Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical and Translational Medicine
Published in: Clinical and Translational Medicine 1/2017

Open Access 01-12-2017 | Review

Phosgene-induced acute lung injury (ALI): differences from chlorine-induced ALI and attempts to translate toxicology to clinical medicine

Authors: Wenli Li, Juergen Pauluhn

Published in: Clinical and Translational Medicine | Issue 1/2017

Login to get access

Abstract

Background

Phosgene (carbonyl dichloride) gas is an indispensable chemical inter-mediate used in numerous industrial processes. There is no clear consensus as to its time- and inhaled-dose-dependent etiopathologies and associated preventive or therapeutic treatment strategies.

Methods

Cardiopulmonary function was examined in rats exposed by inhalation to the alveolar irritant phosgene or to the airway irritant chlorine during and following exposure. Terminal measurements focused on hematology, protein extravasation in bronchoalveolar lavage (BAL), and increased lung weight. Noninvasive diagnostic and prognostic endpoints in exhaled breath (carbon dioxide and nitric oxide) were used to detect the clinically occult stage of pulmonary edema.

Results

The first event observed in rats following high but sublethal acute exposure to phosgene was the stimulation of alveolar nociceptive vagal receptors. This afferent stimulation resulted in dramatic changes in cardiopulmonary functions, ventilation: perfusion imbalances, and progressive pulmonary edema and phospholipoproteinosis. Hematology revealed hemoconcentration to be an early marker of pulmonary edema and fibrin as a discriminating endpoint that was positive for the airway irritant chlorine and negative for the alveolar irritant phosgene.

