INTRODUCTION

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Surgical lung volume reduction (LVR), a novel treatment option for advanced, diffuse, pulmonary emphysema, may provide significant improvement of dyspnea and pulmonary function in carefully selected patients (1). The resection of severely destructed areas of the lungs may reduce hyperinflation and improve expiratory airflow by restoring elastic recoil (3, 5). Other mechanisms involved in the favorable effects of LVR may include improvement of the inspiratory force of the diaphragm (6) by increasing its curvature, length, and zone of apposition to the rib cage (7, 8).

Previous investigations on the respiratory mechanical effects of LVR involved instrumentation of the airway and required performance of specialized breathing maneuvers (3, 5, 6). Because of the particular measurement conditions, these data may not reflect certain aspects of physiology that are relevant during natural breathing at rest. Therefore, our purpose was to employ respiratory inductive plethysmography (RIP) for the nonobtrusive study of natural breathing patterns in patients with severe, diffuse pulmonary emphysema before and several months after LVR. RIP estimates ventilation from sensors placed around the rib cage and abdomen. The separate volume changes of the latter as well as their synergistic behavior are also measured (9). Similar information cannot be obtained by conventional spirometry. Because LVR is thought to improve the inspiratory action of the diaphragm (6), we hypothesized that it would increase the contribution of abdominal volume changes to tidal volumes (VT). Furthermore, we expected, that reduction of hyperinflation and airway obstruction by LVR would reduce rib cage-abdominal paradoxical motion, an expression of increased inspiratory muscle loading (10). By grouping patients according to surgical outcome, we tried to identify the preoperative breathing pattern characteristics associated with the greatest improvement in lung function after surgery.

	METHODS

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Patients

We studied 19 patients with advanced pulmonary emphysema (mean ± SD age, 63 ± 10 yr; range, 42 to 75 yr; six women) who underwent bilateral (17 patients) or unilateral (two patients) video-assisted thoracoscopic resection of approximately 20 to 30% of their lungs. Fourteen of them were part of a group of 20 patients who participated in a prospective study on thoracoscopic LVR. Their clinical data, surgical technique, and outcomes have been published (4). Selection criteria for surgery included dyspnea at rest or minimal exertion, radiologic signs of diffuse pulmonary emphysema without bullae occupying > 20% of the volume of either hemithorax, severe bronchial obstruction (FEV₁ < 35% of predicted) (11), severe hyperinflation (TLC > 130% of predicted) (11), and absence of substantial hypercapnia (Pa_CO2 < 55 mm Hg) (4). Eleven healthy subjects (mean age ± SD, 35 ± 5 yr; range, 30 to 47 yr; three women) recruited among hospital staff served as normal control subjects. They were nonsmokers and had normal pulmonary function studies. Patients and normal subjects gave informed consent to participate in the study, which was approved by the hospital committee for human studies.

Measurements

In each patient breathing patterns were recorded with computer- assisted respiratory inductive plethysmography (RIP) (RespitracePT; Noninvasive Monitoring Systems, Inc., Miami Beach, FL) (12) at two occasions: within 1 mo before surgery (preoperatively) and 1.5 to 7 mo after surgery (postoperatively). In addition, in four patients (three preoperatively, one postoperatively) repeated recordings for 3 successive days were obtained to assess day-to-day variability of breathing patterns. In all 19 patients recordings were obtained during relaxed wakefulness while they rested in a supine position, and in five patients additional recordings were also obtained in a 60° head-up position achieved by means of a tilt table. In all normal subjects, breathing patterns were recorded in supine and in 60° head-up positions. The order of body position (either first supine or first 60° head-up) was random. Transducers were placed around the chest, within 3 cm below the nipples, and around the abdomen at the level of the umbilicus. Qualitative diagnostic calibration (QDC) (13) for 5 min of natural breathing provided the relative gains for the rib cage and abdominal signals. Their sum was calibrated in liters by comparison with the output of a spirometer. Then, breathing patterns were recorded for at least 20 min without physical connection of the airway to any instrumentation. At the end of the recording sessions accuracy of RIP calibration was verified by comparison of the RIP sum signal with the spirometer output over 20 to 40 breaths. The calibration and validation procedures were repeated after changes in body position from supine to 60 ° head-up and vice versa. The bias (mean difference from spirometric values) and limits of agreement (mean difference from spirometric values ± 2 SD) for tidal volume (VT) measurements by RIP were 2% ± 13% in patients, and 2% ± 14% in normal subjects, respectively (14). Lung volumes were measured by spirometry and body plethysmography (11). Arterial blood gas analyses were also obtained. Dyspnea was assessed by the Medical Research Council Dyspnea Score (15).

