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CHEST/105/4/APRIL.1994 1053

Respiratory Muscle Rest Using NasalBiPAP Ventilation in Patients WithStable Severe COPD*

Jeffrey P. Renston, M.D.; Anthony F. DiMarco, M.D., F.C.G.P.; and

Gerald S. Supinski, M.D., F.C.C.P.

To more systematically evaluate the effect of respi-

ratory muscle rest on indices of ventilatory func-

tion, nine outpatients with stable, severe COPD

were treated with nasal pressure-support ventila-

tion delivered via a nasal ventilatory support system

(BiPAP, Respironics, mc) for 2 h a day for 5 consecu-

tive days. An additional eight control patients were

treated with sham-BiPAP. Maximum inspiratory pres-

sure (MIP), maximum expiratory pressure (MEP), max-

imum voluntary ventilation (MVV), arterial blood gas

values, Borg dyspnea score, dyspnea-associated func-

tional impairment scales, and distance walked in 6 mm

were measured in subjects prior to and following the

week-long trial. Nasal BiPAP produced a 66.3 ± 6 per-

cent reduction in peak integrated diaphragmatic elec-

tromyographic (EMG) activity. There were no statisti-

cally significant changes in MIP, MEP, MVV, arterial

pH, PaCO2, or Pa02 or in objective measures of func-

tional impairment from dyspnea in either group after

ventilator or sham treatment. However, nasal BiPAP

reduced the Borg category score during resting, sponta-

neous breathing from 2.0 ± 0.4 to 0.7 ± 0.3 (p<O.Ol) after

5 days of treatment. In contrast, sham BiFAP-treated

patients had no change in their dyspnea score, which

was 1.8 ± 0.4 and 1.3 ± 0.4 before and after sham treat-

ment, respectively. Nasal BiPAP also increased distance

walked in 6 mm from 780 ± 155 to 888 ± 151 ft (p<0.01)

(23,400 ± 4,650 to 26,640 ± 4,530 cm) (p<O.Ol), whereas

sham-BiPAP had no effect (768 ± 96 and 762±106 ft

[23,040 ± 2,880 and 22,860 ± 3,180 cmD before and after

sham treatment, respectively). In conclusion, these re-

sults indicate that nasal pressure-support ventilation,

delivered via nasal BiPAP, improves exercise capacityand reduces dyspnea over the short term in selected

outpatients with stable severe COPD. Whether such

short-term improvement can be sustained merits further

study. (Chest 1994; 105:1058-60)

BiPAPventilatory support system; EMGelec-tromyogram; MEPmaximum expiratory pressure;MIP=maximum inspiratory pressure; MVV=maximumvoluntary ventilation

C hronic fatigue of the respiratory muscles has

been postulated to contribute to the dyspnea,

decreased ventilatory capacity and reduced exercise

tolerance of individuals with severe COPD.”2 If this

hypothesis is correct, then resting the respiratory

muscles of these patients would be expected to

ameliorate these abnormalities.

In keeping with such a possibility, resting the

respiratory muscles using noninvasive negative or

positive pressure ventilation has resulted in im-

proved ventilatory function, respiratory muscle

strength, and sense of well-being in several studies

of patients with moderate to severe COPD. For

example, using negative pressure ventilation, in-

cluding an iron lung, Cropp and DiMarco3 demon-

strated significant improvement in duration of sus-

tained ventilation, maximum inspiratory pressure

(MIP), and reduction in degree of hypercapnia in

5From the Department of Medicine, Pulmonary Division,

MetroHealth Medical Center, Cleveland.Manuscript received October 27, 1992; revision accepted Au-gust 30, 1993.Reprint requests: Dr. Renston, MetroHealth Medical Center,2500 MetroHealth Drive, Cleveland 44109-1998

