Publications by authors named "James B Fink"

121 Publications

Aerosol-Generating Procedures and Virus Transmission.

Respir Care 2022 08 6;67(8):1022-1042. Epub 2022 Apr 6.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee.

During the early phase of the COVID-19 pandemic, many respiratory therapies were classified as aerosol-generating procedures. This categorization resulted in a broad range of clinical concerns and a shortage of essential medical resources for some patients. In the past 2 years, many studies have assessed the transmission risk posed by various respiratory care procedures. These studies are discussed in this narrative review, with recommendations for mitigating transmission risk based on the current evidence.
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http://dx.doi.org/10.4187/respcare.10160DOI Listing
August 2022

Does Valved Holding Chamber Improve Aerosol Lung Deposition with a Jet Nebulizer? A Randomized Crossover Study.

Pharmaceutics 2022 Mar 4;14(3). Epub 2022 Mar 4.

Department of Physical Therapy, Universidade Federal de Pernambuco, Recife 50710-560, PE, Brazil.

Using valved holding chambers (VHC) during aerosol therapy has been reported to improve the inhaled dose with various aerosol devices, including vibrating mesh nebulizers. The aim of this study was to quantify the pulmonary deposition of a jet nebulizer (JN) with and without a VHC, and a mesh nebulizer (MN) with a VHC in a randomized cross-over trial with seven healthy consenting adults. Our hypothesis was that the use of a VHC would improve deposition with the JN. Diethylnitriaminopentacetic acid with technetium (DTPA-Tc99m), with the activity of 1 mC with 0.9% saline solution was nebulized. The radiolabeled aerosol was detected by 2D planar scintigraphy after administration. The pulmonary deposition was greater with a JN with a VHC (4.5%) than a JN alone (3.2%; = 0.005. However, an MN with a VHC (30.0%) was six-fold greater than a JN or JN with a VHC ( < 0.001). The extrapulmonary deposition was higher in the JN group without a VHC than in the other two modalities ( < 0.001). Deposition in the device was greater with a JN + VHC than an MN+/VHC ( < 0.001). Lower residual drug at the end of the dose was detected with an MN than either JN configuration. The exhaled dose was greater with a JN alone than either an MN or JN with VHC ( < 0.001). In conclusion, the addition of the VHC did not substantially improve the efficiency of aerosol lung deposition over a JN alone.
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http://dx.doi.org/10.3390/pharmaceutics14030566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956008PMC
March 2022

Reliability of Mesh Aerosol Devices Used During INHALE Trial.

Authors:
James B Fink

J Aerosol Med Pulm Drug Deliv 2022 04 14;35(2):107-108. Epub 2022 Feb 14.

Allied Health Graduate Program, Rush University, Chicago, Illinois, USA.

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http://dx.doi.org/10.1089/jamp.2022.0001DOI Listing
April 2022

Optimizing high-flow nasal cannula flow settings in adult hypoxemic patients based on peak inspiratory flow during tidal breathing.

Ann Intensive Care 2021 Nov 27;11(1):164. Epub 2021 Nov 27.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.

Background: Optimal flow settings during high-flow nasal cannula (HFNC) therapy are unknown. We investigated the optimal flow settings during HFNC therapy based on breathing pattern and tidal inspiratory flows in patients with acute hypoxemic respiratory failure (AHRF).

Methods: We conducted a prospective clinical study in adult hypoxemic patients treated by HFNC with a fraction of inspired oxygen (FO) ≥ 0.4. Patient's peak tidal inspiratory flow (PTIF) was measured and HFNC flows were set to match individual PTIF and then increased by 10 L/min every 5-10 min up to 60 L/min. FO was titrated to maintain pulse oximetry (SpO) of 90-97%. SpO/FO, respiratory rate (RR), ROX index [(SpO/FO)/RR], and patient comfort were recorded after 5-10 min on each setting. We also conducted an in vitro study to explore the relationship between the HFNC flows and the tracheal FO, peak inspiratory and expiratory pressures.

Results: Forty-nine patients aged 58.0 (SD 14.1) years were enrolled. At enrollment, HFNC flow was set at 45 (38, 50) L/min, with an FO at 0.62 (0.16) to obtain an SpO/FO of 160 (40). Mean PTIF was 34 (9) L/min. An increase in HFNC flows up to two times of the individual patient's PTIF, incrementally improved oxygenation but the ROX index plateaued with HFNC flows of 1.34-1.67 times the individual PTIF. In the in vitro study, when the HFNC flow was set higher than PTIF, tracheal peak inspiratory and expiratory pressures increased as HFNC flow increased but the FO did not change.

Conclusion: Mean PTIF values in most patients with AHRF were between 30 and 40 L/min. We observed improvement in oxygenation with HFNC flows set above patient PTIF. Thus, a pragmatic approach to set optimal flows in patients with AHRF would be to initiate HFNC flow at 40 L/min and titrate the flow based on improvement in ROX index and patient tolerance.

Trial Registration: ClinicalTrials.gov (NCT03738345). Registered on November 13th, 2018. https://clinicaltrials.gov/ct2/show/NCT03738345?term=NCT03738345&draw=2&rank=1.
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http://dx.doi.org/10.1186/s13613-021-00949-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626729PMC
November 2021

Aerosol particle concentrations with different oxygen devices and interfaces for spontaneous breathing patients with tracheostomy: a randomised crossover trial.

ERJ Open Res 2021 Oct 22;7(4). Epub 2021 Nov 22.

