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The role of particle size in aerosolised pathogen transmission: A review

  • Jan Gralton
    Affiliations
    School of Public Health and Community Medicine, The University of New South Wales, Australia

    Virology, UNSW and POWH Research Laboratories, Prince of Wales Hospital, Australia
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  • Euan Tovey
    Affiliations
    Woolcock Institute of Medical Research, University of Sydney, Australia
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  • Mary-Louise McLaws
    Affiliations
    School of Public Health and Community Medicine, The University of New South Wales, Australia
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  • William D. Rawlinson
    Correspondence
    Corresponding author. Virology Research, Department of Microbiology, South Eastern Area Laboratory Service, Prince of Wales Hospital, Randwick, NSW 2031, Australia. Tel.: +61 2 93829113; fax: +61 2 93828533.
    Affiliations
    Virology, UNSW and POWH Research Laboratories, Prince of Wales Hospital, Australia

    School of Medicine, The University of New South Wales, Australia

    School of Biotechnology and Biological Sciences, The University of New South Wales, Australia
    Search for articles by this author
Published:December 10, 2010DOI:https://doi.org/10.1016/j.jinf.2010.11.010

      Summary

      Understanding respiratory pathogen transmission is essential for public health measures aimed at reducing pathogen spread. Particle generation and size are key determinant for pathogen carriage, aerosolisation, and transmission. Production of infectious respiratory particles is dependent on the type and frequency of respiratory activity, type and site of infection and pathogen load. Further, relative humidity, particle aggregation and mucus properties influence expelled particle size and subsequent transmission. Review of 26 studies reporting particle sizes generated from breathing, coughing, sneezing and talking showed healthy individuals generate particles between 0.01 and 500 μm, and individuals with infections produce particles between 0.05 and 500 μm. This indicates that expelled particles carrying pathogens do not exclusively disperse by airborne or droplet transmission but avail of both methods simultaneously and current dichotomous infection control precautions should be updated to include measures to contain both modes of aerosolised transmission.

      Keywords

      Introduction

      Natural human respiratory activities include breathing, talking, sneezing, and coughing.
      Several mechanisms of particle generation from these activities have been postulated.
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      Respiratory Physiology.
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      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
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      Physical dynamics of the cough mechanism.
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      Effect of airway opening on production of exhaled particles.
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      The mechanism of breath aerosol formation.
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      Size distribution of exhaled particles in the range from 0.01 to 2.0 [mu]m.
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      Submicron droplet formation in the human lung.
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      • et al.
      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
      Early studies propose that normal breathing produces particles through the processes of condensation and high-speed atomization.
      • Slonim N.B.
      • Chapin J.L.
      Respiratory Physiology.
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      Warm and wet gas in the alveolar region transits from the lungs into the upper airways, where the gas cools to a liquid state
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      Respiratory Physiology.
      and turbulent high-speed airflow expels liquid as particles during exhalation.
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      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      Further atomization of particles also occurs during talking, sneezing and coughing, due to increased turbulent airflows expelling particles at higher velocities.
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      Physical dynamics of the cough mechanism.
      A later study suggested particle generation during breathing occurs from the re-opening of small airways during inhalation
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      The human lung as aerosol particle Generator.
      ; this mechanism has been supported by recent data examining mechanisms during exhalation
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      Effect of airway opening on production of exhaled particles.
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      The mechanism of breath aerosol formation.
      where particles are formed by the bursting of liquid films that cover the airway openings.
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      • Almstrand A.-C.
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      Size distribution of exhaled particles in the range from 0.01 to 2.0 [mu]m.
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      • Koch W.
      Submicron droplet formation in the human lung.
      The vigorous vibration and energetic movement of the vocal chords during speech and coughing have also been suggested to be responsible for the majority of particle generation.
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      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • Mengersen K.
      • Corbett S.
      • et al.
      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
      This review examines the role of particle size in the aerosolised spread of infectious disease. Specifically we first detail why particle size is important. We then provide an overview of the literature that has measured particle sizes generated from different respiratory activities. Subsequently, we briefly discuss the different sizing methods and their limitations. This review also highlights some of the extraneous factors, outside the act of particle generation, that further complicates particle sizing and the use of size in infection control precautions. We conclude by identifying remaining gaps in the current knowledge of particle size and their implications.

      The importance of particle size

      Aerosolised disease transmission can be classified as either droplet or airborne transmission. Droplet transmission is defined as the transmission of diseases by expelled particles that have a propensity to settle quickly to the ground, usually within 1 m of the site of generation, due to their size.
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      Conversely, airborne transmission is defined as the transmission of infection by expelled particles that are comparatively smaller in size. These particles can remain suspended in the air for prolonged periods and thereby potentially expose a greater number of susceptible individuals to possible infection at a greater distance from the source.
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      This paradigm between droplet and airborne transmission has been underpinned by early studies by Wells, who described the settling of expelled particles as being a function of size, time and evaporation,
      • Wells W.F.
      On airborne infection: study II. Droplets and droplet nuclei.
      and by Hamburger and Robertson, whom described the distance travelled by particles expelled during sneezing and coughing events as a function of time.
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      Expulsion of Group A hemolytic streptococci in droplets and droplet nuclei by sneezing, coughing and talking.
      The World Health Organisation employ a 5 μm cut-off to delineate between airborne (≤5 μm) and droplet transmission (>5 μm).
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      While we will use this framework in this review, we will later discuss how this single cut-off delineation fails to acknowledge that the size of particles and the resulting behaviour follows a continuum and may overlap either side of this cut-off. There are also physiological concerns which warrant a better understanding of the role of particle size in disease transmission. Deposition models have concluded that particles <10 μm in diameter are more likely to penetrate deeper into the respiratory tract while particles ≥10 μm in diameter are more likely to impact onto the surfaces of the upper airways and are less likely to penetrate into the lower pulmonary region.
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      Although small particles may also deposit in the upper airways,
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      • Cheng Y.S.
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      Diffusional deposition of ultrafine aerosols in a human nasal cast.
      • Cheng Y.S.
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      • Swift D.L.
      Aerosol deposition in human nasal airway for particles 1 nm to 20 μm radiation.
      the usual behaviour is for small particles to travel with the inhaled air current and avoid impaction within the nasal region; this enables deposition lower in the respiratory tract
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      Deposition pattern of droplets from medical nebulizers in the human respiratory tract.
      • Licht W.
      The movement of aerosol particles.
      and the establishment of infection in this region.
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      Distribution and deposition of inhaled particles in respiratory tract.
      Similar reasoning is also used by Nicas (2005), who used an equilibrium size of 10 μm in diameter in risk calculations of airborne transmission.
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      • Hubbard A.
      Toward understanding the risk of secondary airborne infection: emission of respirable pathogens.
      Based upon the likelihood of deposition in the respiratory tract rather than generated particle size, Weber and Stilianakis, in their review article, suggest a cut-off of 10 μm in diameter to separate particles likely to transmit disease (particles ≤10 μm in diameter) from those that are less likely (particles >10 μm in diameter).
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      • Stilianakis N.I.
      Inactivation of infuenza A viruses in the environment and modes of transmission: a critical review.
      This group also used this cut-off in recent computer models and proposed likely predominant airborne transmission of particles ≤10 μm in sustained disease outbreaks and likely predominant droplet transmission in short-term epidemic outbreaks.
      • Stilianakis N.I.
      • Drossinos Y.
      Dynamics of infectious disease transmission by inhalable respiratory droplets.
      Other factors, such as infectious dose at different sites, are also implicated in the establishment of infection in the respiratory tract and have been reviewed elsewhere.
      • Tellier R.
      Review of aerosol transmission of influenza A virus.
      Compared with upper respiratory tract infections, lower respiratory tract infections are associated with increased severity, morbidity and fatality
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      the initiation of other chronic respiratory illness
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      Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study.
      and the effects of comorbid factors.
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      • et al.
      Effects of viral lower respiratory tract infection on lung function in infants with cystic fibrosis.
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      Clinicopathologic studies of children who die of acute lower respiratory tract infections: mechanisms of death.
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      • Couch R.B.
      Impact of respiratory virus infections on Persons with chronic Underlying conditions.
      Better understanding of the site of deposition of infected particles, the relationship between particle size and pathogen load and the critical pathogen load of particles required for the establishment of infection in the different regions of the airways is necessary before particle size can be robustly established as an index of transmissibility for infection control measures.