Conclusions

The application of each gas produced typical ALI/ARDS (acute lung injury/acute respiratory distress syndrome) characteristics. Phosgene-induced ALI showed evidence of persistent apnea periods, bradycardia, and shifts of vascular fluid from the peripheral to the pulmonary circulation. Carbon dioxide in expired gas was suggestive of increased ventilation dead space and appeared to be a harbinger of progressively developing lung edema. Treatment with the iNOS inhibitor aminoguanidine aerosol by inhalation reduced the severity of phosgene-induced ALI when applied at low dose-rates. Symptomatic treatment regimens were considered inferior to causal modes of treatment.
Literature
1.
United States Army (2005) Potential military chemical/biological agents and compounds, field manual 3–11.9. US Army Training and Doctrine Command, Fort Monroe, January 2005
2.
United States Army (1990) Potential military chemical/biological agents and compounds, field manual 3–9. Headquarters, Department of the Army, Washington, DC, 12 December 1990. In: McKone TE, Huey BM, Downing E, Duffy LM (eds) Strategies to protect the health of deployed US forces: detecting, characterizing, and documenting exposures. National Research Council, National Academy Press, Washington, 2000
3.
Heller CE (1984). Chemical warfare in World War I: the American experience, 1917–1918, Leavenworth p. 10. Combat Studies Institute, US Army Command and General Staff College, Fort Leavenworth, September 1984
4.
Sidell FR, Takafuji ET and Franz DR (Eds) (1997) Medical aspects of chemical and biological warfare. Office of the Surgeon General, Department of the Army, The Borden Institute, Walter Reed Army Medical Center, Washington, 1997
5.
National Research Council (NRC) (2002). Phosgene: acute exposure guideline levels, Appendix 1 in Acute Exposure Guideline Levels for selected airborne chemicals, vol 2. Committee on Acute Exposure Guideline Levels, Committee on Toxicology, National Research Council, National Academies Press, Washington, p. 15–70. ISBN: 0-309-56773-4
6.
Gilchrist HL, Matz PB (1933) The residual effects of warfare gases: III phosgene and IV arsenical compounds. US War Department, US Government Printing Office, Washington
7.
Gilchrist HL (1928) Comparative study of World War casualties from gas and other weapons. Chemical Warfare School, Edgewood Arsenal, MD, US Government Printing Office, Washington
8.
Craighill MD, Morse RE (1922) A digest of reports concerning the toxic effect of phosgene on man and the laboratory animal, EAMRD-5. Medical Research Division, Edgewood Arsenal, MD, May 1922
9.
Jugg B (2016) Chapter 4: toxicology and treatment of phosgene induced lung injury in issues in toxicology No. 26, chemical warfare toxicology, vol 1: fundamental aspects. Worek F, Jenner J, Thiermann H (eds). London, The Royal Society of Chemistry 2016. Published by the Royal Society of Chemistry. http://​www.​rsc.​org
10.
Romano JR Jr, Romano JR, Salem H, Lukey BR, Lukey BJ (2007) Harry salem chemical warfare agents: chemistry, pharmacology, toxicology, and therapeutics, 2nd edn. CRC Press, Boca Raton. ISBN 978-1-4200-4661-8
11.
12.
Sommerville DR, Bray JJ, Reutter-Christy SA, Jablonski RE, Shelly EE (2016) Review and assessment of chlorine mammalian lethality data and the development of a human estimate R-1 (No. CBRNIAC-SS3-628). Aberdeen, Battelle Eastern Science and Technology Center
13.
Sommerville DR (2016) Allometric modeling of mammalian cyanogen chloride inhalation lethality, chapter 9. In: Worek F, Jenner J, Thiermann H (eds) Chemical warfare toxicology, issues in toxicology, vol 26. Royal Society of Chemistry, Cambridge, pp 264–306CrossRef
14.
Moore S, Gates M (1946) Chapter 3: phosgene. In: Renshaw B (ed) Summary technical report of division 9, NRDC, Vol 1: chemical warfare agents and related chemical problems, parts 1–2, NRDC-DIV-9-VOL-1-PT1-2. Office of Scientific Research and Development, National Defense Research Committee, Washington1946. AD# 234270
