Publications by authors named "James B Fink"

107 Publications

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 Apr 13. 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
April 2021

Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy among Adult Critical Care Subjects.

Respir Care 2021 Apr 6. Epub 2021 Apr 6.

CHRU Tours, Médecine Intensive Réanimation, CIC INSERM 1415, CRICS-TriggerSEPresearch network, Tours, France; and INSERM, Centre d'étude des pathologies respiratoires, U1100, Université de Tours, Tours, France.

Background: Therapy with high-flow nasal cannula (HFNC) has been broadly utilized. However, no consensus has been achieved on practical implementation of HFNC and how to provide aerosol delivery during HFNC therapy in adult subjects.

Methods: An online anonymous questionnaire survey, endorsed by four academic societiesfrom America, Europe, mainland China and Taiwan, was administered from May to December, 2019.Clinicians who had worked in adult intensive care unit for more than one year and had used HFNC to treat subjects within 30 days were included.

Results: 2,279 participants clicked on the survey link, 1358 respondents completed the HFNC section, while 1014 completed the whole survey. Post-extubation hypoxemia and moderate hypoxemia were major indications for HFNC. Initial flow was set mainly at 40-50 L/min. Aerosol delivery via HFNC was utilized by 24% (248/1014) of participants, 30% (74/248) of whom reported reducing flow during aerosol delivery. For subjects who required aerosol treatment during HFNC therapy, 40% (403/1014) of participants reported placing a nebulizer with a mask or mouthpiece while pursuing HFNC (a method shown to reduce inhaled dose) while 33% (331/1014) discontinued HFNC to use conventional aerosol devices. Vibrating mesh nebulizer (VMN) 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
April 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 Apr 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
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

A narrative review on trans-nasal pulmonary aerosol delivery.

Crit Care 2020 08 17;24(1):506. Epub 2020 Aug 17.

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

The use of trans-nasal pulmonary aerosol delivery via high-flow nasal cannula (HFNC) has expanded in recent years. However, various factors influencing aerosol delivery in this setting have not been precisely defined, and no consensus has emerged regarding the optimal techniques for aerosol delivery with HFNC. Based on a comprehensive literature search, we reviewed studies that assessed trans-nasal pulmonary aerosol delivery with HFNC by in vitro experiments, and in vivo, by radiolabeled, pharmacokinetic and pharmacodynamic studies. In these investigations, the type of nebulizer employed and its placement, carrier gas, the relationship between gas flow and patient's inspiratory flow, aerosol delivery strategies (intermittent unit dose vs continuous administration by infusion pump), and open vs closed mouth breathing influenced aerosol delivery. The objective of this review was to provide rational recommendations for optimizing aerosol delivery with HFNC in various clinical settings.
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http://dx.doi.org/10.1186/s13054-020-03206-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430014PMC
August 2020

Novel Toxicology Program to Support the Development of Inhaled VentaProst.

Int J Toxicol 2020 Sep/Oct;39(5):433-442. Epub 2020 Aug 13.

Aerogen Pharma Corporation, San Mateo, CA, USA.

Currently, off-label continuous administration of inhaled epoprostenol is used to manage hemodynamics during mitral valve surgery. A toxicology program was developed to support the use of inhaled epoprostenol during mechanical ventilation as well as pre- and postsurgery via nasal prongs. To support use in patients using nasal prongs, a Good Laboratory Practice (GLP), 14-day rat, nose-only inhalation study was performed. No adverse findings were observed at ∼50× the dose rate received by patient during off-label use. To simulate up to 48 hours continuous aerosol exposure during mechanical ventilation, a GLP toxicology study was performed using anesthetized, intubated, mechanically ventilated dogs. Dogs inhaled epoprostenol at approximately 6× and 13× the dose rate reported in off-label human studies. This novel animal model required establishment of a dog intensive care unit providing sedation, multisystem support, partial parenteral nutrition, and management of the intubated mechanically ventilated dogs for the 48-hour duration of study. Aerosol was generated by a vibrating mesh nebulizer with novel methods required to determine dose and particle size in-vitro. Continuous pH 10.5 epoprostenol was anticipated to be associated with lung injury; however, no adverse findings were observed. As no toxicity at pH 10.5 was observed with a formulation that required refrigeration, a room temperature stable formulation at pH 12 was evaluated in the same ventilated dog model. Again, there were no adverse findings. In conclusion, current toxicology findings support the evaluation of inhaled epoprostenol at pH 12 in surgical patients with pulmonary hypertension for up to 48 hours continuous exposure.
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http://dx.doi.org/10.1177/1091581820945985DOI Listing
August 2020

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

J Aerosol Med Pulm Drug Deliv 2020 12 12;33(6):300-304. Epub 2020 Aug 12.