Dept of Cardiopulmonary Sciences, Division of Respiratory Care, Rush University Medical Center, Chicago, IL, USA.

https://bit.ly/2Y1HSO2.
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http://dx.doi.org/10.1183/23120541.00486-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607113PMC
October 2021

Mitigating Fugitive Aerosols During Aerosol Delivery via High-Flow Nasal Cannula Devices.

Respir Care 2022 04 17;67(4):404-414. Epub 2021 Nov 17.

Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee.

Background: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted clinical interest in recent years. However, both HFNC and nebulization are categorized as aerosol-generating procedures (AGPs). In vitro studies raised concerns that AGPs had high transmission risk. Very few in vivo studies examined fugitive aerosols with nebulization via HFNC, and effective methods to mitigate aerosol dispersion are unknown.

Methods: Two HFNC devices (Airvo 2 and Vapotherm) with or without a vibrating mesh nebulizer were compared; HFNC alone, surgical mask over HFNC interface, and HFNC with face tent scavenger were used in a random order for 9 healthy volunteers. Fugitive aerosol concentrations at sizes of 0.3-10.0 μm were continuously measured by particle sizers placed at 1 and 3 ft from participants. On a different day, 6 of the 9 participants received 6 additional nebulizer treatments via vibrating mesh nebulizer or small-volume nebulizer (SVN) with a face mask or a mouthpiece with/without an expiratory filter. In vitro simulation was employed to quantify inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 and Vapotherm.

Results: Compared to baseline, neither HFNC device generated higher aerosol concentrations. Compared to HFNC alone, vibrating mesh nebulizer via Airvo 2 generated higher 0.3-1.0 μm particles (all < .05), but vibrating mesh nebulizer via Vapotherm did not. Concentrations of 1.0-3.0 μm particles with vibrating mesh nebulizer via Airvo 2 were similar with vibrating mesh nebulizer and a mouthpiece/face mask but less than SVN with a mouthpiece/face mask (all < .05). Placing a surgical mask over HFNC during nebulization reduced 0.5-1.0 μm particles (all < .05) to levels similar to the use of a nebulizer with mouthpiece and expiratory filter. In vitro the inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 was ≥ 6 times higher than vibrating mesh nebulizer via Vapotherm.

Conclusions: During aerosol delivery via HFNC, Airvo 2 generated higher inhaled dose and consequently higher fugitive aerosols than Vapotherm. Simple measures, such as placing a surgical mask over nasal cannula during nebulization via HFNC, could effectively reduce fugitive aerosol concentrations.
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http://dx.doi.org/10.4187/respcare.09589DOI Listing
April 2022

Efficacy of Various Mitigation Devices in Reducing Fugitive Emissions from Nebulizers.

Respir Care 2022 04 9;67(4):394-403. Epub 2021 Nov 9.

Department of Cardiopulmonary Sciences, Division of Respiratory Care, Rush University, Chicago, Illinois.

Background: Fugitive aerosol concentrations generated by different nebulizers and interfaces in vivo and mitigation of aerosol dispersion into the environment with various commercially available devices are not known.

Methods: Nine healthy volunteers were given 3 mL saline with a small-volume nebulizer (SVN) or vibrating mesh nebulizer (VMN) with a mouthpiece, a mouthpiece with an exhalation filter, an aerosol mask with open ports for SVN and a valved face mask for VMN, and a face mask with a scavenger (Exhalo) in random order. Five of the participants received treatments using a face tent scavenger (Vapotherm) and a mask with exhalation filter with SVN and VMN in a random order. Treatments were performed in an ICU room with 2 particle counters positioned 1 and 3 ft from participants measuring aerosol concentrations at sizes of 0.3-10.0 μm at baseline, before, during, and after each treatment.

Results: Fugitive aerosol concentrations were higher with SVN than VMN and higher with a face mask than a mouthpiece. Adding an exhalation filter to a mouthpiece reduced aerosol concentrations of 0.3-1.0 μm in size for VMN and 0.3-3.0 μm for SVN (all < .05). An Exhalo scavenger over the mask reduced 0.5-3.0 μm sized particle concentrations for SVN (all < .05) but not VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosol concentrations regardless of the nebulizer type.

Conclusions: SVN produced higher fugitive aerosol concentrations than VMN, whereas face masks generated higher aerosol concentrations than mouthpieces. Adding an exhalation filter to the mouthpiece or a scavenger to the face mask reduced aerosol concentrations for both SVN and VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosols as effectively as a mouthpiece with an exhalation filter. This study provides guidance for reducing fugitive aerosol emissions from nebulizers in clinical practice.
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http://dx.doi.org/10.4187/respcare.09546DOI Listing
April 2022

Bronchodilator Delivery via High-Flow Nasal Cannula: A Randomized Controlled Trial to Compare the Effects of Gas Flows.

Pharmaceutics 2021 Oct 11;13(10). Epub 2021 Oct 11.

Rush University Medical Center, Department of Cardiopulmonary Sciences, Division of Respiratory Care, Chicago, IL 60612, USA.

