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Effect of Ambient Level of Carbon Monoxide on Cardiopulmonary Disease
CHEST VOLUME 74 I NUMBER 1 I JULY, 1978
with acute electrocardiographic changes in apparently healthy 6re-fighters at work.9-10 In addition, ischemic heart disease has been demonstrated in fire-fighters with normal coronary arteries." An increased level of carboxyhemoglobin after exposure to heavy traftic on the freeway caused a reduction in exercise time until the onset of angina, associated with a decrease in the product of systolic blood pressure times heart rate at the onset of angina, both immediately after and two hours after breathing air on the freeway.P Two double-blind, randomized studies have confirmed that exposure to carbon monoxide in concentrations found during heavy atmospheric pollution with carbon monoxide aggravates exercise-induced angina.I3.14 Well demonstrated in a double-blind, randomized study that exposure to a level of carbon monoxide of 50 ppm for two hours aggravates intermittent claudication of the calf or thigh. Experimental data have also implicated carbon monoxide in concentrations found in heavy tobacco smoking in the pathogenesis of coronary atherosclerosis.I' Cohen and associates" found an association between atmospheric pollution with carbon monoxide in Los Angeles and mortality in patients with acute myocardial infarction admitted to 35 hospitals in Los Angeles. Decreases in mortality from cardiovascular disease and from chronic pulmonary disease were also observed in San Francisco County and in Alameda County during the fuel crisis of 1974.18 DeBias et all' showed that inhalation of carbon monoxide sufficient to raise the mean arterial level of carboxyhemoglobin to 10.2 percent was a significant factor in enhancing ventricular fibrillation in monkeys with acute myocardial infarction. Furthermore, weJO demonstrated in a blind, randomized study that breathing a level of carbon monoxide of 100 ppm for two hours to raise the mean arterial level of carboxyhemoglobin to 6.34 percent caused a reduction in the threshold for ventricular fibrillation in dogs with acute myocardial injury. On the basis of the available evidence, we must consider that heavy atmospheric pollution with carbon monoxide, as well as cigarette smoking, plays a role in the pathogenesis of cardiopulmonary
EDITORIALS
Effect of Ambient Level of Carbon Monoxide on Cardiopulmonary Disease and colleagues (see page 10) have demK onstrated that the ambient level of carbon urt
monoxide in Denver has a significant low-level association with the frequency of acute cardiorespiratory events in an emergency room. Their data lead one to conclude that carbon monoxide from the macroenvironment should be considered a risk factor for cardiopulmonary disease. As the afBnity ~ hemoglobin for carbon monoxide is approximately 245 times greater than its affinity for oxygen, carbon monoxide displaces oxygen from hemoglobin, decreasing the amount of oxygen available to the myocardium. Carbon monoxide also induces a leftward shift of the oxyhemoglobin dissociation curve, causing tighter binding of oxygen to hemoglobin, further reducing the availability of oxygen to the myocardium. Furthermore, carbon monoxide causes a negative in0tropic effect on the myocardium.I In addition, carbon monoxide causes myocardial oxygen extraction and extraction ratios to be reduced and the myocardial lactate extraction ratio to be changed to lactate production in patients with coronary heart disease.s Carbon monoxide also combines with myoglobin and can impair the facilitated diHusion of oxygen to the mitochondria.' In addition, carbon monoxide combines directly with cytochrome oxidase (aa ), slowing oxidation of reduced nicotinamide-adenine dinucleotide.s Wei demonstrated in a double-blind, randomized crossover study that patients with chronic obstructive pulmonary disease who breathed a level of carbon monoxide of 100 ppm for one hour had a reduction in the mean exercise time of 33 percent. Increased levels of carboxyhemoglobin of the magnitude observed after heavy atmospheric pollution with carbon monoxide also impair the exercise performance in normal persons. &-8 Furthermore, exposure to carbon monoxide has also been associated
1
disease. The excellent study by Kurt and his associates provides further evidence documenting that heavy atmospheric pollution with carbon monoxide contributes to cardiopulmonary disease. Wilbert S. Aronow, M.D., F.C.C.P.· Long Beach, Calif. -Chief Cardiovascular Section, and Assistant Chief of Medicine for Research, Veterans Administration Hospital, Long Beach, Calif; and Professor of Medicine, of MediCal Pharmacology and Therapeutics, and of Community and Environmental Medicine, Vice-Chief of Cardiovascular Division, and Chief of Cardiovascular Research, University of California, Irvine. Reprint requests: Dr. Aronow, VA HospUol, Long Beoch, Colifomia 90822
