Effect of CPAP on respiratory effort and dyspnea during exercise in severe COPD BASIL J. PETROF, EDOARDO CALDERINI, AND STEWART B. GOTTFRIED Department of Medicine, Montreal General Hospital and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H3G lA4, Canada

PETROF, BASIL J., EDOARDO CALDERINI, AND STEWART B. GOTTFRIED. Effect of CPAP on respiratory effort and dyspnea during exercise in severe COPD. J. Appl. Physiol. 69(l): 179188, 1990.-Recent work has demonstrated the ability of continuous positive airway pressure (CPAP) to relieve dyspnea during exercise in patients with severe chronic obstructive pulmonary disease (COPD). The present study examined the effects of CPAP (7.5-10 cmH*O) on the pattern of respiratory muscle activation and its relationship to dyspnea during constant work load submaximal bicycle exercise [20 t 4.8 (SE) W] in eight COPD patients (forced expiratory volume in 1 s = 25 t 3% predicted). Tidal volume, respiratory rate, minute ventilation, and end-expiratory lung volume increased with exercise as expected. There was no change in breathing pattern, endexpiratory lung volume, or pulmonary compliance and resistance with the addition of CPAP. CPAP reduced inspiratory muscle effort, as indicated by the pressure-time integral of transdiaphragmatic (SPdi . dt ) and esophageal pressure (J’Pes . dt, P < 0.01 and P c 0.05, respectively). In contrast, the pressure-time integral of gastric pressure (SPga= dt), usedas an index of abdominal muscle recruitment during expiration, increased (P < 0.01). Dyspnea improved with CPAP in five of the eight patients. The amelioration of dyspnea was directly related to reductions in SPes. dt (P c 0.001) but inversely related to increases in j’Pga* dt (P < 0.01). In conclusion, CPAP reduces inspiratory muscle effort during exercise in COPD patients. However, the expected improvement in dyspnea is not seen in all patients and may be explained by more marked increases in expiratory muscle effort in some individuals. dynamic hyperinflation; expiratory flow limitation; intrinsic positive end-expiratory pressure; inspiratory threshold load; respiratory muscle fatigue; expiratory muscle recruitment

WITH severe chronic obstructive pulmonary disease (COPD) frequently breathe along their maximal expiratory flow-volume relationship during normal tidal breathing at rest (7, 33, 37). In these individuals, the increased ventilatory requirements of exercise are met by increasing end-expiratory lung volume above its resting level, thus allowing an increase in expiratory flow rates (7, 37). This phenomenon is known as dynamic hyperinflation and has been described in patients with severe COPD during exercise as well as a number of other circumstances (10, 25, 31, 32). Under these conditions, failure to reach the relaxation volume of the respiratory system before the next inspiration necessarily results in positive elastic recoil pressure being present at the end of expiration. This implies that the inspiratory PATIENTS

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muscles must develop sufficient force to overcome the opposing positive recoil pressure before inspiratory airflow can be initiated. Thus a significant additional burden is placed on the inspiratory muscles, which are already disadvantaged as the result of force-length considerations, abnormal thoracic geometry, and other factors (34). The application of continuous positive airway pressure (CPAP) has recently been demonstrated to reduce the work of breathing and dyspnea in patients with severe COPD and acute respiratory failure during weaning from mechanical ventilation (32). In this clinical setting, CPAP was able to decrease inspiratory muscle effort by counterbalancing the end-expiratory recoil pressure associated with dynamic hyperinflation. O’Donnell et al. (28) recently reported that CPAP improved exercise endurance and dyspnea in exercising COPD patients. However, the effect of CPAP on respiratory muscle effort was not directly examined. The purpose of the present study was to examine the effect on CPAP on the pattern of respiratory muscle activation and its relationship to dyspnea in patients with severe COPD during constant work load exercise. METHODS

Eight patients (7 males, 1 female) from the Respiratory Disease Clinic of the Montreal General Hospital were recruited to participate in the study. All had clinical, roentgenological, and physiological evidence of severe irreversible airway obstruction. Results of routine pulmonary function tests are provided in Table 1. The presence of expiratory flow limitation under resting conditions was verified in each subject by virtue of the fact that tidal expiratory flow fell along or exceeded the maximum forced expiratory flow-volume curve (33). All patients were clinically stable at the time of evaluation without cardiovascular disease or other significant illness that might have interfered with exercise performance. The investigative protocol was approved by the institutional ethics committee, and written informed consent was obtained from the patient in all cases. Flow (V) was measured at the mouth with a heated pneumotachograph (Fleisch no. 3) connected to a differential pressure transducer (Validyne MP-45, &2 cmH20). Tidal volume (VT) was determined by electrical integration of the flow signal (Hewlett-Packard 8815A). Equipment resistance was 1.2 cmHzOo 1-l s at a V rate of 1 l/

0 1990 the American

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180

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TABLE

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IN

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1. Patient characteristics and pulmonary function data Patient No.

