INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Since its reintroduction by Cooper and colleagues (1, 2) and Wakabayashi (3) in the early 1990s, lung volume reduction surgery (LVRS) has emerged as a useful therapeutic option for patients with severe, nonbullous emphysema. In a majority of carefully selected patients, LVRS has been shown to improve dyspnea, exercise tolerance, and quality of life (1), though the pathophysiologic mechanisms responsible for these improvements are still not fully understood (7). The major early effects of LVRS are a reduction in static lung volumes, in particular functional residual capacity (FRC) and residual volume (RV), and an increase in lung elastic recoil, which leads to a reduction in the degree of airflow obstruction and dynamic pulmonary hyperinflation (1).

In addition to its effects on lung and airway mechanics, LVRS improves the function of the respiratory muscles, in particular the diaphragm. Global inspiratory muscle strength, as assessed by mouth pressure during maximal static inspiratory efforts (8) and by nasal pressure during sniffs (8), has shown consistent short-term improvements after surgery. A similar observation has been made for transdiaphragmatic pressure (Pdi) measured during sniffs (9) and Mueller (10, 13) or combined Mueller-expulsive (11) maneuvers, and during supramaximal twitch stimulation of the phrenic nerves (11, 13). In addition, the contribution of the diaphragm to inspiratory pressure generation and tidal volume has been reported to increase, both at rest (13) and during exercise (14, 15). Thus, by decreasing the load placed on the respiratory muscle pump and increasing diaphragmatic strength, LVRS enhances diaphragmatic neuromechanical coupling (13), reduces dyspnea, and improves maximal ventilatory and exercise capacity.

The improvement in diaphragm function has been ascribed, at least in part, to a reduction in muscle foreshortening (16) and flattening produced by the hyperinflation. The effects of LVRS on diaphragm dimensions, however, have only been assessed by a single study based on standard chest radiographs, which had several technical limitations and did not include any measurement of diaphragm configuration (17). In the present study, we have used a technique of three-dimensional (3D) diaphragm imaging based on spiral computed tomography (CT) (16, 18) to assess diaphragm dimensions and configuration at different lung volumes in 11 patients before and after LVRS, and in 11 matched normal subjects.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Patients

Eleven patients who fulfilled the previously published inclusion and exclusion criteria for LVRS (19) were recruited from two medical centers (Erasme University Hospital, Brussels, Belgium [n = 3] and University Hospital, Zürich, Switzerland [n = 8]). All patients had severe emphysema and hyperinflation, but they were clinically stable at the time of the studies, which were performed immediately before and at least 3 mo after surgery. Six patients were treated orally with prednisolone before surgery, at a dose of less than 15 mg/d. The study was approved by the Human Studies Committee of the respective institutions, and informed consent was obtained from each patient. No systematic preoperative and postoperative rehabilitation was performed.

Normal Control Subjects

Eleven nonsmoking normal subjects who had no history of respiratory disease and had normal standard pulmonary function tests underwent measurements of diaphragm surface area and curvature. They were matched for age, sex, height, and weight with the patients.

Surgical Technique

Bilateral lung resections were performed via a median sternotomy in three patients (in Brussels) and by thoracoscopy in eight patients (in Zürich). The goal for resection was to remove 20 to 40% of the volume of each lung, guided by the visual judgment of the surgeon. Target areas for surgical resection were identified preoperatively with quantitative ventilation-perfusion scans and high-resolution CT.

Physiologic Measurements

Measurements of FRC, TLC, and RV were obtained with the patient seated in a constant-volume body plethysmograph, and measurements of FEV₁ were made using a Sensormedics 2400 Unit (Sensormedics, Anaheim, CA) following the guidelines of the American Thoracic Society (20). Only postbronchodilator values expressed as a percent of the predicted values (21) are reported. Six-minute walk distance was measured in all patients in an air-conditioned hall following standard instructions (22).

Diaphragm Imaging

The spiral CT technique used to obtain 3D reconstructions of the diaphragm (Figure 1) and to measure supine lung volumes, and the method used to compute the surface area of the diaphragm (A_di), of the dome (A_do), and of the zone of apposition (A_ap) has been previously described in detail (16, 18, 23). For determination of the mean curvature of the dome (23), a second-order polynomial was fitted to selected coronal and sagittal slices by means of a least-mean-square fit. The mean curvature was then calculated (23) for slices that yielded a reasonably good fit (r²  0.7); a r² value below 0.7 generally indicated a flat muscle without well-defined curvature. By convention, a positive sign was given to curvatures that were concave toward the abdomen, and a negative sign was given to curvatures that were convex toward the abdomen. In the coronal plane, the right and left curvatures were calculated as the average curvatures of three retrocardial slices. In the sagittal plane, three right and three left midsagittal slices were used. We selected these specific slices because they did not include portions of the dome apposed to the heart or the mediastinum where the contour of the muscle cannot be precisely identified.

