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Airborne spread of infectious agents in the indoor environment

      Highlights

      • Different stages of the spread of infectious agents were analyzed.
      • Short-range airborne route is potentially very important.
      • Short-range airborne route may be controlled by masks and personalized ventilation.
      • Displacement ventilation may not be applicable to control respiratory diseases.

      Background

      Since the 2003 severe acute respiratory syndrome epidemic, scientific exploration of infection control is no longer restricted to microbiologists or medical scientists. Many studies have reported on the release, transport, and exposure of expiratory droplets because of respiratory activities. This review focuses on the airborne spread of infectious agents from mucus to mucus in the indoor environment and their spread as governed by airflows in the respiratory system, around people, and in buildings at different transport stages.

      Methods

      We critically review the literature on the release of respiratory droplets, their transport and dispersion in the indoor environment, and the ultimate exposure of a susceptible host, as influenced by airflows.

      Results

      These droplets or droplet nuclei are transported by expired airflows, which are sometimes affected by the human body plume and use of a face mask, as well as room airflow. Room airflow is affected by human activities such as walking and door opening, and some droplets are eventually captured by a susceptible individual because of his or her inspired flows; such exposure can eventually lead to long-range spread of airborne pathogens. Direct exposure to the expired fine droplets or droplet nuclei results in short-range airborne transmission. Deposition of droplets and direct personal exposure to expired large droplets can lead to the fomite route and the droplet-borne route, respectively.

      Conclusions

      We have shown the opportunities for infection control at different stages of the spread. We propose that the short-range airborne route may be important in close contact, and its control may be achieved by face masks for the source patients and use of personalized ventilation. Our discussion of the effect of thermal stratification and expiratory delivery of droplets leads to the suggestion that displacement ventilation may not be applicable to hospital rooms where respiratory infection is a concern.

      Key Words

      Since the 2003 severe acute respiratory syndrome epidemic, the 2009 H1N1 influenza pandemic, and the 2014 Middle East respiratory syndrome epidemic, scientific exploration of infection control is no longer restricted to microbiologists or medical scientists. Fluid mechanics has played a role in understanding the mechanism of transmission and in developing engineering interventions; for example, the studies of airflow dynamics by Yu et al
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      Evidence of airborne transmission of the severe acute respiratory syndrome virus.
      provided plausible evidence of airborne transmission of severe acute respiratory syndrome. Airborne spread of infectious agents is directly relevant to the airborne route, and indirectly to the droplet-borne and fomite routes. Breathing, talking, sneezing, and coughing are major sources of some respiratory pathogens. Up to 40,000 droplets are expelled at a velocity of 100 m/s during a sneeze,
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      Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies.
      and a cough can generate approximately 3,000 droplet nuclei.
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      Mycobacterium tuberculosis.
      We now understand to some degree where and how respiratory droplets are formed and the pathogen content in each size of droplet. Turbulence and coherent structures in the airflow, mostly invisible, transport respiratory droplets between people. For example, vortex structures in coughing probably carry particles over long distances.
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      Vortices, complex flows and inertial particles.
      Our body's thermal plumes can bring fine droplet nuclei upward, and vortices generated during door opening and wakes behind walking individuals can transport contaminated air out of an isolation room. Turbulence generated by supply air jets causes mixing and dilution of room air. Understanding these airflows is crucial to minimizing spread of infectious agents and infection transmission.
      Here, we review the release of respiratory droplets, their transport and dispersion in the indoor environment, and the ultimate exposure of a susceptible host, as influenced by airflows. Microbial survival in the environment is beyond the scope of this article.