1 2 3 4 5 6 7 8 Mean AI SE %Pred* t SE

Sex

M M M M F M M M

Age, Yr

FW.o, liters

FVC, liters

TLC, liters

FRC, liters

W liters

DLW, ml - min-’ . Torr-’

MVV, l/min

59 58 67 58 60 70 57 78

0.40 1.01 0.63 0.96 0.59 0.93 0.71 0.84

1.75 2.39 1.69 2.37 1.08 2.96 1.63 3.83

7.88 7.30 5.46 5.19 5.83 6.33 7.34 7.65

6.57 5.14 4.13 3.32 4.94 4.29 5.39 5.38

5.26 4.32 3.63 2.89 4.67 3.08 4.69 3.51

16.1 17.6 7.2 15.2 6.2 9.1 16.7 5.8

23 55 34 39 24 41 29 34

63 k3

0.76 to.08

2.21 to.33

6.62 to.40

4.90 kO.37

4.01 to.32

11.7 t1.9

35 k4

57 k7

110 k4

138 -+11

182 t19

47 t7

25 k3

FEVl.o, forced expiratory volume in 1 s; FVC, forced vital capacity; TLC, total lung capacity; FRC, functional residual * Predicted values for spirometry, volume; DL~O, diffusing capacity for CO; MVV, maximum voluntary ventilation. determined lung volumes, and diffusing capacity obtained from Refs. 19, 12, and 11, respectively.

s. The dead space of the experimental circuit was 210 ml. Mouth pressure (Pm) was recorded proximal to the pneumotachograph by using a differential pressure transducer (Validyne MP-45, tlO0 cmH20). Esophageal (Pes) and gastric (Pga) pressures were measured with balloontipped catheter systems. Both balloons were connected by polyethylene catheters to separate differential pressure transducers (Validyne MP-45, tlO0 cmHz0). The esophageal balloon was filled with 0.75 ml of air and properly positioned by using the “occlusion test” as previously described (l), whereas the gastric balloon was filled with 1.5 ml of air. Pes was subtracted from Pm and Pga to determine transpulmonary and transdiaphragmatic (Pdi) pressure, respectively. A direct-current-coupled respiratory inductive plethysmograph (RIP, Respitrace) was employed to measure changes in end-expiratory lung volume. The bands were placed circumferentially around the rib cage (RC) and abdomen (AB) such that their midpositions were aligned with the nipples and umbilicus, respectively. Care was taken to avoid overlap of the AB band with the lower rib cage, and the bands were held in place with adhesive tape. The relative contributions of the RC and AB compartments to changes in lung volume were determined by the isovolume technique (36), using the integrated V signal from the pneumotachograph for volume calibration of the RIP. The mean absolute deviation of VT measured by the RIP from that determined with the pneumotachograph during exercise was 8.7 t 2.3% (SE). Exercise was performed with patients seated on an electrically braked cycle ergometer (Bosch 551). Body position was maintained constant by rigid fixation of the mouthpiece, handle bars, and seat. A vertical bar was attached to the latter posteriorly to prevent anteroposterior movement or changes in spinal curvature (7). All the above signals obtained during the exercise protocol were initially recorded on an eight-channel strip chart recorder (Hewlett Packard 7718A) as well as FM magnetic tape (Vetter model D). Signals were later played back to a personal computer (Compaq 386) through a 12-bit analog-to-digital converter at a sampling

capacity; RV, residual plethysmographically

rate of 100 Hz for subsequent data analysis. Procedure and data analysis. Patients wore noseclips and began to breathe through the experimental circuit while seated on the bicycle. After l-2 min of quiet breathing, resting data were recorded. The patients were then required to exercise at a constant work load for a 2- to 3-min interval. The work load chosen for each individual was the highest level that could be sustained for a continuous 6- to 8-min period, as previously determined in preliminary trials. Approximately 7.5-10 cmH20 of CPAP was then applied for another 2-3 min. The CPAP circuit consisted of a continuous high flow (-100 l/min) source (modified Downs flow generator model 9250) placed distal to the pneumotachograph as well as a 7-liter reservoir bag and spring-loaded threshold resistor valve (Vital Signs). In one patient O2 was introduced into the circuit, and fractional inspired 02 concentration (FIN,) was monitored (Hudson Ventronics 5577 oxygen analyzer) and maintained constant at 0.40 throughout the period of evaluation. The remaining seven patients breathed room air during both rest and exercise conditions. Arterial 02 saturation (Ohmeda Biox 3700 pulse oximeter) and the electrocardiogram were continuously monitored throughout the study. The level of dyspnea during the application of CPAP was compared with that during the immediately preceding control period. Patients were instructed to indicate any change in the sense of breathlessness by pointing to a bidirectional ordinal scale (0 = no change, -l/+1 = very slight worsening/improvement, -2/+2 = slight worsening/improvement, -3/+3 = moderate worsening/ improvement, -4/+4 = marked worsening/improvement, -5/+ 5 = very marked worsening/improvement). Measurements were obtained from 15 to 20 consecutive breaths during the last minute of each experimental condition. Tidal excursions of Pes, Pga, and Pdi were determined. VT was obtained from the integrated flow signal, while the duration of inspiration (TI), expiration (TE), and total breathing cycle (TT) were analyzed from the flow tracing. Inspiratory pulmonary resistance (RL) and elastance (EL) were also determined by using the