      Particles and the spread of infection

      The probability of the spread of infection by aerosolised particles is broadly dictated by 1) the clinical manifestation of disease 2) site of infection 3) the presence of a pathogen and 4) type of pathogen (see Table 1).
      Table 1Factors affecting disease transmission via aerosolised modes.
      FactorsEffect
      Type of respiratory activityDifferent activities (for example breathing, coughing, sneezing, talking) produce different numbers and sizes of particles
      Frequency of respiratory activityFrequent activities associated with clinical disease are more likely to spread pathogen
      Number of particles generatedActivities that atomize more particles are more likely to spread pathogen
      Site of infectionActivities that generate aerosols from the infected region of the respiratory tract are likely to propagate disease
      Pathogen loadSufficient pathogen load must be present in expelled particles to establish infection in a susceptible individual.
      Pathogen typeThe size of the pathogen may determine the size and infectivity of expelled particles.

      Clinical manifestations of disease

      The relative contributions of the different respiratory activities for the spread of disease remains contentious due to the numerous factors involved, such as the frequency of different respiratory activities, the number of particles produced per activity, and the pathogen load size distribution of different sized particles. Recently respiratory viruses have been detected in particles during tidal breathing – an activity that is continuous but previously assumed to produce a low number of particles.
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      Exhalation of respiratory viruses by breathing, coughing and talking.
      • Fabian P.
      • McDevitt J.J.
      • DeHaan W.H.
      • Fung R.O.P.
      • Cowling B.J.
      • Chan K.H.
      • et al.
      Influenza virus in human exhaled breath: an observational study.
      • Fabian P.
      • McDevitt J.J.
      • Lee W.M.
      • Houseman E.A.
      • Milton D.K.
      An optimized method to detect influenza virus and human rhinovirus from exhaled breath and the airborne environment.
      • Huynh K.N.
      • Oliver B.G.
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      • Rawlinson W.
      • Tovey E.R.
      A new method for sampling and detection of exhaled respiratory virus aerosols.
      Other studies suggest that vibration of the vocal chords and vocalisation (associated with intermittent activities such as coughing, sneezing and talking) contributes more to particle atomization
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • Mengersen K.
      • Corbett S.
      • et al.
      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
      • Winslow C.E.
      • Robinson E.A.
      An investigation of the extent of bacterial pollution of the atmosphere by mouth-Spray.
      • Koeniger H.
      Untersuchungen uber die Frage der Tropfcheninfection.
      and the production of particles that carry microorganisms.
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      Disease propagation may also be associated with the frequency of the different respiratory activity. While sneezing may produce more particles containing virus than coughing,
      • Duguid J.P.
      The size and the duration of air-carriage of respiratory droplets and droplet-nuclei.
      • Morrow P.E.
      Physics of airborne particles and their deposition in the lung.
      • Buckland F.E.
      • Tyrrell D.A.J.
      Experiments on the spread of Colds: !. Laboratory studies on the Dispersal of nasal Secretion.
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      Couch et al. (1966) found that coughing is more frequent than sneezing during infection with Coxsackievirus A, – implying that coughing is the more efficient method of transmission for this infection.
      • Couch R.B.
      • Cate T.R.
      • Douglas R.G.J.
      • Gerone P.J.
      • Knight V.
      Effect of route of inoculation on experimental respiratory disease in volunteers and evidence for airborne transmission.
      It can be speculated that since coughing is one of the most common clinical symptoms associated with influenza infections,
      • Lee C.-S.
      • Lee J.-H.
      Dynamics of clinical symptoms in patients with pandemic influenza A (H1N1).
      • Monto A.S.
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      • Colopy M.
      • Schweinle J.
      Clinical signs and symptoms predicting influenza infection.
      coughing may also drive the aerosolised spread of this infection. While limited cough frequency data is available, evidence from modelling of flow dynamics also lends support to such speculation
      • Gupta J.K.
      • Lin C.-H.
      • Chen Q.
      Flow dynamics and characterization of cough.
      as does the observations of sneezing counter-indicating an influenza diagnosis.
      • Call S.A.
      • Vollenweider M.A.
      • Hornung C.A.
      • Simel D.L.
      • McKinney W.P.
      Does this patient have influenza?.

      Site of infection

      The site of infection should also be considered in terms of understanding the source of aerosolised particles. As a starting proposition, to ensure expelled particles carry pathogen, the site of infection should be the same or very close to the site of particle generation. As earlier discussed, coughing and speech are reported to produce particles from vibrations of vocal chords.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • Mengersen K.
      • Corbett S.
      • et al.
      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
      This implies that infection of the larynx is the optimal location for propagation of pathogen by these activities. Particle generation during breathing has recently been associated with opening of the small airways,
      • Gebhart J.
      • Anselm A.
      • Heyder J.
      • Stalhofen W.
      The human lung as aerosol particle Generator.
      • Almstrand A.-C.
      • Bake B.
      • Ljungstrom E.
      • Larsson P.
      • Bredberg A.
      • Mirgorodskaya E.
      • et al.
      Effect of airway opening on production of exhaled particles.
      • Johnson G.R.
      • Morawska L.
      The mechanism of breath aerosol formation.
      indicating that infection of the lower respiratory tract is important for aerosolised transmission from breathing. If particle generation occurs outside of the site of infection, we speculate that there is a reduced likelihood that particles will contain a sufficient pathogen load to establish secondary infection. If multiple sites are infected, the number of particles carrying pathogen will be increased if simultaneous respiratory events occurs (for example simultaneous coughing and breathing); conversely, dilution of the number of particles carrying pathogen will occur if simultaneous atomization occurs at additional but non-infected sites. An example of this dilution is the observation that the majority of particles produced during sneezing arise from the mouth
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      despite sneezing being a reflex of the irritation of the nasal region and generating particles from the lower respiratory tract with additional secretions from the nasal region.
      • Seijo-Martinez M.
      • Varela-Freijanes Grandes J.
      • Vazquez F.
      Sneeze related area in the medulla: localisation of the human sneezing centre?.
      • Hyden D.
      • Arlinger S.
      On light-induced sneezing.
      • Martin R.A.
      • Handel S.F.
      • Aldama A.E.
      Inability to sneeze as a manifestation of medullary neoplasm.
      The relative proportions of particles that arise from the different areas of the respiratory tract during a respiratory activity and the change in these proportions during simultaneous respiratory activities, in healthy and in infected states, is poorly described in the literature and precludes further discussion of the site of infection and the site of particle generation are in disease spread.

      The presence of pathogen

      Obviously secondary infection can only result if pathogen is present in expelled particles. Early observations indicated that regardless of the frequency of respiratory activities or the number of particles generated by the different activities, very few particles actually carry pathogens
      • Duguid J.P.
      The size and the duration of air-carriage of respiratory droplets and droplet-nuclei.
      and that efficient disease transmission is more reliant upon pathogen load in particles and the flow of saliva than atomization of particles.
      • Rubbo S.D.
      • Benjamin M.
      Transmission of Haemolytic streptococci.
      Of further significance is the relationship between particle size and infectivity. While it may be that many particles carry pathogen, pathogens may be inactivated due to desiccation and other environmental factors. Computer models have pointed out that aerosolised transmission dynamics are pathogen-specific, due to pathogen-specific peak shedding and inactivation rates
      • Atkinson M.P.
      • Wein L.M.
      Quantifying the routes of transmission for pandemic influenza.
      and that models need to include an inactivation parameter to account for pathogens that are no longer infectious.
      • Li S.
      • Eisenberg J.N.S.
      • Spicknall I.H.
      • Koopman J.S.
      Dynamics and control of infections transmitted from person to person through the environment.