patients with severe COPD. Several other studies

have also demonstrated improvement in ventilatory

parameters following ventilatory support in similar

patients.4’3 In contrast, other investigations using

similar protocols have failed to demonstrate im-

provement in ventilatory function.’�’8 Several fac-

tors may have contributed to these observed dis-

crepancies, including variation in the utility or

composition of control groups, the use of subjective

rather than objective measures of dyspnea and

exercise tolerance, differences in the degree of

respiratory muscle rest achieved, and patient selec-

tion. For example, while half of these studies used a

control group,S.7�U�lti.19 none of them employed sham

or blinded controls. In addition, only two studies

measured changes in sensation of dyspnea, exercise

tolerance, or sense of well-being using objective

scales to assess these parameters.6”9 As a result, the

relationship between respiratory muscle rest and

ventilatory function in patients with COPD remains

controversial.20’2’

A number of ventilatory devices have been uti-

lized to provide respiratory muscle rest. The nasal

ventilatory support system (BiPAP, Respironics, mc,Murrysville, Pa) employs nasal pressure-support

Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21693/ on 04/28/2017

1054 Respiratory Muscle Rest Using Nasal BiPAP Ventilation (Renston, DiMarco, Supinski)

as a means of noninvasively delivering positive

airway pressure to patients with respiratory fail-

ure.2224 This system is small, easy to use, and

appears to be better tolerated than negative pres-

sure devices, which are cumbersome and impracti-

cal for patient use. Consequently, the nasal BiPAP

system may be more amenable for clinical use in the

outpatient setting.

The purpose of the present study was twofold.

First, using objective clinical measurements, we

endeavored to more systematically evaluate the

influence of respiratory muscle rest on indices of

ventilatory function, including respiratory muscle

strength, gas exchange and, in particular, on exer-

cise tolerance, severity of dyspnea, and patient

sense of well-being. Second, we sought to deter-

mine the utility of a less complex and more practical

noninvasive ventilatory device-the nasal BiPAP

ventilatory system-for resting the respiratory

muscles. We report, herein, the results of a prospec-

tive, randomized, sham-controlled trial of respira-

tory muscle rest on ventilatory function, using nasal

BiPAP, in a group of outpatients with stable, severe

COPD.

Patient Selection

METHODS

Seventeen outpatients with severe COPD were identified

from the records of the pulmonary function laboratory at

MetroHealth Medical Center. Severe COPD was defined as an

FEV1 less than 50 percent of the predicted value or a ratio of FEy1

to forced vital capacity less than 55 percent of the predicted value.

Patients were in stable condition at the time of study; all had had

pulmonary function tests and arterial blood gas measurements

performed within approximately the previous 12 months. Pa-

tients with congestive heart failure, asthma, lung cancer, tho-

racic cage abnormalities, prior thoracic surgery, restrictive pul-

monary disease, obstructive sleep apnea, degenerative joint

disease, or who had experienced an exacerbation of COPD or

pulmonary infection within the preceding 6 weeks were ex-

cluded. Patients were alternately assigned to the two study groups.

Informed consent was obtained from all patients prior to

participation. The protocol was approved by the Committee on

Human Investigation at our institution.

Surface Die phragmatic Electromyogram (EMG)

To assess the effectiveness of nasal BiPAP in reducing the

work of the inspiratory muscles, surface diaphragmatic EMG

activity was monitored by placing gel electrodes over the sixth to

seventh intercostal space near the right costal margin and

recording EMG activity before and after initiation of nasal

B1PAP. The EMG signal was amplified using a preamplifier

(WPI), filtered (10 to 10,000 Hz), rectified, integrated using a

filter (Paynter), and recorded on a four-channel recorder (Gould).

Tidal volume and respiratory rate were measured using a

pneumotachograph (Fleisch) (± 2 cm H20) placed in-line be-

tween the nasal mask and ventilator tubing.

Measurement of Physiologic Parameters

Patients performed a 6-mm walk test, which has been shown

to be a simple and reproducible index of exercise tolerance.ss

During the 6-mm walk test, patients were asked to walk as far as

possible within a 6-mm period while breathing room air or their

previously prescribed level of home oxygen. They were allowed

to stop, rest, and resume walking at their own discretion.