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CPAP

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Mead and Whittenberger method (24). Average V-volume plots during exercise with and without CPAP were compared in individual patients. These were obtained by separately dividing both inspiration and expiration into 25 equal time intervals. Data from each interval for all breaths analyzed were then averaged to provide the mean tidal v-volume relationship for the two conditions. The pressure-time integral for the inspiratory muscles (JPes . dt) and the diaphragm (JPdi. dt) was obtained by measuring the area under the Pes and Pdi vs. time relationship, respectively (23). In addition, the pressure-time integral for the expiratory abdominal muscles (JPga . dt ) was calculated by determining the area under the Pga vs. time relationship during expiration. These were all computed as values for a l-min period. Results are expressed as means t SE unless otherwise specified. Comparisons between exercise periods before and during the use of CPAP were made by using the Student’s t test for paired data. Statistical significance was defined as P < 0.05.

IN

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181

Pes (cmH20

Pga (cmH20

Pdi

RC (Liters)

AB (Liters)

RESULTS

The changes in breathing pattern parameters and respiratory mechanics from rest to exercise are shown in Table 2. After 2-3 min of exercise at a constant work load (mean 20 t 4.8 W) minute ventilation averaged -70% of the previously determined maximum voluntary ventilation (mean 71 t 7.9%). Minute ventilation increased significantly compared with resting conditions as the result of increases in both VT and breathing frequency. There were also significant increases in mean inspiratory (VT/TI) and expiratory (VT/TE) v rates during exercise. Inspiratory RL and EL were not significantly altered, although the latter tended to increase with exercise (16, 37). The effects of CPAP on respiration during constant work load exercise for a representative patient (4) are shown in Fig. 1. As can be seen, the application of CPAP led to more positive values for both the maximal expiratory and minimal inspiratory levels of Pes. However, total tidal excursions of Pes were reduced by CPAP, whereas VT remained essentially unchanged. Tidal excursions of Pdi were also substantially decreased during CPAP. In addition, note that the peak level of Pga during 2. Ventilatory parameters and respiratory mechanics in all patients

TABLE

Rest

\jE, l/min VT, liters f, breaths/min TI, s TE, s TI/TT VT/TI, l/s VT/TE, l/s RL, cmH20 - 1-l s EL, cmH20/1 l

16.80t1.16 0.8OkO.06 21.4t1.7 1.09-eo.10 1.8OkO.16 0.36~0.02 0.82t0.07 0.43kO.04 5.3kO.7 6.7-r-1.6

Exercise

Alone

24.80&1.45* 0.97~0.08" 26.321.9” 0.86t0.08” 1.50&0.09* 0.36kO.02 1.15t0.07* 0.64kO.04" 5.9t0.7 10.4t3.2

Exercise

+ CPAP

25.75&1.64* 1.06&0.10* 25.8&2.7* 0.81t0.06* 1.66-eO.16 0.33kO.02 1.32ko.ll”t 0.65&0.05* 5.4kO.5 10.5k3.5

Values are means t SE. i7E, minute ventilation; f, breathing frequency; VT/TI, mean inspiratory flow; VT/TE, mean expiratory flow. * P < 0.05, rest vs. exercise alone or exercise + CPAP. t- P < 0.05, exercise alone vs. exercise + CPAP.

