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

doi:10.1378/chest.100.1.106

Chest

Volume 100, Issue 1, July 1991, Pages 106-111

https://doi.org/10.1378/chest.100.1.106 Get rights and content

The purpose of this study was to characterize cardiovascular and ventilatory responses to exercise in single lung transplantation (SLT) recipients with nonseptic, severe obstructive lung disease (SLT-OB). We also investigated whether the hyperinflated native lung in SLT-OB recipients could limit normal increases in tidal volume by mechanically constraining the transplanted lung, resulting in ventilation-perfusion imbalance in the lung graft. Data from six SLT-OB recipients (five women, one man) and six age-matched SLT recipients (two women, four men) with severe interstitial lung disease (SLT-IN) were compared. Resting arterial O₂ and CO₂ tensions were normal 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 accounted 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 following SLT-OB was decreased, but was comparable to that of SLT-IN recipients. None of the SLT-OB recipients reached predicted maximum minute ventilation and only one experienced mild arterial O₂ desaturation, suggesting peripheral muscle abnormalities from corticosteroid use and deconditioning as limiting factors rather than a ventilatory limitation. Tidal volumes at end exercise in the SLT-OB recipients were normal. Our quantitative lung scan and exercise testing data suggest that ventilation-perfusion imbalance and resulting gas exchange abnormalities from lung graft constraint and compression do not occur at rest or with exercise after SLT for obstructive lung disease.

Section snippets

Subjects and Methods

Twenty-five autologous SLTs have been performed by the Organ Transplant Service of the University of Texas Health Science Center at San Antonio between March 1988 and June 1990. Of the 25 SLT recipients, 13 have been performed for end-stage obstructive lung 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

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-0B group than in the SLT-IN group. 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 α₁-antitrypsin deficiency, one had

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

ACKNOWLEDGMENTS

We wish to thank Mr. Al Taylor and Mr. Bill Franks for their excellent help in performing the pulmonary function and exercise tests, and Toya Harris for her excellent secretarial help in preparing the manuscript.

References (24)

S Miyoshi et al.
Cardiopulmonary exercise testing after single and double lung transplantation
Chest
(1990)
EP Trulock et al.
Single lung transplanatation for severe chronic obstructive pulmonary disease
Chest
(1989)
KJ Killian et al.
Respiratory muscles and dyspnea
Clin Chest Med
(1988)
SL Bowyer et al.
Steroid myopathy: incidence and detection in a population with asthma
J Allergy Clin Immunol
(1985)
RF Grossman et al.
Results of single-lung transplantation for bilateral pulmonary fibrosis
N Engl J Med
(1990)
PM Stevens et al.
Regional ventilation and perfusion after lung transplantation in patients with emphysema
N Engl J Med
(1970)
FJ Veith et al.
Single lung transplantation in experimental and human emphysema
Ann Surg
(1973)
Calhoon JH, Grover FL, Gibbons WJ, Levine SL, Bailey SR, Nichols L, et al. Single lung transplantation: alternative...
H Mal et al.
Unilateral lung transplantation in end-stage pulmonary emphysema
Am Rev Respir Dis
(1989)
AL Ries et al.
Accuracy of two ear oximeters at rest and during exercise in pulmonary patients
Am Rev Respir Dis
(1985)

NL Jones et al.

Normal standards for an incremental progressive cycle ergometer test

Am Rev Respir Dis

(1985)

Wasserman K, Hansen JE, Sue DY, Whipp BJ. Principles of exercise testing and interpretation. Philadelphia: Lea &...

