©@~GYA](w~O©£lfO@~®
TO THe eDITOR
Mycotoxicosis? To the Editor: Recently the possibility of a "new lung disease" has been discussed; 1 and the term, mycotoxicosis, has been applied to a syndrome similar to farmer's lung caused by the inhalation of massive amounts of fungi but diHering from the classic syndrome by an absence of precipitins to extracts of inhaled material and by the presence of fungal spores in biopsy material. The absence of precipitins to respirable material, eg, moldy hay dust, does not, however, exclude a reaction to that material when inhaled," while the 8nding of fungal spores in autopsy material from the human lung is not uncommon. The term, mycotoxicosis, applies to reactions caused by toxins of fungal origin; S and, in general, such toxins are ingested.s To apply this term to pulmonary diseases caused by fungal inhalation firstly assumes toxins to be present in the dust and secondly assumes the toxins would produce a farmer's lung-like episode. We offer another explanation. Certain dusts, eg, moldy hay dust, and thermophilic actinomycetes can activate the alternative pathway of complement," the system assuming significance at high concentrations of dust. The response in the cases reported by Emanuel et al 6 could well be due to activation of this pathway by inhaled dust. Indeed, our recent experimental work" shows that many features of farmer's lung can be produced by zymosan (a classic activator of the alternative pathway of complement) or moldy hay dust in unsensitized animals. Thus, we consider that the "new lung disease" is probably an "old lung disease" where the complement system is activated "para-immunologically," instead of by immune-complex activation. H such a mechanism applies in these high-dose cases, the term, mycotoxicosis, is as inappropriate as the term, toxomyeosis."
1. H. Edwards, Ph.D.; Anthony Seaton, M.D.;
and R. M. E. Seal, F.R.C.Path. Medical Research Council Pneumoconiosis Unit Llandough H oapital Penarth, Glamorgan, Wales
REFERENCES 1 Fink IN: A new lung disease? (editorial). Chest 67:254, 1975 2 Grant IW,B, Blyth W, Wardrop VE, et al: Prevalence of farmer's lung in Scotland: A pilot survey. Br Med J 1:530534, 1972 3 Forgacs J: Mycotoxicoses. Adv Vet Sci 7 :273-382, 1962 4 Wright DE: Toxins produced by fungi. Annu Rev Microbiol22:269-282, 1968 5 Edwards JH: A quantitative study on the activation of the
CHEST, 69: 4, APRIL, 1976
alternative pathway of complement by mouldy hay dust and thermophilic actinomycetes. Coo Allergy, to be published 6 Emanuel DA, Wenzel FJ, Lawton BR: Pulmonary mycotoxicosis. Chest 67 :293-297, 1975 7 Edwards JH, Wagner JC, Seal RME: Pulmonary responses to particulate materials capable of activating the alternative pathway of complement. Clin Allergy, to be published 8 Kovats F, Bugyi B: Occupational Mycotic Diseases of. the Lung. Budapest, Hungary, Akademia! Kiad6, 1968, p 120
Systolic Time Intervals To the Editor: The report on left ventricular performance in chronic obstructive pulmonary disease by Unger and colleagues,' although not conclusive, is consistent both with our observations and with the recent studies of ejection fraction by Steele and colleagues.t My quarrel with this report is in the presentation and handling of the systolic time intervals, namely: (1) data on heart rate should always be meaningful, with both means and standard deviations, rather than the authors' statement of average heart rate and that this exceeded 100 beats per minute in ten patients; (2) rate correction of preejection period (PEP) should be discarded on the basis of recent careful studies'"" showing correlation coefficients which are not only extremely low but also nonsignificant and because pacing-induced "pure" rate changes within wide limits do not affect isovolumic contraction time or PEP; and (3) the mean ratio of PEP to left ventricular ejection time (PEP/LVET) in their Figures 3 and 4 is clearly wrong, owing to its calculation from the wrong numerators and denominators (those familiar with the systolic time