title: Corticosteroids found ineffective for phosgene-induced acute lung injury in rats.
abstract: Various therapeutic regimes have been proposed with limited success for treatment of phosgene-induced acute lung injury (P-ALI). Corticoids were shown to be efficacious against chlorine-induced lung injury but there is still controversy whether this applies also to P-ALI. This study investigates whether different regimen of curatively administered budesonide (BUD, 10 mg/kg bw, i.p. bid; 100 mg/m(3)×30 min, nose-only inhalation), mometasone (MOM, 3 mg/kg bw, i.p. bid) and dexamethasone (DEX, 10, 30 mg/kg bw, i.p. bid), show efficacy to alleviate P-ALI. Efficacy of drugs was judged by nitric oxide (eNO) and carbon dioxide (eCO2) in exhaled air and whether these non-invasive biomarkers are suitable to assess the degree of airway injury (chlorine) relative to alveolar injury (phosgene). P-ALI related analyses included lung function (enhanced pause, Penh), morbidity, increased lung weights, and protein in bronchial alveolar lavage fluid (BALF) one day postexposure. One of the pathophysiological hallmarks of P-ALI was indicated by increased Penh lasting for approximately 20 h postexposure. Following the administration of BUD, this increase could be suppressed; however, without significant improvement in survival and lung edema (increased lung weights and BALF-protein). Collectively, protocols shown to be efficacious for chlorine (Chen et al., 2013) were ineffective and even increased adversity in the P-ALI model. This outcome warrants further study to seek for early biomarkers suitable to differentiate chlorine- and phosgene-induced acute lung injury at yet asymptomatic stage. The patterns of eNO and eCO2 observed following exposure to chlorine and phosgene may be suitable to guide the specialized clinical interventions required for each type of ALI.
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100069, China; Department of Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Sa
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Toxicology, Bayer Pharma AG, 42096 Wuppertal, Germany. Electronic address: juergen.pauluhn@bayer.com.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pauluhn
authors.affiliation: Department of Pharmacology Vascular Diseases, Cardiology & Hematology, Bayer Pharma AG, 42096 Wuppertal, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Trübel
authors.affiliation: Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing Hospital, Ministry of Health, Beijing 100730, China. Electronic address: cyh-birm@263.net.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy*; D000305:Adrenal Cortex Hormones / Q000633:toxicity*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019819:Budesonide / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003907:Dexamethasone / Q000627:therapeutic use; D004032:Diet; D008297:Male; D000068656:Mometasone Furoate; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010705:Phosgene / Q000633:toxicity*; D011244:Pregnadienediols / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002619:Chemical Warfare Agents; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D010705:Phosgene; D002245:Carbon Dioxide; D009569:Nitric Oxide; D019819:Budesonide; D003907:Dexamethasone
keywords: Acute lung injury; Biomarkers in exhaled air; Chlorine; Corticosteroid; Phosgene