Cardiopulmonary Exercise Responses after Single Lung Transplantation for Severe Obstructive Lung Disease

Cardiopulmonary Exercise Responses after Single Lung Transplantation for Severe 'Obstructive Lung Disease* William]. Gibbons, M.D., F.C.C.~; Stephanie M. Uroine, M.D.; Charles L. Bryan, M.D., F.C.C.R; Jay Segarra, M.D.; John H. Calhoon, M.D.;]. Kent 1Hnkle, M.D.; and Stephen G. Jenkinson, M.D., F.C.C.R

The purpose ofthis study was to characterize cardiovascular and ventilatory respooses to exercise in siogle lung transplantation (SLT) recipients with nonseptic, severe obstructive IUDI disease (SLT-OB). We also investigated whether the hyperio8ated native lung in SLT-OB recipients could limit normal increases in tidal volume by mechanically constraiDing the transplantecllung, resulting in ventilationperfusioD imbalaoce in the lung graft. Data from six SLTOB recipients (&vewomen, one man) and six age-matched SLT recipients (two women, four men) with severe interstitiallUDI disease (SLT-IN) were compared. Resting arterial O. and CO. tensiODS were nonnaI and comparable between the SLT groups. Spirometry results were reduced but comparable between SLT groups. Total lung capacity was significantly larger in patients with SLT-OB than in patients with SLT-IN. Diffusion capacity was not different between SLT groups when differences in alveolar volume were accouDtecI fOr. Quantitative perfusion to the lung graft was comparable between the SLT groups, but quantitative ventilation was greater in patients with SLT-OB than in

patients with SLT-IN. Maximum exercise capacity foIIowiDI S~T-oB was decreased, but was comparable to that of SLT-IN recipients. None or the SLT-oB recipieDts reached preclictecl maDmum minute ventilalioD aacI oaIy ODe ape-

lung transplantation (SLT) has become the Single transplant procedure of choice for patients with

these early SLT recipients had concomitant acute graft rejection and/or infection. Moreover, decreased ventilation to the lung graft and impaired oxygenation were not consistent findings following SLT-oB performed by other groups. 4 Recentl~ we and others have successfully performed SLT in carefully selected patients with nonseptic, severe obstructive lung disease.5-7 Limited ~ormationis presently available about cardiovascular and respiratory responses during exercise after SLTOB.5 The purpose of this study was to compare cardiovascular and ventilatory responses to exercise in SLT-OB recipients with those of patients who had undergone SLT for interstitial lung disease (SLT-IN). We investigated whether the hyperin8ated native lung in SLT-OB (Fig 1) could limit normal increases in tidal volume by mechanically constraining the transplanted lung, resulting in ventilation-perfusion imbalance and gas exchange abnormality in the lung graft.

end-stage pulmonary fibrosis since 1983. 1 Improvements in pulmonary function and exertional capacity have been documented in patients with severe pulmonary fibrosis after SLT.l.2 Exercise capacity after SLT for pulmonary fibrosis is comparable to that after double lung transplantation for emphysema. 2 Single lung transplantation for end-stage obstructive lung disease is much more controversial.Y Decreased ventilation to the lung graft following SLT for severe obstructive lung disease (SLT-OB) has been an important concern because of potential graft compression by the hyperinHated native lung," Increased shunting in the lung graft was postulated to explain impairment in oxygenation." However, it was not clear whether *From the Pulmonary Diseases/Critical Care Division of the ~ent of Medicine and the Cardio-Thoracic Surgery Division of the Department of Surgery, the University of Texas Health Science Center at San Antonio and the Audie L. Murphy Memorial Veterans Administration Hospital, San Antonio, Texas. Supported in part by NIH grant H -30556 and the General Medical ReSearch Service of the Veterans Administration. Manuscript received June 25; revision accepted November 6. &print rsquut&: Dr. Uvine, 7400 Merton M'nfer Blvd, Pulmonary