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Anesthetic considerations for nontransplant procedures in lung transplant patients
2011, Journal of Clinical Anesthesia
Citation Excerpt :
In single LTx recipients with pulmonary fibrosis, 60% to 70% of blood flow is directed toward the transplanted lung [25]. In single LTx for obstructive lung disease, the perfusion is directed mostly toward the transplanted lung while ventilatory flow, as mentioned above, preferentially distributes to the native lung, thereby creating a variable degree of ventilation/perfusion mismatch [26]. All transplanted patients are placed on an antirejection protocol.
Lung transplantation has become an accepted option for many patients with end-stage pulmonary diseases. Anesthesia and surgery following lung transplantation may be required for various diseases that may affect both systemic organs and the transplanted graft. When a patient with a lung transplant undergoes surgery, there is the potential for interference with lung function, depending on the type of intervention and its anatomical site. Accurate preoperative evaluation, an understanding of the physiology of the transplanted lung, proper airway instrumentation, individualized management of intraoperative ventilation, and fluid balance are essential for a positive perioperative outcome.
Physical Activity in Daily Life 1 Year After Lung Transplantation
2009, Journal of Heart and Lung Transplantation
Citation Excerpt :
Pulmonary function was therefore most likely not related to the capacity of performing daily tasks. Our data are in accordance with earlier findings indicating that, even after single-lung transplantation, exercise capacity is primarily limited by peripheral muscle abnormalities rather than by ventilatory factors.34 Earlier studies showed that muscle groups were not uniformly affected with more pronounced leg muscle weakness.9,32
Reduced physical fitness has been reported to occur after lung transplantation. Pre- and post-transplant factors, including an inactive lifestyle, have been proposed as possible causes. However, daily physical activity has not been objectively assessed so far in lung recipients. The purpose of this study was to objectively measure daily physical activity in lung recipients.
Twenty-two clinically stable patients with single (n = 7) and bilateral lung grafts (n = 15) underwent measurements of physical activity with activity monitors at least 12 months after surgery. Results were compared with findings from 22 healthy, age- and gender-matched control subjects.
Substantial and statistically significant differences in daily activity were observed. Steps, standing time and moderate-intensity activity of lung recipients were reduced by 42%, 29% and 66%, respectively, relative to controls. Daily sedentary time was increased by 30%. Daily steps correlated with self-reported physical functioning (r = 0.81), 6-minute walk distance (r = 0.68), quadriceps force (r = 0.66) and maximum workload (r = 0.63).
This study has shown for the first time that daily activity is substantially reduced after lung transplantation and related to measures of physical fitness and health-related quality of life. Future studies need to examine whether physical activity can be modified to improve functional recovery after lung transplantation.
Sources of graft restriction after single lung transplantation for emphysema
2007, Journal of Thoracic and Cardiovascular Surgery
Citation Excerpt :
Importantly, although chest wall volume reduction after lung transplantation restricts the volume of the graft and impairs ventilatory function of the lungs, there is no clear evidence in our data that it contributes to mortality or serious morbidity.3-7
After single lung transplantation for emphysema, the volume of the graft at total lung capacity is usually less than its predicted volume in the donor. We sought to determine the contributions of donor–recipient size matching, postoperative native lung hyperinflation, and postoperative chest wall volume reduction to graft restriction after transplantation.
In 19 patients, we estimated individual lung volumes from thoracic computed tomographs taken near total lung capacity before and after single lung transplantation for emphysema to analyze sources of graft restriction. Pulmonary function was assessed by spirometry, and in 5 patients, inspiratory function was assessed with esophageal manometry.
