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Review
. 2024 Jul;21(7):1103-1114.
doi: 10.1080/17425247.2024.2388838. Epub 2024 Aug 12.

Dos and don'ts to optimize transnasal aerosol drug delivery in clinical practice

Affiliations
Review

Dos and don'ts to optimize transnasal aerosol drug delivery in clinical practice

Arzu Ari et al. Expert Opin Drug Deliv. 2024 Jul.

Abstract

Introduction: Transnasal aerosol drug delivery has become widely accepted for treating acutely ill infants, children, and adults. More recently aerosol administration to wider populations receiving high and low-flow nasal oxygen has become common practice.

Areas covered: Skepticism of insufficient aerosol delivery to the lungs has been tempered by multiple in vitro explorations of variables to optimize delivery efficiency. Additionally, clinical studies demonstrated comparable clinical responses to orally inhaled aerosols. This paper provides essential clinical guidance on how to improve transnasal aerosol delivery based on device-, settings-, and drug-related optimization to serve as a resource for educational initiatives and quality enhancement endeavors at healthcare institutions.

Expert opinion: Transnasal aerosol delivery is proliferating worldwide, but indiscriminate use of excessive-high flows, poor selection and placement of aerosol devices and circuits can greatly reduce aerosol delivery and efficacy, potentially compromising treatment to acute and critically ill patients. Attention to these details can improve inhaled dose by an order of magnitude, making the difference between effective treatment and the progression to more invasive ventilatory support, with greater inherent risk and cost. These revelations have prompted specific recommendations for optimal delivery, driving advancements in aerosol generators, formulations, and future device designs to administer aerosols and maximize treatment effectiveness.

Keywords: Aerosols; adults; children; drug delivery; flow rate; high flow nasal cannula; nebulizers; transnasal.

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Review
. 2023 Jan 18:9:1098427.
doi: 10.3389/fmed.2022.1098427. eCollection 2022.

Aerosol delivery through high-flow nasal therapy: Technical issues and clinical benefits

Affiliations
Review

Aerosol delivery through high-flow nasal therapy: Technical issues and clinical benefits

Cecilia Calabrese et al. Front Med (Lausanne). .

Abstract

High-flow nasal cannula (HFNC) therapy is an oxygen delivery method particularly used in patients affected by hypoxemic respiratory failure. In comparison with the conventional "low flow" oxygen delivery systems, it showed several important clinical benefits. The possibility to nebulize drugs via HFNC represents a desirable medical practice because it allows the administration of inhaled drugs, mostly bronchodilators, without the interruption or modification of the concomitant oxygen therapy. HFNC, by itself has shown to exert a small but significant bronchodilator effect and improves muco-ciliary clearance; thus, the nebulization of bronchodilators through the HFNC circuit may potentially increase their pharmacological activity. Several technical issues have been observed which include the type of the nebulizer that should be used, its position within the HFNC circuit, and the optimal gas flow rates to ensure an efficient drug delivery to the lungs both in "quiet" and "distressed" breathing patterns. The aim of this review has been to summarize the scientific evidence coming from "in vitro" studies and to discuss the results of "in vivo" studies performed in adult subjects, mainly affected by obstructive lung diseases. Most studies seem to indicate the vibrating mesh nebulizer as the most efficient type of nebulizer and suggest to place it preferentially upstream from the humidifier chamber. In a quite breathing patterns, the inhaled dose seems to increase with lower flow rates while in a "distressed" breathing pattern, the aerosol delivery is higher when gas flow was set below the patient's inspiratory flow, with a plateau effect seen when the gas flow reaches approximately 50% of the inspiratory flow. Although several studies have demonstrated that the percentage of the loaded dose nebulized via HFNC reaching the lungs is small, the bronchodilator effect of albuterol seems not to be impaired when compared to the conventional inhaled delivery methods. This is probably attributed to its pharmacological activity. Prospective and well-designed studies in different cohort of patients are needed to standardize and demonstrate the efficacy of the procedure.

Keywords: HFNC; aerosol–therapeutic; bronchodilators; high-flow nasal cannula; jet nebulizer; vibrating mesh nebulizer.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Review
. 2021 Apr;9(7):596.
doi: 10.21037/atm-20-3946.

Administration of dry powders during respiratory supports

Affiliations
Review

Administration of dry powders during respiratory supports

Wei-Ren Ke et al. Ann Transl Med. 2021 Apr.

