J. Ashley Jefferson, MD Seattle, WA Elizabeth Escudero, MD Lima, Peru Richard J. Johnson, MD Aurora, CO Erik R. Swenson, MD Seattle, WA Abdias Hurtado, MD Lima, Peru
Correspondence to: Lonny Yarmus, DO, FCCP, Section of Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans St, Ste 7125, Baltimore, MD 21208; e-mail: lyarmus@ jhmi.edu. © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-2197
References 1. Yarmus L, Gilbert C, Lechtzin N, Imad M, Ernst A, FellerKopman D. Safety and feasibility of interventional pulmonologists performing bedside percutaneous endoscopic gastrostomy tube placement. Chest. 2013;144(2):436-440. 2. Abuksis G, Mor M, Segal N, et al. Percutaneous endoscopic gastrostomy: high mortality rates in hospitalized patients. Am J Gastroenterol. 2000;95(1):128-132. 3. Tokunaga T, Kubo T, Ryan S, et al. Long-term outcome after placement of a percutaneous endoscopic gastrostomy tube. Geriatr Gerontol Int. 2008;8(1):19-23. 4. Kovitz KL. Three cheers for the crumbling silo: the lesson of how a minor procedure can have a major impact. Chest. 2013; 144(2):368-369. 5. Pandian V, Miller CR, Mirski MA, et al. Multidisciplinary team approach in the management of tracheostomy patients. Otolaryngol Head Neck Surg. 2012;147(4):684-691.
Increased Oxidative Stress at Altitude To the Editor: We read with interest the study in CHEST (February 2013) by Bailey et al1 in which they describe increased oxidative-nitrosative stress in people who live in a high altitude. In their article, they stated that “there are no studies, to our knowledge, that have examined this response during lifelong exposure to high altitude in healthy, well-adapted and maladapted highlanders.”1 Hypoxia has been associated with oxidative stress in in vitro experiments,2 in animal models exposed to hypobaric hypoxia,3 in humans acutely exposed to high altitude,4 and in simulated altitude.5 We would like to highlight our prior study. We investigated oxidative stress in both acute exposure to high altitude (48 h in volunteers at sea level; n 5 28) and chronic exposure to high altitude in the Andes (healthy residents at high altitude [n 5 25] and residents at high altitude [n 5 27] with abnormal adaptation to highaltitude living, a condition known as chronic mountain sickness).6 Assessment of oxidative stress was performed by measuring oxidation products in plasma (thiobarbituric acid reactive substances) and urine (F2-isoprostanes [8-isoprostaglandin F2a]). As an assessment of antioxidant status, we measured total plasma glutathione. Our study confirmed that both acute (48 h) and chronic exposure to high altitude are associated with increased levels of lipid peroxidation, and these levels correlate with increased plasma levels of total glutathione. Patients chronically living at high altitude have elevated levels of plasma total glutathione and lipid peroxidation products, and the subgroup with chronic mountain sickness, or Monge disease, has significantly greater levels of lipid peroxidation compared to control subjects at sea level and control subjects at high altitude. Indeed, in our study, the subjects with the highest degree of oxidative stress also had elevated blood cobalt levels, likely related to contamination from the local mines.7 Currently, we are conducting a clinical trial to see if we can both chelate the cobalt and reduce the oxidative stress with N-acetylcysteine. journal.publications.chestnet.org
Affiliations: From the Division of Nephrology (Dr Jefferson), University of Washington; Carlos Monge Cassinelli Nephrology Center (Drs Escudero and Hurtado), University of Cayetano Heredia; Division of Nephrology (Dr Johnson), University of Colorado; and Division of Pulmonary and Critical Care Medicine, Department of Medicine (Dr Swenson), VA Puget Sound Health Care System, University of Washington. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: J. Ashley Jefferson, MD, University of Washington, Division of Nephrology, 1959 NE Pacific St, Box 356174, Seattle, WA 98195; e-mail: [email protected] © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-2062
References 1. Bailey DM, Rimoldi SF, Rexhaj E, et al. Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia. Chest. 2013;143(2):444-451. 2. Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem. 1998;273(19):11619-11624. 3. Sarada SK, Dipti P, Anju B, et al. Antioxidant effect of betacarotene on hypoxia induced oxidative stress in male albino rats. J Ethnopharmacol. 2002;79(2):149-153. 4. Richalet JP, Hornych A, Rathat C, Aumont J, Larmignat P, Rémy P. Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia. Respir Physiol. 1991;85(2): 205-215. 5. Joanny P, Steinberg J, Robach P, et al. Operation Everest III (Comex’97): the effect of simulated sever hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise. Resuscitation. 2001;49(3):307-314. 6. Jefferson JA, Simoni J, Escudero E, et al. Increased oxidative stress following acute and chronic high altitude exposure. High Alt Med Biol. 2004;5(1):61-69. 7. Jefferson JA, Escudero E, Hurtado ME, et al. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002;359(9304):407-408.