Department of Medicine, Graduate School of Medicine, University of Tennessee Health Science Center, Knoxville, Tennessee, USA.

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.
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http://dx.doi.org/10.1089/jamp.2020.1615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757542PMC
December 2020

Managing humidity support in intubated ventilated patients with coronavirus disease 2019 (COVID-19).

Infect Control Hosp Epidemiol 2020 Aug 12:1-2. Epub 2020 Aug 12.

Department of Respiratory Therapy, Chang Gung University, Taoyuan, Taiwan.

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http://dx.doi.org/10.1017/ice.2020.418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463149PMC
August 2020

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

Eur Respir J 2020 05 14;55(5). Epub 2020 May 14.

CHRU Tours, Médecine Intensive Réanimation, CIC INSERM 1415, CRICS-TriggerSep network, Tours France; and INSERM, Centre d'étude des pathologies respiratoires, U1100, Université de Tours, Tours, France.

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http://dx.doi.org/10.1183/13993003.00892-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163690PMC
May 2020

Optimal Connection for Tiotropium SMI Delivery through Mechanical Ventilation: An In Vitro Study.

Pharmaceutics 2020 Mar 24;12(3). Epub 2020 Mar 24.

Department of Respiratory Therapy, Chang Gung Memorial Hospital, Chiayi 61301, Taiwan.

We aimed to quantify Soft Mist Inhalers (SMI) delivery to spontaneous breathing model and compare with different adapters via endotracheal tube during mechanical ventilation or by manual resuscitation. A tiotropium SMI was used with a commercial in-line adapter and a T-adapter placed between the Y-adapter and the inspiratory limb of the ventilator circuit during mechanical ventilation. The SMI was actuated at the beginning of inspiration and expiration. In separate experiments, a manual resuscitator with T-adapter was attached to endotracheal tube, collecting filter, and a passive test lung. Drug was eluted from collecting filters with salt-based solvent and analyzed using high-performance liquid chromatography. Results showed the percent of SMI label dose inhaled was 3-fold higher with the commercial in-line adapter with actuation during expiration than when synchronized with inspiration. SMI with T-adapter delivery via ventilator was similar to inhalation (1.20%) or exhalation (1.02%), and both had lower delivery dose than with manual resuscitator (2.80%; = 0.01). The inhaled dose via endotracheal tube was much lower than inhaled dose with spontaneous breathing (22.08%). In conclusion, the inhaled dose with the commercial adapter was higher with SMI actuated during expiration, but still far less than reported spontaneous inhaled dose.
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http://dx.doi.org/10.3390/pharmaceutics12030291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151005PMC
March 2020

The Clinical Impact of Flow Titration on Epoprostenol Delivery via High Flow Nasal Cannula for ICU Patients with Pulmonary Hypertension or Right Ventricular Dysfunction: A Retrospective Cohort Comparison Study.

J Clin Med 2020 Feb 7;9(2). Epub 2020 Feb 7.