Patients were given no encouragement and eye contact was kept

minimal. Maximum inspiratory pressure, maximum expiratory

pressure (MEP), maximum voluntary ventilation (MVV), and an

arterial blood gas determination were also performed. Measure-

ments of MIP and MEP were performed at residual volume and

total lung capacity, respectively, according to the method pro-

posed by Black and Hyatt,26 using a pressure gauge calibrated

between 0 and 150 cm H2O pressure (Magnehelic; Dwyer

Instruments, mc). The average value of three efforts was

utilized for the MIP and MEP measurement. Maximum volun-

tary ventilation was measured over 15 s during maximal

breathing effort. Arterial blood gas determinations were per-

formed at rest, while patients were in the sitting position and

breathing room air or their prescribed level of home oxygen.

Assessment of Dyspnea and Functional Impairment

To assess severity of dyspnea, we administered the modified

Borg category scale,27 an instrument that categorizes severity of

dyspnea from “O=nothing at all” to “lOmaximal.” Patients

were shown a reproduction of the modified Borg scale and asked

to indicate the category that most closely described their cur-

rent level of breathlessness at that moment.

To more objectively assess the impact of lung disease on

ability to perform activities of daily living, functional impair-

ment from breathlessness was evaluated using three different

clinical scales designed for this purpose. First, the Modified

Medical Research Council Dyspnea Scale28 rates functional

impairment associated with breathlessness from “Onot troubled

by breathlessness, except with strenuous exercise” to “4too

breathless to leave the house or breathless when dressing or

undressing.” A second scale, the Oxygen-cost diagram,29 is a

visual analogue scale that rates breathlessness from “0=breath-

less while sleeping” to “40breathless with brisk walking

uphill.” The third scale, termed the BiPAP “Functional Impair-

ment Scale,” is a brief questionnaire devised by us. which rates

breathlessness as “none” (1 point), “moderate” (2 points), or

“severe” (3 points) for each of several daily tasks, including

combing hair, brushing teeth, making the bed, bathing, walking,

and shopping, resulting in a total score between 12 (no breath-

lessness) and 36 (maximal breathlessness). If patients did not

perform an activity, they were asked to estimate their antici-

pated degree of dyspnea. We devised this scale in an attempt to

better discriminate breathlessness associated with various rou-

tine activities of daily living. Patients were presented facsimiles

of these various scales and asked to respond by identifying their

current functional level. All dyspnea and functional impairment

scales were administered at rest, immediately before initiation

of physiologic testing.

Protocol

To reduce the possibility of a learning effect, all patients

executed a practice 6-mm walk test and MIP and MEP maneu-

vers prior to beginning the 5-day study.ss Patients were then

randomized to receive either nasal BiPAP (nasal BiPAP, model

S/T-D; Respironics, Inc, Murrysville, Pa) (nine patients) or

sham-BiPAP (eight patients). Nasal BiPAP was initiated in the

experimental group using the “spontaneous” mode by slowly

increasing inspiratory positive airway pressure until diaphragm

EMG activity was reduced to a minimum. This usually required

between 15 and 20 cm H2O pressure. Expira tory positive airway

pressure was maintained at 2 cm H2O pressure. Patients were


CHESTI1O5/4/APRIL, 1994 1055

instructed to keep their mouths closed at all times to avoid air

leaks. Patients receiving sham-BiPAP were connected to the

BiPAP ventilator with a T piece interposed between the nasal

mask and ventilator tubing, with the power turned on, and both

inspiratory positive airway pressure and expiratory positive

airway pressure adjusted to the minimum of 2 cm H2O pressure.

Dead space between the nasal mask and T piece was minimal.

Control patients received no special instructions. Patients had

no knowledge of the purpose of the study or function of the

device. All other conditions and patient interactions were iden-

tical in both groups.

