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Published ahead of print on September 11, 2002, doi:10.1164/rccm.200111-087OC
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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 1461-1469, (2002)
© 2002 American Thoracic Society

Original Article

Diaphragm Length during Tidal Breathing in Patients with Chronic Obstructive Pulmonary Disease

Robert B. Gorman, David K. McKenzie, Neil B. Pride, Jane F. Tolman and Simon C. Gandevia

Prince of Wales Medical Research Institute and University of New South Wales, Sydney, Australia

Correspondence and requests for reprints should be addressed to Prof. Simon Gandevia, Prince of Wales Medical Research Institute, Barker St., Randwick, NSW 2031, Australia. E-mail: s.gandevia{at}unsw.edu.au


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Diaphragm function is compromised in severe chronic obstructive pulmonary disease (COPD) by hyperinflation, but its ability to shorten and contribute to tidal volume is uncertain. We estimated coronal diaphragm length by measuring zone of apposition length with ultrasound and rib cage diameters with magnetometers, in 10 male patients with severe COPD and 10 age- and sex-matched control subjects. Diaphragm length was 20% shorter in patients at residual volume (413 and 536 mm in patients and control subjects, respectively) and FRC (381 and 456 mm, respectively), but was not different at total lung capacity (312 and 336 mm, respectively). Zone of apposition length was reduced 50% at residual volume and FRC in patients, but was larger at a given absolute lung volume than in control subjects. There were no differences in tidal volume (0.8 L), tidal changes in zone of apposition length (20 mm) and diaphragm length (38 and 42 mm), and tidal volume displaced by the diaphragm (0.6 L), even though mean FRC in patients was similar to predicted total lung capacity. Although the diaphragm is shorter at FRC in patients with COPD, its motion and change in length during tidal breathing is similar to that in control subjects.

Key Words: ultrasound • chronic obstructive pulmonary disease • tidal volume • diaphragm length


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Both the resistive and the elastic loads faced by the inspiratory muscles are increased in patients with severe chronic obstructive pulmonary disease (COPD). There may also be dynamic hyperinflation, which acts as an inspiratory threshold load. In addition, with hyperinflation the performance of the inspiratory pump is compromised by unfavorable length-tension properties of the inspiratory muscles. It follows that, to maintain ventilation, drive to the inspiratory muscles should be increased. Previous studies have shown increased transpulmonary pressure swings for a given tidal volume (VT) and increased acceleration of inspiratory flow and pressure in patients with COPD compared with control subjects (1). However, these global estimates of increased drive do not provide any indication of the distribution of that drive among the individual inspiratory synergists. Previous methods to evaluate the contribution of different inspiratory muscles to tidal ventilation in patients with COPD have included analysis of the separate pressure changes and/or motion of the thoracic and abdominal compartments (2–4), or quantitative measures of surface EMG normalized to the greatest activity recorded (5–7). Neural drive can be directly assessed by measurement of the discharge frequency of single motor units. Compared with age-matched control subjects, patients with severe COPD had a 20–30% increase in mean firing frequency of single motor units of the scalene and parasternal intercostal muscles (8) and a 70% increase in the discharge frequency of diaphragm motor units during resting breathing (9). These results demonstrated that inspiratory drive is increased in COPD and that diaphragmatic activation is disproportionately increased. However, it is not known to what extent the elevated firing rates of diaphragm motor units result in muscle shortening or volume displacement.

It is well accepted that the diaphragm is the principal generator of VT in normal subjects at rest. However, it is generally believed that in extreme hyperinflation the shortening capacity of the diaphragm, and hence its ability to contribute to VT, would be compromised (for review see Reference 10). Contradicting that view, it has recently been shown using fluoroscopy that diaphragm motion during tidal breathing is similar in patients with COPD and control subjects (11), but diaphragm dimensions were not measured in that study. There have been several reports comparing diaphragm length measurements in control subjects and patients with COPD. These studies have relied on imaging using either chest radiographs (3, 12, 13) or CT scans (14) to obtain static lengths of the diaphragm at specific lung volumes. Measurements of diaphragm dimensions have also been made in patients with COPD before and after lung volume reduction surgery (15–17). In addition, Singh and coworkers (13) have estimated the volume displaced by the diaphragm over the vital capacity range in patients with emphysema and control subjects using static radiographs. Dynamic MRI has recently been used by Suga and colleagues (18) to measure diaphragm and chest wall movement during slow vital capacity maneuvers in control subjects and patients with emphysema before and after lung volume reduction surgery. Ultrasonography allows accurate measurement of the length of the zone of apposition of the diaphragm against the chest wall, and combined with magnetometry allows the continuous estimation of diaphragm length under dynamic conditions (19, 20). This method eliminates the risk of radiation associated with cineradiography or videofluoroscopy, is more accessible than dynamic MRI, and has been validated by radiography in healthy subjects (21) and patients with advanced COPD (22).

