Aerosol drug delivery to the lungs during nasal high flow therapy: An in vitro study

TY - JOUR

T1 - Aerosol drug delivery to the lungs during nasal high flow therapy

T2 - An in vitro study

AU - Wallin, Martin

AU - Tang, Patricia

AU - Chang, Rachel Yoon Kyung

AU - Yang, Mingshi

AU - Finlay, Warren H.

AU - Chan, Hak Kim

PY - 2019/2/15

Y1 - 2019/2/15

N2 - Background: Aerosol delivery through a nasal high flow (NHF) system is attractive for clinicians as it allows for simultaneous administration of oxygen and inhalable drugs. However, delivering a fine particle fraction (FPF, particle wt. fraction < 5.0 μm) of drugs into the lungs has been very challenging, with highest value of only 8%. Here, we aim to develop an efficient nose-to-lung delivery system capable of delivering improved quantities (FPF > 16%) of dry powder aerosols to the lungs via an NHF system. Methods: We evaluated the FPF of spray-dried mannitol with leucine with a next generation impactor connected to a nasopharyngeal outlet of an adult nasal airway replica. In addition, we investigated the influence of different dispersion (20-30 L/min) and inspiratory (20-40 L/min) flow rates, on FPF. Results: We found an FPF of 32% with dispersion flow rate at 25 L/min and inspiratory flow rate at 40 L/min. The lowest FPF (21%) obtained was at the dispersion flow rate at 30 L/min and inspiratory flow rate at 30 L/min. A higher inspiratory flow rate was generally associated with a higher FPF. The nasal cannula accounted for most loss of aerosols. Conclusions: In conclusion, delivering a third of inhalable powder to the lungs is possible in vitro through an NHF system using a low dispersion airflow and a highly dispersible powder. Our results may lay the foundation for clinical evaluation of powder aerosol delivery to the lungs during NHF therapy in humans.

AB - Background: Aerosol delivery through a nasal high flow (NHF) system is attractive for clinicians as it allows for simultaneous administration of oxygen and inhalable drugs. However, delivering a fine particle fraction (FPF, particle wt. fraction < 5.0 μm) of drugs into the lungs has been very challenging, with highest value of only 8%. Here, we aim to develop an efficient nose-to-lung delivery system capable of delivering improved quantities (FPF > 16%) of dry powder aerosols to the lungs via an NHF system. Methods: We evaluated the FPF of spray-dried mannitol with leucine with a next generation impactor connected to a nasopharyngeal outlet of an adult nasal airway replica. In addition, we investigated the influence of different dispersion (20-30 L/min) and inspiratory (20-40 L/min) flow rates, on FPF. Results: We found an FPF of 32% with dispersion flow rate at 25 L/min and inspiratory flow rate at 40 L/min. The lowest FPF (21%) obtained was at the dispersion flow rate at 30 L/min and inspiratory flow rate at 30 L/min. A higher inspiratory flow rate was generally associated with a higher FPF. The nasal cannula accounted for most loss of aerosols. Conclusions: In conclusion, delivering a third of inhalable powder to the lungs is possible in vitro through an NHF system using a low dispersion airflow and a highly dispersible powder. Our results may lay the foundation for clinical evaluation of powder aerosol delivery to the lungs during NHF therapy in humans.

KW - Aerosol

KW - Inhalable drugs

KW - Lungs

KW - Nasal cannula

KW - Nasal high flow

KW - Powders

KW - Pulmonary disease, chronic obstructive

UR - http://www.scopus.com/inward/record.url?scp=85061581347&partnerID=8YFLogxK

U2 - 10.1186/s12890-019-0807-9

DO - 10.1186/s12890-019-0807-9

M3 - Journal article

C2 - 30767769

AN - SCOPUS:85061581347

SN - 1471-2466

VL - 19

JO - BMC Pulmonary Medicine

JF - BMC Pulmonary Medicine

IS - 1

M1 - 42

ER -