Graft volumes after transplantation were 54% ± 17% of those predicted for the donors (mean ± SD, P < .0001), and pulmonary function after transplantation was significantly correlated with graft volume. The greatest contribution to graft restriction was the decrease in chest wall volume after transplantation, which was −0.87 L (−31% ± 29% of the graft’s predicted volume; P < .0001). Volume expansion of the contralateral lung contributed −0.44 L (−18% ± 24%; P = .0018). Other effects, including donor–patient size matching, were not significant. In 5 patients, the maximum negative inspiratory esophageal pressure at total lung capacity was low (−6 ± 2 cm H₂O, normal range ∼−17 to −29 cm H₂O).
After single lung transplantation for emphysema, decreased volume of the chest wall was more important than increased volume of the native lung in causing restriction of the graft and decreased pulmonary function. Chest wall restriction is likely due to diminished inspiratory muscle function.
Limiting Factors of Exercise Performance 1 Year After Lung Transplantation
2006, Journal of Heart and Lung Transplantation
Citation Excerpt :
Schwaiblmair and colleagues3 also demonstrated a reduced LT within 3 months after transplantation. Accordingly, Gibbons et al21 investigated 12 SLT recipients within 7 months after transplantation and observed a low LT. In the absence of a ventilatory, oxygen uptake or cardiac limitation, these data indicate that peripheral muscle dysfunction is a major cause of decreased exercise capacity after LTx. However, 8 patients also showed an increase in alveolar–arterial oxygen tension of >2 kPa at maximal exercise, indicating a peripheral limitation in combination with an oxygen uptake limitation.
After lung transplantation (LTx) exercise capacity frequently remains limited, despite significantly improved pulmonary function. The aim of this study was to evaluate maximal exercise capacity and peripheral muscle force before and 1 year after LTx, and to determine whether peripheral muscle force and lactate threshold (LT) limit exercise capacity 1 year after LTx.
Twenty-five subjects (mean age 43 years, 8 women and 17 men, 4 single-lung transplantations) were included in the study. Measurements included maximal exercise capacity, lactate threshold (symptom-limited bicycle ergometer test) and muscle force test (hand-held dynamometer) were performed before and 1 year after LTx.
Before LTx, all patients showed severe exercise intolerance (mean ± SD): work capacity (W_peak), 11.6 ± 18 W; peak oxygen uptake (Vo₂), 8.6 ± 3.6 ml/min/kg. After LTx, exercise capacity improved significantly: W_peak, 69 ± 27 W (p < 0.001); peak Vo₂, 15.7 ± 4.3 ml/min/kg (p < 0.001). Ventilatory factors did not appear to limit exercise capacity. Quadriceps muscle force pre- vs post-LTx was: 248 ± 73 N vs 281 ± 68 N (p < 0.05). Post-LTx, a significant correlation was found between LT and exercise capacity (r = 0.76, p < 0.001), between muscle force and exercise capacity (r = 0.41, p < 0.05) and between the LT and muscle force (r = 0.53, p < 0.01).
The occurrence of an early and pathologic LT and peripheral muscle weakness contributes to the limitation of exercise capacity and reflects a peripheral deficit post-LTx.
Lung transplantation in patients with pulmonary fibrosis
2005, Revue de Pneumologie Clinique
La transplantation pulmonaire s’est développée au cours des 15 dernières années pour traiter différentes formes de maladies respiratoires évoluées. Parmi elles figure en bonne place la fibrose pulmonaire idiopathique. Dans cette indication, le type de transplantation effectuée est principalement la greffe mono-pulmonaire, et dans une moindre mesure la greffe bi-pulmonaire. Ces deux interventions donnent des résultats voisins en termes de survie. La survie post-transplantation pour les fibroses se situe approximativement à 65-70 % à 1 an et à 40 % à 5 ans, c’est-à-dire à un niveau un peu inférieur à ce qui est noté dans la BPCO ou la mucoviscidose. En l’absence de complications, l’intervention permet le retour à une activité quasi normale. Parmi les complications menaçant le patient en post-opératoire, il faut citer particulièrement l’œdème de réimplantation, l’infection, le rejet et les complications bronchiques. A distance, une forme de rejet chronique appelée « syndrome de bronchiolite oblitérante » va se développer chez près d’un patient sur deux. Ces complications expliquent les résultats de la transplantation pulmonaire qui sont encore largement perfectibles. Malgré cela, la survie après greffe pour fibrose sont supérieurs à ceux de la survie spontanée en liste d’attente, la fibrose idiopathique étant la pathologie associée à la mortalité la plus élevée sur liste. Les patients doivent être référés très tôt pour leur bilan pré-transplantation car leur pronostic individuel est très difficile à prédire.
