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Beyond asthma and chronic obstructive pulmonary disease (COPD), inhalation therapy is a mainstay in the management of bronchiectasis, cystic fibrosis, and pulmonary artery hypertension. Several US Food and Drug Administration off-label indications for inhalational medications include hypoxia secondary to acute respiratory distress syndrome (ARDS) and intraoperative and postoperative pulmonary hypertension during and following cardiac surgery, respectively.1-11 Therapeutic delivery of aerosols to the lung may be provided via nebulization, pressurized metered-dose inhalers (pMDI), and other devices (eg, dry powder inhalers, soft-mist inhalers, and smart inhalers).12 The most common aerosolized medications given in the clinical setting are bronchodilators.12
Product selection is often guided by practice guidelines (Table 1), consideration of the formulation’s advantages and disadvantages (Table 2), and/or formulary considerations. For example, current guidelines for COPD state that there is no evidence for superiority of nebulized bronchodilator therapy over handheld devices in patients who can use them properly.2 Due to equivalence, nebulized formulations are commonly used in hospitals, emergency departments (EDs) and ambulatory clinics based on the drug’s unit cost. In contrast, a pMDI is often more cost-effective for use in ambulatory patients who are administering multiple doses from the same canister.
The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend droplet and contact precautions for all patients suspected or diagnosed with novel coronavirus-19 (COVID-19).13,14 Airborne precautions must be applied when performing aerosol-generating medical procedures (AGMPs), including but not limited to, open suctioning of the respiratory tract, intubation, bronchoscopy, and cardiopulmonary resuscitation (CPR). Data from the severe acute respiratory syndrome (SARS-CoV) epidemic suggest that nebulization of medication is also an AGMP.15-17
Institutions must ensure that their health care workers (HCWs) are wearing appropriate personal protective equipment (PPE) including gloves, long-sleeved gowns, eye protection, and fit-tested particulate respirators (N95 mask) for airborne procedures and are carefully discarding PPE after use.13,14 Due to severe shortages in available respirators in the US supply chain, the CDC has temporarily modified WHO recommendations. Face masks are now an acceptable alternative to protect HCWs from splashes and sprays from procedures not likely to generate aerosols and for cleaning of rooms, although there is no evidence to support this decision.
Internationally, HCWs are falling ill with COVID-19. Data from Italy and Spain show that about 9% to 13% of these countries’ cases are HCWs.18,19 Within the US, the Ohio health department reports approximately 16% of cases are HCWs.20 It is possible that 20% of frontline HCWs will become infected.21 Evolving laboratory research shows that COVID-19 remains viable in aerosols for up to 3 hours postaerosolization, thus making aerosol transmission plausible.22 Nebulizers convert liquids into aerosols and during dispersal may potentially cause secondary inhalation of fugitive emissions.23 Since interim CDC infection control guidance is to allow only essential personnel to enter the room of patients with COVID-19, many facilities will rely on their frontline nursing staff to clean and disinfect high-touch surfaces following routine care activities.24
Achieving adequate fomite disinfection following viral aerosolization may pose a significant problem for any patient receiving scheduled doses of nebulized medications. Additionally, for personnel who clean rooms following intermittent drug nebulization while wearing PPE that includes a face mask, protection from aerosolized virus may be inadequate. Subsequently, fugitive emissions from nebulized medications may potentially contribute to both nosocomial COVID-19 transmission and viral infections in the medical staff until proven otherwise by studies conducted outside of the laboratory. Prevention of infection in the medical staff is imperative since federal health care systems cannot sustain a significant loss of its workforce.
Recommendations
We recommend that health care systems stop business as usual and adopt public health recommendations issued by Canadian and Hong Kong health care authorities for the management of suspected or confirmed COVID-19 disease.25-28 We have further clarified and expanded on these interventions. During viral pandemics, prescribers and health care systems should:
- Deprescribe nebulized therapies on medical wards and intensive care units as an infection control measure. Also avoid use in any outpatient health care setting (eg, community-based clinics, EDs, triage).