VOLUME

(Liters) FIG. 1. Effects of CPAP on respiration during constant work load exercise in patient 4. Positive deflections for all pressures are in upward direction. RC and AB, volume displacements of rib cage and abdomen, respectively. Inspiratory flow and volume are in upward direction. See text for interpretation.

expiration exceeded that recorded during inspiration before the application of CPAP. This reversal of the normal Pga pattern during exercise is indicative of expiratory abdominal muscle activation (6). The addition of CPAP resulted in a small but definite increment in the peak expiratory Pga value as well as a decrease in the endexpiratory position of the AB signal from the RIP, indicating a further increase in the level of abdominal muscle recruitment (20). To the extent that the end-expiratory position of the RC signal was stable whereas that of the AB signal decreased slightly, there was also a minimal reduction in end-expiratory lung volume during CPAP compared with exercise alone in this individual patient. The effects of both exercise alone and exercise with CPAP on end-expiratory lung volume for all patients are demonstrated in Fig. 2. From rest to exercise, there was a prompt increase in end-expiratory lung volume that averaged 0.31 t 0.16 liter (P C 0.01). Moreover, all the hyperinflation tended to occur in the rib cage compartment, whereas abdominal volume actually decreased minimally. After CPAP administration, there was no significant change for the group in either total or individual compartmental end-expiratory volume compared with exercise alone. However, there was a tendency for further inflation of the rib cage with concomitant deflation of the abdominal compartment during CPAP. Figure 3 illustrates the effect of CPAP during exercise on the tidal excursions of Pes and Pdi for all patients. The maximal expiratory and minimal inspiratory values

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182

CPAP

DURING 0 aa m

600

EXERCISE ALONE

EXERCISE

RIB CAGE ABDOMEN SUM

EXERCISE + CPAP

FIG. 2. Effects of both exercise alone and exercise with CPAP on end-expiratory lung volume compared with resting conditions. Values are means k SE.

20

1

* P ( 0.01

A Pes

(cmH20)

CONTROL

CPAP

IN

COPD

exercise with and without CPAP. VT, breathing frequency, and minute ventilation were not significantly altered by the use of CPAP. There was a trend toward shortening of TI and prolongation of TE during CPAP, and hence a reduction in TI/TT, that did not achieve statistical significance. However, there was a significant increase in VT/TI during CPAP, although VT/TE was unchanged. Both inspiratory RL and EL were stable for the group during exercise with and without CPAP. It should also be noted that although arterial O2 saturation tended to decrease from rest to exercise conditions (93.3 + 1.1 to 90.8 t 1.3%; P > 0.05), it remained stable with subsequent application of CPAP (90.7 t 1.5%). In addition, peak heart rate during exercise averaged 66% of the predicted maximum and was unaffected by CPAP administration. Average tidal v-volume curves for each exercising patient before and during the application of CPAP are provided in Fig. 4. As can be seen, volume-matched expiratory flows were mildly reduced by CPAP in all but two of the patients. The exceptions were patients 7 and 8, in whom expiratory v at isovolume was slightly increased during CPAP. In addition, tidal inspiratory flows were increased during CPAP administration in six of eight patients. Figure 5 shows changes in group mean values of the pressure-time integral for the inspiratory muscles and the diaphragm resulting from the application of CPAP during exercise. This measurement is considered an index of O2 utilization by the respiratory muscles (23). There were substantial decreases in both JPesdt (565 t 82 to 422 t 48 cmH,O; P < 0.05) and JPdidt (435 t 62 to 246 t 40 cmH,O; P c 0.01) during CPAP administration. These changes amounted to 25 and 43% reductions for JPes dt and JPdi . dt, respectively. The level of expiratory abdominal muscle activity during exercise with and without CPAP is demonstrated in Fig. 6. There was a significant increase in the peak expiratory Pga level during CPAP (8.9 t 1.8 to 12.9 t 2.0 cmH,O; P c 0.01). In addition, JPga* dt was also substantially increased by the use of CPAP (235 t 55 to 388 t 56 cmHzO; P c 0.01). Thus expiratory abdominal muscle recruitment increased during CPAP administration. When asked to indicate changes in the degree of breathlessness during exercise with CPAP compared with exercise alone, five patients (1, 3, 4, 5, and 6) reported improvement, whereas the remaining three individuals (2, 7, and 8) expressed worsening of the level of dyspnea. Figure 7 shows the effects of CPAP on respiration during exercise in one patient (2) who is representative of those who reported an increase in breathlessness during CPAP administration. Note that there was an increase in the maximal expiratory level of Pes (reflecting increased expiratory effort), whereas the minimal inspiratory value of Pes was unchanged. Accordingly, in contrast to the record in Fig. 1, the total tidal excursions of Pes actually increased during CPAP. Nonetheless, there was a substantial reduction in the tidal excursions of Pdi during CPAP, whereas VT remained stable. Of interest is the striking increase in peak l

+ P ( 0.01

L A Pdi (cm&O

CONTROL FIG. 3. Tidal excursions of Pes and Pdi before tion of CPAP. Values are means k SE.