Subjects received nasal BiPAP (or sham-BiPAP) for 2 h/d over

5 consecutive days, while seated in a comfortable chair. The

optimal regimen for nasal BiPAP is unknown. This regimen was

selected because patients indicated they would be willing to use

the nasal BiPAP instrument as outpatients for about 2 h/d. We

empirically chose 5 consecutive days because this represented a

practical time frame for patient participation.

Physiologic parameters and degree of dyspnea and functional

impairment were assessed at rest in all patients on the first day

of the study prior to beginning the ventilator trial and again 15

mm following termination of ventilation on the fifth study day.

All participants completed the entire study protocol without

discomfort or adverse effects on respiration or sense of well-

being.

Statistical Analysis

Patient demographic information was analyzed using un-

paired Student’s t tests Nasal BiPAP vs sham-BiPAP control values

obtained at baseline (day 1) were compared using unpaired Student’s

tests for the following measurements: arterial pH, PaCO2, PaO2,

MIP, MEP, MVV, Borg dyspnea score, distance walked in 6 mm,

and scales of functional impairment. Values at baseline (day 1)

compared with postventilation (day 5) treatment within groups,

for the above measurements, as well as for surface diaphragm

EMG activity, respiratory rate, and tidal volume, were com-

pared using paired Student’s t tests A Borsferroni correction was em-

ployed to correct for assessment of multiple variables in the

study. Using the Bonferroni correction, comparisons were taken

as statistically significant only if they had a p value less than

0.02.

All results are expressed as the mean ± SEM.

Demographics

RESULTS

The characteristics of the study group are shown

in Table 1. There were six women and three men

with a mean age of 62 years in the nasal BiPAP

group, and five women and three men with a mean

age of 68 years in the sham-BiPAP group. Mean

FEy, was 0.76±0.08 L and 0.73±0.06 L for the

nasal BiPAP and sham-BiPAP treated groups, re-

spectively.

Diaphragmatic EMG

The peak heights of the integrated EMG signals

were averaged over five consecutive breaths before,

and again, 1 mm after initiation of BiPAP ventila-

tion. For the group as a whole, nasal BiPAP pro-

duced a mean reduction in the amplitude of the

surface diaphragmatic EMG activity of 66.3±6

percent. The reduction in surface diaphragmatic

EMG activity was maximal within 5 to 10 breaths

after initiation of nasal BiPAP in all patients. There

were no statistically significant differences in respi-

ratory rate (15.9 ± 1.2 and 16.3 ± 1.8 breaths/mm)

or tidal volume (0.65±0.10 and 0.92±0.18 L)measured immediately before and after application

of nasal BiPAP, respectively, for each parameter.We interpreted the reduction in surface diaphrag-

matic EMG activity to be an indication that dia-

phragm muscle activation was being reduced by

nasal BiPAP administration.

Pulmonary Function

The results of arterial blood gas measurements at

baseline (day 1) and following 5 days of ventilator

treatment (day 5) are shown in Figure 1. There

were no statistically significant differences in values

at baseline between the two groups. No significant

change in arterial blood gas measurements was

observed in either study group following the week-

long ventilator trial.

Values for MIP, MEP, and MVV at baseline and

on day 5 of ventilator treatment, for the sham- and

nasal BiPAP groups, are shown in Figure 2. There

were no statistically significant differences in these

measures at baseline or after ventilator treatment in

either study group.

