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Bullous Emphysema
Bullous Emphysema* Progressive Incremental Exercise Testing to Evaluate Candidates for Bullectomy Mlchoel F. Tenholder, M.D.; Prestoo A.]on&, MD.,F.C.C.P.; ]01eph I. Matthews, M.D., F.C.C.P.; and Robert G. Hooper, M.D., F.C.C.P.
Various tests of both fanctlon and IUUltomy have been used in .-tients being considered for IIID'gieal resection of giant pulmonary buDae. A youag _.uent bad an excellent respoase to removal of a larp bulla in the right long. In addition to roentKenographk: evalnation, ven-
tilation perfusion IK'BnniDI, and routine preoperative pulmonary function stndies, we performed progressive incremental exercl&e testing to determine botb preoperative and postoperative ventilatory and cardiac meamrements. We feel that propealve incremental exercl&e pnlmonary function adds another dimension to the aeledion and follow-up of .-dents being cousldered for operative
bnOectomy.
T
he management of bullous lung disease is difficult because of the frequent concomitant underlying emphysema and coexistent cardiac decompensation. Surgical management has few indications, but selected patients have subjective relief of dyspnea, objective im•From the Pulmonary Disease Service, Walter Reed Army Medical Center, Washington, D.C. The opinions or assertions contained herein are the private views of the writers and are not to be construed as of&cial or as reflecting views of the Department of the Army and the Department of Defense. Reprint requests: Dr. Tenholder, Heolth Sciences Library Eisenhower Medical Center, Fort Gordon, Georgia 30905 '
provement in Po2 and may return to gainful employment after bullectomy. The correlation between the clinical improvement achieved and the pulmonary function study results is not always a close one. 1 •2 Re6nements in selection of patients has progressed to include assessment of the density of compressed lung, mediastinal shift and herniation of lung tissue, nuclear medicine scans of zonal ventilation and perfusion, 8 and occasionally, even pulmonary angiography to identify zones of functioning capillary circulation.8 •4 Evaluation of pulmonary function has added the knowledge that postoperative increase in PA0 2 and reductions in FRC can be expected.s Progressive incremental exercise testing in this patient provided an accurate method of correlating subjective improvement in dyspnea and objective improvement in gas exchange and increased functional work capacity.
CASE
REPoRT
A 34-year-old active duty sergeant, paratrooper, was admitted to Walter Reed Army Medical Center for exertional dyspnea. In the two months prior to admission, he could no longer run one mile without severe dyspnea. He reported no previous difficulty with eight-mile training runs. He smoked one pack of cigarettes daily for 16 years, but denied other respiratory symptoms. On physical examination, the patient was a muscular man with a respiratory rate of 18 at rest. The right lung showed decreased breath sounds with some distant rhonchi. Cardiac exam was normal. A chest roentgenogram (Fig 1) showed a large solitary bullous lesion on the right side. Xenon ventilation scan showed delayed ventilatory washout to the right lung, while a technetium perfusion study revealed decreased perfusion to the right apex and crowded perfusion to the right base (Fig 2A). Arterial blood gas studies showed moderate hypoxemia, and pulmonary function tests demonstrated mild reduction of
FIGURE 1. The preoperative PA and lateral chest roentgenogram.
802 TENHOLDER ET Al
CHEST, 77: 6, JUNE, 1980
RPO
R
~(~
· -
· ·-, ,,_. , :
~;J;':a);t,lo,l~,...
