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Jinho Lee1, Danbi Yoo1, Seunghun Ryu1, Seunghon Ham2, Kiyoung Lee1,3, Myoungsouk Yeo4, Kyoungbok Min5, Chungsik Yoon 1,3
1 Department of Environmental Health Sciences, Seoul National University Graduate School of Public Health, Seoul 08826, Korea Received:
January 26, 2018
Download Citation: ||https://doi.org/10.4209/aaqr.2018.01.0031
Lee, J., Yoo, D., Ryu, S., Ham, S., Lee, K., Yeo, M., Min, K. and Yoon, C. (2019). Quantity, Size Distribution, and Characteristics of Cough-generated Aerosol Produced by Patients with an Upper Respiratory Tract Infection. Aerosol Air Qual. Res. 19: 840-853. https://doi.org/10.4209/aaqr.2018.01.0031
It is generally recognized that most nosocomial infections are spread by exposure to expelled particles at close range (usually within 1 m) or through contact. Although the Korea Centers for Disease Control established a 2-m cut-off for transmittance from patients during the Middle East Respiratory Syndrome (MERS) outbreak in Korea in 2015, questions have been raised regarding possible infection due to aerosols transported beyond this distance. The aim of this study was to characterize cough-generated aerosol emissions from cold patients and to determine the transmission distance of cough particles in indoor air. The study was conducted using subjects with acute upper respiratory infections. The number and size distribution of the particles generated from each cough were measured after participants coughed into a stainless steel chamber in a clean room. The total particle concentration was measured for each subject in the near field (< 1 m) and far field (> 2 m). The number of particles emitted by the cough of an infected patient was 560 ± 5513% greater than that generated by patients after recovery (P < 0.001). The number of particles was also significantly higher (P < 0.001) than the background concentration when infected patients were coughing, even in the far field. These results suggest that the 2-m cut-off should be reconsidered to effectively prevent airborne infections.
Infectious diseases have many pathways of transmission. Infectious disease transmission through respiratory secretions can be divided into droplet transmission and airborne transmission. The World Health Organization (2014) defined droplet transmission as the transmission of diseases by particles expelled at close range, usually within 1 m from the site of generation, and occasionally through contact. They also recommended a 5-µm aerosol diameter cut-off to classify droplet (> 5 µm) or airborne (< 5 µm) transmission. This size-based relationship between droplet and airborne transmission is underpinned by Wells (1934) and Hamburger and Robertson (1948). It is generally recognized that most nosocomial infections are spread by contact (Beggs, 2003). However, several studies of the airborne transmission of infectious pathogens in indoor environments, using this framework of single cut-off delineation, have failed to acknowledge the size of particles. In addition many studies have not considered that pathogens are not exclusively dispersed by airborne or droplet transmission, but can use both pathways simultaneously (Gralton et al., 2011). Although many nosocomial infections are associated with direct person-to-person contact in indoor environments, there is a strong association between the transmission of many pathogens, such as measles, smallpox, tuberculosis, and severe acute respiratory syndrome (SARS), and indoor air movement (Li et al., 2007). Hence, determining aerosol diameter and indoor airflow is important to understand pathogen-containing aerosol movement. Nevertheless, some studies have suggested that infections are airborne-transmitted among humans in healthcare settings, because epidemic diseases, such as influenza, are believed to have a relationship with respiratory airborne transmission (Roy and Milton, 2004). Human coughing seems to promote the spread of cough-generated aerosols by producing more airborne aerosols than vocalizing or breathing (Morawska et al., 2009). According to Blachere et al. (2009), viral RNA of seasonal influenza was detected in the emergency room of a hospital and aerosol transmission was implicated (Wong et al., 2010). Inadequate categorization of close contact by the Korea Centers for Disease Control and Prevention (KCDC) was suggested as the key factor in the spread of Middle East respiratory syndrome (MERS) in South Korea in 2015. “Guidelines for the Management of Middle East Respiratory Syndrome (MERS),” published by the KCDC in December 2014, refers to the contact person as “a person who has had physical contact with (or been within 2 m of) a confirmed or suspected patient,” and does not consider the possibility of airborne transmission of aerosols. Consequently, the response guidelines of the Korea Ministry of Health and Welfare and the KCDC for MERS outbreaks pertaining to close contact are considered inadequate due to insufficient data (Choi et al., 2015). Due to the wide-ranging and potentially long-term transmission of cough-generated airborne particles, it is important to understand the dynamics of cough particles of different sizes. Coughing can release higher concentrations of particles than breathing or talking, because it discharges a large quantity of airborne particles at a high discharge velocity. It has been demonstrated experimentally that the influenza A virus remains infectious in small particle aerosols and can transit across rooms (Noti et al., 2012). The influenza virus and viral RNA can be detected in droplets > 5 µm and nuclei < 5 µm (Lindsley et al., 2010; Milton et al., 2013). It is very likely that a cough jet from a respiratory disease patient contains pathogens and spreads airborne diseases that can be inhaled into the respiratory tracts of other individuals. Furthermore, cough particles have a wide range of