Dyspnea and Functional Impairment Scales

Figure 3 shows the severity of dyspnea, as as-

sessed by the modified Borg category scale,27 in the

Table 1-Characteristics of the Patients With COPDWho Participated in the Study

Group Age, yr/Sex

FEV1,

L (% predicted)

FEV1/FVC,

%

Nasal BiPAP, n9

1 62/F 0.95 (50) 42

2 59/F 0.58 (26) 28

3 61/F 0.91 (40) 34

4 68/F 1.01 (54) 40

5 62/F 0.45 (22) 23

6 60/F 0.49 (23) 32

7 61/M 0.71 (21) 34

8 57/M 0.73 (22) 24

9 64/M 1.05 (32) 36

Mean 62 0.76 (32) 33

Sham-BiPAP, n8

1 73/F 0.71 (38) 42

2 75/F 0.65 (27) 29

3 71/F 0.69 (45) 30

4 60/F 1.04 (58) 47

5 69/F 0.95 (53) 55

6 63/M 0.56 (26) 29

7 76/M 0.50 (22) 29

8 53/M 0.77 (23) 28

Mean 68 0.73 (37) 36


Sham-Bipap

Nasal BipapSham-BipapNasal Bipap

60

40

20

0

0C’4

I

EC)

a-

0

E(5

a-w

DaylDay5

nasal BiPAP and sham-BiPAP groups, before and

following termination of ventilator treatment. There

was no statistically significant difference between

groups at baseline (day 1). Nasal BiPAP produced a

reduction in category of dyspnea, as measured by

the Borg score, whereas sham-BiPAP had no effect.

During resting spontaneous breathing, the Borg

category score was reduced by 67 percent by nasal

BiPAP treatment (p<O.Ol; sham-BiPAP produced

only a 27 percent reduction,which was not statisti-

cally significant.

Following the 5-day ventilator trial, values for the

modified medical research council dyspnea scale

and oxygen-cost scales in the sham-BiPAP group

suggested impairment, whereas in the nasal

BiPAP group, values for all functional impairment scales

suggested improvement (Table 2). However, these

changes were not statistically significant.

Distance Walked

The mean net change in distance walked in 6 mmon day 5, compared with the baseline value, for the

1056

��Li�i�!ELLI��Ji I

Day? DayS Day? Day5

FIGURE 1. Arterial blood gas measurements at baseline (day 1)and following 5 days (day 5) of sham- and nasal BiPAP treat-

ment. No statistically significant difference was observed in pH,

PaCO2, or Pa02 in either study group at baseline or following theweek-long ventilatory trial.

‘�0Lii‘�LL1_

Dayl Doy5

FIGURE 2. MIP, MEP, and MVV values at baseline (day 1) and

following 5 days (day 5) of sham- and nasal BiPAP treatment. No

statistically significant difference was observed in MIP, MEP, orMVV in either study group at baseline or following the week-

long ventilatory trial.

sham- and nasal BiPAP-treated groups, is shown in

Figure 4. There was no statistically significant dmf-ference in baseline values between groups. How-

ever, all patients receiving nasal BiPAP walked

Sham-Bipap

� 3.0 Nasal Bipap

�2.0 j j

IDay 1 Day 5 Day I Day 5

FIGURE 3. Modified Borg category scale dyspnea score at

baseline (day 1) and following 5 days (day 5) of sham- and nasal

BiPAP treatment. There was a statistically significant reductionin category of dyspnea in the nasal BiPAP- treated group (p<O.Ol),

but not the sham-BiPAP group, during resting spontaneous

breathing (auarbitrary units).


Sham-Bipap

Nasal Bipap-I-

a, ___�_ 160

-oa,

120

0

a,C.) 80C0‘I,

� 40

C

a,0) 0 -

C0

-c0 -40

FIGURE 4. Change in distance walked in 6 mm following 5 days

of sham- and nasal BiPAP treatment. Distance walked in 6 mmincreased significantly in the nasal BiPAP-treated group (p<O.Ol),but not the sham-BiPAP group.

CHEST/105/4/APRIL,1994 1051

Table 2-Values for Dyspnea-Related Functional Impairment With Activities of Daily Living as A8sessed by Three

Scales *

Scale

Sham-BmPAP Nasal BiPAP

Day 1 Day 5 Day 1 Day 5

MMRCDI 2.9±0.4 3.3±0.4 3.1±0.4 2.6±0.5Oxygen-cost diagram 15.5 ± 2.4 13.4 ± 2.0 16.6 ± 3.7 17.0 ± 4.0

BiPAP “functional impairment”� 24.4± 1.5 23.5± 1.9 24.1±2.0 22.3±2.1

SNo significant improvement in each group.

