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Acute Cavitary Histoplasmosis—Fact or Fiction?
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CHEST VOLUME 65 I NUMBER 5 I MAY, 1974
Evidence of acute cavitation in humans is scarce, perhaps reflecting the difficulty in timing the points of infection and cavitation. In studying two epidemics of histoplasmosis in the same location, Tosh' found eight persons with severe pulmonary involvement including, radiologically, "unilateral involvement with extensive infiltration, honeycombing, or definite cavitation involving the upper lobes." He suggested the development of the cavitary cases as being exogenous reinfection and stated, "The concept of endogenous reinfection in these individuals is untenable. That eight individuals in a oommunity of this size would develop chronic pulmonary histoplasmosis as a result of breakdown during the period of the acute epidemic of histoplasmosis is beyond the realm of chance." If Tosh's assumption is correct, the time sequence between exposure and cavitation indicates the cavitation to be an acute manifestation. Another example is a six-year-old girl recently admitted to the Clinical Mycology Unit, State Hospital, Paris, Kentucky. From a precisely defined time of onset, it was possible to observe radiologically the development of cavitation before the diagnosis was verified and treatment instituted, a period of three to four weeks. Chronic progressive pulmonary histoplasmosis with cavitation was first described in 1948.5 •6 As reviewed and defined by Furcolow and Brasher? in 1956: "Chronic progressive histoplasmosis closely resembles reinfection type of tuberculosis, and could be considered to be reinfection histoplasmosis. This classification is based on the finding in some cases of negative tuberculin tests, positive histoplasmin skin tests, positive serologic tests, positive cultures for the fungus, and the presence of chronic cavitary disease of the apices in association with calcified lesions in the hilar area." This has remained a consensus with cavitation being regarded as a chronic manifestation. . It is of interest, though, that Silverman et alB in 1955 when discussing lesions of the "apical, subapical, and other locations" questioned: "whether these foci occasionally break down and are the source of cavity formation, or whether the cavities which are occasionally observed in histoplasmosis have a completely different origin, is not known at
EDITORIALS
Acute Cavitary HistoplasmosisFact or Fiction? To compare and characterize one disease with another is a medical tradition. The results of such comparisons and characterizations historically have certainly increased knowledge of diseases. Yet, there have also been instances where such tradition has been a deterrent to looking for other explanations of disease phenomena. Periodically new data suggest new approaches to an understanding of disease processes and offer alternate ways of looking at the steps involved in the pathogenesis and the course of disease. Almost invariably, further detailed study and observation is needed to provide perspective. Cavitary histoplasmosis is most frequently compared to cavitary tuberculosis. Like tuberculosis, it is considered to be a manifestation of reinfection, either endogenous or exogenous, and evidence of chronicity of the disease. However, some recent observations in experimental animals and in humans suggest that cavitary histoplasmosis may be an acute manifestation in at least some instances. If these observations are valid, new questions must be raised in the consideration of the pathogenesis of histoplasmosis, ie, acute and chronic disease pathways. In studies of Rhesus monkeys infected with Histoplasma capsulatum by intratracheal inoculation, pulmonary cavitation was found to be dose related and to occur as early as three weeks post-infection.' Cavitation in the Rhesus monkey appears to be related to host immune status," Circulating antibodies appeared significantly later in animals developing cavities than those without, although the onset of delayed hypersensitivity was about the same in both groups. The rate of cavitation could be manipulated immunologically and raised or lowered by the use of selected antigens. Cavitary histoplasmosis can also be produced in dogs infected via intrabronchial catheterization," Canine cavitation also appears to be dose related and occurs as early as one to two weeks after infection.