sizes and different transport characteristics. Lindsley et al. (2012) reported that cough particles have a size range of 0.35–10 µm and Yang et al. (2007) reported a mean size distribution of cough droplets of 0.62–15.9 µm, with nuclei sizes of 0.58–5.42 µm. A review conducted by Gralton et al. (2011) summarized the size of coughed particles from a large number of studies and concluded that the size of cough-generated particles ranged 0.1–100 µm. However, no study has been performed on the transmission of cough-generated airborne nanosized particles (< 0.1 µm) at a distance greater than the direct contact distance. This study focused on the emission and persistence of airborne particles before sedimentation and their potential for long-range transmission. Hence, the objectives were to characterize cough-generated aerosol emissions and to determine their characteristics in indoor air under the relative humidity and temperature conditions of a healthcare facility. MATERIALS AND METHODSThis study consisted of two experiments; one was conducted in a cylindrical exposure chamber and the other was conducted in a clean room. The exposure chamber was used to estimate the quantity and size distribution of cough-generated aerosols. We observed cough-generated aerosol diffusion in the near field (< 1 m) and far field (> 2 m) in a clean room, as well as variations in number and surface area concentrations with size and distance. The two experiments were repeated after the subjects recovered, to assess any differences between pre- and post-recovery. RecruitmentPatients with cold symptoms were recruited from August to November 2016 using posters in communities and social networks. Subjects were diagnosed with acute upper respiratory infections (hereafter, “colds”) at medical institutions, which was confirmed through production of a medical certificate. Subjects were excluded if their symptoms had receded between the time they obtained certification and the first experiment. For inclusion in the study, all subjects were required to be 18–39 years of age, male or a non-pregnant female, to have no other health problems, to be a lifetime non-smoker, and to have received no vaccination against influenza within the last six months (thus eliminating any bias from including influenza patients). Subjects were asked a few questions about their illness and current symptoms. Twelve subjects were recruited to the study. Of these, ten (five males and five females; mean age: 22–33 years) were confirmed as having a cold on their first visit to the experimental room. They returned for the second test session after their symptoms had resolved. All recruitment and study processes were approved prior to the start of the study by the Seoul National University Institutional Review Board (IRB No. 1608/001-015). Instrumentation and Monitoring ProcedureA scanning mobility particle sizer (SMPS; NanoScan Model 3910; TSI Inc., Shoreview, MN, USA) and an optical particle spectrometer (OPS; Model 3330; TSI Inc.) were used to measure the particle concentration and size distribution in real time (1-min measurement intervals). The detectable size ranges of the instruments were 10–420 nm for the SMPS and 300–10,000 nm for the OPS. An ultrasonic spirometer (EasyOne; Medical Technologies, Andover, MA, USA) was used to measure the mean coughed aerosol volume and peak air flow during coughing, and a 40-L stainless steel cylinder chamber was used to collect coughed aerosols. The collection chamber was fitted with an inlet port for the spirometer and an outlet linked to the SMPS and OPS. The subjects participated in two experiments. As shown in Fig. 1(a), the 40-L stainless steel chamber was used to evaluate aerosol emissions. To evaluate the emissions of cough-generated aerosols, the participant was seated in front of the steel chamber and asked to breathe high efficiency particulate air (HEPA)-filtered air normally for 5 min to remove background aerosols from their respiratory tract. At the same time, an air pump was used to remove background particles from the chamber. After breathing for 5 min, the air pump was turned off, and the subject was asked to inhale as deeply as possible and then cough with maximum force through the spirometer mouthpiece, which was connected to the chamber. After coughing, the participant breathed normally and exhaled the aerosol that remained in their respiratory tract, but the aerosol emitted during this stage was not included in the concentration per cough shown in Table 2. After analysis, the chamber was evacuated for 10 min using the air pump, and the subject was asked to repeat the coughing procedure two more times for a total of three coughs. After each participant finished the procedure, the spirometer mouthpieces and equipment, including the chamber, were cleaned with disinfectant and UV light. The second experiment to evaluate the characteristics of the cough-generated aerosol in an indoor environment was conducted in a clean room, which controlled background particulates to < 10 particles cm–3 using a HEPA filter-equipped ventilation system. The volume of the clean room was 40.32 m3 (7.0 m [W] × 2.4 m [L] × 2.4 m [H]). The participant was asked to put on dustproof clothing and to take an air shower to exclude the possibility of any particulate matter from other sources, such as dust dispersion. The temperature and relative humidity were constantly monitored using a real-time thermo-hygrometer (Model TR-72U; T&D Inc., Redmond, WA, USA) to ensure that the room conditions were maintained. Fig. 1(b) shows the sampling system. Direct reading instruments for measuring the particle concentration and size distribution were placed in each sampling location. Based on the reported respiratory disease air transmission from previous studies, the clean room area was divided into a near field (< 1 m) and far field (> 2 m). SMPS-1 was located 0.5 m from