RATIONALE. There is an urgent need for new drugs for both COVID-19 patients and those with other forms of the acute respiratory distress syndrome (ARDS). ARDS in influenza-infected mice is associated with reduced levels of liponucleotides (essential precursors for de novo phospholipid synthesis) in alveolar type II epithelial cells. We found previously that early or late post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline decreased hypoxemia, pulmonary edema, lung dysfunction, and inflammation without altering viral replication. Because it is a truism that mice with ARDS are far easier to cure than people, we wished to show that parenteral liponucleotide administration could likewise attenuate ARDS in a more clinically-relevant real-world situation. METHODS. Client-owned pet dogs admitted to the Small Animal ICU at The Ohio State University Veterinary Medical Center for aspiration pneumonia were enrolled in a randomized, double-blinded, placebo-controlled trial of treatment with vehicle (0.1 ml/kg sterile 0.9% saline, i.v.;n=8 dogs) or CDP-choline (5 mg/kg in 0.1 ml/kg 0.9% saline, i.v.;n=9 dogs) every 12 hours over the first 48 hours after admission. Dogs received standard of care supportive therapy and supplemental O2 (in an O2 tent or via nasal cannula) as deemed necessary by the attending clinician. Vital signs, blood pressure, and peripheral O2 saturations were recorded every 8 hours. Arterial blood gases were measured every 12 hours. Venous blood was collected on admission and at 48 hours for clinical chemistry and CBC/differential counts. Written consent was obtained from all owners, who received a $400 financial incentive (in the form of a contribution to hospital expenses) to participate. RESULTS. Dogs in the treatment arm were significantly younger, but there were no other significant differences between placebo- and CDP-choline-treated dogs on admission. All dogs exhibited tachycardia, tachypnea, hypertension, hypoxemia, hypocapnia, lymphopenia, and neutrophilia. Administration of CDP-choline resulted in rapid, progressive, and clinically significant increases in PaO2:FiO2 values and declines in alveolar-arterial (A-a) gradients that did not occur in placebo (saline)-treated animals. CDP-choline treatment also prevented platelet consumption over the first 48 hours after admission but had no detectable detrimental effects in sick dogs. CONCLUSIONS. CDP-choline acts rapidly to promote gas exchange in dogs with spontaneous aspiration pneumonia. Because CDP-choline has been shown to be very safe in human subjects, it should be considered as a potential adjunct therapy in ARDS and/or COVID-19 patients.
Liponucleotides Improve Gas Exchange in Dogs with Aspiration Pneumonia