Data Analysis

Computer-assisted breathing pattern analysis was performed with dedicated software (RespiEvents version 4.3an; Noninvasive Monitoring Systems). Graphic analysis included time series and rib cage versus abdominal volume (Konno and Mead) plots (9). The parameters listed in Table 1 and illustrated in Figure 1 were measured breath by breath. Rib cage-abdominal synchrony was quantified by calculating their relative phase shift (phase angle) according to the method described by Agostoni and Magnoni (16). Paradoxic motion as percent of time period of inspiratory and expiratory compartmental excursions was indicated when rib cage or abdominal compartments moved in an opposite direction to their sum (17). The labored breathing index (LBI) was calculated as a measure of the total amount of volume displacement of rib cage and abdomen in relation to the effective tidal volume similar to parameters described previously such as the total compartmental displacement to tidal volume ratio (18) or the maximal compartmental amplitude to tidal volume ratio (17) (Figure 1). Individual medians for each breathing pattern parameter over 250 to 350 breaths were determined with the exception of tilt table studies in which analysis was limited to periods of 45 to 55 artifact-free breaths since certain patients were not able to remain immobile for longer periods of time in the 60° head-up position. Differences between preoperative and postoperative results in patients and between patients and control subjects were evaluated by t tests for dependent and independent samples, respectively (19). The effects of body position and surgery in patients and of body position in normal subjects were evaluated by analysis of variance followed by the Newman-Keuls multiple comparisons procedure when appropriate. Statistical significance was assumed if the null-hypothesis was rejected with a probability of p < 0.05. 

View larger version (29K): [in this window] [in a new window]   Figure 1.   The principles of quantitative breathing pattern analysis of respiratory inductive plethysmographic recordings are schematically visualized by time series plots of rib cage (RC) and abdominal (AB) volumes along with their sum (Sum) (panel A) and their time derivatives corresponding to flow (panel B). Tidal volumes (VT = inspiratory amplitude of sum signal) and the duration of inspiratory (I) and expiratory (E) phases of the breathing cycles are derived from the sum signal. Asynchronous and paradoxical compartmental motion is assessed in several ways: ABParadoxI (ABParadoxE), the abdominal inspiratory (expiratory) paradox times are marked with horizontal bars (panel A). They are defined as the fractions of inspiratory (expiratory) times during which the abdomen moves in opposite direction to the sum signal. Rib cage inspiratory and expiratory paradox times (RCParadoxI, RCParadoxE) are determined in an analogous way. The LBI is computed as the sum of the integrals of absolute values of the derivatives of rib cage ( RC) and abdominal ( AB) volume signals divided by the integral of the derivative of the sum signal ( Sum) over the duration of inspiration (panel B): ···The phase angle (PhAng) between rib cage and abdominal waveforms is derived from the ratio of the distance delimited by the intercepts of the rib cage versus abdominal volume (Konno and Mead [9]) loop on a line parallel to the X-axis at 50% of rib cage tidal volume (m), divided by abdominal tidal volume (s) (panel C ). End-expiration and end-inspiration are marked by a closed circle and an open circle, respectively.

	RESULTS

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Breathing patterns in patients before LVR were characterized by deep inspirations at an elevated rate, resulting in a high ventilation () in comparison with normal subjects (Table 2). As fractional inspiratory time (TI/Ttot) was reduced, mean inspiratory flow (VT/TI), a measure that reflects respiratory center drive, was high. The fraction of inspiratory and expiratory times during which the rib cage and the abdomen moved in opposite directions to the tidal volume signal [RCParadoxI(E), ABParadoxI(E)] was considerable (Table 2 and Figure 2). Continuous rib cage versus abdominal volume plots described loops that deviated extensively from the straight line that would connect end-expiratory with end-inspiratory and again with end-expiratory points, if synchronization of the two compartments over the breathing cycle was perfect (Figure 2). Accordingly, the phase angle (PhAng), which quantifies the phase shift between rib cage and abdominal volume changes (16), was high (Table 2). In normal subjects, the 60° head-up position resulted in an increase in and VT/TI compared with values in the supine position, and the contribution of abdominal volume excursions to VT was reduced. Qualitatively similar changes in and VT/TI were observed in the five patients in whom measurements in the 60° head-up position were performed. In this position, their PhAng as well as their LBI exceeded corresponding values in the supine position (Table 2).

