Myth Buster: Is nebulisation an aerosol generating procedure?


Dr. Krishna Prasad G
MBBS, DNB (EM), MRCEM, MNAMS

This question has popped up multiple times in the current line of work dealing with COVID 19-suspect patients. The available PPE’s are meant to give protection against such virus embedded aerosols since COVID-19 is said to be spread mainly by droplet transmission. So, I thought I will go through the available literature and get more information on this topic.

So, Question number 1 – What is an aerosol and how is it generated?

An aerosol (abbreviation of "aero-solution") is a suspension of fine solid particles or liquid droplets in air or another gas [1]. The particles are released under pressure. Aerosol generating procedures and their effects on health care workers is a poorly studied topic. In medical context, Aerosol-generating procedures (AGP) are procedures that stimulate coughing and promote the generation of aerosols [2]. A single cough can generate up to 3000 droplets [3]. Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. This cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections. Coughing causes both mucus aerosolization and droplet generation. [4]. Toilet flushing is also well-known as a source of aerosols [5].

Question number 2 - How is COVID-19 transmitted?

The virus is ‘thought’ to spread mainly from person-to-person.

  •        Between people who are in close contact with one another (within about 6 feet).
  •        Through respiratory droplets produced when an infected person coughs or sneezes.

These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs [6].

Other modes of transmission including vertical and faeco-oral are also proposed [7].

Infection prevention, medical, and public health professionals should be communicating to everyone that the exact modes of transmission for SARS-CoV-2—the technical name of the virus that causes COVID-19—are unknown. There are no studies, yet, to support any particular mode of transmission over another.

The WHO says, "Based on the available evidence, the COVID-19 virus is transmitted between people through close contact and droplets, not by airborne transmission." The WHO derived its COVID-19 guidance from its MERS guidance, China's experience with COVID-19, and WHO experience with SARS and MERS. Droplet transmission is usually defined as "respiratory droplets carrying infectious pathogens [that] transmit infection when they travel directly from the respiratory tract of the infectious individual to susceptible mucosal surfaces of the recipient, generally over short distances, necessitating facial protection."

The Chinese Center for Disease Control and Prevention, which has dealt with by far more COVID-19 cases than any other agency, says that COVID-19 transmission occurs primarily by respiratory droplets and close contact, with the "possibility of aerosol transmission in a relatively closed environment for a long time exposure to high concentrations of aerosols."

Underlying the CDC and WHO statements about transmission is this: Inhalation of particles near the source may be an important mode of transmission [8].

Question number 3 – What is the difference between a droplet and an aerosol?

NIOSH defines aerosols as a suspension of tiny particles or droplets in the air. Aerosol transmission has been defined as person-to-person transmission of pathogens through the air by means of inhalation of infectious particles. Particles up to 100 μm in size are considered inhalable (inspirable). These aerosolized particles are small enough to be inhaled into the oronasopharynx, with the smaller, respirable size ranges (eg, < 10 μm) penetrating deeper into the trachea and lung.  Aerosols are emitted not only by "aerosol-generating procedures," but may also be transmitted whenever an infected person coughs, sneezes, talks, or exhales. Pathogens transmitted by respiratory aerosols can travel short or long range from the source depending on the size and shape of the particles, the initial velocity (eg, cough vs exhalation), and environmental conditions (eg, humidity, airflow) [9].

The virus that causes COVID-19 is approximately 0.125 micron (125 nanometers) in diameter [10].

In simple terms, an aerosol can generate droplets of different sizes. Larger droplets travel short distances and settle down. Smaller droplets travel long distances and disperse.

But, contrary to popular belief, the larger particles (5 to 15 micrometers [µm]) will not immediately drop to the ground but will remain airborne for several minutes. Smaller particles (less than 5 µm) will remain in the air for many minutes or even hours [8].

Question number 4 – What are the implications?

Healthcare workers, whose work brings them close to more people with more severe symptoms in relatively enclosed spaces, are at more risk than the general public at being exposed to a dose of infectious particles that could lead to infection.