(1) Background: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted increasing clinical interest. In vitro studies report that the ratio of HFNC gas flow to patient inspiratory flow (GF:IF) is a key factor in the efficiency of trans-nasal aerosol delivery. (2) Methods: In a randomized controlled trial, patients with a history of COPD or asthma and documented positive responses to inhaled bronchodilators in an outpatient pulmonary function laboratory were recruited. Subjects were randomized to receive inhalation at gas flow ratio settings of: GF:IF = 0.5, GF:IF = 1.0, or GF = 50 L/min. Subjects were assigned to inhale saline (control) followed by salbutamol via HFNC with cumulative doses of 0.5 mg, 1.5 mg, 3.5 mg, and 7.5 mg. Spirometry was performed at baseline and 10-12 min after each inhalation. (3) Results: 75 subjects (49 asthma and 26 COPD) demonstrating bronchodilator response were enrolled. Per the robust ATS/ERS criteria no difference was observed between flows, however using the criteria of post-bronchodilator forced expiratory volume in the first second (FEV) reaching the screening post-bronchodilator FEV with salbutamol, a higher percentage of subjects receiving GF:IF = 0.5 met the criteria at a cumulative dose of 1.5 mg than those receiving GF:IF = 1.0, and GF = 50 L/min (64% vs. 29% vs. 27%, respectively, = 0.011). Similarly at 3.5 mg (88% vs. 54% vs. 46%, respectively, = 0.005). The effective dose at GF:IF = 0.5 was 1.5 mg while for GF = 50 L/min it was 3.5 mg. (4) Conclusions: During salbutamol delivery via HFNC, cumulative doses of 1.5 mg to 3.5 mg resulted in effective bronchodilation. Applying the robust ATS/ERS criteria no difference was observed between the flows, however using the more sensitive criteria of subjects reaching post screening FEV to salbutamol via HFNC, a higher number of subjects responded to the doses of 0.5 mg and 1.5 mg when HFNC gas flow was set at 50% of patient peak inspiratory flow.
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http://dx.doi.org/10.3390/pharmaceutics13101655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539308PMC
October 2021

Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits.

Pharmaceutics 2021 Sep 29;13(10). Epub 2021 Sep 29.

Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter ( = 5); low dose surfactant ( = 5) and standard dose surfactant ( = 5) via aerosol; and descriptive controls (no treatment, = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO from pre-treatment baseline following surfactant ( < 0.05) with greater ventilation efficiency with aerosol ( < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation.
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http://dx.doi.org/10.3390/pharmaceutics13101580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540270PMC
September 2021

The Impact of High-Flow Nasal Cannula Device, Nebulizer Type, and Placement on Trans-Nasal Aerosol Drug Delivery: An In Vitro Study.

Respir Care 2021 Oct 20. Epub 2021 Oct 20.

Division of Respiratory Care, Department of Cardiopulmonary Sciences, Rush University, Chicago, Illinois.

Background: Aerosol delivery via high-flow nasal cannula (HFNC) has been increasingly used in recent years. However, the effects of different HFNC devices, nebulizer types, and placement on aerosol deposition remain largely unknown.

Methods: An adult manikin with anatomically correct upper airway was used with a collection filter placed between the manikin's trachea and a breathing simulator, composed of a dual-chamber model lung driven by a critical care ventilator. Three HFNC device configurations were compared, with vibrating mesh nebulizer and small-volume nebulizer placed at the humidifier (inlet for Optiflow and outlet for Airvo 2) and proximal to the nasal cannula at gas flows of 10, 20, 40 and 60 L/min, in quiet and distressed breathing patterns. Albuterol (2.5 mg) was nebulized for each condition (no. = 3). The drug was eluted from the collection filter and assayed with ultraviolet spectrophotometry (276 nm).

Results: At all settings, except when a nebulizer was placed proximal to the nasal cannula with the Optiflow and when the HFNC flow was set at 60 L/min, the vibrating mesh nebulizer generated a higher inhaled dose than did the small-volume nebulizer (all < .05). With the exception of distressed breathing at an HFNC flow of 10 L/min, the inhaled dose with the vibrating mesh nebulizer placed at the humidifier was greater than with the vibrating mesh nebulizer placed proximal to the nasal cannula (all < .05), Optiflow provided a higher inhaled dose than did Airvo 2 with either AirSpiral or 900PT501 circuits with the vibrating mesh nebulizer placed at the humidifier (all < .05).

Conclusions: During transnasal aerosol delivery, the vibrating mesh nebulizer generated a higher inhaled dose than did the small-volume nebulizer when the nebulizer was placed at the humidifier. With the vibrating mesh nebulizer placed at the humidifier and an HFNC flow > 10 L/min, the inhaled dose was higher than with the vibrating mesh nebulizer placed proximal to the nasal cannula, and the inhaled dose was higher with Optiflow than with Airvo 2.
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http://dx.doi.org/10.4187/respcare.09133DOI Listing
October 2021

Aerosol Delivery via Continuous High-Frequency Oscillation During Mechanical Ventilation.

Respir Care 2022 04 2;67(4):415-420. Epub 2021 Sep 2.

Division of Respiratory Care, Department of Cardiopulmonary Sciences, Rush University Medical Center, Chicago, Illinois.

Background: As the use of continuous high-frequency oscillation combined with nebulization during mechanical ventilation becomes more prevalent clinically, it is important to evaluate its aerosol delivery efficacy.

Methods: A bench study was conducted that simulated 2 adult and 2 pediatric conditions. A continuous high-frequency oscillation device integrated into the inspiratory limb of a conventional critical care ventilator was attached to an endotracheal tube (ETT) with a collection filter and test lung. High-frequency oscillation with high-flow setting was used with jet nebulizers attached to the manifold, and a vibrating mesh nebulizer placed between the ETT and the ventilator circuit versus at the inlet of the humidifier. Albuterol (2.5 mg in 3 mL) was nebulized for each condition (no. = 3). The drug was eluted from the collection filter and assayed with ultraviolet spectrophotometry (276 nm).