      Type of pathogen

      A number of fungal, bacterial and viral pathogens is responsible for causing respiratory infections by utilising aerosolised modes of transmission (see Table 2). The size of these pathogens may firstly dictate the size of the particle carrying the pathogen. For example, larger pathogens such as bacteria have been found in larger particles
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      • Buckland F.E.
      • Tyrrell D.A.J.
      Experiments on the spread of Colds: !. Laboratory studies on the Dispersal of nasal Secretion.
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      • Heymann B.
      Ueber die Ausstreuung infectioser Tropfchen beim Husten der Phthisiker.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      whereas particles produced from virally infected individuals have been much smaller
      • Fabian P.
      • McDevitt J.J.
      • DeHaan W.H.
      • Fung R.O.P.
      • Cowling B.J.
      • Chan K.H.
      • et al.
      Influenza virus in human exhaled breath: an observational study.
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      • Hersen G.
      • Moularat S.
      • Robine E.
      • Ghin E.
      • Corbet S.
      • Vabret A.
      Impact of health on particle size of exhaled respiratory aerosols: case-control study.
      (see Fig. 1). Secondly, the size of pathogens may dictate the infectivity of particles. Large pathogens, such as bacteria and fungi, may not be able to be carried at high concentration in particles without breaking up into smaller particles soon after expulsion. In light of this, some large sized pathogens may find it difficult to establish an infection if a high concentration of pathogen is required.
      Table 2Common respiratory pathogens transmitted by aerosolised routes of transmission, as reviewed by the CDC, 2007.
      • Siegel J.D.
      • Rhinehart E.
      • Jackson M.
      • Chiarello L.
      • Committee H.I.C.P.A.
      Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings.
      Fungal pathogensBacterial pathogensViral pathogens
      Aspergillus spp. (spores)Neisseria meningitidisRhinoviruses
      Mycoplasma pneumoniaeInfluenza viruses
      Bordetella pertussisRespiratory Syncytial virus
      Streptococcus spp.SARS-associated coronavirus
      Staphylococcus aureusRubeola virus
      Mycobacterium tuberculosisVaricella Zoster virus
      Norovirus
      Rotavirus
      Figure thumbnail gr1
      Figure 1The changing size scale of particle sizes and demarcations of particle size. This schematic indicates the size range of expelled from individuals prior to and after 1979. The black arrow refers to the size range identified from healthy and infected individuals. The red dashed line refers to the size range identified from individuals with known bacterial infections. The yellow dashed line refers to the size range identified from individuals with known viral infections.

      Particles in the past

      The PubMed database was used to find studies of expelled particle sizes. The following search strings were used: aerosol AND size, particle AND size, bioaerosol AND size. Our search criteria included: i) an open date limit to 2010; ii) must be in English or translated into English and ii) published studies. Retrieved studies were also reviewed for additional references that did not appear in the PubMed search. Due to the limited number of studies available, conference abstracts were also included in this review. Airborne-sized particles were considered to be particles ≤5 μm in size and droplet-sized particles were considered to be particles >5 μm in size.
      Early studies of particle size utilised methods of impaction upon solid
      • Duguid J.P.
      The size and the duration of air-carriage of respiratory droplets and droplet-nuclei.
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      • Heymann B.
      Ueber die Ausstreuung infectioser Tropfchen beim Husten der Phthisiker.

      Strausz W. Z Hyg. 1926;105:416 [cited by Duguid, 1946].

      • Loudon R.G.
      • Roberts R.M.
      Droplet explusion from the respiratory tract.
      and liquid interfaces
      • Duguid J.P.
      The size and the duration of air-carriage of respiratory droplets and droplet-nuclei.
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      • Downie A.W.
      • Meiklejohn M.
      • St. Vincent L.
      • Rao A.R.
      • Sundara Babu B.V.
      • Kempe C.H.
      The recovery of Smallpox virus from patients and their environment in a Smallpox hospital.
      and high-speed photography
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      (Table 3). The most basic of the described impactors is the microscope slide and the paper strip. These surfaces are held close to the mouth and nose and capture expelled particles during respiratory activities. The surfaces are then examined by microscopy to measure particle size.
      • Duguid J.P.
      The size and the duration of air-carriage of respiratory droplets and droplet-nuclei.
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      • Heymann B.
      Ueber die Ausstreuung infectioser Tropfchen beim Husten der Phthisiker.
      • Xie X.
      • Li Y.
      • Sun H.
      • Liu L.
      Exhaled droplets due to talking and coughing.
      This type of impaction is inherently biased towards the collection of droplet-sized particles because of the propensity for airborne-sized particles to remain suspended in the air and not impact. More complex solid impactors, such as the sieve sampler used by Eichenwald et al.
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      (and the Andersen sampler used later by Fennelly et al.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      and Wainwright et al.
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      ) utilises the difference in inertial mass that accompanies changes in particle size to differentiate between different particle sizes. The larger particles, with increased inertial mass, impact on the earlier stages of the sampler while small particles, with less inertial mass, are able to avoid impaction and move through to the latter stages of the sampler. This method is normally used to size particles carrying bacterial and fungal pathogens on an agar surface for later cultivation. A liquid impactor, also known as a liquid impinger, operates similarly to a solid impactor in terms of relying upon inertial mass. However, instead of particles impacting onto a solid surface, liquid impingement requires particles to impact into a liquid, which is then cultivated. Often liquid impingers are accompanied by pre-impinger to initially collect the largest particles. However, as noted by Gerone et al.,
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      droplet-sized particles may be difficult to collect for sizing with a sampler or impactor because of rapid settling after expulsion preventing any collection upon an impaction surface. Previous studies have identified that collection efficiency by impaction is impeded by the effects of drying, which reduces particle size beyond the limits of collection
      • Li C.-S.
      • Hao M.-L.
      • Lin W.-H.
      • Chang C.-W.
      • Wang C.-S.
      Evaluation of microbial samplers for bacterial microorganisms.
      • Fabian P.
      • McDevitt J.J.
      • Houseman E.A.
      • Milton D.K.
      Airborne influenza virus detection with four aerosol samplers using molecular and infectivity assays: considerations for a new infectious virus aerosol sampler.
      • Tseng C.-C.
      • Li C.-S.
      Collection efficiencies of aerosol samplers for virus-containing aerosols.
      • Stewart S.L.
      • Grinshpun S.A.
      • Willeke K.
      • Terzieva S.
      • Ulevicius V.
      • Donnelly J.
      Effect of impact stress on microbial recovery on an agar surface.
      • Saldanha R.
      • Manno M.
      • Saleh M.
      • Ewaze J.O.
      • Scott J.A.
      The influence of sampling duration on recovery of culturable fungi using the Andersen N6 and RCS bioaerosol samplers.
      • Hogan C.J.
      • Kettleson E.M.
      • Lee M.-H.
      • Ramaswami B.
      • Angenent L.T.
      • Biswas P.
      Sampling methodologies and dosage assessment techniques for submicrometre and ultrafine virus aerosol particles.
      • Grinshpun S.A.
      • Willeke K.
      • Ulevicius V.
      • Juozaitis A.
      • Terzieva S.
      • Donnelly J.
      • et al.
      Effect of impaction, bounce and Reaerosolization on the collection efficiency of impingers.
      and particle bounce (particles bouncing off the impaction surface and onto non-collection surfaces).
      • Grinshpun S.A.
      • Willeke K.
      • Ulevicius V.
      • Juozaitis A.
      • Terzieva S.
      • Donnelly J.
      • et al.
      Effect of impaction, bounce and Reaerosolization on the collection efficiency of impingers.
      Physical slippage (particles slipping onto the wrong collection surface for sizing) may also reduce the accuracy of particle sizing. Impaction may be also inhibited by a small particle size which will remain aerosolised or bounce off the settling surface
      • Esmen N.A.
      • Ziegler P.
      • Whitfield R.
      The adhesion of particles upon impaction.
      • Lai C.-Y.
      • Huang S.-H.
      • Chang C.-P.
      • Lin J.-Y.
      Reducing particle bounce and loading effect for a multi-hole impactor.
      • Chang M.
      • Kim S.
      • Sioutas C.
      Experimental studies on particle impaction and bounce: effects of substrate design and material.
      • Dzubay T.G.
      • Hines L.E.
      • Stevens R.K.
      Particle bounce errors in cascade impactors.
      • Yamamoto N.
      • Fujii M.
      • Endo O.
      • Kumagai K.
      • Yanagisawa Y.
      Broad range observation of particle deposition on greased and non-greased impaction surfaces using a line-sensing optical microscope.
      – this gives rise to a proclivity for the collection of heavier, large particles, rather than airborne-sized particles. The physical nature of impaction may cause particles to also spread, splash or finger and inevitably distort the true particle size if identified by microscopy.
      • Ukiwe C.
      • Kwok D.Y.
      On the maximum spreading diameter of impacting droplets on well-prepared solid surfaces.
      • Moita A.S.
      • Moreira A.L.
      The deformation of single droplets impacting onto a flat surface.
      • Bhunia Impingement Splattering S.K.
      • Disturbance Surface
      Evolution on turbulent liquid jets in Gases.
      • Hawke S.R.
      Effects of a thin, flexible nozzle on droplet formation and impingement.
      • Park H.
      • Carr W.W.
      • Zhu J.
      • Morris J.F.
      Single drop impaction on a solid surface.
      • Sikalo S.
      • Marengo M.
      • Tropea C.
      • Ganic E.N.
      Analysis of impact of droplets on horizontal surfaces.
      Table 3Studies that have investigated the size of particles from natural respiratory activities.
      Author, DateMethod of sizing (device, where possible)Infection Status of participantsPredominant particle size range for activity (μm)
      HealthyInfected (bacterial/viral)BreathingCoughingSneezingTalking
      Heymann et al.,1899
      • Heymann B.
      Ueber die Ausstreuung infectioser Tropfchen beim Husten der Phthisiker.
      Solid impaction (glass slide with microscopy)Bacterial Mycobacterium tuberculosis30–500
      Strauz et al., 1926

      Strausz W. Z Hyg. 1926;105:416 [cited by Duguid, 1946].