Pulmonary Function Study
svc
A
LPO
POST L
FVC FEVt FEVt% TLC RV FRC
LPO R
RPO
L
R
A LAT
R
L
FIGVIIE 2A (upper) . Prebullectomy ventilation and perfusion lung scans, Oct 23, 1978. FicVRE 2B (lower). Postbullectomy ventilation and perfusion lung scans, Jan 11, 1979. vital capacity, increased residual volume, and moderate air flow obstruction (Table 1). Surgical excision of a large bulla was performed Oct 30, 1978. The patient tolerated the procedure well except for a persistent air leak for ten days postoperatively. After surgery, he has returned to active duty although restricted &om further parachuting activity. The patient is able to run without dyspnea. A repeated chest roentgenogram and lung scan (Fig 2B) confirm re-expansion of the right lung. Mild air trapping remains in the right upper lung field. Postoperative spirometry and blood gas determinations are shown in Table 1. EXERCISE TFSllNG
The results of exercise testing on a stationary bicycle ergometer during progressive incremental testing (PIT) and steady state testing (SST) demonstrate improvement in this patient. These tests were performed one week prior to surgery and six weeks after surgery. During the PIT, the patient pedaled at no load and increased by 25 watts per minute until the procedure was terminated by fatigue. The ECG (lead V5 ), expiratory airflow, tidal volume, minute ventilation, mixed expired 0 2 and C0 2 concentration, and Hewlett Packard ear oximetry were continuously monitored.8 • 7 During the SST, the same factors were measured and arterial blood gas determinations were obtained. No blood gas determinations were obtained during the postoperative SST. The SST was performed with the patient exercising at 50 and 100 watts for five minutes with the measurements made in the fifth minute of exercise. The preoperative and postoperative PIT are represented graphically in Figure 3. The steady state determinations appear in Table 2.
CHEST, 77: 6, JUNE, 1980
and Blood C.. DwiG
SplroJrWJ~ry
Preoperative,
L
Percent Percent Pre- Postoperative, Predieted L dieted
3.48
79
3.67
82
2.96
67
3.44
77
1.78
49
2.49
67
6.89
113
5.73
93
3.41
190
2.06
124
4.15
123
3.53
104
60%
72%
PAO,
78
95
Diffusion
65%
65%
The preoperative PIT demonstrated an appropriate relationship between oxygen consumption and the following factors: work load, heart rate, and ventilation at all levels of work. In addition, the ventilation was appropriate for the carbon dioxide production. The maximum ventilation achieved used 116 percent of the predicted ventilatory reserve and was obtained with a relatively small tidal volume and rapid respiratory rate. Significant desaturation occurred during the PIT. Data from the SST demonstrated significantly impaired gas exchange and elevated dead space ventilation. The postoperative PIT demonstrated changes in several aspects. Maximum work was increased and again limited by ventilation with 103 percent of the ventilatory reserve being utilized. This was obtained by an increase in the tidal volume at higher work loads. Significantly less desaturation occurred. The SST findings confirmed those of the PIT. DISCUSSION
A discrepancy between symptomatic relief of dyspnea and objective improvement in pulmonary function studies after surgical correction of bullae has long been recognized.1 •2 This discrepancy and the variability of symptomatic relief by surgery has led to some controversy regarding the appropriate criteria for surgical therapy. Clinical experience suggests several factors (single large bulla, significant compressed normal lung, and absence of severe chronic obstructive pulmonary disease) that are important predictors of good surgical results. 8 Identification of the mechanisms responsible for dyspnea could add significantly to our ability to predict which individuals may benefit from surgical procedures. The objective measurements of the subjective complaints of dyspnea have continued to be refined and PIT can identify the physiologic mechanisms of maximum exercise limitation and abnormal physiologic responses at submaximal exercise levels. 8 •7 With a more accurate understanding of these mechanisms in this disease process, our criteria for surgical therapy can be further defined. The use of PIT in this individual demonstrates
BULLOUS EMPHYSEMA 803
(IE
80 70 60 50 40 30 20
2.8 2.4 2.0
"'CIIe
1.6 1.2 .8 .4
... r-------------------~50
97 96
45
SaOz 95
40
94
35
93
30
RR
1.65 1.50 1.35 1.20 TV 1.05 .90 .75
180 160 Fe 140 120
100 t - - - - - - - - - - - - - - : l " i
175 150 125
.flO
20
30
40
50
60
70
80
(IE
0.