15.
Reutter SA, Sommerville DR, Miller LL (2003) Review and recommendations for human toxicity estimates for FM 3-11.9, ECBC-TR-349. US Army Edgewood Chemical Biological Center, Review and Assessment of Phosgene Mammalian Lethality Data and the Development of a Human Estimate, Proving Ground, MD, September 2003. As cited by (1) United States Army, Potential Military Chemical/Biological Agents and Compounds, Field Manual 3–11.9. Fort Monroe, VA, US Army Training and Doctrine Command, January 2005
16.
17.
Li W, Rosenbruch M, Pauluhn J (2015) Effect of PEEP on phosgene-induced lung edema: pilot study on dogs using protective ventilation strategies. Exp Toxicol Pathol 67:109–116PubMedCrossRef
18.
Summerhill EM, Hoyle GW, Jordt SE, Jugg BJ, Martin JG, Matalon S, Patterson SE, Prezant DJ, Sciuto AM, Svendsen ER, White CW, Veress LA (2017) ATS terrorism and inhalational disasters section of the environmental, occupational, and population health assembly. An Official American Thoracic Society Workshop report: chemical inhalational disasters: biology of lung injury, development of novel therapeutics, and medical preparedness. Ann Am Thorac Soc. 2017. doi: 10.​1513/​AnnalsATS.​201704-297WS. [Epub ahead of print]
19.
Grainge C, Brown R, Jugg BJ, Smith AJ, Mann TM, Jenner J, Rice P, Parkhouse DA (2009) Early treatment with nebulised salbutamol worsens physiological measures and does not improve survival following phosgene induced acute lung injury. J R Army Med Corps 155:105–109PubMedCrossRef
20.
Pauluhn J (2006) Acute head-only exposure of dogs to phosgene. part III. comparison of indicators of lung injury in dogs and rats. Inhal Toxicol 18:609–621PubMedCrossRef
21.
Parkhouse DA, Brown RF, Jugg BJ, Harban FM, Platt J, Kenward CE, Jenner J, Rice P, Smith AJ (2007) Protective ventilation strategies in the management of phosgene-induced acute lung injury. Mil Med 172:295–300PubMedCrossRef
22.
Patt HM, Tobias JM, Swift MN, Postel S, Gerard RW (1946) Hemodynamics in pulmonary irritant poisoning. Am J Physiol 147:329–339PubMed
23.
Hoyle GW, Svendsen ER (2016) Special issue: countermeasures against chemical threats II: persistent effects of chlorine inhalation on respiratory health. Ann NY Acad Sci 1378:33–40PubMedCrossRef
24.
Holmes WW, Keyser BM, Paradiso DC, Ray R, Andres DK, Benton BJ, Rothwell CC, Hoard-Fruchey HM, Dillman JF, Sciuto AM, Anderson DR (2016) Conceptual approaches for treatment of phosgene inhalation-induced lung injury. Toxicol Lett 26(244):8–20CrossRef
25.
Smith A, Brown R, Jugg B, Platt J, Mann T, Masey C, Jenner J, Rice P (2009) The effect of steroid treatment with inhaled budesonide or intravenous methylprednisolone on phosgene-induced acute lung injury in a porcine model. Mil Med 174:1287–1294PubMedCrossRef
26.
Levitt JE, Matthay MA (2012) Clinical review: early treatment of acute lung injury-paradigm shift toward prevention and treatment prior to respiratory failure. Crit Care 16:223PubMedPubMedCentralCrossRef
27.
Kallet RH, Alonso JA, Pittet JF, Matthay MA (2004) Prognostic value of the pulmonary dead-space fraction during the first 6 days of acute respiratory distress syndrome. Respir Care. 49:1008–1014PubMed
28.
Tusman G, Sipmann FS, Bohm SH (2012) Rationale of deadspace measurement by volumetric capnography. Anesth Analg 114:866–874PubMedCrossRef
29.
Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, Matthay MA (2002) Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 346:1281–1286PubMedCrossRef
30.
Fengmei G, Jin C, Songqiao L, Congshan Y, Yi Y (2012) Dead space fraction changes during PEEP titration following lung recruitment in patients with ARDS. Respir Care 57:1578–1585PubMedCrossRef
31.
Nieman GF, Satalin J, Andrews P, Aiash H, Habashi NM, Gatto LA (2017) Personalizing mechanical ventilation according to physiologic parameters to stabilize alveoli and minimize ventilator induced lung injury (VILI). Intensive Care Med Exp 5:8PubMedPubMedCentralCrossRef
32.