      Solid impaction (glass slide with microscopy)Unknown infection70–85
      Jennision, 1942
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      High-speed photographyHealthyUnknown infection>100
      No size stratification was made by authors on the basis of diseased state.
      7–100
      No size stratification was made by authors on the basis of diseased state.
      Duguid et al., 1946
      • Duguid J.P.
      The size and the duration of air-carriage of respiratory droplets and droplet-nuclei.
      Solid impaction (glass slide with microscopy)Healthy
      Assumed to be healthy individuals but not explicitly described in literature.
      100–125 (DN: 8–16)100–125 (DN: 4–8)100–125 (DN: 8−16)
      Eichenwald et al., 1960
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      Liquid impaction (impinger)

      Solid impaction (sieve sampler)
      Bacterial<5.0
      Buckland et al., 1964
      • Buckland F.E.
      • Tyrrell D.A.J.
      Experiments on the spread of Colds: !. Laboratory studies on the Dispersal of nasal Secretion.
      Liquid impaction (impinger)Bacterial

      Unknown spp.
      80–180
      Gerone et al., 1966
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      Solid Impaction

      Liquid Impaction
      Viral

      Unknown spp.
      <1.0–1.0<1.0–1.0
      Loudon et al., 1967
      • Loudon R.G.
      • Roberts R.M.
      Droplet explusion from the respiratory tract.
      Solid impaction (paper with microscopy)Healthy
      Assumed to be healthy individuals but not explicitly described in literature.
      55.585
      Papineni et al., 1997
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      Papineni and Rosenthal (1997) measured particles generated from breathing using optical and solid impaction methods – particles from coughing and talking were measured only by optical methods.
      Optical technology (optical particle counter)

      Solid impaction (glass slide with transmission electron microscopy)
      HealthyOPC: <0.6

      SI:>1.0
      OPC: <0.6OPC: <0.6
      Edwards et al., 2004
      • Edwards D.A.
      • Man J.C.
      • Brand P.
      • Katstra J.P.
      • Stone H.A.
      • Nardell E.
      • et al.
      Inhaling to mitigate exhaled bioaersols.
      Optical technology (optical particle counter)Healthy0.15–0.19
      Fennelly et al., 2004
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      Solid impaction (Andersen sampler)Bacterial Unknown spp.≤3.3
      Yang et al., 2007
      • Yang S.
      • Lee G.W.M.
      • Chen C.-M.
      • Wu C.-C.
      • Yu K.-P.
      The size and concentration of droplets generated by coughing in human Subjects.
      Time-of-flight technology (aerodynamic particle size)

      Charge separation (scanning mobility particle sizer)
      Healthy0.62–15.9 (DN 0.58–5.42)
      Fang et al., 2008
      • Fang M.
      • Lau A.P.S.
      • Chan C.K.
      • Hung C.T.
      • Lee T.W.
      Aerodynamic properties of biohazardous aerosols in hospitals.
      Time-of-flight technology (aerodynamic particle sizer)HealthyUnknown infectionH:<1.0 I: Unknown
      Fabian et al., 2008
      • Fabian P.
      • McDevitt J.J.
      • DeHaan W.H.
      • Fung R.O.P.
      • Cowling B.J.
      • Chan K.H.
      • et al.
      Influenza virus in human exhaled breath: an observational study.
      Optical technology (optical particle counter)Viral

      Unknown spp.
      0.3–0.5
      Hersen et al., 2008
      • Hersen G.
      • Moularat S.
      • Robine E.
      • Ghin E.
      • Corbet S.
      • Vabret A.
      Impact of health on particle size of exhaled respiratory aerosols: case-control study.
      Electrical impaction (electrical low pressure impactor)HealthyViral

      Unknown spp.
      H: 0.09–<0.16

      I: 0.09–>9.97
      Li et al., 2008
      • Li Y.G.
      • Chwang A.T.Y.
      • Seto W.H.
      • Ho P.L.
      • Yuen P.L.
      Understanding droplets produced by nebulisers and respiratory activities.
      Solid impaction (glass slide with microscopy)

      Optical technology (dust monitor)
      Healthy
      Assumed to be healthy individuals but not explicitly described in literature.
      50–10050–10050–100
      Morawska et al., 2008
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • Mengersen K.
      • Corbett S.
      • et al.
      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
      Time-of-flight technology (aerodynamic particle sizer)Healthy0.1–1.00.1–1.00.1–1.0
      Chao et al., 2009
      • Chao C.Y.H.
      • Wan M.P.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • et al.
      Characterization of expiration air jets and droplet size distributions immediately at the mouth opening.
      Optical technology (interferometric Mie imaging)Healthy4–84–8
      Xie et al., 2009
      • Xie X.
      • Li Y.
      • Sun H.
      • Liu L.
      Exhaled droplets due to talking and coughing.
      Solid impaction (glass slide with microscopy)

      Optical technology (dust monitor)
      Healthy50–7550−75
      Morawska et al., 2009

      Morawska L, Johnson GR, Ristovski Z, Hargreaves M, Mengersen K, Chao C, et al., editors. Droplets expelled during human expiratory activities and their origins. Paper-1023. In: 11th International conference on indoor air quality and climate paper, Copenhagen, Denmark; 2009.

      Time-of-flight technology (aerodynamic particle sizer)Healthy0.4–1.10.4–10.00.4–4.0
      Wainwright et al., 2009
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      Solid impaction (Andersen sampler)Bacterial

      Unknown infection
      ≤3.3
      Almstrand et al., 2010
      • Almstrand A.-C.
      • Bake B.
      • Ljungstrom E.
      • Larsson P.
      • Bredberg A.
      • Mirgorodskaya E.
      • et al.
      Effect of airway opening on production of exhaled particles.
      Optical technology (optical particle counter)Healthy0.3–0.4
      Haslbeck et al., 2010
      • Haslbeck K.
      • Schwarz K.
      • Hohlfeld J.M.
      • Seume J.R.
      • Koch W.
      Submicron droplet formation in the human lung.
      Time-of-flight technology (laser spectrometer)Healthy0.1–7.0
      Holmgren et al., 2010
      • Holmgren H.
      • Ljungström E.
      • Almstrand A.-C.
      • Bake B.
      • Olin A- C.
      Size distribution of exhaled particles in the range from 0.01 to 2.0 [mu]m.
      Optical technology (optical particle counter)

      Charge separation (scanning mobility particle sizer)
      HealthyOPC: 0.4–4.0

      SMPS: 0.01–0.3
      Lindsley et al., 2010
      • Lindsley W.G.
      Environmental and source measurements of airborne influenza. Current research issues – personal protective equipment for healthcare workers to prevent transmission of pandemic influenza and other viral respiratory infections.
      Solid impaction (Two-stage aerosol sampler)Viral

      Influenza spp.
      <1.0
      Milton et al., 2010

      Milton DK, Fabian P, Angel M, Perez DR, McDevitt JJ. Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks swine origin H1N1: the first pandemic of the 21st Century; April 18–20, 2010; [Atlanta, Georgia].