interval will be initially alerted by the apparent mean value of over 0.50 and the many high values which are characteristic of cardiomyopathy or left bundle-branch block). Using the study's average heart rate of 92 beats per minute and the slope factors from the equations of Weissler et al," the apparent mean indices in Figure 3 yield a PEP of 113 msec (ie, 150 minus 0.4 x 92) and LVET of 254 msec (ie, 383 minus 1.7 x 92). H PEP/LVET equals 113/254, then Figure 3 should show a mean value of approximately 0.44, rather than about 0.52. Despite these criticisms, there is much information and interpretation of value in this work. The systolic time intervals are valuable adjunctive studies when valid, but they should always be handled with care. David H. Soodick, M.D., D.Sc., F.C.C.P. Professor of Medicine Tufts University School of Medicine Lemuel Shattuck Hospital, Boston REFERENCES
1 Unger K, Shaw D, Karliner JS, et al: Evaluation of left ventricular performance in acutely ill patients with chronic obstructive lung disease. Chest 68: 135-142, 1975
COMMUNICATIONS TO THE EDITOR 589
2 Steele P, VanDyke D, Sutton F, et al: Left ventricular ejection fraction in severe chronic obstructive airways disease. Am 1 Med 59:21-28, 1975 3 Harris WS, Weissler AM, Brooks RH: Vagal influences of left ventricular contraction in man: A cause for prolongation of the pre-ejection period. Clin Res 14:426, 1966 4 Talley RC, Meyer IF, McNay JL: Evaluation of the preejection period as an estimate of myocardial contractility in dogs. Am 1 Cardiol 27 :384-391, 1971 5 Takahashi M, Moritz DL: Systolic intervals in children with normal and diseased hearts. Am 1 Cardiol 29:294, 1972 6 Fabian 1, Epstein E], Coulshed N: Duration of phases of left ventricular systole using indirect methods: 1. Normal subjects. Br Heart 1 34 :874-881, 1972 7 Zoneraich S, Zoneraich 0, Rodenrys 1: Computerized system for noninvasive techniques: 1. Its value for systolic time intervals. Am 1 CardioI33:643-648, 1974 8 Weissler AM, Harris WS, Schoenfeld CD: Bedside technics for the evaluation of ventricular function in man. Am 1 Cardiol23:577-583, 1969
Smoking, Carboxyhemoglobin Levels, and Oxygen Therapy To the Editor:
In the article by LiIker et al entitled "Portable Oxygen in Chronic Obstructive Lung Disease with Hypoxemia
and Cor Pulmonale: A Controlled Double-Blind Cross. over Study" (Chest 68:236-241, 1975), a very important factor was either not mentioned or not considered. Nine patients with severe chronic obstructive pulmonary disease (COPD) and severe hypoxemia were studied. It does not state anywhere in the study whether or not these patients were smoking during the time of the study, and neither oxygen saturation nor carboxyhemoglobin levels were measured. Of the nine patients, three patients had improvement in exercise capacity. The authors noted that although oxygen therapy corrected the hypoxemia, there was no significant change in the red blood cell count, hemoglobin level, or reticulocyte count. The authors concluded that further studies are needed to evaluate the patients who show a striking improvement while receiving portable oxygen therapy and yet are not clearly separated from the others. Lilker et al stressed the need for studying differences in the reactivity of the pulmonary vascular bed and left ventricular failure. In our experience, it is not uncommon for patients, even with severe COPD, to continue to smoke heavily and have markedly elevated carboxyhemoglobin levels.' Many of these patients may have secondary polycythemia with severe hypoxemia; however, it is unlikely that oxygen therapy will benefit them because the desaturation is due to binding of hemoglobin with carbon monoxide. Recently, other patients have been described with polycythemia secondary to heavy smoking, so that this is a real cause of reversible secondary polycythemia.s In any study designed to determine the effects of
570
CO.UNICA~IONS
TO THE EDITOR