-MINUTE VENTILATION IL/MINI So Oa - 'lo HEIIOILOIIIN SATUIIATIOII Fe - HEAIIT IIATE IIEATS/111111 WOIIK -IWATTSI Oo. - OXYIEJI CONSUMPTION I L/MINI
WORK 100
7S 50 25 .7 .9
1.1 1.3 1.5 1.7 1.9 2.1 2.3 Voa
fco 1 -
CARlON DIOXIDE I'IIOOUCTION IL/Mifll IIEIPIIIATOIIY II ATE IIIIEATIIS/ MINI TV- TIDAL VOLUME ILl
It It -
li'IGuBE 3. Results of progressive incremental exercise testing prebuDeclany (dashed line) and postbullectomy (solid line).
its value to identify the mechanism responsible for dyspnea and to resolve the discrepancy between the dramatic symptomatic improvement in the face of modest postoperative improvement in ventilatory measurements. The use of progressive incremental exercise testing in this individual identified both a ventilatory and gas exchange mechanism which could account for symptomatic dyspnea. While signillcant symptomatic improvement followed surgery, the patient was able to perform only slightly more work and still was limited by his ventilatory reserve. Maximum ventilation obtained preoperatively was 70 L/minute which represented a value of 112 percent of predicted (FEV1 X 35). While maximum ventilation was utilized at the maximal exercise level ( 150 watts), the subject reported subjective dyspnea over the last half of the exercise study (75 to 150 watts). Postoperatively, the patient reached 84 L/ minute ventilation which represented a value of 96 percent of predicted. On the postoperative study, dyspnea was noted only at the maximal exercise level ( 175 watts). Static function studies do predict the result of the maximum ventilation levels; however, they fail to convey the results of the dynamic study in that this improvement accounted for only one additional level of work and one additional minute of exercise time. While maximum ventilation levels improved only enough to progress one work load level, the patient reported dramatic relief of his dyspnea throughout the study. The signiflcant·improvement in oxygenation can account for
... TENHOLDER ET AL
this symptomatic reJief. Ear oximetry showed a steady decline in arterial oxygen saturation with increasing levels of exercise preoperatively. When studied at steady state, the fall :in oxygenation was more dramatic than during the PIT. Postoperatively, gas exchange was markedly improved. While the reduced DLco88 suggest that desaturation Table 2---&ead,- S~a~e
Teadq
50 Watts Work
100 Watts Work
~~
Before Mter Before Mter
Rate (breaths/min) Tidal volume (L) Minute ventilation (L/min)
35 1.21 42.3
1.65
Respiratory quotient
.81
34
1.24 42.0
1.81
49 1.43
70 2.39
.91
.83
39
1.51 59 2.25 .92
p A(h (mm Hg)
64
82*
55
74*
BAOa (percent saturation)
92
96t
86
95t
Alveolar ventilation (L/min)
30.0
35.7:1: 47.1
48.7:1:
Dead space (percent total ventilation)
29
15:1:
17:1:
33
*Estimated from saturation from ear oximetry. tMeasured by ear oximetry. :j:Calculated from bohr equation with end tidal volume of PAC<>,.•
CHEST, 77: 6, JUNE, 1980
:._·-.-:;
may occur with exercise, our experience indicates that less than baH of the individuals with a reduced OLeo have significant exercise-induced reduction in oxygenation. 9 The postoperative study results in this patien't •llfe' · typical of that situation. Consequently, the only way to identify exercised-induced desaturation is with exercise testing. It appears that only the improvement in oxygenation can account for the symptomatic improvement. Improvement in oxygenation is most likely the result of improved ventilation/perfusion relationships. While the static volumes and maximum ventilation did improve
postoperatively, these changes are not dramatic and are
not, in our judgment, sufficient to account for the symptomatic improvement. Work of breathing was not measured; however, between the preoperative and postoperative study, no significant change in oxygen consumption or ventilation at each work load was noted. Dead space ventilation was mildly elevated on the preoperative study and when estimated by noninvasive techniques, was normal postoperatively. Interestingly, the relationship of ventilation to oxygen consumption was unchanged on the PIT (Fig 1). The PIT offers a unique opportunity to observe dynamic physiologic responses through all levels of exercise and to quantitate abnormalities in those responses. By using PIT in the preoperative and postoperative assessment of individuals with bullous disease, a clearer picture of the mechanisms limiting exercise and producing symptoms should develop. Such information would make the decision for surgery more selective and improve surgical results. This report suggests that significant desaturation with exercise may be a favorable indicator for good surgical results in the symptomatic patient with giant bullae; however, only the study of a larger series of patients can confirm this finding.