We used ultrasonography and magnetometry to measure diaphragm length at different lung volumes and the breath-by-breath shortening of the diaphragm during tidal breathing in patients with COPD and control subjects. We also estimated volume displaced by movement of the diaphragm in tidal breathing. Preliminary data have been presented in an abstract (23).


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
The studies were performed on 10 male patients with severe COPD, but no significant neuromuscular, renal, hepatic, or endocrine disease, and 10 male control subjects who were matched for age and size. All of the patients had recurrent admissions to hospital for infective exacerbations and most had been treated for episodic or chronic cor pulmonale. All were using inhaled corticosteroids and had been treated with short courses of oral corticosteroids during exacerbations. The patients were all smokers or ex-smokers and their anthropometric and lung function data are listed in Table 1 . Absolute lung volumes were measured in nine of the patients with COPD and eight of the control subjects. Subjects provided written informed consent to the procedures, which were approved by the institutional human ethics committee.


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  		TABLE 1. Anthropometric and lung volume data

 
Measurement of Length of Zone of Apposition
Movement of the diaphragm was measured with a linear ultrasound probe (80 or 120 mm) placed vertically against the subject's chest wall just anterior to the right midaxillary line (images updated at 20 to 30 Hz; XP124/4; Acuson Corp., Mountain View, CA). In this position the zone of apposition of the diaphragm against the chest wall could be visualized, as well as the point where the diaphragm peeled away from the chest wall (costal recess). Measurements were made online using cursors and confirmed offline (see Reference 24). The costal origin of the diaphragm was identified when the subject breathed in to total lung capacity (TLC), where the length of the zone of apposition approaches zero with active inspiration (25; glottis open; see EXPERIMENTAL PROTOCOL). With ultrasound, thickening of the diaphragm muscle layer in the zone of apposition during inspiration can be easily visualized. During inspiration to TLC the costal origin of the diaphragm was identified by the change in angle and thickening of the diaphragmatic muscle fibers, and by the lack of thickening or movement of abdominal muscle layers caudal to the diaphragmatic origin (Figure 1) . The distance between the costal origin of the diaphragm and the point where the diaphragm peeled away from the chest wall was measured to give the length of the zone of apposition (LZapp) at any lung volume or time point (± 1 mm). The thickness of the diaphragm and its depth under the skin were also measured at FRC (to the nearest 0.5 mm; 50 mm linear probe).



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  		Figure 1. (A) Experimental setup showing placement of the ultrasound probe, magnetometer receivers, and inductance band to measure abdominal movement. Airflow was measured at the mouth with a pneumotachometer. (B) Transverse cross-section of the rib cage and diaphragm showing LZapp and DLat at RV, FRC, and TLC. (C) Three ultrasound images (left to right) from one breath showing movement of the chest wall apposed diaphragm as the healthy subject inhaled from about half inspiratory capacity to near TLC. Diaphragm and abdominal muscle layers, the ribs (dark area) and the air-filled lung (light area) can be identified. The diaphragm muscle layer thickens and as TLC is approached the diaphragm begins to angle away from the chest wall, allowing identification of the costal origin of the diaphragm (marked across the images as a dotted horizontal line). The abdominal muscle (transversus abdominis) does not change configuration or thickness. The two crosses on the right image show the position of two cursors used during the experiment to measure diaphragm thickness, as well as LZapp and diaphragm depth. The vertical scale bars (large marks) and the horizontal scale bar both represent 1 cm.

 
Measurement of Chest Diameters
The lateral diameter of the chest wall (coronal plane, DLat) was measured with magnetometers (Fastrak; Polhemus Inc., Colchester, VT) taped to the skin on the left and right sides in the midaxillary line at the level of the xiphisternum. The antero-posterior diameter (DAp) of the chest wall was measured with magnetometers placed on the xiphisternum and on the spine so that the two magnetometer receivers were at the same horizontal level, which was approximately the level of the diaphragm at FRC. The position in space of each of the magnetometers was recorded based on Cartesian coordinates relative to a reference transmitter. A computer program (LabVIEW; National Instruments, Austin, TX) then calculated the straight-line distance between the magnetometer pairs to give a continuous recording of DLat and DAp. The depth of the diaphragm under the skin (measured near the right mid-axillary line by ultrasound; see above) was doubled and then subtracted from both lateral and AP diameters for all subsequent analyses. This assumption that the depth of the diaphragm near the right mid-axillary line was equal to the depth of the diaphragm in the sagital plane was found to be a reasonable approximation based on measurements of CT scans.

Other Measurements
Airflow at the mouth was measured with a pneumotachometer and integrated to give changes in volume. Abdominal movement was measured with inductive plethysmograph bands (Respitrace; Ambulatory Monitoring Inc., Ardsley, NY).