479
the present." Cavitary histoplasmosis has been an accepted clinical entity for 25 years, most often (traditionally?) with the prefix of chronic. With the current indications that cavitary histoplasmosis may be acute, at least in some instances, it would be feasible to document even more closely than usual, the time of exposure (when it can be determined) and the first demonstration of cavitary disease on all patients seen. Such information would define: (a) if pulmonary cavitation can be an acute process, (b) if so, how often it occurs acutely in contrast to the accepted chronic development, and (c) would aid in the identification in the relationship of the patient's immune responses to cavitation, either early or late, in the course of his disease. Ernest W. Chick, M.D., F.C.C.P. and-David S. Bauman, Ph.D.· Lexington, Kentucky ·From the Research Laboratory in Mycology, Veterans Administration Hospital and the Mycology Program, Depart-
ment of Community Medicine, University of Kentucky College of Medicine. Reprint reque6t8: Dr. Chick, Department of Community Medtcfne, Umversity of KentucK" CoUege of MedWlne, Le:dngton
4.0506
REFERENCES 1 Bauman OS, Chicle EW: Experimental histoplasmosis in rhesus monkeys. 1. Infectious dose and extrapulmonary dissemination determination. Chest 63:254-258,1973 2 Bauman DS, Chicle EW: Acute cavitary histoplasmosis in rhesus monkeys. Influence of immunologic status. Infect ,\ Imm 8:245-248, 1973 3 Chick EW, Bauman OS, Rams JO, et al: Extrapubnonary Dissemination and Pulmonary Cavitation in Canine and Simian Histoplasmosis. Am Rev Resp Dis (Abstract) 103: 876-877,1971 4 Tosh FE: Reinfection histoplasmosis. In Ajello, Chick, and Furcolow ( eels ) Histoplasmosis. Springfield, Charles C Thomas, 1971, pp 260-267 5 Johnson HE, Batson R: Benign pulmonary histoplasmosis: A case report with a quicle review of the literature. Dis Chest 14:517-524, 1948 6 Bunnell IL, Furcolow ML: A report on ten proved cases of histoplasmosis. Public Health Rep 63:299-316, 1948 7 Furcolow ML, Brasher CA: Chronic progressive (cavitary) histoplasmosis as a problem in tuberculosis sanitariums. Am Rev TB Pul Dis 73:609-619, 1956 8 Silverman FN, Schwarz J, Lahey MD, et al: Histoplasmosis. Am J Med 19:410-459, 1955
The Problem of Assessment of Left Ventricular Performance. in Coronary Artery Disease Reduced coronary blood flow frequently causes myocardial ischemia and/or infarction which may produce abnormalities of left ventricular (LV) function. These abnormalities may affect its overall systolic function, localized wall motion or diastolic 480 EDITORIALS
properties. 1.2 It is important to evaluate these properties individually and not interchange or Confuse them. For example, LV ejection fraction is a parameter of systolic function, end-diastolic pressure is an indicator of the diastolic properties of the LV, and the two may not correlate in an individual patient. Thus, the variables that are measured should relate directly to one's goals. Left ventricular systolic function may be considered in terms of muscle or pump function. In intact man, assessment of LV muscle function or contractile state is not easy. Calculations from the isovolumic phase of LV contraction" have considerable conceptual limitations when applied to the intact left ventricle of patients who may have regional areas of wall motion abnormality, and also when used to compare patients, perhaps because of unknown changes in the constant of series elasticity" However, in individual patients, they are useful and sensitive in detecting changes in inotropy with interventions.s Another limitation to the use of these \indices in clinical practice has been the tedious nature of the computations that have to be made. A simplified technique has been developed for calculating maximum velocity of contractile element shortening (Vmax) by the formula: Vmax = 2x (peak dp/dt) (K x LVP') where LVP' is pressure at the time of the peak of the first derivative of LV pressure (peak dpl dt). This method requires only two measurements (peak dp/dt and LVP') and gives values of Vmax similar to those obtained by other methods based on the two-compartment muscle model (r = 0.98). 6 Mean velocity of minor LV equator shortening (mean Vef) and mean circumferential fiber shortening rate are parameters obtained from the ejection phase of LV contraction. Although they may be reliable indicators of LV function in the individual patient, they are sensitive to changes in preload and afterload,? The contractile state of the heart may also be defined by more complex methods," Changes in LV muscle function may not result in easily identifiable alteration of LV pump funetion,"