Keeler JR, Hurt HH, Nold JB, Lennox WJ (1990) Estimation of the LCt50 of phosgene in sheep. Drug Chem Toxicol 13(2–3):229–239PubMedCrossRef
33.
Pauluhn J, Carson A, Costa DL, Gordon T, Kodavanti U, Last JA et al (2007) Workshop summary: phosgene-induced pulmonary toxicity revisited: appraisal of early and late markers of pulmonary injury from animals models with emphasis on human significance. Inhal Toxicol 19:789–810PubMedCrossRef
34.
Acute Exposure Guideline Levels for Selected Airborne Chemicals (2002): Phosgene,vol 2. National Research Council of the National Academies. Washington, The National Academies Press, US 15–70
35.
United States EPA (1986) Health assessment document for phosgene. Draft. , Cincinnati, OH, Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office. EPA/600/8-86/022A
36.
Franch S, Hatch GE (1986) Pulmonary biochemical effects of inhaled phosgene. J Toxicol Environ Health 19:413–423PubMedCrossRef
37.
Pauluhn J (2006) Acute nose-only exposure of rats to phosgene. part I: concentration × time dependence of LC50s and non-lethal-threshold concentrations and analysis of breathing patterns. Inhal Toxicol 18:423–435PubMedCrossRef
38.
Pauluhn J (2006) Acute nose-only exposure of rats to phosgene. Part II: concentration × time dependence of changes in bronchoalveolar lavage during a follow-up period of 3 Months. Inhal Toxicol 18:595–607PubMedCrossRef
39.
Jonasson S, Wigenstam E, Koch B, Bucht A (2013) Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids. Toxicol Appl Pharmacol 271:168–174PubMedCrossRef
40.
Coman DR, Bruner HD, Horn RC, Friedman M, Boche RD, McCarthy MD, Gibbon MH, Schultz J (1947) Studies on experimental phosgene poisoning: I. The pathologic anatomy of phosgene poisoning, with special reference to the early and late phases. Am J Pathol 23:1037–1073PubMedPubMedCentral
41.
Li WL, Hai CX, Pauluhn J (2011) Inhaled nitric oxide aggravates phosgene model of acute lung injury. Inhal Toxicol 23:842–851PubMedCrossRef
42.
Li WL, Liu FF, Wang C, Truebel H, Pauluhn J (2013) Novel insights into phosgene induced acute lung injury in rats: role of dysregulated cardiopulmonary reflexes and nitric oxide in lung edema pathogenesis. Toxicol Sci 131:612–628PubMedCrossRef
43.
Liu FF, Li WL, Pauluhn J, Trübel H, Wang C (2013) Rat models of acute lung injury: exhaled nitric oxide as a sensitive, noninvasive real-time biomarker of prognosis and efficacy of intervention. Toxicology 310C:104–114CrossRef
44.
Liu F, Pauluhn J, Trübel H, Wang C (2014) Single high-dose dexamethasone and sodium salicylate failed to attenuate phosgene-induced acute lung injury in rats. Toxicology 315:17–23PubMedCrossRef
45.
Li WL, Pauluhn J (2015) Chapter 19: Mechanisms involved in the inhalation toxicity of phosgene. In: Salem H, Katz SA (eds) Inhalation toxicology, 3rd edn. CRC Press, New York, pp 459–488
46.
Luo S, Pauluhn J, Trübel H, Wang C (2014) Corticosteroids found ineffective for phosgene-induced acute lung injury in rats. Toxicol Lett 229:85–92PubMedCrossRef
47.
Luo S, Trübel H, Wang C, Pauluhn J (2014) Phosgene- and chlorine-induced acute lung injury in rats: comparison of cardiopulmonary function and biomarkers in exhaled breath. Toxicology 326:109–118PubMedCrossRef
48.
Pauluhn J (2004) Comparative analysis of pulmonary irritation by measure-ments of Penh and protein in bronchoalveolar lavage fluid in Brown Norway rats and Wistar rats exposed to irritant aerosols. Inhal Toxicol 16:159–175PubMedCrossRef
49.
Pauluhn J, Hai CX (2011) Attempts to counteract phosgene-induced acute lung injury by instant high-dose aerosol exposure to hexamethylenetetramine, cysteine or glutathione. Inhal Toxicol 23:58–64PubMedCrossRef
50.
Pauluhn J (2015) Chapter 6: time scaling of dose and time to response: the toxic load exponent. In: Salem H, Katz SA (eds) Inhalation toxicology, 3rd edn. CRC Press, New York, pp 121–136
51.
Pauluhn J, Thiel A (2007) A simple approach to validation of directed-flow nose-only inhalation chambers. J Appl Toxicol 27:160–167PubMedCrossRef