Experimental Protocol
Subjects were seated comfortably for the experiment. Measurements were made while the subject breathed through the pneumotachometer and, for comparison, without the mouthpiece. The subjects were given no instructions on breathing strategies and did not have any visual feedback of airflow, volume or thoracoabdominal motion. Rib cage diameters, airflow and volume, and abdominal movement were recorded continuously on computer while the ultrasound measurements were made. The ultrasound probe was placed against the skin and the change in LZapp with tidal breathing was measured as the subject breathed quietly by visually aligning cursors with the costal recess at the average end-inspiratory and end-expiratory position (FRC) over 5–10 breaths. The measurements were made after breathing had stabilized, with the ultrasound image monitored continuously until the end-expiratory and end-inspiratory levels remained stable for 30 seconds or more. Based on observations during the experiments, we assumed that the peak-to-peak displacement of the diaphragm corresponded to the end-inspiratory and end-expiratory positions. The subject was then asked to breathe in to TLC (glottis open) so that the costal origin of the diaphragm could be located on the ultrasound image. The absolute value of LZapp between the costal origin and the costal recess position previously located at FRC was then measured. The subject was then asked to exhale completely to measure LZapp at residual volume (RV). The ultrasound images from this maneuver were stored and replayed repeatedly at varying speeds to visualize the full extent of the zone of apposition at RV. For most subjects, measurements of LZapp at RV could be made directly from the costal origin to the costal recess at RV (if the change in LZapp was less than the probe length of 80 or 120 mm). However, in larger subjects, with a longer LZapp at RV, measurements were made from the costal recess at FRC to RV and then added to the previously measured LZapp at FRC.

To ensure consistent results, the subjects repeated the breathing maneuvers a number of times and the ultrasound measurements were averaged for each subject. For each subject, the difference between maximum and minimum values recorded for all measurements (LZapp at RV, FRC, and TLC, and tidal {Delta}LZapp) was calculated and averaged to give an estimate of the variation in LZapp between maneuvers or breaths. Across subjects, this variation averaged 4.6 ± 1.8 mm (ranging from 1.2 ± 1.6 to 8.0 ± 4.2 mm).

Estimation of LDi
The length of the diaphragm (LDi) in the midaxillary coronal plane was estimated from the measurements of LZapp and the lateral rib cage diameter (DLat) using the equation of Petroll and coworkers (21): LDi (mm) = 1.968 x LZapp + 0.924 x DLat + 69.6. Simply stated, the equation reflects that LDi is equal to the sum of the left and right LZapp (assumed equal), DLat, and a correction for the curvature of the dome. The equation was validated for patients with COPD by McKenzie and colleagues (22), who showed that the length of the diaphragm dome (LDome) did not change significantly between RV and TLC.

For comparison of the relative shortening of the diaphragm, the length of the noncontractile central tendon of the diaphragm was fixed for all subjects at 25% of the average LDi at FRC in our control subjects (25). This length (114 mm) was subtracted from LDi of the patients with COPD and control subjects to calculate the relative shortening of diaphragmatic muscle fibers during tidal breathing.

Estimation of Displaced Volume
The volume displaced by movement of the diaphragm relative to its insertion ({Delta}VDi) during tidal breathing was estimated from measurements of the change in LZapp, and the lateral and AP rib cage diameters (DLat and DAp, respectively). The cross-sectional area of the rib cage (ARc) was assumed to approximate an ellipse (diameters, DLat and DAp; 26) minus the area of the spinal column (ASp): ARc = ({pi}/4 x DLat x DAp) - ASp (27). The volume displaced by motion of the diaphragm was assumed to approximate a truncated elliptical cone with height equal to the mean vertical displacement of the diaphragm around the rib cage (mean {Delta}LZapp), and cross-sectional area of the rib cage changing from the start (ARc1) to the end (ARc2) of inspiration: {Delta}VDi = mean {Delta}LZapp x 1/3 x (ARc1+ ARc2 + (ARc1 x ARc2)1/2). Because LZapp varies around the rib cage, we multiplied our measurement of coronal LZapp by a constant ratio to get an estimate of mean LZapp. The ratio of mean {Delta}LZapp around the circumference of the rib cage to coronal {Delta}LZapp (measured in this study in the midaxillary coronal plane) was estimated as 0.77 at FRC from the data of Gauthier and coworkers (28). In their Appendix A, Gauthier and coworkers (28) estimated mean LZapp as the surface area of the zone of apposition (396 and 892 cm2 at TLC and FRC, respectively) divided by the internal circumference of the rib cage (78.0 and 74.15 cm, respectively), giving a mean LZapp of 5.1 cm at TLC and 12.0 cm at FRC. For our measurement method LZapp approached zero at TLC (see RESULTS and DISCUSSION), so we subtracted Gauthier and colleagues' (28) mean and coronal LZapp at TLC (5.1 and 5.4 cm, respectively) from their values at FRC (12.0 and 14.4 cm, respectively) before expressing mean LZapp as a fraction of coronal LZapp: (12.0–5.1)/(14.4–5.4) = 0.77. The area of the spinal column was measured from chest CT scan images of three subjects (including two patients with COPD in the present study) and the values averaged to give an approximation of ASp for all subjects. The measurements were made at the level of the diaphragm dome at TLC using image analysis software (Scion Image; Scion Corp., Frederick, MD).

