Source: Annual Congress 2010 - Acute respiratory failure
Disease area: Respiratory critical care

Abstract

In patients with Acute Lung Injury (ALI), mortality and the capacity of patients to resolve pulmonary oedema are inversely correlated. Alveolar liquid clearance is facilitated by ion gradients generated by sodium ion channels (ENaC) located at the apical side of type II alveolar cells.
We report the development of inhalation therapy that assists in alveolar liquid clearance by activating ENaC of alveolar cells.
Patch clamp measurement on human epithelial type II pulmonary cells demonstrated that synthetic peptides manufactured by Fmoc technology were capable of activating ENaC in a concentration-dependant manner. Formulation of peptide in WFI followed by nebulisation with Aeroneb ProX mesh-nebuliser, produced aerosol particles of diameters less than 4 μm, thus enabling the aerosol to penetrate the lower respiratory tract. Peptides activity was unaffected by the nebulisation procedure. Nebulised peptides were detected in lung tissue by using a combination of liquid chromatography (LC) and mass spectrometry (MS). With IRB approval, ALI was induced in pigs and 25 mg synthetic peptide was nebulised and inhaled into the lung of test animals followed by mechanical ventilation for five hours. Inhalation of synthetic peptide resulted in significant increase in paO₂ values and reduction of pulmonary oedema as measured by extravascular lung water content. Haemodynamic parameters remained unchanged during time of observation.
Our data demonstrate for the first time that small synthetic peptides can be inhaled into the lower respiratory tract as aerosol retaining biological activity to protect lung tissue from injury and to resolve pulmonary oedema.

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B. Fischer, S. Tzotzos, H. Pietschmann, H. Fischer, R. Lucas, P. Hazemi, R. Lemmens-Gruber, E. Hartmann, K. Markstaller, H. Mascher (Vienna, Baden, Austria; Augusta, United States Of America; Mainz, Germany). Development of inhalation therapy for prevention and treatment of acute lung injury. Eur Respir J 2010; 36: Suppl. 54, 2286

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