- Avoid initiation of nebulized unproven therapies (eg, n-acetylcysteine, hypertonic saline).1
- Use alternative bronchodilator formulations as appropriate (eg, oral β-2 agonist, recognizing its slower onset) before prescribing nebulized agents to patients who are uncooperative or unable to follow directions needed to use a pMDI with a spacer or have experienced a prior poor response to a pMDI with spacer (eg, OptiChamber Diamond, Philips).25,27
- Limit nebulized drug utilization (eg, bronchodilators, epoprostenol) to patients who are on mechanical ventilation and will receive nebulized therapies via a closed system or to patients housed in negative pressure hospital rooms.22 Use a viral filter (eg, Salter Labs system) to decrease the spread of infection for those receiving epoprostenol via face mask.25
- Adjust procurement practices (eg, pharmacy, logistics) to address the transition from nebulized drugs to alternatives.
- Add a safety net to the drug-ordering process by restricting new orders for nebulized therapies to the prior authorization process.27 Apply the exclusion criterion of suspected or definite COVID-19.
- Add a safety net to environmental service practices. Nursing staff should track patients who received ≥ 1 nebulizations via open (before diagnosis) or closed systems so that staff wear suitable PPE to include a N-95 mask while cleaning the room.
Conclusions
To implement the aggressive infection control guidance promulgated here, we recommend collaboration with infection control, pharmacy service (eg, prior authorization team, clinical pharmacy team, and procurement team), respiratory therapy, pulmonary and other critical care physicians, EDs, CPR committee, and other stakeholders. When making significant transitions in clinical care during a viral pandemic, guidelines must be timely, use imperative wording, and consist of easily identifiable education and/or instructions for the affected frontline staff in order to change attitudes.29 Additionally, when transitioning from nebulized bronchodilators to pMDI, educational in-services should be provided to frontline staff to avoid misconceptions regarding pMDI treatment efficacy and patients’ ability to use their pMDI with spacer.30
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System in Nashville.
1. Strickland SL, Rubin BK, Haas CF, Volsko TA, Drescher GS, O’Malley CA. AARC Clinical Practice Guideline: effectiveness of pharmacologic airway clearance therapies in hospitalized patients. Respir Care. 2015;60(7):1071-1077.
2. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2020 GOLD Report. https://goldcopd.org/gold-reports/. Accessed March 26, 2020.
3. Van Geffen WH, Douma WR, Slebos DJ, Kerstjens HAM. Bronchodilators delivered by nebulizer versus pMDI with spacer or DPI for exacerbations of COPD (Review). Cochrane Database Syst Rev. 2016;8:CD011826.
4. Global Initiative for Asthma. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf. Accessed March 26, 2020.
5. Global Initiative for Asthma. Difficult-to-treat and severe asthma in adolescent and adult patients: diagnosis and management. https://ginasthma.org/wp-content/uploads/2019/04/GINA-Severe-asthma-Pocket-Guide-v2.0-wms-1.pdf. Accessed March 26, 2020.
6. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulizers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.
7. Welsh EJ, Evans DJ, Fowler SJ, Spencer S. Interventions for bronchiectasis: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2015;7:CD010337.
8. Taichman DB, Ornelas J, Chung L, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST Guideline and Expert Panel Report. CHEST. 2014;146(2):449-475.
9. Griffiths MJD, McAuley DF, Perkins GD, et al. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Resp Res. 2019;6(1):e000420.
10. McGinn K, Reichert M. A comparison of inhaled nitric oxide versus inhaled epoprostenol for acute pulmonary hypertension following cardiac surgery. Ann Pharmacother. 2016;50(1):22-26.
11. Dzierba AL, Abel EE, Buckley MS, Lat I. A review of inhaled nitric oxide and aerosolized epoprostenol in acute lung injury or acute respiratory distress syndrome. Pharmacotherapy. 2014;34(3):279-290.
12. Pleasants RA, Hess DR. Aerosol delivery devices for obstructive lung diseases. Respir Care. 2018;63(6):708-733.
13. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected Accessed March 26, 2020.
14. Centers for Disease Control and Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html. Revised March 7, 2020. Accessed March 26, 2020.
