write the review about this article
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
� ORIGINAL ARTICLE
EFFECTS OF CPAP ON THE PHYSICAL EXERCISE TOLERANCE OF MODERATE TO
SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE
! MICHEL SILVA REIS1,2, HUGO VALVERDE REIS1,2, DANIEL TEIXEIRA SOBRAL1,2, APARECIDA MARIA
CATAI3, AUDREY BORGHI-SILVA4
! 1Research Group in Cardiorespiratory Physical Therapy (GECARE), Department of Physical Therapy, Faculty of
Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil 2Physical Education Undergraduation Program, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil 3Laboratory of Cardiovascular Physical Therapy, Department of Physical Therapy, UFSCar, São Carlos, SP, Brazil 4Laboratory of Cardiopulmonary Physical Therapy, Department of Physical Therapy, Universidade Federal de São
Carlos (UFSCar), São Carlos, SP, Brazil
! ! Received September 21, 2016; accepted April 18, 2017
Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure
(CPAP) on the exercise tolerance of patients with moderate to severe chronic obstructive pulmonary
disease (COPD). Methods: ten men with COPD (69 ± 9 years), FEV1/FVC (58.90 ± 11.86%) and FEV1
(40.98 ± 10.97% of predict) were submitted to a symptom-limited incremental exercise test (IT) on
the cyclo ergometer. Later, on another visit, they were randomized to perform a constant load
exercise protocol until maximal tolerance with and without CPAP (5cmH2O) in the following
conditions: i) 50% of the peak workload; and ii) 75% of the peak workload. Heart rate (HR), arterial
pressure (AP) and peripheral oxygen saturation were obtained at rest and during the exercise
protocols. For statistical procedures, Shapiro-Wilk normality test and two-way ANOVA with Tukey
post hoc (p<0.05) were performed. Results: There was a signi`icant improvement in exercise time
tolerance during the 75% of the peak workload protocol with CPAP when compared with
spontaneous breath (SB) (438±75 vs. 344±73ms, respectively). Conclusion: CPAP with 5 cmH2O
seems to be useful to improve exercise tolerance in patients with COPD. !
! ! ! ! ! Corresponding Author
Michel Silva Reis (msreis@hucff.ufrj.br)
! Journal of Respiratory and CardioVascular Physical Therapy
KEYWORDS: Noninvasive ventilation; COPD; exercise tolerance; CPAP
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
INTRODUCTON
Patients with chronic obstructive pulmonary disease
(COPD) present a reduced physical exercise tolerance that
can be determined by ventilatory and/or peripheral
mechanism1,2. Progressive increase in the expiratory
air`low resistance, which limits the tidal volume gain
beyond the expiratory and inspiratory reserve volumes,
may be accentuated because these patients ventilate in
higher pulmonary volumes at rest. Thus, they reach the
maximal pulmonary capacity during physical exercise
early3. Nowadays, peripheral muscular dysfunction has
gained evidence, mainly its in`luence on the premature
physical exercise interruption4. Facts such as chronic
hypoxemia, oxidative stress, nutritional depletion,
peripheral muscular disuse, medicament effects and vagal-
sympathetic imbalance contribute to this peripheral
muscular dysfuction4. Beyond these factors, another
limiting capacity aspect of physical exercise is the blood
`low redistribution to peripheral muscles despite the
ventilatory muscles, especially in high intensity exercises5.
Hence, there are known forms to decrease the ventilatory
overload with repercussion on physical exercise tolerance
such as oxygen supplementation6,7, the use of
bronchodilators8, heliox9,10,11,12,13 and non-invasive
ventilation (NIV)1,9,14,15. NIV improves the functional
residual capacity by reducing the pulmonary shunt,
generating a higher ventilatory reserve16. Furthermore, it
reduces the work of breathing and it has been explored in
recent study during physical activity with COPD patients5
and other chronic diseases17, since there is a reduction in
sympathetic response in peripheral musculature, which
promotes a higher blood `low with higher tolerance on
physical exercise5,17.
Therefore, our study has the objective to evaluate acute
effects of continuous positive airway pressure (CPAP) on
physical exercise capacity of COPD subjects.