      Unknown methodViral

      Influenza spp.
      0.05–5.0
      Expelled particle size range0.01–100<0.1–500<1.0–1250.1–125
      Key: DN: Droplet nuclei; H: Healthy; I: Infected; OPC: Optical particle counter; SI: Solid impactor; SMPS: Scanning Mobility Particle Sizer.
      a Assumed to be healthy individuals but not explicitly described in literature.
      b No size stratification was made by authors on the basis of diseased state.
      c Papineni and Rosenthal (1997) measured particles generated from breathing using optical and solid impaction methods – particles from coughing and talking were measured only by optical methods.
      Jennison et al. used high-speed photography to resolve and measure particles ≥5 μm but was unable to measure smaller particles.
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      Accurate measurement was confounded however by the limited depth of field involved, making particles outside the field of focus appear larger than they are. This study however has importantly contributed to our understanding that different respiratory activities expel different amounts of particles – specifically, while sneezing produces a greater number of particles than coughing, particles from both activities are of a similar size (a sneeze produces 40,000 – 4600 particles with 80% of these particles being smaller than 100 μm compared with coughing which produced up to few hundred particles sized between 20 and >100 μm).
      The bias in the methods used in earlier studies weighted the predominant particle size for the four natural respiratory activities towards the production of typical droplet-sized particles rather than airborne-sized particles
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      • Duguid J.P.
      The size and the duration of air-carriage of respiratory droplets and droplet-nuclei.
      • Buckland F.E.
      • Tyrrell D.A.J.
      Experiments on the spread of Colds: !. Laboratory studies on the Dispersal of nasal Secretion.
      • Heymann B.
      Ueber die Ausstreuung infectioser Tropfchen beim Husten der Phthisiker.

      Strausz W. Z Hyg. 1926;105:416 [cited by Duguid, 1946].

      • Loudon R.G.
      • Roberts R.M.
      Droplet explusion from the respiratory tract.
      with the exception of two studies
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      (Table 3): Gerone et al.
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      identified airborne-sized atomization from coughing and sneezing while Eichenwald et al. identified airborne-sized atomization from breathing.
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      Five studies
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      • Buckland F.E.
      • Tyrrell D.A.J.
      Experiments on the spread of Colds: !. Laboratory studies on the Dispersal of nasal Secretion.
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      • Eichenwald H.F.
      • Kotsevalov O.
      • Fasso L.A.
      The “Cloud Baby”: an example of bacterial-viral interaction.
      • Heymann B.
      Ueber die Ausstreuung infectioser Tropfchen beim Husten der Phthisiker.
      demonstrated that a particle size range of <1.0–500 μm was associated with the carriage of microorganisms expelled from breathing, coughing and sneezing. Despite obvious confounding by incomplete capture of all expelled particles and poor resolution of smaller particles, these early studies have consequentially promoted the belief that droplet transmission was the most dominant mode of transmission of infectious aerosols.

      Particles in the present

      More recently, impaction methods have been used less frequently while the use of charge separation, optical and time-of-flight (TOF) technologies has increased (Table 3). An additional 18 studies have attempted to determine the particle size of expelled aerosols; six studies have used impaction methods
      • Xie X.
      • Li Y.
      • Chwang A.T.Y.
      • Ho P.L.
      • Seto W.H.
      How far droplets can move in indoor environments – revisiting the Wells evaporation-falling curve.
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      • Li Y.G.
      • Chwang A.T.Y.
      • Seto W.H.
      • Ho P.L.
      • Yuen P.L.
      Understanding droplets produced by nebulisers and respiratory activities.
      • Lindsley W.G.
      Environmental and source measurements of airborne influenza. Current research issues – personal protective equipment for healthcare workers to prevent transmission of pandemic influenza and other viral respiratory infections.
      while fourteen studies have employed optical, charge separation or TOF methods alone or in combination with impaction methods.
      • Almstrand A.-C.
      • Bake B.
      • Ljungstrom E.
      • Larsson P.
      • Bredberg A.
      • Mirgorodskaya E.
      • et al.
      Effect of airway opening on production of exhaled particles.
      • Holmgren H.
      • Ljungström E.
      • Almstrand A.-C.
      • Bake B.
      • Olin A- C.
      Size distribution of exhaled particles in the range from 0.01 to 2.0 [mu]m.
      • Haslbeck K.
      • Schwarz K.
      • Hohlfeld J.M.
      • Seume J.R.
      • Koch W.
      Submicron droplet formation in the human lung.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • Mengersen K.
      • Corbett S.
      • et al.
      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
      • Xie X.
      • Li Y.
      • Chwang A.T.Y.
      • Ho P.L.
      • Seto W.H.
      How far droplets can move in indoor environments – revisiting the Wells evaporation-falling curve.
      • Fabian P.
      • McDevitt J.J.
      • DeHaan W.H.
      • Fung R.O.P.
      • Cowling B.J.
      • Chan K.H.
      • et al.
      Influenza virus in human exhaled breath: an observational study.
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      • Xie X.
      • Li Y.
      • Sun H.
      • Liu L.
      Exhaled droplets due to talking and coughing.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      • Chao C.Y.H.
      • Wan M.P.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • et al.
      Characterization of expiration air jets and droplet size distributions immediately at the mouth opening.
      • Yang S.
      • Lee G.W.M.
      • Chen C.-M.
      • Wu C.-C.
      • Yu K.-P.
      The size and concentration of droplets generated by coughing in human Subjects.
      • Edwards D.A.
      • Man J.C.
      • Brand P.
      • Katstra J.P.
      • Stone H.A.
      • Nardell E.
      • et al.
      Inhaling to mitigate exhaled bioaersols.
      • Fang M.
      • Lau A.P.S.
      • Chan C.K.
      • Hung C.T.
      • Lee T.W.
      Aerodynamic properties of biohazardous aerosols in hospitals.

      Morawska L, Johnson GR, Ristovski Z, Hargreaves M, Mengersen K, Chao C, et al., editors. Droplets expelled during human expiratory activities and their origins. Paper-1023. In: 11th International conference on indoor air quality and climate paper, Copenhagen, Denmark; 2009.

      Of the six studies that used impaction methods,
      • Xie X.
      • Li Y.
      • Chwang A.T.Y.
      • Ho P.L.
      • Seto W.H.
      How far droplets can move in indoor environments – revisiting the Wells evaporation-falling curve.
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      • Li Y.G.
      • Chwang A.T.Y.
      • Seto W.H.
      • Ho P.L.
      • Yuen P.L.
      Understanding droplets produced by nebulisers and respiratory activities.
      • Lindsley W.G.
      Environmental and source measurements of airborne influenza. Current research issues – personal protective equipment for healthcare workers to prevent transmission of pandemic influenza and other viral respiratory infections.
      two studies determined that the predominant expelled particle size was of droplet-sized particles (range 50–100 μm)
      • Xie X.
      • Li Y.
      • Sun H.
      • Liu L.
      Exhaled droplets due to talking and coughing.
      • Li Y.G.
      • Chwang A.T.Y.
      • Seto W.H.
      • Ho P.L.
      • Yuen P.L.
      Understanding droplets produced by nebulisers and respiratory activities.
      whereas three studies
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      • Lindsley W.G.
      Environmental and source measurements of airborne influenza. Current research issues – personal protective equipment for healthcare workers to prevent transmission of pandemic influenza and other viral respiratory infections.
      complemented the majority of findings from optical, TOF and charge studies
      • Almstrand A.-C.
      • Bake B.
      • Ljungstrom E.
      • Larsson P.
      • Bredberg A.
      • Mirgorodskaya E.
      • et al.
      Effect of airway opening on production of exhaled particles.
      • Holmgren H.
      • Ljungström E.
      • Almstrand A.-C.
      • Bake B.
      • Olin A- C.
      Size distribution of exhaled particles in the range from 0.01 to 2.0 [mu]m.
      • Haslbeck K.
      • Schwarz K.
      • Hohlfeld J.M.
      • Seume J.R.
      • Koch W.
      Submicron droplet formation in the human lung.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • Mengersen K.
      • Corbett S.
      • et al.
      Size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities.
      • Fabian P.
      • McDevitt J.J.
      • DeHaan W.H.
      • Fung R.O.P.
      • Cowling B.J.
      • Chan K.H.
      • et al.
      Influenza virus in human exhaled breath: an observational study.
      • Hersen G.
      • Moularat S.
      • Robine E.
      • Ghin E.
      • Corbet S.
      • Vabret A.
      Impact of health on particle size of exhaled respiratory aerosols: case-control study.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      • Yang S.
      • Lee G.W.M.
      • Chen C.-M.
      • Wu C.-C.
      • Yu K.-P.
      The size and concentration of droplets generated by coughing in human Subjects.
      • Edwards D.A.
      • Man J.C.
      • Brand P.
      • Katstra J.P.
      • Stone H.A.
      • Nardell E.
      • et al.
      Inhaling to mitigate exhaled bioaersols.
      • Fang M.
      • Lau A.P.S.
      • Chan C.K.
      • Hung C.T.
      • Lee T.W.
      Aerodynamic properties of biohazardous aerosols in hospitals.