CPAP and during

applica-

of Pes tended to increase equally during CPAP for the group as a whole. Consequently, the total tidal excursions of Pes were not significantly altered by CPAP. However, Pes was significantly less negative at end inspiration during the use of CPAP (-15.8 t 1.9 to -12.6 t 2.3 cmH,O; P c 0.01). In addition, there was a significant reduction in the tidal excursions of Pdi during CPAP administration (23.7 t 2.4 to 19.2 t 2.2 cmH,O; P c

0.01). Table 2 provides group mean values for breathing pattern parameters and respiratory mechanics during

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CPAP

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EXERCISE

IN

183

COPD

3

I/-- .l. I\ El\\

/--.\ Ic;-i

I\s\.II

I

I

\

I

\

\

\

\

.

/

--

.

.

2.0

VOLUME

FIG.

(solid

4. Average line).

tidal

V-volume

curves

for individual

patients

during

exercise

(L)

with

(dashed

20

* P ( 0.05

Am (cmH$3

line)

and without

CPAP

* P ( 0.01

10

n

CPAP

CONTROL

CONTROL * P ( 0.01

500

* P ( 0.01

CPAP

250

0 CONTROL CONTROL FIG.

Values

5. JPes . dt and JPdi are means k SE.

l

dt before

FIG.

CPAP and during

application

of CPAP.

Tidal SE.

6. Effect excursions

CPAP

of CPAP on expiratory abdominal muscle activity. of Pga and JPga.dt are shown. Values are means t

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184

CPAP

DURING

EXERCISE

CPAP

Pm (cmHZ0)

o

p#P

Pdi (cmH20

DISCUSSION

The results of the present study indicate that in patients with severe COPD, the application of CPAP during exercise leads to a decrease in the pressure-time integral for the inspiratory muscles in general and for the diaphragm in particular. This finding suggests a substantial reduction in the 0, cost of breathing during inspiration with CPAP (23). In addition, decreases in inspiratory muscle effort during CPAP were significantly correlated with reductions in breathlessness. There are several mechanisms whereby CPAP could assist inspiratory muscles under the present experimental conditions. The increase in ventilation observed during exercise in these patients occurred at the expense of a significant increase in end-expiratory lung volume. This breathing strategy is typical of patients with severe airflow obstruction, and it is adopted because the increased elastic recoil pressure present at higher lung volumes allows an increase in expiratory flows (7, 33, 37). It is important to recognize, however, that the dynamic increase in end-expiratory lung volume during exercise also results in the presence of positive elastic recoil pressure at end expiration. Under these conditions, the inspiratory muscles must first generate sufficient force to overcome the opposing positive recoil pressure before inspiratory airflow will begin. In this regard, dynamic hyperinflation imposes the equivalent of an inspiratory threshold load on the respiratory system (5). The application of CPAP, by counterbalancing the positive recoil pressure present at end expiration, should reduce the inspiratory threshold load imposed and thereby facilitate inspiratory muscle function. This approach has been recently investigated in dy-

RC (Liters)

AB (Liters)

FLOW (L/s)

211

VOLUME (Liters)

FIG. 7. Effects of CPAP on respiration during exercise in patient 2, who reported worsening of dyspnea during CPAP administration. Note marked increase in peak expiratory level of Pga during CPAP, indicating a substantial increase in expiratory abdominal muscle recruitment. See text for further explanation.

expiratory Pga and the decrease in end-expiratory abdominal volume that occurred after CPAP, signifying a marked increment in the degree of expiratory abdominal muscle recruitment. In addition, although there was a rise in the end-expiratory volume of the rib cage compartment during CPAP, this was offset by the accompanying decrease in abdominal volume, such that overall end-expiratory lung volume was unchanged. Figure 8 illustrates the relationship between changes in dyspnea during CPAP and concurrent changes in the 4

5

5

4

tE

3

3

1 s

r P=

r = .92 P= .OOl

'

2

1

10

0

-10

-20

-.30

- 40

-50

A / Pts-dt

0 -10

( x control )

JPga

l

.60 .ll

0 .e-1Q2

20

FIG.

COPD

pressure-time integral of Pes, Pdi, and Pga. There was a highly significant correlation between reductions in breathlessness and decreases in JPes. dt with CPAP (P c 0.005). There was also a tendency for improvement in dyspnea with reductions in JPdLdt. This latter relationship, however, did not achieve statistical significance (P = 0.11). In addition there was a significant inverse relationship between improvement in dyspnea and increases in JPga*dt during CPAP administration (P < 0.01). Hence, those patients with the largest decreases in inspiratory muscle effort and the smallest accompanying increases in expiratory muscle recruitment during CPAP experienced the greatest benefit in terms of respiratory sensation.

