American Journal of Respiratory and Critical Care Medicine

Since lung volume reduction surgery (LVRS) reduces end-expiratory lung volume, we hypothesized that it may improve diaphragm strength. We evaluated 37 patients for pulmonary rehabilitation and LVRS. Before and 8 wk after pulmonary rehabilitation, 24 patients had spirometry, lung volumes, diffusion capacity, incremental symptom limited maximum exercise test, 6-min walk test, maximal static inspiratory and expiratory mouth pressures, and transdiaphragmatic pressures during maximum static inspiratory efforts and bilateral supramaximal electrophrenic twitch stimulation measured. Twenty patients (including 7 patients who crossed over after completing pulmonary rehabilitation) had baseline measurements postrehabilitation, and 3 mo post-LVRS. Patients were 58 ± 8 yr of age, with severe COPD and hyperinflation (FEV1, 0.69 ± 0.21 L; RV, 4.7 ± 1.4 L). Nineteen patients had bilateral LVRS performed via median sternotomy and stapling, and 1 patient had unilateral LVRS via thorascopy with stapling. After rehabilitation, spirometry and Dl CO/ Va were not different, and lung volumes showed a slight worsening in hyperinflation. Gas exchange, 6-min walk distance, maximum oxygen uptake (V˙ o 2max), and breathing pattern during maximum exercise did not change after rehabilitation, but total exercise time was significantly longer. Inspiratory muscle strength (Pi max, Pdimax combined, Pdimax sniff, Pdimax, Pditwitch), was unchanged after rehabilitation. In contrast, after LVRS, FVC increased 21%, FEV1 increased 34%, TLC decreased 13%, FRC decreased 23%, and FRCtrapped gas and RV decreased by 57 and 28%, respectively. Pco 2 was lower (44 ± 6 versus 48 ± 6 mm Hg, p < 0.003) and 6-min walk distance increased (343 ± 79 versus 250 ± 89 m, p < 0.001), as did total exercise time during maximum exercise (9.2 ± 1.9 versus 6.9 ± 2.7 min, p < 0.01). Minute ventilation (29  ± 8 versus 21 ± 6 L /min, p < 0.001) and tidal volume (1.0 ± 0.33 versus 0.84 ± 0.25 L, p < 0.001) during maximum exercise increased whereas respiratory rate was lower (28 ± 6 versus 32 ± 7 breaths / min, p < 0.02). Measurements of respiratory muscle strength (Pi max, 74 ± 28 versus 50 ± 18 cm H2O, p < 0.002; Pdimax combined, 80 ± 25 versus 56 ± 29 cm H2O, p < 0.01; Pdimax sniff, 71 ± 7 versus 46 ± 27 cm H2O, p < 0.01; Pditwitch, 15 ± 5 versus 7 ± 5 cm H2O, p < 0.01) were all greater post-LVRS. Inspiratory muscle workload as measured by Pdi Tti was lower following LVRS (0.07 ± 0.02 versus 0.09 ± 0.03, p < 0.03). On multiple regression analysis, increases in Pi max correlated significantly with decreases in RV and FRCtrapped gas after LVRS (r = 0.67, p < 0.03). We conclude that LVRS significantly improves diaphragm strength that is associated with a reduction in lung volumes and an improvement in exercise performance. Future studies are needed to determine the relationship and stability of these changes over time.

Lung volume reduction surgery (LVRS) has been advocated in select patients with severe, nonbullous, diffuse emphysema (1-7). Cooper and colleagues (1) reported the results of this surgery in 20 patients with severe chronic obstructive pulmonary disease (COPD) (mean FEV1, 0.77 L) and hyperinflation (TLC, 8.5 L). These authors found that 6 mo after surgery mean FEV1 increased by 82% (0.77 to 1.4 L), arterial Po 2 increased from 64 to 72 mm Hg, and 6-min walk distance increased by 33%. Other investigators have confirmed the beneficial effects of bilateral volume reduction (2) and, to a lesser extent, unilateral volume reduction (3-7), on improving spirometry and gas exchange, reducing residual volume, and enhancing exercise performance (8-11).

Several investigators have reported conflicting results on the effect of LVRS on respiratory muscle function (8-12). Although some have shown that LVRS increases diaphragm strength (12), and alters respiratory muscle recruitment during exercise (10), others have shown no significant effect (11). Moreover, the effect of LVRS versus pulmonary rehabilitation on lung function, exercise capacity, or respiratory muscle strength has not been carefully delineated in any of these earlier reports (1-12).

Herein, we examine the effects of LVRS versus pulmonary rehabilitation on diaphragm strength in patients with severe, nonbullous diffuse emphysema.

Patient Selection

Thirty-seven patients were evaluated for LVRS. Twenty-four patients underwent 8 wk of intensive outpatient pulmonary rehabilitation. A total of 20 patients, including seven of the previous 24 patients who underwent 8 wk of pulmonary rehabilitation, met LVRS criteria shown in Table 1. After being considered an acceptable candidate, patients had the protocol and LVRS explained to them in detail (Figure 1). The study was approved by our Institutional Review Board for Human Research (Temple University School of Medicine, Philadelphia, PA).


