sions is much more questionable. Such patients may present a considerable problem because of intractable pain and associated life-threatening arrhythmias. Attempted surgery for aortocoronary bypass in these patients has not been encouraging. Dhurandhar et al4 reported a case of spasm in an otherwise normal right coronary artery, with death occurring during recurrent pain soon after surgery in the presence of a patent graft. Betriu et al5 reported that surgery on three patients with insignificant lesions was followed by one postoperative death, one postoperative infarct, and the other patient having recurrent angina. Gaasch et al2 also reported the findings in two such patients, with recurrent pain occurring after surgery in one and with postoperative ventricular fibrillation and death in the other. Such poor results could be attributed to diffuse spasm along the involved vessel or possibly to spasm involving vessels other than those bypassed, since multivessel spasm has on occasion been observed on angiographic studies. Johnson et al conclude on the basis of two of their patients that symptomatic improvement can result from surgery when medical treatment has failed. One of these patients did remain asymptomatic after 20 months; it is of interest that in this case, there was a graft to the left anterior descending coronary artery where a "plaque" was demonstrated, although spasm was observed both in this vessel and in the right coronary artery. The other patient had only rare angina, although this may have been due to an anterior intraoperative infarction, since electrocardiographic changes during the variant angina had been anterior in location. Experience with surgery in such patients is certainly too limited at present to warrant any definite conclusions, but the available literature suggests that successful results should not be expected and that at present, this form of therapy should be attempted only as a last resort. Samuel J. Shubrooks, Jr., M.D* Boston •Assistant Professor of Medicine, Harvard Medical School and New England Deaconess Hospital. Reprint requests: Dr. Shubrooks, 110 Francis Street, Boston 02215 REFERENCES
1 McAlpin RN, Kattus AA, Alvaro AB: Angina pectoris at rest with preservation of exercise capacity: Prinzmetal's variant angina. Circulation 47:946-958, 1973 2 Gaasch WH, Lufschanowski R, Leachman RD, et al: Surgical management of Prinzmetal's variant angina. Chest 66:614-621, 1974 3 Shubrooks SJ Jr, Bete JM, Hutter AM Jr, et al: Variant angina pectoris: Clinical and anatomic spectrum and results of coronary bypass surgery. Am J Cardiol 36:142-147,
782
EDITORIALS
1975 4 Dhurandhar RW, Watt DL, Silver MD, et al: Prinzmetal's variant forms of angina with arteriography evidence of coronary spasm. Am J Cardiol 30:902-905, 1971 5 Betriu A, Solignac A, Bourassa MG: The variant form of angina: Diagnostic and therapeutic implications. Am Heart J 87:272-278, 1974
Controversy over Intermittent Positive Pressure Breathing r p h e Sugarloaf Conference of 1974 regarding the value of therapy with intermittent positive-pressure breathing (IPPB) for chronic obstructive pulmonary disease concluded: Although overall results have failed to demonstrate a beneficial effect of the addition of IPPB to conventional therapeutic regimens, in most studies there were some (italics theirs) patients in whom function improved. It seems essential to categorize more carefully patients being studied in order to help determine whether or not there are certain patients, whose characteristics can be specifically defined, who will benefit from IPPB therapy. 1
Precise recommendations for the application or abandonment of the highly controversial therapy with IPPB were not presented. The general recommendation of the conference was to encourage additional rigorous and controlled studies to document whether or not there are physiologic and psychologic advantages of treatment with IPPB, compared to other forms of therapy. A followup report,2 presented in San Francisco last May, indicated that the number of published reports on this highly charged subject unfortunately has decreased. Editors of medical journals may have become more demanding in requiring articles with more objective evaluations. A welcome addition to the literature on this controversy (by Shim and associates) is contained in this issue of Chest (see page 798). Among other things, Shim et al have carefully and systematically studied the production of sputum, one of the most objective effects of respiratory therapy .i These investigators concluded that therapy with IPPB did increase the volume of sputum, compared to other modes of therapy, but not to a statistically significant degree. Unfortunately, it is possible that this study will be added to the list of publications condemning this mode of treatment. Nevertheless, a careful reading of their report can offer insight into the reasons for such diametrically contrary results in studies of therapy with IPPB. An initial pitfall lies in the characteristics of patients evaluated in almost all studies. It is well known that so-called chronic obstructive pulmonary disease CHEST, 73: 6, JUNE, 1978