View larger version (32K): [in this window] [in a new window]   Figure 2.   Breathing patterns recorded with respiratory inductive plethysmography in a patient before and after surgical lung volume reduction. (Top panels) Time series plots of rib cage and abdominal volumes and their sum. Preoperatively, breathing cycles of the rib cage lagged behind that of the abdomen. During a significant fraction of inspiratory and expiratory times either the rib cage or the abdomen moved in the opposite direction to the sum signal (horizontal bars). Postoperatively the volume curves were nearly in phase, and the amount of paradoxical motion had improved. Dotted vertical lines demarcate inspiratory (I) and expiratory (E) breathing cycle phases of the sum signal. (Bottom panels) Continuous rib cage versus abdominal volume (Konno and Mead [9]) plots. Preoperatively, desynchronization between rib cage and abdominal motion is reflected in widely opened loops. Postoperatively, the loops approach the straight connection between end-expiratory (closed circles) and end-inspiratory (open circles) points, onto which they would fall if synchronization was perfect. Arrows indicate the direction of loop rotation.

Mean values of time, volume, and flow components of breathing patterns did not undergo significant changes after LVR (Table 2). However, contribution of abdominal volume displacements to VT increased significantly, and the amount of paradoxical motion of the abdomen (ABParadoxI) and the rib cage (RCParadoxI) during inspiration, as well as the phase angle (PhAng), decreased (Table 2, and Figures 2 and 3). This indicated an improvement in the synchronization of rib cage-abdominal movements. While postoperative recordings in the 60° head-up position were associated with an increase in compared with the supine position (in five patients), neither the PhAng nor the LBI were increased by the postural stress, which was in contrast to the preoperative findings.

View larger version (26K): [in this window] [in a new window]   Figure 3.   Effect of surgical lung volume reduction on contribution of abdominal volume changes to tidal volume (AB/VT) (top panel ) and on the fraction of inspiratory time with paradoxical abdominal motion (ABParadoxI) (bottom panel ). Individual values of 19 patients and group means (horizontal lines) are displayed.

In four patients, in whom repeated measurements on 3 consecutive days were obtained, variability, as assessed by calculation of the coeffients of variation, was greatest for the fraction of inspiration and expiration with paradoxical motion of the abdomen, and lowest for Ttot (Table 3).

Pulmonary function testing demonstrated significant postoperative reduction of hyperinflation and airway obstruction. Arterial blood gas analysis revealed normocapnia (range of Pa_CO2, 8 to 45 mm Hg) with mild hypoxemia (range of Pa_O2, 54 to 90 mm Hg) preoperatively that was slightly improved after surgery (Table 4). Sensation of breathlessness after LVR had improved in 18 patients and remained unchanged in one (Table 4).

Patients with the greatest postoperative improvement in airway obstruction (as assessed by an increase in FEV₁ > 30%, n = 9) and hyperinflation (as assessed by a > 15% decrease in the RV/TLC ratio, n = 13) did not significantly differ from the rest of the patients (with an increase in FEV₁  30% and a decrease in RV/TLC  15%, respectively) neither with respect to conventional preoperative pulmonary function nor to breathing pattern parameters, with the exception of a relatively well-preserved abdominal contribution to VT (Table 5). Separation of patients into two groups according to a preoperative AB/VT ratio > 50% or  50% revealed greater improvements in FEV₁ and RV after LVR in the former group (Table 6). None of the eight patients with a preoperative AB/VT ratio > 50% had a postoperative decrease in FEV₁ or FVC, or an increase in TLC or RV, whereas among 11 patients with preoperative AB/VT ratios  50% deterioration after LVR occurred in one and two patients for FVC and FEV₁, respectively, and in two and three patients for RV and TLC, respectively.

	DISCUSSION

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Major Findings

Our study confirms and extends previous findings of improved pulmonary function and sensation of dyspnea after LVR in patients with severe, diffuse emphysema (1). In contrast to earlier investigations, which involved instrumentation of the airway to measure pulmonary mechanics during specialized respiratory maneuvers, we intended to study breathing patterns under more natural conditions. We found that time, volume, and flow components of breathing patterns were not significantly changed after LVR. However, analysis of the separate volume changes of rib cage and abdomen revealed marked improvement of asynchronous and paradoxical motion, and the contribution of abdominal volume changes to VT increased.