Inclusion criteria
A.New York Heart Association Class III–IV
B.Evidence of airflow obstruction and hyperinflation by pulmonary function studies (i.e., FEV1 < 30% of predicted, postbronchodilator administration, FRC or TLC > 120% of predicted)
C.Hyperinflation documented by chest X-ray and diffuse bullous emphysema documented by high-resolution CT scan
D.Ventilation–perfusion mismatch documented in planned resected lung tissue by quantitative ventilation perfusion lung scan
Exclusion criteria
A.Patients with severe and refractory hypoxemia (PaO2 /Fi O2 ratio < 150)
B.Severe hypercapnic respiratory failure requiring mechanical ventilation
C.The presence of significant cardiovascular disease
D.The presence of severe pulmonary hypertension (mean pulmonary artery pressure > 50 mm Hg)
E.Severe debilitated state with total body weight < 70% of ideal body weight
F.Presence of significant extrapulmonary end organ dysfunction expected to limit survival
G.Psychosocial dysfunction
H.Continued smoking
Definition of abbreviation: CT = computed tomography.

Physiologic Measurements

Before and 8 wk after rehabilitation, 24 subjects performed a variety of pulmonary function studies (e.g., spirometry before and after bronchodilator administration, lung volumes measured by helium dilution and body plethysmography, diffusion capacity), incremental symptom-limited maximum exercise test, 6-min walk test, measurement of volitional maximum static inspiratory and expiratory mouth pressures, and transdiaphragmatic pressures measured during maximum static inspiratory efforts and during bilateral supramaximal twitch electrophrenic stimulation. Thirteen patients had similar physiologic measurements before and 3 mo after LVRS. In addition, seven patients had the preceding measurements made before and after 8 wk of outpatient pulmonary rehabilitation and then 3 mo post-LVRS.

Pulmonary function testing. Pulmonary function testing was performed (13) with a System 6200 Autobox DL plethysmograph (SensorMedics Corp., Yorba Linda, CA), using American Thoracic Society guidelines. Vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC were measured. Airway resistance (Raw) and thoracic gas volumes were measured in a body plethysmograph. Functional residual capacity (FRC) was also measured by helium dilution technique. FRCtrapped gas is the difference between FRC measurements made by body plethysmography and helium dilution.

Diffusion capacity for carbon monoxide (Dl CO) was measured by the single-breath technique. It is reported as the carbon monoxide-diffusing capacity per unit of alveolar volume (Dl CO /Va).

Maximum voluntary ventilation (MVV) was measured with the subjects seated upright and instructed to breathe maximally in a deep and rapid manner for a sustained period of 12 s. At least two trials were performed, with the highest value reported.

All data reported are postbronchodilator results presented in absolute numbers and as a percentage of normal predicted values (14).

Exercise testing. Patients underwent incremental, maximal treadmill exercise (Precor, 9.4 sp; Precor, Bothell, WA) starting at 0% incline and 1 mph. Incline increased by 3% and speed by 1.5 mph every 3 min until symptom-limited maximum. Oxygen uptake (V˙o 2), carbon dioxide production (Vco 2 ), minute ventilation (V˙e), tidal volume (Vt), and respiratory rate (fb) were also recorded by a metabolic cart (SensorMedics 2900). Transcutaneous oxygen saturation (Nellcor N-200, Nellcor, Chula Vista, CA) and multiple-lead EKG (ECG Horizon; SensorMedics) were continuously recorded. Patients requiring oxygen with exercise used the same level of inspired oxygen at each exercise evaluation. At each exercise test conclusion, dyspnea was rated using a visual analog scale from 0 (no breathlessness) to 10 (severe breathlessness) (15). On a different day, a walk distance test was measured, with subjects encouraged to ambulate in a 100-ft corridor their maximum distance in 6 min (16).

Respiratory muscle pressures. Mouth pressures were measured using a previously reported technique (17). Pi max was measured from functional residual capacity (FRC), whereas Pe max was measured near total lung capacity (TLC). Tests were repeated until at least three attempts varied less than 5%, the average of three tests were then reported.

Transdiaphragmatic pressure measurement. Following topical anesthesia (4% lidocaine), two thin-walled balloon-tipped catheters were placed via the nares, one into the lower esophagus (esophageal pressure, Pes) and the other into the stomach (gastric pressure, Pga) (18). Both catheters were connected to pressure transducers (range, ± 100 cm H2O; Validyne, Northridge, CA). Transdiaphragmatic pressure (Pdi) was displayed as the electronic subtraction of Pes from Pga. A plaster cast was then placed over the anterior abdomen to minimize outward displacement of the abdominal wall during electrophrenic stimulation. Voluntary Pdi was measured against an occluded airway using a combined expulsive–Mueller maneuver (Pdimax combined) during visual oscilloscopic feedback with subjects seated upright in a high-backed chair (19). In addition, maximum transdiaphragmatic pressures were measured during a maximum sniff maneuver (Pdimax sniff) (20) and uncoached maximum inspiratory effort (Pdimax). The average of three values of Pdimax during each separate maneuver, all within 5% of each other, are reported.