Section(lllE), San Antonio 68286

108

rieDced ~d arterial O. desaturatioa, sugesdag peripheral muscle abnormalities from corticosteroid use and cIecooditioDiDg • IimitiDg factors rather than a veotillllory limitation. Tidal volumes at endexercise in the SLT-oB recipients were normal. Our quantitative IUDI scaD ·and aercise testiDg cI8ta suggest that ventilatioa-perEusioa imbabmce ___ resuItiDI gas ach.nge &om .......... ~ t and compression do DOt occur at rest or • exercise after SLT £or obstructive JUDI disease. (Claal 1991;100:1"11) COPD-ehrooic obstructive puImoaary eJiseue; Om. . . . . breath ditFusioo ~; SaO. arIeIiaI ~ IIIIuratiaaI SLT=siD&Ie .... tnDspIantMloD; SLT-IN-sewere iDtentitiaI .........; SLT-OB ~, teVere obatrucIiYe .... disease; V-Q ventiJation-perfulioo

=

=

SUBJECfS AND METHODS 1\venty-five autologous SLTs have been performed by the Organ Transplant Service of the University of'Texas Health Science Center at San Antonio between March 1988and June 1990. orthe 25 SLT recipients, 13 have heen performed for end-stage obstructive hmg

I

FIGURE 1A (upper). Inspiratory posteroanterior chest roentgenogram of a 44-year-old male SLT recipient with a. -antitrypsin deficiency taken two months followingSLT. Note the leftward shift of the mediastinum due to hyperinBation of the native right lung. FIGURE 1B (lower). Expiratory posteroanterior chest roentgenogram from the same patient taken two months following SLT. Note the compression of the transplanted left lung by the hyperinBated native right lung during a maximum exhalation. disease. Eleven of 13 recipients are alive, with five less than two months after SLT. In particular, patients with severe obstructive lung disease who have no pulmonary infections or Significant extrapulmonary disease have been selected by our program for SLT.· With each SLT, an attempt is made to match the recipient thorax with an appropriately sized donor lung. A size match is arbitrarily deemed acceptable if the donor chest circumference is within 7.5 cm of the recipient chest circumference.· As part of their routine clinical care, each SLT recipient at our institution undergoes symptom limited, graded maximum cardiopulmonary exercise testing with gas exchange measurements approximately every three months after transplantation . The purpose of this testing is to document improvements in functional capacity, to determine an exercise prescription as part of their postoperative recovery, and to monitor for arterial O. desaturation that may suggest early acute rejection. For the purposes of this investigation, maximum exercise studies performed in the first six SLT-OB recipients and six SLT-INrecipients who underwent studies at least two months after transplant were compared . Three patients with