is neither a clinical nor a pathologic entity, but rather a heterogeneous collection of conditions. Chronic obstructive pulmonary disease ranges from descriptions of the "dry" ai-antitrypsin-deficient patient at one end of the spectrum to the "wet bronchitic" patient at the other end. Therefore, in each study, there must be a rigorous definition of which particular group of these patients is under scrutiny. A sizable number of patients (150 to 200) may be required in a study of therapy with IPPB, in order to control errors of sampling. A group of 18 patients defined only as having "chronic obstructive pulmonary disease" is a treacherous platform from which to reach conclusions of any magnitude. It is difficult for those of us who are primarily clinicians to appreciate how rigorous statistical standards must be to eventually lead us out of our present controversy; for example, the lack of statistical significance of a difference between treatments does not prove that there is no real difference. It merely shows that there was insufficient evidence from the study to exclude chance as an explanation for whatever differences were observed. On the other hand, samples sized in the thousands have the power to detect clinically trivial differences as statistically significant. The situation requires a balanced approach. The magnitude of clinical differences worth detecting should be determined in advance of a study. Also, the tolerable probabilities of error should be determined for (1) the failure to detect such a difference and (2) detecting a difference when there is none. It should be kept in mind that these decisions regarding clinical and statistical significance all require value judgments, an area where there is much room for honest disagreement between thoughtful persons. The next step, in line with the recommendations from the Sugarloaf Conference, would be to take the responders, of which there were some in the study of Shim et al, and compare them as a group with the nonresponders using multiple observations. This could be carried further by using discriminant or other techniques of classification to derive a mechanism of prediction to identify potential responders, ie, the indications for therapy with IPPB. Finally, a study of cross-validation on an entirely new sample group would be necessary to confirm the results. This would carry us much further toward identifying, and limiting, the indications for therapy with IPPB. The effects of carryover in sequential measurements of the type presented by Shim et al also make valid conclusions more difficult. The production of sputum, even in patients with chronic obstructive pulmonary disease, is not necessarily an endless reservoir that can be relied upon for sequential meaCHEST, 73: 6, JUNE, 1978
surements. It is possible that the production of sputum under one set of circumstances may immediately influence the subsequent production of sputum significantly, regardless of the circumstances. Finally, the major point of departure in the controversy over IPPB is not addressed in this study, ie, the patient's subjective response to the therapy. Few clinicians can help but be impressed by the adamant support of some patients for the "benefits" of treatment with IPPB, whatever that support may indicate. This clinical impression must be evaluated in every careful study of therapy with IPPB, if the prejudices of many of us are to be laid to rest. We cannot yet leave the patient's response out of the evaluation of treatment with IPPB. Whether or not further tests of physical endurance, consumption of oxygen, or other yardsticks not yet available can be used to be more specific in measuring this subjective response remains to be seen. Further development of the data of Shim et al, along the lines of the recommendations from the Sugarloaf Conference, to define applicable areas of treatment with pressure breathing is urgently anticipated. Theodore H. Noehren, Af.D., F.C.C.P. and Melville R. Klauber, Ph.D. Salt LakfrCity REFERENCES
1 Final reports-summaries and recommendations, Conference on die Scientific Basis of Respiratory Therapy, Philadelphia, May 2-4, 1974. Am Rev Respir Dis 110:13, 1974 2 Murray J F : Symposium on respiratory therapy post-Sugarloaf, San Francisco, May, 1977, Annual Scientific Assembly, American Thoracic Society.
