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The technique of sampling exhaled air is attractive because it is noninvasive and so allows repeated sampling with ease and no risk for the patient. Knowledge of the biomarkers' origin is important to correctly understand and interpret the data. Endogenous particles, formed in the airways, are exhaled and reflect chemical composition of the respiratory tract lining fluid. However, the formation mechanisms and formation sites of these particles are unknown. We hypothesize that airway opening following airway closure causes production of airborne particles that are exhaled. The objective of this study was to examine production of exhaled particles following varying degrees of airway closure. Ten healthy volunteers performed three different breathing maneuvers in which the initial lung volume preceding an inspiration to total lung capacity was varied between functional residual capacity (FRC) and residual volume (RV). Exhaled particle number concentrations in the size interval 0.30-2.0 microm were recorded. Number concentrations of exhaled particles showed a 2- to 18-fold increase after exhalations to RV compared with exhalations where no airway closure was shown [8,500 (810-28,000) vs. 1,300 (330-13,000) particles/expired liter, P = 0.012]. The difference was most noticeable for the smaller size range of particles (<1 microm). There were significant correlations between particle concentrations for the different maneuvers. Our results show that airway reopening following airway closure is an important mechanism for formation of endogenous exhaled particles and that these particles originate from the terminal bronchioles.

BackgroundOriginally, 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 bodyGeneration 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (10.1186/s12931-019-0970-9) contains supplementary material, which is available to authorized users.

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