Electrophrenic stimulation. Compound diaphragm action potentials (CDAPs) were measured bilaterally by a pair of 3-mm EMG surface electrodes placed 2 mm apart in the seventh intercostal space in the anterior axillary line. The site for optimum phrenic nerve stimulation was located by using anatomic landmarks (21). Stimulus voltage was incrementally increased until there was no further increase in CDAP amplitude. Once maximum stimulus voltage was achieved, it was further increased by 20% to ensure supramaximal diaphragm activation.

A modified neck brace housing the right and left phrenic nerve stimulus probes was used to ensure consistency in phrenic nerve stimulation. The phrenic nerves were stimulated transcutaneously (S88 stimulator; Grass, Quincy, MA) with 100–140 V (approximately 30 mA), 0.1 ms in duration, to produce diaphragm twitch pressures (Pditwitch). There was an approximately 20 to 30 min interval between the end of maximum voluntary static maneuvers and the onset of Pditwitch testing.

Pditwitch at FRC. With the subject seated with upright posture, bilateral phrenic nerve stimulation was delivered at functional residual capacity (FRC) after closure of an in-line three-way valve at end expiration. Pes was continuously monitored to ensure that end-expiratory lung volume had returned to a consistent baseline before valve closure. Six to 15 consecutive twitches (each twitch separated by at least a 3-s pause) were delivered at FRC. Twitches analyzed were those considered acceptable after ensuring that the FRC was at baseline and twitch morphology was consistent. Three values, all within 5%, were averaged and reported as Pditwitch.

Surgical Technique

Lung resections were performed via median sternotomy and bilateral stapling (n = 19 patients) or unilateral thorascopy with stapling (1 patient). The goal for resection was to remove 20–40% of the volume of each lung, guided by the visual judgment of the same surgeon. High- resolution computed tomography of the chest and quantitative ventilation–perfusion scans were used preoperatively to target resection of lung regions with the worst emphysema, poorest perfusion, and greatest gas trapping.

Pulmonary Rehabilitation

Pulmonary rehabilitation consisted of twenty-four 2-h sessions over an 8-wk period. Rehabilitation included education, physical and respiratory care instruction; psychosocial support; and supervised exercise training by an exercise physiologist. After baseline exercise tests, all subjects received an individualized exercise prescription based on symptom-limited maximum. Patients used a motor-driven treadmill, performed arm cycling, and lifted arm and leg weights under supervision. The intensity of the program was increased on an individual basis.

Data Analysis

All data are expressed as mean ± SD except where otherwise noted. Student paired two-tailed t tests were used to compare data before and after rehabilitation and before and after LVRS. Stepwise and multiple linear regressions were used to evaluate changes associated with increases in diaphragm strength. All statistical analyses were conducted using a commercially available computer software program (Sigmastat, version 2.0; Jandel, San Rafael, CA). p Value < 0.05 was considered statistically significant.

Patient Characteristics

Baseline demographic characteristics are shown in Table 2. Baseline physiologic data are shown in Table 3. All subjects had severe airflow obstruction (FEV1, 0.69 ± 0.21 L), hyperinflation, and air trapping (TLC, 7.1 ± 1.7 L; RV, 4.7 ± 1.4 L), and decreased exercise performance (V˙o 2max 12.4 ± 3.2 ml/kg/min).


SexF (23); M (14)
Age, yr58 ± 8
Smoking, pack-years59 ± 24
Prednisone use, %39
Theophylline use, %32
β-Agonist use, %100
Anticholinergic use, %92
O2 at rest, %62
O2 during exercise, %86
Albumin, mg/dl4.0 ± 0.64
% IBW119 ± 22

Definition of abbreviation: % IBW = percent ideal body weight.


Number of patients, n37
FVC, L (% predicted)2.4 ± 0.7 (69 ± 14)
FEV1, L (% predicted)0.69 ± 0.21 (28 ± 8.3)
TLC, L (% predicted)7.1 ± 1.7 (136 ± 17)
RV, L (% predicted)4.7 ± 1.4 (246 ± 57)
Dl CO/Va, min/mm Hg2.2 ± 0.64 (57 ± 16)
PaO2 /Fi O2 322 ± 59
6 MWD, m274 ± 106
o 2max, ml/kg/min12.4 ± 3.2 (48 ± 14)
e max, L/min25.5 ± 8.6

Definition of abbreviations: FVC = forced vital capacity; FEV1 = forced expiratory volume in 1 s; TLC = total lung capacity; RV = residual volume; Dl CO/Va = diffusion capacity/alveolar volume; 6 MWD = 6-min walk distance; V˙ o 2max = maximum oxygen consumption during symptom-limited exercise test; V˙ e max = maximum minute ventilation during symptom-limited exercise test.

Physiologic Data before and after 8 wk of Pulmonary Rehabilitation

Spirometry and lung volumes. Table 4 shows spirometry, lung volumes, and diffusing capacity before and 8 wk after rehabilitation in 24 subjects. FVC, FEV1, and FEV1/FVC were not different before and after rehabilitation, TLC, RV, FRCtrapped gas, and FRC were either slightly increased or unchanged after rehabilitation. Raw was significantly decreased but Dl CO/Va remained unchanged.


