Aerosolized KL<sub>4</sub>surfactant improves short-term survival and gas exchange in spontaneously breathing newborn pigs with hydrochloric acid-induced acute lung injury

Lampland, Andrea; Wolfson, Marla R.; Mazela, Jan; Henderson, Christopher; Gregory, Timothy J.; Meyers, Pat A.; Plumm, Brenda; Worwa, Cathy; Mammel, Mark C.

doi:10.1002/ppul.22844

Cited by 24 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, surface activity of the recombinant SP-C surfactant has recently come under attack after disappointing results in clinical studies of patients with acute lung injury (Spragg et al, 2011). A recent study (Lampland et al, 2014) in spontaneously breathing newborn pigs with acute lung injury showed similar improvements in short-term survival and pulmonary gas exchange with aerosolized and intratracheally instilled liquid KL 4 surfactant (Surfaxin ® , Discovery Laboratories Inc., Warrington, PA, USA). However, the oxygenation response in the spontaneously breathing newborn pigs was rather limited with PaO 2 values ∼200 mm Hg, indicating the limited surface activity of KL 4 -based surfactant mixtures (Walther et al, 1998).…”

Section: Discussionmentioning

confidence: 91%

Aerosol delivery of synthetic lung surfactant

Walther

Hernández-Juviel

Waring

2014

PeerJ

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 91%

Aerosol delivery of synthetic lung surfactant

Walther

Hernández-Juviel

Waring

2014

PeerJ

View full text Add to dashboard Cite

show abstract

“…The success of rescue therapy for chemical-induced ALI using synthetic surfactant with advanced and robust SP-B and SP-C mimics represents a significant breakthrough, as previous experiments have indicated only minimal or no improvement in lung function with animal-derived and first generation synthetic surfactant preparations (Lamm & Albert, 1990; Brackenbury et al, 2001; Zimmermann et al, 2010; Lampland et al, 2014). Lamm & Albert (1990) tested Survanta, a modified natural surfactant based on a bovine lung extract, in rabbit lungs after intratracheal injection of HCl, but found no improvement in arterial oxygenation.…”

Section: Discussionmentioning

confidence: 99%

“…Brackenbury et al (2001) treated rabbits pretreated with intratracheal HCl with natural ovine surfactant, bovine lipid extract surfactant and recombinant SP-C surfactant (Venticute) and found none of them effective. Recent studies by Zimmermann et al (2010) and Lampland et al (2014) compared intratracheal instillation and aerosol delivery of KL4 surfactant (Surfaxin ® , Discovery Laboratories, Warrington, PA) with continuous positive airway pressure (CPAP) only in newborn pigs with acute lung injury after HCl instillation. Both KL4 preparations improved survival, but arterial oxygenation did not increase very much over the surfactant pretreatment values.…”

Section: Discussionmentioning

confidence: 99%

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Walther

Hernández-Juviel

Gordon

et al. 2014

PeerJ

View full text Add to dashboard Cite

Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions.Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical) ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C) mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS.Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB), a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight), the clinical surfactant Infasurf®, a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS) assays.Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary-alveolar protein leakage and surfactant dysfunction after HCl instillation than following lung lavage. At the end of the duration of the experiments, synthetic surfactants provided more clinical stability in ALI/ARDS than Infasurf, and the protein content of bronchoalveolar lavage fluid was lowest for the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA.Conclusion. Advanced synthetic surfactant with robust SP-B and SP-C mimics is better equipped to tackle surfactant inactivation in chemical ALI than synthetic surfactant with only a single surfactant peptide or animal-derived surfactant.

show abstract

“…A comparison of jet and ultrasonic nebulizer administration of Exosurf and Survanta in rabbits after lavage lung injury demonstrated significant differences in the amount of drug delivered determined by both the type of nebulizer (ultrasonic Ͼ jet) and the specific surfactant (Exosurf Ͼ Survanta). 20 Irrespective of delivery method, however, neither drug had 21 Survival, lung histology, and interleukin-8 levels were all better with aerosolized and instilled KL4 surfactant relative to a control population supported by CPAP alone. Ruppert et al 22 used a powder aerosolizer with Venticute, an artificial surfactant with recombinant surfactant protein C, in both lung lavage and bleomycin rabbit injury models and showed rapid normalization of oxygenation to pre-injury levels.…”

Section: Aerosolized Surfactants Anti-inflammatory Drugs and Analgementioning

confidence: 99%

Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics

Willson

2015

Respir Care

View full text Add to dashboard Cite

Drug delivery by aerosol may have several advantages over other modes, particularly if the lung is the target organ. Aerosol delivery may allow achievement of higher concentrations while minimizing systemic effects and offers convenience, rapid onset of action, and avoidance of the needles and sterile technique necessary with intravenous drug administration. Aerosol delivery may change the pharmacokinetics of many drugs, however, and an awareness of the caveats of aerosolized drug delivery is mandatory to ensure both safety and adequate drug delivery. This paper discusses the administration of surfactants, anti-inflammatory agents, and analgesics by the aerosol route.

show abstract

Aerosolized KL₄surfactant improves short-term survival and gas exchange in spontaneously breathing newborn pigs with hydrochloric acid-induced acute lung injury

Abstract: AERO KL4 S produced similar improvements in survival, physiology, inflammatory markers, and morphology as ETT KL4 S in an ALI model.

Cited by 24 publications

References 38 publications

Aerosol delivery of synthetic lung surfactant

Aerosol delivery of synthetic lung surfactant

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics

Contact Info

Product

Resources

About

Aerosolized KL4surfactant improves short-term survival and gas exchange in spontaneously breathing newborn pigs with hydrochloric acid-induced acute lung injury

Abstract: AERO KL4 S produced similar improvements in survival, physiology, inflammatory markers, and morphology as ETT KL4 S in an ALI model.

Cited by 24 publications

References 38 publications

Aerosol delivery of synthetic lung surfactant

Aerosol delivery of synthetic lung surfactant

Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

Aerosolized Surfactants, Anti-Inflammatory Drugs, and Analgesics

Contact Info

Product

Resources

About

Aerosolized KL₄surfactant improves short-term survival and gas exchange in spontaneously breathing newborn pigs with hydrochloric acid-induced acute lung injury