REFERENCES 1 Fain WR, Conn JH, Campbell GD, et al: Excision of giant pulmonary emphysematous cysts. Surgery 1967; 62:552559 2 Foreman S, Weill H, DukeR, et al: Bullous disease of the lung: physiologic improvement after surgery. Ann Intern Med 1968; 69:757-767 3 Harris J: Severe bullous emphysema: successful surgical management despite poor preoperative blood gas levels and marked pulmonary hypertension. Chest 1976; 70:658660
4 Delarue NC, et al: Surgical treatment for pulmonary emphysema. Can ad J Surg 1977; 20:222-223 5 Boushy SF, Billig DM, Kohen R: Changes in pulmonary function after bullectomy. Am J Med 1969; 47:916-923 6 Jones NL, Campbell EJM, Edwards RHT, et al: Clinical exercise testing. Philadelphia: WB Saunders, 1975: 214 7 Wasserman K, Whipp BJ: Exercise physiology in health and disease. Am Rev Respir Dis 1975; 112-219-249 8 Laurenzi GA, Turino GM, Fishman AP: Bullous disease of the lung. Am J Med 1962; 32:361-378 9 Matthews Jl, Hooper RG: Exercise testing prethoracotomy: value in patients with impaired pulmonary functions. Am Rev Respir Dis 1979; 119:149
CHEST, 77: 6, JUNE, 1980
Melphalan-Induced Pulmonary Interstitial Fibrosis* Gary Goucher, M.D.;•• Virgjnla Rowland, M.D.;t and Joseph Hawkins, M.D.t
DUfuse interstitial fibrosis developed in a patient receiving therapy with melpbalan for mnltlple myeloma. With cessation of the administration of the alkyladng agent and corticosteroid, we describe pl'OII'ellive radiographic improvement in this patient, accompanied by persistent
severe Impairment in gas exchange.
he reported side effects of melphalan. a derivative of T mechlorethamine (nitrogen mustard) useful in the treatment of multiple myeloma, have been predominantly hematologic. 1 Pulmonary reactions to other alkylating agents are well-known, 2 but reports dealing with suspected pulmonary toxic effects of melphalan are rare. 3 •4 Our purpose is to call attention to possible melphalan-induced pulmonary toxic effects. CASE REPORT
A 53-year-old white woman was evaluated in January 1977 for pain of ten weeks' duration in the lower part of the back and legs. Multiple myeloma was suspected, but serum electrophoretic studies and examination of the bone marrow were inconclusive. In the course of evaluation, the patient was found to have primary hypothyroidism and was started on therapy with levothyroxine. Symptomatic treatment of her musculoskeletal pain was unsuccessful. Repeated electrophoretic studies of serum levels of immunoglobulins over the next several months continued to show spikes in the level of IgG. In view of this finding and the protracted course of the illness, the diagnosis of multiple myeloma was reconsidered. Consequently, in October 1977, therapy was begun with prednisone ( 100 mg) and melphalan ( 12 to 16 mg daily) for four days, repeated cyclicly every three weeks. Little improvement was noted, and the treatment · was discontinued in May 1978, after a total dosage of melphalan of 592 mg. Beginning in February 1978, while receiving melphalan. the patient developed a mild cough, with production of clear sputum. In May 1978, she was admitted with complaints of dyspnea, pleuritic pain in the right anterior portion of the chest, and yellow sputum. The patient was afebrile and had a respiration rate of 24/ min, and a few dry rales were present in the right lower lung field. The roentgenogram of the chest, which had been normal in September 1977, prior to beginning therapy with melphalan, now showed diffuse bilateral interstitial infiltrates ( Fig 1). Levels of arterial blood gases (patient breathing room air) were as follows: arterial oxygen pressure, 70 mm Hg; arterial carbon dioxide tension, 31 mm Hg; pH, 7.43; and bicarbonate, .20 mEq/L. The baseline singlebreath carbon monoxide diffusing capacity ( Dsb) was 8 ml/min/mm Hg (predicted value, 25 ± 5 mVmin/mm Hg). °From Maricopa County General Hospital, Phoenix. ..Pulmonary Fellow and Arizona Lung Association Fellow. tPulmonary Attending Physician. tChief of Pulmonary Disease.
