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

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.

[1]  A. Elberry,et al.  Effect of pressures and type of ventilation on aerosol delivery to chronic obstructive pulmonary disease patients , 2022, Beni-Suef University Journal of Basic and Applied Sciences.

[2]  A. Modrykamien,et al.  Evaluation of aerosolized epoprostenol for hypoxemia in non-intubated patients with coronavirus disease 2019 , 2022, Hospital practice.

[3]  X. Drouot,et al.  β Agonist Delivery by High-Flow Nasal Cannula During COPD Exacerbation , 2021, Respiratory Care.

[4]  J. Fink,et al.  Bronchodilator Delivery via High-Flow Nasal Cannula: A Randomized Controlled Trial to Compare the Effects of Gas Flows , 2021, Pharmaceutics.

[5]  C. Burtin,et al.  Worldwide Clinical Practice of High-Flow Nasal Cannula and Concomitant Aerosol Therapy in the Adult ICU Setting , 2021, Respiratory Care.

[6]  N. Heuzé-Vourc’h,et al.  Pressurized Metered Dose Inhaler Aerosol Delivery Within Nasal High-Flow Circuits: A Bench Study. , 2021, Journal of aerosol medicine and pulmonary drug delivery.

[7]  A. Elberry,et al.  Aerosol delivery aspects within a high flow therapy system in chronic obstructive pulmonary disease patients , 2020 .

[8]  M. Hindle,et al.  CFD Guided Optimization of Nose-to-Lung Aerosol Delivery in Adults: Effects of Inhalation Waveforms and Synchronized Aerosol Delivery , 2020, Pharmaceutical Research.

[9]  K. Roberts,et al.  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 , 2020, Journal of clinical medicine.

[10]  J. Fink,et al.  In vitro comparison between inspiration synchronized and continuous vibrating mesh nebulizer during trans-nasal aerosol delivery , 2020, Intensive Care Medicine Experimental.

[11]  Jian Luo,et al.  Dose Response to Transnasal Pulmonary Administration of Bronchodilator Aerosols via Nasal High-Flow Therapy in Adults with Stable Chronic Obstructive Pulmonary Disease and Asthma , 2019, Respiration.

[12]  Arzu Ari,et al.  Impact of Gas Flow and Humidity on Trans-Nasal Aerosol Deposition via Nasal Cannula in Adults: A Randomized Cross-Over Study , 2019, Pharmaceutics.

[13]  K. Abdalla,et al.  Evaluation of a New Interface Combining High-Flow Nasal Cannula and CPAP , 2019, Respiratory Care.

[14]  K. Roberts,et al.  Epoprostenol Delivered via High Flow Nasal Cannula for ICU Subjects with Severe Hypoxemia Comorbid with Pulmonary Hypertension or Right Heart Dysfunction , 2019, Pharmaceutics.

[15]  J. Fink,et al.  The Ratio of Nasal Cannula Gas Flow to Patient Inspiratory Flow on Trans-nasal Pulmonary Aerosol Delivery for Adults: An in Vitro Study , 2019, Pharmaceutics.

[16]  E. Fernández,et al.  Comparison of aerosol delivery across combinations of drug delivery interfaces with and without concurrent high-flow nasal therapy , 2019, Intensive Care Medicine Experimental.

[17]  Mohamed E A Abdelrahim,et al.  Aerosol Delivery Through an Adult High-Flow Nasal Cannula Circuit Using Low-Flow Oxygen , 2019, Respiratory Care.

[18]  L. Plantier,et al.  Nasal high-flow bronchodilator nebulization: a randomized cross-over study , 2018, Annals of Intensive Care.

[19]  Madhu Sasidhar,et al.  Inhaled Epoprostenol Through Noninvasive Routes of Ventilator Support Systems , 2018, The Annals of pharmacotherapy.

[20]  Hiroto Suzuki,et al.  A high-flow nasal cannula system with relatively low flow effectively washes out CO2 from the anatomical dead space in a sophisticated respiratory model made by a 3D printer , 2018, Intensive Care Medicine Experimental.

[21]  Andrew G. Miller,et al.  High-Flow Nasal Cannula in Pediatric Patients: A Survey of Clinical Practice , 2018, Respiratory Care.