REFERENCFS 1 Aronow WS, Cassidy I, Vangrow IS, et al: mect of cigarette smoking and breathing carbon monoxide on car2
3 4
5 6 7
8 9 10 11 12 13
14 15
diovascular hemodynamics in anginal patients. Circulation 50:340-347, 1974 et at: Systemic and Ayres SM, Mueller HS, Gregory myocardial hemodynamic responses to relatively small concentrations of carboxyhemoglobin ( COHB). Arch Environ Health 18:699-709, 1969 Wittenberg JB: The molecular mechanism of hemoglobinfacilitated oxygen diffusion. I BioI Chern 241:104-114, 1966 Whereat AF: Is atherosclerosis a disorder of intramitochondrial respiration? Ann Intern Med 73:125-127, 1970 Aronow WS, Ferlinz J, Glauser F: Effect of carbon monoxide on exercise performance in chronic obstructive pulmonary disease. Am J Med 63:904-908, 1977 Ekblom B, Huot R: Response to submaximal and maximal exercise at different levels of carboxyhemoglobin. Acta Physiol Scand 86:474-482, 1972 Drinkwater BL, Raven PB, Horvath SM, et al: Air pollution, exercise and heat stress. Arch Environ Health 28:177-181, 1974 Aronow WS, Cassidy I: Effect of carbon monoxide on maximal treadmill exercise: A study in normal persons. Ann Intern Med 83:496-499, 1975 Kurt TL, Peters 1M: Epidemiology of cardiac risks in fire fighters with Holter electrocardiograms and carbon monoxide sampling. Circulation 52:11-204, 1975 Radford LP, Levine MS: Occupational exposures to carbon monoxide in Baltimore firefighters. I Occup Med 18:628-632, 1976 Barnard RI, Gardner GW, Diaco NV: "Iscbemic" heart disease in fire fighters with normal coronary arteries. J Occup Med 18:818-820, 1976 Aronow WS, Harris CN, Isbell MW, et at: Effect of freeway travel on angina pectoris. Ann Intern Med 77 :669-616, 1972 Anderson EW, Andelman RJ, Strauch IM, et at: Effect of low-level carbon monoxide exposure on onset and duration of angina pectoris: A study of ten patients with ischemic heart disease. Ann Intern Med 79:46-50, 1973 Aronow WS, Isbell MW: Carbon monoxide effect on exercise-induced angina pectoris. Ann Intern Med 79: 392-395, 1973 Aronow WS, Stemmer EA, Isbell MW: Effect of carbon monoxide exposure on intermittent claudication. Circulation 49:415-417, 1974
2 EDITORIALS
n,
16 Aronow WS: Carbon monoxide and cardiovascular disease. In Wynder EL, HoHman D, Gori GB (eels): Smoking and Health: Modifying the Risk for the Smoker (vol 1) (publication (NIH] 76-1221). US Department of Health, Education, and Welfare, 1976, pp 321-328 17 Cohen SI, Deane M, Goldsmith JR: Carbon monoxide and survival from myocardial infarction. Arch Environ Health 19:510-517, 1969 18 Brown SM, Marmot MG, Sacks ST, et at: Effect on mortality of the 1974 fuel crisis. Nature 257:306-307, 1975 19 DeBias DA, Banerjee CM, Birkhead NC, et at: Effects of carbon monoxide inhalation on ventricular fibrillation. Arch Environ Health 31:42-46, 1976 20 Aronow WS, Stemmer EA, Wood B, et at: Carbon m0noxide and ventricular fibrillation threshold in dogs with acute myocardial injury. Am Heart I, to be published
The Staging of Lung Cancer Staging a cancer of the lung is the estimation of the anatomic extent of the primary tumor and the absence or presence of spread to the regional lymph nodes and of more distant metastases. The estimation can be made after a clinical-diagnostic examination, after an exploratory thoracotomy, after the thorough examination of a therapeutically resected specimen, after a recurrence of the cancer following successful primary treatment, and even after an autopsy. The anatomic extent or stage can be described in a narrative statement, or the physician may use a system for staging such as that developed by the American Joint Committee for Cancer Staging and End Results Reporting and adopted by several national and international groups interested in lung ~cer.l-a
The system was developed by the retrospective study of more than 2,000 cases of lung cancer. Since publication in 1973, the system has been tested by application to thousands of additional cases of cancer of the lung. This resulted in a few minor revisions. The new version of the system for staging has been published by the American Joint Committee, along with systems for staging of cancers at all of the common primary sites. This Manual for Staging of Cancer-1977 may be obtained on request by writing to the American Joint Committee for Cancer Staging and End Results Reporting, 55 EErie St, Chicago 60611. All members of the American College of Chest Physicians and readers of Chest should obtain a copy of this manual and study the system for staging of lung cancer. Routine use of the system in the diagnosis and treatment of patients with lung cancer will stimulate thoroughness in the evaluation of each patient. Use of the system in communications about individual patients will increase the clarity of such communications. Use of the system in the