      Release, transport, and exposure

      Release of droplets from mucus to mouth

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      Fig 1Schematic diagram revealing the origin and generation mechanism of respiratory droplets. (A) Instability of the airway lining fluid
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      defined a critical capillary number (Ca = µU/σ, where µ is the dynamic viscosity of the liquid, U is the axial speed of the air-liquid meniscus propagation, and σ is the surface tension between the lining fluid and the air) above which droplets may be formed during normal breathing. In addition, experiments simulating the film droplet formation process showed that small fluid films generate droplets as efficiently as large films, and droplets may well be generated from films with diameters <1 mm (ie, the diameter of terminal bronchioles).
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      Third, the reported number and size of released droplets vary significantly. In terms of the total mass of saliva, 1.1-6.7 mg of saliva were collected on a mask during a single cough, and 18.7 mg were collected while counting from 1-100.
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      Study on transport characteristics of saliva droplets produced by coughing in a calm indoor environment.
      There were 1-320 droplets per liter of exhaled air found for breathing, 24-23,600 found for coughing, and 4-600 found for speaking.
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      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
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      optical particle counting,
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      aerodynamic particle counting and scanning mobility particle sizing,
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      interferometric Mie imaging,
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      Characterization of expiration air jets and droplet size distributions immediately at the mouth opening.
      and laser aerosol particle spectrometry.
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      Quantity and size distribution of cough-generated aerosol particles produced by influenza patients during and after illness.
      found that individuals infected with influenza virus produce a significantly greater volume of aerosol during clinical illness compared with during the asymptomatic stage (P = .0143). This enhancement in aerosol generation during illness may play an important role in influenza virus transmission.
      Finally, we are interested in the quantity of pathogens in each size category of aerosols. The size of viruses varies from 0.02-0.3 µm, and the size of bacteria varies from 0.5-10 µm in their naked form. It is anticipated that small viral pathogens travel readily within the lungs and between individuals and their environment in small droplet nuclei. The influenza virus RNA detected by quantitative polymerase chain reaction in human exhaled breath suggests that it may be contained in fine particles generated during tidal breathing.
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      Spread of droplets from the mouth and nose to the indoor environment

      When the expiratory flow is weak during the full respiratory cycle, the body plume also plays a role. Weak expiratory flows (eg, those blocked by the use of a face mask) may be captured by the body plume (Fig 2). Expiratory flows are also where most droplet nuclei are formed under typical room conditions. Exhaled flow rate over time may be represented as a sinusoidal function for breathing, a constant for talking, and a combination of gamma probability distribution functions for coughing.
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      The peak velocities of coughing and breathing can be 6-22 m/s (>10 m/s on average) and 1-5 m/s, respectively.
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      Fig 2
      Fig 2Escaped microbial aerosols of an infected individual with a mask (A) and without a mask (B) as affected by the body plume and inhalation of the airborne infectious agent(s) of a nearby individual without a mask (C) and with a mask (D).
      Among all respiratory activities, coughing has probably been studied the most. The Schlieren technique using human volunteers reveals the turbulent cough jet with a leading vortex,
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      Spread of droplets in the indoor environment

