Respiratory Medicine (2014) 108, 1460e1468

Available online at www.sciencedirect.com

ScienceDirect
journal homepage: www.elsevier.com/locate/rmed

Effects of noninvasive ventilation on

treadmill 6-min walk distance and regional
chest wall volumes in cystic fibrosis:
Randomized controlled trial
Cibelle Andrade Lima a,
`le de Fa
tima Dornelas de Andrade b,*,
Arme
o b,
Shirley Lima Campos b, Daniella Cunha Branda
Guilherme Fregonezi c, Ianny Pereira Mourato b,
Andrea Aliverti d, Murilo Carlos Amorim de Britto e
a
Universidade Federal de Pernambuco e UFPE, Rua Pessoa de Melo, 333, 702, Madalena, Recife,
PE 50721610, Brazil
b
Universidade Federal de Pernambuco e UFPE, Departamento de Fisioterapia, Av. Jornalista Anibal
Fernandes, Cidade Universitaria, Recife, PE 50740-560-901, Brazil
c
Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte, Campus Universitario
Lagoa Nova, Caixa Postal 1524, CEP:59072-970 Natal-RN, Brazil
d
Dipartimento di Elettronica, Informazione e Bioingegneria Politecnico di Milano, Piazza Leonardo da
Vinci, 32, I-20133 Milan, Italy
e
Instituto Materno Infantil de Pernambuco, Rua dos Coelhos 300, Pos Graduacao, Boa Vista,
Mailbox: 1393, Recife, PE 50070-550, Brazil

Received 5 December 2013; accepted 9 April 2014

Available online 23 April 2014

KEYWORDS
Cystic fibrosis;
Exercise tolerance;
Exercise test;
Noninvasive
ventilation

Summary
Background: Dyspnea and exercise intolerance are the symptoms that most affect the quality
of life of children and adolescents with respiratory disorders resulting from cystic fibrosis (CF).
Objective: To evaluate the effect of noninvasive ventilation (NIV) on treadmill 6-min walk distance and regional chest wall volumes in cystic fibrosis patients.
Method: Crossover clinical trial, randomized, controlled and open with 13 children and adolescents with CF, aged 7e16 years, with pulmonary impairment (NTC01987271). The patients

* Corresponding author. Universidade Federal de Pernambuco, Departamento de Fisioterapia, Av. Jornalista Anbal Fernandes,
Cidade Universita
ria, Recife, PE 50740-560, Brazil. Tel.: 55 81 21268496; fax: 55 81 21268937.
E-mail addresses: cibellea@yahoo.com (C.A. Lima), armeledornelas@yahoo.com, armeledornelas@hotmail.com (A.dF.D. de Andrade),
shirleylcampos@uol.com.br (S.L. Campos), daniellacunha@hotmail.com (D.C. Branda
o), gfregonezi@msn.com (G. Fregonezi),
iannymourato@hotmail.com (I.P. Mourato), andrea.aliverti@biomed.polimi.it (A. Aliverti), murilobritto@ig.com.br (M.C.A. de Britto).
http://dx.doi.org/10.1016/j.rmed.2014.04.006
0954-6111/ 2014 Elsevier Ltd. All rights reserved.

Effects of NIV on treadmill 6-min WD and regional chest wall volumes in CF

1461

performed a treadmill walking test (TWT) during 6 min, with and without NIV on a BiLEVEL
mode, an interval of 24e48 h between tests. Before and after each test, patients were assessed by spirometry and optoelectronic plethysmography.
Results: Walking distance in TWT with NIV was significantly higher that without ventilatory support (mean  sd: 0.41  0.08 vs. 0.39  0.85 km, p Z 0.039). TWT with NIV increase forced
expiratory volume on 1 s (FEV1; p Z 0.036), tidal volume (Vt; p Z 0.005), minute ventilation
(MV; p Z 0.013), pulmonary rib cage volume (Vrcp; p Z 0.011), and decrease the abdominal
volume (Vab; p Z 0.013) after test. There was a significant reduction in oxygen saturation
(p Z 0.018) and permanent increase in respiratory rate after 5 min (p Z 0.021) after the
end test without NIV.
Conclusion: During the walking test on the treadmill, the NIV change thoracoabdominal kinematics and lung function in order to optimized ventilation and tissue oxygenation, with
improvement of walk distance. Consequently, NIV is an effective tool to increase functional
capacity in children and adolescents with cystic fibrosis.
2014 Elsevier Ltd. All rights reserved.