15. Wong RSM, Hui DS. Index patient and SARS outbreak in Hong Kong. Emerg Infect Dis. 2004;10(2):339-341.
16. Wong T-W, Lee C-K, Tam W, et al; Outbreak Study Group. Emerg Infect Dis. 2004;10(2):269-276.
17. Seto WH, Tsang D, Yung RWH, et al; Advisors of Expert SARS group of Hospital Authority. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet. 2003;361(9368):1519-1520.
18. Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. https://jamanetwork.com/journals/jama/fullarticle/2763401?resultClick=1. Published March 17, 2020. Accessed March 26, 2020.
19. Jones S. Spain: doctors struggle to cope as 514 die from coronavirus in a day. The Guardian. March 24, 2020. https://www.theguardian.com/world/2020/mar/24/spain-doctors-lack-protection-coronavirus-covid-19. Accessed March 27, 2020.
20. 16% of Ohio’s diagnosed COVID-19 cases are healthcare workers. https://www.wlwt.com/article/16-of-ohio-s-diagnosed-covid-19-cases-are-healthcare-workers/31930566#. Updated March 25, 2020. Accessed March 27, 2020.
21. Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30627-9/fulltext. Accessed March 27, 2020.
22. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as Compared with SARS-CoV-1 [published online ahead of print, 2020 Mar 17]. N Engl J Med. 2020;10.1056/NEJMc2004973.
23. McGrath JA, O’Sullivan A, Bennett G, et al. Investigation of the quantity of exhaled aerosol released into the environment during nebulization. Pharmaceutics. 2019;11(2):75.
24. Centers for Disease Control and Prevention. Healthcare Infection prevention and control FAQs for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/infection-control/infection-prevention-control-faq.html. Revised March 24, 2020. Accessed March 26, 2020.
25. Practice standards of respiratory procedures: post SARS era. Use of aerosolized medications. December 2003. http://www.hkresp.com/hkts.php?page=page/hkts/detail&meid=93742. Accessed March 26, 2020.
26. Wax RS, Christian MD. Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients. Can J Anesth. 2020. [ePub ahead of print.]
27. Newhouse MT. RE: transmission of coronavirus by nebulizer- as serious, underappreciated risk! https://www.cmaj.ca/content/re-transmission-corona-virus-nebulizer-serious-underappreciated-risk. Accessed March 26, 2020. [ePub ahead of print.]
28. Moira C-Y. Severe acute respiratory syndrome (SARS) and healthcare workers. Int J Occup Environ Health. 2004;10(4):421-427.
29. Timen A, Hulscher MEJL, Rust L, et al. Barriers to implementing infection prevention and control guidelines during crises: experiences of health care professionals. Am J Infect Control. 2010;38(9):726-733.
30. Khoo SM, Tan LK, Said N, Lim TK. Metered-dose inhaler with spacer instead of nebulizer during the outbreak of severe acute respiratory syndrome in Singapore. Respir Care. 2009;54(7):855-860.
Beyond asthma and chronic obstructive pulmonary disease (COPD), inhalation therapy is a mainstay in the management of bronchiectasis, cystic fibrosis, and pulmonary artery hypertension. Several US Food and Drug Administration off-label indications for inhalational medications include hypoxia secondary to acute respiratory distress syndrome (ARDS) and intraoperative and postoperative pulmonary hypertension during and following cardiac surgery, respectively.1-11 Therapeutic delivery of aerosols to the lung may be provided via nebulization, pressurized metered-dose inhalers (pMDI), and other devices (eg, dry powder inhalers, soft-mist inhalers, and smart inhalers).12 The most common aerosolized medications given in the clinical setting are bronchodilators.12
Product selection is often guided by practice guidelines (Table 1), consideration of the formulation’s advantages and disadvantages (Table 2), and/or formulary considerations. For example, current guidelines for COPD state that there is no evidence for superiority of nebulized bronchodilator therapy over handheld devices in patients who can use them properly.2 Due to equivalence, nebulized formulations are commonly used in hospitals, emergency departments (EDs) and ambulatory clinics based on the drug’s unit cost. In contrast, a pMDI is often more cost-effective for use in ambulatory patients who are administering multiple doses from the same canister.
