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In this study, we used a clinically relevant baboon model of Streptococcus pneumoniae pneumonia to 1) test a novel, ventilator-compatible CO delivery system; 2) establish a safe and effective CO dosing regimen; and 3) investigate the local and systemic effects of CO therapy on inflammation and acute lung injury (ALI). Animals were inoculated with S. pneumoniae (10<jats:sup>8<\/jats:sup>-10<jats:sup>9<\/jats:sup>CFU) ( n = 14) or saline vehicle ( n = 5); in a subset with pneumonia ( n = 5), we administered low-dose, inhaled CO gas (100\u2013300 ppm \u00d7 60\u201390 min) at 0, 6, 24, and\/or 48 h postinoculation and serially measured blood carboxyhemoglobin (COHb) levels. We found that CO inhalation at 200 ppm for 60 min is well tolerated and achieves a COHb of 6\u20138% with ambient CO levels \u2264 1 ppm. The COHb level measured at 20 min predicted the 60-min COHb level by the Coburn-Forster-Kane equation with high accuracy. Animals given inhaled CO + antibiotics displayed significantly less ALI at 8 days postinoculation compared with antibiotics alone. Inhaled CO was associated with activation of mitochondrial biogenesis in the lung and with augmentation of renal antioxidative programs. These data support the feasibility of safely delivering inhaled CO gas during mechanical ventilation and provide preliminary evidence that CO may accelerate the resolution of ALI in a clinically relevant nonhuman primate pneumonia model.<\/jats:p>","DOI":"10.1152\/ajplung.00240.2015","type":"journal-article","created":{"date-parts":[[2015,8,29]],"date-time":"2015-08-29T02:44:24Z","timestamp":1440816264000},"page":"L834-L846","source":"Crossref","is-referenced-by-count":32,"title":["Effects of inhaled CO administration on acute lung injury in baboons with pneumococcal pneumonia"],"prefix":"10.1152","volume":"309","author":[{"given":"Laura E.","family":"Fredenburgh","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan D.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean R.","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Respiratory Care, Massachusetts General Hospital, Boston, Massachusetts;"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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