severe obstructive lung disease underwent left-sided SLT and three had right-sided SLT. Each exercise study was performed at a time the SLT recipient appeared clinically stable without clinical or roentgenographic evidence of acute rejection or infection. Exercise studies were performed using a symptom-limited , graded exercise protocol (one minute of unloaded pedaling followed by 10 W/min) with an electrically braked ergometer (Corival 400, Quinton Co, Seattle, WA). All exercise studies were performed after the subject had fasted for at least 2 h prior to the test. Subjects pedaled at a speed to 50 to 60 rpm throughout the study. Arterial oxygen saturation (S.O.) was monitored noninvasively with a finger oximeter (OxyShuttle, Sensormedics Corp, Anaheim, CAl. Arterial O. desaturation was defined as a fall in SaO. of5 percent or more." Monitored cardiac parameters included heart rate and rhythm by three-lead electrocardiography (Lifepak 7, Marquette Co , Milwaukee, WI) and blood pressure by arm cuff technique. Oxygen consumption , carbon dioxide production , minute ventilation, tidal volume, and respiratory rate were measured breath by breath continuously throughout exercise by a metabolic cart (Horizon System, Sensormedics Corp, Anaheim, CAl. The Horizon system reported 3O-s data averages for each parameter. Air Rowand gas measurements were corrected for ambient temperature, barometric pressure , and water vapor. The predicted values of Jones et al" for graded maximum exercise tests were used . Predicted maximum minute ventilation was calculated as FEV. multiplied by 40. The anaerobic threshold during exercise was determined noninvasively as the O. consumption value during exercise at which (1) minute ventilation rose out of proportion to O. consumption. (2) the respiratory quotient rose above 1.0, and (3) the ventilatory equivalent for O. rose out of proportion to the ventilatory equivalent for CO•. ·o Anaerobic threshold values below 40 percent predicted maximum oxygen consumption were considered low. '0 As part of the routine protocol used for graded exercise testing in our clinical pulmonary function and exercise testing laboratory, subjects were asked to rate their degree of breathlessness at each exercise workload using a modified Borg category scale. 11." The categorical breathlessness scale used ranges from a rating of "0" which corresponds to "nothing at all" up to a rating of "10" which corresponds to "maximal" breathlessness. Spirometric and single-breath carbon monoxide diffusingcapacity measurements were performed within one week of the exercise study with a calibrated system (Collins Pulmonary Testing System, Braintree, MA). Static lung volume measurements were made using a body plethysmograph (Could body plethysmograph , Houston, TX). Results were reported as absolute values and as percent predicted........ Quantitative ventilation-perfusion (V-Q) lung scans were performed within one week of the exercise study using xenon 133 gas and -Tc labeled albumin. Ventilation scans were performed following the inhalation of 20 JoLg of xenon 133 gas in the erect position. Inspiratory, equilibrium, and washout views were obtained. Perfusion scanning was performed after the intravenous administration of 5 JoLg of technetium microspheres (Tc maa). Posterior static films were obtained for quantitative analysis of ventilation and perfusion. Data were compared between transplant groups using Student's t tests for unpaired data." Valuesfor p less than 0.05 were considered statistically significant. RESULTS

The clinical characteristics of the transplant recipients are shown in Table 1. Mean age, height, weight, and blood hemoglobin concentrations were not significantly different between groups. More women were present in the SLT-oB group than in the SLT-IN group. CHEST I 100 I 1 I JULY. 1991

107

QUANTITATIVE LUNG SCAN DATA

Table l-Subjecta' CharacteriBtica·

n Age, yr Sex Height, em ~ight,

kg

'Dme,mo Diagnoses

SLT-IN

SLT-OB

100

6 47.3±16.1 2F,4M 171.9± 10.2 68.8±15.7 6.0±1.4 4 idiopathic PF

6

80

1 sarcoidosis 1 bleomycin PF 13.3± 1.2 0.88±0.13

Hemoglobin, Wdl Chest circumference ratio

44.2±5.7 5F,IM 165.8±12.1 63.7± 15.2 4.5±2.6

••

DSLT-W ~SLT-oB

eo

% 40

4 a.-antitrypsin deficiency IBO lCOPD 13.1±0.5 1.01±0.05t

*Values are group means ± SO. tp
The elapsed time from SLT to the maximum exercise study was not different between the two groups, and ranged from 4.0 to 7.2 months in SLT-IN and from 2.3 to 8.7 in SLT-OB. Four SLT-OB recipients had (11antitrypsin deficiency, one had idiopathic bronchiolitis obliterans, and one had severe chronic airflow obstruction due to smoking. The donor to recipient chest circumference ratio was lower in the SLT-IN group compared with the SLT-OB group. Pulmonary function testing and resting arterial blood gas data of the transplant recipients are shown in 'Iable 2. Spirometry results were comparable in SLT-OB and SLT-IN, and obstructive ventilatory defects in SLT-OB were mild or normalized after SLT. Single breath diffusion capacity (Dco) was significantly lower in the SLT-IN group than the SLT-OB group, but when adjusted for alveolar volume, the

20

VENTLATION PERFUSION TO TtE TRANSPLANTED LUNG FIGURE 2. Group means ± SD. Double asterisk indicates p
difference in Dco did not reach statistical significance. Static lung volumes were significantly increased in the SLT-OB group, reflecting hyperinflation in the native lung. Resting arterial O2 and CO2 tensions were normal and comparable in the two study groups. Quantitative perfusion to the lung graft (Fig 2) was comparable in the SLT-OB and SLT-IN groups, but ventilation to the transplanted lung was significantly greater in the SLT-OB group than in the SLT-INgroup. Cardiovascular data from graded maximum exercise testing of the transplant recipients are shown in Table 3. Four SLT-IN recipients and five SLT-OB recipients stopped exercise because of leg fatigue. Two SLT-IN recipients and one SLT-OB recipient stopped exercise because of dyspnea. The rate of rise in O2 consumption with increasing exercise workload, following unloaded pedaling, was low in both SLT-IN and SLT-OB recip-