Baseline (n = 24)8 Weeks Postrehabilitation (n = 24)
ActualPercentage PredictedActualPercentage Predictedp Value
FVC, L2.43 ± 0.6871 ± 132.45 ± 0.6473 ± 150.72
FEV1, L0.74 ± 0.230 ± 7.20.75 ± 0.230 ± 7.60.53
FEV1/FVC0.31 ± 0.040.30 ± 0.030.55
Body plethysmography
TLC, L6.8 ± 1.2134 ± 167.1 ± 1.4138 ± 180.05
RV, L4.3 ± 0.9231 ± 374.6 ± 1.2240 ± 520.09
FRC, L5.4 ± 1.0180 ± 315.4 ± 1.3182 ± 300.92
FRC, L (helium dilution)* 4.5 ± 1.2157 ± 394.2 ± 1.0145 ± 310.04
FRCtrapped gas, L0.9 ± 0.91.2 ± 1.10.06
MVV, L31 ± 1033 ± 110.10
Dl CO/Va, min/mm Hg2.3 ± 0.659 ± 172.3 ± 0.860 ± 200.4
Raw, cm H2O/L/s5.8 ± 2.3404 ± 1274.9 ± 1.5344 ± 880.03

Definition of abbreviations: FRC = functional residual capacity; MVV = maximum voluntary ventilation; Raw = airway resistance; FRCtrapped gas = difference between FRC measured by body plethysmography and helium dilution techniques.

*n = 22.

n = 20.

n = 18.

Gas exchange and exercise performance. Table 5 shows gas exchange and cardiopulmonary exercise studies before and after rehabilitation. Oxygenation and Pco 2 were not different following rehabilitation. V˙o 2max, V˙e max, Vt max, and maximum respiratory rate were also not different postrehabilitation during maximum exercise. Total exercise time was greater postrehabilitation (6.9 ± 1.7 versus 5.9 ± 1.6 min, p < 0.002), but the 6-min walk distance was unchanged.


Baseline (n = 22)8 Weeks Postrehabilitation (n = 22)p Value
Gas exchange
PaO2 /Fi O2 331 ± 58328 ± 660.78
PaCO2 , mm Hg45 ± 645 ± 70.87
6 MWD,* m293 ± 105300 ± 1110.57
Symptom-limited maximal  treadmill exercise
Total exercise time, min5.9 ± 1.66.9 ± 1.70.002
o 2max, ml/kg/min13.1 ± 3.212.9 ± 2.80.6
e max, L/min28 ± 927 ± 80.31
Vt max, L0.9 ± 0.290.9 ± 0.300.37
fbmax, breaths/min36 ± 936 ± 70.81

Definition of abbreviations: Vt max = maximum tidal volume; fbmax = maximum breathing frequency.

*n = 24.

n = 23.

Respiratory muscle strength. Table 6 shows maximum mouth and transdiaphragmatic pressures, and Pditwitch before and after pulmonary rehabilitation. Respiratory muscle function did not change following rehabilitation. Pdimax, Pditwitch, Pi max, Pdimax sniff, Pdimax combined, Pe max, and Pdi Tti were similar before and after rehabilitation.


Baseline (n = 22)Postrehabilitation (n = 22)p Value
Pi max, cm H2O48 ± 2153 ± 230.17
Pe max, cm H2O89 ± 3393 ± 350.11
Pdimax combined,* cm H2O67 ± 3371 ± 410.5
Pdimax sniff, cm H2O63 ± 2968 ± 300.33
Pdimax, cm H2O56 ± 2762 ± 380.18
Pditwitch, cm H2O11 ± 512 ± 70.65
Pdi TTi 0.1 ± 0.050.08 ± 0.040.35

Definition of abbreviations: Pi max = maximum inspired mouth pressure; Pe max = maximum expired mouth pressure; Pdimax combined = maximum transdiaphragmatic pressure during combined expulsive-Mueller maneuver; Pdimax sniff = transdiaphragmatic pressure during maximum sniff; Pdimax = transdiaphragmatic pressure during maximum uncoached inspiratory effort; Pditwitch = transdiaphragmatic pressure during twitch stimulation; Pdi TTi = Pdi/Pdimax × Ti/Ttot.

*n = 16.

n = 20.

n = 17.

Physiologic Data before and after LVRS

Spirometry and lung volume. Table 7 shows spirometry, lung volumes, and diffusing capacity before and 3 mo after LVRS in all 20 subjects. Before surgery, subjects were severely obstructed and moderately to severely hyperinflated. Three months following LVRS, FVC increased 21%, FEV1 increased 34%, TLC decreased 13%, FRC decreased 23%, and FRCtrapped gas and residual volume decreased by 57 and 28%, respectively. Raw also decreased 34% postoperatively.


Before (n = 20)3 mo Post-LVRS (n = 20)p Value
ActualPercentage PredictedActualPercentage Predicted
FVC, L2.4 ± 0.7767 ± 172.9 ± 0.6780 ± 160.001
FEV1, L0.64 ± 0.1926 ± 90.86 ± 0.236 ± 100.001
FEV1/FVC0.31 ± 0.110.30 ± 0.070.8
Body plethysmography
TLC, L7.5 ± 1.9138 ± 216.5 ± 1.4120 ± 200.001
RV, L5.0 ± 1.7257 ± 703.6 ± 1.1189 ± 590.001
FRC, L6.0 ± 1.6193 ± 304.6 ± 1.3150 ± 300.001
FRC, L (helium dilution)* 4.4 ± 1.3140 ± 343.8 ± 1.2124 ± 300.001
FRCtrapped gas,* L1.56 ± 1.00.66 ± 0.660.001
MVV, L26 ± 935 ± 40.001
Dl CO/Va, min/mm Hg2.1 ± 0.5955 ± 162.3 ± 0.5259 ± 140.19
Raw, cm H2O/L/s7.3 ± 2.7543 ± 2224.8 ± 1.6356 ± 1270.001

For definition of abbreviations, see Table 4.

