Management of phosgene-induced acute lung injury

Grainge, Christopher; Rice, Paul

doi:10.3109/15563650.2010.506877

Cited by 73 publications

(53 citation statements)

References 67 publications

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“…This mechanism causes extreme oxidative damage and quickly depletes glutathione stores, worsening the free radical damage. Multiple animal studies and human case reports have shown an increase in vascular permeability, alveolar leakage, and development of pulmonary edema [5][6][7]. Animal models have demonstrated that the pulmonary edema is the result of increased permeability of the alveolar membrane [8].…”

Section: Discussionmentioning

confidence: 99%

“…The second and likely more harmful mechanisms by which phosgene causes its effects is through acylation. By this mechanism, phosgene reacts with hydroxyl, thiol, amine, and sulfhydryl groups on proteins, carbohydrates, and lipids [5,6]. This mechanism causes extreme oxidative damage and quickly depletes glutathione stores, worsening the free radical damage.…”

Section: Discussionmentioning

confidence: 99%

“…In the first mechanism, phosgene hydrolyses into hydrogen chloride and carbon dioxide when it comes into contact with water in the respiratory tract. At normal physiologic conditions, only small amounts of hydrochloric acid are produced [5,6]. The second and likely more harmful mechanisms by which phosgene causes its effects is through acylation.…”

Section: Discussionmentioning

confidence: 99%

“…The delayed effects are dependent upon the total inhaled dose rather than on exposure concentration. Individuals may be symptom-free for up to 48 h following an acute exposure before developing a cough, shortness of breath, tachypnea, and respiratory distress [6].…”

Section: Discussionmentioning

confidence: 99%

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Phosgene Exposure: A Case of Accidental Industrial Exposure

2013

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Introduction Phosgene is a rare exposure with strong clinical implications. We report a phosgene exposure that resulted in the patient's death. Case Report A 58 year-old man arrived to the emergency department 1 hour after exposure to phosgene with complaints of a sore throat. Initial vital signs were blood pressure 175/118 mmHg, heart rate 98/min, respirations 12/min, and oxygen saturation of 93% on room air. Physical exam revealed few scattered rhonchi, without signs of distress. Initial arterial blood gases (ABG's) revealed pH 7.42, pCO2 43 mmHg, pO2 68 mmHg, HCO3 27 meq/L, and oxygen saturation of 93% on room air. Initial chest x-ray 2 hours after the exposure demonstrated clear lung fields. Approximately 2.5 hours after the exposure, he began complaining of dyspnea, restlessness and his oxygen saturation dropped below 90%.He received nebulized albuterol, 1 gram intravenous methylprednisolone, and 100 % oxygen via face mask. Minimal improvement was noted and he was intubated. The post intubation chest x-ray, 3.5 hours after the exposure, revealed diffuse alveolar infiltrates. Acetylcysteine, terbutaline, and IV steroids were administered without improvement. The patient died 30 hours after exposure. Discussion There are many misunderstandings concerning phosgene due to its rare presentation. Traditional treatment modalities are often unproven in human trials and were unsuccessful in this case. Conclusion This case highlights the significant toxicity that results from phosgene exposure and the challenges of the limited treatment modalities. There is concern for the use of this agent in chemical terrorism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phosgene Exposure: A Case of Accidental Industrial Exposure

2013

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“…Phosgene is a weak topical irritant to the eyes and upper respiratory tract, but, because phosgene readily penetrates into the alveolar region of the lung, it is a strong inducer of severe pulmonary edema, respiratory distress, hypoxia, and death due to respiratory failure (36,37). The onset of pulmonary edema can be delayed and often follows a symptom-free period (37). Phosgene was used as a chemical warfare agent in World War I (38).…”

mentioning

confidence: 99%

Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

Leikauf

Concel

Bein

et al. 2013

Am J Respir Cell Mol Biol

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In this study, a genetically diverse panel of 43 mouse strains was exposed to phosgene and genome-wide association mapping performed using a high-density single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was also used to improve the genetic resolution in the identification of genetic determinants of phosgene-induced acute lung injury (ALI). We prioritized the identified genes based on whether the encoded protein was previously associated with lung injury or contained a nonsynonymous SNP within a functional domain. Candidates were selected that contained a promoter SNP that could alter a putative transcription factor binding site and had variable expression by transcriptomic analyses. The latter two criteria also required that >10% of mice carried the minor allele and that this allele could account for >10% of the phenotypic difference noted between the strains at the phenotypic extremes. This integrative, functional approach revealed 14 candidate genes that included Atp1a1, Alox5, Galnt11, Hrh1, Mbd4, Phactr2, Plxnd1, Ptprt, Reln, and Zfand4, which had significant SNP associations, and Itga9, Man1a2, Mapk14, and Vwf, which had suggestive SNP associations. Of the genes with significant SNP associations, Atp1a1, Alox5, Plxnd1, Ptprt, and Zfand4 could be associated with ALI in several ways. Using a competitive electrophoretic mobility shift analysis, Atp1a1 promoter (rs215053185) oligonucleotide containing the minor G allele formed a major distinct faster-migrating complex. In addition, a gene with a suggestive SNP association, Itga9, is linked to transforming growth factor b1 signaling, which previously has been associated with the susceptibility to ALI in mice.

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