Abstract
Background Oxygen-delivering modalities like humidified high-flow nasal cannula (HFNC) and noninvasive positive-pressure ventilation (NIV) are suspected of generating aerosols that may contribute to transmission of disease such as coronavirus disease 2019. We sought to assess if these modalities lead to increased aerosol dispersal compared to the use of non-humidified low-flow nasal cannula oxygen treatment (LFNC).
Methods Aerosol dispersal from 20 healthy volunteers using HFNC, LFNC and NIV oxygen treatment was measured in a controlled chamber. We investigated effects related to coughing and using a surgical face mask in combination with the oxygen delivering modalities. An aerodynamic particle sizer measured aerosol particles (APS3321, 0.3–20 µm) directly in front of the subjects, while a mesh of smaller particle sensors (SPS30, 0.3–10 µm) was distributed in the test chamber.
Results Non-productive coughing led to significant increases in particle dispersal close to the face when using LFNC and HFNC but not when using NIV. HFNC or NIV did not lead to a statistically significant increase in aerosol dispersal compared to LFNC. With non-productive cough in a room without air changes, there was a significant drop in particle levels between 100 cm and 180 cm from the subjects.
Conclusions Our results indicate that using HFNC and NIV does not lead to increased aerosol dispersal compared to low-flow oxygen treatment, except in rare cases. For a subject with non-productive cough, NIV with double-limb circuit and non-vented mask may be a favourable choice to reduce the risk for aerosol spread.
Abstract
High-flow nasal cannula or NIV oxygen treatment does not lead to an increase in aerosol dispersal compared to the use of low-flow nasal cannula oxygen. For a coughing patient, using dual-limb NIV may reduce the risk of aerosol spread. https://bit.ly/3AnoyJu
Introduction
For coronavirus disease 2019 (COVID-19) patients experiencing reduced lung function with insufficient oxygenation, using humidified high-flow nasal cannula oxygenation (HFNC) and noninvasive ventilation (NIV) have been reported to reduce the frequency of intubation and subsequent invasive mechanical ventilation [1]. HFNC has been associated with a reduction in intensive care unit length of stay [2]. As these treatment modalities are suspected to be aerosol-generating procedures [3], some medical centres were initially reluctant to use them and thereby lowered the threshold for intubation. With increasing numbers of COVID-19 patients overwhelming the capacity of intensive care unit beds with invasive ventilation, many patients have been treated in stepdown units with HFNC or NIV. For the health and safety of healthcare workers, it is important to assess to what extent these procedures generate aerosols. Documentation for airborne transmission being a component for the spread of COVID-19 is surfacing [4, 5]. At the same time, there are reports that the potential viral load of aerosolised particles may be low [6].
Several recent approaches have investigated aerosol dispersal and spread during oxygen therapies, and research is still ongoing to answer these questions [7–13]. While the present evidence is non-conclusive on whether HFNC or NIV oxygen treatment has high aerosol dispersal potential, results from recent studies suggest that they do not lead to significantly increased aerosol dispersal compared to low-flow oxygen modalities [14–17].
In our study aerosol levels were measured in a controlled chamber, where 20 healthy volunteers used HFNC, non-humidified low-flow nasal cannula (LFNC) and NIV in biphasic positive airway pressure (BIPAP) mode. We investigated the parameter “coughing” with all oxygen modalities, and for HFNC we also investigated using a “surgical face mask”. An aerodynamic particle sizer was used to measure (optical) aerosol particles (0.3–20 µm) directly in front (30 cm) of the subject, while smaller optical particle sensors (0.3–10 µm) were distributed in the test chamber.
We sought to assess the following questions:
Does the use of HFNC or NIV lead to increased aerosol dispersal compared to the use of LFNC?
How does non-productive coughing contribute to aerosol dispersal in settings with HFNC/NIV/LFNC?
How is the spatial distribution of aerosols in a confined space influenced by HFNC/NIV/LFNC?
Methods
We recruited healthy adult volunteers aged >18 years. The recruitment process and study were approved by the regional committee for medical and health research ethics in Norway (approval reference: REK 153325), and written consent was obtained from the subjects.
