title: Aerosol delivery of synthetic lung surfactant.
abstract: Background. Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in premature infants with respiratory distress syndrome due to lack of lung surfactant. If this approach fails, the next step is often intubation, mechanical ventilation (MV) and intratracheal instillation of clinical lung surfactant. Objective. To investigate whether aerosol delivery of advanced synthetic lung surfactant, consisting of peptide mimics of surfactant proteins B and C (SP-B and SP-C) and synthetic lipids, during nCPAP improves lung function in surfactant-deficient rabbits. Methods. Experimental synthetic lung surfactants were produced by formulating 3% Super Mini-B peptide (SMB surfactant), a highly surface active SP-B mimic, and a combination of 1.5% SMB and 1.5% of the SP-C mimic SP-Css ion-lock 1 (BC surfactant), with a synthetic lipid mixture. After testing aerosol generation using a vibrating membrane nebulizer and aerosol conditioning (particle size, surfactant composition and surface activity), we investigated the effects of aerosol delivery of synthetic SMB and BC surfactant preparations on oxygenation and lung compliance in saline-lavaged, surfactant-deficient rabbits, supported with either nCPAP or MV. Results. Particle size distribution of the surfactant aerosols was within the 1-3 µm distribution range and surfactant activity was not affected by aerosolization. At a dose equivalent to clinical surfactant therapy in premature infants (100 mg/kg), aerosol delivery of both synthetic surfactant preparations led to a quick and clinically relevant improvement in oxygenation and lung compliance in the rabbits. Lung function recovered to a greater extent in rabbits supported with MV than with nCPAP. BC surfactant outperformed SMB surfactant in improving lung function and was associated with higher phospholipid values in bronchoalveolar lavage fluid; these findings were irrespective of the type of ventilatory support (nCPAP or MV) used. Conclusions. Aerosol delivery of synthetic lung surfactant with a combination of highly active second generation SP-B and SP-C mimics was effective as a therapeutic approach towards relieving surfactant deficiency in spontaneously breathing rabbits supported with nCPAP. To obtain similar results with nCPAP as with intratracheal instillation, higher dosage of synthetic surfactant and reduction of its retention by the delivery circuit will be needed to increase the lung dose.
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center , Torrance, CA , USA ; Department of Pediatrics, David Geffen School of Medicine, University of California, LA , USA.
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Walther
authors.affiliation: Department of Pediatrics, Division of Medical Genetics, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center , Torrance, CA , USA.
authors.forename: José M
authors.initials: JM
authors.lastname: Hernández-Juviel
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, LA , USA ; Department of Medicine, Division of Molecular Medicine, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Harbor-UCLA Medical Center , Torrance, CA , USA ; Department of Medicine, David Geffen School of Medicine, University of California, LA , USA ; Department of Physiology & Biophysics, School of Medicine, University of California , Irvine, CA , USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Waring
keywords: Aerosol delivery; Captive bubble surfactometry; Lung function; Mechanical ventilation; Nasal continuous positive airway pressure; Surfactant protein B; Surfactant protein C; Surfactant-deficient rabbits; Synthetic lung surfactant