Statistics
Comparisons of lung function measurements, diaphragm dimensions, and parameters of tidal breathing were made between patients with COPD and control subjects using t tests. Pearson correlation coefficients and linear regression analyses were used to investigate relationships between the measurements made during tidal breathing. Lung volume was expressed as %TLC for comparisons at "functional" lung volumes (RV, FRC, TLC) to assess the impact of COPD on diaphragm function. To assess the changes to diaphragm and rib cage dimensions in patients with COPD, comparisons were also made at absolute lung volumes (expressed as %predicted TLC). Both normalizations removed the effect of the size of the subject. An ANOVA with lung volume (%TLC or %predicted TLC) as a covariate was used to compare the lung volume - LZapp and lung volume - LDi relationships between patients with COPD and control subjects. Data are quoted as mean ± SD and the level of significance was set at p < 0.05 unless otherwise stated.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The control subjects and patients with COPD were well matched in age, height, and weight, whereas the patients displayed marked hyperinflation and airflow limitation (Table 1). In the patients, PaCO2 ranged from 39 to 53 mm Hg and seven patients had hypercapnia (PaCO2 > 45 mm Hg). Three patients had resting hypoxemia (PAO2 < 55 mm Hg; range for all patients, 51 to 77 mm Hg), and two of these were also hypercapnic.

Static Measurements at RV, FRC, and TLC
Mean values for static measurements of LZapp, DLat, DAp, and LDi (in the midaxillary coronal plane) at RV, FRC, and TLC are shown in Table 2 . As expected, both LZapp and LDi were significantly shorter in the patients at RV and FRC. However, at TLC the difference in LDi between groups was not significant. There was no significant difference between patients and control subjects in either the lateral or AP diameter of the chest (DLat and DAp) at any lung volume. Therefore, most of the difference in LDi between patients and control subjects at FRC and RV can be attributed to a difference in LZapp.


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  		TABLE 2. Measurements of the diaphragm at total lung capacity, frc, and residual volume

 
The thickness of the diaphragm at FRC measured just anterior to the midaxillary line near the midpoint of the zone of apposition did not differ between the patients and control subjects (Table 2). However, to compare thickness at equal LDi we estimated diaphragm thickness in the control subjects at the average LDi for the patients with COPD (381 mm at FRC). If thickness varied in inverse proportion to LDi, then at 381 mm diaphragm thickness would be 3.9 ± 0.9 mm for the control subjects (thickness at 381 mm = LDi at FRC/381 x thickness at FRC). This value is larger than the 3.1 ± 1.1 mm for the patients with COPD, but the difference was not significant (p = 0.13). The depth of the diaphragm (distance from skin to thoracic or pleural surface of the diaphragm) was slightly greater in the patients (17 versus 14 mm in the control subjects, p < 0.05, see Table 2).

There was a strong correlation between both LZapp and LDi, and lung volume (Figure 2) . The data for patients with COPD show the same relationship between LZapp and LDi and functional lung volume (expressed as %TLC) as the control subject data (Figures 2A and 2C). They are simply shifted towards high lung volumes with a resultant reduction in LZapp and LDi. There was no significant difference in LZapp or LDi between patients with COPD and control subjects when the effect of functional lung volume was removed in an ANOVA. However, when absolute lung volume (expressed as %predicted TLC) was used, the ANOVA revealed that LZapp and LDi were significantly larger at a given absolute lung volume in patients with COPD than control subjects (Figures 2B and 2D).



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  		Figure 2. Correlation between LZapp and functional lung volume expressed as %TLC (A; R = 0.97 and 0.90 for control subjects and patients with COPD, respectively; p < 0.001) and absolute lung volume expressed as %predicted TLC (B; R = 0.95 and 0.84; p < 0.001); and correlation between LDi and functional lung volume (C; R = 0.90 and 0.85; p < 0.001) and absolute lung volume (D; R = 0.86 and 0.81; p < 0.001). Data plotted for control subjects (n = 8) and patients with COPD (n = 9) at TLC, FRC, and RV.

 
Dynamic Measurements during Tidal Breathing
Figure 3 shows a continuous recording of VT, DLat, DAp, and abdominal movement during tidal breathing in a control subject and a patient with COPD. The measurement of LZapp was made by placing cursors on the ultrasound screen at average end-inspiration and end-expiration over 5–10 consecutive breaths during stable breathing. The patient illustrated in Figure 3 showed paradoxical motion of DLat compared with DAp (Hoover's sign), and a very short LZapp.