Experimental protocol
The protocol comprised three oxygen modalities, LFNC, HFNC and NIV (figure 1b), split into eight events. We included coughing events with all modalities and included a test with a surgical face mask (Medline, EN14683 Type II, Cheshire, England) within the HFNC modality. The subjects were instructed to provoke coughing (voluntary intensity) every 30 s during the coughing tests. To counter potential carryover effects by protocol sequence, the modality order was separated into four differently ordered subsets where the 20 subjects were divided evenly. For LFNC and HFNC we used an Airvo 2 (Fisher & Paykel Healthcare Limited, Auckland, New Zealand) with an Optiflow nasal cannula (Fisher & Paykel Healthcare Limited, Auckland, New Zealand). The following flowrates were used: LFNC=4 L·min−1, HFNC=increments of 10 L·min−1, starting at 10 and ending at 60 L·min−1. For NIV (dual-limb) in BIPAP mode (spontaneous, IPAP 10, EPAP 5, support frequency 4) we used a Hamilton C6 (Hamilton Medical, Bonaduz, Switzerland) with silicone facial masks (Respireo Hospital F, NonVented disposable, Air Liquide Medical Systems, Antony, France).
a) Overview of the test chamber, sensor locations (Sensirion, SPS30: mesh sensors: A-I, three sensors at 30 cm, three at 100 cm, two at 180 cm and one at 285 cm) (TSI, APS 3321: “breathing zone single sensor”: sample point 20 cm from participant face) and other equipment. The test person was seated on a chair, with an approximate breathing zone elevation of 120 cm above the floor. The sensors were positioned 120 cm above the floor. b) Protocol structure with oxygen modalities and event elements and details. Before and between each 10-min event a 15-min period of filtering out the particles of the test chamber was performed. LFNC: low-flow nasal cannula; HFNC: high-flow nasal cannula; NIV: noninvasive positive-pressure ventilation. HF: high flow; IPAP: inspiratory positive airway pressure; EPAP: expiratory positive airway pressure
Test chamber
The test chamber (figure 1a) with no external active air supply or internal air currents had an internal volume of 11.36 m3 (l:w:h: 234.5×234.5×206.5 cm), with an anteroom to reduce aerosol contamination. A City M Air Purifier (CAMFIL, Riverdale, NJ, USA) with an airflow of 7.2 m3·min−1 was used to zero the particle levels before and between each event. Each subject wore a disposable polypropylene non-woven coverall (Worksafe).
Measurement and equipment
Two different classes of aerosol instruments were used to count and measure particle sizes. A TSI model 3321 Aerodynamic Particle Sizer® (TSI Incorporated, Shoreview, MN, USA) was used to sample the air in the breathing-zone 30 cm in front of the subject. Nine small particle sensors (SPS30, Sensirion AG, Staefa ZH, Switzerland) were used (custom-made wireless setup) for simultaneous particle counting at different locations (figure 1a). Both instruments measure the aerosol concentration over a range of particle sizes, from 0.3 µm (optical size) or 0.5 µm (aerodynamic size) to 20 µm for the APS 3321, and from 0.3 µm (optical size) to 10 µm for the SPS30. For readability we use the name “breathing-zone single sensor” for the APS 3321, and “mesh sensors” for the SPS30 sensors.
Prior to performing the experiments, the particle sensors were tested with particle generation from humans and with a NaCl aerosol generator. Temperature and relative humidity in the test chamber were continuously logged during the experiments with an AM2320 sensor (Guangzhou Aosong Electronics Co., Ltd, Guangzhou, China). There was low variation with a mean of 26.0±0.7 STD °C and 47.1±5.6 STD % relative humidity.
Data analysis and statistics
Comparisons were made of the particle concentration between all pairwise combinations of events relevant to the research questions. As the distributions in concentration values were highly skewed and deviated from a normal distribution (confirmed by Shapiro–Wilk test), comparisons of medians were conducted. To quantify differences between events, median differences were calculated, and their 95% confidence intervals were estimated using the bootstrap method. The Wilcoxon signed rank test was used to quantify the statistical significance of the differences. These comparisons were done on both datasets (breathing-zone single sensor and mesh sensors).
To obtain statistical estimates of changes in particle concentration over time, the particle concentration was modelled as a function of time using a linear mixed-effects model with random intercept and slope, using the averaged particle concentrations over each minute as model input. A full covariance matrix based on Cholesky parameterisation was used as covariance structure in the models, selected based on the Akaike information criterion on models fit on the breathing-zone single sensor dataset. The particle concentration dependency on the four distance-categories of the mesh sensors (figure 1a) was modelled statistically for each event using a linear mixed-effects model with random intercept and fixed slope. Estimation of Spearman correlations between emitted particle levels and age, sex and weight were done in Graphpad 9.0.0. All other statistical calculations were done in Matlab R2019b.