The Wuhan, China, experience supports the likelihood of close-range aerosol transmission. After initially receiving and treating COVID-19 patients in the existing healthcare system and experiencing healthcare worker infections, China deployed a tiered hospital model very similar to that used for Ebola patients in the United States. Patients with critical or severe symptoms were moved into designated wards or hospitals while those with mild symptoms were cohorted in temporary hospitals in repurposed buildings. Healthcare workers wore full protection, including a gown, head-covering, N95 filtering face piece respirators, eye protection, and gloves. A recent non-peer-reviewed report from Germany supports aerosol transmission of COVID-19 at close range [8].

Question number 5 – What are aerosol generating procedures?

Aerosol-generating procedures (AGP) are procedures that stimulate coughing and promote the generation of aerosols [11].

Procedures that are believed to generate aerosols and droplets as a source of respiratory pathogens include positive pressure ventilation (BiPAP and CPAP), endotracheal intubation, airway suction, high frequency oscillatory ventilation, tracheostomy, chest physiotherapy, nebulizer treatment, sputum induction, and bronchoscopy. Although those procedures are known to stimulate coughing and to promote the generation of aerosols, their risk of transmission of infection is not known with certainty. It is worth emphasizing that the scientific evidence for the creation of aerosols associated with these procedures, the burden of potential viable microbes within the created aerosols, and the mechanism of transmission to the host have not been well studied. It is unclear whether these procedures pose a higher risk of transmission and whether HCWs caring for patients undergoing the aerosol generating procedures are at higher risk of contracting the diseases compared to HCWs caring for patients not undergoing these procedures [2].

Question number 6 – What is the available literature regarding nebulisation is an aerosol generating procedure?

Loeb et al studied the factors that predispose health care workers from SARS in Toronto. Relative Risk was more than 1 in the following procedures: intubation, suctioning before intubation, nebulizer treatment, manipulation of oxygen mask, manual ventilation, manipulation of BiPAP mask etc. Even though, there was no statistical significance (p value 0.09) in regarding to nebulizer treatment, it is worth to note that the study cohort was small [12].

In another study during the SARS outbreak, risk factors that carried higher risk included presence in the room during fiberoptic intubation (OR = 2.79, p = .004) or ECG (OR = 3.52, p = .002), unprotected eye contact with secretions (OR = 7.34, p = .001), patient APACHE II score ≥20 (OR = 17.05, p = .009) and patient Pa02/Fi02 ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission. Number of cases reported was zero among health care workers exposed to cases during nebulisation therapy [13].

In a literature review published by NHS Scotland (Published November 2019), it is mentioned that nebulisation does not result in an increased risk of aerosols. During nebulisation, the aerosols produced are derived from the fluid in the nebuliser chamber and not from the patient. This conclusion is made from two studies, namely:
  1. Tran K, Cimon K, Severn M, et al. Aerosol generating procedures (AGP) and risk of transmission of acute respiratory diseases (ARD): A systematic review. PloS One 2012; 7. Conference Abstract.
  2. Simonds A, Hanak A, Chatwin M, et al. Evaluation of droplet dispersion during noninvasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections. Health Technology Assessment 2010; 14: 131-172. DOI: 10.3310/hta14460-02.



But at the same time, the same literature review mentions that, given the extremely limited volume and quality of studies available this hierarchy should be used for academic purposes only and not for clinical decision making [14].

Final comments

Nebulisation is a no longer considered an aerosol generating procedure, which means it is a procedure that does not stimulate coughing [14]. But if a patient who is already coughing due to any reason including a COVID-19 infection, it can involve aerosol and droplet generation from the patient’s lungs, irrespective of using nebuliser or not.

A cough is typically characterized by inhalation to a high lung volume, closure of the glottis, an increase in intrathoracic pressure, a sudden opening of the glottis, and a high initial peak in outward air flow followed by a gradual decrease. After exiting the mouth, the cough air flow forms a jet that gradually widens and then dissipates. During coughs, large amounts of aerosol particles from the respiratory tract can be carried into the environment. The aerosols produced during coughing and sneezing are reported to cover a broad size range, usually spanning the detection limits of the measurement technique used, and the amount of aerosol produced varies greatly from person to person.