      The transport of expiratory droplets can be considered in terms of 2 stages, with the primary being the expiratory flow, followed by secondary dispersion via room airflow. The airflow in buildings is typically designed to be <0.25 m/s on average for thermal comfort. Typical airflows are turbulent, and they are affected by many parameters, such as air distribution systems,
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      Door-opening motion can potentially lead to a transient breakdown in negative-pressure isolation conditions: the importance of vorticity and buoyancy airflows.
      These influences are illustrated in Figure 3. However, droplet size seems to be the most important factor affecting dispersion and deposition.
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      Size of droplets affects their dispersion and deposition on surfaces and the survival of microorganisms within the droplets. Physical characteristics of the indoor environment, such as temperature and relative humidity and design of the ventilation system, are also important.
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      The survival of pathogens inside the droplets is likewise subject to various environmental conditions and has been reviewed by Tang.
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      Fig 3
      Fig 3Droplet transport in an isolation room by expired airflow, thermal plume
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      , door vortices (adapted with permission from Elsever
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      ), human walking
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      , 2-way buoyancy airflow, and ventilation airflow.
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      Asignificant downwash that occurs behind the body has the effect of laterally spreading the lower portions of the wake.
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      Potential airborne transmission between two isolation cubicles through a shared anteroom.
      Using large eddy simulation, Choi and Edwards
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      found that backward transport (opposite to the direction of walking) can also occur because of downwash effects and tip vortex formation. Wake-induced transport of material in the direction of the walking motion continues because of inertial effects, even after the person stops. When the walking effect is combined with hinged door opening, the latter is the dominant transport mechanism, and human-induced wake motion enhances compartment-to-compartment transport. In addition, when isolation room air has a temperature different from that of the corridor, the 2-way airflow effect at the openings plays an important role in aerosol dispersal.
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      • Niu J.L.
      CFD study of the thermal environment around a human body: a review.
      The plume becomes fully turbulent at the middle chest level. It reaches a maximum velocity (0.2-0.3 m/s) approximately 0.5 m above the head. The thickness of the plume can reach 15 cm in the breathing zone, so airflow from the lower part of the human body is drawn into the mouth during inhalation, which makes up approximately two-thirds of total inhaled air. The total air flux in the plume is in the 20-35 L/s range.
      • Craven B.A.
      • Settles G.S.
      A computational and experimental investigation of the human thermal plume.
      The rising thermal plume entrains and transports pollutants when the pollution source is on the floor, leading to a higher concentration in the microenvironment, particularly in the breathing zone of the standing or seated person, more so than in the ambient environment.
      • Lewis H.E.
      • Foster A.R.
      • Mullan B.J.
      • Cox R.N.
      • Clark R.P.
      Aerodynamics of human microenvironment.
      • Rim D.
      • Novoselac A.
      Transport of particulate and gaseous pollutants in the vicinity of a human body.
      When the cough of a source patient penetrates the area around another person's lower body, the thermal plume can bring the fine droplet nuclei upward.
      The thermal plume also can act as an air curtain to protect the person from the penetration of airflow expired by other people.
      • Liu L.
      Expiratory droplet exposure between individuals in a ventilated room.
      In displacement ventilation, the reduction in plume buoyancy caused by stratification is substantial.
      • Craven B.A.
      • Settles G.S.
      A computational and experimental investigation of the human thermal plume.
      In downward ventilation, the thermal plume can be preserved at head height if it meets the downward air at 0.25 m/s,
      • Nielsen P.V.
      Control of airborne infectious diseases in ventilated spaces.
      which compromises the transport dominated by the thermal plume. Many factors influence the thermal plume (eg, gestures, clothing insulation, the blocking effect of a table, movement of people).
      • Clark R.P.
      • Edholm O.G.
      Man and his thermal environment.
      • Zukowska D.
      • Melikov A.
      • Popiolek Z.
      Impact of personal factors and furniture arrangement on the thermal plume above a sitting occupant.
      • Spitzer I.M.
      • Marr D.R.
      • Glauser M.N.
      Impact of manikin motion on particle transport in the breathing zone.
      When walking at a speed of >0.2 m/s, the effect of the thermal plume would give way to the human aerodynamic wake.
      • Edge B.A.
      • Paterson E.G.
      • Settles G.S.
      Computational study of the wake and contaminant transport of a walking human.
      It is worth mentioning that plumes induced by other heat sources also contribute to pollutant transport. In the smallpox outbreak in Meschede, Germany,
      • Wehrle P.F.
      • Posch J.
      • Richter K.H.
      • Henderson D.A.
      An airborne outbreak of smallpox in a German hospital and its significance with respect to other recent outbreaks in Europe.
      a radiator in the index patient's room introduced an upward plume flow because of a partially open window, resulting in the spread of smallpox.