Table 2-PulmontJ'lI Function and Arterial Blood GGa Data· FVC

FEV. L

("pred)

SLT·IN 1 2 3 4

FEV/ (L)

("pred)

FVC

Z) 0.76 1.02 0.74 25 2.75 T1 3.28 0.83 64 2.74 78 3.16 0.86 65 3.85 0.85 3.30 100 83 1.27 43 1.87 51 0.67 5 2.25 58 2.69 54 0.84 6 Meao±SD 2.18 ±0.97 63.2±27.6 2.65±1.04 57.0±19.3 0.80±0.~ SLT-QB 45 2.71 0.66 1 1.79 51 47 1.22 1.59 0.76 2 48 70 2.18 2.44 0.89 3 63 2.07 0.75 4 1.55 54 61 1.71 0.62 1.~ 44 59 5 47 1.78 1.49 0.84 6 46 Mean±SD 1.55±0.40 51.2±9.9 2.m±0.44 54.7±7.2 0.75±0.10

Dco, (mlImm HWmin) 9.0 17.3 9.1 8.7 6.9 6.7 9.6±3.9 21.2 14.4 21.9 16.4 11.2 15.8 16.8t±4.1

("pred)

(DUVA)

45 5.10 62 5.22 40 2.55 2.37 39 31 3.91 24 1.44 4O.2±13.0 3.43±1.55

TLC, L

2.19 4.85 4.72 5.52 3.07 4.04 4.07±1.24

71 6.15 8.59 72 5.92 6.51 102 6.65 5.26 78 3.76 6.46 3.78 6.24 59 72 4.55 6.73 75.7*±14.3 5.14±1.27 6.63t±1.00

(" pred)

PIO., mmHg

PaCO., mmHG

42 95 38 66 ~ 39 68 79 38 82 102 26 71 62 29 56 83 32 62.7±13.3 86.2±1l.1 33.6±5.5 116 139

78 85 !n 83 131 85 143 99 125 74 124.51 ±18.2 84.0±8.5

37 34

31 37 36

41 36.1±3.2

*v.Iues are group means ± SD. tp
108

ExerciseResponses after Single Lung Transplantation (Gibbons et aJ)

Table 3-Cartlioooacular ftJrameten*

VO.max

\\brkload max,

SLTIN 1

2 3

w

" pred

~

21 47 51 51 23 29 36.8± 14.1

100 00

4 5

100

6

00

Mean ±SD

~

68.3± 33.1

TlDle, min

HRmax,

BPsystoIic mal,

OIPolsemu,

Umin

, pred

JDLIminltg

bpm

, pred

mI O~

mIIbeatItg

.. pred

4 11 10 11

0.45 1.55 1.23

23

143 148 157

0.<& 0.11) 0.007 0.117 0.m8 0.078 0.097± O.O'J)

116

178

un

36 38 39

21)

143

1M 83

0.71 0.81 0.99± 0.40

3.0 10.5 7.5 8.8 5.7 5.6 6.85± 2.66

43

4

T1 00 97 86 70 89 85.2± 10.1

I)

