Aerosolized KL4 surfactant improves short-term survival and gas exchange in spontaneously breathing newborn pigs with hydrochloric acid-induced acute lung injury

Pediatr Pulmonol. 2014 May;49(5):482-9. doi: 10.1002/ppul.22844. Epub 2013 Sep 3.


Background: Surfactant therapy may be beneficial in acute lung injury (ALI). In spontaneously breathing newborn pigs with ALI supported with continuous positive airway pressure (CPAP), we evaluated the hypothesis that aerosolized KL4 surfactant (AERO KL4 S) would provide a similar therapeutic effect as intratracheal KL4 surfactant (ETT KL4 S) when compared to controls.

Methods: We randomized pigs with HCl-induced ALI to: (1) 175 mg/kg KL4 surfactant via endotracheal tube (ETT); (2) AERO KL4 S (22.5 mg/min phospholipid) for 60 min via continuous positive airway pressure (CPAP); or (3) sham procedure on CPAP. We obtained physiologic data and arterial blood gases throughout the 3-hr study. At study end, lungs were excised for analysis of interleukin-8 (IL-8), myeloperoxidase (MPO) levels and histomorphometric data.

Results: Pigs treated with ETT KL4 S and AERO KL4 S had improved survival and sustained pO2 compared to controls. The AERO KL4 S group had higher pH compared to controls. Lung IL-8 levels were lower in the AERO KL4 S group compared to controls. Histomorphometric analysis showed less hemorrhage in the ETT and AERO KL4 S groups compared to controls. The AERO KL4 S group had more open lung units per fixed-field than the ETT KL4 S or controls.

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

Keywords: CPAP; acute lung injury; aerosol; surfactant.

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Administration, Inhalation
  • Aerosols / pharmacology*
  • Animals
  • Animals, Newborn
  • Continuous Positive Airway Pressure
  • Disease Models, Animal
  • Hydrochloric Acid / toxicity
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8 / drug effects
  • Interleukin-8 / metabolism
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Peptides / pharmacology*
  • Peroxidase / drug effects
  • Peroxidase / metabolism
  • Pulmonary Gas Exchange / drug effects*
  • Random Allocation
  • Survival Rate
  • Swine


  • Aerosols
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • KL4 surfactant
  • Peptides
  • Peroxidase
  • Hydrochloric Acid