Abstract

Inhaled drugs are routinely used for the treatment of respiratory-supported patients. To date, pressurized metered dose inhalers and nebulizers are the two platforms routinely employed in the clinical setting. The scarce utilization of the dry powder inhaler (DPI) platform is partly due to the lack of in vivo data that proves optimal delivery and drug efficacy are achievable. Additionally, fitting a DPI in-line to the respiratory circuit is not as straightforward as with the other aerosol delivery platforms. Importantly, there is a common misconception that the warm and humidified inspiratory air in respiratory supports, even for a short exposure, will deteriorate powder formulation compromising its delivery and efficacy. However, some recent studies have dispelled this myth, showing successful delivery of dry powders through the humidified circuit of respiratory supports. Compared with other aerosol delivery devices, the use of DPIs during respiratory supports possesses unique advantages such as rapid delivery and high dose. In this review, we presented in vitro studies showing various setups employing commercial DPIs and effects of ventilator parameters on the aerosol delivery. Inclusion of novel DPIs was also made to illustrate characteristics of an ideal inhaler that would give high lung dose with low powder deposition loss in tracheal tubes and respiratory circuits. Clinical trials are urgently needed to confirm the benefits of administration of dry powders in ventilated patients, thus enabling translation of powder delivery into practice.

Keywords: Dry powder inhaler (DPI); inhaled drug; mechanical ventilation; nasal high flow system; respiratory support.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3946). The series “Medical Aerosol in Acute and Critical Care” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

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Review
. 2021 Apr;9(7):593.
doi: 10.21037/atm-20-1682.

A path to successful patient outcomes through aerosol drug delivery to children: a narrative review

Affiliations
Review

A path to successful patient outcomes through aerosol drug delivery to children: a narrative review

Arzu Ari. Ann Transl Med. 2021 Apr.

Abstract

Although using aerosolized medications is a mainstay of treatment in children with asthma and other respiratory diseases, there are many issues in terms of device and interface selection, delivery technique and dosing, as well as patient and parental education that have not changed for half a century. Also, due to many aerosol devices and interfaces available on the market and the broad range of patient characteristics and requirements, providing effective aerosol therapy to children becomes a challenge. While aerosol delivery devices are equally effective, if they are age-appropriate and used correctly, the majority of aerosol devices require multiple steps to be used efficiently. Unfortunately, many children with pulmonary diseases have problems with the correct delivery technique and do not gain therapeutic benefits from therapy that result in poor disease management and increased healthcare costs. Therefore, the purpose of this paper is to review the current knowledge on aerosol delivery devices used in children and guide clinicians on the optimum device- and interface-selection, delivery technique, and dosing in this patient population. Strategies on how to deliver aerosolized medications in crying and distressed children and how to educate parents on aerosol therapy and promote patient adherence to prescribed medications are also provided. Future directions of aerosol therapy in children should focus on these issues and implement policies and clinical practices that highlight the potential solutions to these problems.

Keywords: Aerosols; and children; facemask; high flow nasal cannula; inhalers; nebulizers.

Conflict of interest statement

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-1682). The series “Medical Aerosol in Acute and Critical Care” was commissioned by the editorial office without any funding or sponsorship. AA reports personal fees from Bayer Pharmaceuticals, personal fees from Sunovion Pharmaceuticals, grants and personal fees from Aerogen Ltd., Grants from ARC Medical, outside the submitted work. The author has no other conflicts of interest to declare.

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Review
. 2021 Apr;9(7):592.
doi: 10.21037/atm-20-2280.

Fugitive aerosols in the intensive care unit: a narrative review

Affiliations
Review

Fugitive aerosols in the intensive care unit: a narrative review

Ciarraí O'Toole et al. Ann Transl Med. 2021 Apr.

Abstract

The risk of unintended inhalation of fugitive aerosols is becoming a topic of increasing interest in the healthcare arena. These fugitive aerosols may be bioaerosols, generated by the patient themselves through cough or sneeze, or they may be therapeutic medical aerosols, generated by therapeutic medical aerosol generators with the intent of delivery to a specific patient's respiratory tract. This review focus' on therapeutic aerosols in the intensive care unit (ICU) only, those typically generated by nebulisers. In the intensive care environment, patients are generally in receipt of ventilatory support, and the literature suggests that these different support interventions influence fugitive therapeutic medical aerosol emissions in a variety of ways. Predominant ventilatory support interventions include, but are not limited to, invasive mechanical ventilation (MV), non-invasive mechanical ventilation (NIV), high flow nasal therapy (HFNT), and supplemental oxygen delivery in spontaneously breathing patients. Further, factors such as nebuliser type, patient interface, patient breathing pattern, nebuliser position in the patient breathing circuit and medication formulation characteristics also have been shown to exert influence on aerosol concentrations and distance from the source. Here we present the state of the art knowledge in this, as yet, poorly described field of research, and identify the key risks, and subsequently, opportunities to mitigate the risks of unintended exposure of both patients and bystanders during and for periods following the administration of therapeutic aerosols.

