Particle Size Concentration Distribution and Influences on Exhaled Breath Particles in Mechanically Ventilated Patients
et al. (2014) Particle Size Concentration Distribution and Influences on Exhaled Breath Particles in
Mechanically Ventilated Patients. PLoS ONE 9(1): e87088. doi:10.1371/journal.pone.0087088
Particle Size Concentration Distribution and Influences on Exhaled Breath Particles in Mechanically Ventilated Patients
Gwo-Hwa Wan 0
Chieh-Liang Wu 0
Yi-Fang Chen 0
Sheng-Hsiu Huang 0
Yu-Ling Wang 0
Chun-Wan Chen 0
Julian W. Tang, Alberta Provincial Laboratory for Public Health/University of Alberta, Canada
0 1 Department of Respiratory Therapy, College of Medicine, Chang Gung University , Tao-Yuan, Taiwan , 2 Department of Internal Medicine, Taichung Veterans General Hospital , Chiayi Branch, Chiayi, Taiwan , 3 Department of Respiratory Therapy, Chung Shan Medical University Hospital , Taichung, Taiwan , 4 Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University , Taipei, Taiwan , 5 Department of Respiratory Therapy, Taichung Veterans General Hospital , Taichung, Taiwan , 6 Instititute of Occupational Safety and Health, Council of Labor Affairs , New Taipei City , Taiwan
Humans produce exhaled breath particles (EBPs) during various breath activities, such as normal breathing, coughing, talking, and sneezing. Airborne transmission risk exists when EBPs have attached pathogens. Until recently, few investigations had evaluated the size and concentration distributions of EBPs from mechanically ventilated patients with different ventilation mode settings. This study thus broke new ground by not only evaluating the size concentration distributions of EBPs in mechanically ventilated patients, but also investigating the relationship between EBP level and positive expiratory end airway pressure (PEEP), tidal volume, and pneumonia. This investigation recruited mechanically ventilated patients, with and without pneumonia, aged 20 years old and above, from the respiratory intensive care unit of a medical center. Concentration distributions of EBPs from mechanically ventilated patients were analyzed with an optical particle analyzer. This study finds that EBP concentrations from mechanically ventilated patients during normal breathing were in the range 0.47-2,554.04 particles/breath (0.001-4.644 particles/mL). EBP concentrations did not differ significantly between the volume control and pressure control modes of the ventilation settings in the mechanically ventilated patients. The patient EBPs were sized below 5 mm, and 80% of them ranged from 0.3 to 1.0 mm. The EBPs concentrations in patients with high PEEP (. 5 cmH2O) clearly exceeded those in patients with low PEEP (# 5 cmH2O). Additionally, a significant negative association existed between pneumonia duration and EBPs concentration. However, tidal volume was not related to EBPs concentration.
Funding: This study was supported by grants GMRPD1A0051 and GMRPD1B0051 from the Institute of Occupational Safety and Health of Taiwan. The funders
had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
. These authors contributed equally to this work.
Human lungs emit non-volatile aerosols and volatile organic
compounds in exhaled breath. Humans produce exhaled breath
particles (EBPs) according to their respiratory patterns. The
mechanisms of EBPs production include: production of wind shear
forces in the respiratory system under high speed flow conditions,
like coughing, sneezing, singing, laughing, and talking, with EBPs
subsequently exiting via the attached airway mucosa [1,2]; airflow
passes through the oropharyngeal bifurcation during normal
breathing and then becomes turbulent flow that produces aerosols
; bronchiole fluid film burst (BFFB) results from the reopening
of terminal airways following deep exhalation, with airflow then
passing through the film and causing EBPs to break out [3,4].
Several studies evaluated the characterization of concentration
and size distribution of EBPs [5,6]. Exhaled breath particles
concentrations were associated with human activity patterns and
varied among individulas. EBPs concentration was positively
associated with tidal volume, ventilation ratio [tidal volume (VT)/
vital capacity (VC)] , deep exhalation , and long breath
holding at residual volume . However, the ratio of functional
residual capacity to total lung capacity (. 0.45)  and short
breath holding at total lung capacity  were negatively associated
with the EBPs concentrations. Additionally, inspiratory and
expiratory flow did not affect the emission rate of EBPs .