I Dyspnea: minimal0; maximal4 (MMRCDmodified medical research council dyspnea scale).

I Dyspnea: minimal 40; maximal 0.

�Dyspnea: minimall2; maximal=36.

further following the week-long ventilator trial,

with distance walked in 6 mm increasing from

780±155 to 888 ±151 ft (23,400 ± 4,650 to 26,640 ±

4,530 cm) (p<O.Oi). In the control group, mean dis-

tance walked averaged 768 ± 96 and 762 ± 106 ft

(23,040±2,880 and 22,860±3,180 cm) before and

after sham treatment, respectively (p=NS).

DISCUSSION

In this study, nasal pressure-support ventilation,

delivered via the nasal BiPAP ventilatory system,

administered for 2 h/d for 5 consecutive days,

significantly reduced severity of dyspnea and im-

proved distance walked in 6 mm in outpatients with

stable severe COPD.

Methodologic Considerations

Several points regarding methodology must be

considered in the interpretation of our results.

First, we used surface diaphragmatic EMG activity

to demonstrate the adequacy of respiratory muscle

rest by the nasal BiPAP system. Measurement of

surface diaphragmatic EMG activity may be prone

to artifact due to motion of the chest and abdominalwall, and to electrical interference from nearby

muscles. An alternative technique for measuring

diaphragm muscle contractile activity includes use

of transdiaphragmatic balloon pressure catheters.

However, use of such catheters is more invasive and

can potentially induce air leaks, thus compromising

the function of the nasal mask. Our findings of

marked reductions in surface diaphragmatic EMG

activity suggest that the work of the diaphragm was

reduced. Our results are in keeping with those of

Ambrosino et a18 and others10 who showed reduc-

tions of up to 53 percent in surface diaphragmatic

EMG signals in patients with COPD who received

noninvasive positive pressure ventilation.

Second, we employed the 6-mm walk test23 to

assess low-intensity exercise tolerance in our pa-

tients, which has been shown to objectively measure

exercise tolerance in patients with chronic bronchi-

tis.30 The 6-mm walk test may be a better indicator

of the level of dyspnea and functional impairment

experienced by patients with COPD in their daily

lives, compared with other tests, such as cycle

ergometry or use of a treadmill, both of which

measure high-intensity exercise tolerance.’6

Finally, we administered nasal BiPAP for 2 h/d

for 5 consecutive days. This regimen was chosen to

assure optimal patient comfort, compliance, and

tolerance. Longer periods of nasal BiPAP utiliza-

tion, reported in other studies, have met with lim-

ited patient acceptance9”9 and resulted in a signifi-

cant patient dropout rate. It is possible that alternative

regimens, such as longer sessions or duration of use,

might have led to greater improvement in sensationof dyspnea and exercise tolerance. In our study, all

patients completed the protocol, suggesting thatthis regimen was well accepted and potentially

suitable for routine clinical use by outpatients with

severe COPD.