Results
Descriptive statistics
20 healthy adult subjects were included in the study: seven were female, mean±sd age was 43±11.3 years and mean±sd weight was 80±18.7 kg. Descriptive statistics for the measurements by the breathing-zone single sensor are presented in table 1. As visualised in figure 2a and b, there was a large spread in the particle concentration among subjects, with a consistent dispersion around 100% for most events. The distributions were positively skewed with tails of extreme values. Most of the particles measured by the breathing-zone single sensor were in the range of 0.3–5 µm (figure 2e). Our measurement-setup fulfilled the criteria for representative aerosol sampling (intake) and high transport efficiency (tubing) for particle sizes ≤5 µm. The particle dispersal from coughing produced spiked measurements, with the largest spikes attributed to only a few individuals (figure 3 and supplementary Figures E1–E3). No correlations were found between aerosol dispersion and age, sex or weight.
Descriptive statistics for particles measured in the breathing-zone of the test subject (30 cm from mouth)
Average particles per litre of air (PPL) concentration over 10 min (red dot) between each of the eight events in each experiment, grouped according to participant (violin plots with two segment y-axes). a) Breathing-zone single sensor (particle size range 0.3–20 μm). b) average over nine mesh sensors (particle size range 0.3–10 μm). Categorical comparisons of average concentration of particles per litres of air, during the eight events of each experiment, with each red dot representing the results from 1 of 20 participants, measured by the breathing-zone single sensor (APS 3321) (c) and the average over all nine mesh sensors (d). The median is indicated with a thin black dashed line. LF: low-flow; C: cough; HF: high-flow; M: mask. e) Particle size distribution measured with the breathing-zone sensor; NIV: noninvasive positive-pressure ventilation.
Mean and median particles per litre of air, from 20 participants, for three particle size groups, measured with the breathing-zone single sensor (APS 3321), during the eight events of the experiment. The median and means show smoothed time series (moving mean with a 3-s window). The smoothing was used to increase readability and instead of a series of spikes, a smoothed square-like step response is shown for the periods with large spikes. LFNC: low-flow nasal cannula; HFNC: high-flow nasal cannula; NIV: noninvasive positive-pressure ventilation.
Inferential statistics
The results from pairwise comparisons of events are shown in table 2 (breathing-zone single sensor dataset). There was a median increase in particle concentration during HFNC compared to LFNC, but the confidence intervals were wide, including changes in both directions. For particles >5 µm, we measured a statistically significant difference between HFNC and LFNC, but the total particle count in this size range was small (median difference 0.5 particles/litre). Comparing events with and without coughing, there was a relatively large increase in particle concentration when coughing during LFNC, and to a lower extent during HFNC. The median particle concentration was lower with HFNC+cough compared to LFNC+cough, but this difference was not statistically significant. Compared to LFNC+cough and HFNC+cough, NIV+cough led to lower levels of particle dispersion, especially in the particle range ≤1.0 µm.
Statistical pairwise comparisons between events
Wearing a surgical face mask reduced the mean particle concentration during HFNC, both with and without coughing, but the differences were not statistically significant. Comparing NIV with LFNC, the particle concentrations were similar. None of the mesh sensors measured a statistically significant difference in particle concentration between HFNC and LFNC. In agreement with the breathing-zone single sensor dataset, the largest differences were attributed to coughing, with the largest effects registered by the sensors near the breathing-zone. For details see supplementary Table E1.
Concentration versus time
Trends over time were close to zero for the events without coughing (table 3, figure 3). Although not statistically significant, the estimated trends were largest for LFNC and HFNC with coughing. With HFNC there were typically some early spikes before a slow reduction over time, resulting in slightly negative estimates. For details see supplementary Figures E1–E3. The results were similar for the three mesh sensors that were close to the subject (figure 1, supplementary Table E2).
Estimates of change in particle concentrations over time
Concentration versus distance
With the mesh sensors there were few distance-dependent differences detected except for events involving coughing (table 4, figure 4). With coughing, the differences between 30 and 100 cm were small, but the particle concentration was significantly reduced at 180 and 285 cm. Notably for HFNC-M, the particle concentration was lowest at the closest distance but significantly increased 100 cm in front of the subject.
Estimates of differences to intercept (30 cm) in mean particle concentration at different distances in the measurement chamber
Mean particle concentration in particles per litre of air (y-axes) within each episode, for all mesh sensors. The particle concentration number includes particle sizes (0.3–10 μm). The placement of the plots within the graph is similar to the sensor position during the experiments, with the distance to each sensor shown in the subfigure headings. The distribution of measurements between participants is presented as violin plots, where the median is indicated with a thin black dashed line, and the quartiles with thinner dashed lines. LF: low-flow; C: cough; HF: high-flow; M: mask; NIV: noninvasive positive-pressure ventilation.