Previous studies indicated that the maximum and minimum
concentrations of EBPs during normal breathing in healthy
individuals were 0.151,383 droplets/mL [5,6,810] and 0.01
2.1 droplets/mL [1,5,6], respectively. Additionally, previous
studies focused on healthy adults found that the highest EBPs
concentrations occurred during sneezing  and coughing [6,11]
while the lowset occurred during nasal breathing  and talking
Exhaled particle size distribution was in the interval 0.32.0 mm
. A previous study showed that the count median diameter of
EBPs was 0.28 mm, and only 2% of EBPs were larger than 0.5 mm
Figure 1. Diagram of exhaled breath particles sampling in mechanically ventilated patients. A: portable DUSTcheck monitor, B:
expiratory breathing circuit, C: water trap, D: heated humidifier, E: Mechanical ventilator system.
Thoracolumbar compression fracture
Respiratory rate, breath/min
Duration of ventilation, day
Data are presented with n or mean(sem). PC: pressure control; VC: volume control; COPD: chronic obstructive pulmonary disease; FiO2: fractional inhaled oxygen
concentration; PEEP: positive expiratory end airway pressure.
. The mean particle sizes of EBPs were less than 1 mm during
normal breathing [1,5,6] and 1125 mm during coughing [5,6,8
10]. Particle size is a key factor for disease transmission .
Patients with airway infection may exhale particles with
pathogens, thus increasing airborne transmission risk. A previous study
showed that 25% of patients with pulmonary tuberculosis exhaled
3633 CFU (colony forming unit) of Mycobacterium tuberculosis when
coughing, and levels of this pathogen primarily ranged 0.6
3.3 mm. The level of exhaled particles with Mycobacterium tuberculosis
during coughing clearly decreased following one week of treatment
with anti-truberculosis drugs .
In clinical practice, patients with acute respiratory failure or
severe diseases (chronic obstructive pulmonary disease,
neuromuscular disease, etc.) must use ventilators for life support [14,15].
Ventilator mode was set based on patient clinical condition,
operator familiarity, and hopital preference. The pressure control
(PC) mode and volume control (VC) mode settings are commonly
used in hospital ventilator systems. Patient inspiratory flow and
volume are changed by in response to patient ventilation demand
under pressure control mode setting, while under the volume
control mode setting patients are provided with fixed inspiratory
flow and volume.
To date, most studies focused on EBPs concentration
distributions in healthy individuals with various respiratory patterns and
performing various activities. Few studies assessed the relationships
among patient characteristics, ventilator mode setting, and size
concentration distributions of EBPs. Therefore, this investigation
focused on the relationships among size concentration distribution
of EBPs, ventilator setting (mode, tidal volume, and PEEP), and
pulmonary disease in mechanically ventilated patients.
Materials and Methods
Mechanically ventilated patients aged over 20 years were
recruited from the respiratory intensive care unit of a medical
center in central Taiwan. These patients used pressure control
mode (n = 24) or volume control mode (n = 24) for ventilation
control. This investigation was approved by the Institutional
Review Board of Taichung Veterans General Hospital. Informed
written consent was obtained from the families of each subject
before their participation.