Results: During continuous high-frequency oscillation, the mean inhaled dose with jet nebulizers was low (<2% with the adult settings and <1% with the pediatric settings). Across both adult and pediatric conditions, when the vibrating mesh nebulizer was placed between the ETT and the Y-piece during continuous high-frequency oscillation, the inhaled dose was higher than with the placement of the vibrating mesh nebulizer at the inlet of the humidifier, median 11.1% (IQR 7.0%-13.7%) median 6.0% (IQR 3.9%-7.2%) ( = .002) respectively, but still lower than the inhaled dose with the vibrating mesh nebulizer placed at the inlet of the humidifier with continuous high-frequency oscillation off, median 22.7% (IQR 19.5%-25.4%) versus median 11.1% (IQR 7.0%-13.7%) ( < .001). The inhaled dose with the 10-year-old scenario was higher than with the 5-year-old scenario in all settings except aerosol delivery via continuous high-frequency oscillation.

Conclusions: During invasive mechanical ventilation with continuous high-frequency oscillation, aerosol delivery with jet nebulizers in the manifold resulted in a marginal inhaled dose. The vibrating mesh nebulizer at the ETT during continuous high-frequency oscillation delivered 6-fold more aerosol than did the jet nebulizer, while delivering only half of the inhaled dose with the vibrating mesh nebulizer placed at the inlet of the humidifier without continuous high-frequency oscillation.
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http://dx.doi.org/10.4187/respcare.08914DOI Listing
April 2022

Quantifying Delivered Dose with Jet and Mesh Nebulizers during Spontaneous Breathing, Noninvasive Ventilation, and Mechanical Ventilation in a Simulated Pediatric Lung Model with Exhaled Humidity.

Pharmaceutics 2021 Jul 30;13(8). Epub 2021 Jul 30.

Department of Respiratory Care, College of Health Profession, Texas State University, Round Rock, TX 78665, USA.

Acutely ill children may transition between spontaneous breathing (SB), noninvasive ventilation (NIV), and mechanical ventilation (MV), and commonly receive the same drug dosage with each type of ventilatory support and interface. This study aims to determine the aerosol deposition with jet (JN) and mesh nebulizers (MN) during SB, NIV, and MV using a pediatric lung model. Drug delivery with JN (Mistymax10) and MN (Aerogen Solo) was compared during SB, NIV, and MV using three different lung models set to simulate the same breathing parameters (Vt 250 mL, RR 20 bpm, I:E ratio 1:3). A heated humidifier was placed between the filter and test lung to simulate exhaled humidity (35 ± 2 °C, 100% RH) with all lung models. Albuterol sulfate (2.5 mg/3 mL) was delivered, and the drug deposited on an absolute filter was eluted and analyzed with spectrophotometry. Aerosol delivery with JN was not significantly different during MV, NIV, and SB ( = 0.075), while inhaled dose obtained with MN during MV was greater than NIV and SB ( = 0.001). The delivery efficiency of MN was up to 3-fold more than JN during MV ( = 0.008), NIV ( = 0.005), and SB ( = 0.009). Delivered dose with JN was similar during MV, NIV, and SB, although the delivery efficiency of MN differs with different modes of ventilation.
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http://dx.doi.org/10.3390/pharmaceutics13081179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400423PMC
July 2021

In-vitro and in-vivo comparisons of high versus low concentrations of inhaled epoprostenol to adult intubated patients.

Respir Res 2021 Aug 21;22(1):231. Epub 2021 Aug 21.

Department of Cardiopulmonary Sciences, Division of Respiratory Care, Rush University, 600 S Paulina St, Suite 765, Chicago, IL, 60612, USA.

Background: Inhaled epoprostenol (iEPO) has been shown to reduce pulmonary artery pressure and improve oxygenation. iEPO is mainly delivered via a syringe pump with feed tubing connected to a vibrating mesh nebulizer with high or low formulation concentration delivery.

Methods: An in vitro study and a two-period retrospective case-control study were implemented. The in vitro study compared iEPO delivery via invasive ventilation at low concentrations of 7.5, and 15 mcg/mL and high concentration at 30 mcg/mL, to deliver the ordered dose of 30 and 50 ng/kg/min for three clinical scenarios with predicted body weight of 50, 70 and 90 kg. While in the clinical study, adult patients receiving iEPO via invasive ventilation to treat refractory hypoxemia, pulmonary hypertension, or right ventricular failure were included. 80 patients received low concentration iEPO at multiple concentrations (2.5, 7.5, and 15 mcg/mL, depending on the ordered dose) from 2015 to 2017, while 84 patients received high concentration iEPO at 30 mcg/mL from 2018 to 2019.

Results: In the in vitro study, there were no significant differences in aerosol deposition between high vs low concentrations of iEPO at a dose of 50 ng/kg/min. In the clinical study, age, gender, ethnicity, and indications for iEPO were similar between high and low concentration groups. After 30-120 min of iEPO administration, both delivery strategies significantly improved oxygenation in hypoxemic patients and reduced mean pulmonary arterial pressure (mPAP) for patients with pulmonary hypertension. However, no significant differences of the incremental changes were found between two delivery groups. Compared to low concentration, high concentration delivery group had better adherence to the iEPO weaning protocol (96% vs 71%, p < 0.001), fewer iEPO syringes utilized per patient (5 [3, 10] vs 12 [6, 22], p = 0.001), and shorter duration of invasive ventilation (6 [3, 12] vs 9 [5, 18] days, p = 0.028). Intensive care unit length of stay and mortality were similar between two groups.