Complications following Fiberoptic Bronchoscopy The " G o o d News" and the "Bad News" THhe flexible fiberoptic bronchoscope has firmly established itself in the field of pulmonary disease as a superb diagnostic and therapeutic instrument.1 The "good news" is that when performed in experienced hands, fiberoptic bronchoscope procedures are safe, well tolerated by the patient, and have a high diagnostic yield.2,8 The "bad news" is that there is a tendency for physicians to overlook the inherent risks involved, mainly because the procedure is so readily performed. In this issue of Chest (see page 813), Pereira and associates, with the help of 12 cooperative investigators, have called our attention to these risks by means of their article entitled "A Prospective Cooperative Study of Complications following Flexible Fiberoptic EDITORIALS
783
1 McAlpin RN, Kattus AA, Alvaro AB: Angina pectoris at rest with preservation of exercise capacity: Prinzmetal's variant angina. Circulation 47:946-958, 1973 2 Gaasch WH, Lufschanowski R, Leachman RD, et al: Surgical management of Prinzmetal's variant angina. Chest 66:614-621, 1974 3 Shubrooks SJ Jr, Bete JM, Hutter AM Jr, et al: Variant angina pectoris: Clinical and anatomic spectrum and results of coronary bypass surgery. Am J Cardiol 36:142-147,
782
EDITORIALS
1975 4 Dhurandhar RW, Watt DL, Silver MD, et al: Prinzmetal's variant forms of angina with arteriography evidence of coronary spasm. Am J Cardiol 30:902-905, 1971 5 Betriu A, Solignac A, Bourassa MG: The variant form of angina: Diagnostic and therapeutic implications. Am Heart J 87:272-278, 1974
Controversy over Intermittent Positive Pressure Breathing r p h e Sugarloaf Conference of 1974 regarding the value of therapy with intermittent positive-pressure breathing (IPPB) for chronic obstructive pulmonary disease concluded: Although overall results have failed to demonstrate a beneficial effect of the addition of IPPB to conventional therapeutic regimens, in most studies there were some (italics theirs) patients in whom function improved. It seems essential to categorize more carefully patients being studied in order to help determine whether or not there are certain patients, whose characteristics can be specifically defined, who will benefit from IPPB therapy. 1
Precise recommendations for the application or abandonment of the highly controversial therapy with IPPB were not presented. The general recommendation of the conference was to encourage additional rigorous and controlled studies to document whether or not there are physiologic and psychologic advantages of treatment with IPPB, compared to other forms of therapy. A followup report,2 presented in San Francisco last May, indicated that the number of published reports on this highly charged subject unfortunately has decreased. Editors of medical journals may have become more demanding in requiring articles with more objective evaluations. A welcome addition to the literature on this controversy (by Shim and associates) is contained in this issue of Chest (see page 798). Among other things, Shim et al have carefully and systematically studied the production of sputum, one of the most objective effects of respiratory therapy .i These investigators concluded that therapy with IPPB did increase the volume of sputum, compared to other modes of therapy, but not to a statistically significant degree. Unfortunately, it is possible that this study will be added to the list of publications condemning this mode of treatment. Nevertheless, a careful reading of their report can offer insight into the reasons for such diametrically contrary results in studies of therapy with IPPB. An initial pitfall lies in the characteristics of patients evaluated in almost all studies. It is well known that so-called chronic obstructive pulmonary disease CHEST, 73: 6, JUNE, 1978