10

(cmH20

4'b+

IN

8. Relationship between changes in dyspnea dt. Points represent values l for each in .dividual

during patient.

CPAP Solid

-20

-30

-40

A / l’diadt ( X control

- 50

- 60

- 70

100

)

and concurrent 1ine, regression

150

A / Pgasdt ( % control )

changes equation;

in JPes. dt, JPdi l dt, and r, correlation coefficient.

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CPAP

DURING

EXERCISE

namically hyperinflated patients with severe COPD and acute respiratory failure by Petrof and co-workers (32). The positive end-expiratory recoil pressure (PEEP) present, commonly referred to as intrinsic PEEP (PEEPi) in this setting (10, 25, 31), could be readily quantified in these patients and amounted to -10 cmH20. When applied during periods of weaning from mechanical ventilation, CPAP was able to counterbalance and largely eliminate the inspiratory threshold load imposed by PEEP;, reducing the work of breathing by -50% (32). Although the presence of expiratory muscle recruitment during exercise precludes accurate measurement of PEEP; in the present study, the increase in elastic recoil pressure related to exercise-induced hyperinflation should have been on the order of 5 cmHz0.’ In addition, Milic-Emili et al. (25) and others (14) have reported that dynamic hyperinflation and PEEPi are frequently present in stable COPD patients at rest. It should be noted that in the present study, resting values of minute ventilation obtained with patients breathing on the experimental circuit were elevated. Comparable levels of resting ventilation have been observed by other investigators under similar experimental conditions (7)) the relatively high resting values most likely related to the effects of the mouthpiece per se as well as the increased circuit dead space (35). Such increases in minute ventilation further predispose to the development of dynamic hyperinflation and PEEP; (10, 31). To the extent that considerable dynamic hyperinflation may very well have been present at rest, the absolute level of PEEPi during exercise was presumably significantly greater than the value calculated from the change in lung volume from rest to exercise alone. It is therefore reasonable to assume that the magnitude of PEEPi during exercise was substantial and that CPAP aided the inspiratory muscles by reducing the threshold load imposed. Dodd and co-workers (7) have also emphasized the role of expiratory abdominal muscles in providing assistance to the muscles of inspiration in exercising COPD patients. These authors underscored the point that elastic and gravitational energy is stored in the diaphragm when abdominal muscles are recruited during expiration. Subsequent recovery of this energy on abdominal muscle relaxation at the onset of inspiration can accelerate diaphragmatic descent and generate inspiratory airflow. Moreover, active contraction of abdominal muscles may help optimize diaphragmatic length and thus place that muscle at greater mechanical advantage (7, 20, 21). To the extent that CPAP administration resulted in increased use of expiratory abdominal muscles, their ability to act as “accessory muscles of inspiration” by assisting the diaphragm in this fashion was probably enhanced. The increase in abdominal muscle recruitment observed during CPAP was of varying magnitude but present in all patients. Martin and co-workers (21) also ’ The increase in end-expiratory elastic recoil pressure related to exercise-induced hyperinflation was calculated according to the formula, APel,rs = Ers x AEELV, where APel,rs is change in elastic recoil pressure of the total respiratory system, Ers is elastance of the total respiratory system (chest wall elastance assumed to be normal), and AEELV is change in end-expiratory lung volume associated with exercise.

IN

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185

reported that CPAP (mean level of 12 cmHzO) resulted in a marked increase in the level of expiratory abdominal muscle activation in asthmatic patients with induced bronchoconstriction. In contrast, Petrof et al. (32) applied CPAP (up to 15 cmH20) in patients with severe COPD during weaning from mechanical ventilation and found no evidence of abdominal muscle recruitment. This may well be explained by the fact that patients in the latter study were semirecumbent during the application of CPAP whereas Martin et al. (21) and others have examined the response to CPAP in the upright position (3). It is well established that posture alone has an important influence on the level of abdominal muscle activation (8). In this regard, Henke and colleagues (16) reported that expiratory abdominal muscle recruitment normally present during upright bicycle exercise was largely abolished when normal subjects exercised while supine. Although factors such as abnormal gas exchange, pulmonary hypertension, and limb weakness may play a role in some instances, the reduction in exercise tolerance in patients with COPD is generally related to the reduced ventilatory capacity and sense of dyspnea that they experience (2). Such patients breathe at a relatively high fraction of their maximum ventilatory capacity. The correspondingly high fraction of maximum inspiratory force-generating capacity required for such levels of ventilation will contribute to the extreme sense of dyspnea experienced (9). This will also increase the likelihood of respiratory muscle fatigue (34). In fact, evidence for respiratory muscle fatigue has been demonstrated during high-intensity exercise in normal subjects as well as in patients with COPD (15, 29). Based on experimental studies in normal subjects during loaded breathing, the sense of dyspnea may in fact be increased relative to the degree of respiratory muscle effort in the presence of respiratory muscle fatigue (38). To the extent that this is applicable to exercising COPD patients, this would further impair exercise performance. In the present study, there was a significant relationship between decreases in breathlessness and reductions in JPesdt but not JPdidt. Other studies have also found that the sensation of inspiratory effort is closely related to Pes but not Pdi (9). Bradley and co-workers (4) were also unable to demonstrate any association between the development of diaphragmatic fatigue and dyspnea. These authors speculated that previous studies indicating that respiratory muscle fatigue per se increased breathlessness were possibly accounted for by fatigue of rib cage muscles rather than the diaphragm. This is supported by recently reported findings of Ward et al. (39) that, in the presence of diaphragmatic fatigue, increases in dyspnea are highly correlated with activation of the sternocleidomastoid and intercostal muscles but not the diaphragm. The disproportionate distribution of the volume of hyperinflation to the rib cage compartment during exercise necessarily implies shortening of inspiratory intercostal and accessory muscle with attendant reduction in their ability to generate pressure. Consequently, these muscles may be particularly prone to the development of

