Origin of Exhaled Breath Particles from Healthy and Human Rhinovirus-Infected Subjects

Abstract

Background: Exhaled breath studies suggest that humans exhale fine particles during tidal breathing, but little is known of their physical origin in the respiratory system during health or disease. Methods: Particles generated by 3 healthy and 16 human rhinovirus (HRV)-infected subjects were counted using an optical particle counter with nominal diameter-size bins ranging between 0.3 and 10 mm. Data were collected from HRV-infected subjects during tidal breathing. In addition, data from healthy subjects were collected during coughs, swallows, tidal breathing, and breathing to total lung capacity (TLC) and residual volume (RV). Using general additive models, we graphed exhaled particle concentration versus airflow during exhalation. Exhaled particles were collected from expired air on gelatin filters and analyzed for HRV via quantitative PCR. Results: HRV-infected subjects exhaled from 0.1 to 7200 particles per liter of exhaled air during tidal breathing (geometric mean ¼ 32 part/L). A small fraction (24%) of subjects exhaled most (81%) of the particles measured and 82% of particles detected were 0.300-0.499 mm. Minute ventilation, maximum airflow during exhalation, and forced expiratory volume 1 second (FEV 1 % predicted) were positively correlated with particle production. No human rhinovirus was detected in exhaled breath samples. Three healthy subjects exhaled less than 100 particles per liter of exhaled air during tidal breathing and increased particle concentrations more with exhalation to RV than with coughing, swallowing, or rapid exhalation. Conclusions: Submicron particles were detected in the exhaled breath of healthy and HRV-infected subjects. Particle concentrations were correlated with airflow during the first half of exhalation, and peaked at the end of exhalation, indicating both lower and upper airways as particle sources. The effect of breathing maneuver suggested a major contribution from lower airways, probably the result of opening collapsed small airways and alveoli.

Viable influenza A virus in airborne particles expelled during coughs versus exhalations

“…Larger particles are thought to be created by shear forces acting on fluid‐covered upper airways, where air velocities are much higher than in the deeper regions. This phenomenon is thought to occur primarily during coughing because the air flow rates are much higher than during breathing 29, 30, 31. Since, in this theory, deep lung particle generation occurs during both breathing and coughing while upper airway particle generation occurs only during coughing, then the modest increase in the number of positive samples seen during coughing compared to exhalation in our experiments supports the idea that much of the infectious aerosol is originating in the deep lung regions.…”

“…Humans produce more aerosol particles when they cough vs. when they exhale 27, 28. Most of the aerosol particles produced during normal breathing are thought to originate deep in the respiratory tract, while coughing may produce aerosol both from the lower airways and also from the upper airways 29, 30, 31. Thus, if coughing produces much more infectious aerosol than exhaling, this would suggest that much of the virus in cough‐generated particles may be coming from the upper airways.…”

Quantity and Size Distribution of Cough-Generated Aerosol Particles Produced by Influenza Patients During and After Illness

“…These results are consistent with those reported by others; virtually all studies of human aerosol particle generation that have compared subjects have found tremendous person-to-person variation. (8)(9)(10)(11)(12)(13) This phenomenon may lead to a "superspreader" effect; that is, if some people produce much greater quantities of infectious aerosols, they may be much more likely to spread influenza to others. (9,18) The cough aerosol particle volume also varied greatly from patient to patient; the average aerosol volumes ranged from 2.4 to 144 pL/cough when ill and 0.5 to 145 pL/cough after recovery.…”

“…Fabian et al (11) tested 10 patients with influenza and found that the concentration of particles exhaled by these subjects ranged from 67 to 8500 particles/liter of air; similar results were later reported for patients with rhinovirus infections. (13) Almstrand et al (15) also found that the exhaled particle concentrations varied considerably from subject to subject and with the depth of breathing, but that the exhaled concentrations for each subject were fairly consistent during repeated testing for each respiratory maneuver studied.…”

“…Most of these studies used healthy subjects, but a few have looked at aerosol production by individuals with respiratory viral infections, including influenza (10)(11)(12) and rhinovirus. (10,13) All of these studies have consistently found a tremendous variation in the numbers of aerosol particles expelled by individuals. Edwards et al (14) tested 11 healthy subjects and reported that the concentration of particles in their exhaled breath varied from 1 particle/liter to over 10,000 particles/liter.…”