is neither a clinical nor a pathologic entity, but rather a heterogeneous collection of conditions. Chronic obstructive pulmonary disease ranges from descriptions of the "dry" ai-antitrypsin-deficient patient at one end of the spectrum to the "wet bronchitic" patient at the other end. Therefore, in each study, there must be a rigorous definition of which particular group of these patients is under scrutiny. A sizable number of patients (150 to 200) may be required in a study of therapy with IPPB, in order to control errors of sampling. A group of 18 patients defined only as having "chronic obstructive pulmonary disease" is a treacherous platform from which to reach conclusions of any magnitude. It is difficult for those of us who are primarily clinicians to appreciate how rigorous statistical standards must be to eventually lead us out of our present controversy; for example, the lack of statistical significance of a difference between treatments does not prove that there is no real difference. It merely shows that there was insufficient evidence from the study to exclude chance as an explanation for whatever differences were observed. On the other hand, samples sized in the thousands have the power to detect clinically trivial differences as statistically significant. The situation requires a balanced approach. The magnitude of clinical differences worth detecting should be determined in advance of a study. Also, the tolerable probabilities of error should be determined for (1) the failure to detect such a difference and (2) detecting a difference when there is none. It should be kept in mind that these decisions regarding clinical and statistical significance all require value judgments, an area where there is much room for honest disagreement between thoughtful persons. The next step, in line with the recommendations from the Sugarloaf Conference, would be to take the responders, of which there were some in the study of Shim et al, and compare them as a group with the nonresponders using multiple observations. This could be carried further by using discriminant or other techniques of classification to derive a mechanism of prediction to identify potential responders, ie, the indications for therapy with IPPB. Finally, a study of cross-validation on an entirely new sample group would be necessary to confirm the results. This would carry us much further toward identifying, and limiting, the indications for therapy with IPPB. The effects of carryover in sequential measurements of the type presented by Shim et al also make valid conclusions more difficult. The production of sputum, even in patients with chronic obstructive pulmonary disease, is not necessarily an endless reservoir that can be relied upon for sequential meaCHEST, 73: 6, JUNE, 1978
surements. It is possible that the production of sputum under one set of circumstances may immediately influence the subsequent production of sputum significantly, regardless of the circumstances. Finally, the major point of departure in the controversy over IPPB is not addressed in this study, ie, the patient's subjective response to the therapy. Few clinicians can help but be impressed by the adamant support of some patients for the "benefits" of treatment with IPPB, whatever that support may indicate. This clinical impression must be evaluated in every careful study of therapy with IPPB, if the prejudices of many of us are to be laid to rest. We cannot yet leave the patient's response out of the evaluation of treatment with IPPB. Whether or not further tests of physical endurance, consumption of oxygen, or other yardsticks not yet available can be used to be more specific in measuring this subjective response remains to be seen. Further development of the data of Shim et al, along the lines of the recommendations from the Sugarloaf Conference, to define applicable areas of treatment with pressure breathing is urgently anticipated. Theodore H. Noehren, Af.D., F.C.C.P. and Melville R. Klauber, Ph.D. Salt LakfrCity REFERENCES
1 Final reports-summaries and recommendations, Conference on die Scientific Basis of Respiratory Therapy, Philadelphia, May 2-4, 1974. Am Rev Respir Dis 110:13, 1974 2 Murray J F : Symposium on respiratory therapy post-Sugarloaf, San Francisco, May, 1977, Annual Scientific Assembly, American Thoracic Society.
Complications following Fiberoptic Bronchoscopy The " G o o d News" and the "Bad News" THhe flexible fiberoptic bronchoscope has firmly established itself in the field of pulmonary disease as a superb diagnostic and therapeutic instrument.1 The "good news" is that when performed in experienced hands, fiberoptic bronchoscope procedures are safe, well tolerated by the patient, and have a high diagnostic yield.2,8 The "bad news" is that there is a tendency for physicians to overlook the inherent risks involved, mainly because the procedure is so readily performed. In this issue of Chest (see page 813), Pereira and associates, with the help of 12 cooperative investigators, have called our attention to these risks by means of their article entitled "A Prospective Cooperative Study of Complications following Flexible Fiberoptic EDITORIALS
783