The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend droplet and contact precautions for all patients suspected or diagnosed with novel coronavirus-19 (COVID-19).13,14 Airborne precautions must be applied when performing aerosol-generating medical procedures (AGMPs), including but not limited to, open suctioning of the respiratory tract, intubation, bronchoscopy, and cardiopulmonary resuscitation (CPR). Data from the severe acute respiratory syndrome (SARS-CoV) epidemic suggest that nebulization of medication is also an AGMP.15-17
Institutions must ensure that their health care workers (HCWs) are wearing appropriate personal protective equipment (PPE) including gloves, long-sleeved gowns, eye protection, and fit-tested particulate respirators (N95 mask) for airborne procedures and are carefully discarding PPE after use.13,14 Due to severe shortages in available respirators in the US supply chain, the CDC has temporarily modified WHO recommendations. Face masks are now an acceptable alternative to protect HCWs from splashes and sprays from procedures not likely to generate aerosols and for cleaning of rooms, although there is no evidence to support this decision.
Internationally, HCWs are falling ill with COVID-19. Data from Italy and Spain show that about 9% to 13% of these countries’ cases are HCWs.18,19 Within the US, the Ohio health department reports approximately 16% of cases are HCWs.20 It is possible that 20% of frontline HCWs will become infected.21 Evolving laboratory research shows that COVID-19 remains viable in aerosols for up to 3 hours postaerosolization, thus making aerosol transmission plausible.22 Nebulizers convert liquids into aerosols and during dispersal may potentially cause secondary inhalation of fugitive emissions.23 Since interim CDC infection control guidance is to allow only essential personnel to enter the room of patients with COVID-19, many facilities will rely on their frontline nursing staff to clean and disinfect high-touch surfaces following routine care activities.24
Achieving adequate fomite disinfection following viral aerosolization may pose a significant problem for any patient receiving scheduled doses of nebulized medications. Additionally, for personnel who clean rooms following intermittent drug nebulization while wearing PPE that includes a face mask, protection from aerosolized virus may be inadequate. Subsequently, fugitive emissions from nebulized medications may potentially contribute to both nosocomial COVID-19 transmission and viral infections in the medical staff until proven otherwise by studies conducted outside of the laboratory. Prevention of infection in the medical staff is imperative since federal health care systems cannot sustain a significant loss of its workforce.
Recommendations
We recommend that health care systems stop business as usual and adopt public health recommendations issued by Canadian and Hong Kong health care authorities for the management of suspected or confirmed COVID-19 disease.25-28 We have further clarified and expanded on these interventions. During viral pandemics, prescribers and health care systems should:
- Deprescribe nebulized therapies on medical wards and intensive care units as an infection control measure. Also avoid use in any outpatient health care setting (eg, community-based clinics, EDs, triage).
- Avoid initiation of nebulized unproven therapies (eg, n-acetylcysteine, hypertonic saline).1
- Use alternative bronchodilator formulations as appropriate (eg, oral β-2 agonist, recognizing its slower onset) before prescribing nebulized agents to patients who are uncooperative or unable to follow directions needed to use a pMDI with a spacer or have experienced a prior poor response to a pMDI with spacer (eg, OptiChamber Diamond, Philips).25,27
- Limit nebulized drug utilization (eg, bronchodilators, epoprostenol) to patients who are on mechanical ventilation and will receive nebulized therapies via a closed system or to patients housed in negative pressure hospital rooms.22 Use a viral filter (eg, Salter Labs system) to decrease the spread of infection for those receiving epoprostenol via face mask.25
- Adjust procurement practices (eg, pharmacy, logistics) to address the transition from nebulized drugs to alternatives.
- Add a safety net to the drug-ordering process by restricting new orders for nebulized therapies to the prior authorization process.27 Apply the exclusion criterion of suspected or definite COVID-19.
- Add a safety net to environmental service practices. Nursing staff should track patients who received ≥ 1 nebulizations via open (before diagnosis) or closed systems so that staff wear suitable PPE to include a N-95 mask while cleaning the room.