52 45 40 29 4O.7± 12.6

10.4 17.8 15.9 16.0 12.2 11.3 13.9± 3.0

170

166

128

24 33.2± 9.1

165.5±

M.9

m.4

1.26 0.74 0.64 0.57 0.63 0.72 0.76± 0.25

38 51 32 36 66 36 43.3± 13.0

78

9.5 6.2 5.1 4.6 4.8 5.1 5.88± 1.86

0.101 0.1(S

38

133

84 122

0.M9

28 31 38

54

I.m

7 7.8± 3.3

137

125

144 142.3± 10.8

mm Hg

SLT-QB 1 2 3 4 5

6 Mean ±SD

00 50 60 00 50

70 63.3 ± 15.1

37 46 40 51 &J 48 48.6± 11.1

10 6 7 7 6 8

7.3± 1.5

13.4 13.0 11.2 9.1 11.8 12.4 11.8±

133 119 125 123

132

141 128.8t± 8.0

1.5

~

75 71 81 81 75.7t± 5.1

0.073 0.(8) O.MS O.cm!± 0.012

44

M.9±

172 214 174 174 229 184.3±

6.4

36.3

~

sV
.. pred

mJJmiDIW

89

4.3 9.8 7.8 7.9 7.3 9.0 7.7± 1.9

100 107.8±

8.4 8.0 5.5 3.7 6.8 5.9 6.4± 1.8

151

1m 1m 154 If:i.1±

ms.6

*Values are group means±SD. Workload max=maximum achieved workload; TIme=duration of the exercise test; Vo.max=oxygen consumption at maximum exercise; HRmax = heart rate at maximum exercise; BPsystolic max = systolic blood pressure at maximum exercise; SVoJ = rate of rise in V02 with increasing exercise workload, following unloaded pedaling. tp
ients," but not significantly different between groups. The maximum exercise workload and O2 consumption of SLT-OB recipients was decreased, but was comparable to that of SLT-IN recipients. Exercise duration lasted an average of 7 min in both groups. Maximum heart rate was lower in SLT-OB recipients than in SLT-IN recipients. Oxygen pulse at end exercise was

low in both SLT-IN and SLT-OB groups and was not different between the two groups. Systolic blood pressure at end exercise was appropriate for the level of exertion and was not different between the two groups. Ventilatory data from graded maximum exercise testing of the transplant recipients are shown in Table

Table 4- Ventilatory ftJrtJmeten* VEmax, "MVV

VTmaX,

Vnnu,

L

'FVC

72.2

82 66

73.0 86.2

66

55 64 47 61

33.8

01

0.56 2.10 1.48 2.34 1.00

66.7 59.5± 24.3

74 70.3± 6.5

55.9 32.2 28.1 23.9 22.8 23.1 31.ot± 12.7

78 66 32 39 53 39

VEmaI,

Umin

fbmax, bpm

RQmu

Muimum Dyspoea BIting

1.00 1.. 1.:'» 1.28 1.01 1.23 1.18± 0.14

5 9 7 1 5 5.2± 2.7

A'f,

Best "

max "

95 96 96 98 87 96 94.7± 3.9

95 00 94

UminV<>s

SLT-IN 1 2 3 4

5 6 Mean±SD

25.0

01

1.57

1.52± 0.66

57 58 56.9± 5.9

45.0 34.5

49.4 37.0 33.8 42.6 4O.4± 6.3

77 00 00.2± 6.8

35 45 54 47 72 5O.6± 13.8

33 41 52 49 53 45.6± 8.5

96 94 97 97 f11 90 95.2t± 2.8

41 43 37 39 32 31 37.2t± 4.8

39

89

SLT-QB 1

2 3 4 5 6 Mean±SD

51.2± 17.9

1.57 0.99

1.29

0.99 1.~

0.94 1.14± 0.24

58 62 53 48 63 53 56.1± 6.0

35.6 32.0

21.7 24.1

21.2 24.5 1i.5t± 5.9

98 96 97 95 98 96 96.7±

1.2

40 36

36 31 31 35.5± 3.8

NA 0.00

0.95 0.71 0.63 0.49 0.74±

o.m

0.87 0.74 0.53 0.42 0.51 0.59 0.61± 0.17

NA 32

40

rr

36 18

~.6±

8.8

rr 51

rr

Ii 54 ~

35.7± 13.0

1.10 1.(1 I.• 1.17 1.13 1.13 1.15± O.(M)