chronic low-How oxygen administration, an accurate smoking history and measurement of carboxyhemoglobin level or actual oxygen saturation must be done. A difference in response may have been due to the fact that the three patients who seemed to respond were nonsmokers, whereas the other six patients continued to smoke heavily. In patients who continue to smoke heavily, it would not be expected that oxygen would bring about a significant improvement of their desaturation. We feel this is a critical point to include in any study such as that presented by LiIker et al. Perhaps if they had data on smoking histories, carboxyhemoglobin levels, or oxygen saturations, they did not present it due to space limitations; however, if they neglected this factor, perhaps reassessing their patients in this way may shed light on what separates the responder from the nonresponder, Allan L. Goldman, M.D. Assistant ProfessOt' of Medicine Chief, Pulmona'l/ Disease Section Department of Internal Medicine University of South Florida College of Medicine Tampa Veteran8 Administration Hospital
Tompa, Fla
REFERENCES
1 Goldman AL: Carboxyhemoglobinemia and oxygen desaturation in cigar smokers. Am Rev Respir Dis III :942, 1975 2 Sagone AL lr, Lawrence T, Balcerzak SP: Effect of smoking on tissue oxygen supply. Blood 41:845-851, 1973
To the Editor: I thank Dr. Goldman for his Constructive criticism. To our knowledge, none of the patients smoked during the entire three months of the study, as judged by what they told us, what their families told us, and the observations made by the physician on his weekly visits, as well as the patient's reassessments while in the hospital. E. S. Laker, M.D. Director, Reapirat011l Unit St. 10seph~s Hospital, Toronto and Lecturer, Department of Medicine U niveI'dt" of Toronto
Corticosteroids and Pericarditis of Acute Myocardial Infarction To the Editor: In an article entitled "Pericarditis of Acute Myocardial Infarction" (Chest 67:647-653, 1975), Toole and Silverman describe the use of corticosteroids for the symptomatic treatment of pericarditis associated with acute myocardial infarction. They indicate that this therapy is without major complications and provides the advantage of decreased narcotic use. Bulkley and Roberts! described a patient treated with
CHEST, 69: 4, APRIL, 1976
TO THe eDITOR
Mycotoxicosis? To the Editor: Recently the possibility of a "new lung disease" has been discussed; 1 and the term, mycotoxicosis, has been applied to a syndrome similar to farmer's lung caused by the inhalation of massive amounts of fungi but diHering from the classic syndrome by an absence of precipitins to extracts of inhaled material and by the presence of fungal spores in biopsy material. The absence of precipitins to respirable material, eg, moldy hay dust, does not, however, exclude a reaction to that material when inhaled," while the 8nding of fungal spores in autopsy material from the human lung is not uncommon. The term, mycotoxicosis, applies to reactions caused by toxins of fungal origin; S and, in general, such toxins are ingested.s To apply this term to pulmonary diseases caused by fungal inhalation firstly assumes toxins to be present in the dust and secondly assumes the toxins would produce a farmer's lung-like episode. We offer another explanation. Certain dusts, eg, moldy hay dust, and thermophilic actinomycetes can activate the alternative pathway of complement," the system assuming significance at high concentrations of dust. The response in the cases reported by Emanuel et al 6 could well be due to activation of this pathway by inhaled dust. Indeed, our recent experimental work" shows that many features of farmer's lung can be produced by zymosan (a classic activator of the alternative pathway of complement) or moldy hay dust in unsensitized animals. Thus, we consider that the "new lung disease" is probably an "old lung disease" where the complement system is activated "para-immunologically," instead of by immune-complex activation. H such a mechanism applies in these high-dose cases, the term, mycotoxicosis, is as inappropriate as the term, toxomyeosis."