Conclusions
To implement the aggressive infection control guidance promulgated here, we recommend collaboration with infection control, pharmacy service (eg, prior authorization team, clinical pharmacy team, and procurement team), respiratory therapy, pulmonary and other critical care physicians, EDs, CPR committee, and other stakeholders. When making significant transitions in clinical care during a viral pandemic, guidelines must be timely, use imperative wording, and consist of easily identifiable education and/or instructions for the affected frontline staff in order to change attitudes.29 Additionally, when transitioning from nebulized bronchodilators to pMDI, educational in-services should be provided to frontline staff to avoid misconceptions regarding pMDI treatment efficacy and patients’ ability to use their pMDI with spacer.30
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System in Nashville.
Beyond asthma and chronic obstructive pulmonary disease (COPD), inhalation therapy is a mainstay in the management of bronchiectasis, cystic fibrosis, and pulmonary artery hypertension. Several US Food and Drug Administration off-label indications for inhalational medications include hypoxia secondary to acute respiratory distress syndrome (ARDS) and intraoperative and postoperative pulmonary hypertension during and following cardiac surgery, respectively.1-11 Therapeutic delivery of aerosols to the lung may be provided via nebulization, pressurized metered-dose inhalers (pMDI), and other devices (eg, dry powder inhalers, soft-mist inhalers, and smart inhalers).12 The most common aerosolized medications given in the clinical setting are bronchodilators.12
Product selection is often guided by practice guidelines (Table 1), consideration of the formulation’s advantages and disadvantages (Table 2), and/or formulary considerations. For example, current guidelines for COPD state that there is no evidence for superiority of nebulized bronchodilator therapy over handheld devices in patients who can use them properly.2 Due to equivalence, nebulized formulations are commonly used in hospitals, emergency departments (EDs) and ambulatory clinics based on the drug’s unit cost. In contrast, a pMDI is often more cost-effective for use in ambulatory patients who are administering multiple doses from the same canister.
The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend droplet and contact precautions for all patients suspected or diagnosed with novel coronavirus-19 (COVID-19).13,14 Airborne precautions must be applied when performing aerosol-generating medical procedures (AGMPs), including but not limited to, open suctioning of the respiratory tract, intubation, bronchoscopy, and cardiopulmonary resuscitation (CPR). Data from the severe acute respiratory syndrome (SARS-CoV) epidemic suggest that nebulization of medication is also an AGMP.15-17
Institutions must ensure that their health care workers (HCWs) are wearing appropriate personal protective equipment (PPE) including gloves, long-sleeved gowns, eye protection, and fit-tested particulate respirators (N95 mask) for airborne procedures and are carefully discarding PPE after use.13,14 Due to severe shortages in available respirators in the US supply chain, the CDC has temporarily modified WHO recommendations. Face masks are now an acceptable alternative to protect HCWs from splashes and sprays from procedures not likely to generate aerosols and for cleaning of rooms, although there is no evidence to support this decision.
Internationally, HCWs are falling ill with COVID-19. Data from Italy and Spain show that about 9% to 13% of these countries’ cases are HCWs.18,19 Within the US, the Ohio health department reports approximately 16% of cases are HCWs.20 It is possible that 20% of frontline HCWs will become infected.21 Evolving laboratory research shows that COVID-19 remains viable in aerosols for up to 3 hours postaerosolization, thus making aerosol transmission plausible.22 Nebulizers convert liquids into aerosols and during dispersal may potentially cause secondary inhalation of fugitive emissions.23 Since interim CDC infection control guidance is to allow only essential personnel to enter the room of patients with COVID-19, many facilities will rely on their frontline nursing staff to clean and disinfect high-touch surfaces following routine care activities.24
Achieving adequate fomite disinfection following viral aerosolization may pose a significant problem for any patient receiving scheduled doses of nebulized medications. Additionally, for personnel who clean rooms following intermittent drug nebulization while wearing PPE that includes a face mask, protection from aerosolized virus may be inadequate. Subsequently, fugitive emissions from nebulized medications may potentially contribute to both nosocomial COVID-19 transmission and viral infections in the medical staff until proven otherwise by studies conducted outside of the laboratory. Prevention of infection in the medical staff is imperative since federal health care systems cannot sustain a significant loss of its workforce.