52.
53.
Epstein MA, Epstein RA (1978) A theoretical analysis of the barometric method for measurement of tidal volume. Respir Physiol 32:105–120PubMedCrossRef
54.
Krenzelok EP (2003) Phosgene in medical management of chemical casualities handbook—United States Army Medical Research Institute of Chemical Defence-Chemical Casualty Division, 3rd edn. American Society Heatlh-System Pharmacists, Inc, Bethesda, pp 105–107
55.
Duniho SM, Martin J, Forster JS, Cascio MB, Moran TS, Carpin LB, Sciuto AM (2002) Acute pulmonary changes in mice exposed to phosgene. Toxicol Pathol 30:339–349PubMedCrossRef
56.
United States Army (1945) Fasciculus on chemical warfare medicine-vol III-skin and systemic poisons. Prepared for the committee on medical research of the office of scientific research and development by the committee on treatment of the gas casualties division of medical sciences of the national research council. 1945; Washington, DC, p 212
57.
Gould NS, Day BJ (2011) Targeting maladaptive glutathione responses in lung disease. Biochem Pharmacol 81:187–193PubMedCrossRef
58.
Diller WF (1980) The methenamine misunderstanding in the therapy of phosgene poisoning. Arch Toxicol 46:199–206PubMedCrossRef
59.
Lailey AF, Hill L, Lawston IW, StantonD Upshall DG (1991) Protection by cysteine esters against chemically induced pulmonary edema. Biochem Pharmacol 42:S47–S54PubMedCrossRef
60.
Potts AM, Simon FP, Gerad RW (1949) The mechanism of action of phosgene and diphosgene. Arch Biochem 24:329–337PubMed
61.
Slade R, Crissman K, Norwood J, Hatch G (1993) Comparison of antioxidant substances in bronchoalveolar lavage cells and fluid from humans, guinea pigs, and rats. Exp Lung Res 19:469–484PubMedCrossRef
62.
Kodavanti UP, Costa DL, Giri SN, Starcher B, Hatch GE (1997) Pulmonary structural and extracellular matrix alterations in Fischer 344 rats following subchronic exposure. Fundam Appl Toxicol 37:54–63PubMedCrossRef
63.
Diller WF, Zante R (1982) Dosis-wirkungs-beziehungen bei phosgen-einwirkung auf mensch und tier. Zbl Arbeitsmed 32:360–368
64.
Schelegle ES (2003) Functional morphology and physiology of slowly adapting pulmonary stretch receptors. Anat Rec A Discov Mol Cell Evol Biol 270:11–16PubMedCrossRef
65.
Berthiaume Y, Lesur O, Dagenais A (1999) Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium. Thorax 54:150–160PubMedPubMedCentralCrossRef
66.
Jacquez JA (1979) Respiratory physiology—reflexes affecting respiration. Hemisphere Publishing Corporation, Washington, pp 331–350
67.
Hamelmann E, Schwarze J, Takeda K, Oshiba A, Larsen GL, Irvin CG, Gelfand EW (1997) Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 156:766–775PubMedCrossRef
68.
Hantos Z, Brusasco V (2002) Assessment of respiratory mechanics in small animals: the simpler the better? J Appl Physiol 93:1196–1197PubMedCrossRef
69.
Mitzner W, Tankersley C, Lundblad LK, Adler A, Irvin CG, Bates J (2003) Interpreting Penh in mice. J Appl Physiol 94:828–832PubMedCrossRef
70.
Mitzner W, Tankersley C (1998) Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 158:340–341PubMedCrossRef
71.
Peták F, Habre W, Donati YR, Hantos Z, Barazzone-Argiroffo C (2001) Hyperoxia-induced changes in mouse lung mechanics: forced oscillations vs. barometric plethysmography. J Appl Physiol 90:2221–2230PubMedCrossRef
72.
Frazer DG, Reynolds JS, Jackson MC (2011) Determining when enhanced pause (Penh) is sensitive to changes in specific airway resistance. J Toxicol Environ Health A 74:287–295PubMedCrossRef
73.
Lundblad LKA, Irvin CG, Hantos Z, Sly P, Mitzner W, Bates JHT (2007) Penh is not a measure of airway resistance! Eur Respir J 30:805PubMedCrossRef
74.
Liu F, Li W, Pauluhn J, Trübel H, Wang C (2013) Lipopolysaccharide-induced acute lung injury in rats: comparative assessment of intratracheal instillation and aerosol inhalation. Toxicology 304:158–166PubMedCrossRef
75.
76.
Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462PubMedCrossRef