1. H. Edwards, Ph.D.; Anthony Seaton, M.D.;
and R. M. E. Seal, F.R.C.Path. Medical Research Council Pneumoconiosis Unit Llandough H oapital Penarth, Glamorgan, Wales
REFERENCES 1 Fink IN: A new lung disease? (editorial). Chest 67:254, 1975 2 Grant IW,B, Blyth W, Wardrop VE, et al: Prevalence of farmer's lung in Scotland: A pilot survey. Br Med J 1:530534, 1972 3 Forgacs J: Mycotoxicoses. Adv Vet Sci 7 :273-382, 1962 4 Wright DE: Toxins produced by fungi. Annu Rev Microbiol22:269-282, 1968 5 Edwards JH: A quantitative study on the activation of the
CHEST, 69: 4, APRIL, 1976
alternative pathway of complement by mouldy hay dust and thermophilic actinomycetes. Coo Allergy, to be published 6 Emanuel DA, Wenzel FJ, Lawton BR: Pulmonary mycotoxicosis. Chest 67 :293-297, 1975 7 Edwards JH, Wagner JC, Seal RME: Pulmonary responses to particulate materials capable of activating the alternative pathway of complement. Clin Allergy, to be published 8 Kovats F, Bugyi B: Occupational Mycotic Diseases of. the Lung. Budapest, Hungary, Akademia! Kiad6, 1968, p 120
Systolic Time Intervals To the Editor: The report on left ventricular performance in chronic obstructive pulmonary disease by Unger and colleagues,' although not conclusive, is consistent both with our observations and with the recent studies of ejection fraction by Steele and colleagues.t My quarrel with this report is in the presentation and handling of the systolic time intervals, namely: (1) data on heart rate should always be meaningful, with both means and standard deviations, rather than the authors' statement of average heart rate and that this exceeded 100 beats per minute in ten patients; (2) rate correction of preejection period (PEP) should be discarded on the basis of recent careful studies'"" showing correlation coefficients which are not only extremely low but also nonsignificant and because pacing-induced "pure" rate changes within wide limits do not affect isovolumic contraction time or PEP; and (3) the mean ratio of PEP to left ventricular ejection time (PEP/LVET) in their Figures 3 and 4 is clearly wrong, owing to its calculation from the wrong numerators and denominators (those familiar with the systolic time interval will be initially alerted by the apparent mean value of over 0.50 and the many high values which are characteristic of cardiomyopathy or left bundle-branch block). Using the study's average heart rate of 92 beats per minute and the slope factors from the equations of Weissler et al," the apparent mean indices in Figure 3 yield a PEP of 113 msec (ie, 150 minus 0.4 x 92) and LVET of 254 msec (ie, 383 minus 1.7 x 92). H PEP/LVET equals 113/254, then Figure 3 should show a mean value of approximately 0.44, rather than about 0.52. Despite these criticisms, there is much information and interpretation of value in this work. The systolic time intervals are valuable adjunctive studies when valid, but they should always be handled with care. David H. Soodick, M.D., D.Sc., F.C.C.P. Professor of Medicine Tufts University School of Medicine Lemuel Shattuck Hospital, Boston REFERENCES
1 Unger K, Shaw D, Karliner JS, et al: Evaluation of left ventricular performance in acutely ill patients with chronic obstructive lung disease. Chest 68: 135-142, 1975
COMMUNICATIONS TO THE EDITOR 589
2 Steele P, VanDyke D, Sutton F, et al: Left ventricular ejection fraction in severe chronic obstructive airways disease. Am 1 Med 59:21-28, 1975 3 Harris WS, Weissler AM, Brooks RH: Vagal influences of left ventricular contraction in man: A cause for prolongation of the pre-ejection period. Clin Res 14:426, 1966 4 Talley RC, Meyer IF, McNay JL: Evaluation of the preejection period as an estimate of myocardial contractility in dogs. Am 1 Cardiol 27 :384-391, 1971 5 Takahashi M, Moritz DL: Systolic intervals in children with normal and diseased hearts. Am 1 Cardiol 29:294, 1972 6 Fabian 1, Epstein E], Coulshed N: Duration of phases of left ventricular systole using indirect methods: 1. Normal subjects. Br Heart 1 34 :874-881, 1972 7 Zoneraich S, Zoneraich 0, Rodenrys 1: Computerized system for noninvasive techniques: 1. Its value for systolic time intervals. Am 1 CardioI33:643-648, 1974 8 Weissler AM, Harris WS, Schoenfeld CD: Bedside technics for the evaluation of ventricular function in man. Am 1 Cardiol23:577-583, 1969