Response To the Editor: We thank Dr Jefferson and colleagues for their interest in our publication in CHEST1 describing the vascular implications of altered free radical metabolism during the course of human acclimatization to terrestrial high altitude. Our study revealed that, compared with lowlander control subjects, systemic free radical formation was moderately elevated in healthy well-adapted Andean highlanders, with more exaggerated increases observed in those CHEST / 145 / 2 / FEBRUARY 2014
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Correspondence to: Lonny Yarmus, DO, FCCP, Section of Interventional Pulmonology, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 1800 Orleans St, Ste 7125, Baltimore, MD 21208; e-mail: lyarmus@ jhmi.edu. © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-2197
References 1. Yarmus L, Gilbert C, Lechtzin N, Imad M, Ernst A, FellerKopman D. Safety and feasibility of interventional pulmonologists performing bedside percutaneous endoscopic gastrostomy tube placement. Chest. 2013;144(2):436-440. 2. Abuksis G, Mor M, Segal N, et al. Percutaneous endoscopic gastrostomy: high mortality rates in hospitalized patients. Am J Gastroenterol. 2000;95(1):128-132. 3. Tokunaga T, Kubo T, Ryan S, et al. Long-term outcome after placement of a percutaneous endoscopic gastrostomy tube. Geriatr Gerontol Int. 2008;8(1):19-23. 4. Kovitz KL. Three cheers for the crumbling silo: the lesson of how a minor procedure can have a major impact. Chest. 2013; 144(2):368-369. 5. Pandian V, Miller CR, Mirski MA, et al. Multidisciplinary team approach in the management of tracheostomy patients. Otolaryngol Head Neck Surg. 2012;147(4):684-691.
Increased Oxidative Stress at Altitude To the Editor: We read with interest the study in CHEST (February 2013) by Bailey et al1 in which they describe increased oxidative-nitrosative stress in people who live in a high altitude. In their article, they stated that “there are no studies, to our knowledge, that have examined this response during lifelong exposure to high altitude in healthy, well-adapted and maladapted highlanders.”1 Hypoxia has been associated with oxidative stress in in vitro experiments,2 in animal models exposed to hypobaric hypoxia,3 in humans acutely exposed to high altitude,4 and in simulated altitude.5 We would like to highlight our prior study. We investigated oxidative stress in both acute exposure to high altitude (48 h in volunteers at sea level; n 5 28) and chronic exposure to high altitude in the Andes (healthy residents at high altitude [n 5 25] and residents at high altitude [n 5 27] with abnormal adaptation to highaltitude living, a condition known as chronic mountain sickness).6 Assessment of oxidative stress was performed by measuring oxidation products in plasma (thiobarbituric acid reactive substances) and urine (F2-isoprostanes [8-isoprostaglandin F2a]). As an assessment of antioxidant status, we measured total plasma glutathione. Our study confirmed that both acute (48 h) and chronic exposure to high altitude are associated with increased levels of lipid peroxidation, and these levels correlate with increased plasma levels of total glutathione. Patients chronically living at high altitude have elevated levels of plasma total glutathione and lipid peroxidation products, and the subgroup with chronic mountain sickness, or Monge disease, has significantly greater levels of lipid peroxidation compared to control subjects at sea level and control subjects at high altitude. Indeed, in our study, the subjects with the highest degree of oxidative stress also had elevated blood cobalt levels, likely related to contamination from the local mines.7 Currently, we are conducting a clinical trial to see if we can both chelate the cobalt and reduce the oxidative stress with N-acetylcysteine. journal.publications.chestnet.org
Affiliations: From the Division of Nephrology (Dr Jefferson), University of Washington; Carlos Monge Cassinelli Nephrology Center (Drs Escudero and Hurtado), University of Cayetano Heredia; Division of Nephrology (Dr Johnson), University of Colorado; and Division of Pulmonary and Critical Care Medicine, Department of Medicine (Dr Swenson), VA Puget Sound Health Care System, University of Washington. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: J. Ashley Jefferson, MD, University of Washington, Division of Nephrology, 1959 NE Pacific St, Box 356174, Seattle, WA 98195; e-mail: [email protected] © 2014 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-2062
References 1. Bailey DM, Rimoldi SF, Rexhaj E, et al. Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia. Chest. 2013;143(2):444-451. 2. Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem. 1998;273(19):11619-11624. 3. Sarada SK, Dipti P, Anju B, et al. Antioxidant effect of betacarotene on hypoxia induced oxidative stress in male albino rats. J Ethnopharmacol. 2002;79(2):149-153. 4. Richalet JP, Hornych A, Rathat C, Aumont J, Larmignat P, Rémy P. Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia. Respir Physiol. 1991;85(2): 205-215. 5. Joanny P, Steinberg J, Robach P, et al. Operation Everest III (Comex’97): the effect of simulated sever hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise. Resuscitation. 2001;49(3):307-314. 6. Jefferson JA, Simoni J, Escudero E, et al. Increased oxidative stress following acute and chronic high altitude exposure. High Alt Med Biol. 2004;5(1):61-69. 7. Jefferson JA, Escudero E, Hurtado ME, et al. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002;359(9304):407-408.
Response To the Editor: We thank Dr Jefferson and colleagues for their interest in our publication in CHEST1 describing the vascular implications of altered free radical metabolism during the course of human acclimatization to terrestrial high altitude. Our study revealed that, compared with lowlander control subjects, systemic free radical formation was moderately elevated in healthy well-adapted Andean highlanders, with more exaggerated increases observed in those CHEST / 145 / 2 / FEBRUARY 2014
423