      Exposure of susceptible hosts to respiratory droplets

      A susceptible host can be close to a patient (eg, during conversation) or at a distance from a patient (eg, sharing the same classroom) but sitting sufficiently far away.
      For 2 people in close contact, exposure can be caused by the direct spray route during which large droplets are deposited directly on the mucous membranes of the susceptible host (large droplet route) or by direct inhalation of fine droplets or droplet nuclei (airborne route). The latter is referred to as the short-range airborne route because exposure occurs when the 2 individuals are in close contact. For both the large droplet route and the short-range airborne route, expired droplets from the infected person can penetrate the thermal plume of the susceptible host, reaching the mucus or inhalation zone of the susceptible individual (Fig 2).
      • Liu L.
      Expiratory droplet exposure between individuals in a ventilated room.
      When the susceptible individual is sufficiently far from an infected individual, direct inhalation of the contaminated room air is referred to as the airborne route. The infection risk of the susceptible host caused by inhaled droplets depends on the quantity of pathogen he or she carries and on the site at which the droplets deposit within the respiratory tract. Inhaled particles can deposit in different regions of the respiratory tract (eg, head airway region, tracheobronchial region, pulmonary region). Deposition mechanisms include inertial impaction (limited to large particles), settling (most important in small airways), Brownian motion of submicrometer particles, and interception.
      • Hinds W.C.
      Aerosol technology: properties, behavior, and measurement of airborne particles.
      Recent studies on airflow and particle transport in the human respiratory tract were reviewed by Kleinstreuer and Zhang.
      • Kleinstreuer C.
      • Zhang Z.
      Airflow and particle transport in the human respiratory system. Annual review of fluid mechanics.
      Airflows are complex in the nasal cavities and oral airways; particles deposit largely at stagnation points, disrupting axial particle motion. According to the International Commission on Radiological Protection model
      • International Commission on Radiological Protection (ICRP)
      Human respiratory tract model for radiological protection, annals of the ICRP, publication 66.
      for adults engaged in light work, total deposition is dominated by deposition in the head airways of particles >1 µm; the number of particles >10 µm that can penetrate the head airways is negligible.
      We define 3 major routes of droplet exposure (Fig 4): the direct spray route, the long-range airborne route, and the fomite route, which is not discussed here. The direct spray route can be divided into 2 subroutes in terms of size and destination of the expiratory droplets and droplet nuclei: the short-range airborne route (<10 µm) and the droplet-borne route (>10 µm). This is basically in line with the definitions from the U.S. Centers for Disease Control and Prevention
      • Garner J.S.
      Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals.
      ; however, we distinguish the short-range and long-range airborne routes.
      Fig 4
      Fig 4Illustration of different transmission routes. Small droplets (<5 µm), sometimes called aerosols, are responsible for the short-range airborne route, long-range airborne route, and indirect contact route; large droplets are responsible for the direct spray route and indirect contact route.
      The definition of the transmission route of a specific pathogen also must account for its virulence and infectious dose, and different modes are not mutually exclusive. The infectious dose of a pathogen is the number of microorganisms required to cause an infection. Data from research performed on biological warfare agents suggest that both bacteria and viruses can produce disease with as few as 1-100 infectious units (eg, brucellosis: 10-100 infectious units, Q fever: 1-10 infectious units, tularemia: 10-50 bacterial cells, smallpox: 10-100 infectious units, viral hemorrhagic fevers: 1-10 viral particles).
      • Brankston G.
      • Gitterman L.
      • Hirji Z.
      • Lemieux C.
      • Gardam M.
      Transmission of influenza A in human beings.
      There remains considerable controversy over the relative importance of the alternative modes of transmission of influenza virus. Brankston et al
      • Brankston G.
      • Gitterman L.
      • Hirji Z.
      • Lemieux C.
      • Gardam M.
      Transmission of influenza A in human beings.
      concluded in a review that natural influenza virus transmission in humans generally occurs over short distances, rather than over long distances, whereas Tellier
      • Tellier R.
      Review of aerosol transmission of influenza A virus.
      • Tellier R.
      Aerosol transmission of influenza A virus: a review of new studies.
      concluded that aerosol transmission occurs at appreciable rates. Weber and Stilianakis
      • Weber T.P.
      • Stilianakis NI.
      Inactivation of influenza A viruses in the environment and modes of transmission: a critical review.
      found that contact, large droplet, and small droplet (aerosol) transmission are all potentially important modes of transmission for influenza virus. Our purpose here is not to make conclusions about the relative importance of each route but to comment on the impact of airflows on the spread of infectious agents.