Conclusion: Compared to low concentration delivery of iEPO, high concentration iEPO via a vibrating mesh nebulizer maintained clinical benefits and increased clinician compliance with an iEPO weaning protocol, required less medication preparation time, and shortened duration of invasive ventilation.
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http://dx.doi.org/10.1186/s12931-021-01827-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379597PMC
August 2021

Delivered dose with jet and mesh nebulisers during spontaneous breathing, noninvasive ventilation and mechanical ventilation using adult lung models.

ERJ Open Res 2021 Jul 12;7(3). Epub 2021 Jul 12.

Dept of Respiratory Care, Texas State University, Round Rock, TX, USA.

What is the delivered dose with jet and mesh nebulisers during spontaneous breathing (SB), noninvasive ventilation (NIV), and mechanical ventilation (MV) using an adult lung model with exhaled humidity (EH)? The delivery of salbutamol sulfate (2.5 mg per 3 mL) with jet (Mistymax10) and mesh nebulisers (Aerogen Solo) was compared during SB, NIV, and MV using breathing parameters (tidal volume 450 mL, respiratory rate 20 breaths per min, inspiratory:expiratory ratio 1:3) with three lung models simulating exhaled humidity. A manikin was attached to a sinusoidal pump a filter at the bronchi to simulate an adult with SB. A ventilator (V60) was attached a facemask to a manikin with a filter at the bronchi connected to a test lung to simulate an adult receiving NIV. A ventilator-dependent adult was simulated through a ventilator (Servo-i) operated with a heated humidifier (Fisher & Paykel) attached to an endotracheal tube (ETT) with a heated-wire circuit. The ETT was inserted into a filter (Respirgard II). A heated humidifier was placed between the filter and test lung to simulate exhaled humidity (35±2°C, 100% relative humidity). Nebulisers were placed at the Y-piece of the inspiratory limb during MV and positioned between the facemask and the leak-port during NIV. A mouthpiece was used during SB. The delivered dose was collected in an absolute filter that was attached to the bronchi of the mannequin during each aerosol treatment and measured with spectrophotometry. Drug delivery during MV was significantly greater than during NIV and SB with a mesh nebuliser (p=0.0001) but not with a jet nebuliser (p=0.384). Delivery efficiency of the mesh nebuliser was greater than the jet nebuliser during MV (p=0.0001), NIV (p=0.0001), and SB (p=0.0001). Aerosol deposition obtained with a mesh nebuliser was greater and differed between MV, NIV, and SB, while deposition was low with a jet nebuliser and similar between the modes of ventilation tested.
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http://dx.doi.org/10.1183/23120541.00027-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273293PMC
July 2021

Narrative review of practical aspects of aerosol delivery via high-flow nasal cannula.

Authors:
Jie Li James B Fink

Ann Transl Med 2021 Apr;9(7):590

Department of Cardiopulmonary Sciences, Division of Respiratory Care, Rush University Medical Center, Chicago, IL, USA.

Using high-flow nasal cannula (HFNC) as a "vehicle" to administer aerosolized medication has attracted clinicians' interest in recent years. In this paper, we summarize the current evidence to answer the common questions raised by clinicians about this new aerosol delivery route and best practices of administration. Benefits of trans-nasal aerosol delivery include increased comfort, ability to speak, eat, and drink for patients while meeting a range of oxygen requirements, particularly for those who need to inhale aerosolized medication for long periods. Aerosol administration via HFNC has been shown to be well tolerated by children and adults, with comparable or better delivery efficacy than other interfaces, ranging from 2-20%. and scintigraphy studies among pediatric and adult populations reported that the inhaled dose delivered via a vibrating mesh nebulizer is 2 to 3 fold greater than that via a jet nebulizer. For adults, placement of nebulizer at the inlet of humidifier increases inhaled dose while reducing rainout obstructing nasal prongs. When HFNC gas flow is set below patient inspiratory flow, aerosol deposition is higher than when the gas flow exceeds patient inspiratory flow; thus, if tolerated, titrating down HFNC gas flow during trans-nasal aerosol delivery, with close monitoring and the use of unit dose with high concentration are recommended. Trans-nasal pulmonary aerosol delivery has not been shown to increase bioaerosols generated by patients, but gas flow may disperse aerosols. Placement of a surgical or procedure mask over HFNC might reduce aerosol dispersion.
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http://dx.doi.org/10.21037/atm-20-7383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105792PMC
April 2021

Aerosol delivery via invasive ventilation: a narrative review.

Ann Transl Med 2021 Apr;9(7):588

Department of Respiratory Care, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

In comparison with spontaneously breathing non-intubated subjects, intubated, mechanically ventilated patients encounter various challenges, barriers, and opportunities in receiving medical aerosols. Since the introduction of mechanical ventilation as a part of modern critical care medicine during the middle of the last century, aerosolized drug delivery by jet nebulizers has become a common practice. However, early evidence suggested that aerosol generators differed in their efficacies, and the introduction of newer aerosol technology (metered dose inhalers, ultrasonic nebulizer, vibrating mesh nebulizers, and soft moist inhaler) into the ventilator circuit opened up the possibility of optimizing inhaled aerosol delivery during mechanical ventilation that could meet or exceed the delivery of the same aerosols in spontaneously breathing patients. This narrative review will catalogue the primary variables associated with this process and provide evidence to guide optimal aerosol delivery and dosing during mechanical ventilation. While gaps exist in relation to the appropriate aerosol drug dose, discrepancies in practice, and cost-effectiveness of the administered aerosol drugs, we also present areas for future research and practice. Clinical practice should expand to incorporate these techniques to improve the consistency of drug delivery and provide safer and more effective care for patients.
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http://dx.doi.org/10.21037/atm-20-5665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105868PMC
April 2021

Demystifying medical aerosols in acute and critical care.