*n = 19.

Gas exchange and exercise performance. Table 8 shows gas exchange and cardiopulmonary exercise studies before and after LVRS in all patients. Postoperatively, there were no significant changes in oxygenation; however, carbon dioxide tensions were lower (44 ± 6 versus 48 ± 6 mm Hg, p < 0.003). After LVRS, 6-min walk distance (343 ± 79 versus 250 ± 89 m, p < 0.001), total exercise time (9.2 ± 1.9 versus 6.9 ± 2.7 min, p < 0.001) and V˙o 2max (15.7 ± 4 versus 11.5 ± 3 ml/kg/ min, p < 0.001) all significantly increased. Following surgery, minute ventilation (29 ± 8 versus 21 ± 6 L/min, p < 0.001) during maximum exercise was greater, and was associated with a higher tidal volume (1.0 ± 0.33 versus 0.84 ± 0.25 L, p < 0.001) and lower respiratory rate (28 ± 6 versus 32 ± 7 breaths/min, p < 0.02) at peak exercise.


8 wk (n = 20)3 mo Post-LVRS (n = 20)p Value
Gas exchange
PaO2 /Fi O2 313 ± 65322 ± 400.46
PaCO2 , mm Hg48 ± 644 ± 60.003
6 MWD, m250 ± 89343 ± 790.001
Symptom-limited maximal  treadmill exercise*
Total exercise time, min6.9 ± 2.79.2 ± 1.90.008
o 2max, ml/kg/min11.5 ± 315.7 ± 40.001
e max, L/min21 ± 629 ± 80.001
Vt max, L0.84 ± 0.251.0 ± 0.330.001
fbmax, breaths/min32 ± 728 ± 60.02

For definition of abbreviations, see Table 5.

*n = 15.

Respiratory muscle strength. Table 9 shows maximum mouth and transdiaphragmatic pressures, and Pditwitch before and after LVRS. Following surgery, Pi max, Pdimax combined, Pdimax sniff, Pdimax, and Pditwitch were all greater. Pe max was not different. Tension time index for the diaphragm (Pdi/Pdimax × Ti/Ttot), however, was lower.


Baseline (n = 16 )3 mo Post-LVRS (n = 16 )p Value
Pi max, cm H2O50 ± 1874 ± 280.002
Pe max, cm H2O80 ± 3186 ± 380.39
Pdimax combined,* cm H2O56 ± 2980 ± 250.007
Pdimax sniff, cm H2O46 ± 2771 ± 170.007
Pdimax, cm H2O51 ± 2378 ± 300.001
Pditwitch, cm H2O6.7 ± 515 ± 50.007
Pdi TTi 0.09 ± 0.030.07 ± 0.020.03

For definition of abbreviations, see Table 6.

*n = 13.

n = 14.

n = 11.

Body weight. In 20 patients who underwent LVRS, there was no significant difference in body weight before and after surgery (148 ± 23 versus 151 ± 24% IBW, p < 0.31).

Determinants of Increases in Diaphragm Strength Post-LVRS

In single regression analysis, increases in Pdimax combined, Pdimax, and Pdimax sniff were not found to correlate with the reductions in FRC (r = 0.16, p = 0.57), RV (r = 0.22, p = 0.44), RV/TLC (r = 0.29, p = 0.28), FRCtrapped gas (r = 0.26, p = 0.35), or reductions in PaCO2 (r = 0.04, p = 0.88). Similarly, no correlation was found with these parameters and the measured increases in Pdisniff, Pditwitch, and Pi max (Table 10).


Pdimax Pdisniff Pditwitch Pi max
FRC, L0.160.570.170.560.230.490.220.42
RV, L0.210.440.250.390.050.870.440.086
FRCtrapped gas, L0.260.350.380.200.390.270.420.12
PaCO2 , mm Hg0.040.880.120.680.0060.980.080.77
% IBW0.010.970.010.960.200.570.300.26

*Multiple linear regression using RV and trapped gas as dependent variables and Pi max as independent variable showed r = 0.67 and p = 0.03.

Stepwise multiple regression found that postoperative reductions in RV and FRCtrapped gas were strong determinants of the postoperative increases in Pi max (r = 0.67, p < 0.03). However, RV and trapped gas at FRC were not predictive of postoperative increases in Pdimax (r = 0.33, p = 0.49), Pditwitch (r = 0.44, p = 0.47), and Pdimax sniff (r = 0.42, p = 0.38).