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  		Figure 3. Raw traces of tidal volume (VT), lateral diameter of the rib cage (DLat), antero-posterior diameter of the rib cage at midline (DAp), and abdominal movement in a control subject (A) and a patient with COPD (B). Measurement of LZapp was made at end-inspiration, and end-expiration and averaged over 5–10 breaths.

 
On the mouthpiece, there was no difference in VT, minute ventilation, and respiratory frequency between patients with COPD and control subjects (Table 3) . Total ventilation was similarly increased above expected values for quiet breathing in both groups. However, inspiratory time (TI) was significantly shorter in the patients (TI = 1.1 seconds for patients with COPD versus 1.7 seconds for control subjects), indicating an increase in mean inspiratory flow and inspiratory drive. There were no differences between patients with COPD and control subjects in the tidal change in LZapp ({Delta}LZapp) or change in LDi ({Delta}LDi; Table 3). For the patient and control groups combined, {Delta}LZapp and {Delta}LDi were correlated with VT (R = 0.76 and 0.85, respectively, p < 0.01). During tidal breathing off the mouthpiece, {Delta}LZapp and {Delta}LDi were not significantly different from the values measured while the subjects breathed through the mouthpiece. Off the mouthpiece, patients with COPD and control subjects breathed with a smaller TI (TI = 1.4 seconds on versus 1.2 seconds off the mouthpiece, combined data, p < 0.05), but respiratory frequency was not significantly different.


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  		TABLE 3. Measurements during tidal breathing

 
The relative change in LDi with tidal breathing was similar in the patients (10 ± 3% of LDi at FRC) and control subjects (9 ± 3%; not significant). The estimated relative shortening of the diaphragmatic muscle fibers (see METHODS; 25) was 15 ± 4% and 12 ± 4% for the patients with COPD and control subjects, respectively (not significant) during tidal breathing. The relative change in LZapp during tidal breathing was significantly greater in the patients compared with control subjects (62 ± 23% of LZapp at FRC for the patients versus 28 ± 9% for control subjects, p < 0.05).

Figure 4 shows the variation in the relationship between the AP and lateral diameters of the rib cage in typical control subjects and patients with COPD. In all subjects, DAp increased with inspiration, and in all the control subjects, DLat increased with inspiration and increasing DAp, with varying degrees of hysteresis. The patients with COPD exhibited three patterns: (1) three patients showed a similar pattern to that of the control subjects (top trace); (2) three patients exhibited a large amount of hysteresis (middle trace); and (3) four patients exhibited paradoxical motion with DLat decreasing with inspiration and increasing DAp (bottom trace). These latter four patients exhibited Hoover's sign on clinical examination.



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  		Figure 4. Raw traces of the lateral diameter of the rib cage plotted against the antero-posterior diameter (DLat versus DAp) measured with magnetometers during representative single breaths from end-expiration (open squares) to end-inspiration (open circle) and back to end-expiration. The arrows indicate increasing time with inspiration (thick line) followed by expiration (thin line). In all subjects DAp increased with inspiration. (A) Data from three control subjects showing DLat increasing with DAp during inspiration with varying degrees of hysteresis. (B) The three patterns exhibited by patients with COPD: DLat increasing with DAp during inspiration like the control subjects (top), large amount of hysteresis (middle), and DLat decreasing as DAp increased during inspiration (i.e., paradoxical, bottom). Note that the scales of each graph are not equal, with some subjects exhibiting greater changes in diameter than others.

 
The mean changes in rib cage diameters during tidal breathing are listed in Table 3. The mean tidal change in DAp ({Delta}DAp) was not different between groups. Nor was there a statistical difference in the tidal change in lateral diameter ({Delta}DLat) between patients with COPD and control subjects, but there was a wide variation in the patients with COPD. DLat decreased with inspiration in six patients with COPD and increased in four.

The change in lateral diameter in tidal breathing ({Delta}DLat) was linearly related to PaCO2 in the patients (R = 0.77, p < 0.01; Figure 5) . Patients with a negative {Delta}DLat (in-drawing of the chest wall with inspiration) had lower PaCO2 values than those with a positive {Delta}DLat. The data from one of the patients did not fit the linear relationship well as the in-drawing of the lateral chest wall was much greater than expected (excluding this outlier, R = 0.94, p < 0.01). This patient also had the lowest FEV1 (11% predicted). {Delta}DLat was not directly correlated with other measures of the severity of COPD, such as FEV1, and it was not related to LZapp at the end of inspiration. However, multiple linear regression analysis of data from the patients with COPD showed that {Delta}DLat in the patients could be expressed as a linear combination of PaCO2, FEV1, and TI ({Delta}DLat = 0.1 x PaCO2 + 2.2 x FEV1 + 1.0 x TI - 7.7; R = 0.94, p < 0.01). Based on this analysis, the patients with the lowest PaCO2, FEV1, and TI had the more negative {Delta}DLat.