Ann Transl Med 2021 Apr;9(7):587

Chief Science Officer, Aerogen Pharma Corp. San Mateo, CA, USA.

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http://dx.doi.org/10.21037/atm-21-964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105827PMC
April 2021

Aerosol drug delivery to tracheotomized patients with COVID-19: Pragmatic suggestions for clinicians.

Can J Respir Ther 2021 30;57:49-52. Epub 2021 Apr 30.

Department of Respiratory Care, Texas State University, College of Health Professions, Round Rock, TX, USA.

Because of the wide and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of hospitalized patients with coronavirus disease 2019 (COVID-19) has rapidly increased medically complex and resource-intensive treatment requirements in health care settings. Although tracheostomy is frequently needed for critically ill patients requiring extended mechanical ventilation, it has been described as an aerosol-generating procedure that puts health care professionals at an increased risk of viral transmission. In addition, the delivery of aerosolized medications to this patient population has become controversial because of concerns on the transmission of SARS-CoV-2 via droplets. Although aerosol therapy in spontaneously breathing patients with COVID-19 was described in recent publications, innovations in aerosol drug delivery to COVID-19 patients with tracheostomy have not been presented. Therefore, empirically based guidance on how to deliver aerosols safely and effectively to tracheotomized patients with COVID-19 is still lacking. This paper provides recommendations and rationales for device selection, interface selection, delivery techniques, and infection control based on the evolving body of literature.
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http://dx.doi.org/10.29390/cjrt-2020-054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086593PMC
April 2021

Comparison of Vibrating Mesh and Jet Nebulizers During Noninvasive Ventilation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

J Aerosol Med Pulm Drug Deliv 2021 12 13;34(6):358-365. Epub 2021 Apr 13.

Division of Respiratory Care, Department of Cardiopulmonary Sciences, Rush University Medical Center, Chicago, Illinois, USA.

Advances in aerosol technology have improved drug delivery efficiency during noninvasive ventilation (NIV). Clinical evaluation of the efficacy of aerosol therapy during NIV in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) is very limited. The aim of our study was to compare the efficacy of bronchodilators administered through a vibrating mesh nebulizer (VMN) and jet nebulizer (JN) during NIV in patients with acute exacerbation of COPD. Prospective randomized cross-over study included 30 patients treated with NIV for acute exacerbation of COPD in an acute care hospital. Patients were consented and enrolled after stabilization of acute exacerbation (3-5 days after admission). Subjects were randomly assigned into two treatment arms receiving salbutamol (2.5 mg): with VMN (Aerogen Solo) and JN (Sidestream) positioned between the leak port and the nonvented oronasal mask during bilevel ventilation with a single-limb circuit. Measurements (clinical data, pulmonary function tests [PFTs], and arterial blood gases) were performed at baseline, 1, and 2 hours after treatment. All measured PFT parameters significantly increased in both groups, but numerically results were better after inhalation with VMN than with JN: for forced expiratory volume in 1 second (FEV) (mean increase from baseline to 120 minutes-165 ± 64 mL vs. 116 ± 46 mL,  = 0.001) and for forced vital capacity (FVC) (mean increase-394 ± 154 mL vs. 123 ± 57 mL,  < 0.001). There was also a statistically significant reduction in respiratory rate and in Borg dyspnea score after therapy with VMN in comparison with the conventional JN. In both groups, there were improvements in PaCO, but with VMN these changes were significantly higher. Bronchodilator administration in patients with acute exacerbation of COPD during NIV with VMN resulted in clinically significant improvements in FVC and in Borg dyspnea score. Additional studies required to determine the impact on clinical outcomes.
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http://dx.doi.org/10.1089/jamp.2020.1665DOI Listing
December 2021

Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy in the Adult ICU Setting.

Respir Care 2021 Sep 6;66(9):1416-1424. Epub 2021 Apr 6.

CHRU Tours, Médecine Intensive Réanimation, CIC Institut National de la Santé et de la Recherche Médicale 1415, CRICS-TriggerSEP F-CRIN Research Network, Tours, France.

Background: High-flow nasal cannula (HFNC) oxygen therapy has been broadly used. However, no consensus has been achieved on the practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult patients.

Methods: An online anonymous questionnaire survey endorsed by 4 academic societies from America, Europe, mainland China, and Taiwan was administered from May to December 2019. Clinicians who had worked in adult ICUs for > 1 year and had used HFNC to treat patients within 30 days were included.

Results: A total of 2,279 participants clicked on the survey link, 1,358 respondents completed the HFNC section of the questionnaire, whereas 1,014 completed the whole survey. Postextubation hypoxemia and moderate hypoxemia were major indications for HFNC. The initial flow was mainly set at 40-50 L/min. Aerosol delivery via HFNC was used by 24% of the participants (248/1,014), 30% (74/248) of whom reported reducing flow during aerosol delivery. For the patients who required aerosol treatment during HFNC therapy, 40% of the participants (403/1,014) reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC whereas 33% (331/1,014) discontinued HFNC to use conventional aerosol devices. A vibrating mesh nebulizer was the most commonly used nebulizer (40%) and was mainly placed at the inlet of the humidifier.

Conclusions: The clinical utilization of HFNC was variable, as were indications, flow settings, and criteria for adjustment. Many practices associated with concomitant aerosol therapy were not consistent with available evidence for optimal use. More efforts are warranted to close the knowledge gap.
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http://dx.doi.org/10.4187/respcare.08996DOI Listing
September 2021

Breath-Synchronized Nebulized Surfactant in a Porcine Model of Acute Respiratory Distress Syndrome.