Measurement of exhaled breath particles
To ensure accurate measurement of EBPs concentrations, this
study used a lung model to assess the background particle
concentrations of the ventilator circuit system using the central
piping air system. The PB840 (Puritan Bennett 840, Tyco
Healthcare, Mansfield, MA) and Servo-i (Maquet, Inc.,
Bridgewater, NJ) ventilators were used for the lung model testing and
identical ventilation parameters were set. For the volume control
mode, the ventilation parameter settings in the lung model
included tidal volume of 500 mL, respiratory rate of 14 breaths/
minute, peak inspiratory flow of 50 liters/minute, and inhaled
oxygen concentration of 40%. The Servo-i ventilator has an
automatic control system and so there was no fixed inspiratory
flow. The tidal volume and ventilation parameter levels were
observed in evaluation of the leakage of the ventilator circuit
systems. A portable DUSTcheck monitor (Model 1.108; Grimm
Labortechnik Ltd., Ainring, Germany) was used to measure the
particle concentrations in the ventilator circuit systems. The
DUSTcheck monitor detects aerosol particles in the size range of
0.320 mm in 15 size channels and represents the results in
number concentration. The sample flow rate of the DUSTcheck
monitor was 1.2 L/min which was only higher than the air flow
rate in the first and the last 0.1 second during an exhalation
maneuver. The particle concentrations were recored every 6
seconds. The air sampling for each test lasted 7 minutes, and the
mean value of 5-minute data was presented. The mean exhaled
paritcle number concentrations were represented as number
concentration (particles/mL) and multiplied by tidal volume to
determine the total paricle amounts per breath (particles/breath)
in each sample. Figure 1 shows the diagram of EBP sampling in
the mechanically ventilated patients. In order to take
representative samples independent of particle size, it is necessary to remove
the sample stream isokinetically. Unfortunately, the velocity of air
during expiratory activities varies widely with breathing pattern
and time. This makes the isokinetic sampling unfeasible in this
Clinical data collection
This study collected patient demographic and medical details
(such as age, gender, height, weight, diagnosis, etc.) and record
ventilation parameters (such as ventilator mode, inhaled oxygen
concentration, tidal volume, inspiratory flow, PEEP, etc.) to assess
the relationships among personal characteristics, ventilator
settings, and EBPs concentrations in mechanically ventilated
Statistical analyses used SPSS version 13.0 (SPSS, Inc.,
Chicago, IL, USA). Figures were graphed using SigmaPlot 12.0
software (Systat software, Inc., San Jose, CA, USA) and GraphPad
Prism 5.0 software (GraphPad Software, Inc., San Diego, CA,
USA). The significance level for all tests was set to 0.05. The
concentrations of EBPs were calculated based on 5-minute
averages. Furthermore, the figures for PEEP level were assigned
to a high level group (.5 cmH2O) and a low level group
(#5 cmH2O) using the median as the cutoff. The figures for tidal
volume were also classified into high (.500 mL) and low
(#500 mL) level groups using the median as the cutoff. The
nonparametric Kruskal-Wallis and Mann-Whitney U tests for
non-normally distributed data were used to identify group
differences in continuous variables.
This study measured compressed air from the central piping air
system and found it to contain 0.001 particles/mL and 0.0023
particles/mL of particles sized above 0.3 mm for the PB840 and
Servo-i ventilator systems, respectively. No particles were found in
the piping air of the inspiratory breathing circuit system when a
high efficiency particulate air (HEPA) filter was fitted to the
ventilator system. Each experiment thus required a HEPA filter
mounted in the inspiratory circuit of ventilator system.
The mechanically ventilated patients (24 with PC mode and 24
with VC mode) were aged between 52 and 91 years old. The
patient heights and weights were 146175 centimeters and 35
90 kilograms, respectively. Disease diagnoses inlcuded asthma,
chronic obstructive pulmonary disease (COPD),
encephalomyelitis, empyema, epilepsy, hepatoma, lung cancer, pneumonia,
pulmonary tuberculosis (TB), rectal cancer, sepsis, septic shock,
thoracolumbar compression fracture, and urosepsis (Table 1). The
fractional inhaled oxygen concentration for mechanically
ventilated patients was 30%50%, and the setting of inhaled tidal
volume depended on personal ideal body weight to achieve the
target of 10 mL/kg. The patient respiratory rate ranged from 12
to 31 beats/minute, and the PEEP levels were 510 cmH2O in the
mechanically ventilated patients. The mean ventilator-days in the
mechanically ventilated patients with the PC and VC modes were
8.33 and 9.58 days, respectively.
This study found high variability of EBP concentrations among
patients. The EBP concentrations for mechanically ventilated
patients with PC mode during normal breathing were 0.47
1,163.87 particles/breath (0.0012.527 particles/mL) (Fig. 2).