Many parameters can be used to assess LV pump function. Cardiac output is a time-honored index of cardiac performance. However, it is not a sensitive indicator of LV function because it is influenced by many extracardiac factors, and many homeostatic mechanisms help to maintain a normal cardiac output. A reduced output without hypovolemia implies that many of the reserves of the heart have been utilized or are not available and often connotes advanced heart disease. Stroke work is a measure of both pressure and volume loads on the LV, and at times more precision can be provided by estimates of external cardiac work. For example, it has been CHEST, 65: 5, MAY, 1974
CHEST VOLUME 65 I NUMBER 5 I MAY, 1974
Evidence of acute cavitation in humans is scarce, perhaps reflecting the difficulty in timing the points of infection and cavitation. In studying two epidemics of histoplasmosis in the same location, Tosh' found eight persons with severe pulmonary involvement including, radiologically, "unilateral involvement with extensive infiltration, honeycombing, or definite cavitation involving the upper lobes." He suggested the development of the cavitary cases as being exogenous reinfection and stated, "The concept of endogenous reinfection in these individuals is untenable. That eight individuals in a oommunity of this size would develop chronic pulmonary histoplasmosis as a result of breakdown during the period of the acute epidemic of histoplasmosis is beyond the realm of chance." If Tosh's assumption is correct, the time sequence between exposure and cavitation indicates the cavitation to be an acute manifestation. Another example is a six-year-old girl recently admitted to the Clinical Mycology Unit, State Hospital, Paris, Kentucky. From a precisely defined time of onset, it was possible to observe radiologically the development of cavitation before the diagnosis was verified and treatment instituted, a period of three to four weeks. Chronic progressive pulmonary histoplasmosis with cavitation was first described in 1948.5 •6 As reviewed and defined by Furcolow and Brasher? in 1956: "Chronic progressive histoplasmosis closely resembles reinfection type of tuberculosis, and could be considered to be reinfection histoplasmosis. This classification is based on the finding in some cases of negative tuberculin tests, positive histoplasmin skin tests, positive serologic tests, positive cultures for the fungus, and the presence of chronic cavitary disease of the apices in association with calcified lesions in the hilar area." This has remained a consensus with cavitation being regarded as a chronic manifestation. . It is of interest, though, that Silverman et alB in 1955 when discussing lesions of the "apical, subapical, and other locations" questioned: "whether these foci occasionally break down and are the source of cavity formation, or whether the cavities which are occasionally observed in histoplasmosis have a completely different origin, is not known at
EDITORIALS
Acute Cavitary HistoplasmosisFact or Fiction? To compare and characterize one disease with another is a medical tradition. The results of such comparisons and characterizations historically have certainly increased knowledge of diseases. Yet, there have also been instances where such tradition has been a deterrent to looking for other explanations of disease phenomena. Periodically new data suggest new approaches to an understanding of disease processes and offer alternate ways of looking at the steps involved in the pathogenesis and the course of disease. Almost invariably, further detailed study and observation is needed to provide perspective. Cavitary histoplasmosis is most frequently compared to cavitary tuberculosis. Like tuberculosis, it is considered to be a manifestation of reinfection, either endogenous or exogenous, and evidence of chronicity of the disease. However, some recent observations in experimental animals and in humans suggest that cavitary histoplasmosis may be an acute manifestation in at least some instances. If these observations are valid, new questions must be raised in the consideration of the pathogenesis of histoplasmosis, ie, acute and chronic disease pathways. In studies of Rhesus monkeys infected with Histoplasma capsulatum by intratracheal inoculation, pulmonary cavitation was found to be dose related and to occur as early as three weeks post-infection.' Cavitation in the Rhesus monkey appears to be related to host immune status," Circulating antibodies appeared significantly later in animals developing cavities than those without, although the onset of delayed hypersensitivity was about the same in both groups. The rate of cavitation could be manipulated immunologically and raised or lowered by the use of selected antigens. Cavitary histoplasmosis can also be produced in dogs infected via intrabronchial catheterization," Canine cavitation also appears to be dose related and occurs as early as one to two weeks after infection.