MELPHALAN-INDUCED lmRSTITIAL FIBROSIS 805
Various tests of both fanctlon and IUUltomy have been used in .-tients being considered for IIID'gieal resection of giant pulmonary buDae. A youag _.uent bad an excellent respoase to removal of a larp bulla in the right long. In addition to roentKenographk: evalnation, ven-
tilation perfusion IK'BnniDI, and routine preoperative pulmonary function stndies, we performed progressive incremental exercl&e testing to determine botb preoperative and postoperative ventilatory and cardiac meamrements. We feel that propealve incremental exercl&e pnlmonary function adds another dimension to the aeledion and follow-up of .-dents being cousldered for operative
bnOectomy.
T
he management of bullous lung disease is difficult because of the frequent concomitant underlying emphysema and coexistent cardiac decompensation. Surgical management has few indications, but selected patients have subjective relief of dyspnea, objective im•From the Pulmonary Disease Service, Walter Reed Army Medical Center, Washington, D.C. The opinions or assertions contained herein are the private views of the writers and are not to be construed as of&cial or as reflecting views of the Department of the Army and the Department of Defense. Reprint requests: Dr. Tenholder, Heolth Sciences Library Eisenhower Medical Center, Fort Gordon, Georgia 30905 '
provement in Po2 and may return to gainful employment after bullectomy. The correlation between the clinical improvement achieved and the pulmonary function study results is not always a close one. 1 •2 Re6nements in selection of patients has progressed to include assessment of the density of compressed lung, mediastinal shift and herniation of lung tissue, nuclear medicine scans of zonal ventilation and perfusion, 8 and occasionally, even pulmonary angiography to identify zones of functioning capillary circulation.8 •4 Evaluation of pulmonary function has added the knowledge that postoperative increase in PA0 2 and reductions in FRC can be expected.s Progressive incremental exercise testing in this patient provided an accurate method of correlating subjective improvement in dyspnea and objective improvement in gas exchange and increased functional work capacity.
CASE
REPoRT
A 34-year-old active duty sergeant, paratrooper, was admitted to Walter Reed Army Medical Center for exertional dyspnea. In the two months prior to admission, he could no longer run one mile without severe dyspnea. He reported no previous difficulty with eight-mile training runs. He smoked one pack of cigarettes daily for 16 years, but denied other respiratory symptoms. On physical examination, the patient was a muscular man with a respiratory rate of 18 at rest. The right lung showed decreased breath sounds with some distant rhonchi. Cardiac exam was normal. A chest roentgenogram (Fig 1) showed a large solitary bullous lesion on the right side. Xenon ventilation scan showed delayed ventilatory washout to the right lung, while a technetium perfusion study revealed decreased perfusion to the right apex and crowded perfusion to the right base (Fig 2A). Arterial blood gas studies showed moderate hypoxemia, and pulmonary function tests demonstrated mild reduction of
FIGURE 1. The preoperative PA and lateral chest roentgenogram.
802 TENHOLDER ET Al
CHEST, 77: 6, JUNE, 1980
RPO
R
~(~
· -
· ·-, ,,_. , :
~;J;':a);t,lo,l~,...
Pulmonary Function Study
svc
A
LPO
POST L
FVC FEVt FEVt% TLC RV FRC
LPO R
RPO
L
R
A LAT
R
L
FIGVIIE 2A (upper) . Prebullectomy ventilation and perfusion lung scans, Oct 23, 1978. FicVRE 2B (lower). Postbullectomy ventilation and perfusion lung scans, Jan 11, 1979. vital capacity, increased residual volume, and moderate air flow obstruction (Table 1). Surgical excision of a large bulla was performed Oct 30, 1978. The patient tolerated the procedure well except for a persistent air leak for ten days postoperatively. After surgery, he has returned to active duty although restricted &om further parachuting activity. The patient is able to run without dyspnea. A repeated chest roentgenogram and lung scan (Fig 2B) confirm re-expansion of the right lung. Mild air trapping remains in the right upper lung field. Postoperative spirometry and blood gas determinations are shown in Table 1. EXERCISE TFSllNG
The results of exercise testing on a stationary bicycle ergometer during progressive incremental testing (PIT) and steady state testing (SST) demonstrate improvement in this patient. These tests were performed one week prior to surgery and six weeks after surgery. During the PIT, the patient pedaled at no load and increased by 25 watts per minute until the procedure was terminated by fatigue. The ECG (lead V5 ), expiratory airflow, tidal volume, minute ventilation, mixed expired 0 2 and C0 2 concentration, and Hewlett Packard ear oximetry were continuously monitored.8 • 7 During the SST, the same factors were measured and arterial blood gas determinations were obtained. No blood gas determinations were obtained during the postoperative SST. The SST was performed with the patient exercising at 50 and 100 watts for five minutes with the measurements made in the fifth minute of exercise. The preoperative and postoperative PIT are represented graphically in Figure 3. The steady state determinations appear in Table 2.