Recommendations
We recommend that health care systems stop business as usual and adopt public health recommendations issued by Canadian and Hong Kong health care authorities for the management of suspected or confirmed COVID-19 disease.25-28 We have further clarified and expanded on these interventions. During viral pandemics, prescribers and health care systems should:
- Deprescribe nebulized therapies on medical wards and intensive care units as an infection control measure. Also avoid use in any outpatient health care setting (eg, community-based clinics, EDs, triage).
- Avoid initiation of nebulized unproven therapies (eg, n-acetylcysteine, hypertonic saline).1
- Use alternative bronchodilator formulations as appropriate (eg, oral β-2 agonist, recognizing its slower onset) before prescribing nebulized agents to patients who are uncooperative or unable to follow directions needed to use a pMDI with a spacer or have experienced a prior poor response to a pMDI with spacer (eg, OptiChamber Diamond, Philips).25,27
- Limit nebulized drug utilization (eg, bronchodilators, epoprostenol) to patients who are on mechanical ventilation and will receive nebulized therapies via a closed system or to patients housed in negative pressure hospital rooms.22 Use a viral filter (eg, Salter Labs system) to decrease the spread of infection for those receiving epoprostenol via face mask.25
- Adjust procurement practices (eg, pharmacy, logistics) to address the transition from nebulized drugs to alternatives.
- Add a safety net to the drug-ordering process by restricting new orders for nebulized therapies to the prior authorization process.27 Apply the exclusion criterion of suspected or definite COVID-19.
- Add a safety net to environmental service practices. Nursing staff should track patients who received ≥ 1 nebulizations via open (before diagnosis) or closed systems so that staff wear suitable PPE to include a N-95 mask while cleaning the room.
Conclusions
To implement the aggressive infection control guidance promulgated here, we recommend collaboration with infection control, pharmacy service (eg, prior authorization team, clinical pharmacy team, and procurement team), respiratory therapy, pulmonary and other critical care physicians, EDs, CPR committee, and other stakeholders. When making significant transitions in clinical care during a viral pandemic, guidelines must be timely, use imperative wording, and consist of easily identifiable education and/or instructions for the affected frontline staff in order to change attitudes.29 Additionally, when transitioning from nebulized bronchodilators to pMDI, educational in-services should be provided to frontline staff to avoid misconceptions regarding pMDI treatment efficacy and patients’ ability to use their pMDI with spacer.30
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System in Nashville.
1. Strickland SL, Rubin BK, Haas CF, Volsko TA, Drescher GS, O’Malley CA. AARC Clinical Practice Guideline: effectiveness of pharmacologic airway clearance therapies in hospitalized patients. Respir Care. 2015;60(7):1071-1077.
2. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2020 GOLD Report. https://goldcopd.org/gold-reports/. Accessed March 26, 2020.
3. Van Geffen WH, Douma WR, Slebos DJ, Kerstjens HAM. Bronchodilators delivered by nebulizer versus pMDI with spacer or DPI for exacerbations of COPD (Review). Cochrane Database Syst Rev. 2016;8:CD011826.
4. Global Initiative for Asthma. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf. Accessed March 26, 2020.
5. Global Initiative for Asthma. Difficult-to-treat and severe asthma in adolescent and adult patients: diagnosis and management. https://ginasthma.org/wp-content/uploads/2019/04/GINA-Severe-asthma-Pocket-Guide-v2.0-wms-1.pdf. Accessed March 26, 2020.
6. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulizers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.
7. Welsh EJ, Evans DJ, Fowler SJ, Spencer S. Interventions for bronchiectasis: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2015;7:CD010337.
8. Taichman DB, Ornelas J, Chung L, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST Guideline and Expert Panel Report. CHEST. 2014;146(2):449-475.
9. Griffiths MJD, McAuley DF, Perkins GD, et al. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Resp Res. 2019;6(1):e000420.
10. McGinn K, Reichert M. A comparison of inhaled nitric oxide versus inhaled epoprostenol for acute pulmonary hypertension following cardiac surgery. Ann Pharmacother. 2016;50(1):22-26.
11. Dzierba AL, Abel EE, Buckley MS, Lat I. A review of inhaled nitric oxide and aerosolized epoprostenol in acute lung injury or acute respiratory distress syndrome. Pharmacotherapy. 2014;34(3):279-290.