! MATERIALS AND METHODS
Subject
Ten men with a clinical diagnosis of COPD volunteered to
participate in this cross-sectional study. Subjects were
recruited from a public primary health care facility and to
be included in the study presented with the following
characteristics: stable pulmonary function with forced
! expiratory volume in the `irst second/forced vital capacity
(FEV1/FVC) < 70%18, ex-smokers, and presenting dyspnea
and symptoms with minor or moderate efforts19. Exclusion
criteria were: consumption of alcoholic beverages, users of
addicting drugs, and regular physical activity in the past six
months. All subjects were submitted to clinical evaluation
and pulmonary function tests, functional capacity
evaluation according to the British Modi`ied Medical
Research Council (MRC)19, biochemical tests,
electrocardiogram (ECG) and a symptom-limited physical
exercise test prior to the study. All of them signed an
informed consent form, and the protocol was approved by
the Ethics Committee from Universidade Federal de São
Carlos (UFSCar), São Carlos, SP, Brazil (protocol 238/06).
Experimental protocol
The research was conducted in an acclimatized laboratory
at temperatures between
22 °C and 24 °C and relative humidity between 50% and
60%, during the same period of the day (between 8 a.m.
and 12 p.m.). Prior to and on the day of the test, each
subject was asked to ensure they avoided consumption of
stimulating beverages and physical activity for 24 hours,
and consumed light meals and slept for at least eight hours.
Initially, the subjects were familiarized with the
experimental equipment and environment and the
researchers involved in the study. Prior to the tests, they
were evaluated and examined to ensure that the directions
given had been strictly followed. In addition, systolic and
diastolic blood pressure, lung auscultation and peripheral
saturation of Oxigen (SpO2) were assessed.
Pulmonary function
Spirometry was performed using a Vitalograph®
spirometer (Hand-Held 2021 instrument. Ennis, Ireland).
The FVC test was conducted to determine the FEV1 and
FEV1/FVC ratio. Technical procedures, criteria for
acceptability and reproducibility, were performed
according to the guidelines recommended by the American
Thoracic Society20. The reference values used were those
suggested by Knudson et al. 21.
Incremental physical exercise protocol
The assessment was performed by a cardiologist to
determine the maximum load the patients were able to
achieve. In addition, this step was considered important to
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
assess clinical and functional conditions of the
cardiovascular and peripheral muscular systems of the
subjects and to identify evidence of cardiorespiratory
comorbidities elicited by physical exercise. Initially, the
patients were evaluated using an ECG with the standard 12-
lead ECG, followed by the evaluation of the
electrocardiographic signal from the derivations MC5, DII
modi`ied and V2 in the following conditions: supine, sitting,
apnea (15 s) and hyperventilated (15 s). The exercise test
was performed on a cycloergometer with electromagnetic
brakes (Quinton 400 Corival Ergometer, Groningen,
Netherlands) and power increments externally controlled
by a microprocessor model Workload Program (Quinton,
Groningen, Netherlands). The subjects remained seated
with the knees `lexed at 5-10°. Initially, a 2-minute warm up
period was performed with no load, corresponding to 4
watts (W). Following the warm up, the subjects performed
increments of 5W every 3 minutes at 60 rpm, until physical
exhaustion or it was impossible for them to maintain the
pedaling speed. The test was stopped on the `irst
indications of signs and/or symptoms such as dizziness,
nausea, cyanosis, complex arrhythmias, excessive sweating,
angina and peripheral oxygen desaturation. During the test,
they were monitored from the MC5 derivation, DII modi`ied
and V2. Measurements of heart rate (HR), blood pressure
(auscultation method) and electrocardiographic recordings
were performed in the 30 `inal seconds of each power level
and at the 1st, 3rd, 6th and 9th minutes of recovery. At the end
of the recovery period, with the subject in the supine
position, the standard 12-lead ECG was performed. In
addition to the aforementioned variables, using formulae
recommended by the American Heart Association (which
considers peak load and body mass), peak oxygen
consumption (VO2 peak) achieved by the subjects was
obtained. Throughout the test, peripheral oxygen
saturation (SpO2) was measured using pulse oximetry
(Oxyfast, Takaoka, Brazil).