      Morawska L, Johnson GR, Ristovski Z, Hargreaves M, Mengersen K, Chao C, et al., editors. Droplets expelled during human expiratory activities and their origins. Paper-1023. In: 11th International conference on indoor air quality and climate paper, Copenhagen, Denmark; 2009.

      which described a shift towards a predominant particle size comparable to that of airborne-sized particles (range of 0.01–≤5 μm). An exception to the latter statement is the study by Chao et al. using interferometric Mie imaging (an out-of-focus imaging method which identifies and sizes particles based on the Mie theory of light-scattering properties of spheres
      • Glover A.R.
      • Skippon S.M.
      • Boyle R.D.
      Interferometric laser imaging for droplet sizing: a method for droplet-size measurement in sparse spray systems.
      ) which the investigators acknowledged that the technique is limited in its capacity to detect submicron particles.
      • Chao C.Y.H.
      • Wan M.P.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • et al.
      Characterization of expiration air jets and droplet size distributions immediately at the mouth opening.
      The sixth impaction study examined impacted particles from breathing using transmission electron microscopy and found the most predominant particle size was >1.0 μm but were unable to define an upper size limit.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      Interestingly, five studies determined expelled particle size to be either side of the 5 μm delineation for airborne and droplet transmission.
      • Xie X.
      • Li Y.
      • Chwang A.T.Y.
      • Ho P.L.
      • Seto W.H.
      How far droplets can move in indoor environments – revisiting the Wells evaporation-falling curve.
      • Hersen G.
      • Moularat S.
      • Robine E.
      • Ghin E.
      • Corbet S.
      • Vabret A.
      Impact of health on particle size of exhaled respiratory aerosols: case-control study.
      • Chao C.Y.H.
      • Wan M.P.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • et al.
      Characterization of expiration air jets and droplet size distributions immediately at the mouth opening.
      • Yang S.
      • Lee G.W.M.
      • Chen C.-M.
      • Wu C.-C.
      • Yu K.-P.
      The size and concentration of droplets generated by coughing in human Subjects.

      Morawska L, Johnson GR, Ristovski Z, Hargreaves M, Mengersen K, Chao C, et al., editors. Droplets expelled during human expiratory activities and their origins. Paper-1023. In: 11th International conference on indoor air quality and climate paper, Copenhagen, Denmark; 2009.

      The size range found from TOF devices are not unexpected as these devices are more efficient at enumerating particles in the range of 0.7–10 μm and have reduced efficiency for enumerating particles beyond.
      • Kinney P.D.
      • Pui D.Y.H.
      Inlet efficiency study for the TSI aerodynamic particle sizer.
      • Armendariz A.
      • Leith D.
      Concentration measurement and counting efficiency for the aerodynamic particle sizer 3320.
      • Peters T.M.
      • Leith D.
      Concentration measurement and counting efficiency of the aerodynamic particle sizer 3321.
      Furthermore, any deviation from a spherical particle shape will affect the acceleration of the particle through the measurement zone, resulting in either under-sizing if particles are non-spherical or over estimating particle size if particles are elongated.
      • Marshall I.A.
      • Mitchell J.P.
      The behaviour of spheroidal particles in time-of-flight aerodynamic particle sizers.
      Another issue to consider is that the output parameters from different sizing technologies are also different; for examples as detailed in Table 4, impaction and TOF devices measure the aerodynamic diameters of particles whereas devices that measure charge separation measure the mobility diameter. These different output measures confound comparison of particle size.
      Table 4Technologies used to measure expelled particles for size.
      TechnologyPrinciples of measurementOutput parameterExamples
      Solid impactionMechanical impaction onto a solid surface; device may separate particle by an inertial (size) differential caused by size or may require downstream microscopy to determine sizeAerodynamic diameter (Optical diameter, if microscopy is used)Seive sampler, Andersen sampler, Glass slide (with microscopy)
      Liquid impactionMechanical impaction into liquid; device separate particles by an inertial (size) differential caused by sizeAerodynamic diameterLiquid impinger
      Electrical impactionCharges particles to create an inertial differential. Particles impact on different impactor plates according to their charge. Particles on each plate are then enumeratedAerodynamic diameterElectrical low pressure impactor
      OpticalRelies upon on the light-scattering properties of particles to change with changes in sizeOptical diameterOptical particle counter,

      Interferonic Mie imaging
      High-speed photographyMeasurement of particles taken in sharp focus at high speedImage diameterHigh-speed photography
      Time-of-flightEmits a laser beam which particles pass through. Obstruction of the laser beam caused by the particles is detectedAerodynamic diameterAerodynamic particle size
      Charge separationCharges particles and then separates particles according to how fast particles move across an electrical fieldMobility diameterScanning mobility particle sizer
      Despite the inherent weaknesses of TOF technology and interferometric Mie imaging, these recent findings suggest that the burden of infectious disease carriage lies with the airborne-sized particles. Yet, very few published studies, contemporary or otherwise, have attempted to make a clear association between carriage of specific pathogens and particle size.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      • Lindsley W.G.
      Environmental and source measurements of airborne influenza. Current research issues – personal protective equipment for healthcare workers to prevent transmission of pandemic influenza and other viral respiratory infections.

      Milton DK, Fabian P, Angel M, Perez DR, McDevitt JJ. Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks swine origin H1N1: the first pandemic of the 21st Century; April 18–20, 2010; [Atlanta, Georgia].

      This is a limited evidence for a definitive understanding of whether pathogen is carried by a certain particle size or if carriage occurs indiscriminate of size or pathogen type. Furthermore, evident in two recent studies,
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      as with one of the older studies,
      • Gerone P.J.
      • Couch R.B.
      • Keefer G.V.
      • Douglas R.G.
      • Derrenbacher E.B.
      • Knight V.
      Assessment of experimental and natural viral aerosols.
      is the misconception that one particle is representative of one microorganism. This may not necessarily be the case. Analogous to the cultivation of colonies of microorganisms,
      • Prescott L.M.
      • Harley J.P.
      • Klein D.A.
      Microbial growth. Microbiology.
      one particle may be representative of one microbe or an aggregation of microbes. Furthermore, particles generated in one respiratory event may not all be generated from the same site in the respiratory tract. While this does not afflict the delineation of particle size, it does infer that the establishment of infection may be affected by the factors of particle size, sites of atomization and pathogen load of particles.