Discussion
We investigated the aerosol dispersal from the respiratory tract of 20 healthy adult volunteers in a test chamber with a close to zero particle baseline level, while using LFNC, HFNC or NIV, combined with the parameters “coughing” and “surgical face mask”. The key findings were that HFNC or NIV did not lead to large increases in aerosol dispersal compared to LFNC, except in rare cases (3/20). When investigating changes in particle concentration at different distances, there were no large differences between LFNC, HFNC and NIV.
There was a tendency for small increases in median particles during HFNC compared to LFNC, for the lower particle ranges (<5 µm). Helgeson et al. [14] reported a similar non-significant increase at 4 cm from the mouth of the subjects when using HFNC or oxymask. For the particle range >5 µm we measured a statistically significant difference at 30 cm, but the overall number of particles measured in this range was low, with a median difference of just 0.5 particles per litre (table 2). The main contribution to this increase came from three subjects that dispersed more particles (of all sizes measured) when using HFNC compared to LFNC (table 2, figure 2c and d), indicating that in rare cases healthcare workers could expect patients connected to HFNC to disperse more particles. Comparing NIV with LFNC, the particle concentrations were similar, indicating that NIV did not lead to increased aerosol dispersal (table 2, figure 2c and d). The mesh sensors dataset showed similar results for pairwise comparisons between events for all sensors (supplementary Table E1). There was a trend with HFNC with spikes during the first minutes (supplementary Figures E1–E3) that could be related to the nasal irritation that some of the subjects (30%) reported during this period. This nasal irritation might explain the slightly higher median with HFNC compared to LFNC.
Our results generally agree with recent studies that indicate that HFNC does not lead to significantly increased aerosol dispersal compared to LFNC in a group of healthy adults [7–9, 11]. The large spread in individual aerosol dispersal among the 20 subjects (figure 2), despite measures to reduce confounders and background noise, indicates that there are strong individual factors influencing aerosol dispersal. To compare the extremes, the individual with the lowest aerosol dispersal produced a mean of 52 particles·L−1 for the eight events of the protocol, while the individual with the highest aerosol dispersal produced a mean of 425 particles·L−1.
We used a controlled chamber and zeroed particles between each event to ensure accurate measurement of aerosol dispersal from the subjects without dampening effects from active air circulation. Most of the recent studies have investigated particle dispersion in a negative-pressure room to reduce the ambient background [11, 16, 18], but this does not completely exclude ambient particles that potentially can contribute to the measurements. Wilson et al. [15] used zeroing of particle levels between measurements like we did.
The airflows used for HFNC and LFNC were similar to what is typically used in the clinic, and to what have been used in recent studies, while our setup with a mesh of sensors in the test chamber was more extensive than other recent studies [11, 14–16, 18]. Gaeckle et al. [11] and Wilson et al. [15] used funnels to accurately capture all dispersed aerosols, but this approach does not allow for the ability to measure how aerosols spread spatially from the subject. Bem et al. [16] measured at the four cardinal directions from the subject during HFNC, capturing particle dispersion in a circle around the subject at 30 cm and 1 m when using HFNC (60 L·min−1), but to achieve the spatial resolution they measured eight separate times with a handheld instrument. We measured simultaneously at 10 different locations to the sides and in front of the subject for a distance up to 2.85 m (figure 1). Our results corroborate the results reported by Bem et al. [16] in that there were no significant differences in particle levels between LFNC and HFNC for the particle range below 5 µm.
While we found few differences in particle levels versus different distances for LFNC, HFNC and NIV without coughing, we did detect a difference in particle levels as a function of distance for episodes involving coughing. LFNC+cough and HFNC+cough led to relatively large increases in particle concentration close to the subjects (table 3, figure 3), indicating how coughing can lead to a build-up of aerosol particles (10-min period) in an enclosed space with no air circulation, where aerosol concentration drop-off occurred between 100 cm and 180 cm (figure 4, table 4). In a hospital setting there will typically be an active room ventilation creating airflows moving in the room. The turbulences formed by these air currents will vary with each location. Consequently, making exact predictions about safe distances are difficult. If the clinical setting involves low air-change rates like in a standard patient room, our results indicate that a clinician treating (LFNC or HFNC) a coughing patient may be exposed to significantly lower particle levels at 180 cm distance compared to a 100-cm distance or closer.