Introduction
Cystic fibrosis (CF) is a multisystemic disorder in which the
respiratory system is affected in 95% of the cases, and the
primary cause of death in young adults with the disease [1].
Pulmonary impairment is progressive with recurring infectious and inflammatory processes of varying intensity,
involving symptoms such as hypersecretivity and production
of thick tracheobronchial mucus, peripheral airway
obstruction, signs of hyperinflation associated or not to
collapsed lung and atelectasis. These processes culminate
in dyspnea and exercise intolerance, symptomatology that
limits activities of daily living and interferes with the
quality of life of cystic fibrosis patients [1e4].
In addition to respiratory limitations, other factors also
account for reduced functional capacity (FC), including peripheral muscle weakness, systemic inflammation, oxidative
stress, malnutrition and the inactivity. These factors are a
vicious cycle for deteriorated aerobic conditioning and
increased mortality levels in this population [5e8].
Even though there is still no curative treatment, survival
rates have been increasing due to early diagnosis, multiprofessional management in specialized centers and access
to adequate therapy, mainly in the control of pulmonary
infections, adequate nutrition and as normal a lifestyle as
possible. In this respect, there is a need to investigate
strategies that facilitate physical activities, improving
physical conditioning and exercise tolerance in this population [9,10].
Noninvasive ventilation (NIV) has been used to treat
patients with acute and chronic respiratory failure. Studies
with chronic pulmonary patients, including those with
cystic fibrosis, show the benefits of using on alveolar
ventilation, gas exchange, reduced air trapping and pulmonary hyperinflation. It is also an effective instrument in
improving ventilatory pattern and reducing respiratory
work. However, the immediate effect of this intervention
on daily activities and functional capacity in cystic fibrosis
patients remains unknown and encourages this research
[6,11e20].
Thus, the aim of the present study was to assess the
effect of using NIV during the treadmill walking test on walk

distance, as well as the cardiovascular and thoracoabdominal kinematic variables of children and adolescents with CF.
The primary outcome variable is walk distance (WD) in
the TWT and the secondary outcomes are peripheral O2
saturation (SpO2), heart rate (HR), respiratory rate (RR),
score on the Borg dyspnea scale (BDS), forced expiratory
volume in the first second (FEV1), forced vital capacity
(FVC), forced expiratory flow of 25%e75% of FVC (FEF
25e75), minute volume (MV), tidal volume (Vt), pulmonary
rib cage volume (Vrcp), abdominal rib cage volume (Vrca)
abdominal volume (Vab), inspiratory time (Ti), expiratory
time (Te), total ventilatory cycle time (Ttot), duty cycle
(Ti/Ttot) and frequency/tidal volume ratio (RR/Vt).

Method
This is an open randomized controlled crossover clinical
trial. Sample selection was by convenience and patients
were screened at the Pneumology outpatient facility of the
Instituto de Medicina Integral Professor Fernando Figueira
(IMIP) in Recife, Brazil.
The sample was calculated using a software developed
by the Mallinckrodt General Clinical Research Center
(MGH), based on the results of the first 10 volunteers, for a
statistical power of detecting differences between procedures of 80% and a significance level of 0.05. A sample
size of n Z 13 patients was determined, considering that
the real difference between the walk distance between
procedures with and without NIV is 30 m and the standard
deviation of the differences in variables 34 m.
Inclusion criteria were clinical diagnosis of CF, FEV1
<80% of predicted, age between 7 and 16 years, clinically
stable patients and with no history of hospitalization for
respiratory failure in the last three months.
Exclusion criteria were patients with recent history of
hemoptysis, pneumothorax or evidence of emphysematous
bubbles detected by chest X-ray, Burkholderia cepacia
colonization, the need for more than two physiotherapy
sessions per day, gastroesophageal reflux, orthopedic
trauma or cardiovascular conditions that prevents the
treadmill walk test, and the presence of heart failure.

1462
Moreover, patients with contraindication for NIV, according
to the AARC GUIDELINE (2003) [21], were also excluded.
All patients agreed to take part in the study by giving
their informed consent, in accordance with resolution 196/
96 of the National Health Council.