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  		Figure 5. Graph of {Delta}DLat during tidal breathing versus PaCO2 for patients with COPD. The regression line (R = 0.94, p < 0.01) is plotted for the data excluding the outlier (open square, including the outlier R = 0.77, p < 0.01).

 
Correlations were also sought between indices of severity of the lung disease and measurements of the diaphragm and chest wall during tidal breathing. {Delta}DAp was negatively correlated with vital capacity (VC; R = -0.73 for both groups combined, p < 0.01), indicating that the patients with smaller VC had greater tidal expansion of the rib cage in the AP direction than control subjects with larger VC.

An estimate of volume displaced by excursion of the diaphragm ({Delta}VDi) during tidal breathing was made from {Delta}LZapp, DLat and DAp (see METHODS). This estimate of {Delta}VDi was not significantly different between patients with COPD (0.6 ± 0.2 L) and control subjects (0.6 ± 0.3 L), and VT measured at the mouth minus {Delta}VDi was not significantly different between patients with COPD and control subjects (0.2 ± 0.2 L and 0.2 ± 0.2 L, respectively). The values of {Delta}VDi and VT were significantly correlated (R = 0.65, p < 0.01). The difference between VT and {Delta}VDi should be proportional to the tidal change in rib cage volume, but in the present study we only measured the change in ARc ({Delta}ARc) at the level of the zone of apposition. Nevertheless, we found that {Delta}ARc was significantly correlated with the difference between VT and {Delta}VDi (R = 0.64, p < 0.01). The patients with COPD tended to have a smaller {Delta}ARc than the control subjects, but this was not significant (6.8 ± 12.9 cm2 versus 12.1 ± 3.7 cm2, respectively, p = 0.22). The failure to show a difference reflected the greater variability in {Delta}ARc of the patients with COPD (range, -18.4 to 29.4 cm2 versus 6.9 to 18.3 cm2 for the control subjects). Five of the patients with COPD had values of {Delta}ARc less than the smallest value for the control subjects (6.9 cm2).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In patients with severe COPD, we found marked reductions in the length of the diaphragm in the coronal plane (LDi) at both FRC and RV compared with the matched control subjects (see also References 3, 12–14). These reductions are consistent with the marked hyperinflation and reduced VC of these patients. In spite of their chronically shortened diaphragms at FRC, the patients with COPD showed similar shortening of the diaphragm and its zone of apposition (LZapp) during tidal breathing as control subjects. This preservation of the ability to shorten the diaphragm during tidal breathing in patients with COPD was possible because at a given absolute lung volume LDi and LZapp were actually longer in the patients with COPD compared with control subjects (Figures 2B and 2D). However, at end-inspiration during tidal breathing, LZapp was much shorter for patients with COPD (15 mm) than control subjects (51 mm), so the patients had little margin to increase VT by further shortening of the diaphragm. At predicted TLC, LZapp was not eliminated in the patients with COPD, and at TLC, LDi was similar in the patients with COPD and control subjects (312 versus 336 mm, respectively), suggesting that shortening of the diaphragm cannot fully explain the hyperinflation in patients with COPD.

There are important technical differences between the present method, using ultrasound and magnetometers, and other imaging techniques used to measure LDi and LZapp. In previous radiographic studies, LDi was measured in a midline coronal plane from PA films (as simulated in the present ultrasound study), and sometimes also in a sagittal plane from a lateral film. In neither case can it be assumed that the most cranial lung-apposed profile of the diaphragm lies in a single plane. With MRI or CT techniques, the three-dimensional reconstruction of the contour of the lung-apposed diaphragm allows comprehensive analysis of lengths and surface area of the diaphragm dome. However, this limitation of measurements from chest radiographs is unlikely to introduce significant error because measurements of the coronal length of the diaphragm dome (LDome) from chest radiographs (20–22) are similar to those from CT (14, 29) and MRI (28) in both patients with COPD and control subjects.

In advanced emphysema, dome shape is sometimes abnormal or changes as lung volume increases. However, LDome did not change significantly over the VC range for nine of the present patients, in whom we had previously obtained PA radiographs at RV, FRC, and TLC (22). Using CT, Cassart and coworkers (14) also found no change in dome surface area between FRC and TLC in patients with COPD. The present ultrasound method provided no information on dome shape, but we used an equation to estimate LDi that allowed for dome curvature. The equation was derived from PA chest radiographs of normal subjects (21), and was validated radiographically in patients from the present study (22). Although the diaphragm is "flatter" with reduced index of curvature, KDome (= coronal LDome/DLat), in patients with COPD (13), using this equation only led to a maximum 5% overestimate of coronal LDi and all values were within the 95% confidence interval of LDi measured directly from PA radiographs (22).