There was a significant reduction in measured particle levels when comparing HFNC+cough or LFNC+cough with NIV+cough, indicating that for a patient with non-productive cough, NIV with double-limb circuit and non-vented mask can be a favourable choice to reduce aerosol dispersal. For patients with productive cough, other modalities may be favourable. Gaeckle et al. [11] reported that NIV might have a dampening effect on aerosol dispersal. Wilson et al. [15] reported a lower increase in particles when using single-limb NIV compared to dual-limb NIV (we used dual-limb).
Wearing a surgical mask (HFNC+mask+cough) had a dampening effect on the large cough-spikes of particles in the medium (>1 µm and ≤5 µm) and large (>5 µm) particle size range (supplementary Figures E1–E3). As a comparison, Wilson et al. [15] reported that using a surgical mask halved the number of particles measured in most instances they tested when using HFNC and NIV on 10 healthy volunteers.
Our primary interest was in the 0.3–5.0 µm particle size range (figure 2e), which are typically the dehydrated remains from slightly larger primary respiratory droplets. While particles in this size range represent only a fraction of the total volume emitted from the respiratory tract and have lower viral load potential than the larger particles, they are emitted in huge numbers compared to the larger particles [19] and can remain airborne for longer periods of time (hours) under all temperature and relative humidity conditions [20]. At the same time, particles in this range are known as the “breathable/inhalable fraction” and will typically reach and be deposited in the bronchioles and the alveoli of the lower airways [21]. The smallest particle size (0.3 µm) in the range we measured (figure 2e) is known as “the most penetrating particle size” due to the difficulty of capturing this particle size with particle filters [22].
Limitations
This was an explorative study, where the effect sizes and individual variations were unknown prior to the study. Owing to the large individual variation, the study sample size (n=20) may have limited the power to detect true differences between groups. For future studies we recommend including a larger number of subjects to better account for individual variation. Patients with respiratory disease might have changes in airway parameters, resulting in different aerosol generation characteristics than from healthy adult subjects [23]. Thus, our results might underestimate aerosol dispersal compared to people affected by respiratory disease. Our results in a controlled chamber might not apply for a clinical setting, where room ventilation frequencies and sizes are different.
Provoked coughing by healthy adults may be a poor representation of actual aerosol dispersal by patients that have airway-related diseases. Also, there was large individual variation in coughing intensity. Although the measurements of the low-cost mesh sensors tended to agree with the more precise breathing-zone single sensor, the results based on these sensors are probably less accurate [24]. While we aimed at creating a similar setting for each subject, there were minor variations in sitting positions and the angles between the breathing-zone of the subjects and the sensors that might have influenced the accuracy of the particle measurements. The poor ability for the SPS30 sensor to separate particle sizes in bins [24] was a limitation for our ability to discern how different particle sizes propagate spatially.
Conclusion
In the study group of 20 healthy individuals, using HFNC and NIV did not lead to increased aerosol dispersal compared to low-flow oxygen treatment, except in rare cases. For a subject with non-productive cough, NIV with double-limb circuit and non-vented mask may be a favourable choice to reduce the risk for aerosol spread.
Supplementary material
Supplementary Material
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Supplementary material 00206-2021.SUPPLEMENT
Supplementary material ONLINE DATA SUPPLEMENT
Acknowledgements
The authors are grateful for the contributions from the participants in the study, the Department of Respiratory Medicine, the Department of Anesthesiology at Oslo University Hospital, the biostatistician Jon Michael Gran, and Gunnar Skogan at the Norwegian Defence Research Establishment.
Footnotes
Author contributions: R. Strand-Amundsen, C. Tronstad, O. Elvebakk, T. Martinsen, M. Dybwad, E. Lingaas and T.I. Tønnessen designed the study, analysed the results, and wrote and edited the article. O. Elvebakk included the healthy volunteers. R. Strand-Amundsen, T.I. Tønnessen, M. Dybwad and E. Lingaas allocated equipment, resources and facilities. C. Tronstad performed the statistical analysis. R. Strand-Amundsen, C. Tronstad, O. Elvebakk and T. Martinsen performed the experiments. All authors read and approved the final manuscript.
Provenance: Submitted article, peer reviewed.
This article has supplementary material available from openres.ersjournals.com
Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on request.
Conflict of interest: R. Strand-Amundsen has nothing to disclose.
Conflict of interest: C. Tronstad has nothing to disclose.
Conflict of interest: O. Elvebakk has nothing to disclose.
Conflict of interest: T. Martinsen has nothing to disclose.
Conflict of interest: M. Dybwad has nothing to disclose.
Conflict of interest: E. Lingaas has nothing to disclose.
Conflict of interest: T.I. Tønnessen has nothing to disclose.
- Received March 22, 2021.
- Accepted September 11, 2021.
- Copyright ©The authors 2021
This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org
References