View larger version (44K): [in this window] [in a new window]   Figure 1.   Three-dimensional reconstruction of diaphragm at FRC in one patient with emphysema before (A) and after (B) LVRS. Reconstruction is shown from a posterior-superior left lateral perspective.

Data Analysis

Data are expressed as mean ± SE throughout the text, Tables, and Figures. Statistical analyses were performed using Student's paired and unpaired t tests, when appropriate. A p value of less than 5% was considered statistically significant.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Patients Characteristics

Six men and five women with a mean age of 57.5 ± 2.9 yr were studied before and at a median time of 94 d after surgery. The anthropometric and functional characteristics of the 11 patients and control subjects are shown in Table 1. Before surgery, the patients were severely obstructed and hyperinflated. Surgery produced significant (p < 0.001) reductions in TLC (19.0 ± 2.9%), FRC (30.4 ± 3.5%), RV (35.3 ± 3.2%), and RV/TLC (19.4 ± 4.9%). There was a 51 ± 11% increase in FEV₁ for the group as a whole, and only two patients experienced a less than 20% increase in FEV₁. Postoperatively, there was no significant change in blood gas measurements, but the 6-min walk distance increased significantly (p < 0.01). All patients also reported improved function during their activities of daily living after LVRS.

Comparison of Diaphragm Dimensions between Patients before LVRS and Normal Control Subjects

A_di and A_ap decreased as lung volume increased in both the normal subjects and the patients; as a result, A_di and A_ap at FRC were reduced in the patients to 77 ± 6% and 53 ± 5% (p < 0.001) of the values measured in the normal subjects. In contrast, A_do changed little with lung volume, and its value at FRC was not significantly different in the two groups. As observed in our previous study (16), the relationships between diaphragm surface area and lung volume in the two groups fitted almost a single line.

In the normal subjects, only one of 132 (11 subjects × 2 planes × 3 volumes × 2 sides) sets of coronal and sagittal slices had a r² value of less than 0.7 for the fit of diaphragm curvature, and the dome was always concave toward the abdomen. Four of the 11 patients had 10 sets of slices with r² values below 0.7, and on seven occasions, this was observed on the left side in the sagittal plane; furthermore, in one of these four patients and in two additional patients the left portion of the dome was convex toward the abdomen in the sagittal plane at TLC. Average values for right and left curvatures in the coronal and sagittal planes as a function of lung volume are shown in Figure 2. In the two groups, the curvature of the dome was greater in the coronal than in the sagittal plane (p < 0.001), and values of curvature decreased as lung volume increased. The difference in muscle curvature at FRC between normal subjects and patients reached statistical significance in the sagittal (p < 0.001) but not in the coronal plane.

View larger version (23K): [in this window] [in a new window]   Figure 2.   Average values (± SE) of diaphragm curvature measured at FRC, midinspiratory capacity, and TLC and plotted as a function of supine lung volume in 11 patients with emphysema before LVRS and 11 normal control subjects. Curvature (which is the inverse of radius of curvature) is expressed in cm1.

Comparison of Diaphragm Dimensions between Patients before and After LVRS

Average values for A_di, A_ap, and A_do as a function of supine lung volume in 11 patients before and after LVRS are displayed in Figure 3. Data obtained postoperatively were displaced toward smaller lung volumes, but here again, the relationships between diaphragm surface area and lung volume before and after surgery fitted almost a single line. At FRC, LVRS increased A_di and A_ap by 17 ± 4% (p < 0.02) and 43 ± 8% (p < 0.001), respectively, but it had no effect on A_do. Surgery also increased the proportion of total surface area apposed to the rib cage (A_ap/A_di) at FRC from 40 ± 1% to 49 ± 2% (p < 0.001). Despite these improvements, postoperative values of A_di, A_ap, and A_ap/A_di at FRC were still 11% (p < 0.05), 24% (p < 0.005), and 16% (p < 0.001) smaller than the values recorded in the normal subjects. As expected, the change in A_di at FRC was inversely correlated with the change in FRC, but this correlation was weak (r = 0.47) because two patients did not experience any increase in diaphragm dimensions after surgery. Average preoperative and postoperative values of left and right diaphragm curvature in the coronal and the sagittal planes at the three lung volumes studied for slices with r²  0.7 are shown in Figure 4. Surgery had no significant effect on curvature, except in the left sagittal plane at TLC where the curvature increased significantly after LVRS (p < 0.001). It should be stressed, however, that all patients after surgery had curvatures that were concave toward the abdomen.

View larger version (18K): [in this window] [in a new window]   Figure 3.   Average values (± SE) of total surface area of the diaphragm (Adi), surface area of the dome (Ado), and surface area of the zone of apposition (Aap) measured at FRC, midinspiratory capacity, and TLC and plotted as a function of supine lung volume in 11 patients with emphysema before and after LVRS.