Identification of the costal insertion of the diaphragm is a major difference between CT and MRI studies compared with this study and studies using chest radiographs. With chest radiographic methods, it has been assumed that the origin of the diaphragm can be identified during maximal inspiration at TLC, at the costo-phrenic angle where the diaphragm peels away from the chest wall (20, 21, 25, 30). This assumption, that LZapp is zero at TLC, has been supported by postmortem inspections of the insertions of the diaphragm on the chest wall (25). The ultrasound method used here allows the costal origin of the diaphragmatic muscle fibers to be identified with confidence during active inspiratory effort at TLC (Figure 1). As TLC is approached, there is a change in angle relative to the rib and the thickness of the muscle as the insertional slips are visualized. By contrast, in CT and MRI studies (14, 28, 29) the origin of the diaphragm has been identified from a marker placed just caudal to the costal margin with mean LZapp at TLC ranging from 45 to 58 mm (unilateral LZapp, estimated as bilateral LZapp/2) in the coronal plane. Gauthier and coworkers (28) suggested that this method overestimates LZapp by up to 20 mm, but our results indicate that the overestimate may be larger. However, any differences in method of determining the costal origin would not affect measurements of the change in LZapp during tidal breathing or estimates of volume displacement.

Posture and whether the diaphragm was measured while active or relaxed are further sources of difference between studies. In this and previous studies using chest radiographs (13, 20–22, 25, 30), measurements were made with the subjects upright and static lung volumes maintained by active muscle contraction (except for FRC) with the glottis open. In contrast, measurements with MRI and CT (14, 28, 29) have been obtained with the subject supine relaxing against a closed airway at the selected volumes. With the respiratory muscles relaxed and the subject supine, the abdominal contents and fluid shifts may push the diaphragm cephalad, especially at FRC, and increase LZapp compared with studies in which the subjects were upright and the diaphragm active. However, this is unlikely to account for all the difference between our measurements of LZapp at TLC and those from MRI and CT studies. Previous reports suggest a modest 2–4% decrease in active TLC with supine posture (31), and with relaxation of the inspiratory muscles against a closed airway we could expect a further 3% decrease due to gas compression. If lung volume was reduced by 7% then LZapp at TLC would be 18 mm according to the relationship between LZapp and functional lung volume shown in Figure 2A. This effect accounts for only about a third of the LZapp at TLC reported in the studies using MRI or CT.

Absolute dimensions of the diaphragm at TLC reported in previous studies have been consistently smaller in patients with COPD than in control subjects. In our study, the difference in LDi (312 versus 336 mm, respectively) was not statistically significant, but the values are similar to previous reports using chest radiographs (13, 20–22, 25). In both the radiologic study of Singh and coworkers (13) and the CT study of Cassart and colleagues (14), the differences were significant (312 versus 346 mm, p < 0.05; and 389 versus 441 mm, p < 0.01, respectively). Therefore, some of the increase in TLC in patients with COPD may result from flattening of the diaphragm with a reduced volume contained by its dome. Singh and coworkers (13) estimated that flattening of the diaphragm accounted for 0.8 L of the 2.0 L difference in TLC between patients with COPD and control subjects.

Our results and those of Singh and coworkers (13) suggest that in addition to flattening of the diaphragm, the rest of the increase in TLC in patients with COPD must be largely accommodated by expansion of the rib cage, whereas the data of Cassart and colleagues (14, 15) suggest it is accommodated by reducing the zone of apposition. In the CT study of Cassart and coworkers (14) patients with COPD and control subjects showed the same relationship between diaphragm surface area and absolute lung volume (Figure 2 in Reference 14) and also between LZapp and absolute lung volume. As absolute lung volume increased above predicted TLC in patients with COPD, the zone of apposition decreased, but still accounted for 36% of the total diaphragm surface even at the increased TLC of severe emphysema. In a further CT study (15), diaphragm surface area before and after lung volume reduction surgery was also tightly related to absolute lung volume. By contrast, in agreement with Singh and coworkers (13), we observed that LZapp was longer at isovolume in patients with COPD than control subjects. The disparity between studies may be explained by the methodological differences discussed above. However, the possibility of large reserves of rib cage–apposed diaphragm at TLC in patients with COPD as reported by Cassart and colleagues (13) is relevant to the role of any mismatch between lung and chest wall size in determining success of lung volume reduction surgery (32, 33).

The increased LZapp at isovolume in patients with COPD suggests relative overinflation of the rib cage (see also Reference 13). Although we found no increase in the dimensions of the lower rib cage, this may not reflect changes in the middle and upper rib cage in patients with COPD. Previous studies of rib cage diameters at different levels at TLC (34, 35) agree with our results in showing no increase in transverse diameter of the rib cage despite the increased TLC in severe COPD. However, some (13, 34), but not all (35), studies have found an increase in AP diameters at TLC. Nevertheless, in a CT three-dimensional reconstruction (34), which should be the most accurate, AP diameters in the upper rib cage were actually smaller in patients with COPD than in control subjects at a given absolute lung volume. Therefore, the different techniques give conflicting answers as to how the increase in TLC is accommodated in COPD: by adaptive changes in relative expansion of rib cage or diaphragm/abdominal compartments, including changes in the diaphragm contour.