Lung transplantation has been developed over the last fifteen years as a therapeutic option for different forms of advanced-stage lung disease. Idiopathic pulmonary fibrosis is a good indication. For these patients, single lung transplantation is usually preferred, bilateral lung transplantation to a lesser extent. Survival is similar for these two types of transplantation. The post-transplantation survival in patients with pulmonary fibrosis is about 65-70% at one year and 40% at five years. This rate is lower than observed for COPD or cystic fibrosis. If there are no complications, the patient can recover nearly normal lifestyle. Among the different complications, reimplantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.
Maximal exercise capacity and peripheral skeletal muscle function following lung transplantation
1999, Journal of Heart and Lung Transplantation
There have been many suggestions that diminished exercise capacity in patients that have undergone lung transplantation is due, in part, to peripheral muscle dysfunction, brought on by either detraining or immunosuppressive therapy. There is limited data quantifying skeletal muscle function in this population, especially in those more than 18 months post-procedure. The present study sought to quantitate skeletal muscle function and cardiopulmonary responses to graded exercise in 19 lung transplant recipients, 15 of which were mostly more than 18 months post-procedure.
Ten single- (SLT) and 9 double-lung transplantation (DLT) underwent anthropometric measures and performed expiratory spirometry, whole body plethysmography to assess lung volumes, static maximal mouth pressures to assess respiratory muscle strength, progressive exercise testing on a cycle ergometer (with cardiac output measurements being performed every second workload) and isokinetic cycling to assess peripheral muscle power and work capacity.
The DLT group was younger than the SLT group (23.0 [21.0–32.0] vs 47.5 [43.0–55.0] median [interquartile range], p < .05) with no differences in height, weight, or BMI. Despite the DLT group having significantly better spirometric values (FEV₁: 86% vs 56.5% median) and less airtrapping (RV/TLC: 30% vs 53.5%), both groups were equally limited in exercise capacity (W_max)(38.0 percent predicted [30.0–65.0] vs 37.5 percent predicted [30.0–44.0], SLT vs DLT), leg power (76.1 percent predicted [53.8–81.4] vs 69.0 percent predicted [58.3–76.0]) and leg work capacity (63.3 percent predicted [34.7–66.8] vs 38.4 percent predicted [27.5–57.3]). This lack of difference in performance persisted when the analysis was limited to those more than 18 months post-procedure. Respiratory muscle strength was also not different for the two groups, and was within normal limits. W_max was best correlated with leg work capacity (r = .84), but also with leg power, RV/TLC, FEV₁ (r = .49, −.52, .58). When normalized for age, height, and sex, percent predicted W_max only correlated with percent predicted leg work capacity (r = .58). Cardiac output was appropriate for the work performed.
We conclude that peripheral skeletal muscle work capacity is reduced following lung transplantation and mostly responsible for the limitation of exercise performance. While the causes of muscular dysfunction have yet to be clarified, the preservation of respiratory muscle strength with the concomitant reduction in leg power and work capacity suggests that most of the muscular dysfunction post-transplantation is attributable to detraining.

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: 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.

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Chest

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

Section snippets

Subjects and Methods

Results

Discussion

ACKNOWLEDGMENTS

Chest

Chest

Clin Chest Med

J Allergy Clin Immunol

Results of single-lung transplantation for bilateral pulmonary fibrosis

N Engl J Med

Regional ventilation and perfusion after lung transplantation in patients with emphysema

N Engl J Med

Single lung transplantation in experimental and human emphysema

Ann Surg

Unilateral lung transplantation in end-stage pulmonary emphysema

Am Rev Respir Dis

Accuracy of two ear oximeters at rest and during exercise in pulmonary patients

Am Rev Respir Dis

Normal standards for an incremental progressive cycle ergometer test

Am Rev Respir Dis