77.
Stavrakis P (1971) The use of hexamethylenetetramine (HMT) in treatment of acute phosgene poisoning. Ind Med 40:30–31
78.
Lee L-Y (2009) respiratory sensations evoked by activation of bronchopulmonary C-fibers. Respir Physiol Neurobiol 167:26–35PubMedCrossRef
79.
80.
Paintal AS (1981) Effects of drugs on chemoreceptors, pulmonary and cardiovascular receptors. In: Widdicombe JG (ed) International encyclopedia of pharmacology and therapeutics, Section 104, respiratory pharmacology. Pergamon Press, Oxford, pp 217–239
81.
Ivanhoe F, Meyers FH (1964) Phosgene poisoning as an example of neuroparalytic acute pulmonary edema: the sympathetic vasomotor reflex involved. Chest 46:211–218
82.
Bruner RD, Boche, RD (1948) Electrocardiographic study of heart and effect of vagotomy in phosgene poisoning. In: Proceedings of the society for experimental biology and medicine 68: 279–281
83.
Büch T, Schäfer E, Steinritz D, Dietrich A, Gudermann T (2013) Chemosensory TRP channels in the respiratory tract: role in toxic lung injury and potential as “sweet spots” for targeted therapies. Rev Physiol Biochem Pharmacol 165:31–65PubMedCrossRef
84.
Andres D, Keyser B, Benton B, Melber A, Olivera D, Holmes W, Paradiso D, Anderson D, Ray R (2016) Transient receptor potential (TRP) channels as a therapeutic target for intervention of respiratory effects and lethality from phosgene. Toxicol Lett 244:21–27PubMedCrossRef
85.
Hatch G, Kodavanti U, Crissman K, Slade R, Costa D (2001) An ‘injury-time integral’ model for extrapolating from acute to chronic effects of phosgene. Toxicol Ind Health 17(5–10):285–293PubMedCrossRef
86.
Bernik TR, Friedman SG, Ochani M, DiRaimo R, Ulloa L, Yang H et al (2002) Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 195:781–788PubMedPubMedCentralCrossRef
87.
Verscheure S, Massion PB, Verschuren F, Damas P, Magder S (2016) Volumetric capnography: lessons from the past and current clinical applications. Crit Care 20:184PubMedPubMedCentralCrossRef
88.
Cepkova M, Kapur V, Ren X, Quinn T, Zhuo H, Foster E et al (2007) Pulmonary dead-space fraction and pulmonary artery systolic pressure as early predictors of clinical outcome in acute lung injury. Chest 132:836–842PubMedCrossRef
89.
Lucangelo U, Bernable F, Vatua S, Degrassi G, Villagra A, Fernandez R et al (2008) Prognostic value of different dead space indices in mechanically ventilated patients with acute lung injury and ARDS. Chest 133:62–71PubMedCrossRef
90.
Raurich JM, Vilar M, Colomar A, Ibáñez J, Ayestarán I, Pérez-Bárcena J, Llompart-Pou JA (2010) Prognostic value of the pulmonary dead-space fraction during the early and intermediate phases of acute respiratory distress syndrome. Respir Care. 55:282–287PubMed
91.
West JB (2008) Respiratory physiology: the essentials, vol 8. Lippencott Williams & Williams, Philadelphia, p 26
92.
93.
Enghoff H (1938) Volumen inefficax: bemerkungen zur Frage des schädlichen Raumes. Upsala LäkFör Förh 44:191–218
94.
95.
Baron RM, Carvajal IM, Fredenburgh LE, Liu X, Porrata Y, Cullivan ML et al (2004) Nitric oxide synthase down-regulates surfactant protein B expression and enhances endotoxin-induced lung injury in mice. FASEB J 18:1276–1278PubMed
96.
Chen HL, Bai H, Xi MM, Liu R, Qin XJ, Liang X et al (2013) Ethyl pyruvate protects rats from phosgene-induced pulmonary edema by inhibiting cyclooxygenase-2 and inducible nitric oxide synthase expression. J Appl Toxicol 33:71–77PubMedCrossRef
97.
Siddiki H, Kojicic M, Li G, Yilmaz M, Thompson TB, Hubmayr RD et al (2010) Bedside quantification of dead-space fraction using routine clinical data in patients with acute lung injury: secondary analysis of two prospective trials. Crit Care 14:R141PubMedPubMedCentralCrossRef
98.
Baron RM, Carvajal IM, Liu X, Okabe RO, Fredenburgh LE, Macias AA et al (2004) Reduction of nitric oxide synthase-2 expression by distamycin A improves survival from endotoxemia. J Immunol 173:4147–4153PubMedCrossRef
99.