4

4 4 4.5 4 4 4 4.1± 0.2

*Values are group means ± SD. Vemex = minute ventilation at maximum exercise; If,MVV =percent calculated maximum voluntary ventilation; VTDlax = tidal volume at maximum exercise; %FVC = percent forced vital capacity; fb max =breathing frequency at maximum exercise; SaO. =arterial oxygen saturation; AT=anaerobic threshold; RQmax=respiratory quotient at maximum exercise; vElVCOa =ventilatory equivalent for CO. measured at the anaerobic threshold; and VEIV0,. ventilatory equivalent for O. measured at the anaerobic threshold. tp
1"

4. Maximum minute ventilation in liters per minute was lower in SLT-OB than in SLT-IN recipients, but there was no significant difference when maximum minute ventilation was expressed as percentage of estimated maximum voluntary ventilation. In addition, there was evidence of breathing reserve present at end exercise, as indicated by the individual maximum minute ventilation values expressed as percentage of estimated maximum voluntary ventilation. Maximum tidal volume was normal, ie, between 50 percent and 60 percent of the resting forced vital capacity'? and not different between the two groups. In keeping with their higher absolute maximum minute ventilation levels, maximum breathing frequency was signi6cantly higher in SLT-IN recipients than in SLT-OB recipients. Arterial O 2 desaturation occurred at maximum exercise in two SLT-IN recipients (patients 4 and 5) and one SLT-OB recipient (patient 6). Maximum dyspnea ratings were not significantly different between the two groups. Ventilatory equivalents for O 2 and CO 2 at the anaerobic threshold and indices of dead space ventilation during exercise were higher than normal in both groups. 10 The SLT-OB group had significantly lower ventilatory equivalents for O 2 and CO2 than the SLT-IN group. The anaerobic threshold was low but comparable in SLT-IN and SLT-OB recipients. DISCUSSION

In patients with severe chronic obstructive pulmonary disease, exercise capacity is usually severely impaired for ventilatory reasons. Ventilatory demand during exercise is increased due to excessive dead space ventilation, and ventilatory capacity is reduced due to impaired respiratory system mechanics. 18 Oxygenation is impaired during exercise because of V-Q imbalance, resulting in reduced oxygen delivery to exercising peripheral muscles. 18 The present study has documented that although exercise capacity is decreased following SLT for end-stage obstructive lung disease, it is more than sufficient for the performance of activities of daily living. The decreased maximum exercise capacity after SLT-OB was comparable to that of SLT-IN recipients in this study, and it is comparable to that of heart-lung and double lung transplant recipients whose cases have been reported in the literature. 2,19,00 The findings of this study indicate that maximum exercise capacity after SLT for end-stage obstructive lung disease is not reduced for ventilatory reasons. Although maximum minute ventilation at end exercise was increased relative to maximum workload in the SLT-OB group, none of our SLT-OB recipients reached their estimated maximum voluntary ventilation or a maximum breathing frequency above 45 per minute (Table 4). Only one SLT-OB recipient (patient 6) experienced mild arterial O 2 de saturation at maximum 110