Measurement Technique

For the calibration of the respiratory inductive plethysmograph the assumption is made that the RIP transducers approximate volumetric excursions of the rib cage and abdomen, which each move with a single degree of freedom. This may not apply to patients with severe chronic obstructive lung disease (COPD) who may show multiple degrees of freedom of chestwall movements (20). Because RIP measures changes in cross-sectional area enclosed by the transducers but does not track changes in shape of the chestwall, we were not able to detect deformations of the rib cage such as the lateral indrawing of its lower margins during inspiration, known as the Hoover sign (21). Furthermore, if the assumptions underlying the principles of RIP are not fulfilled, the accuracy of RIP to measure VT may be affected (9). However, the minor bias (2%) and the relatively narrow limits of agreement (bias ± 13%) of VT estimates by RIP in comparison with spirometry at the end of the recording sessions suggest that contributions of any additional degrees of freedom to lung volume changes were minor or in a constant relation to the cross-sectional areas measured by the two RIP transducers. These data validate RIP calibrated by the qualitative diagnostic calibration (QDC) procedure (13) for monitoring VT in patients with severe COPD. Day-to-day variability for the indices of timing and amplitude of breathing pattern was relatively small, but in certain patients it was considerable for parameters that reflect the amount of paradoxical motion of the abdomen [ABParadox(I, E)] (Table 3). This may hamper the interpretation of a single measurement of these parameters in an individual subject. However, the systematic trend for a postoperative decrease in ABParadox(I and E) suggests that this reflects physiologic changes associated with LVR.

Prepoperative Breathing Pattern

Consistent with previous observations in nonhypercapnic patients with COPD and moderate to severe airway obstruction the of 8.78 L/min in our patients was higher than the corresponding value of 5.90 L/min in normal subjects (Table 2) (22). This was related to higher f and greater VT in patients, although the differences in these parameters in comparison with normal control subjects were not statistically significant. Because pulmonary emphysema is associated with increased dead space ventilation (23), a high was required to avoid major increases in Pa_CO2 (> 55 mm Hg), one of our exclusion criteria for surgery. In contrast, in extremely severe COPD (mean FEV₁ 17% of predicted) associated with hypercapnia, may be reduced (24). The increased respiratory rate was achieved by a greater reduction in TI than in TE, hence TI/Ttot was reduced. This may reflect the combined effects of a high respiratory center drive, as suggested by increased VT/TI, and a prolonged relative time of expiration because of loss of elastic recoil of emphysematous lungs and increased airway resistance.

The contribution of abdominal volume changes to VT was reduced to 43% in patients in comparison with a mean value for AB/VT of 57% in normal supine subjects (Table 2). In addition, several indices of a synchrony and of paradoxical motion were elevated (Table 2). Reductions in the ratio of abdominal to rib cage VT excursions associated with paradoxical motion of the abdomen during inspiration have been previously described in COPD (17, 20). Esophageal and gastric pressure recordings suggest that this response to increased mechanical ventilatory load in COPD may relate to changes in amplitude and timing of ventilatory muscle recruitment from one where most of the effective ventilatory pressure is generated by the diaphragm to one where most of the pressure is generated by the rib cage inspiratory muscles and by expiratory muscles (25). Alternatively or in addition, changes in the ratio of rib cage to abdominal compliance may also have contributed to predominant thoracic breathing in hyperinflated patients with COPD (26). We have not recorded relaxation curves of rib cage and abdominal volumes to support this hypothesis.

Consistent with a reduced abdominal compliance and increased lung volume in the upright position (26), in normal subjects AB/VT decreased in the upright relative to the supine position (Table 2) as described previously (17, 27). In patients with COPD, the effect of the 60° head-up position on AB/VT was variable, and the mean decrease in AB/VT was not statistically significant (Table 2). This may relate to the broad range of baseline (supine) values for AB/VT of 15 to 59% in the five patients in whom comparisons with the upright position were available, which may have prevented a further increase in AB/ VT in certain patients with already high supine values. Furthermore, on the basis of transdiaphragmatic pressure and EMG recordings of the diaphragm, Druz and Sharp (28) demonstrated that the response to the gravitational stress of the upright position in patients with COPD may vary in that the neural drive to the diaphragm in some, but not in all, patients increases in the upright position (28). In the current study, pronounced paradoxical and asynchronous rib cage-abdominal motion, as assessed by increases in the PhAng and LBI (Table 2), is consistent with ineffective contraction of the already flattened diaphragm because of further reduction or even reversal of its curvature in the upright position.