Protocol of constant load in spontaneous breath and during
CPAP application
All tests were performed in four or two days (two tests per
day) with an interval of 48 hours between the days. For the
implementation of this protocol, initially, the subjects were
kept at rest in the sitting position for about 10 minutes,
aiming to achieve basal values for HR. At the same time,
instantaneous HR was obtained at rest in the sitting
position for 15 minutes. Subsequently, subjects were
randomized by drawing to perform submaximal exercise at
a constant load until maximum tolerance, with and without
application of continuous positive airway pressure (CPAP –
5 cm H2O, Breas PV101, Sweden) using a Confortgel nasal
mask (Respironics, Murrysville, PA) under the following
conditions: i) 50% of the peak load of the incremental test
and ii) 75% of the peak load of the incremental test.
Subjects were positioned in the horizontal electronically
braked cyclo ergometer (Quinton 400 Corival Ergometer,
Groningen, Netherlands) with knees `lexed between 5° and
10°. Initially, they remained seated on the cycle ergometer
at rest for 1 minute and then were instructed to pedal at a
cadence of 60 rpm until maximum tolerance, that was
de`ined when the subject could not keep the cadence. SpO2
(Oxyfast, Takaoka, Brazil) and ECG (Eca`ix 500, São Paulo,
Brazil), in leads MC5, DII modi`ied and V2, were
continuously monitored throughout the experimental
protocol. Blood pressure and the modi`ied BORG scale (CR
– 10) were carefully veri`ied every two minutes to avoid
interference in the collection of the variables. Constant
workload tests were performed on a single day and at the
same time to avoid circadian in`luences with an interval of
30 minutes or until cardiovascular variables returned to
baseline values. A team of trained researchers conducted
the tests and carefully monitored the signs and/or
symptoms of exercise intolerance and who could determine
when to immediately stop the test. Data analysis
The maximum time for completion of the physical exercise
during the protocol of constant workload was identi`ied by
tolerance time. The HR, subjective sensation of effort for
dyspnea, and discomfort of the lower limb variables were
assessed at baseline and at the peak of the protocol.
Statistical analysis
Data were subjected to a normality test (Shapiro-Wilk) and
homogeneity test (Levene test). Since a normal distribution
was observed, parametric statistical tests were used. Next,
a two-way ANOVA test with Tuckey post hoc was applied for
comparisons in the two exercise load conditions,
spontaneous breath and with CPAP. Analyses were
performed with GraphPad Instat 3 (San Diego, CA, USA),
with a signi`icance level of p<0.05. All data were presented
as means and standard deviation.
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
RESULTS
We had 24 COPD patients, from which 12 were excluded
and two abandoned the current study, resulting in 10
analyzed patients, as shown in Figure 1.
In Table 1 we can observe age, anthropometric data, clinical
characteristics and incremental cardiopulmonary data of
the subjects. All individuals of the study were mild to
moderate in Global initiative for chronic obstructive lung
disease (GOLD)18 classi`ication, functional class of MRC
between I and III and were with optimized drug therapy.
Additionally, the incremental cardiopulmonary test showed
that COPD patients present low functional capacity (VO2
<15 ml/kg/min).
! !
! Table 2 exposes the cardiorespiratory data at rest and
constant work load physical exercises with and without
CPAP on the intensities of 50 and 75% of the incremental
test. We noted a higher improve in the physical exercise
time tolerance when the patients were with CPAP in the
intensity of 75% of the incremental test compared with the
condition without CPAP.
Figure 2 shows the time of tolerance to physical exercise of
patients in the intensity of 75% of the incremental test
without CPAP (SB) and with CPAP, in which we can see
signi`icantly higher values with the use of CPAP compared
with the spontaneous breath condition. (p<0.05).
!
! !
Figure 1. Flowchart of the study.
! ! ! ! ! ! ! ! !