CHEST, 74: 1, JULY, 1978
with acute electrocardiographic changes in apparently healthy 6re-fighters at work.9-10 In addition, ischemic heart disease has been demonstrated in fire-fighters with normal coronary arteries." An increased level of carboxyhemoglobin after exposure to heavy traftic on the freeway caused a reduction in exercise time until the onset of angina, associated with a decrease in the product of systolic blood pressure times heart rate at the onset of angina, both immediately after and two hours after breathing air on the freeway.P Two double-blind, randomized studies have confirmed that exposure to carbon monoxide in concentrations found during heavy atmospheric pollution with carbon monoxide aggravates exercise-induced angina.I3.14 Well demonstrated in a double-blind, randomized study that exposure to a level of carbon monoxide of 50 ppm for two hours aggravates intermittent claudication of the calf or thigh. Experimental data have also implicated carbon monoxide in concentrations found in heavy tobacco smoking in the pathogenesis of coronary atherosclerosis.I' Cohen and associates" found an association between atmospheric pollution with carbon monoxide in Los Angeles and mortality in patients with acute myocardial infarction admitted to 35 hospitals in Los Angeles. Decreases in mortality from cardiovascular disease and from chronic pulmonary disease were also observed in San Francisco County and in Alameda County during the fuel crisis of 1974.18 DeBias et all' showed that inhalation of carbon monoxide sufficient to raise the mean arterial level of carboxyhemoglobin to 10.2 percent was a significant factor in enhancing ventricular fibrillation in monkeys with acute myocardial infarction. Furthermore, weJO demonstrated in a blind, randomized study that breathing a level of carbon monoxide of 100 ppm for two hours to raise the mean arterial level of carboxyhemoglobin to 6.34 percent caused a reduction in the threshold for ventricular fibrillation in dogs with acute myocardial injury. On the basis of the available evidence, we must consider that heavy atmospheric pollution with carbon monoxide, as well as cigarette smoking, plays a role in the pathogenesis of cardiopulmonary
EDITORIALS
Effect of Ambient Level of Carbon Monoxide on Cardiopulmonary Disease and colleagues (see page 10) have demK onstrated that the ambient level of carbon urt
monoxide in Denver has a significant low-level association with the frequency of acute cardiorespiratory events in an emergency room. Their data lead one to conclude that carbon monoxide from the macroenvironment should be considered a risk factor for cardiopulmonary disease. As the afBnity ~ hemoglobin for carbon monoxide is approximately 245 times greater than its affinity for oxygen, carbon monoxide displaces oxygen from hemoglobin, decreasing the amount of oxygen available to the myocardium. Carbon monoxide also induces a leftward shift of the oxyhemoglobin dissociation curve, causing tighter binding of oxygen to hemoglobin, further reducing the availability of oxygen to the myocardium. Furthermore, carbon monoxide causes a negative in0tropic effect on the myocardium.I In addition, carbon monoxide causes myocardial oxygen extraction and extraction ratios to be reduced and the myocardial lactate extraction ratio to be changed to lactate production in patients with coronary heart disease.s Carbon monoxide also combines with myoglobin and can impair the facilitated diHusion of oxygen to the mitochondria.' In addition, carbon monoxide combines directly with cytochrome oxidase (aa ), slowing oxidation of reduced nicotinamide-adenine dinucleotide.s Wei demonstrated in a double-blind, randomized crossover study that patients with chronic obstructive pulmonary disease who breathed a level of carbon monoxide of 100 ppm for one hour had a reduction in the mean exercise time of 33 percent. Increased levels of carboxyhemoglobin of the magnitude observed after heavy atmospheric pollution with carbon monoxide also impair the exercise performance in normal persons. &-8 Furthermore, exposure to carbon monoxide has also been associated
1
disease. The excellent study by Kurt and his associates provides further evidence documenting that heavy atmospheric pollution with carbon monoxide contributes to cardiopulmonary disease. Wilbert S. Aronow, M.D., F.C.C.P.· Long Beach, Calif. -Chief Cardiovascular Section, and Assistant Chief of Medicine for Research, Veterans Administration Hospital, Long Beach, Calif; and Professor of Medicine, of MediCal Pharmacology and Therapeutics, and of Community and Environmental Medicine, Vice-Chief of Cardiovascular Division, and Chief of Cardiovascular Research, University of California, Irvine. Reprint requests: Dr. Aronow, VA HospUol, Long Beoch, Colifomia 90822