View larger version (42K): [in this window] [in a new window]   Figure 4.   Average values (± SE) of diaphragm curvature at FRC, mid-inspiratory capacity (FRC+), and TLC in 11 patients with emphysema before and after LVRS. Curvature (which is the inverse of radius of curvature) is expressed in cm1. ***p < 0.001.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

The effects of LVRS on static and dynamic lung volumes, gas exchange, and 6-min walk distance reported here are very similar to those found by previous investigators (1). The following discussion will therefore focus on the effects of emphysema and LVRS on diaphragm dimensions and configuration.

Effects of Emphysema on Diaphragm Dimensions and Configuration

The current studies have shown that patients with severe emphysema have marked reductions in A_di and A_ap at FRC, but they have diaphragm dimensions similar to those of normal subjects when compared at similar absolute lung volumes. These results are in all respects similar to those reported in our previous work (16). A few studies using CT or MRI have provided qualitative information on the shape of the diaphragm in normal subjects (24) and emphysema patients (26), but to the best of our knowledge, no quantification of diaphragm curvature has been reported so far. In the normal subjects, we found that the muscle curvature decreased gradually on going from FRC to TLC, but that the effect of lung volume was relatively small (the change in curvature was  0.013 cm¹/L). As a result, although the curvature of the muscle at FRC was smaller in the patients than in the normal control subjects, this difference reached statistical significance only in the sagittal plane. In addition, despite the fact that the patients were markedly hyperinflated (i.e., their FRC was similar to the predicted TLC), none of them had a diaphragm convexity directed downward at FRC. Altogether, these observations thus confirm that motion of the diaphragm from FRC up to volumes corresponding to the predicted TLC may be adequately modeled as the axial motion of a (widening) piston in a cylinder (24, 27), i.e., the increase in volume is accommodated by descent of the dome through a reduction in A_ap. This model, however, may not apply at volumes greater than the predicted TLC. Values of sagittal and right coronal curvature were significantly smaller (p < 0.001) at TLC in the patients than at any lung volume in the control subjects (Figure 2), and six of 11 patients had a muscle that was either flat or had a convexity directed downward in the sagittal plane at FRC+ and TLC. This suggests that the diaphragm has to undergo substantial changes in configuration to accommodate increases in volume in excess of the predicted TLC where there is very little or no more muscle apposed to the rib cage.

Effects of LVRS on Diaphragm Dimensions and Configuration

LVRS produced significant increases in A_di, which were entirely accounted for by increases in A_ap. Yet, despite this improvement, postoperative values of A_di, A_ap, and A_ap/A_di at FRC remained significantly smaller than normal. The mechanism underlying the increase in A_di and A_ap after LVRS is likely to be the reduction in the degree of hyperinflation. However, the relationship between the reduction in FRC and the increase in A_di did not reach statistical significance because two patients with approximately 20% decreases in FRC did not modify their diaphragm dimensions. An error in the placement of the metallic wire used to identify the loci of origin of diaphragmatic fibers might explain the discordant response of these two patients (18).

Using plain chest radiographs obtained at active TLC, Lando and colleagues (17) have recently reported that the length of the right hemidiaphragm apposed to the rib cage increased after LVRS, but this increase was observed only in the coronal plane and total diaphragm length did not change significantly. These data are difficult to interpret and compare with the present results for several reasons. First, Lando and colleagues (17) used a technique originally proposed by Braun and colleagues (28), which is not appropriate to measure diaphragm length apposed to the rib cage at TLC. Second, length measurements obtained from plain chest radiographs may not be entirely accurate because the diaphragm silhouette is a composite picture that includes portions of the muscle that belong to different planes. Finally, changes in diaphragm length at active TLC may not be representative of those occurring at relaxed FRC because contraction of the diaphragm and other respiratory muscles may influence diaphragm dimensions.

The present study did not demonstrate any significant effect of LVRS on diaphragm curvature at FRC. Our measurements, however, were performed with the subjects in the supine posture where the weight of the abdominal contents acts to displace the diaphragm in the cranial direction; this may have minimized the preoperative alterations in configuration and the improvements provided by LVRS. Furthermore, the absence of changes in curvature at FRC does not necessarily imply that surgery had no beneficial effect on the configuration of the muscle during tidal breathing. A 1 to 1.5 liter decrease in FRC, as generally occurs with LVRS (1), will make tidal breathing take place within the normal vital capacity range rather than above the predicted TLC (Figure 2). Because the curvature of the muscle is particularly sensitive to increases in volume in excess of the predicted TLC (see above), decreasing FRC might thus reduce the alterations in curvature that occur during tidal breathing; this phenomenon might be particularly relevant when tidal volume increases, as during exercise.

In conclusion, by decreasing lung volume, LVRS makes the diaphragm dome move upward and increases the area of muscle apposed to the rib cage. On the other hand, the configuration of the muscle at supine FRC is not improved by the procedure. This is because, within the normal vital capacity range, diaphragm curvature does not change much with lung volume.