24 eligible patients
12 patients
10 patients included
Two excluded
! Abandoned the protocol (n=1)
Mobility issues by severe dyspnea (n=1)
12 excluded
! Uncontrolled arterial blood pressure (n=4)
Current smokers (n=3)
Suspected cancer (n=2)
Refusal of participant (n=2)
Consumption of alcoholic beverage (n=1)
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
Table 1. Anthropometrics and clinical characteristics of Chronic Obstructive Pulmonary Disease (COPD) Subjects.
Values are means ± SD. FEV1: forced expiratory volume in the `irst second; FEV1/FVC: forced expiratory volume in the `irst
second and forced vital capacity ratio; SpO2: peripheral oxygen saturation; RR: respiratory rate; SAP: systolic arterial
pressure; DAP: diastolic arterial pressure; HR: heart rate. MRC: Medical Research Council.
! ! ! !
COPD (n=10)
Age (years) 69 ± 9
Height (cm) 167 ± 8.96
Weight (Kg) 64.44 ± 8.96
Body mass index (kg/m²) 23.21 ± 3.33
Spirometrics
FEV1 (L) 0.8 ± 0.2
FEV1 (% predict) 40.98 ± 10.97
FEV1/FVC (%) 58.90 ± 11.86
FVC (% predict) 68 ± 13
MRC
Class I n=1
Class II n=3
Class III n=6
Clinical characteristics
SpO2 (%) 92 ± 3
RR (ipm) 15 ± 4
Drugs
Short-acting bronchodilator 6
Long-acting bronchodilator 10
Incremental test
At rest
SAP (mmHg) 124 ± 11
DAP (mmHg) 75 ± 5
HR (bpm) 70 ± 12
Peak
SAP (mmHg) 171 ± 17
DAP (mmHg) 80 ± 9
HR (bpm) 110 ± 20
VO2peak (mL.kg.min) 10.15 ± 3.19
Power (watts) 27 ± 18
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
Table 2. Cardiopulmonary variables and Borg during exercise
Values are means and SD. SB: spontaneous breath; CPAP: continuous positive airway pressure; RF: respiratory frequency in
incursions per minute; HR: heart rate in beat per minute; SAP: systolic arterial pressure; DAP: diastolic arterial pressure;*
p<0.05: rest vs. exercise (t student paired test); Ϯ p<0.05: SB vs. CPAP in 75% of incremental test (two-way ANOVA with Tukey
post hoc).
�
Figure 2. Tolerance time for Chronic Obstructive Pulmonary Disease Subjects during submaximal exercise at 75% of
incremental test. SB: spontaneous breath. Median (bold line).
! !
! !
Variables 50% incremental test 75% incremental test
SB CPAP SB CPAP
At rest
RF (ipm) 12± 4 13± 3 12± 4 14± 3
HR (bpm) 75± 8 78± 7 75± 8 75± 7
SAP (mmHg) 120 ±7 125± 6 120 ±7 132± 8
DAP (mmHg) 72 ±8 74± 8 72 ±8 74± 8
Submaximal exercise peak
Tolerance time (s) 448±80 469±70 364±65 431±84
HR (bpm) 123±20* 124±19* 124±17* 122±18*
SAP (mmHg) 171±8* 168±7* 175±7* 170±7*
DAP (mmHg) 80±5 90±10 90±10 90±5
Dyspnea score 6±1 5±1 6±1 6±1
Leg effort score 5±0 5±1 5±1 5±1
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
DISCUSSION
The main `inding of this study is the increase in the time of
tolerance of physical exercise in the intensity of 75% of the
incremental test with CPAP compared with the condition of
spontaneous breath.
The patients were eutrophic, with level of obstruction of
expiratory air`low from mild to moderate; all of them
maintained the use of medications during the study
protocol. During the incremental test, all subjects showed
an increase in the hemodynamic variables reaching a mean
of the estimated VO2 in the peak of exercise of 10.15ml/kg/
min.