REFERENCFS 1 Aronow WS, Cassidy I, Vangrow IS, et al: mect of cigarette smoking and breathing carbon monoxide on car2
3 4
5 6 7
8 9 10 11 12 13
14 15
diovascular hemodynamics in anginal patients. Circulation 50:340-347, 1974 et at: Systemic and Ayres SM, Mueller HS, Gregory myocardial hemodynamic responses to relatively small concentrations of carboxyhemoglobin ( COHB). Arch Environ Health 18:699-709, 1969 Wittenberg JB: The molecular mechanism of hemoglobinfacilitated oxygen diffusion. I BioI Chern 241:104-114, 1966 Whereat AF: Is atherosclerosis a disorder of intramitochondrial respiration? Ann Intern Med 73:125-127, 1970 Aronow WS, Ferlinz J, Glauser F: Effect of carbon monoxide on exercise performance in chronic obstructive pulmonary disease. Am J Med 63:904-908, 1977 Ekblom B, Huot R: Response to submaximal and maximal exercise at different levels of carboxyhemoglobin. Acta Physiol Scand 86:474-482, 1972 Drinkwater BL, Raven PB, Horvath SM, et al: Air pollution, exercise and heat stress. Arch Environ Health 28:177-181, 1974 Aronow WS, Cassidy I: Effect of carbon monoxide on maximal treadmill exercise: A study in normal persons. Ann Intern Med 83:496-499, 1975 Kurt TL, Peters 1M: Epidemiology of cardiac risks in fire fighters with Holter electrocardiograms and carbon monoxide sampling. Circulation 52:11-204, 1975 Radford LP, Levine MS: Occupational exposures to carbon monoxide in Baltimore firefighters. I Occup Med 18:628-632, 1976 Barnard RI, Gardner GW, Diaco NV: "Iscbemic" heart disease in fire fighters with normal coronary arteries. J Occup Med 18:818-820, 1976 Aronow WS, Harris CN, Isbell MW, et at: Effect of freeway travel on angina pectoris. Ann Intern Med 77 :669-616, 1972 Anderson EW, Andelman RJ, Strauch IM, et at: Effect of low-level carbon monoxide exposure on onset and duration of angina pectoris: A study of ten patients with ischemic heart disease. Ann Intern Med 79:46-50, 1973 Aronow WS, Isbell MW: Carbon monoxide effect on exercise-induced angina pectoris. Ann Intern Med 79: 392-395, 1973 Aronow WS, Stemmer EA, Isbell MW: Effect of carbon monoxide exposure on intermittent claudication. Circulation 49:415-417, 1974
2 EDITORIALS
n,
16 Aronow WS: Carbon monoxide and cardiovascular disease. In Wynder EL, HoHman D, Gori GB (eels): Smoking and Health: Modifying the Risk for the Smoker (vol 1) (publication (NIH] 76-1221). US Department of Health, Education, and Welfare, 1976, pp 321-328 17 Cohen SI, Deane M, Goldsmith JR: Carbon monoxide and survival from myocardial infarction. Arch Environ Health 19:510-517, 1969 18 Brown SM, Marmot MG, Sacks ST, et at: Effect on mortality of the 1974 fuel crisis. Nature 257:306-307, 1975 19 DeBias DA, Banerjee CM, Birkhead NC, et at: Effects of carbon monoxide inhalation on ventricular fibrillation. Arch Environ Health 31:42-46, 1976 20 Aronow WS, Stemmer EA, Wood B, et at: Carbon m0noxide and ventricular fibrillation threshold in dogs with acute myocardial injury. Am Heart I, to be published
The Staging of Lung Cancer Staging a cancer of the lung is the estimation of the anatomic extent of the primary tumor and the absence or presence of spread to the regional lymph nodes and of more distant metastases. The estimation can be made after a clinical-diagnostic examination, after an exploratory thoracotomy, after the thorough examination of a therapeutically resected specimen, after a recurrence of the cancer following successful primary treatment, and even after an autopsy. The anatomic extent or stage can be described in a narrative statement, or the physician may use a system for staging such as that developed by the American Joint Committee for Cancer Staging and End Results Reporting and adopted by several national and international groups interested in lung ~cer.l-a
The system was developed by the retrospective study of more than 2,000 cases of lung cancer. Since publication in 1973, the system has been tested by application to thousands of additional cases of cancer of the lung. This resulted in a few minor revisions. The new version of the system for staging has been published by the American Joint Committee, along with systems for staging of cancers at all of the common primary sites. This Manual for Staging of Cancer-1977 may be obtained on request by writing to the American Joint Committee for Cancer Staging and End Results Reporting, 55 EErie St, Chicago 60611. All members of the American College of Chest Physicians and readers of Chest should obtain a copy of this manual and study the system for staging of lung cancer. Routine use of the system in the diagnosis and treatment of patients with lung cancer will stimulate thoroughness in the evaluation of each patient. Use of the system in communications about individual patients will increase the clarity of such communications. Use of the system in the
CHEST, 74: 1, JULY, 1978