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

(1) Background: inhaled epoprostenol (iEPO) delivered via high-flow nasal cannula (HFNC) has been reported to be effective for pulmonary hypertension and right ventricular dysfunction. In vitro studies have identified HFNC gas flow as a key factor in trans-nasal aerosol delivery efficiency; however, little evidence is available on the clinical impact of flow titration on trans-nasal aerosol delivery. At our institution, iEPO via HFNC was initiated in 2015 and the concept of flow titration during iEPO via HFNC has been gradually accepted and carried out by clinicians in the recent years. (2) Methods: a retrospective review of the electronic medical records for all adult patients who received iEPO via HFNC in a tertiary teaching hospital. Pre- and post- iEPO responses were reported for patients whose HFNC flow was titrated or maintained constant during iEPO delivery. Positive response to iEPO was defined as the reduction of mean pulmonary arterial pressure (mPAP) > 10% for pulmonary hypertension patients or the improvement of oxygenation [pulse oximetry (SpO)/fraction of inhaled oxygen (FO)] > 20%. The number of responders to iEPO was compared between groups with titrated vs constant flow. (3) Results: 51 patients who used iEPO to treat pulmonary hypertension and/or right ventricular dysfunction were reviewed. Following iEPO administration via HFNC, mPAP decreased (43.6 ± 11.7 vs. 36.3 ± 9.7 mmHg, < 0.001). Among the 51 patients, 24 had concomitant refractory hypoxemia, their oxygenation (SpO/FO) improved after iEPO delivery (127.8 ± 45.7 vs. 157.6 ± 62.2, < 0.001). During iEPO initiation, gas flow was titrated in 25 patients and the remaining 26 patients used constant flow. The percentage of patients in the flow titration group who met the criteria for a positive response was higher compared to the group with constant flow (85.7% vs. 50%, = 0.035). Pre- vs post-iEPO responses were significant in the flow titration group included improvement in cardiac output ( = 0.050), cardiac index ( = 0.021) and FO reduction ( = 0.016). These improvements in hemodynamics and FO were not observed in the constant flow group. (4) Conclusion: in patients with pulmonary hypertension and/or right ventricular dysfunction, trans-nasal iEPO decreased pulmonary arterial pressure. It also improved oxygenation in patients with combined refractory hypoxemia. These improvements were more evident in patients whose gas flow was titrated during iEPO initiation than those patients using constant flow.
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http://dx.doi.org/10.3390/jcm9020464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074129PMC
February 2020

More than just a screen to liberate from mechanical ventilation: treat to keep extubated?

Ann Transl Med 2019 Dec;7(Suppl 8):S338

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

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http://dx.doi.org/10.21037/atm.2019.09.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976406PMC
December 2019

In vitro comparison between inspiration synchronized and continuous vibrating mesh nebulizer during trans-nasal aerosol delivery.

Intensive Care Med Exp 2020 Jan 31;8(1). Epub 2020 Jan 31.

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

Background: Compared to continuous vibrating mesh nebulizer (VMN), inspiration synchronized VMN has shown increased inhaled dose during noninvasive ventilation; however, its use during aerosol delivery via high-flow nasal cannula (HFNC) is still unknown.

Methods: An adult manikin was connected to a dual-chamber model lung, which was driven by a critical care ventilator to simulate spontaneous breathing. A HFNC system was utilized with temperature at 37 ° C while gas flow at 5, 10, 20, 40, and 60 L/min. Inspiration synchronized and continuous aerosol generation were compared at different positions (at the inlet of humidifier vs close to patient). One milliliter of albuterol (2.5 mg/mL) was used in each run (n = 3). Collection filter was placed at the trachea and was removed after each run. Drug was eluted from the filter and assayed with UV spectrophotometry (276 nm).

Results: When nebulizer was placed close to patient, inhaled dose was higher with inspiration synchronized than continuous aerosol generation at all gas flows (p = 0.05) except at 5 L/min. When placed at the inlet of humidifier, compared to continuous, inspiration synchronized aerosol generated higher inhaled dose with gas flow set below 50% of patient inspiratory flow [23.9 (20.6, 28.3)% vs 18.1 (16.7, 19.6)%, p < 0.001], but lower inhaled dose with gas flow set above 50% of patient inspiratory flow [3.5 (2.2, 9.3)% vs 9.9 (8.2, 16.4)%, p = 0.001]. Regardless of breathing pattern, continuous aerosol delivered greater inhaled dose with nebulizer placed at humidifier than close to patient at all gas flows except at 5 L/min.

Conclusion: When the HFNC gas flow was set higher than 50% of patient inspiratory flow, no significant advantage was found in inspiration synchronized over continuous aerosol. However, inspiration synchronized aerosol generated 30% more inhaled dose than continuous with gas flow set below 50% of patient inspiratory flow, regardless of nebulizer placement. Continuous nebulizer needs to be placed at the inlet of humidifier.
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http://dx.doi.org/10.1186/s40635-020-0293-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994578PMC
January 2020

Recent advances in aerosol devices for the delivery of inhaled medications.

Expert Opin Drug Deliv 2020 02 20;17(2):133-144. Epub 2020 Jan 20.