      Relevance to infection control

      Respiratory infection could be reduced or eliminated by interruptions in 3 phases: release of pathogen at the source, transport of pathogen by air or by surface touch, and protection of the susceptible person.

      Prevention of droplet release at origin by saline inhalation

      There are 2 ways of altering mucus properties.
      • Vasudevan M.
      • Lange C.F.
      Property dependence of onset of instability in viscoelastic respiratory fluids.
      • Vasudevan M.
      • Lange C.F.
      Surface tension effects on instability in viscoelastic respiratory fluids.
      The first is to lower the mucus viscosity and increase elasticity and surface tension for total suppression, and the second is to enlarge droplet size by decreasing the elasticity and surface tension and increasing the viscosity. The latter approach is preferred because the droplets generated would be smaller and more dangerous if full suppression was not achieved. Edwards et al
      • Edwards D.A.
      • Man J.C.
      • Brand P.
      • Katstra J.P.
      • Sommerer K.
      • Stone H.A.
      • et al.
      Inhaling to mitigate exhaled bioaerosols.
      found that delivering approximately 1 g of isotonic saline orally via nebulized aerosols (droplets 5.6 µm in diameter) reduced the total amount of expired aerosols (among super-producing individuals) by approximately 72% over a 6-hour period. In vitro tests using a simulated cough machine indicated that a mucus mimetic nebulized with saline produces a larger droplet size after the forced convection of air over its surface than when air is forced over the mucus mimetic alone (ie, without saline nebulization). In a subsequent study, Clark et al
      • Clark R.E.A.
      • Katstra J.
      • Man J.C.
      • Dehaan W.
      Pulmonary delivery of anti-contagion aerosol to diminish exhaled bioaerosols and airborne infectious disease.
      report that delivering isotonic saline aerosols (5.6-µm droplets) into the endotracheal tube of anesthetized bull calves showed a dose-responsive effect on exhaled bioaerosols; 6 minutes of treatment resulted in a decrease of up to 50% of exhaled aerosols for at least 120 minutes, compared with the pretreatment case. Inhaling safe surface-active materials, such as isotonic saline, to suppress exhaled bioaerosols was reviewed and recommended for controlling airborne transmission
      • Fiegel J.
      • Clarke R.
      • Edwards D.A.
      Airborne infectious disease and the suppression of pulmonary bioaerosols.
      ; however, more studies are required to clearly elucidate the potential of this new approach.

      Use of masks for infected individuals and for susceptible individuals

      Two reviews
      • Cowling B.J.
      • Zhou Y.
      • Ip D.K.M.
      • Leung G.M.
      • Aiello A.E.
      Face masks to prevent transmission of influenza virus: a systematic review.
      • Bin-Reza F.
      • Lopez Chavarrias V.
      • Nicoll A.
      • Chamberland M.E.
      The use of masks and respirators to prevent transmission of influenza: a systematic review of the scientific evidence.
      highlight the limited evidence base supporting the efficacy of face masks in reducing influenza virus transmission. They suggested that surgical masks may reduce infectiousness, rather than protect against infection, especially when airborne transmission is important. Influenza viruses (with sizes in the 80- to 120-nm range) and other viruses of similar size are capable of penetrating the mask in either direction. The N95 respirators are efficient in removing very fine droplet nuclei, but face masks are not. However, face masks, if worn by an infected person, can suppress the expired jets (Fig 2A) and reduce the close contact transmission via both the droplet-borne and short-range airborne routes.