Crit Care Explor 2021 Feb 15;3(2):e0338. Epub 2021 Feb 15.

Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA.

Objectives: Effective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model.

Design: Preclinical study.

Setting: Research laboratory.

Subjects: Anesthetized pigs.

Intervention: In vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao/Fio <100) with lung lavages and ventilator-induced lung injury during invasive ventilation.

Measurements And Main Results: Mass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals ( = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao/Fio (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects ( = 3) maintained Pao/Fio less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups.

Conclusions: Breath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.
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http://dx.doi.org/10.1097/CCE.0000000000000338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886457PMC
February 2021

Placing a mask on COVID-19 patients during high-flow nasal cannula therapy reduces aerosol particle dispersion.

ERJ Open Res 2021 Jan 25;7(1). Epub 2021 Jan 25.

CHRU Tours, Médecine Intensive Réanimation, CIC INSERM 1415, CRICS-TriggerSEP Research Network, Tours, France.

https://bit.ly/2HLg5cE.
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http://dx.doi.org/10.1183/23120541.00519-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607969PMC
January 2021

Effects of Inhaled Epoprostenol and Prone Positioning in Intubated Coronavirus Disease 2019 Patients With Refractory Hypoxemia.

Crit Care Explor 2020 Dec 16;2(12):e0307. Epub 2020 Dec 16.

Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN.

Objectives: To evaluate the effects of inhaled epoprostenol and prone positioning, individually and in combination in mechanically ventilated patients with coronavirus disease 2019 and refractory hypoxemia.

Design: Retrospective study.

Setting: Academic hospital adult ICUs.

Patients: Adult patients who received inhaled epoprostenol and prone positioning during invasive ventilation were enrolled. Patients were excluded if inhaled epoprostenol was initiated: 1) at an outside hospital, 2) after prone positioning was terminated, 3) during extracorporeal membrane oxygenation or cardiopulmonary resuscitation, and 4) with Pao/Fio greater than 150 mm Hg.

Interventions: Inhaled epoprostenol and prone positioning.

Results: Of the 43 eligible patients, 22 and seven received prone positioning and inhaled epoprostenol alone, respectively, prior to their use in combination, Pao/Fio was not different pre- and post-prone positioning or inhaled epoprostenol individually (89.1 [30.6] vs 97.6 [30.2] mm Hg; = 0.393) but improved after the combined use of inhaled epoprostenol and prone positioning (84.0 [25.6] vs 124.7 [62.7] mm Hg; < 0.001). While inhaled epoprostenol and prone positioning were instituted simultaneously in 14 patients, Pao/Fio was significantly improved (78.9 [27.0] vs 150.2 [56.2] mm Hg, = 0.005) with the combination. Twenty-seven patients (63%) had greater than 20% improvement in oxygenation with the combination of inhaled epoprostenol and prone positioning, and responders had lower mortality than nonresponders (52 vs 81%; = 0.025).

Conclusions: In critically ill, mechanically ventilated patients with coronavirus disease 2019 who had refractory hypoxemia, oxygenation improved to a greater extent with combined use of inhaled epoprostenol and prone positioning than with each treatment individually. A higher proportion of responders to combined inhaled epoprostenol and prone positioning survived compared with nonresponders. These findings need to be validated by randomized, prospective clinical trials.
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http://dx.doi.org/10.1097/CCE.0000000000000307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746203PMC
December 2020

The utilization of aerosol therapy in mechanical ventilation patients: a prospective multicenter observational cohort study and a review of the current evidence.

Ann Transl Med 2020 Sep;8(17):1071

Department of Respiratory and Critical Care Medicine, West China Medical Center, Sichuan University, Chengdu, China.

Background: Aerosol delivery via mechanical ventilation has been reported to vary significantly among different intensive care units (ICU). The optimal technique for using each aerosol generator may need to be updated with the available evidence.

Methods: A 2-week prospective multicenter observational cohort study was implemented to record aerosol delivery for mechanically ventilated adult patients in Chinese ICUs. Our data included the type of aerosol device and its placement, ventilator type, humidification, and aerosolized medication administered. A guide for the optimal technique for aerosol delivery during mechanical ventilation was summarized after a thorough literature review.

Results: A total of 160 patients (105 males) from 28 ICUs were enrolled, of whom 125 (78.1%) received aerosol therapy via invasive ventilation. Among these 125 patients, 53 received ventilator-integrated jet nebulizer, with 64% (34/53) of them placed the nebulizer close to Y piece in the inspiratory limb. Further, 56 patients used continuous nebulizers, with 84% (47/56) of them placed the nebulizer close to the Y piece in the inspiratory limb. Of the 35 patients who received aerosol therapy via noninvasive ventilation, 30 received single limb ventilators and continuous nebulizers, with 70% (21/30) of them placed between the mask and exhalation port. Only 36% (58/160) of the patients received aerosol treatments consistent with optimal practice.

Conclusions: Aerosol delivery via mechanical ventilation varied between ICUs, and only 36% of the patients received aerosol treatments consistent with optimal practice. ICU clinicians should be educated on the best practices for aerosol therapy, and quality improvement projects aim to improve the quality and outcome of patients with the optimal technique for aerosol delivery during mechanical ventilation are warranted.
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http://dx.doi.org/10.21037/atm-20-1313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575997PMC
September 2020

Airborne Particulate Concentrations During and After Pulmonary Function Testing.

