained at approximately 0.1 m/s controls the wind tunnel airflow. The airflow transports exhaled particles downstream to the aerodynamic particle sizer (APS) where the particles are measured. A relative humidity (RH) probe monitors the humidity. Reprinted from the original article by permission

Fig. 2

At low specified flow rates the participants exhaled to (a) residual volume (RV), (b) closing point (CP), i.e., the lung volume at which extensive airway closure begins, or (c) normal tidal exhalation to functional residual capacity (FRC). Participants then inhaled to total lung capacity (TLC) and immediately exhaled into the equipment back to FRC. By permission of the author

Fig. 3

Schematic presentation of the equipment Almstrand et al. [22]. Participants inhale thorough a HEPA filter and exhale into the equipment. The box containing the equipment was maintained at approximately 36 °C. An optical particle sizer and an impactor allowed for counting and sampling of exhaled particles. Exhaled air that was not directly drawn into the impactor and counter was buffered in a reservoir and subsequently drawn into the impactor and counter and replaced by humidified particle-free air. Particles < 4.6 μm were sampled and the size distribution determined. By permission of the author

Fig. 4

Schematic illustration of the airway reopening concept. When airways close, opposing airway walls get in contact creating a plug of respiratory tract lining fluid. As the airway walls distend during inspiration, forming a meniscus that finally breaks and generate particles. By permission of the author

Fig. 5

DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) mass and exhaled sampled particle mass as determined in samples from eleven individuals that performed ten exhalations using the airway reopening maneuver. Note the linear association through the origin between the collected particle mass and collected DPPC mass. The DPPC weight percent concentration (wt%) is shown for each sample in the lower panel. By permission of the author