      Environmental ventilation for the long-range airborne route

      A multidisciplinary systematic review
      • Li Y.
      • Leung G.M.
      • Tang J.W.
      • Yang X.
      • Chao C.Y.
      • Lin J.Z.
      • et al.
      Role of ventilation in airborne transmission of infectious agents in the built environment—a multidisciplinary systematic review.
      suggested that ventilation rate and airflow patterns contribute directly to the airborne spread of infectious agents; however, the minimum ventilation rate for effective airborne transmission control is unknown at present. The current minimum requirement is 12 air changes per hour for negative-pressure airborne isolation rooms.
      • Centers for Disease Control and Prevention (CDC)
      Guidelines for environmental infection control in health-care facilities.
      • World Health Organization (WHO)
      Infection prevention and control of epidemic- and pandemic-prone acute respiratory diseases in health care: WHO interim guidelines.
      Natural ventilation may offer a low-cost alternative.
      • World Health Organization (WHO)
      Infection prevention and control of epidemic- and pandemic-prone acute respiratory diseases in health care: WHO interim guidelines.
      • Escombe A.R.
      • Oeser C.C.
      • Gilman R.H.
      • Navincopa M.
      • Ticona E.
      • Pan W.
      • et al.
      Natural ventilation for the prevention of airborne contagion.
      The current negative-pressure isolation rooms with a ceiling supply and bottom return system are recommended, but gaseous and fine particles were found to be removed more efficiently by ceiling-level exhausts, and large particles were removed mainly by deposition, rather than by ventilation.
      • Qian H.
      • Li Y.
      Removal of exhaled particles by ventilation and deposition in a multibed airborne infection isolation room.
      Displacement ventilation has been recommended as a more energy-efficient approach in nonhospital settings. However, in the case of the isolation room, the stable thermal stratification zone may cause the lock-up phenomenon to occur
      • Stymne H.
      • Sandberg M.
      • Mattsson M.
      Dispersion pattern of contaminants in a displacement ventilated room – implications for demand control.
      if the exhaled pollutant is not caught by the thermal plume penetrating into the upper zone, resulting in a longer residence time of pollutants.
      • Li Y.
      • Nielsen P.V.
      • Sandberg M.
      Displacement ventilation in hospital environments.
      Displacement ventilation can create what might be referred to as inversion clouds in rooms. Because deposition is the main mechanism for removing large droplets,
      • Qian H.
      • Li Y.
      Removal of exhaled particles by ventilation and deposition in a multibed airborne infection isolation room.
      floor cleaning in hospitals is absolutely necessary.

      Personalized ventilation for the short-range airborne route

      This may be a less well-known technology in the infection control community. Its principle is based on detectable jets of air with a high momentum directed at a person's face.
      • Pantelic J.
      • Sze-To G.N.
      • Tham K.W.
      • Chao C.Y.H.
      • Khoo Y.C.M.
      Personalized ventilation as a control measure for airborne transmissible disease spread.
      • Alain M.
      • Kamel G.
      • Nesreen G.
      A simplified combined displacement and personalized ventilation model.
      It may not be effective when the mobility of the subject is considered. An air supply pillow was suggested for hospital use.
      • Nielsen P.V.
      • Jiang H.
      • Polak M.
      Bed with integrated personalized ventilation for minimizing cross infection.
      The personalized ventilation (PV) system can be supplemented with a general ventilation system in the room. Experiments with PV, together with vertical ventilation from ceiling-mounted terminals, show increased efficiency of personal protection by a factor of up to 35.
      • Nielsen P.V.
      • Jiang H.
      • Polak M.
      Bed with integrated personalized ventilation for minimizing cross infection.
      A combination of PV and the personalized exhaust method was suggested.
      • Yang J.
      • Sekhar S.C.
      • Cheong K.W.D.
      • Raphael B.
      Performance evaluation of a novel personalized ventilation–personalized exhaust system for airborne infection control.

      Conclusions

      By reviewing the airborne spread of infectious agents from mucus to mucus in the indoor environment, we have shown the opportunities for infection control at different stages of the spread. We propose that the short-range airborne route may be important in close contact, and its control may be achieved by face masks for the source patients and the use of PV. Our discussion of the effect of thermal stratification and expiratory delivery of droplets leads to the suggestion that displacement ventilation may not be applicable to hospital rooms where respiratory infection is a concern. The saline inhalation method was discussed after a discussion of the mechanisms of droplet formation and origin.

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