Keywords: Aerosols; exposure; fugitive; intensive care unit (ICU); jet nebulizer (JN); secondary inhalation; vibrating mesh nebuliser (VMN).

Conflict of interest statement

Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-2280). The series “Medical Aerosol in Acute and Critical Care” was commissioned by the editorial office without any funding or sponsorship. CO, JAM, and MAB reports grants from Irish Research Council, during the conduct of the study. MJ, AO, and RM reports personal fees from Aerogen Limited, outside the submitted work. The authors have no other conflicts of interest to declare.

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Review
. 2021 Apr;9(7):590.
doi: 10.21037/atm-20-7383.

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

Affiliations
Review

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

Jie Li et al. Ann Transl Med. 2021 Apr.

Abstract

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%. In vitro and in vivo 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.

Keywords: Aerosol therapy; high-flow nasal cannula (HFNC); oxygen therapy.

Conflict of interest statement

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7383). The series “Medical Aerosol in Acute and Critical Care” was commissioned by the editorial office without any funding or sponsorship. JBF served as the unpaid Guest Editor of the series. Dr. Li reports grants from Fisher & Paykel Healthcare, during the conduct of the study; grants from Rice foundation, other from Fisher & Paykel Healthcare, other from AARC, outside the submitted work. Dr. Fink is Chief Science Officer for Aerogen Pharma Corp, San Mateo, CA, USA. The authors have no other conflicts of interest to declare.

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Review
. 2021 Mar 1:57:22-25.
doi: 10.29390/cjrt-2020-041. eCollection 2021.

How to deliver aerosolized medications through high flow nasal cannula safely and effectively in the era of COVID-19 and beyond: A narrative review

Affiliations
Review

How to deliver aerosolized medications through high flow nasal cannula safely and effectively in the era of COVID-19 and beyond: A narrative review

Arzu Ari et al. Can J Respir Ther. .

Abstract

Background: The treatments of COVID-19 involve some degree of uncertainty. Current evidence also shows mixed findings with regards to bioaerosol dispersion and airborne transmission of COVID-19 during high flow nasal cannula (HFNC) therapy. While coping with this global pandemic created hot debates on the use of HFNC, it is important to bring detached opinions and current evidence to the attention of health care professionals (HCPs) who may need to use HFNC in patients with COVID-19.

Aim: The purpose of this paper is to provide a framework on the selection, placement, and use of nebulizers as well as HFNC prongs, gas flow, and delivery technique via HFNC to help clinicians deliver aerosolized medications through HFNC safely and effectively in the era of COVID-19 and beyond.

Methods: We searched PubMed, Medline, CINAHL, and Science Direct to identify studies on aerosol drug delivery through HFNC using the following keywords: ("aerosols," OR "nebulizers") AND ("high flow nasal cannula" OR "high flow oxygen therapy" OR "HFNC") AND ("COVID-19," OR "SARS-CoV-2"). Twenty-eight articles including in vitro studies, randomized clinical trials, scintigraphy studies, review articles, prospective and retrospective research were included in this review.

Discussion and results: It is not clear if the findings of the previous studies on bacterial contamination could be applied to viral transmission because they do not provide data that could be extrapolated to the risk of SARS-CoV-2 transmission. In the face of the unknown risk with the transmission of COVID-19 during HFNC therapy, the benefits of HFNC must be weighed against the risk of infection to HCPs and other patients. Due to the limited number of ventilators available in hospitals and the confirmed effectiveness of HFNC in treating hypoxemic respiratory failure, HFNC may prevent early intubation, and prolonged intensive care unit stays in patients with COVID-19.

Conclusion: Clinicians should review the magnitude of this risk based on current evidence and use the suggested strategies of this paper for safe and effective delivery of aerosolized medications through HFNC in the era of COVID-19 and beyond.

Keywords: COVID-19; aerosols; drug delivery; high flow nasal cannula; infection control; nebulizers.

