DiBlasi Robert M, Crandall Coral N, Engberg Rebecca J, Bijlani Kunal, Ledee Dolena, Kajimoto Masaki, Walther Frans J
Department of Respiratory Care Therapy, Seattle Children's Hospital, Seattle, WA 98105, USA.
Center for Respiratory Biology and Therapeutics, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Pharmaceutics. 2023 Sep 22;15(10):2368. doi: 10.3390/pharmaceutics15102368.
Aerosolized lung surfactant therapy during nasal continuous positive airway pressure (CPAP) support avoids intubation but is highly complex, with reported poor nebulizer efficiency and low pulmonary deposition. The study objective was to evaluate particle size, operational compatibility, and drug delivery efficiency with various nasal CPAP interfaces and gas humidity levels of a synthetic dry powder (DP) surfactant aerosol delivered by a low-flow aerosol chamber (LFAC) inhaler combined with bubble nasal CPAP (bCPAP). A particle impactor characterized DP surfactant aerosol particle size. Lung pressures and volumes were measured in a preterm infant nasal airway and lung model using LFAC flow injection into the bCPAP system with different nasal prongs. The LFAC was combined with bCPAP and a non-heated passover humidifier. DP surfactant mass deposition within the nasal airway and lung was quantified for different interfaces. Finally, surfactant aerosol therapy was investigated using select interfaces and bCPAP gas humidification by active heating. Surfactant aerosol particle size was 3.68 µm. Lung pressures and volumes were within an acceptable range for lung protection with LFAC actuation and bCPAP. Aerosol delivery of DP surfactant resulted in variable nasal airway (0-20%) and lung (0-40%) deposition. DP lung surfactant aerosols agglomerated in the prongs and nasal airways with significant reductions in lung delivery during active humidification of bCPAP gas. Our findings show high-efficiency delivery of small, synthetic DP surfactant particles without increasing the potential risk for lung injury during concurrent aerosol delivery and bCPAP with passive humidification. Specialized prongs adapted to minimize extrapulmonary aerosol losses and nasal deposition showed the greatest lung deposition. The use of heated, humidified bCPAP gases compromised drug delivery and safety. Safety and efficacy of DP aerosol delivery in preterm infants supported with bCPAP requires more research.
在经鼻持续气道正压通气(CPAP)支持下进行雾化肺表面活性物质治疗可避免插管,但操作极为复杂,据报道雾化器效率低且肺部沉积率低。本研究的目的是评估通过低流量雾化室(LFAC)吸入器与气泡式经鼻CPAP(bCPAP)联合递送的合成干粉(DP)表面活性物质气雾剂在不同经鼻CPAP接口和气体湿度水平下的粒径、操作兼容性和药物递送效率。用粒子冲击器对DP表面活性物质气雾剂的粒径进行表征。在早产婴儿的鼻腔气道和肺部模型中,通过将LFAC气流注入带有不同鼻管的bCPAP系统来测量肺压力和肺容积。LFAC与bCPAP和非加热型旁通加湿器相结合。对不同接口量化鼻腔气道和肺部内的DP表面活性物质质量沉积。最后,通过主动加热,使用选定的接口和bCPAP气体加湿来研究表面活性物质气雾剂治疗。表面活性物质气雾剂的粒径为3.68 µm。在启动LFAC和bCPAP时,肺压力和肺容积处于肺保护的可接受范围内。DP表面活性物质的气雾剂递送导致鼻腔气道(0 - 20%)和肺部(0 - 4