Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.

Review of aerosol delivery in the emergency department.

Aerosol delivery is a vital therapeutic strategy for both adult and pediatric patients presenting to the emergency department with respiratory distress. Aerosolized bronchodilators are frequently used as rescue medications for patients with diagnoses of asthma, chronic obstructive pulmonary disease (COPD), or pneumonia. Historically, emergency department providers utilized jet nebulizers (JNs) for medication delivery, but were challenged by a need for increasingly higher bronchodilator doses to elicit the desired response. Advancements in technology have led to the development of newer specialized aerosol delivery devices and treatment strategies which provide clinicians with improved options for aerosol delivery but may also cause some uncertainty regarding appropriate device selection. Initial investigations comparing these devices presented valuable evidence of in vitro benefit but were unable to demonstrate corresponding improvement in clinical results. More recently there has been an influx of clinical evidence that suggests improved clinical outcomes associated with more efficient aerosol delivery devices such as vibrating mesh nebulizers (VMN) compared to the standard JN device. VMN will likely become an increasingly important tool in emergency department treatment of patients with respiratory distress. Additional controlled studies are needed both to examine the effects of VMN on patient outcomes, as well as to analyze how performance differences between aerosol devices may affect dosing strategies. Future efforts should also focus on applying new evidence in the form of updated consensus guidelines and standardized treatment strategies.

Reducing Aerosol-Related Risk of Transmission in the Era of COVID-19: An Interim Guidance Endorsed by the International Society of Aerosols in Medicine.

National and international guidelines recommend droplet/airborne transmission and contact precautions for those caring for coronavirus disease 2019 (COVID-19) patients in ambulatory and acute care settings. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, an acute respiratory infectious agent, is primarily transmitted between people through respiratory droplets and contact routes. A recognized key to transmission of COVID-19, and droplet infections generally, is the dispersion of bioaerosols from the patient. Increased risk of transmission has been associated with aerosol generating procedures that include endotracheal intubation, bronchoscopy, open suctioning, administration of nebulized treatment, manual ventilation before intubation, turning the patient to the prone position, disconnecting the patient from the ventilator, noninvasive positive-pressure ventilation, tracheostomy, and cardiopulmonary resuscitation. The knowledge that COVID-19 subjects can be asymptomatic and still shed virus, producing infectious droplets during breathing, suggests that health care workers (HCWs) should assume every patient is potentially infectious during this pandemic. Taking actions to reduce risk of transmission to HCWs is, therefore, a vital consideration for safe delivery of all medical aerosols. Guidelines for use of personal protective equipment (glove, gowns, masks, shield, and/or powered air purifying respiratory) during high-risk procedures are essential and should be considered for use with lower risk procedures such as administration of uncontaminated medical aerosols. Bioaerosols generated by infected patients are a major source of transmission for SARS CoV-2, and other infectious agents. In contrast, therapeutic aerosols do not add to the risk of disease transmission unless contaminated by patients or HCWs.

Lung deposition and systemic bioavailability of different aerosol devices with and without humidification in mechanically ventilated patients.

BACKGROUND: During mechanical ventilation medical aerosol delivery has been reported to be upto two fold greater with dry inhaled gas than with heated humidity. Urine levels at 0.5 h post dose (URSAL0.5%) has been confirmed as an index of lung deposition and 24 h (URSAL24%) as index of systemic absorption. Our aim was to determine the effect of humidification and aerosol device type on drug delivery to ventilated patients using urine levels. METHODS: In a randomized crossover design, 36 (18female) mechanically ventilated patients were assigned to one of three groups. Groups 1 and 2 received 5000 µg salbutamol using vibrating mesh (VM) and jet nebulizers (JN), respectively, while group 3 received 1600 µg (16 puffs) of salbutamol via metered dose inhaler with AeroChamber Vent (MDI-AV). All devices were placed in the inspiratory limb of ventilator downstream from the humidifier. Each subject received aerosol with and without humidity at >24 h intervals with >12 h washout periods between salbutamol doses. Patients voided urine 15 min before each study dose and urine samples were collected at 0.5 h post dosing and pooled for the next 24 h. RESULTS: The MDI-AV and VM resulted in a higher percentage of urinary salbutamol levels compared to the JN (p < 0.05). Urine levels were similar between humidity and dry conditions. CONCLUSIONS: Our findings suggest that in-vitro reports overestimate the impact of dry vs. heated humidified conditions on the delivery of aerosol during invasive mechanical ventilation.

Aerosol Delivery Through Adult High Flow Nasal Cannula With Heliox and Oxygen.