      Factors that influence particle size

      Another point of difference raised by more recent studies that investigated multiple respiratory activities, similar-sized particles were generated by different activities.
      • Xie X.
      • Li Y.
      • Sun H.
      • Liu L.
      Exhaled droplets due to talking and coughing.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      • Li Y.G.
      • Chwang A.T.Y.
      • Seto W.H.
      • Ho P.L.
      • Yuen P.L.
      Understanding droplets produced by nebulisers and respiratory activities.
      • Chao C.Y.H.
      • Wan M.P.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • et al.
      Characterization of expiration air jets and droplet size distributions immediately at the mouth opening.
      • Edwards D.A.
      • Man J.C.
      • Brand P.
      • Katstra J.P.
      • Stone H.A.
      • Nardell E.
      • et al.
      Inhaling to mitigate exhaled bioaersols.
      • Morawska L.
      Droplet fate in indoor environments, or can we prevent the spread of infection?.
      Such results may be due to the capabilities of the sizing devices used, however it is prudent to also consider the extraneous or host factors that may drive such similar-sized particles to become vehicles of droplet transmission or vehicles of airborne transmission (Table 5). Further, we now consider the following factors in more detail: 1) relative humidity and evaporation, 2) aggregation and 3) mucus properties.
      Table 5Factors determining how particles facilitate aerosolised transmission.
      VariableEffect
      Relative humidityIncreases in relative humidity slows down evaporation, reducing its effects on particle size
      • Wells W.F.
      On airborne infection: study II. Droplets and droplet nuclei.
      • Schaffer F.L.
      • Soergel M.E.
      • Straube D.C.
      Survival of airborne influenza virus: effects of propagating host, relative humidity and composition of spray Fluids.
      • Lowen A.C.
      • Mubareka S.
      • Steel J.
      • Palese P.
      Influenza virus transmission is dependent on relative humidity and temperature.
      • Hemmes J.H.
      • Winkler K.C.
      • Kool S.M.
      Virus Survival as a Seasonal factor in influenza and Poliomyelitis.
      Aggregation (Particle concentration per expulsion)Promotes particle aggregation and increases particle size
      • Fiegel J.
      • Clarke R.
      • Edwards D.A.
      Airborne infectious disease and the suppression of pulmonary bioaerosols.
      Pre-exposure to saline in the airwaysIncreases particle size and reduces particle number
      • Edwards D.A.
      • Man J.C.
      • Brand P.
      • Katstra J.P.
      • Stone H.A.
      • Nardell E.
      • et al.
      Inhaling to mitigate exhaled bioaersols.
      • Zayas G.
      • Dimitry J.
      • Zayas A.
      • O’Brien D.
      • King M.
      A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion.
      Disease stateInduces changes to mucus composition and increases particle size and number
      • Hersen G.
      • Moularat S.
      • Robine E.
      • Ghin E.
      • Corbet S.
      • Vabret A.
      Impact of health on particle size of exhaled respiratory aerosols: case-control study.
      • Zayas G.
      • Dimitry J.
      • Zayas A.
      • O’Brien D.
      • King M.
      A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion.

      Evaporation and relative humidity

      Wells reported that a water particle of 170 μm diameter generated in dry air (0% water saturation) will fall 2 m in 3 s and will evaporate completely upon settlement to the ground.
      • Wells W.F.
      On airborne infection: study II. Droplets and droplet nuclei.
      Under the same conditions, it is also predicted that particles larger than ≥170 μm diameter will fall in the same distance more rapidly while smaller particles will take longer to settle and may remain suspended in the air for a prolonged period, and are likely to completely evaporate. The Wells’ evaporation curve is conceptually important for understanding particle fate however the extent and speed of evaporation may be further limited by the presence of hygroscopic salts within expelled particle.
      • Nicas M.
      • Nazaroff W.W.
      • Hubbard A.
      Toward understanding the risk of secondary airborne infection: emission of respirable pathogens.
      Since the first publication of the Well’s evaporation curve, other studies have demonstrated it to be incorrect in its details, identifying a comparatively smaller critical particle size (the particle size when the time-of total evaporation equals the total time-of falling 2 m)
      • Xie X.
      • Li Y.
      • Chwang A.T.Y.
      • Ho P.L.
      • Seto W.H.
      How far droplets can move in indoor environments – revisiting the Wells evaporation-falling curve.
      and longer settling times.
      • Wan M.P.
      • Chao C.Y.H.
      Transport characteristics of expiratory droplets and droplet nuclei in indoor environments with different Ventilation airflow patterns.
      • Nichol K.
      • Bigelow P.
      • O’Brien-Pallas L.
      • McGeer A.
      • Manno M.
      • Holness D.L.
      The individual, environmental, and organizational factors that influence nurses’ use of facial protection to prevent occupational transmission of communicable respiratory illness in acute care hospitals.
      Also reported by Wells is the effect of relative humidity – where particles are expected to reach equilibrium size slower at higher humidity. Nicas et al. also further comments on the role of relative humidity, indicating that it affects both the rate of evaporation and the equilibrium (final) size of the particle.
      • Nicas M.
      • Nazaroff W.W.
      • Hubbard A.
      Toward understanding the risk of secondary airborne infection: emission of respirable pathogens.
      Relative humidity may also play a role in affecting particle trajectory.
      • Schaffer F.L.
      • Soergel M.E.
      • Straube D.C.
      Survival of airborne influenza virus: effects of propagating host, relative humidity and composition of spray Fluids.
      • Lowen A.C.
      • Mubareka S.
      • Steel J.
      • Palese P.
      Influenza virus transmission is dependent on relative humidity and temperature.
      • Hemmes J.H.
      • Winkler K.C.
      • Kool S.M.
      Virus Survival as a Seasonal factor in influenza and Poliomyelitis.
      In particular, increases in vertical and lateral particle movement have previously been associated with decreased relative humidity.
      • Wells W.F.
      On airborne infection: study II. Droplets and droplet nuclei.
      • Xie X.
      • Li Y.
      • Chwang A.T.Y.
      • Ho P.L.
      • Seto W.H.
      How far droplets can move in indoor environments – revisiting the Wells evaporation-falling curve.

      Aggregation

      Particles may grow after expulsion by aggregation with other particles if released in high concentrations.
      • Verreault D.
      • Moineau S.
      • Duchaine C.
      Methods for sampling of airborne viruses.
      This would predispose an expelled particle that begins its existence as a vehicle of airborne transmission to then shift to behave as a vehicle of droplet transmission.

      Mucus properties

      From the 26 studies investigating particle size (Table 3), only thirteen have sized particles from infected individuals. For the purposes of better understanding disease transmission dynamics, particles from healthy individuals may have limited value. In the one study that compared particle sizes from both healthy and infected individuals,
      • Hersen G.
      • Moularat S.
      • Robine E.
      • Ghin E.
      • Corbet S.
      • Vabret A.
      Impact of health on particle size of exhaled respiratory aerosols: case-control study.
      it was found that particles from infected individuals were larger than those from healthy individuals. Disease-induced changes, such as increases in mucus composition, quantity and viscosity, have also been observed,
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      • Kozlova I.
      • Vanthanouvong V.
      • Marie J.
      • Roomans G.M.
      Composition of airway surface liquid determined by X-ray microanalysis.
      • Vanthanouvong V.
      • Kozlova I.
      • Johannesson M.
      • Nääs E.
      • Nordvall S.L.
      • Dragomir A.
      • et al.
      Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.
      which may suggest that the increase in size is directly related to increases in mucus viscosity. Differences in mucus composition at the mucus–air interface may be accountable for the inter-individual variability observed in studies of different respiratory activities.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      • Xie X.
      • Li Y.
      • Sun H.
      • Liu L.
      Exhaled droplets due to talking and coughing.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      • Fairchild C.I.
      • Stampfer J.F.
      Particle concentration in exhaled breath.

      Current research gaps

      Improved understanding of the behaviour of particles in the transmission of aerosolised disease has the capacity to stimulate the update of current infection control precautions.
      Firstly, the relationship between particle size and particle carriage needs to be clearly understood if infection control policies are to utilise a size demarcation, such as 5 μm, to classify modes of transmission. While there is evidence describing the carriage of Mycobacterium tuberculosis (about 3.0 μm in size) in particles ≤3.3 μm, few other pathogens have been studied in such detail. Specifically, the size of the particles carrying respiratory viruses, which are 100-fold smaller than a M. tuberculosis bacilli, have only been recently determined for influenza.
      • Lindsley W.G.
      Environmental and source measurements of airborne influenza. Current research issues – personal protective equipment for healthcare workers to prevent transmission of pandemic influenza and other viral respiratory infections.

      Milton DK, Fabian P, Angel M, Perez DR, McDevitt JJ. Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks swine origin H1N1: the first pandemic of the 21st Century; April 18–20, 2010; [Atlanta, Georgia].