Our data confirm that LVRS in patients with severe nonbullous diffuse emphysema improves spirometry and exercise tolerance and reduces lung volume (1-12). Moreover, our data show that LVRS improves diaphragm strength, lowers inspiratory muscle workload during ventilation, and affords emphysema patients a more comfortable breathing pattern (less rapid and shallow) during maximum exercise. These data clearly demonstrate that LVRS improves diaphragm, lung, and airway mechanics, in contrast to pulmonary rehabilitation alone.

The adverse effects of hyperinflation on diaphragm mechanics have been reported by others (22-29). These effects include diaphragm precontraction length foreshortening (22– 25), reduced radius of diaphragm curvature (23), impaired diaphragm blood flow (26), decreased diaphragm insertional rib cage action (27), increased internal elastic load (22), and a decrease in the area of apposition of the costal diaphragm with the chest wall (28, 29). As a result, hyperinflation reduces the diaphragm force-generating capacity and limits the ability of the patient with COPD to tolerate increased ventilatory workloads during exercise, or when complicating medical conditions occur. A treatment modality such as LVRS, that simultaneously decreases ventilatory workload and improves respiratory pump action, has the combined advantage of diminishing ventilatory workload while simultaneously improving maximum breathing capacity.

Several studies have reported the effects of LVRS on respiratory muscle recruitment during exercise and on inspiratory muscle strength. Bloch and coworkers (10) found in 19 patients with severe emphysema, who underwent bilateral or unilateral LVRS, that abdominal paradoxical motion monitored by respiratory inductive plethysmography decreased significantly during restful breathing post-LVRS. Benditt and colleagues (9) examined breathing pattern and respiratory muscle recruitment before and after LVRS by examining changes in pleural and gastric pressures. Following LVRS, they found a reduction in end-expiratory esophageal and gastric pressures at rest, and at isoexercise observed a rightward shift in the slope of the esophageal versus gastric pressure plot, suggesting increased use of the diaphragm. Although both studies suggested an improvement in diaphragm strength was responsible for the changes in breathing pattern post-LVRS, no measurements were reported.

Studies examining the effects of LVRS on respiratory muscle strength have reported conflicting results. Teschler and colleagues (12) reported the effects of LVRS on inspiratory muscle strength in 17 severely obstructed and hyperinflated patients with COPD (FEV1, 0.82 ± 0.07 L; RV, 337 ± 31%). Twelve of the 17 patients had unilateral LVRS. The investigators found that mean Pi max increased by 52% and mean Pdimax sniff increased by 28%, 1 mo postoperatively. In contrast, Martinez and co-workers (8) measured maximum mouth and transdiaphragmatic pressures in 17 subjects before and after bilateral LVRS. They found a 21% increase in Pi max after LVRS, but no significant change in Pdimax sniff. Keller and colleagues (11) found no effect of unilateral LVRS on Pi max in 25 subjects despite significant changes in spirometry, lung volume, 6-min walk test, and ventilatory function during maximum exercise testing.

Why LVRS has shown conflicting results on respiratory muscle strength in the preceding reports is unclear. Several explanations could include the small numbers of patients studied, variability in the techniques used to measure respiratory muscle strength, the effect that rehabilitation may have had on patient well-being and muscle strength, and the effect of studying respiratory and exercise mechanics at different time points post-LVRS.

Our study used a variety of techniques in measuring transdiaphragmatic pressure (both volitional and nonvolitional techniques) and found highly significant increases in maximum mouth and transdiaphragmatic pressures post-LVRS. Moreover, in contrast to earlier investigations, we are confident that these changes were not due to other factors, such as pulmonary rehabilitation, adjustments in medications, or other medical interventions. Patients who received pulmonary rehabilitation in our study (the control group) showed no improvements in maximum mouth or transdiaphragmatic pressures despite comparable medical care by the same clinicians.

Although it has been hypothesized that LVRS improves diaphragm function by reducing end-expiratory lung volume, we failed to demonstrate correlations between changes in transdiaphragmatic pressures and reductions in lung volume. Increases in Pi max post-LVRS tended to correlate with reductions in residual volume (r = 0.44, p = 0.08) and multiple linear regression with RV, FRCtrapped gas and Pi max showed significance (r = 0.67 and p = 0.03). It is unclear why Pi max showed a correlation with a reduction in RV while transdiaphragmatic pressure did not. The larger number of subjects studied with Pi max, and the lesser degree of variability in its measurement than in measurements of transdiaphragmatic pressure between subjects, may be potential factors.

Besides a reduction in lung volume, other factors, such as electrolyte abnormalities, or a learning effect in the performance of repeated respiratory tasks, could have been partially responsible for the improvements in diaphragm strength that we found post-LVRS. However, none of our patients had electrolyte imbalances before or after surgery and our control group of rehabilitation patients performed a similar number of repeated ventilatory tasks.

In addition to a reduction in end-expiratory lung volume, a decrease in the arterial partial pressure for carbon dioxide, an increase in body weight, and a change in thoracoabdominal configuration postoperatively all could have been important factors contributing to increases in diaphragm strength. Hypercapnia has been reported to affect diaphragm contractility adversely (30). Autopsy studies have shown that a reduction in body weight is associated with a significant loss in diaphragm mass, thickness, and area (31), and these changes have been shown to decrease maximum respiratory pressures and reduce respiratory reserve (32). In our study, patient body weight did not change post-LVRS. The fact that Pe max was not increased after LVRS suggests that systemic factors, such as electrolyte changes or a reduction in hypercapnia, did not substantially affect global measurements of respiratory muscle strength.