Additionally, the EBP concentrations during normal breathing in
the mechanically ventilated patients with the VC mode were 0.55
2554.04 particles/breath (0.0014.644 particles/mL) (Fig. 3). The
particle size concentration distributions from exhaled breath in the
mechanically ventilated patients with the PC mode (Fig. 4A)
resembled those of patients with the VC mode (Fig. 4B).
Regardless of ventilator mode, most EBP from mechanically
ventilated patients were smaller than 5 mm, and the highest and
lowest EBPs concentrations occurred the size ranges 0.31.0 mm
and 2.55.0 mm, respectively (data not shown).
In this study, the median EBP concentration of mechanically
ventilated patients with the PC mode [33.88 particles/breath
(0.062 particles/mL)] was similar to that for the VC mode [32.54
particles/breath (0.059 particles/mL), p = 0.455] (Fig. 5). To
evaluate the relationships among EBPs concentrations, tidal
volume and PEEP level, this investigation indicated that the
median EBPs concentration from the mechanically ventilated
patients with high PEEP level [77.08 particles/breath (0.184
particles/mL)] significantly exceeded that for patients with low
PEEP level [13.92 particles/breath (0.027 particles/mL),
p = 0.003] (Fig. 6A). However, the EBPs concentration was not
associated with tidal volume in the mechanically ventilated
patients (p = 0.923, Fig. 6B). Additionally, the median (2575
percentiles) EBPs concentrations in the patients without
pneumonia [50.20 particles/breath (0.1 particles/mL), 6.72198.73
particles/breath (0.0150.464 particles/mL)] resembled those in
patients with short duration pneumonia (#7 days) [65.57
particles/breath (0.143 particles/mL), 11.40128.02 particles/
breath (0.0200.257 particles/mL), p = 0.628], but EBP
concentrations clearly differed between the patients without pneumonia
and those with long duration (.7 days) pneumonia [10.75
particles/breath (0.024 particles/mL), 3.6718.04 particles/breath
(0.0080.039 particles/mL), p = 0.005]. The mechanically
ventilated patients with short duration pneumonia displayed higher
median EBP concentration than those with long duration
pneumonia (p = 0.001) (Fig. 6C).
Until recently, few investigations evaluated EBPs size
concentration distribution during normal breathing and coughing in
mechanically ventilated patients with different ventilator settings.
The inspiratory breathing circuit of the ventilator system was fitted
with a HEPA filter to avoid the contamination of exhaled breath
samples with external particles during the study period.
In the study, the EBP concentration and variation of the
mechanically ventilated patients with normal breathing resembled
those of the healthy adults (0.01 2.1 particles/mL) in previous
studies [1,5,6]. However, the EBPs concentration of mechanically
ventilated patients might be underestimated, because these
patients used 35 cm of artificial endotracheal tube with dead
volume for EBPs deposition on the walls of endotracheal tubes.
Two mechanically ventilated patients with PC mode had high
EBPs concentrations [1,037.271,163.87 particles/breath (1.415
2.527 particles/mL)]. One patient was diagnosed with rectal
cancer, and his lung showed severe pulmonary edema and Candida
infection. Another patient was diagnosed lung cancer and
pneumonia, and Acinetobacter baumannii was found in the sputum
of this patient. Furthermore, three mechanically ventilated patients
with VC mode had higher EBPs concentrations [1,037.70
2,554.04 particles/breath (2.0754.644 particles/mL)] than other
mechanically ventilated patients. The possible reason for the
production of high EBPs from the mechanically ventilated patients
may relate to the patient diagnosis (pulmonary tuberculosis, lung
cancer, and pneumonia). Increasing the sample sizes is suggested
to evaluate the relationship between pulmonary disease and EBPs
Human actions such as coughing, sneezing, talking, singing, and
breathing produce EBPs. This study reported that mechanically
ventilated patients produced high EBPs concentrations during
coughing. Similar results have previously been found in studies in
England  and the USA . However, the sample size of
patients with coughing during mechanical ventilation is too small,
so that the EBP concentration distribution of mechanically
ventilated patients during coughing will deserve further evaluation.
