Evaluation of a Novel Dry Powder Surfactant Aerosol Delivery System for Use in Premature Infants Supported with Bubble CPAP

Author:

DiBlasi Robert M.12,Crandall Coral N.234ORCID,Engberg Rebecca J.24,Bijlani Kunal5ORCID,Ledee Dolena6ORCID,Kajimoto Masaki2ORCID,Walther Frans J.78ORCID

Affiliation:

1. Department of Respiratory Care Therapy, Seattle Children’s Hospital, Seattle, WA 98105, USA

2. Center for Respiratory Biology and Therapeutics, Seattle Children’s Research Institute, Seattle, WA 98101, USA

3. Quality and Clinical Effectiveness, Seattle Children’s Hospital, Seattle, WA 98105, USA

4. Center for Clinical and Translational Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA

5. Mechanical Engineering, Zewski Corporation, Magnolia, TX 77354, USA

6. Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA

7. Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA

8. Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA

Abstract

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.

Funder

Bill and Melinda Gates Foundation

Publisher

MDPI AG

Subject

Pharmaceutical Science

Reference36 articles.

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