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Lung Transplantation and Lung Volume Reduction Surgery

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Abstract

Since the publication of the last edition of the Handbook of Physiology, lung transplantation has become widely available, via specialized centers, for a variety of end‐stage lung diseases. Lung volume reduction surgery, a procedure for emphysema first conceptualized in the 1950s, electrified the pulmonary medicine community when it was rediscovered in the 1990s. In parallel with their technical and clinical refinement, extensive investigation has explored the unique physiology of these procedures. In the case of lung transplantation, relevant issues include the discrepant mechanical function of the donor lungs and recipient thorax, the effects of surgical denervation, acute and chronic rejection, respiratory, chest wall, and limb muscle function, and response to exercise. For lung volume reduction surgery, there have been new insights into the counterintuitive observation that lung function in severe emphysema can be improved by resecting the most diseased portions of the lungs. For both procedures, insights from physiology have fed back to clinicians to refine patient selection and to scientists to design clinical trials. This section will first provide an overview of the clinical aspects of these procedures, including patient selection, surgical techniques, complications, and outcomes. It then reviews the extensive data on lung and muscle function following transplantation and its complications. Finally, it reviews the insights from the last 15 years on the mechanisms whereby removal of lung from an emphysema patient can improve the function of the lung left behind. © 2011 American Physiological Society. Compr Physiol 1:1383‐1412, 2011.

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Figure 1. Figure 1.

Average values (± SE) for TLC, FRC, RV, and RV/TLC before (B) and at 6‐month intervals after HLT or BLT. Predicted values are those of the recipient. Note that FRC, RV, and RV/TLC remain greater than predicted after surgery. From Pinet and colleagues .

Figure 2. Figure 2.

Representative axial CT slice in an emphysematous patient with a left transplant. The arrow indicates location of the anterior mediastinal line. Note the shift of the mediastinum toward the graft. Line A is the midsagittal line, and line B was drawn from the vertebral body to the anterior mediastinal line. From Cassart and colleagues .

Figure 3. Figure 3.

Average (± SE) values of TLC and FRC of the native lung and of the graft (Tx) in 10 patients who underwent SLT for emphysema (open bars). Values are compared with those obtained on the ipsilateral side in 10‐matched normal control subjects (hatched bars). Statistical differences are shown only for adjacent bars: **P < 0.005; ***P < 0.001. From Estenne and colleagues .

Figure 4. Figure 4.

Average values (± SE) for FVC, FEV1, FEV1/FVC, and FEF25‐75 during 16 acute episodes of infection or rejection of the allograft in 13 HLT recipients. Values before (open bars), at the time of diagnosis (shaded bars), and 25 ± 5 days after (closed bars) the episodes are shown. *P < 0.05, ***P < 0.001 at the time of diagnosis versus before the episodes. From Van Muylem and colleagues .

Figure 5. Figure 5.

Changes in exhaled NO (eNO), exhaled (eCO), and helium slope (She) over time in one representative BLT recipient who developed BOS. The continuous lines represent the confidence interval of normal values for each marker in this patient. Note that eNO and eCO showed abrupt changes on consecutive measurements and did not increase progressively with BOS stages. On the other hand, She showed a continuous increase as BOS developed .

Figure 6. Figure 6.

Upper panel: average values of transdiaphragmatic pressure (Pdi) elicited by twitch stimulation of the phrenic nerves in 11 transplanted cystic fibrosis (CF) patients and 12 controls, and of diaphragm mass (Mdi) in 12 CF patients and 12 controls. Middle panel: average changes in gastric pressure (Pga) elicited by stimulation of the abdominal muscles 11 transplanted CF patients and 12 controls, and average values of cumulated thickness of the abdominal muscles (Tab) in 12 CF patients and 12 controls. Lower panel: average values of quadriceps peak torque (PT) and cross‐sectional area (quad CSA) in 12 transplanted CF patients and 12 controls. LBM = lean body mass. From Pinet and colleagues .

Figure 7. Figure 7.

Three‐dimensional reconstruction of the diaphragm at functional residual capacity in a patient with a right SLT for emphysema. From Cassart and colleagues .

Figure 8. Figure 8.

Changes in the angle of mediastinal shift toward the graft (see Figure ) and in the cross‐sectional area of the native lung and of the graft during forced expiration. Data are expressed as percent changes relative to values obtained at total lung capacity (TLC); so, an increase in mediastinal angle above 100% indicates that the angle more than doubled during the maneuver. During breath holding at TLC, the angle of mediastinal shift and the cross‐sectional areas of each lung are kept almost constant; once expiration starts, the cross‐sectional area of the graft decreases and the mediastinum is shifted toward the transplanted side. Note that the cross‐sectional area of the native lung decreases much less than that of the graft and barely changes in four of the seven patients .

Figure 9. Figure 9.