Technical procedures
Patients were initially assessed for current and past conditions, medication use and anthropometric data (height,
weight and body mass index e BMI). Next, a randomized
plan was compiled using the Web Site Randomization.com,
applying a generator of random-permuted blocks to define
the order in which patients would execute the TWT, with or
without NIV. A minimum and maximum rest period of 24 and
48 h, respectively, was observed between tests.
Before and five minutes after the TWT with and without
NIV, patients were assessed for variations in compartmental
chest wall volume and ventilatory pattern by optoelectronic plethysmography (OEP), which was followed by the
spirometric test. A 30-min of NIV or rest period, at the
moment when the test is done with and without NIV
respectively, was given after the pulmonary function test
before proceeding to the TWT.
The following procedures were involved:
Walk test on the treadmill during 6 min: Prior to the
test, the patient was familiarized with the treadmill (G635, Pro Action BH-fitness e Germany) and instructed about
test procedures in accordance with ATS guidelines [22]. The
following parameters were assessed before, immediately
after and in the 5th minute post-test: blood pressure (BP),
respiratory rate (RR), heart rate (HR), Borgs scale (BS) and
peripheral O2 saturation (SpO2). HR, RR and SpO2 were also
monitored minute by minute during the test, such that a
drop in SpO2 below 87% or rise in RR to more than 75% of
age-predicted maximal HR were used as criteria for interrupting the test [23].
The test initiated with a speed of 2.5 km/h on the
treadmill [24,25]. Every 30 s of the test, the examiner
asked the patient if the speed could be increased, maintained or decreased, and patients answered using previously agreed upon signals. The speed could not exceed
7 km/h and if it was reached, the question would be reasked in the next 30 s to determine whether the speed
would be maintained or reduced. After the test, the walk
distance (WD) on the treadmill was recorded.
The TWT performed with NIV followed the same procedures described above. However, before the test, patients were submitted to NIV on a BiLEVEL mode
(Synchrony-Respironics, Brazil) for 30 min, as proposed by
Serra et al. [15], with inspiratory airway pressure (IPAP)
level of 12 cmH2O and final expiratory airway pressure
(EPAP) of 6 cmH2O, which can vary by 2 cmH2O more or less
depending on the patients comfort, as proposed by Holland
et al. [6] and Granton and Kesten [26]. In the last six minutes of NIV the patient performed the TWT with the
device.
Optoelectronic plethysmography: The individual was
sitting with 89 retro-reflective sensors at specific thoracic
and abdominal points. Eight cameras were arranged around
the patient for a three-minutes recording of quiet breathing. The three-dimensional co-ordinates markers were

C.A. Lima et al.

recorded by OEP capture software (BTS Bioengineering,
Italy). From this co-ordinates, the following variables were
calculated by OEP before and five minutes after both tests,
with and without NIV: tidal volume, minute volume, pulmonary rib cage volume, abdominal rib cage and abdominal
volume of the chest wall (Vt, MV, Vrcp Vrca, Vab), respiratory rate (RR), inspiratory time (Ti), expiratory time (Te),
total ventilatory cycle time (Ttot), duty cycle, which represents the Ti/Ttot ratio and frequency/tidal volume ratio
(RR/Vt).
Spirometry: Spirometry was conducted using a Microloop MK 8 spirometer (Micro Medical, England) to assess
pulmonary function response, considering a 20-min rest
period between the spirometric test and TWT. Three
reproducible forced maneuvers that met American Thoracic
Society criteria [27] were performed. The highest values
obtained for forced expiratory volume in the first minute
(FEV1), forced vital capacity (FVC), forced vital capacity

Figure 1 Representation of methodology. RR: respiratory

rate, HR: heart rate, SpO2: peripheral oxygen saturation, OEP:
optoelectronic plethysmography, min: minutes, TWT: treadmill
walk test, NIV: noninvasive ventilation.

Effects of NIV on treadmill 6-min WD and regional chest wall volumes in CF

1463

Figure 2 Patient recruitment and follow-up flowchart according to CONSORT (Consolidated Standards of Reporting Trials)
statement. CF: cystic fibrosis, NIV: noninvasive ventilation, OEP: optoelectronic plethysmography.

between 25 and 75% of FVC (FEF 25e75) were recorded for

analysis.
The flowchart of the methodology is represented on
Fig. 1.