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

: Aerosolized medications are commonly prescribed for the treatment of patients with pulmonary diseases, and there has been an increased interest in the development of aerosol delivery devices over the years. Technical innovations have advanced device design, novel features such as breath actuation, dose tracking, portability, and feedback mechanism during treatment that improved the performance of aerosol devices, and effectiveness of inhalation therapy.: The purpose of this paper is to review recent advances in aerosol devices for delivery of inhaled medications.: Drug formulations and device designs are rapidly evolving to make more consistent dosing across a broad range of inspiratory efforts, to maximize dose and target specific areas of the diseased lung.
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http://dx.doi.org/10.1080/17425247.2020.1712356DOI Listing
February 2020

In vitro comparison of unit dose vs infusion pump administration of albuterol via high-flow nasal cannula in toddlers.

Pediatr Pulmonol 2020 02 29;55(2):322-329. Epub 2019 Nov 29.

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

Objectives: Transnasal pulmonary aerosol delivery using high-flow nasal cannula (HFNC) devices has become a popular route of aerosol administration in toddlers. Clinically, albuterol is administered using an infusion pump or unit doses. However, little evidence is available to compare the two administration strategies.

Methods: A toddler manikin (15 kg) with appropriate anatomic airway was connected with collecting filter to a simulator of distressed breathing. HFNC device with mesh nebulizer placed at the inlet of a humidifier at 37°C, with the gas flow set at 25 and 3.75 L/min. Five milligrams of albuterol was delivered in all experiments. With infusion pump administration, albuterol concentrations of 5 and 1 mg/mL were delivered at 4 and 20 mL/hr for 15 minutes. With unit dose administration, 1 mL (5 mg/mL) and 2 mL (2.5 mg/mL) of albuterol were nebulized. Additional tests with mouth open and nebulizers via mask were using 5 mg/1 mL for mesh nebulizer and 5 mg/3 mL for jet nebulizer (n = 3). The drug was eluted from the filter and assayed with UV spectrophotometry (276 nm).

Results: The inhaled dose was higher with unit dose than infusion pump administration with gas flows of 25 L/min (2.66 ± 0.38 vs 1.16 ± 0.28%; P = .004) and 3.75 L/min (10.51 ± 1.29 vs 8.58 ± 0.68%; P = .025). During unit dose administration, compared with closed-mouth breathing, open-mouth breathing generated a higher inhaled dose at 3.75 L/min and lower inhaled dose at 25 L/min. Compared to the nebulizers via mask with both open and closed-mouth breathing, nebulization via HFNC at 3.75 L/min generated greater inhaled dose, while HFNC at 25 L/min generated lower inhaled dose.

Conclusions: During transnasal aerosol delivery, the inhaled dose was higher with medication administrated using unit dose than using an infusion pump.
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http://dx.doi.org/10.1002/ppul.24589DOI Listing
February 2020

Aerosol Delivery During Continuous High Frequency Oscillation for Simulated Adults During Quiet and Distressed Spontaneous Breathing.

Respir Care 2020 Feb 1;65(2):227-232. Epub 2019 Oct 1.

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

Background: Continuous high-frequency oscillation (CHFO) is a therapeutic mode for the mobilization of secretions. The Metaneb CHFO device also incorporates aerosol administration using an integrated jet nebulizer. However, the effectiveness of aerosol delivery and influential factors remain largely unreported.

Methods: A collecting filter was placed between an adult manikin with a representative upper airway and a breath simulator, set to simulate quiet and distressed patterns of spontaneous adult breathing. The Metaneb CHFO device was attached to the manikin via a mask. Two jet nebulizers were tested in 2 different positions: placement in the manifold and placement between manifold and mask. A vibrating mesh nebulizer was placed between the manifold and mask with and without extension tubing. Aerosol administration was compared during CHFO and during nebulization mode alone. Albuterol (2.5 mg in 3 mL) was nebulized for each condition. The drug was eluted from the filter and assayed with ultraviolet spectrophotometry (276 nm).

Results: During CHFO, inhaled doses with jet nebulizers were low (∼ 2%), regardless of nebulizer placement. Inhaled dose was improved with the vibrating mesh nebulizer placed between the manifold and mask (12.48 ± 2.24% vs 2.58 ± 0.48%, = .004). Inhaled doses with the jet nebulizer in the manifold with nebulization mode alone was lower than with the jet nebulizer with an aerosol mask (4.03 ± 1.82% vs 10.39 ± 2.79%, = .004). Inhaled dose was greater with distressed breathing than quiet breathing. The use of a vibrating mesh nebulizer ( < .001) and distressed breathing ( = .001) were identified as predictors of increased inhaled dose.