Regarding the increase in the time of tolerance in the
condition of 75% of incremental test with CPAP, our data
corroborate literature `indings. In another study that
evaluated the time of tolerance of physical exercise of
patients with COPD from mild to moderate with use of
proportional assisted ventilation with titled `lows and
volumes of 5.8±0.9 cm H2O/l and 3.5±0.8 cm H2O/l/s,
respectively, Borghi-Silva et al.5 observed a higher tolerance
in the conditions with the ventilatory support in higher
exercise intensities. In the same way, Bianchi et al.22
showed that 15 patients with COPD presented higher
physical capacity with the association of proportional assist
ventilation (PAV) (8.6±3.6 cm H2O/l and 3±1.3 cm H2O/l)
and high intensity physical exercise (80% of peak
workload). Dyer et al.14 , who studied hospitalized patients
with COPD by acute exacerbation of the disease without
hypercapnia, observed a mean increase of 147 seconds in
the pedal capacity with `ixed load of 20 watts of patients
when submitted to NIV with two pressure levels (Pressure
support ventilation of 10 cm H2O and PEEP of 5 cm H2O).
Lastly, a meta-analysis about NIV and COPD performed by
Shi et al.23 showed that from `ive selected studies24,25,26,27,
two of them had a positive association between NIV and
physical exercise.
The use of NIV has been shown to be effective for patients
with other chronic diseases that curse with peripheral
dysfunction and consequently reduces the physical exercise
tolerance. Reis et al.17 observed an increase in time of
tolerance of physical exercise in patients with chronic heart
failure with reduced left ventricular ejection fraction when
submitted to CPAP of 5 cm H2O in the intensity of 75% of
the incremental test.
! The rational for these `indings base on the bene`its of NIV
on the increase in functional residual capacity with the
maintenance of expanded alveoli and consequent increase
in ventilatory reserve and decrease in ventilatory
workload5,14,17. This effect is especially important when NIV
is associated with physical exercise, since these patients
may early interrupt the exercise by the increase in the
expiratory air`low resistance and consequent dynamic
hyperin`lation28. Additionally, we may also consider that
the lower the ventilatory work demands, the lower the
relative cardiac output to ventilatory muscles decreasing
the sympathetic response of the peripheral muscles and
consequently increasing the blood `low and oxygen supply
to this area, thus increasing the time of physical
tolerance29,30.
Even though blood `low has not been directly evaluated in
this study, our data allow to infer about the possibility of
lower blood `low redistribution to the peripheral muscles,
since the use of CPAP of 5 cm H2O was able to signi`icantly
increase the time of tolerance in physical exercise in a
constant workload protocol with high intensity (75% of the
incremental test). Although the PEEP titration was
recommended, the use of 5cm H2O already was able to
generate a satisfactory response on the time of tolerance of
these patients.
Curiously, the results of 75% of the incremental test were
not reproduced with 50%. Probably, the imposed load on
the constant load protocol with 50% of the incremental test
was insuf`icient to generate a high enough metabolic
demand to increase the overload on ventilatory muscles
and consequently early interrupt the physical exercise.
The limitation of the study is the absence of whole-body
plethysmography to measure the static volumes as well as
the echocardiography to remove the possibility of
coexisting chronic heart failure and arterial blood gas
analysis to separate the hypoxic and hypercapnic patients.
As well as the small sample size, the recruitment of men
only, and the participation of subjects only with mild to
moderate severity disease.
! ! ! !
Jour Resp Cardiov Phy Ther. 2016; 5(1): 12-20.
CONCLUSION
As exposed, our study observed improve in the time
tolerance of physical exercise of patients with COPD from
mild to moderate with CPAP with 5 cm H2O supply during
the constant load protocol with 75% of the incremental
test.
! ACKNOWLEDGMENTS
To Fundação Carlos Chagas de Apoio da Pesquisa do Estado
do Rio de Janeiro (FAPERJ – protocol: E-26/110.827/2012)
and to Conselho Nacional de Desenvolvimento Cientí`ico e
Tecnológico (CNPq – protocol: 487375/2012-2), for
`inancial support. Additionally, we thank our colleagues
from the Research Group in Cardiorespiratory Physical
Therapy (GECARE) from the Department of Physical
Therapy, Universidade Federal do Rio de Janeiro (UFRJ), Rio
de Janeiro, RJ, Brazil.
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