12. Pleasants RA, Hess DR. Aerosol delivery devices for obstructive lung diseases. Respir Care. 2018;63(6):708-733.
13. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected Accessed March 26, 2020.
14. Centers for Disease Control and Prevention. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html. Revised March 7, 2020. Accessed March 26, 2020.
15. Wong RSM, Hui DS. Index patient and SARS outbreak in Hong Kong. Emerg Infect Dis. 2004;10(2):339-341.
16. Wong T-W, Lee C-K, Tam W, et al; Outbreak Study Group. Emerg Infect Dis. 2004;10(2):269-276.
17. Seto WH, Tsang D, Yung RWH, et al; Advisors of Expert SARS group of Hospital Authority. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet. 2003;361(9368):1519-1520.
18. Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. https://jamanetwork.com/journals/jama/fullarticle/2763401?resultClick=1. Published March 17, 2020. Accessed March 26, 2020.
19. Jones S. Spain: doctors struggle to cope as 514 die from coronavirus in a day. The Guardian. March 24, 2020. https://www.theguardian.com/world/2020/mar/24/spain-doctors-lack-protection-coronavirus-covid-19. Accessed March 27, 2020.
20. 16% of Ohio’s diagnosed COVID-19 cases are healthcare workers. https://www.wlwt.com/article/16-of-ohio-s-diagnosed-covid-19-cases-are-healthcare-workers/31930566#. Updated March 25, 2020. Accessed March 27, 2020.
21. Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30627-9/fulltext. Accessed March 27, 2020.
22. van Doremalen N, Bushmaker T, Morris DH, et al. Aerosol and surface stability of SARS-CoV-2 as Compared with SARS-CoV-1 [published online ahead of print, 2020 Mar 17]. N Engl J Med. 2020;10.1056/NEJMc2004973.
23. McGrath JA, O’Sullivan A, Bennett G, et al. Investigation of the quantity of exhaled aerosol released into the environment during nebulization. Pharmaceutics. 2019;11(2):75.
24. Centers for Disease Control and Prevention. Healthcare Infection prevention and control FAQs for COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/infection-control/infection-prevention-control-faq.html. Revised March 24, 2020. Accessed March 26, 2020.
25. Practice standards of respiratory procedures: post SARS era. Use of aerosolized medications. December 2003. http://www.hkresp.com/hkts.php?page=page/hkts/detail&meid=93742. Accessed March 26, 2020.
26. Wax RS, Christian MD. Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients. Can J Anesth. 2020. [ePub ahead of print.]
27. Newhouse MT. RE: transmission of coronavirus by nebulizer- as serious, underappreciated risk! https://www.cmaj.ca/content/re-transmission-corona-virus-nebulizer-serious-underappreciated-risk. Accessed March 26, 2020. [ePub ahead of print.]
28. Moira C-Y. Severe acute respiratory syndrome (SARS) and healthcare workers. Int J Occup Environ Health. 2004;10(4):421-427.
29. Timen A, Hulscher MEJL, Rust L, et al. Barriers to implementing infection prevention and control guidelines during crises: experiences of health care professionals. Am J Infect Control. 2010;38(9):726-733.
30. Khoo SM, Tan LK, Said N, Lim TK. Metered-dose inhaler with spacer instead of nebulizer during the outbreak of severe acute respiratory syndrome in Singapore. Respir Care. 2009;54(7):855-860.
1. Strickland SL, Rubin BK, Haas CF, Volsko TA, Drescher GS, O’Malley CA. AARC Clinical Practice Guideline: effectiveness of pharmacologic airway clearance therapies in hospitalized patients. Respir Care. 2015;60(7):1071-1077.
2. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2020 GOLD Report. https://goldcopd.org/gold-reports/. Accessed March 26, 2020.
3. Van Geffen WH, Douma WR, Slebos DJ, Kerstjens HAM. Bronchodilators delivered by nebulizer versus pMDI with spacer or DPI for exacerbations of COPD (Review). Cochrane Database Syst Rev. 2016;8:CD011826.
4. Global Initiative for Asthma. https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf. Accessed March 26, 2020.
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