Mehta S (2005) The effects of nitric oxide in acute lung injury. Vasc Pharmacol 43:390–403CrossRef
100.
Filipczak PT, Senft AP, Seagrave JC, Weber W, Kuehl PJ, Fredenburgh LE et al (2015) NOS-2 inhibition in phosgene-induced acute lung injury. Toxicol Sci 146:89–100PubMedPubMedCentralCrossRef
101.
Torkunov PA, Shabanov PD (2009) Using NO-synthase inhibitors derived from l-arginine for preventing acute experimental lung edema development in mice. Eksp Klin Farmakol 72:44–46PubMed
102.
Zwart A, Woutersen RA (1988) Acute inhalation toxicity of chlorine in rats and mice: time-concentration-mortality relationships and effects on respiration. J Hazard Mater 19:195–208CrossRef
103.
Jonasson S, Koch B, Bucht A (2013) Inhalation of chlorine causes long-standing lung inflammation and airway hyperresponsiveness in a murine model of chemical-induced lung injury. Toxicology 303:34–42PubMedCrossRef
104.
Leikauf GD, Pope-Varsalona H, Concel VJ, Liu P, Bein K, Berndt A (2012) Integrative assessment of chlorine-induced acute lung injury in mice. Am J Respir Cell Mol Biol 2:234–244CrossRef
105.
Leustik M, Doran S, Bracher A, Williams S, Squadrito GL, Schoeb TR et al (2008) Mitigation of chlorine-induced lung injury by low-molecular-weight antioxidants. Am J Physiol Lung Cell Mol Physiol 295:733–743CrossRef
106.
Borak J, Diller WF (2000) Phosgene exposure: mechanisms of injury and treatment strategies. J Occup Environ Med 43:110–119CrossRef
107.
Withers RMJ, Lees FP (1985) The assessment of major hazards: the lethal toxicity of chlorine, part 2: model of toxicity to man. J Hazard Mater 12:283–302CrossRef
108.
Withers RMJ, Lees FP (1987) The assessment of major hazards: the lethal toxicity of chlorine, part 3: crosschecks from gas warfare. J Hazard Mater 15:301–342CrossRef
109.
Yadav AK, Doran SF, Samal AA, Sharma R, Vedagiri K et al (2011) Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite. Am J Physiol Lung Cell Mol Physiol 300:L362–L369PubMedCrossRef
110.
Yadav AK, Bracher A, Doran SF, Leustik M, Squadrito GL, Postlethwait EM et al (2010) Mechanisms and modification of chlorine-induced lung injury in animals. Proc Am Thorac Soc 7:278–283PubMedPubMedCentralCrossRef
111.
Weill H, George R, Schwarz M, Ziskind M (1969) Late evaluation of pulmonary function after acute exposure to chlorine gas. Am Rev Respir Dis 99:374–379PubMed
112.
113.
Underhill FP (1920) The lethal war gases, physiology and experimental treatment. Yale University Press, New Haven
114.
Underhill FP (1919) The physiology and experimental treatment of poisoning with the lethal war gases. Arch Int Med. 23: 753–770 Cited in WHO, 1997, 1998
115.
116.
Glas GJ, van der Sluijs KF, Schultz MJ, Hofstra J-JH, van der Poll T, Levi M (2013) Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome. J Thromb Haemost 11:17–25PubMedCrossRef
117.
Lemiere C, Malo JL, Boulet LP, Boutet M (1996) Reactive airways dysfunction syndrome induced by exposure to a mixture containing isocyanate: functional and histopathologic behaviour. Allergy 51:262–265PubMedCrossRef
118.
Lemiere C, Malo JL, Boutet M (1997) Reactive airways dysfunction syndrome due to chlorine: sequential bronchial biopsies and functional assessment. Eur Respir J 10:241–244PubMedCrossRef
119.
Fletcher R, Jonson B, Cumming G, Brew J (1981) The concept of dead-space with special reference to the single breath test for carbon dioxide. Br J Anaesth 53:77–88PubMedCrossRef
120.
Withers RMJ, Lees FP (1985) The assessment of major hazards: the lethal toxicity of chlorine, part 1: review of information on toxicity. J Hazard Mater 12:231–282CrossRef
121.
Kehoe RA (1943) Pulmonary irritants. Bull NY Acad Med 19:340–355
122.
Grainge C, Rice P (2010) Management of phosgene-induced acute lung injury. Clin Toxicol Phila 48:497–508PubMedCrossRef
123.
Croinin DO, Chonghaile MN, Higgins B, Laffey JG (2005) Bench-to-bedside review: permissive hypercapnia. Crit Care 9:51CrossRef
124.