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186

CPAP

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fatigue in exercising COPD patients (7). The presence of expiratory abdominal muscle recruitment may theoretically further predispose to rib cage muscle fatigue in two ways. First, in the setting of expiratory V limitation, increased abdominal muscle effort will shift volume from the abdomen into the rib cage without altering overall lung volume (18), thus placing the inspiratory rib cage muscles at a further mechanical disadvantage. Second, a rapid fall in Pes at inspiratory onset related to abdominal muscle relaxation would tend to produce paradoxical rib cage motion unless inspiratory intercostal and accessory muscle activation were increased to stabilize the rib cage and prevent paradox from occurring. It is therefore conceivable that the increased dyspnea observed in those three individuals with the greatest increases in expiratory abdominal muscle recruitment was the result of an adverse effect on rib cage muscle function. Increased expiratory muscle effort per se may have also resulted in worsening of breathlessness. Recent work suggests that active expiration may be associated with a significant increase in O2 consumption and that the expiratory muscles themselves may also develop fatigue under loaded conditions (30). O’Donnell and co-workers (27) reported that application of positive pressure (4-5 cmH20) during expiration alone (i.e., EPAP) had no consistent effect on the sense of breathing effort in COPD patients, whereas normal subjects, in contrast, experienced significant breathlessness. Although not directly examined, they postulated that this observed difference in respiratory sensation might be related to an increase in the level of expiratory muscle activity during positive-pressure breathing in the normal subjects compared with those with COPD. In normal subjects, an increase in downstream impedance during expiration (occurring with the use of either EPAP or CPAP) would require increased expiratory muscle action to maintain the level of expiratory flow and prevent an increase in end-expiratory lung volume. On the other hand, the presence of V limitation in the COPD patients would itself preclude changes in expiratory V-volume events at low levels of applied pressure (18), thus largely eliminating the need for expiratory muscle recruitment. The results of the present study indicate that the level of expiratory flow (at isovolume) during exercise was slightly reduced by the application of CPAP in most patients. This is in contrast to the patients reported by O’Donnell et al. (28) whose volume-matched expiratory flows were unaffected by CPAP, and it is probably related to the higher level of pressure employed in the present study. The increase in expiratory muscle effort during CPAP, although presumably an attempt to reestablish maximum expiratory V, was insufficient to do so in the majority of patients. This may have occurred to minimize unpleasant respiratory sensation arising from rib cage or abdominal muscles, as discussed earlier. Alternatively, there is evidence that patients with severe COPD have a reduced ability to perceive added inspiratory and expiratory resistive loads (13, 26), and this also may have played a role in failure to completely reverse the reduction in expiratory V occurring with CPAP. It is interesting to note that two patients actually