Comparison With Previous Studies

1058 Respiratory Muscle Rest Using Nasal BiPAP Ventilation (Renston, DiMarco, Supinski)

Previous studies aimed at assessing the associa-

tion between respiratory muscle rest and ventilatory

function in patients with COPD have yielded con-

flicting results. Cropp and DiMarco,3 in a prospec-

tive controlled study, reported improved respiratory

muscle strength, endurance, and reduced hyper-

capnia in outpatients with stable severe COPD who

received negative pressure ventilation using either

tank or cuirass ventilators for 3 to 6 h/d over 3

consecutive days. Scano et al7 showed a slight, but

significant, increase in MIP and a reduction in

PaCO2 in patients treated 4 h/d for 7 consecutive

days in a tank ventilator. Compared with nasal

BiPAP used in the present study, the tank ventilator

may have achieved a greater degree of respiratory

muscle rest, as evidenced by the reduction in

hypercapnia seen in these patients. This may also

explain the lack of improvement in respiratory muscle

strength observed in our study, compared with the

previous investigations. Gutierrez et al6 adminis-

tered cuirass ventilation for 8 h, once a week, to

patients with advanced chronic airflow limitation

and demonstrated improvement in MIP and arterial

blood gas measurements, as well as in distance

walked in 12 mm and in quality of life. Gutierrez et

al attributed these changes to correction of chronic

inspiratory muscle fatigue. These results were sup-

ported by Fernandez et a12#{176}who treated patients

with chronic respiratory failure for 6 to 8 h/d for 2

consecutive days with a ventilator (Pneumowrap)

and demonstrated improvement in gas exchange

and respiratory muscle strength. Despite the posi-

tive findings from these latter two investigations, a

placebo effect could not be excluded, since both

studies lacked control groups. Similar results have

been shown in several studies that have employed

noninvasive positive airway pressure ventilation in

patients with severe COPD. Carrey et al” demon-

strated reductions in diaphragmatic EMG activity

and improvement in oxygen saturation and PaCO2 in

some patients with severe COPD given intermittent

positive pressure ventilation for 1 to 2 h. These

changes may have resulted from having set the

ventilator at a slightly higher rate than the spontane-

ous respiratory rate of their study patients. This is in

contrast to our study, in which patients using thenasal BiPAP system were allowed to breathe at their

own spontaneous rate. Finally, Ambrosino et al,8

using nasal BiPAP for 2 h/d for 2 consecutive days,

found improvement in gas exchange in patients with

stable severe COPD. However, the number of pa-

tients tested in their study was small, and sham

control subjects were not utilized.

In contrast to these observed beneficial effects of

noninvasive negative and positive pressure ventila-

tion, Zibrak et al’8 found no change in gas exchange,

respiratory muscle strength, or exercise duration in

patients with severe COPD, using a poncho wrapventilator for 4 h/d for 4 to 6 months. These results

may have been influenced by a significant patient

dropout rate and by intolerance of the ventilatory

device used in their study. Celli et al,’7 using a

ventilator (Pulmowrap) for 3 to 11 h/d for S weeks,

were unable to show any increased benefit of respi-

ratory muscle rest therapy over that achieved by a

comprehensive pulmonary rehabilitation program.

In this study, however, most patients were

normocapnic, compared with our patients who ex-

hibited significant hypercapnia. Since Juan et a13’

have previously shown that hypercapnia can have

deleterious effects on respiratory muscle function,

this may partially explain the negative results ob-

served in their study. Lastly, Strumpf et al’9 found

no improvement in pulmonary function, respiratory

muscle strength, gas exchange, exercise endurance,

or dyspnea ratings in patients who were adminis-

tered nasal BiPAP for 6 to 7 h per night for 3

months. Since patients performed the nasal BiPAP

protocol at home, these negative results may have

been influenced by the lack of supervision and/or by

noncompliance with use of the nasal BiPAP instru-

ment.

Several well-characterized scales were adminis-

tered to our patients to assess the effect of nasal

BiPAP treatment on severity of dyspnea and on the

ability to perform activities of daily living. These

scales provide a means of quantifying the subjective

responses of patients with regard to the effects of

lung disease on sense of well-being. Nasal BiPAP-

treated patients, but not the sham group, showed a

trend toward improvement in all functional scales

following the week-long ventilator trial, In addition,

statistically significant decreases in dyspnea were

achieved as measured by the Borg category scale.

Our results support the findings of Marino and

Braun,5 who reported improvements in dyspnea and

functional ability following long-term intermittent

mechanical ventilation in patients with respiratory

muscle fatigue, and Gutierrez et al,6 who found

significant improvements in quality-of-life score in

patients treated with weekly cuirass ventilation.