Conclusions: Inhaled dose with a jet nebulizer via the Metaneb CHFO device was lower than with a jet nebulizer alone. Placement of a vibrating mesh nebulizer at the airway and distressed breathing increased inhaled dose.
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http://dx.doi.org/10.4187/respcare.07050DOI Listing
February 2020

Size Distribution of Colistin Delivery by Different Type Nebulizers and Concentrations During Mechanical Ventilation.

Pharmaceutics 2019 Sep 5;11(9). Epub 2019 Sep 5.

Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.

Although aerosol delivery through mechanical ventilators has been used to administer various medications, little is known of administration with colistin. This in vitro evaluation aimed to evaluate size distribution of colistin delivery by different types of nebulizers and concentrations during mechanical ventilation. Colistin methanesulfonate (colistin) for injection was dissolved in 6 mL of distilled water to produce a low concentration (L; 156 mg) and a high concentration (H; 312 mg). A dose volume of 6 mL was placed in a vibrating mesh nebulizer (VMN) and a jet nebulizer (JN). The inhaled mass (mean ± SD) of the VMN-L (53.80 ± 14.79 mg) was greater than both the JN-L (19.82 ± 3.34 mg, = 0.001) and JN-H (31.72 ± 4.48 mg, = 0.017). The nebulization time of the VMN-L (42.35 ± 2.30 min) was two times longer than the JN-L (21.12 ± 0.8 min) or JN-H (21.65 ± 0.42 min; < 0.001). The mass median aerodynamic distal to the endotracheal tube was within a similar range at 2.03 to 2.26 μm ( = 0.434), independent of neb or formulation concentration. In conclusion, the VMN-L yields greater inhaled mass than the JN with either concentration. Therefore, a standard nominal dose of colistin results in a higher delivered dose during mechanical ventilation with a VMN compared with a JN and may be considered the preferred device. If JN must be used, multiple doses of low concentration colistin may compensate for poor delivery performance.
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http://dx.doi.org/10.3390/pharmaceutics11090459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781281PMC
September 2019

Dose Response to Transnasal Pulmonary Administration of Bronchodilator Aerosols via Nasal High-Flow Therapy in Adults with Stable Chronic Obstructive Pulmonary Disease and Asthma.

Respiration 2019;98(5):401-409. Epub 2019 Aug 30.

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

Background: There has been increasing interest in transnasal pulmonary aerosol administration, but the dose-response relationship has not been reported.

Objectives: To determine the accumulative bronchodilator dose at which patients with stable mild-to-moderate asthma and chronic obstructive pulmonary disease (COPD) achieve similar spirometry responses before and after bronchodilator tests using albuterol via a metered dose inhaler with a valved holding chamber (MDI + VHC).

Method: Adult patients who met ATS/ERS criteria for bronchodilator responses in pulmonary function laboratory were recruited and consented to participate. After a washout period, patients received escalating doubling dosages (0.5, 1, 2, and 4 mg) of albuterol in a total volume of 2 mL delivered by vibrating mesh nebulizer via a nasal cannula at 37°C with a flow rate of 15-20 L/min using a Venturi air entrainment device. Spirometry was measured at baseline and after each dose. Titration was stopped when an additional forced expiratory volume in 1 second (FEV1) improvement was <5%.

Results: 42 patients (16 males) with stable mild-to-moderate asthma (n = 29) and COPD (n = 13) were enrolled. FEV1 increment after a cumulative dose of 1.5 mg of albuterol via nasal cannula at 15-20 L/min was similar to 4 actuations of MDI + VHC (0.34 ± 0.18 vs. 0.34 ± 0.12 L, p = 0.878). Using ATS/ERS criteria of the bronchodilator test, 33.3% (14/42) and 69% (29/42) of patients responded to 0.5 and 1.5 mg of albuterol, respectively.

Conclusions: With a nasal cannula at 15-20 L/min, transnasal pulmonary delivery of 1.5 mg albuterol resulted in similar bronchodilator response as 4 actuations of MDI + VHC.
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http://dx.doi.org/10.1159/000501564DOI Listing
September 2020