exercise as measured by finger pulse oximetry (Table 4). The mechanism of arterial O 2 de saturation at maximum exercise in this recipient is not clear. This finding was not likely a result of acute rejection because (1) this recipient was asymptomatic and clinically stable without roentgenographic evidence of acute rejection, and (2) this degree ofde saturation was a consistent finding during other graded maximum exercise tests in this recipient. The reduced maximum exercise capacity in our SLT-OB recipients was not due to malingering. A reasonable effort by all of the SLT-OB recipients during exercise testing was suggested by the achievement ofan anaerobic threshold (Table 4).18 The reduced maximum exercise capacity in our SLT-OB group was most likely multifactorial. Deconditioning was suggested by low anaerobic threshold values and the absence of a ventilatory limitation to exercise. Deconditioning in SLT-OB recipients is not surprising in view of the sedentary life-styles adopted before SLT. Deconditioning has been reported as an important factor limiting exercise performance after heart-lung and double lung transplantation. 2,00,21 Mechanisms other than simple deconditioning to explain low maximum oxygen consumption in our SLT recipients also need to be considered. Long-term corticosteroid administration to prevent rejection could have produced a proximal myopathy in our SLT recipients,22 resulting in impaired bicycle exercise performance.P Cortocosteroid administration has been shown to alter diaphragm histopathologic features and biochemistry as well as respiratory muscle endurance in animals.P Cyclosporine therapy for prevention and treatment of rejection has also been associated with peripheral skeletal muscle abnormalities. 24 Another potential contributing factor to low maximum oxygen consumptions in the SLT recipients could be the workload increment used in this study The rate of rise in oxygen consumption relative to workload following unloaded pedaling was low in most of our SLT recipients. A low ratio of change in oxygen consumption to change in workload suggests that anaerobic metabolism provided a relatively greater proportion of energy for the performance of exercise in our SLT recipients than in normal subjects," This could result from large workload increments." However, this potential mechanism of low maximum oxygen consumption should also result in abbreviated exercise duration. Ten of 12 SLT recipients in this study, including all SLT-OB, exercised for at least six minutes. In our view; this suggests that the chosen workload increment, ie, 10 W/min, was not the most important mechanism of reduced maximum O 2 consumption in our SLT recipients. In the present study, quantitative lung scan data ExerciseResponses after Single Lung Transplantation (Gibbons et 8/)

indicated that the majority of ventilation was distributed to the lung graft in our SLT-OBrecipients. These findings suggest that no significant constraint or compression of the transplanted lung occurs at rest despite hyperinflation of the native lung. At maximum exercise, tidal volume and arterial O2 saturation were normal in the SLT-OB group, suggesting that the transplanted lung was not significantly constrained and V-Q imbalance was not exaggerated during exercise. The ventilatory equivalents for O2 and CO 2 measured at the anaerobic threshold were greater than normal in our SLT recipients." This finding most probably reflects increased dead space ventilation resulting from ventilation of the native lung. Because arterial blood gases were not measured in this study we cannot exclude hyperventilation as a mechanism for increased ventilatory equivalents. Mild arterial O2 desaturation at end exercise was noted in our SLT-IN recipient group, and has been previously reported after SLT for pulmonary fibrosis by others," Arterial O2 de saturation is a characteristic response to exercise in patients with bilateral interstitiallung disease because ofV-Q mismatch exaggerated by the increase in pulmonary blood flow that normally accompanies exercise." Mild arterial O2 desaturation in our SLT-IN recipients could have occurred as a result of diffusion limitation in the native lung due to decreased pulmonary capillary transit time. 2 •18 Arterial O2 desaturation could have contributed to the relatively high maximum minute ventilation (as percent estimated maximum voluntary ventilation) in our SLT-IN recipients as compared with that of SLT recipients whose cases were reported by Miyoshi et al.2 An earlier attainment of the anaerobic threshold in our SLT-IN recipients compared with SLT recipients in the study of Miyoshi et al could also potentially contribute to the higher maximum minute ventilation in our SLT-IN recipients. In summary, SLT is a plausible therapeutic alternative for patients with SLT-OB. After SLT-OB, maximum exertional capacity is sufficient to permit performance ofactivities of daily living without hindrance. Because peripheral muscle weakness and deconditioning are probably the most important mechanisms of exercise limitation after SLT-OB, postoperative pulmonary rehabilitation, including exercise training, could be potentially effective in further improving the life-style of these recipients. ACICNOWLEDGMENTS: We wish to thank Mr. AI Taylorand Mr. Bm Franks for their excellent help in performin.g the pulmonary function and exercise tests, and Toya Harris for her excellent secretarial help in preparing the manuscript. REFERENCES 1 Grossman RF, Frost A, Zamel N, Patterson GA, Cooper JD, Myron PR, et ale Results of single-lung transplantation for bilateral pulmonary fibrosis. N Engl J Med 1990;322:727-33 2 MiyoshiS, Trulock E~ Schaefers HJ, Hsieh CM, Patterson GA,