This is the first study to report dynamic changes in LZapp and LDi during tidal breathing in patients with COPD and control subjects. We found no difference in the changes in LZapp and LDi during tidal breathing between patients with COPD and control subjects, and no difference in the estimated volume displaced by the diaphragm ({Delta}VDi) during tidal breathing. Kleinman and coworkers (11) have also recently reported in a fluoroscopy study that diaphragm motion during tidal breathing is similar in patients with COPD and control subjects. These results contradict the established view that displacement of the diaphragm during tidal breathing is reduced in patients with COPD (10, 36). With our experimental setup, ventilation was higher than expected for normal resting breathing, but at end-inspiration the patients with COPD still maintained a small reserve of LZapp.

Dynamic measurements of LZapp, DLat, and DAp, and an estimate of the cross-sectional area of the spinal column (ASp), were used to estimate {Delta}VDi during tidal breathing. A more accurate model using this noninvasive method will require validation with scans of the rib cage and diaphragm in the same subjects, and analysis of the internal dimensions of the lung-apposed rib cage (see References 26, 27, 37), any distortions during tidal breathing, and estimation of the mean LZapp around the rib cage circumference. Our model did not include measurement of any volume displacement caused by changes in the shape of the diaphragm dome or axial movement of the origin of the diaphragm (cf. Reference 13), but we believe that any error due to these factors would be small as the range of diaphragm movement was small.

In the patients with COPD, the tidal change in lateral diameter ({Delta}DLat) could be predicted by a linear combination of PaCO2, FEV1, and TI. This suggests that inspiratory in-drawing of the rib cage (Hoover's sign) was related to both inspiratory drive (related to TI) and disease severity (indicated by FEV1) with increased drive contributing to a lower PaCO2. We found no evidence in these patients that LZapp or LDi at end-inspiration was related to the amount of paradoxical in-drawing of the lateral rib cage during inspiration, contradicting the view that paradoxical motion of the lower rib cage results from a reduced LZapp and more radial alignment of the diaphragmatic muscle fibers (38, 39). There was some hysteresis of the diameters of the rib cage recorded during tidal breathing in the control subjects and patients with COPD (see Figure 4). In most control subjects, this deviation from the relaxation line described by Konno and Mead (40) was small and similar to that shown by McCool and coworkers (41) in tidal breathing and rebreathing (see their Figures 6 and 7). The hysteresis would have been increased by the elevated tidal volumes in our study. In particular, the control subject with the largest tidal volume showed the largest amount of hysteresis.

Diaphragm movement results from coordinated contraction of the diaphragm, rib cage, and abdominal muscles (42). Patients with COPD (2, 43) and exercising, healthy subjects (42) recruit abdominal muscles during late expiration. Active expiration may lengthen the diaphragmatic muscle fibers at the onset of inspiration such that they can generate more tension or shorten more, thus improving the capacity of the diaphragm to displace volume. Any further acute increase in FRC in the patients with COPD (e.g., dynamic hyperinflation in exercise or exacerbation of airway narrowing) or an increase in VT may require increased involvement of the abdominal muscles during expiration. Although the present study cannot apportion the contribution to diaphragm motion in tidal breathing between active contraction and passive movement, active contraction of the diaphragm is likely to be important. Despite the chronically reduced muscle length in patients with COPD, the pressure-generating ability of the diaphragm is largely preserved at FRC (44). This is possible because of chronic adaptations of the diaphragm muscle resulting in a reduction in the length and/or number of sarcomeres in series (45–47), as also suggested in this study by the trend for reduced diaphragm thickness at equal LDi in the patients with COPD compared with control subjects. Moreover, during tidal breathing the firing rate of diaphragmatic motor units in patients with COPD is 70% greater than matched control subjects (9). With the diaphragmatic strength preserved and a greater neural drive, it is likely that active contraction of the diaphragm significantly contributes to its inspiratory movement.

This study has shown that the zone of apposition and "piston-like" properties of the diaphragm are preserved during tidal breathing in patients with COPD with severe hyperinflation. Although diaphragm length is reduced, adaptations to preserve the zone of apposition in patients with COPD allow normal diaphragm shortening and volume displacement during tidal breathing.


   FOOTNOTES
 
This study was supported by the Asthma Foundation of NSW, National Health and Medical Research Council of Australia, and Wellcome-Ramiciotti. J.T. was a Boerhinger Ingelheim Research Fellow of the Australian Lung Foundation.

Received in original form September 19, 2001; accepted in final form September 11, 2002


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
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