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demonstrated an increase in volume-matched expiratory V during CPAP. Although unusual, it is conceivable that the level of expiratory pleural pressure required to produce maximum expiratory flow had not been achieved during exercise alone (33) and that this only occurred with the increased expiratory effort accompanying the use of CPAP. An alternative explanation is that the boundaries of the maximum-effort V-volume relationship were actually exceeded during CPAP. This could have occurred if CPAP produced bronchodilation, thus permitting an increase in the magnitude of maximum . achievable V . In this regard, there were in fact small decreases in RL during CPAP in the two patients in question. In keeping with this observation, Martin and co-workers (21) reported that CPAP produced significant reductions in RL when administered to subjects with acute asthma and speculated that stimulation of airway stretch receptors may have resulted in reflex bronchodilation. Finally, we cannot exclude small errors in relative placement of exercise V-volume curves on the volume axis that could also account for these findings. Pardy and colleagues (29) have suggested that inspiratory muscle fatigue may be an important contributing factor to exercise limitation in patients with severe COPD. If this is indeed the case, then one would expect that CPAP, through its ability to assist the inspiratory muscles, would have a beneficial effect on exercise performance. The recent findings of O’Donnell and coworkers (28) that CPAP improved exercise endurance in COPD patients provide further evidence in support of this notion. It should be pointed out, however, that in their study the only individual without improvement in exercise endurance was also the sole patient who failed to report any reduction in breathlessness during CPAP. Thus it would appear that improvements in exercise endurance may be closely linked with reductions in dyspnea. The present results indicate that although CPAP improves inspiratory muscle performance, it may also result in substantial increases in expiratory muscle recruitment in some patients. In these individuals, expected reductions in dyspnea related to improved inspiratory muscle function may be offset by increased expiratory muscle effort. The level of CPAP chosen should therefore attempt to maximize reductions in inspiratory mu scle effort while minimizing increases in expiratory muscle activity. This should constitute the optimum level of CPAP and provide the greatest benefit to patients in terms of both respiratory sensation and the overall O* cost of breathing. It is conceivable that CPAP administration, by allowing an increase in peak 0, consumption during exercise, might constitute a useful adjunct to pulmonary rehabilitation exercise programs aimed at reversing general physical deconditioning and improving functional status (2, 28). It should be stressed, however, that there is considerable variability in the operating characteristics of currently available CPAP systems (22). Those circuit designs that allow significant reductions in the level of airway pressure to occur during inspiration will tend to nullify any potential benefit with respect to unloading of

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CPAP

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the inspiratory muscles. Conversely, excessive increases in airway pressure during expiration will be associated with an increase in expiratory work of breathing. The ability of CPAP to aid inspiratory muscle function and alleviate dyspnea is therefore critically dependent on maintaining a stable level of airway pressure throughout the respiratory cycle (17,22). This requires a system that provides sufficiently high V to meet the inspiratory V demands of the patient as well as a non-flow-dependent threshold resistor valve (22). In practice, however, this may be difficult to achieve, as is evident from our experimental records. It is likely that a more ideal CPAP delivery system, perhaps utilizing a servo-feedback mechanism to better control airway pressure, would have resulted in greater physiological benefit. In summary, CPAP unloads the inspiratory muscles and improves inspiratory muscle function during exercise in patients with severe COPD. In some patients, however, expected reductions in dyspnea during CPAP may be negated by substantial increases in expiratory abdominal muscle activity. These findings suggest that the level of CPAP applied should be titrated in each individual patient and that respiratory sensation under these conditions may reflect a balance between both inspiratory and expiratory muscle effort. The authors thank Sheila Tremblay for technical assistance and Suzanne Desmarais for typing the manuscript. This investigation was supported in part by the Medical Research Council of Canada and the Canadian Cystic Fibrosis Foundation. B. J. Petrof was the recipient of a Fellowship from the Canadian Cystic Fibrosis Foundation. E. Calderini was supported by San Raffaele Hospital, Milan, Italy. S. B. Gottfried was the recipient of a Parker B. Francis Fellowship in Pulmonary Research from the Puritan-Bennett Foundation and is presently a Medical Research Scholar of the Fonds de la Recherche en Sante du Quebec. Address for reprint requests: S. B. Gottfried, Respiratory Div., Montreal General Hospital, 1650 Cedar Ave., Montreal, Quebec H3G lA4, Canada. Received

17 July

1989; accepted

in final

form

21 February

1990.

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31. PEPE, P. E., AND J. J. MARINI. Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction. The auto-PEEP effect. Am. Reu. Respir. Dis. 126: 166-170, 1982. 32. PETROF, B. J., M. LEGARE, P. GOLDBERG, J. MILIC-EMILI, AND S. B. GOTTFRIED. Continuous positive airway pressure reduces inspiratory work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease. Am. Reu. Respir. Dis. 141: 281-289, 1990. 33. POTTER, W. A., S. OLAFSSON, AND R. E. HYATT. Ventilatory mechanics and expiratory flow limitation during exercise in patients with obstructive lung disease. J. Clin. Invest. 50: 910-919, 1971. 34. ROUSSOS, C., AND P. T. MACKLEM. The respiratory muscles. N. Engl. J. Med. 307: 786-797, 1982. 35. SACKNER, J. D., A. J. NIXON, B. DAVIS, N. ATKINS, AND M. A.

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