Chonghaile MN, Higgins B, Laffey JG (2005) Permissive hypercapnia: role in protective lung ventilation strategies. Curr Opin Crit Care 11:56–62CrossRef
125.
Garg SK (2014) Permissive hypercapnia: is there any upper limit? Indian J Crit Care Med Peer Rev Off Publ Indian Soc Crit Care Med 18:612–614
126.
Thorens JB, Jolliet P, Ritz M, Chevrolet JC (1996) Effects of rapid permissive hypercapnia on hemodynamics, gas exchange, and oxygen transport and consumption during mechanical ventilation for the acute respiratory distress syndrome. Intensive Care Med 22:182–191PubMedCrossRef
127.
Feihl F, Perret C (1994) Permissive hypercapnia. How permissive should we be? Am J Respir Crit Care Med 150:1722–1737PubMedCrossRef
128.
Colmenero-Ruiz M, Fernández-Mondéjar E, Fernández-Sacristán MA, Rivera-Fernández R, Vazquez-Mata G (1997) PEEP and low tidal volume ventilation reduce lung water in porcine pulmonary edema. Am J Respir Crit Care Med 155:964–970PubMedCrossRef
129.
Berthiaume Y, Folkesson HG, Matthay MA (2002) Lung edema clearance: 20 years of progress—invited review: alveolar edema fluid clearance in the injured lung. J Appl Physiol 93:2207–2213PubMedCrossRef
130.
Sciuto AM, Hurt HH (2004) Therapeutic treatments of phosgene-induced lung injury. Inhal Toxicol 16:565–580PubMedCrossRef
131.
Matthay MA, Zimmerman GA (2005) Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol 33:319–327PubMedPubMedCentralCrossRef
132.
Grainge C, Rice P (2010) Management of phosgene-induced acute lung injury. Clin Toxicol 48:497–508CrossRef
133.
Ferrando C, Mugarra A, Gutierrez A, Carbonell JA, García M, Soro M et al (2014) Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation. Anesth Analg 118:657–665PubMedCrossRef
134.
Shen J, Gan Z, Zhao J, Zhang L, Xu G (2014) Ulinastatin reduces pathogenesis of phosgene-induced acute lung injury in rats. Toxicol Ind Health 30:785–793PubMedCrossRef
135.
Nieman GF (1985) Current concepts of lung-fluid balance. Respir Care 30:1062–1076
136.
Nieman GF, Bredenberg CE (1985) High surface tension pulmonary edema induced by detergent aerosol. J Appl Physiol 58:129–136PubMed
137.
138.
Krinke GJ (2000) The laboratory rat. Academic Press, San Diego, p 486
139.
Postel S, Swift M (1945) Evaluation of the bleeding-transfusion treatment of phosgene poisoning. In: Fasciculus on chemical warfare medicine: v. II, respiratory tract. Washington, National Research Council, Committee on Treatment of Gas Casualties. p 664–690. Cited in EPA 1986
140.
Meek WJ, Eyster JAE (1920) Experiments on the pathological physiology of acute phosgene poisoning. Am J Physiol 51:303–320
141.
Mautone AJ, Katz Z, Scarpelli EM (1985) Acute responses to phosgene inhalation and selected corrective measures (including surfactant). Toxicol Ind Health 1(2):37–57PubMedCrossRef
142.
Cameron GR, Courtice FC (1946) The production and removal of oedema fluid in the lung after exposure to carbonyl chloride (phosgene). J Physiol 105:175–185PubMedCentralCrossRef
Metadata
Title
Phosgene-induced acute lung injury (ALI): differences from chlorine-induced ALI and attempts to translate toxicology to clinical medicine
Authors
Wenli Li
Juergen Pauluhn
Publication date
01-12-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical and Translational Medicine / Issue 1/2017
Electronic ISSN: 2001-1326
DOI
https://doi.org/10.1186/s40169-017-0149-2

Other articles of this Issue 1/2017

Clinical and Translational Medicine 1/2017 Go to the issue

Commentary

Re: Choices have consequences: the nexus between DNA repair pathways and genomic instability in cancer


Commentary

Contact allergy to aluminium induced by commonly used pediatric vaccines

Short report

Deletion of Cdc42 in embryonic cardiomyocytes results in right ventricle hypoplasia

Review

Can glypican-3 be a disease-specific biomarker?

Research

Profiling of cardio-metabolic risk factors and medication utilisation among Type II diabetes patients in Ghana: a prospective cohort study

Perspective

A systematic approach to cancer: evolution beyond selection