479
the present." Cavitary histoplasmosis has been an accepted clinical entity for 25 years, most often (traditionally?) with the prefix of chronic. With the current indications that cavitary histoplasmosis may be acute, at least in some instances, it would be feasible to document even more closely than usual, the time of exposure (when it can be determined) and the first demonstration of cavitary disease on all patients seen. Such information would define: (a) if pulmonary cavitation can be an acute process, (b) if so, how often it occurs acutely in contrast to the accepted chronic development, and (c) would aid in the identification in the relationship of the patient's immune responses to cavitation, either early or late, in the course of his disease. Ernest W. Chick, M.D., F.C.C.P. and-David S. Bauman, Ph.D.· Lexington, Kentucky ·From the Research Laboratory in Mycology, Veterans Administration Hospital and the Mycology Program, Depart-
ment of Community Medicine, University of Kentucky College of Medicine. Reprint reque6t8: Dr. Chick, Department of Community Medtcfne, Umversity of KentucK" CoUege of MedWlne, Le:dngton
4.0506
REFERENCES 1 Bauman OS, Chicle EW: Experimental histoplasmosis in rhesus monkeys. 1. Infectious dose and extrapulmonary dissemination determination. Chest 63:254-258,1973 2 Bauman DS, Chicle EW: Acute cavitary histoplasmosis in rhesus monkeys. Influence of immunologic status. Infect ,\ Imm 8:245-248, 1973 3 Chick EW, Bauman OS, Rams JO, et al: Extrapubnonary Dissemination and Pulmonary Cavitation in Canine and Simian Histoplasmosis. Am Rev Resp Dis (Abstract) 103: 876-877,1971 4 Tosh FE: Reinfection histoplasmosis. In Ajello, Chick, and Furcolow ( eels ) Histoplasmosis. Springfield, Charles C Thomas, 1971, pp 260-267 5 Johnson HE, Batson R: Benign pulmonary histoplasmosis: A case report with a quicle review of the literature. Dis Chest 14:517-524, 1948 6 Bunnell IL, Furcolow ML: A report on ten proved cases of histoplasmosis. Public Health Rep 63:299-316, 1948 7 Furcolow ML, Brasher CA: Chronic progressive (cavitary) histoplasmosis as a problem in tuberculosis sanitariums. Am Rev TB Pul Dis 73:609-619, 1956 8 Silverman FN, Schwarz J, Lahey MD, et al: Histoplasmosis. Am J Med 19:410-459, 1955
The Problem of Assessment of Left Ventricular Performance. in Coronary Artery Disease Reduced coronary blood flow frequently causes myocardial ischemia and/or infarction which may produce abnormalities of left ventricular (LV) function. These abnormalities may affect its overall systolic function, localized wall motion or diastolic 480 EDITORIALS
properties. 1.2 It is important to evaluate these properties individually and not interchange or Confuse them. For example, LV ejection fraction is a parameter of systolic function, end-diastolic pressure is an indicator of the diastolic properties of the LV, and the two may not correlate in an individual patient. Thus, the variables that are measured should relate directly to one's goals. Left ventricular systolic function may be considered in terms of muscle or pump function. In intact man, assessment of LV muscle function or contractile state is not easy. Calculations from the isovolumic phase of LV contraction" have considerable conceptual limitations when applied to the intact left ventricle of patients who may have regional areas of wall motion abnormality, and also when used to compare patients, perhaps because of unknown changes in the constant of series elasticity" However, in individual patients, they are useful and sensitive in detecting changes in inotropy with interventions.s Another limitation to the use of these \indices in clinical practice has been the tedious nature of the computations that have to be made. A simplified technique has been developed for calculating maximum velocity of contractile element shortening (Vmax) by the formula: Vmax = 2x (peak dp/dt) (K x LVP') where LVP' is pressure at the time of the peak of the first derivative of LV pressure (peak dpl dt). This method requires only two measurements (peak dp/dt and LVP') and gives values of Vmax similar to those obtained by other methods based on the two-compartment muscle model (r = 0.98). 6 Mean velocity of minor LV equator shortening (mean Vef) and mean circumferential fiber shortening rate are parameters obtained from the ejection phase of LV contraction. Although they may be reliable indicators of LV function in the individual patient, they are sensitive to changes in preload and afterload,? The contractile state of the heart may also be defined by more complex methods," Changes in LV muscle function may not result in easily identifiable alteration of LV pump funetion,"
Many parameters can be used to assess LV pump function. Cardiac output is a time-honored index of cardiac performance. However, it is not a sensitive indicator of LV function because it is influenced by many extracardiac factors, and many homeostatic mechanisms help to maintain a normal cardiac output. A reduced output without hypovolemia implies that many of the reserves of the heart have been utilized or are not available and often connotes advanced heart disease. Stroke work is a measure of both pressure and volume loads on the LV, and at times more precision can be provided by estimates of external cardiac work. For example, it has been CHEST, 65: 5, MAY, 1974