A significant reduction in corticosteroid use postoperatively also could have had a beneficial impact on diaphragm strength. Several human (33) and animal (34) studies have shown the detrimental effects of steroids on diaphragm structure and function. Whether the reduction in postoperative steroid use accounts for some of the increase in diaphragm strength that we observed postoperatively is unclear from our results and cannot be discounted.

One limitation to our study is that diaphragm strength was measured only 3 mo after surgery, a time at which maximum postoperative changes in diaphragm length may not yet have occurred. Similowski and colleagues (35) have shown that adaptive changes may occur in the diaphragm in chronically hyperinflated patients with COPD. In eight well-nourished, chronically hyperinflated, but stable patients with COPD (FEV1, 1.06 ± 0.4 L; TLC, 7.85 ± 1.13 L [mean ± SD]), they demonstrated that while Pditwitch at FRC was lower than that found in normal control subjects, at increased comparable lung volumes (TLC), patients with COPD tended to have greater Pditwitch values.

In our study, measurement of diaphragm strength at one time point (3 mo postoperatively) may not have reflected final diaphragm muscle adaptation to its new precontraction length. We may have underestimated the effects of lung reduction surgery on increasing diaphragm force generation if the diaphragm is still operating on the ascending limb of the length– tension curve and undergoing further lengthening. It is hoped that future studies will evaluate the effects of surgical reductions in lung volume on diaphragm force generation in sequential fashion, so as to determine the maximum effects of acute lung reductions on diaphragm force generation.

Patients receiving comprehensive outpatient pulmonary rehabilitation in our study failed to show any significant changes in lung function, as has been previously reported by others. Similar to a large prospective, randomized controlled trial conducted by Ries and collegues (36), we found significant increases in treadmill endurance time during maximum exercise testing. However, the increase in endurance we report is much less than that reported by Ries and coworkers, whose patients were less obstructed and hyperinflated (FEV1, 1.21 ± 0.55 L, RV/ TLC, 60%) suggesting that their patients were able to tolerate more intensive rehabilitation that resulted in greater improvements.

In summary, LVRS results in significant improvements in spirometry, exercise performance, and diaphragm strength in patients with severe, diffuse, nonbullous emphysema and hyperinflation. Future studies are needed to confirm our results and to determine the long-term stability of these favorable changes over time.

The authors acknowledge the efforts of physical therapy, respiratory therapy, and nursing staff in the care of patients involved in this study. Also, the authors acknowledge the helpful comments of Dr. Gilbert D'Alonzo and the secretarial assistance of Darlene Macon.