The sizes of cough-generated aerosol particles have a substantial impact on their behavior. Current infection control guidelines distinguish between “droplet precautions,” which are needed for diseases thought to spread primarily by larger spray droplets, and “airborne precautions,” needed for diseases that spread via small aerosols. Large droplets (greater than ~50 µm) are primarily affected by gravity; they follow a ballistic trajectory and impact on surfaces or fall onto surfaces within a meter of the source. Intermediate-sized droplets (~10–50 µm) can deposit by impaction but can also be carried further from the source by the cough air flow and can travel 2 m or more before settling. Small droplets (less than ~10 µm) are much less prone to impaction or settling; they can remain airborne for an extended time and be spread throughout a room by air currents, especially after drying [15].

For nebulisation, precautions include [11]:
  •  Put patient in a single well ventilated room.
  • Use adequate PPE.

References:

  1. Internet - https://en.wikipedia.org/wiki/Aerosol
  2. Journal - Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PLoS One. 2012;7(4):e35797. doi: 10.1371/journal.pone.0035797. Epub 2012 Apr 26. PMID: 22563403; PMCID: PMC3338532.
  3. Internet - https://www.bbc.com/future/article/20200317-covid-19-how-long-does-the-coronavirus-last-on-surfaces
  4. Journal - Zayas, G., Chiang, M.C., Wong, E. et al. Cough aerosol in healthy participants: fundamental knowledge to optimize droplet-spread infectious respiratory disease management. BMC Pulm Med 12, 11 (2012). https://doi.org/10.1186/1471-2466-12-11
  5. Journal - Johnson DL, Mead, KR, Lynch RA, et al. Lifting the lid on toilet plume aerosol: a literature review with suggestions for future research. Am J Infect Control 2013 Mar;41(3):254-58
  6. Internet - https://www.cdc.gov/coronavirus/2019-ncov/prepare/transmission.html
  7. Internet - https://www.the-scientist.com/news-opinion/how-covid-19-is-spread-67143
  8. Internet - http://www.cidrap.umn.edu/news-perspective/2020/03/commentary-covid-19-transmission-messages-should-hinge-science
  9. Internet - https://www.medscape.com/viewarticle/741245_3
  10. Journal - Fisher, D., Heymann, D. Q&A: The novel coronavirus outbreak causing COVID-19. BMC Med 18, 57 (2020). https://doi.org/10.1186/s12916-020-01533-w
  11. Internet - https://www.hpsc.ie/a-z/respiratory/influenza/seasonalinfluenza/infectioncontroladvice/File,3625,en.pdf
  12. Journal - Loeb M, McGeer A, Henry B, Ofner M, Rose D, Hlywka T, Levie J, McQueen J, Smith S, Moss L, Smith A, Green K, Walter SD. SARS among critical care nurses, Toronto. Emerg Infect Dis. 2004 Feb;10(2):251-5. doi: 10.3201/eid1002.030838. PMID: 15030692; PMCID: PMC3322898.
  13. Journal - Raboud J, Shigayeva A, McGeer A, Bontovics E, Chapman M, Gravel D, Henry B, Lapinsky S, Loeb M, McDonald LC, Ofner M, Paton S, Reynolds D, Scales D, Shen S, Simor A, Stewart T, Vearncombe M, Zoutman D, Green K. Risk factors for SARS transmission from patients requiring intubation: a multicentre investigation in Toronto, Canada. PLoS One. 2010 May 19;5(5):e10717. doi: 10.1371/journal.pone.0010717. PMID: 20502660; PMCID: PMC2873403.
  14. Internet - https://hpspubsrepo.blob.core.windows.net/hps-website/nss/2893/documents/1_tbp-lr-agp-v1.pdf
  15. Journal - Lindsley WG, Reynolds JS, Szalajda JV, Noti JD, Beezhold DH. A Cough Aerosol Simulator for the Study of Disease Transmission by Human Cough-Generated Aerosols. Aerosol Sci Technol. 2013;47(8):937-944. doi: 10.1080/02786826.2013.803019. Epub 2013 May 13. PMID: 26500387; PMCID: PMC4615563.



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