      Other viruses, such as rhinoviruses, have not been examined and may be carried in particles differently due to differences in shedding and inactivation patterns.
      • Atkinson M.P.
      • Wein L.M.
      Quantifying the routes of transmission for pandemic influenza.
      Furthermore the effectiveness of these size-based precautions need to be evaluated to ensure they are advocating protectiveness. Without a strong evidence base, the effectiveness of infection control policies based on a size demarcation should remain contentious.
      Secondly, improved understanding particle behaviour may illuminate the ‘super-spreaders’ of respiratory diseases. ‘Super-spreaders’ are defined as those individuals who infect a large number of contacts.
      • Riley S.
      • Fraser C.
      • Donnelly C.A.
      • Ghani A.C.
      • Abu-Raddard L.J.
      • Hedley A.J.
      • et al.
      Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health Intervention.
      • Glass L.M.
      • Glass R.J.
      Social contact networks for the spread of pandemic influenza in children and teenagers.
      ‘Super-spreaders’ were responsible for infecting large numbers of susceptible individuals during the Severe Acute Respiratory Syndrome outbreak
      • Small M.
      • Tse C.K.
      • Walker D.M.
      Super-spreaders and the rate of transmission of the SARS virus.
      • Wang S.H.
      • Li Y.M.
      • Sun B.C.
      • Zhang S.W.
      • Zhao W.H.
      • Wei M.T.
      • et al.
      The SARS outbreak in a general hospital in Tianjin, China – the case of super-spreader.
      • Abdullah A.S.M.
      • Tomlinson B.
      • Cockram C.S.
      • Neil Thomas G.
      Lessons from the Severe acute respiratory Syndrome outbreak in Hong Kong.
      and have been identified as possible sources in influenza epidemics.
      • Glass L.M.
      • Glass R.J.
      Social contact networks for the spread of pandemic influenza in children and teenagers.
      Some healthy individuals make more particles than others when they breathe, cough, sneeze or talk
      • Holmgren H.
      • Ljungström E.
      • Almstrand A.-C.
      • Bake B.
      • Olin A- C.
      Size distribution of exhaled particles in the range from 0.01 to 2.0 [mu]m.
      • Haslbeck K.
      • Schwarz K.
      • Hohlfeld J.M.
      • Seume J.R.
      • Koch W.
      Submicron droplet formation in the human lung.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
      • Xie X.
      • Li Y.
      • Sun H.
      • Liu L.
      Exhaled droplets due to talking and coughing.
      • Papineni R.S.
      • Rosenthal F.S.
      The size distribution of droplets in the exhaled breath of healthy human Subjects.
      • Fairchild C.I.
      • Stampfer J.F.
      Particle concentration in exhaled breath.
      and that this may be mirrored with a propensity to be a super-spreader and produce an increased number of pathogens to spread infection during illness. Edwards et al. suggest that this effect may be due to the surface properties of the liquids that line the airways.
      • Edwards D.A.
      • Man J.C.
      • Brand P.
      • Katstra J.P.
      • Stone H.A.
      • Nardell E.
      • et al.
      Inhaling to mitigate exhaled bioaersols.
      Determining why certain individuals have the proclivity to make more particles than others and what factors contribute to this proclivity is important for limiting disease spread at the level of the individual and needs to be further investigated.
      Possibly the most important unanswered question is why some expelled particles during any respiratory activity carry pathogens and why some do not. Evidence from computer models suggest airborne-sized particles are unlikely to carry pathogen
      • Atkinson M.P.
      • Wein L.M.
      Quantifying the routes of transmission for pandemic influenza.
      – this is in contrast to the limited evidence from particle size measurements suggesting possible airborne carriage of both bacterial and viral pathogens.
      • Wainwright C.E.
      • France M.W.
      • O’Rourke P.
      • Anuj S.
      • Kidd T.J.
      • Nissen M.D.
      • et al.
      Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis.
      • Fennelly K.P.
      • Martyny J.W.
      • Fulton K.T.
      • Orme I.M.
      • Cave D.M.
      • Heifets L.B.
      Cough-generated Aerosols of Mycobacterium tuberculosis.
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      • Lindsley W.G.
      Environmental and source measurements of airborne influenza. Current research issues – personal protective equipment for healthcare workers to prevent transmission of pandemic influenza and other viral respiratory infections.
      Further examination of pathogen carriage needs to clarify whether carriage is a function of the particle size, the site of infection, the site of particle generation (which may be different to site of infection), the concentration of the pathogen in the mucus, changes in the nature of the mucus, the virulence of the pathogen itself. Furthermore, are the particles that carry virus similar to those that carry bacteria and fungi? These questions are of paramount significance for understanding the physiological niches pathogens occupy in the human body and during disease transmission. Research efforts needs to be directed towards examining particle ecology and determining the sites of expelled particle generation during different respiratory activities.

      Conclusions

      We conclude from our review, that:
      • Determining the particle size that carries respiratory pathogens has important implications for the use of droplet and airborne infection control measures
      • Infectious particles sized less than 10 μm have more serious health implications as they are able to penetrate into the lower respiratory tract to establish infection
      • Simultaneous particle generation from different respiratory activities may occur but may not be apparent
      • The probability of the propagation of microbial respiratory disease is dependent on the characteristics of clinical disease and the type and presence of a pathogen.
      • Evidence has shown particles generated from respiratory activities range from 0.01 up to 500 μm, with a particle size range of 0.05 to 500 μm associated with infection
      • Few studies to date have directly associated specific pathogen carriage with a particular size range
      • After expulsion, particle size is influenced by host and extraneous factors which may determine how it facilitates aerosolised transmission.
      Despite recent evidence
      • Fabian P.
      • McDevitt J.J.
      • DeHaan W.H.
      • Fung R.O.P.
      • Cowling B.J.
      • Chan K.H.
      • et al.
      Influenza virus in human exhaled breath: an observational study.
      • Fang M.
      • Lau A.P.S.
      • Chan C.K.
      • Hung C.T.
      • Lee T.W.
      Aerodynamic properties of biohazardous aerosols in hospitals.
      • Lindsley W.G.
      • Blanchere F.M.
      • Davis K.A.
      • Pearce T.A.
      • Fisher M.A.
      • Khakoo R.
      • et al.
      Distribution of airborne influenza virus and respiratory syncytial virus in an urgent care medical Clinic.
      • Blachere F.M.
      • Lindsley W.G.
      • Pearce T.A.
      • Anderson S.E.
      • Fisher M.
      • Khakoo R.
      • et al.
      Measurement of airborne influenza virus in a hospital emergency department.
      suggesting the role of aerosol transmission has been severely underestimated in the past, the lack of strong observational data for the trajectory of individual respiratory pathogens, especially for viruses, expelled from different respiratory activities discourages updating of the current infection control (5 μm – 1 m) paradigm.
      • Roy C.J.
      • Milton D.K.
      Airborne transmission of communicable infection – the elusive pathway.
      This may be in light of recent computer models which suggest that while airborne transmission can occur, very few airborne-sized particles can carry pathogen.
      • Atkinson M.P.
      • Wein L.M.
      Quantifying the routes of transmission for pandemic influenza.
      Regardless of the complexities and limitations of sizing particles and the contention of size cut-offs, it remains that particles have been observed to occupy a size range between 0.05 and 500 μm. Even using the conservative cut-off of 10 μm, rather than the 5 μm to define between airborne and droplet transmission, this size range indicates that particles do not exclusively disperse by airborne transmission or via droplet transmission but rather avail of both methods simultaneously. This suggestion is further supported by the simultaneous detection of both large and small particles.
      • Jennison M.W.
      Atomizing of mouth and nose secretions into the air as revealed by high-speed photography.
      • Hersen G.
      • Moularat S.
      • Robine E.
      • Ghin E.
      • Corbet S.
      • Vabret A.
      Impact of health on particle size of exhaled respiratory aerosols: case-control study.
      • Chao C.Y.H.
      • Wan M.P.
      • Morawska L.
      • Johnson G.R.
      • Ristovski Z.D.
      • Hargreaves M.
      • et al.
      Characterization of expiration air jets and droplet size distributions immediately at the mouth opening.
      • Yang S.
      • Lee G.W.M.
      • Chen C.-M.
      • Wu C.-C.
      • Yu K.-P.
      The size and concentration of droplets generated by coughing in human Subjects.

      Morawska L, Johnson GR, Ristovski Z, Hargreaves M, Mengersen K, Chao C, et al., editors. Droplets expelled during human expiratory activities and their origins. Paper-1023. In: 11th International conference on indoor air quality and climate paper, Copenhagen, Denmark; 2009.

      In line with these observations and logic, current dichotomous infection control precautions should be updated to include measures to contain both modes of aerosolised transmission. This may require airborne precautions to be used when at risk of any aerosolised infection, as airborne precautions are considered as a step-up from droplet precautions. Further elucidation of particle size and the dynamics of particles in disease transmission provides the opportunity for increased understanding of the ecological niches of respiratory pathogens and the development of improved measures to counter the spread of communicable respiratory diseases.

      Acknowledgement

      The authors would like to acknowledge the contribution of Dr Jenna Iwasenko for the provision of German translations of the earlier literature.

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