1. Cooper J. D., Trulock E. P., Triantafillou A. N., Patterson G. A., Pohi M. S., Deloney P. A., Sundaresan R. S., Roper C. L.Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J. Thorac. Cardiovasc. Surg.1091995106119
2. Gaissert H. A., Trulock E. P., Cooper J. D., Sundaresan R. S., Patterson G. A.Comparison of early functional results after volume reduction or lung transplantation for chronic obstructive pulmonary disease. J. Thorac. Cardiovasc. Surg1111996296307
3. Naunheim K. S., Keller C. A., Krucylak P. E., Singh A., Ruppel G., Ostrloh J. F.Unilateral video-assisted thoracic surgical lung reduction. Am. Thorac. Surg.61199610921098
4. Little A. G., Swain J. A., Nino J. J., Probhu R. D., Schlachter M. D., Barcia T. C.Reduction pneumoplasty for emphysema early results. Ann. Surg.2221995365374
5. McKenna R. J., Brenner M., Gelb A. F., Mullin M., Singh N., Peters H., Panzera J., Calmese J., Schein M. J.A randomized prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema. J. Thorac. Cardiovasc. Surg.1111996317322
6. Keenan R. J., Landreneau R. J., Sciurba F. C., Ferson P. F., Holbert J. M., Brown M. C., Fetterman L. S., Bowers C. M.Unilateral thorascopic surgical approach for diffuse emphysema. J. Thorac. Cardiovasc. Surg1111996308316
7. Sciurba F. C., Rogers R. M., Keenan R. J., Slivka W. A., Gorcsan J., Ferson P. F., Holbert J. M., Brown M. L., Landreneau R. J.Improvement in pulmonary function and elastic recoil after lung reduction surgery for diffuse emphysema. N. Engl. J. Med334199610951099
8. Martinez F. J., Montes de Oca M., Whyte R. I., Stetz J., Gay S. E., Celli B. R.Lung volume reduction improves dyspnea, dynamic hyperinflation, and respiratory muscle function. Am. J. Respir. Crit. Care Med.155199719841990
9. Benditt J. O., Wood D. W., McCool F. D., Lewis S., Albert R. K.Change in breathing and ventilatory muscle recruitment patterns induced by lung volume reduction surgery. Am. J. Respir. Crit. Care Med.1551997279284
10. Bloch K. E., Yiming L., Zhang J., Bingisser R., Kaplan V., Weder W., Russi E. W.Effect of surgical lung volume reduction on breathing patterns in severe pulmonary emphysema. Am. J. Respir. Crit. Care Med.1561997553560
11. Keller C. A., Ruppel G., Hibbett A., Osterloh J., Waunheim K. S.Thorascopic lung volume reduction surgery reduces dyspnea and improves exercise capacity in patients with emphysema. Am. J. Respir. Crit. Care Med.15619976067
12. Teschler H., Stamatis G., El-Raouf F. A. A., Farhat, Meyer F. J., Costabel U., Konietzko N.Effect of surgical lung volume reduction on respiratory muscle function in pulmonary emphysema. Eur. Respir. J.9199617791784
13. American Thoracic SocietyLung function testing: Selection of reference values and interpretative strategies. Am. Rev. Respir. Dis.144199112021218
14. SensorMedics Corporation. 1992. Normal Predicted Equation Sets: Operator's Manual. SensorMedics Corporation, Yorba Linda, CA.
15. Burdon J. G. W., Juniper E. F., Killian K. J., Hargreave F. E., Campbell E. J. M.The perception of breathlessness in asthma. Am. Rev. Respir. Dis1261982825828
16. Guyatt G. H., Pugsley S. O., Sullivan M. J., Thompson R. J., Berman L., Jones N. L.Effect of encouragement on walking test performance. Thorax391984818822
17. Black L. F., Hyatt R. E.Maximal respiratory pressures: normal values and relationship to age and sex. Am. Rev. Respir. Dis991969696702
18. Milic-Emili J., Mead J. J., Turner J. M., Glauser E. M.Improved technique for estimating pleural pressure from esophageal balloons. J. Appl. Physiol.191964207211
19. Laporta D., Grassino A.Assessment of transdiaphragmatic pressure in humans. J. Appl. Physiol58198514691476
20. Laroche C. M., Mier A. K., Moxham J., Green M.The value of sniff esophageal pressures in the assessment of global inspiratory muscle strength. Am. Rev. Respir. Dis1381988598603
21. Sarnoff S. J., Sarnoff L. C., Whitenberger F. L.Electrophrenic respiration: VII. The motor point of the phrenic nerve in relation to external stimulation. Surg. Gynecol. Obstet.931951190196
22. Smith J., Bellemare F.Effect of lung volume on in vivo contraction characteristics of human diaphragm. J. Appl. Physiol62198718931900
23. Minh V., Dolan G. F., Konopka R. F., Moser K. M.Effect of hyperinflation on inspiratory function of the diaphragm. J. Appl. Physiol.4019766773
24. Evanich M. J., Franceo M. J., Lourenco R. V.Force output of the diaphragm as a function of phrenic nerve firing rate and lung volume. J. Appl. Physiol.351973208212
25. Kim M. J., Druz W. S., Danon J., Machnach W., Sharp J. T.Mechanics of the canine diaphragm. J. Appl. Physiol.411976369382
26. Kawagoe Y., Permutt S., Fessler H. E.Hyperinflation with intrinsic PEEP and respiratory muscle blood flow. J. Appl. Physiol77199424402448
27. D'Angelo E., Sant'Ambrogio G.Direct action of contracting diaphragm on the rib cage in rabbits and dogs. J. Appl. Physiol.361974715719
28. Loring, S. H., and J. Mead. 1982. Action of the diaphragm on the rib cage inferred from a force–balance analysis. J. Appl. Physiol.: Respir. Environ. Exercise Physiol. 53:756–760.
29. Mead, J. 1979. Functional significance of the area of apposition of diaphragm to the rib cage. Am. Rev. Respir. Dis. 119(S):31–32.
30. Jaun G., Calverley P., Talamo C., Schnader J. Y., Roussos C.Carbon dioxide impairs diaphragm function in man. N. Engl. J. Med.3101984874879
31. Arora, N. S., and D. F. Rochester. 1982. Effect of body weight and muscularity on human diaphragm muscle mass, thickness and area. J. Appl. Physiol.: Respir. Environ. Exercise Physiol. 52:64–70.
32. Rochester D. F.Body weight and respiratory muscle function in chronic obstructive pulmonary disease. Am. Rev. Respir. Dis1341986646648
33. DeCramer M., Stas K. J.Corticosteroid-induced myopathy involving respiratory muscles in patients with chronic obstructive pulmonary disease or asthma. Am. Rev. Resp. Dis1461992800802
34. Ferguson G. T., Irvin C. G., Cherniack R. M.Effects of corticosteroids on diaphragm function and biochemistry in the rabbit. Am. Rev. Respir. Dis1411990156163
35. Similowski T., Yan S., Gauthier A. P., Macklem P. T., Bellemare F.Contractile properties of the human diaphragm during chronic hyperinflation. N. Engl. J. Med.3251991917923
36. Ries A. L., Kaplan R. M., Linberg T. M., Prewitt L. M.Effects of pulmonary rehabilitation on physiologic and psychosocial outcome in patients with chronic obstructive pulmonary disease. Ann. Intern. Med.1221995823832
Correspondence and requests for reprints should be addressed to Gerard J. Criner, M.D., Professor of Medicine, Director, Pulmonary and Critical Care Medicine, Temple University School of Medicine, 3401 North Broad Street, Philadelphia, PA 19140. E-mail:


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