Furthermore, this investigation showed that the EBPs
concentrations from the mechanically ventilated patients with the PC mode
were similar to those of mechanically ventilated patients with the
VC mode. This phenomenon possibly occurred because the
recruited patieints were stable and so their respiratory parameters
(tidal volume, oxygen demand, and respiratory rate) did not differ
significnatly between ventilation modes. Moreover, the EBP size
distributions in the mechanically ventilated patients with the PC
mode resembled those for mechanically ventilated patients with
the VC mode. All EBPs were sized below 5 mm and 80% of EBPs
were sized between 0.3 mm and 1.0 mm. This result resembled
those of previous studies involving healthy adults [1,5,6,16] and
patients with the common cold  that exhaled particles sized
below 1 mm.
Previous investigations indicated that tidal volume and
respiratory rate clearly increased EBPs concentrations, while inspiratory
flow did not [2,18]. High tidal volume increased the opportunity
for the re-opening of terminal airways, so EBPs concentrations
tended to be high in healthy adults. The current study showed that
tidal volume was not associated with EBPs concentrations in
mechanically ventilated patients. This result differed from that of
previous studies [2,18]. The possible reason for this phenomenon
relates to the setting of tidal volume (10 ml/kg) based on personal
ideal body weight. The mechanism of EBPs production in
mechanically ventilated patients thus warrants further evaluation.
The setting of PEEP was used to open the alveolars of
mechanically ventilated patients to increase gas diffusion,
functional residual capacity and alveolar compliance, and then to
improve oxygenation, and to decrease oxygen demand and work
of breathing. Therefore, it was speculated that EBPs
concentrations were lower when mechanically ventilated patients have high
PEEP levels. However, this investigation showed that EBPs
concnetrations from mechanically ventilated patients with high
PEEP level exceeded those of such patients with low PEEP level.
This result has two possible causes: 1) 60% of mechanically
ventilated patients with high PEEP level had pneumonia; 2) 40%
of mechanically ventilated patients with high PEEP level had
severe pulmonary edema in X-ray images, and these patients were
infected with Candida, Acinetobacter baumannii, and Mycobacterium
tuberculosis. The relationships among pulmonary infiltration, PEEP
level, and EBPs concentrations thus warrants further investigation.
Additionally, this study demonstrated that patients with
pneumonia for over 7 days had much lower EBPs concentrations
than those with pneumonia for less than 7 days. The reason for
this difference may relate to a good clinical cure effect achieved
through a week-long course of antibiotics in patients with
penumonia. This phenomenon also suggests that EBPs
concentration distributions should be evaluated before and after
antibiotics therapy in mechanically ventilated patients with
pneumonia. Furthermore, six mechanically ventilated patients
had pulmonary infiltration and edema but without pneumonia
(the sputum cultures identified Mycobacterium tuberculosis in two of
the six patients) shown in chest X-ray image, and the EBPs
concentrations of these patients [237.67 1,208.13 particles/
breath (0.22.196 particles/mL)] were higher than those of other
patients without pneumonia [2.35887.69 particles/breath
(0.0051.928 particles/mL)]. Since pathogens might exit the
airways together with EBPs, it is necessary to evaluate the
concentration distribution of exhaled breath bacteria (EBB) from
mechanically ventilated patients. Furthermore, the large bacterial
filters in the expiratory breathing circuits of ventilator systems,
particularly those with repeated disinfection using an autoclave
system, warrant further evaluation of their efficiency in the
filtration of EBPs.
In conclusion, most EBPs in the mechanically ventilated
patients were between 0.3 mm and 1.0 mm. The EBPs
concentrations from mechanically ventilated patients were positively
associated with PEEP level and negatively associated with
pneumonia duration. This study found no relationship between
EBPs concentrations and tidal volume.
The authors thank YH Chen for her assistance during this investigation. T
Knoy is appreciated for his editorial assistance.
Conceived and designed the experiments: G-HW C-LW. Performed the
experiments: G-HW Y-LW C-WC. Analyzed the data: Y-FC S-HH.
Wrote the paper: G-HW.
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