Chest 2021 04 1;159(4):1570-1574. Epub 2020 Nov 1.

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN.

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http://dx.doi.org/10.1016/j.chest.2020.10.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807333PMC
April 2021

In Vitro Evaluation of a Vibrating-Mesh Nebulizer Repeatedly Use over 28 Days.

Pharmaceutics 2020 Oct 15;12(10). Epub 2020 Oct 15.

Department of Respiratory Therapy, Collage of Medicine, Chang Gung University, Taoyuan 33301, Taiwan.

This in vitro study evaluates the performance of a disposable vibrating-mesh nebulizer when used for 28 days. A lung model was used to simulate the breathing pattern of an adult with chronic obstructive pulmonary disease. The vibrating-mesh nebulizer was used for three treatments/day over 28 days without cleaning after each test. Results showed that the inhaled drug dose was similar during four weeks of use ( = 0.157), with 16.73 ± 4.46% at baseline and 15.29 ± 2.45%, 16.21 ± 2.21%, 17.56 ± 1.98%, and 17.13 ± 1.81%, after the first, second, third, and fourth weeks, respectively. The particle size distribution, residual drug volume, and nebulization time remained similar across four weeks of use ( = 0.110, = 0.763, and = 0.573, respectively). Mesh was inspected using optical microscopy and showed that approximately 50% of mesh pores were obscured after 84 runs, and light penetration through the aperture plate was significantly reduced after the 21st use ( < 0.001) with no correlation to nebulizer performance. We conclude that the vibrating-mesh nebulizer delivered doses of salbutamol solution effectively over four weeks without cleaning after each use even though the patency and clarity of the aperture plate were reduced by the first week of use.
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http://dx.doi.org/10.3390/pharmaceutics12100971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602390PMC
October 2020

Practical strategies to reduce nosocomial transmission to healthcare professionals providing respiratory care to patients with COVID-19.

Crit Care 2020 09 23;24(1):571. Epub 2020 Sep 23.

Division of Respiratory Care, Department of Cardiopulmonary Sciences, Rush University Medical Center, 1620 W Harrison St, Tower LL1202, Chicago, IL, 60612, USA.

Coronavirus disease (COVID-19) is an emerging viral infection that is rapidly spreading across the globe. SARS-CoV-2 belongs to the same coronavirus class that caused respiratory illnesses such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). During the SARS and MERS outbreaks, many frontline healthcare workers were infected when performing high-risk aerosol-generating medical procedures as well as when providing basic patient care. Similarly, COVID-19 disease has been reported to infect healthcare workers at a rate of ~ 3% of cases treated in the USA. In this review, we conducted an extensive literature search to develop practical strategies that can be implemented when providing respiratory treatments to COVID-19 patients, with the aim to help prevent nosocomial transmission to the frontline workers.
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http://dx.doi.org/10.1186/s13054-020-03231-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509502PMC
September 2020

Predictive anatomical factors of lung aerosol deposition in obese individuals. Would modified mallampati score be relevant? Clinical trial.

Respir Med 2020 09 12;171:106083. Epub 2020 Jul 12.

Department of Physiotherapy, Universidade Federal de Pernambuco, Recife, Brazil. Electronic address:

Background: Obesity is a highly prevalent condition worldwide that aggravates symptoms of already existing conditions such as asthma and COPD. The limited effectiveness of inhaled medications in these individuals may be related to anatomic characteristics of their upper airways, mainly due to compressive factors.

Methods: Controlled clinical trial with obese and nonobese individuals. The following variables were evaluated: anthropometric characteristics, Lung and airway deposition of radiolabeled aerosol (pulmonary scintigraphy), upper airways anatomy (CT scans), and modified Mallampati score.

Results: 29 subjects (17 nonobese and 12 obese) participated. Obese volunteers presented 30% lower aerosol lung deposition compared to nonobese. Moreover, obese subjects Mallampati classification of 4 presented an aerosol lung deposition two times lower than nonobese subjects (p = 0.021). The cross-sectional area of the retropalatal region and retroglossal region were lower in obese patients (p < 0.05), but no correlation to aerosol lung deposition was observed. BMI was associated with 32% of the variance of lung deposition (p < 0.001; β -0.28; 95% CI -0.43 to -0.11).

Conclusion: High BMI correlated to reduced percentage lung deposition. Also, modified Mallampati class 4 was even more detrimental to aerosol delivery into the lungs. Obese subjects have narrower upper airways, compared to nonobese, but this is not reflected in higher radiolabeled aerosol impaction into their oropharynx and does not predict the percentage of lung deposition in this group.

Clinical Trial Registration: NCT03031093 (clinicaltrials.org).
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http://dx.doi.org/10.1016/j.rmed.2020.106083DOI Listing
September 2020

Author Response to the Letter Entitled "A Good and Reliable Bronchodilator Dose-Response Relationship".

Authors:
Jie Li James B Fink

Respiration 2020 9;99(8):699. Epub 2020 Sep 9.

Division of Respiratory Care, Department of Cardiopulmonary Sciences, Rush University, Chicago, Illinois, USA.

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http://dx.doi.org/10.1159/000508164DOI Listing
December 2020

High-flow nasal cannula for COVID-19 patients: risk of bio-aerosol dispersion.

Eur Respir J 2020 10 8;56(4). Epub 2020 Oct 8.

CHRU Tours, Médecine Intensive Réanimation, CIC INSERM 1415, CRICS-TriggerSep network, Tours, France.

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http://dx.doi.org/10.1183/13993003.03136-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453737PMC
October 2020
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