CHEST, 77: 6, JUNE, 1980
and Blood C.. DwiG
SplroJrWJ~ry
Preoperative,
L
Percent Percent Pre- Postoperative, Predieted L dieted
3.48
79
3.67
82
2.96
67
3.44
77
1.78
49
2.49
67
6.89
113
5.73
93
3.41
190
2.06
124
4.15
123
3.53
104
60%
72%
PAO,
78
95
Diffusion
65%
65%
The preoperative PIT demonstrated an appropriate relationship between oxygen consumption and the following factors: work load, heart rate, and ventilation at all levels of work. In addition, the ventilation was appropriate for the carbon dioxide production. The maximum ventilation achieved used 116 percent of the predicted ventilatory reserve and was obtained with a relatively small tidal volume and rapid respiratory rate. Significant desaturation occurred during the PIT. Data from the SST demonstrated significantly impaired gas exchange and elevated dead space ventilation. The postoperative PIT demonstrated changes in several aspects. Maximum work was increased and again limited by ventilation with 103 percent of the ventilatory reserve being utilized. This was obtained by an increase in the tidal volume at higher work loads. Significantly less desaturation occurred. The SST findings confirmed those of the PIT. DISCUSSION
A discrepancy between symptomatic relief of dyspnea and objective improvement in pulmonary function studies after surgical correction of bullae has long been recognized.1 •2 This discrepancy and the variability of symptomatic relief by surgery has led to some controversy regarding the appropriate criteria for surgical therapy. Clinical experience suggests several factors (single large bulla, significant compressed normal lung, and absence of severe chronic obstructive pulmonary disease) that are important predictors of good surgical results. 8 Identification of the mechanisms responsible for dyspnea could add significantly to our ability to predict which individuals may benefit from surgical procedures. The objective measurements of the subjective complaints of dyspnea have continued to be refined and PIT can identify the physiologic mechanisms of maximum exercise limitation and abnormal physiologic responses at submaximal exercise levels. 8 •7 With a more accurate understanding of these mechanisms in this disease process, our criteria for surgical therapy can be further defined. The use of PIT in this individual demonstrates
BULLOUS EMPHYSEMA 803
(IE
80 70 60 50 40 30 20
2.8 2.4 2.0
"'CIIe
1.6 1.2 .8 .4
... r-------------------~50
97 96
45
SaOz 95
40
94
35
93
30
RR
1.65 1.50 1.35 1.20 TV 1.05 .90 .75
180 160 Fe 140 120
100 t - - - - - - - - - - - - - - : l " i
175 150 125
.flO
20
30
40
50
60
70
80
(IE
0.
-MINUTE VENTILATION IL/MINI So Oa - 'lo HEIIOILOIIIN SATUIIATIOII Fe - HEAIIT IIATE IIEATS/111111 WOIIK -IWATTSI Oo. - OXYIEJI CONSUMPTION I L/MINI
WORK 100
7S 50 25 .7 .9
1.1 1.3 1.5 1.7 1.9 2.1 2.3 Voa
fco 1 -
CARlON DIOXIDE I'IIOOUCTION IL/Mifll IIEIPIIIATOIIY II ATE IIIIEATIIS/ MINI TV- TIDAL VOLUME ILl
It It -
li'IGuBE 3. Results of progressive incremental exercise testing prebuDeclany (dashed line) and postbullectomy (solid line).