the participant to evaluate the aerosol emissions in the direct contact transmission range. SMPS-2 and the OPS were located 3 m from the participant to measure particle dispersion and airborne exposure. The OPS was placed in the far field to observe the transmission of larger particles and their overall size distribution and concentration. Due to a lack of monitoring devices, we did not use the OPS in the near field. Relative humidity and temperature were maintained at 30–50% and 21–25°C, respectively, to represent the indoor air conditions in a hospital or emergency room (Ninomura and Hermans, 2008; Geshwiler, 2003). When the subjects had a cold, the mean temperature in the clean room was 24.0°C (standard deviation [SD] = 0.59) and mean relative humidity was 38.3% (SD = 3.42). After the subjects had recovered, the mean temperature in the clean room was 23.8°C (SD = 0.36) and the mean relative humidity was 37.2% (SD = 1.28). Each experiment was divided into three phases. Before the cough, the HEPA-filtered air circulation system was operated for at least 60 min to remove contaminants from the clean room. After the particulate concentration level was stabilized, the ventilation system was stopped and 30 min of sampling was conducted to obtain a background aerosol concentration. Cao et al. (2015) reported that the existence of a downward air flow from a ventilation system attached to the ceiling can greatly affect aerosol transmission. For this reason, the ventilation system was shut down prior to the experiment, and we assumed that there was no air movement apart from the air flows due to coughing and the sampling instrument intake. The air changes per hour (ACH) of the system during the sampling process were 0.0037 and there were 0.0056 air exchanges per sampling interval. We therefore considered the air flow low enough to be ignored, and assumed that the inlet flow of the monitoring devices did not affect the transport efficiency in the clean room. The coughing phase comprised both coughing and rest periods. The participant was asked to cough continuously for 1 min and then rest for 5 min to exhale the aerosol remaining in the respiratory tract. This cough cycle was repeated five times for 30 min of cough-generated aerosol emissions. After the cough, real-time monitoring was conducted for 30 min to monitor the residence and diffusion of cough-generated aerosols. Calculations and Data AnalysisThe concentration and size distribution data measured by the SMPS and OPS were used to estimate particle number concentrations and the size distribution. The SMPS provided aerosol particle counts in 13 size bins and the OPS provided 5 bins. The particle concentrations of 18 optical bins in the 10 nm–10 µm diameter range were monitored. Data from the SMPS and OPS channels were merged using the Multi Instrument Manager software (MIM-2 ver. 2.0; TSI Inc.) provided by the manufacturer. For effective observation of the characteristics of nanosized aerosol, data were converted from a number concentration into a surface concentration, assuming that the particles were ideal spheres. All data acquired from real-time monitoring were analyzed statistically. Descriptive statistics were recorded to compare the aerosol concentrations during and after coughing. The number and surface area of aerosol particles per cough were presented as arithmetic means (AM) ± SD because the results were acquired from experiments that were repeated three times. The particle concentrations in the clean room experiment are shown as AMs ± SD because data for each phase and location were normally distributed and the size distribution was proven to be unimodal. Because the individual data of subjects were not normally distributed when we tested them with a Shapiro-Wilks Test, the results of each subject’s coughing while ill were compared to coughs done after recovery using the Mann–Whitney U test. However, because the normalized aerosol concentration data in the clean room were normally distributed, the amount of data per experimental phases was the same. A one-way analysis of variance was conducted to compare the particle concentration according to elapsed time (before, during, and after the cough) and Tukey’s HSD test was applied because it is the most reasonable way to control type 1 error and has a lot of statistical power. Tukey’s test was applied to determine the differences in particle concentration by elapsed time. A result was considered significant at P ≤ 0.05. All analyses were conducted using SAS software (v. 9.4; SAS Institute, Cary, NC, USA). SigmaPlot software (ver. 10; Systat Software, San Jose, CA, USA) was used to visualize the results. The particulate concentrations in the chamber were assumed to be the same everywhere and it was also assumed that the aerosol dispersed equally when the concentration was highest 5 min after the cough. Eq. (1) was used to estimate the aerosol emissions for each subject:
where Cparticle,max is the particle concentration inside the chamber 5 min after the cough, Vchamber is chamber volume (m3), and C̅particle,bg is the mean background concentration inside the chamber 5 min before the test. There are several assumptions in Eq. (1) that may lead to inaccuracies when estimating aerosol emissions. Size-resolved particle dynamics, coagulation, and constant particle loss rates were ignored. Because we did not use ventilation systems while sampling, the ventilation rate of each experiment was determined only by the inlet flow of the sampling devices. In the chamber experiment, the total inlet flow of the sampling devices was 1.75 L min–1. The ACH of the system was 2.5 and there were 0.20 air exchanges per sampling period. Because of dilution and deposition, we considered the use of average aerosol number concentration during sampling inappropriate, and therefore Cparticle,max was used as the representative value of a well-mixed state. |