Conflict of interest statement

Dr. Ari discloses relationships with Aerogen Ltd and Philips Healthcare. Mr. Moody received unrestricted research grants from Aerogen Ltd.

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Review
. 2020 Aug 17;24(1):506.
doi: 10.1186/s13054-020-03206-9.

A narrative review on trans-nasal pulmonary aerosol delivery

Affiliations
Review

A narrative review on trans-nasal pulmonary aerosol delivery

Jie Li et al. Crit Care. .

Abstract

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.

Keywords: Aerosol therapy; Asthma; Chronic obstructive pulmonary disease; High-flow nasal cannula; Jet nebulizer; Oxygen therapy; Pulmonary hypertension; Vibrating mesh nebulizer.

Conflict of interest statement

Dr. Dhand reports remuneration from GSK Pharmaceuticals, Boehringer-Ingelheim, Bayer, Mylan, Teva, and Astra-Zeneca Pharmaceuticals outside the submitted work. Dr. Fink is Chief Science Officer for Aerogen Pharma Corp, San Mateo, CA, USA. Dr. MacLoughlin is the Senior Manager Science for Aerogen Ltd., Galway, Ireland. Dr. Li declares to receive research funding from Fisher & Paykel Healthcare, The Daniel and Ada Rice Foundation. None of the companies had a role in the conception of this review, in the literature search or interpretation, in the writing of the manuscript, or in the decision to publish the results.

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Abstract

Some patients with coronavirus disease (COVID-19) present with severe acute respiratory syndrome, which causes multiple organ dysfunction, besides dysfunction of the respiratory system, that requires invasive procedures. On the basis of the opinions of front-line experts and a review of the relevant literature on several topics, we proposed clinical practice recommendations on the following aspects for physiotherapists facing challenges in treating patients and containing virus spread: 1. personal protective equipment, 2. conventional chest physiotherapy, 3. exercise and early mobilization, 4. oxygen therapy, 5. nebulizer treatment, 6. non-invasive ventilation and high-flow nasal oxygen, 7. endotracheal intubation, 8. protective mechanical ventilation, 9. management of mechanical ventilation in severe and refractory cases of hypoxemia, 10. prone positioning, 11. cuff pressure, 12. tube and nasotracheal suction, 13. humidifier use for ventilated patients, 14. methods of weaning ventilated patients and extubation, and 15. equipment and hand hygiene. These recommendations can serve as clinical practice guidelines for physiotherapists. This article details the development of guidelines on these aspects for physiotherapy of patients with COVID-19.

Conflict of interest statement

No potential conflict of interest was reported.

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Review
. 2019 Dec;32(6):341-351.
doi: 10.1089/jamp.2019.1524. Epub 2019 May 14.

Nasal High-Flow Nebulization for Lung Drug Delivery: Theoretical, Experimental, and Clinical Application

Affiliations
Review

Nasal High-Flow Nebulization for Lung Drug Delivery: Theoretical, Experimental, and Clinical Application

Jonathan Dugernier et al. J Aerosol Med Pulm Drug Deliv. 2019 Dec.

Abstract

The use of nasal high-flow (NHF) therapy is rapidly spreading across acute care facilities. This raises the question of optimal delivery of inhaled medication to patients undergoing this noninvasive ventilatory support consisting in delivering heated and humidified high gas flow rates through nasal cannulas. In this article, we review experimental and clinical work evaluating the delivery of inhaled medication within the NHF circuit to target the lung without interrupting the ventilatory support. Using vibrating mesh nebulizers placed immediately upstream or downstream of the humidification chamber, with flow rates of 30-45 L/min in adults and 2-6 L/min in children and infants, about 1%-10% of the drug charged in the nebulizer may be delivered to the lungs. Compared with conventional facemask aerosol interfaces, this amount is significantly lower than amounts delivered to adults (i.e., up to 25% of the nominal dose), but similar to amounts delivered to children and infants, the latter having a predominantly nasal breathing. However, significant clinical effects have been shown in both populations when delivering bronchodilators through NHF. This interface is particularly well tolerated and may be useful to improve aerosol therapy tolerance in the pediatric setting. Thus, among patients undergoing NHF therapy, bronchodilators may be delivered through this route. Whereas other drugs may be delivered this way or if there is a patient-centered benefit to specifically use NHF for aerosol therapy among patients without ongoing ventilatory support, requires further evaluation and technological development.

Keywords: bronchodilator agents; cannula; nebulizers and vaporizers; noninvasive ventilation; oxygen inhalation therapy.

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