Our study did not assess the degree to which the

observed improvement in dyspnea and exercise tol-

erance could be sustained following nasal pressure-

support ventilation. Such improvement may be rather

short lived. Consequently, our results might reflect

short-term improvement related to use of nasal

BiPAP and cannot be taken as unequivocal evidence

that long-term benefit can be achieved or expected


CHEST/105/4/APRIL,1994 1059

from the application of nasal BiPAP, as was em-

ployed in our study protocol.

Mechanism of Action

There are several theoretic mechanisms by which

nasal BiPAP may have influenced respiratory muscle

function.

Nasal BiPAP treatment reduced surface diaphrag-

matic EMG activity, which has been taken as an

indication of inspiratory muscle rest.4 Therefore,

nasal BiPAP may have elicited a beneficial effect by

resting chronically fatigued respiratory muscles.

However, following nasal BiPAP administration, we

observed no statistically significant improvement in

respiratory muscle strength, a measurement that

would be expected to improve with the resting of

fatigued muscles. It is known that some types of

muscle fatigue reduce force output primarily during

submaximal muscle activation (ie, low-frequency

fatigue), and that this type of dysfunction cannot be

detected by simple assessment of muscle function

during maximal levels of muscle activation, as was

done in the present study.”32 Recent work suggests

that low-frequency fatigue may be a clinically im-

portant determinant of respiratory muscle function,

since the respiratory muscles are normally driven at

low excitation frequencies.”16 It is possible that our

study patients were limited primarily by low-fre-

quency muscle fatigue, which was ameliorated by

nasal BiPAP treatment, but was not detected by our

methods used to assess respiratory muscle strength

(ie, maximal static pressure production).

Previous studies have suggested that respiratory

muscle function can be impaired by the presence of

significant hypercapnia or hypoxemia.3’ Since we

observed no significant changes in arterial PaCO2 or

Pa02 measurements following nasal BiPAP treat-

ment, the observed improvement in dyspnea or

exercise tolerance cannot be explained by this mecha-

nism.

Lastly, respiratory muscle afferent neural path-

ways have been shown to play a role in several

aspects of breathing.3,5 Furthermore, changes in

respiratory muscle afferent neural input may result

in delayed effects on respiratory muscle function.34

Nasal BIPAP may have affected respiratory motor

outflow by altering respiratory muscle afferent ac-

tivity in response to changes in respiratory muscle

activation or lung mechanics. Theoretically, such

effects could have contributed, at least in the short

term, to the reduced Borg score and improved

exercise tolerance seen following discontinuation of

nasal BiPAP treatment. However, similar long-term

effects by this mechanism are only speculative.

CONCLUSIONS

In the present study, a sham control group was

employed to reduce placebo effects. Functional

impairment, exercise tolerance, and severity of

dyspnea were assessed using several different ob-

jective scales designed for this purpose in an at-

tempt to lessen inaccuracies associated with subjec-

tive reports by patients. In addition, the regimen of

nasal BiPAP treatment used was well tolerated by

our patients. Our results suggest that, at least in the

short term, nasal pressure-support ventilation, de-

livered via the nasal BiPAP ventilatory system,

results in a reduction in severity of dyspnea and

improvement in exercise tolerance as assessed by

distance walked in 6 mm, in selected outpatients

with stable severe COPD. Whatever the mechanism,

nasal BiPAP treatment appears to be effective and

well tolerated, and may prove beneficial and cost-

effective for use in selected outpatients with stable

severe COPD.

ACKNOWLEDGMENT: We thank Daniel Stofan, and YlonneWatkins and Diane Delletro for expert technical and editorialassistance, respectively. No industry support was obtained for

this study, except for loan of a nasal BiPAP, model S/T-Dventilatory support system (Respironics, mc), the solicitation ofwhich was initiated solely by the authors.

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