its value to identify the mechanism responsible for dyspnea and to resolve the discrepancy between the dramatic symptomatic improvement in the face of modest postoperative improvement in ventilatory measurements. The use of progressive incremental exercise testing in this individual identified both a ventilatory and gas exchange mechanism which could account for symptomatic dyspnea. While signillcant symptomatic improvement followed surgery, the patient was able to perform only slightly more work and still was limited by his ventilatory reserve. Maximum ventilation obtained preoperatively was 70 L/minute which represented a value of 112 percent of predicted (FEV1 X 35). While maximum ventilation was utilized at the maximal exercise level ( 150 watts), the subject reported subjective dyspnea over the last half of the exercise study (75 to 150 watts). Postoperatively, the patient reached 84 L/ minute ventilation which represented a value of 96 percent of predicted. On the postoperative study, dyspnea was noted only at the maximal exercise level ( 175 watts). Static function studies do predict the result of the maximum ventilation levels; however, they fail to convey the results of the dynamic study in that this improvement accounted for only one additional level of work and one additional minute of exercise time. While maximum ventilation levels improved only enough to progress one work load level, the patient reported dramatic relief of his dyspnea throughout the study. The signiflcant·improvement in oxygenation can account for
... TENHOLDER ET AL
this symptomatic reJief. Ear oximetry showed a steady decline in arterial oxygen saturation with increasing levels of exercise preoperatively. When studied at steady state, the fall :in oxygenation was more dramatic than during the PIT. Postoperatively, gas exchange was markedly improved. While the reduced DLco88 suggest that desaturation Table 2---&ead,- S~a~e
Teadq
50 Watts Work
100 Watts Work
~~
Before Mter Before Mter
Rate (breaths/min) Tidal volume (L) Minute ventilation (L/min)
35 1.21 42.3
1.65
Respiratory quotient
.81
34
1.24 42.0
1.81
49 1.43
70 2.39
.91
.83
39
1.51 59 2.25 .92
p A(h (mm Hg)
64
82*
55
74*
BAOa (percent saturation)
92
96t
86
95t
Alveolar ventilation (L/min)
30.0
35.7:1: 47.1
48.7:1:
Dead space (percent total ventilation)
29
15:1:
17:1:
33
*Estimated from saturation from ear oximetry. tMeasured by ear oximetry. :j:Calculated from bohr equation with end tidal volume of PAC<>,.•
CHEST, 77: 6, JUNE, 1980
:._·-.-:;
may occur with exercise, our experience indicates that less than baH of the individuals with a reduced OLeo have significant exercise-induced reduction in oxygenation. 9 The postoperative study results in this patien't •llfe' · typical of that situation. Consequently, the only way to identify exercised-induced desaturation is with exercise testing. It appears that only the improvement in oxygenation can account for the symptomatic improvement. Improvement in oxygenation is most likely the result of improved ventilation/perfusion relationships. While the static volumes and maximum ventilation did improve
postoperatively, these changes are not dramatic and are
not, in our judgment, sufficient to account for the symptomatic improvement. Work of breathing was not measured; however, between the preoperative and postoperative study, no significant change in oxygen consumption or ventilation at each work load was noted. Dead space ventilation was mildly elevated on the preoperative study and when estimated by noninvasive techniques, was normal postoperatively. Interestingly, the relationship of ventilation to oxygen consumption was unchanged on the PIT (Fig 1). The PIT offers a unique opportunity to observe dynamic physiologic responses through all levels of exercise and to quantitate abnormalities in those responses. By using PIT in the preoperative and postoperative assessment of individuals with bullous disease, a clearer picture of the mechanisms limiting exercise and producing symptoms should develop. Such information would make the decision for surgery more selective and improve surgical results. This report suggests that significant desaturation with exercise may be a favorable indicator for good surgical results in the symptomatic patient with giant bullae; however, only the study of a larger series of patients can confirm this finding.