Effects of Surgical Lung Volume Reduction

Although the postoperative reduction of TLC, RV, and FEV₁ indicated that hyperinflation and airway obstruction were improved, Ttot, VT and remained unchanged (Table 2). Because the decrease in Pa_CO2 was minimal, no major improvement in the dead space to VT ratio seems to have occurred after LVR, if a constant CO₂ production is assumed. In patients with COPD voluntary increases of TI/Ttot at constant resulted in a transdiaphragmatic pressure-time integral approaching a fatiguing range (29). Therefore, the force reserve of their diaphragm was exhausted after minor modifications of breathing patterns. Similar mechanisms could have prevented an increase of TI/Ttot to more normal values after LVR.

Consistent with observations by Gilmartin and Gibson (20), who found a negative correlation between end-expiratory lung volume (FRC% predicted) and the amplitude of anteroposterior tidal excursions of the abdomen in COPD, and with our hypothesis that reduction of hyperinflation after LVR improves the range of diaphragmatic motion, the contribution of abdominal volume changes to VT after LVR increased. Our data do not allow us to differentiate between various potential mechanisms of this effect, including a greater force-generating capacity of the diaphragm after LVR related to its greater curvature, and increased length of muscle fibers (8, 30), to derecruitment of accessory inspiratory muscles that act on the rib cage (31, 32), or to changes in relative compliances of rib cage and abdomen.

Asynchronous and paradoxical motion of the rib cage and abdomen has been induced by inspiratory loading and hyperinflation in normal subjects (10, 33). In patients with COPD abdominal paradoxical motion, assessed qualitatively with RIP during exercise, was progressively more pronounced with more abnormal pulmonary function (FEV₁, VC, RV/TLC) at rest (34). The reduction of the PhAng, ABParadoxI, and ABParadoxE in the supine position and the absence of an increase in asynchronous and paradoxical motion in the upright position after LVR are consistent with the expected effects of this operation, namely, reduction of hyperinflation and of the elevated elastic and resistive load associated with severe emphysema.

Correlation of Breathing Patterns with Outcome after LVR

The selection criteria for LVR vary among centers and are still evolving (3, 4, 6). In addition to clinical and radiologic criteria, they include conventional pulmonary function criteria, although in a previous study at our center, none of the conventional pulmonary function parameters was significantly correlated with objective outcome measures after LVR (4). Therefore, we evaluated whether baseline breathing pattern characteristics in patients with the greatest postoperative pulmonary function improvement differed from that in other patients. We found that patients with improvement in FEV₁ > 30% and reduction in RV/TLC > 15% had a greater abdominal contribution to VT (mean AB/VT of 51 and 55%, respectively) than did patients with changes in FEV₁  30% or RV/TLC  15% (mean AB/ VT of 34 and 38%, respectively), whereas there was no difference in any other parameter of breathing pattern or of conventional pulmonary function (Table 5). If patients were then grouped according to their preoperative AB/VT ratio, all predominantly abdominal breathers (AB/VT > 50%) experienced major improvements in all measured parameters of airway obstruction and hyperinflation (FEV₁, FVC, TLC, RV), whereas corresponding improvements were more modest or not consistently present in all of these parameters in the remaining patients (Table 6). The predictive value of breathing pattern characteristics cannot be conclusively appreciated by our data since many factors that may have had significant impact on outcome after LVR such as emphysema morphology and amount of lung tissue and volume removed during surgery, among others, could not be controlled. We believe that the role of breathing pattern analysis in conjunction with other tests employed for the evaluation of candidates for LVR deserves further study. The intraindividual reproducibility (Table 3) (35) and noninvasive nature of breathing pattern recordings make RIP a potentially attractive diagnostic tool.

The study of natural breathing pattern suggests that LVR reduces loading of respiratory muscles while ventilatory requirements remain unchanged in selected patients with advanced pulmonary emphysema. This corroborates the beneficial effects of LVR on hyperinflation, airway obstruction, and elastic recoil (1, 3, 4). Understanding the mechanisms involved in the functional improvement achieved by LVR may improve the selection and management of patients in whom this treatment is performed.