[22]  J. Bräunlich,et al.  Oral Versus Nasal High-Flow Bronchodilator Inhalation in Chronic Obstructive Pulmonary Disease. , 2017, Journal of aerosol medicine and pulmonary drug delivery.

[23]  F. Jamar,et al.  Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission Computed Tomography-Computed Tomography Study. , 2017, Journal of aerosol medicine and pulmonary drug delivery.

[24]  Arzu Ari,et al.  Aerosol Delivery Through Adult High Flow Nasal Cannula With Heliox and Oxygen , 2017, Respiratory Care.

[25]  Mohamed E A Abdelrahim,et al.  Inhaled salbutamol dose delivered by jet nebulizer, vibrating mesh nebulizer and metered dose inhaler with spacer during invasive mechanical ventilation. , 2017, Pulmonary pharmacology & therapeutics.

[26]  L. Pisani,et al.  Use of Nasal High Flow in Stable COPD: Rationale and Physiology , 2017, COPD.

[27]  Ronan Mac Loughlin,et al.  Nasal high flow nebulization in infants and toddlers: An in vitro and in vivo scintigraphic study , 2017, Pediatric pulmonology.

[28]  P. Bartenstein,et al.  Nasal high flow reduces dead space , 2016, Journal of applied physiology.

[29]  J. Bräunlich,et al.  Nasal highflow improves ventilation in patients with COPD , 2016, International journal of chronic obstructive pulmonary disease.

[30]  P. Diot,et al.  Aerosol Therapy in Adults Receiving High Flow Nasal Cannula Oxygen Therapy. , 2016, Journal of aerosol medicine and pulmonary drug delivery.

[31]  J. Fraser,et al.  Nasal high flow oxygen therapy in patients with COPD reduces respiratory rate and tissue carbon dioxide while increasing tidal and end-expiratory lung volumes: a randomised crossover trial , 2016, Thorax.

[32]  A. Boyer,et al.  Physiologic Effects of High-Flow Nasal Cannula Oxygen in Critical Care Subjects , 2015, Respiratory Care.

[33]  F. Blasi,et al.  Heated Humidified High-Flow Nasal Oxygen in Adults: Mechanisms of Action and Clinical Implications. , 2015, Chest.

[34]  L. Brochard,et al.  High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. , 2015, The New England journal of medicine.

[35]  M. Hindle,et al.  Intermittent Aerosol Delivery to the Lungs During High-Flow Nasal Cannula Therapy , 2014, Respiratory Care.

[36]  M. Hindle,et al.  Targeted Lung Delivery of Nasally Administered Aerosols , 2014, Aerosol science and technology : the journal of the American Association for Aerosol Research.

[37]  M. Hindle,et al.  High-efficiency generation and delivery of aerosols through nasal cannula during noninvasive ventilation. , 2013, Journal of aerosol medicine and pulmonary drug delivery.

[38]  J. Hertzog,et al.  Influences of Cannula Size and Flow Rate on Aerosol Drug Delivery Through the Vapotherm Humidified High-Flow Nasal Cannula System , 2013, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[39]  M. Hindle,et al.  Improving Pharmaceutical Aerosol Delivery During Noninvasive Ventilation: Effects of Streamlined Components , 2013, Annals of Biomedical Engineering.

[40]  Arzu Ari,et al.  In vitro comparison of heliox and oxygen in aerosol delivery using pediatric high flow nasal cannula , 2011, Pediatric pulmonology.

[41]  R. Dellinger,et al.  Inhaled nitric oxide and inhaled prostacyclin in acute respiratory distress syndrome: what is the evidence? , 2011, Critical care clinics.

[42]  O. Atalay,et al.  Influence of nebulizer type, position, and bias flow on aerosol drug delivery in simulated pediatric and adult lung models during mechanical ventilation. , 2010, Respiratory care.

[43]  J. Riera,et al.  High-flow oxygen therapy in acute respiratory failure. , 2010, Respiratory care.

[44]  J. Carcillo,et al.  Aerosol delivery through nasal cannulas: an in vitro study. , 2008, Journal of aerosol medicine and pulmonary drug delivery.

[45]  W. Finlay,et al.  Overcoming the adverse effect of humidity in aerosol delivery via pressurized metered-dose inhalers during mechanical ventilation. , 2000, American journal of respiratory and critical care medicine.