Cooper JD. Cardiopulmonary exercise testing after single and double lung transplantation. Chest 1990;97:1130-36 3 Stevens PM, Johnson PC, Bell RL, Beall AC Jr, Jenkins DE. Begional ventilation and perfusion after lung transplantation in patients with emphysema. N EngI J Med 1970;282:245-49 4 Veith FJ, Koerner SK, Siegelman, Torres M, Bardfeld PA, Altai LA, et ale Single lung transplantation in experimental and human emphysema. Ann Surg 1973; 178:463-76 Kaiser LR, Pasque MK, 5 Trulock E~ Egan TM, Kouchoulcos Ettinger N, et ale Single lung transplanatation for severe chronic obstructive pulmonary disease. Chest 1989; 96:738-42 6 Calhoon JH, Grover FL, Gibbons WJ, Levine SL, Bailey SR, Nichols L, et ale Single lung transplantation: alternative indications and tedmique. J Thorac CanIiovasc Surg (in press) 7 Mal H, Andreassian B, Pamela F, Duchatelle J~ Bondeau E, Dubois F, et ale Unilateral·lung transplantation in end-stage pulmonary emphysema. Am Rev Bespir Dis 1989; 140:797-802 8 Ries AL, Farrow JT, Clausen JL. Accuracy of two ear oximeters at rest and during exercise in pulmonary patients. Am Rev Respir Dis 1985; 132:685-89 9 Jones NL, MaJaides L, Hitchcock C, Chypschar T, McCartney N. Normal standards for an incremental progressive cycle ergometer test. Am Rev Respir Dis 1985; 131:7()()..()8 10 Wasserman K, Hansen JE, Sue DY, Whipp BJ. Principles of exercise testing and interpretation. Philadelphia: Lea ~ Febiger; 1987:13,33,34,77-80 11 Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982; 14:377-81 12 Killian KJ, Jones NL. Respiratory muscles and dyspnea. Coo Chest Med 1988;9:237-48 13 Morris JF, Koski A, Johnson Le. Spirometric standards for healthy non-smoking adults. Am Rev Bespir Dis 1971; 103:5767 14 Burrows B, Kasik JE, Niden AH, Barclay WR. Clinical usefulness of the single breath pulmonary diftUsing capacity test. Am Rev Respir Dis 1961;84:789-806 15 Goldman HI, Becklalce MR. Respiratory function tests: normal values at median altitudes and the prediction of normal results. Am Rev Tuberc 1959;79:457-67 16 Colton 1: Statistics in medicine. Boston: Uttle, Brown, &: Co; 1974 17 Spiro SG, Juniper E, Bowman ~ Edwards RH'I: An increasing work rate test for assessing the physiologicstrain of submaximal exercise. Coo Sci Molec Med 1974;46:191-206 18 Sue DY, Wasserman IC. Exercise testing in the pulmonary patient. Curr Pulmonoll987; 8:233-98 19 Banner NR, Uoyd MH, Hamilton RD, Innes JA, Guz A, Yacoub MH. Cardiopulmonary response to dynamic exercise after heart and combined heart-lung transplantation. Br Heart J 1989; 61: 215-23 20 Sciurba Fe, Owens GR, Sanders MH, Griffith B~ Hardesty RL, Paradis IL, et aleEvidence ofan altered pattern ofbreatbing during exercise in recipients of heart-lung transplants. N Engl J 1988;319:1186-92 21 Theodore Jt Morris AJ, Burke CM, Glanville Aft, Van Kessel A, Baldwin JC, et ale Cardiopulmonary function at maximum tolerable constant worlcrateexercise followinghuman heart-lung transplantation. Chest 1987;92:433-39 22 Bowyer SL, LaMothe M~ Hollister JR. Steroid myopathy: incidence and detection in a population with asthma. J Allergy Clin Immunoll985; 76:234-42 23 Ferguson Gl: Irvin CG, Cherniak HM. Effect of corticosteroids on diaphragm function and biochemistry in the rabbit. Am Rev Bespir Dis 1990; 141:156-63 24 Cameron DE, Traill TA. Complications of immunosuppressive the~ In: Baumgartner WA, Reitz BA, AchufF SC, eels. Heart and heart-lung transplantation. Philadelphia: WB Saunden Co; 1990:237-48

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