REFERENCES 1 Fain WR, Conn JH, Campbell GD, et al: Excision of giant pulmonary emphysematous cysts. Surgery 1967; 62:552559 2 Foreman S, Weill H, DukeR, et al: Bullous disease of the lung: physiologic improvement after surgery. Ann Intern Med 1968; 69:757-767 3 Harris J: Severe bullous emphysema: successful surgical management despite poor preoperative blood gas levels and marked pulmonary hypertension. Chest 1976; 70:658660
4 Delarue NC, et al: Surgical treatment for pulmonary emphysema. Can ad J Surg 1977; 20:222-223 5 Boushy SF, Billig DM, Kohen R: Changes in pulmonary function after bullectomy. Am J Med 1969; 47:916-923 6 Jones NL, Campbell EJM, Edwards RHT, et al: Clinical exercise testing. Philadelphia: WB Saunders, 1975: 214 7 Wasserman K, Whipp BJ: Exercise physiology in health and disease. Am Rev Respir Dis 1975; 112-219-249 8 Laurenzi GA, Turino GM, Fishman AP: Bullous disease of the lung. Am J Med 1962; 32:361-378 9 Matthews Jl, Hooper RG: Exercise testing prethoracotomy: value in patients with impaired pulmonary functions. Am Rev Respir Dis 1979; 119:149
CHEST, 77: 6, JUNE, 1980
Melphalan-Induced Pulmonary Interstitial Fibrosis* Gary Goucher, M.D.;•• Virgjnla Rowland, M.D.;t and Joseph Hawkins, M.D.t
DUfuse interstitial fibrosis developed in a patient receiving therapy with melpbalan for mnltlple myeloma. With cessation of the administration of the alkyladng agent and corticosteroid, we describe pl'OII'ellive radiographic improvement in this patient, accompanied by persistent
severe Impairment in gas exchange.
he reported side effects of melphalan. a derivative of T mechlorethamine (nitrogen mustard) useful in the treatment of multiple myeloma, have been predominantly hematologic. 1 Pulmonary reactions to other alkylating agents are well-known, 2 but reports dealing with suspected pulmonary toxic effects of melphalan are rare. 3 •4 Our purpose is to call attention to possible melphalan-induced pulmonary toxic effects. CASE REPORT
A 53-year-old white woman was evaluated in January 1977 for pain of ten weeks' duration in the lower part of the back and legs. Multiple myeloma was suspected, but serum electrophoretic studies and examination of the bone marrow were inconclusive. In the course of evaluation, the patient was found to have primary hypothyroidism and was started on therapy with levothyroxine. Symptomatic treatment of her musculoskeletal pain was unsuccessful. Repeated electrophoretic studies of serum levels of immunoglobulins over the next several months continued to show spikes in the level of IgG. In view of this finding and the protracted course of the illness, the diagnosis of multiple myeloma was reconsidered. Consequently, in October 1977, therapy was begun with prednisone ( 100 mg) and melphalan ( 12 to 16 mg daily) for four days, repeated cyclicly every three weeks. Little improvement was noted, and the treatment · was discontinued in May 1978, after a total dosage of melphalan of 592 mg. Beginning in February 1978, while receiving melphalan. the patient developed a mild cough, with production of clear sputum. In May 1978, she was admitted with complaints of dyspnea, pleuritic pain in the right anterior portion of the chest, and yellow sputum. The patient was afebrile and had a respiration rate of 24/ min, and a few dry rales were present in the right lower lung field. The roentgenogram of the chest, which had been normal in September 1977, prior to beginning therapy with melphalan, now showed diffuse bilateral interstitial infiltrates ( Fig 1). Levels of arterial blood gases (patient breathing room air) were as follows: arterial oxygen pressure, 70 mm Hg; arterial carbon dioxide tension, 31 mm Hg; pH, 7.43; and bicarbonate, .20 mEq/L. The baseline singlebreath carbon monoxide diffusing capacity ( Dsb) was 8 ml/min/mm Hg (predicted value, 25 ± 5 mVmin/mm Hg). °From Maricopa County General Hospital, Phoenix. ..Pulmonary Fellow and Arizona Lung Association Fellow. tPulmonary Attending Physician. tChief of Pulmonary Disease.
MELPHALAN-INDUCED lmRSTITIAL FIBROSIS 805