Results of hemodynamic measurements during exercise in 11 HLT recipients. (A) Heart rate (HR); (B) mean pulmonary artery pressure (PAPm); (C) stroke volume index (SVI); (D) pulmonary artery wedge pressure (PCWP); (E) cardiac index (CI); and (F) right atrial pressure (RAP), at rest, during exercise (at 0, 40, 60, and 80% of predetermined maximal workload), and during recovery (Rec). *P < 0.05, **P < 0.01, ***P < 0.001 compared to preceding stage; #P < 0.05 between rest and recovery. From Vachiery and colleagues .

Figure 10. Figure 10.

Relationships between peak oxygen uptake ( o2) and quadriceps strength (PT) (left) or cross‐sectional area (quad CSA) (right) in 11‐transplanted cystic fibrosis patients and 11 control subjects. The P value refers to the significance of the difference in vertical distance between the two regression lines as tested by covariance analysis. From Pinet and colleagues .

Figure 11. Figure 11.

(A) Three pleural pressure‐lung volume relationships are shown that will be used to illustrate effects of emphysema and lung volume reduction surgery (LVRS). The first, labeled CW, is the relaxed chest wall compliance. The curve labeled CW‐MAX is the compliance of the chest wall during maximal inspiratory muscle contraction. The dashed line, −CL, is the lung compliance expressed relative to pleural pressure, the mirror image of its conventional depiction relative to transpulmonary pressure. Total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) are also shown. (B) In this figure, the dashed line representing the lung compliance has been shifted upward, representing a patient with emphysema. It is assumed that CW and CW‐MAX are unaffected. TLC, FRC, and RV are increased. The thin lines A and B depict the theoretical effects of LVRS. In the case of A, pure bullae that do not contribute to lung elastic recoil are removed. RV falls, but lung compliance does not. In the case of B, the emphysema is diffusely distributed so that the elastic properties of the resected tissue are identical to the lung left behind. There are proportionally equal decreases in compliance and RV. The line labeled M illustrates postoperative inspiratory muscle impairment. (C) The effects of LVRS on maximal elastic recoil pressure (PTLC) and vital capacity (VC) are illustrated. PTLC is indicated by the double‐headed arrows, from top to bottom at baseline, after the resection of pure bullae indicated by line A, and after the resection of diffuse emphysema indicated by line B, respectively. Note that the PTLC increases more after resection of diffuse emphysema, but that VC increases less. Note also that inspiratory muscle impairment attenuates any improvement in VC. VCPRE = Preoperative VC, VCA = vital capacity after resection of pure cysts and bullae. VCB = vital capacity after resection of diffuse emphysema.

Figure 12. Figure 12.

Mean data for 25 patients (A) before and after bilateral lung volume reduction surgery. The cohort was divided into responders (n = 17, shown in B) whose FEV1 improved by >12% or 150 ml, and the nonresponders (C). Responders demonstrated a downward shift of the CW curve reflecting inspiratory muscle capacity. CL, lung compliance and CW, chest wall compliance during maximal inspiratory muscle contraction. From Ingenito et al. .



Figure 1.

Average values (± SE) for TLC, FRC, RV, and RV/TLC before (B) and at 6‐month intervals after HLT or BLT. Predicted values are those of the recipient. Note that FRC, RV, and RV/TLC remain greater than predicted after surgery. From Pinet and colleagues .



Figure 2.

Representative axial CT slice in an emphysematous patient with a left transplant. The arrow indicates location of the anterior mediastinal line. Note the shift of the mediastinum toward the graft. Line A is the midsagittal line, and line B was drawn from the vertebral body to the anterior mediastinal line. From Cassart and colleagues .



Figure 3.

Average (± SE) values of TLC and FRC of the native lung and of the graft (Tx) in 10 patients who underwent SLT for emphysema (open bars). Values are compared with those obtained on the ipsilateral side in 10‐matched normal control subjects (hatched bars). Statistical differences are shown only for adjacent bars: **P < 0.005; ***P < 0.001. From Estenne and colleagues .



Figure 4.

Average values (± SE) for FVC, FEV1, FEV1/FVC, and FEF25‐75 during 16 acute episodes of infection or rejection of the allograft in 13 HLT recipients. Values before (open bars), at the time of diagnosis (shaded bars), and 25 ± 5 days after (closed bars) the episodes are shown. *P < 0.05, ***P < 0.001 at the time of diagnosis versus before the episodes. From Van Muylem and colleagues .



Figure 5.

Changes in exhaled NO (eNO), exhaled (eCO), and helium slope (She) over time in one representative BLT recipient who developed BOS. The continuous lines represent the confidence interval of normal values for each marker in this patient. Note that eNO and eCO showed abrupt changes on consecutive measurements and did not increase progressively with BOS stages. On the other hand, She showed a continuous increase as BOS developed .