Smoking, Carboxyhemoglobin Levels, and Oxygen Therapy To the Editor:
In the article by LiIker et al entitled "Portable Oxygen in Chronic Obstructive Lung Disease with Hypoxemia
and Cor Pulmonale: A Controlled Double-Blind Cross. over Study" (Chest 68:236-241, 1975), a very important factor was either not mentioned or not considered. Nine patients with severe chronic obstructive pulmonary disease (COPD) and severe hypoxemia were studied. It does not state anywhere in the study whether or not these patients were smoking during the time of the study, and neither oxygen saturation nor carboxyhemoglobin levels were measured. Of the nine patients, three patients had improvement in exercise capacity. The authors noted that although oxygen therapy corrected the hypoxemia, there was no significant change in the red blood cell count, hemoglobin level, or reticulocyte count. The authors concluded that further studies are needed to evaluate the patients who show a striking improvement while receiving portable oxygen therapy and yet are not clearly separated from the others. Lilker et al stressed the need for studying differences in the reactivity of the pulmonary vascular bed and left ventricular failure. In our experience, it is not uncommon for patients, even with severe COPD, to continue to smoke heavily and have markedly elevated carboxyhemoglobin levels.' Many of these patients may have secondary polycythemia with severe hypoxemia; however, it is unlikely that oxygen therapy will benefit them because the desaturation is due to binding of hemoglobin with carbon monoxide. Recently, other patients have been described with polycythemia secondary to heavy smoking, so that this is a real cause of reversible secondary polycythemia.s In any study designed to determine the effects of
570
CO.UNICA~IONS
TO THE EDITOR
chronic low-How oxygen administration, an accurate smoking history and measurement of carboxyhemoglobin level or actual oxygen saturation must be done. A difference in response may have been due to the fact that the three patients who seemed to respond were nonsmokers, whereas the other six patients continued to smoke heavily. In patients who continue to smoke heavily, it would not be expected that oxygen would bring about a significant improvement of their desaturation. We feel this is a critical point to include in any study such as that presented by LiIker et al. Perhaps if they had data on smoking histories, carboxyhemoglobin levels, or oxygen saturations, they did not present it due to space limitations; however, if they neglected this factor, perhaps reassessing their patients in this way may shed light on what separates the responder from the nonresponder, Allan L. Goldman, M.D. Assistant ProfessOt' of Medicine Chief, Pulmona'l/ Disease Section Department of Internal Medicine University of South Florida College of Medicine Tampa Veteran8 Administration Hospital
Tompa, Fla
REFERENCES
1 Goldman AL: Carboxyhemoglobinemia and oxygen desaturation in cigar smokers. Am Rev Respir Dis III :942, 1975 2 Sagone AL lr, Lawrence T, Balcerzak SP: Effect of smoking on tissue oxygen supply. Blood 41:845-851, 1973
To the Editor: I thank Dr. Goldman for his Constructive criticism. To our knowledge, none of the patients smoked during the entire three months of the study, as judged by what they told us, what their families told us, and the observations made by the physician on his weekly visits, as well as the patient's reassessments while in the hospital. E. S. Laker, M.D. Director, Reapirat011l Unit St. 10seph~s Hospital, Toronto and Lecturer, Department of Medicine U niveI'dt" of Toronto
Corticosteroids and Pericarditis of Acute Myocardial Infarction To the Editor: In an article entitled "Pericarditis of Acute Myocardial Infarction" (Chest 67:647-653, 1975), Toole and Silverman describe the use of corticosteroids for the symptomatic treatment of pericarditis associated with acute myocardial infarction. They indicate that this therapy is without major complications and provides the advantage of decreased narcotic use. Bulkley and Roberts! described a patient treated with
CHEST, 69: 4, APRIL, 1976