BACKGROUND: Heliox (helium-oxygen mixture) has been shown to reduce turbulence and improve aerosol delivery in a range of clinical settings. We questioned whether heliox as compared with oxygen via high-flow nasal cannula (HFNC) would affect aerosol delivery. We hypothesized that heliox would have a significant effect on aerosol delivery as compared with oxygen with both quiet and distressed breathing patterns. METHODS: A vibrating mesh nebulizer was placed at the inlet of a humidifier via HFNC with small adult cannula distal to the heated-wire circuit with prongs placed into simulated nares with a T-shaped trap and absolute filter connected to a breath simulator set to adult quiet and distressed breathing parameters. Albuterol sulfate (0.083% 2.5 mg/3 mL) was aerosolized with heliox (80:20) and oxygen (100%) at 10, 30, and 50 L/min. Drug eluted from the filter was assayed with UV spectrophotometry (276 nm). Descriptive statistics, Kruskal-Wallis test, and Mann-Whitney U test were used for data analysis. P < .05 was considered statistically significant. RESULTS: Increasing flows with heliox and oxygen significantly decreased percentage inhaled dose (inhaled dose) of aerosol with a quiet breathing pattern (P = .02 and P = .030, respectively). In contrast, with a distressed breathing pattern, inhaled dose at 10 L/min was lower than at 30 and 50 L/min (P = .009 and P = .01, respectively) with both oxygen and heliox (P = .009 and P = .009, respectively). Despite a trend to higher aerosol deposition with heliox versus oxygen, the differences were not significant. CONCLUSIONS: With a distressed breathing pattern, aerosol delivery was greater at 30 and 50 L/min than with a quiet breathing pattern. Trends toward higher inhaled dose with heliox during HFNC were not significant.

Clinical outcome associated with the use of different inhalation method with and without humidification in asthmatic mechanically ventilated patients.

BACKGROUND: Inhaled-medication delivered during mechanical-ventilation is affected by type of aerosol-generator and humidity-condition. Despite many in-vitro studies related to aerosol-delivery to mechanically-ventilated patients, little has been reported on clinical effects of these variables. The aim of this study was to determine effect of humidification and type of aerosol-generator on clinical status of mechanically ventilated asthmatics. METHOD: 72 (36 females) asthmatic subjects receiving invasive mechanical ventilation were enrolled and assigned randomly to 6 treatment groups of 12 (6 females) subjects each received, as possible, all inhaled medication using their assigned aerosol generator and humidity condition during delivery. Aerosol-generators were placed immediately after humidifier within inspiratory limb of mechanical ventilation circuit. First group used vibrating-mesh-nebulizer (Aerogen Solo; VMN) with humidification; Second used VMN without humidification; Third used metered-dose-inhaler with AeroChamber Vent (MDI-AV) with humidification; Forth used MDI-AV without humidification; Fifth used Oxycare jet-nebulizer (JN) with humidification; Sixth used JN without humidification. Measured parameters included clinical-parameters reflected patient response (CP) and endpoint parameters e.g. length-of-stay in the intensive-care-unit (ICU-days) and mechanical-ventilation days (MV-days). RESULTS: There was no significant difference between studied subjects in the 6 groups in baseline of CP. VMN resulted in trend to shorter ICU-days (∼1.42days) compared to MDI-AV (p = 0.39) and relatively but not significantly shorter ICU-days (∼0.75days) compared JN. Aerosol-delivery with or without humidification did not have any significant effect on any of parameters studied with very light insignificant tendency of delivery at humid condition to decrease MV-days and ICU-days. No significant effect was found of changing humidity during aerosol-delivery to ventilated-patient. CONCLUSIONS: VMN to deliver aerosol in ventilated patient resulted in trend to decreased ICU-days compared to JN and MDI-AV. Aerosol-delivery with or without humidification did not have any significant effect on any of parameters studied. However, we recommend increasing the number of patients studied to corroborate this finding.

In vitro comparison of heliox and oxygen in aerosol delivery using pediatric high flow nasal cannula.

Drug administration via high flow nasal cannula (HFNC) has been described in pediatrics but the amount of albuterol delivery with an HFNC is not known. The purpose of this study is to quantify aerosol delivery with heliox and oxygen (O(2)) in a model of pediatric ventilation. A vibrating mesh nebulizer (Aeroneb Solo, Aerogen) was placed on the inspiratory inlet of a heated humidifier and heated wire circuit attached to a pediatric nasal cannula (Optiflow, Fisher & Paykel). Breathing parameters were tidal volume (V(t)) 100 ml, respiratory rate (RR) 20/min, and I-time of 1 sec. Albuterol sulfate (2.5 mg/3 ml) was administered through a pediatric HFNC with O(2) (100%) and heliox (80/20% mixture). A total of 12 runs, using O(2) and heliox were conducted at 3 and 6 L/min (n = 3). Drug was collected on an absolute filter, eluted and measured using spectrophotometry. The percent inhaled dose (mean ± SD) was similar with heliox and O(2) at 3 L/min (11.41 ± 1.54 and 10.65 ± 0.51, respectively; P = 0.465). However at 6 L/min drug deposition was ≥ 2-fold greater with heliox (5.42 ± 0.54) than O(2) (1.95 ± 0.50; P = 0.01). Using a pediatric model of HFNC, reducing delivered flow from 6 to 3 L/min increased inhaled albuterol delivery ≥ 2-fold but eliminated the increase in inhaled drug efficiency associated with heliox.