Figure 6.

Upper panel: average values of transdiaphragmatic pressure (Pdi) elicited by twitch stimulation of the phrenic nerves in 11 transplanted cystic fibrosis (CF) patients and 12 controls, and of diaphragm mass (Mdi) in 12 CF patients and 12 controls. Middle panel: average changes in gastric pressure (Pga) elicited by stimulation of the abdominal muscles 11 transplanted CF patients and 12 controls, and average values of cumulated thickness of the abdominal muscles (Tab) in 12 CF patients and 12 controls. Lower panel: average values of quadriceps peak torque (PT) and cross‐sectional area (quad CSA) in 12 transplanted CF patients and 12 controls. LBM = lean body mass. From Pinet and colleagues .



Figure 7.

Three‐dimensional reconstruction of the diaphragm at functional residual capacity in a patient with a right SLT for emphysema. From Cassart and colleagues .



Figure 8.

Changes in the angle of mediastinal shift toward the graft (see Figure ) and in the cross‐sectional area of the native lung and of the graft during forced expiration. Data are expressed as percent changes relative to values obtained at total lung capacity (TLC); so, an increase in mediastinal angle above 100% indicates that the angle more than doubled during the maneuver. During breath holding at TLC, the angle of mediastinal shift and the cross‐sectional areas of each lung are kept almost constant; once expiration starts, the cross‐sectional area of the graft decreases and the mediastinum is shifted toward the transplanted side. Note that the cross‐sectional area of the native lung decreases much less than that of the graft and barely changes in four of the seven patients .



Figure 9.

Results of hemodynamic measurements during exercise in 11 HLT recipients. (A) Heart rate (HR); (B) mean pulmonary artery pressure (PAPm); (C) stroke volume index (SVI); (D) pulmonary artery wedge pressure (PCWP); (E) cardiac index (CI); and (F) right atrial pressure (RAP), at rest, during exercise (at 0, 40, 60, and 80% of predetermined maximal workload), and during recovery (Rec). *P < 0.05, **P < 0.01, ***P < 0.001 compared to preceding stage; #P < 0.05 between rest and recovery. From Vachiery and colleagues .



Figure 10.

Relationships between peak oxygen uptake ( o2) and quadriceps strength (PT) (left) or cross‐sectional area (quad CSA) (right) in 11‐transplanted cystic fibrosis patients and 11 control subjects. The P value refers to the significance of the difference in vertical distance between the two regression lines as tested by covariance analysis. From Pinet and colleagues .



Figure 11.

(A) Three pleural pressure‐lung volume relationships are shown that will be used to illustrate effects of emphysema and lung volume reduction surgery (LVRS). The first, labeled CW, is the relaxed chest wall compliance. The curve labeled CW‐MAX is the compliance of the chest wall during maximal inspiratory muscle contraction. The dashed line, −CL, is the lung compliance expressed relative to pleural pressure, the mirror image of its conventional depiction relative to transpulmonary pressure. Total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) are also shown. (B) In this figure, the dashed line representing the lung compliance has been shifted upward, representing a patient with emphysema. It is assumed that CW and CW‐MAX are unaffected. TLC, FRC, and RV are increased. The thin lines A and B depict the theoretical effects of LVRS. In the case of A, pure bullae that do not contribute to lung elastic recoil are removed. RV falls, but lung compliance does not. In the case of B, the emphysema is diffusely distributed so that the elastic properties of the resected tissue are identical to the lung left behind. There are proportionally equal decreases in compliance and RV. The line labeled M illustrates postoperative inspiratory muscle impairment. (C) The effects of LVRS on maximal elastic recoil pressure (PTLC) and vital capacity (VC) are illustrated. PTLC is indicated by the double‐headed arrows, from top to bottom at baseline, after the resection of pure bullae indicated by line A, and after the resection of diffuse emphysema indicated by line B, respectively. Note that the PTLC increases more after resection of diffuse emphysema, but that VC increases less. Note also that inspiratory muscle impairment attenuates any improvement in VC. VCPRE = Preoperative VC, VCA = vital capacity after resection of pure cysts and bullae. VCB = vital capacity after resection of diffuse emphysema.



Figure 12.

Mean data for 25 patients (A) before and after bilateral lung volume reduction surgery. The cohort was divided into responders (n = 17, shown in B) whose FEV1 improved by >12% or 150 ml, and the nonresponders (C). Responders demonstrated a downward shift of the CW curve reflecting inspiratory muscle capacity. CL, lung compliance and CW, chest wall compliance during maximal inspiratory muscle contraction. From Ingenito et al. .

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Marc Estenne, Henry E. Fessler, Malcolm M. DeCamp. Lung Transplantation and Lung Volume Reduction Surgery. Compr Physiol 2011, 1: 1383-1412. doi: 10.1002/cphy.c100044