Statistical analysis
Statistical analysis was carried out using SPPS 20.0 statistical software, with a 95% confidence interval for all the
variables.
The ShapiroeWilk test was applied to verify normality
and Levenes test for homogeneity of variances.
The study variables are presented as mean standard
deviation, when distribution is normal, and as median and
interquartile range for non-normal distribution. Inter-group
comparisons were made for characterization variables
using the students t-test for independent samples.
The primary outcome, walk distance (WD) in the TWT,
was analyzed by the students t-test for independent
samples. Intra- and inter-test comparisons were performed
using the Wilcoxon and ManneWhitney tests, respectively,
for cardiorespiratory (RR, HR and SpO2), and pulmonary
function variables (FEV1, FVC, FEF 25e75) as well as those
resulting from OEP analysis (Vt, MV, Vrcp, Vrca, Vab, Ti, Te,
Ttot, Duty Cycle), measured before and after the TWT.

Results
Of the 38 eligible patients, 21 could not be contacted,
three did not meet inclusion criteria and one refused to

take part of the study. Seven of the 13 volunteers, 5 boys

and 2 girls, started the test without NIV and after a rest
period of 24e48 h did the same test with NIV. Six of 13
volunteers, 3 boys and 3 girls did the inverse order (Fig. 2).
The Individual clinical characteristics are exhibited in
Table 1.
All the patients reported regular medical follow-up,
pulmonary impairment (mild, moderate or severe degree), and pancreatic failure with the need for enzyme and

Table 1 Basal clinical characteristics of cystic fibrosis

patients studied.
Patient

FEV1 (%)

Age (years)

BMI (kg/cm2)

1
2
3
4
5
6
7
8
9
10
11
12
13

50
74
79
40
51
35
78
63
79
73
80
63
41

10
9
7
10
7
14
10
7
14
15
11
11
15

14.6
16
16.2
23.1
13.6
17.4
16.4
13.3
18
15.4
16.6
13.9
17.5

FEV1: forced expiratory volume in the first second, kg: kilogram,

cm: centimeters, BMI: body mass index, M: mean, SD: standard
deviation.

1464

Figure 3 Analysis of walk distance on the TWT with and

without NIV. NIV: noninvasive ventilation, m: meters, CI: confidence interval. *Wilcoxon test.

vitamin supplementation. Seven of the 13 patients had

normal BMI for age, according to the World Health Organization (2006) [28], while the rest were classified as low
weight. Furthermore, except for one individual, all the
patients used dornase alfa.
The walk distance was greater on the TWT with NIV, with
a mean of 415.38  77.52 m compared to
386.92  84.89 m for the same test without NIV (p Z 0.039;
Fig. 3).
Fig. 4 shows the RR, counted by ventilator pattern, HR
and SpO2 before, immediately after and 5 min after each
test, separately and between them. Likewise, SBP, DBP and
Borgs dyspnea scale modified (BS) were also evaluated.
The BS is described on Fig. 5.
With respect to the responses of cardiorespiratory variables to the TWT, there was no significant difference between the groups immediately after the tests with and
without NIV. Both groups increased HR and RR, due to the
rise in cardiorespiratory demand caused by physical exercise. However, only in those who underwent the TWT
without NIV was there significant desaturation (p Z 0.018),
with permanent increase in RR after 5 min (p Z 0.001). It is
important to note that at no time the patients reach age-

C.A. Lima et al.

predicted HRmax. Moreover, there was no variation in
intra- and inter-test SBP and DBP.
There was no inter-test difference in perceived exertion, as quantified by Borgs scale. An increase in median
and interquartile range (IR) scores occurred in both groups,
immediately after the test. The post-test without NIV
exhibited an increase from 0 (0e0.75) to 3 (2.5e7.5) points
and in the post-test with NIV from 0 (0e0.5) to 4 (2e6)
points, both with p < 0.001. After 5 min, median (IR) of the
BS returned to 0 (0e1.5) and 1 (0e2) points on the TWT
without and with NIV, respectively, significantly higher than
the initial value only on the TWT with NIV (p Z 0.033). No
significant difference was found between the tests.
The spirometric variables, before and after each test, is
described in Table 2. There was an increase in FEV1 posttest only when exercise was performed with NIV
(p Z 0.036). There were no inter-group differences.
Fig. 6 and Table 3 show the rib cage volumes variation,
as well as variables that reflect ventilatory pattern (MV, RR,
Ti, Te, Ttot, Duty Cycle and RR/Vt). The total volume of the
rib cage increased after exercise, but the rise was only
significant when exercise was associated to NIV. Moreover,
when the TWT is associated to NIV, Vt increased
(p Z 0.005), causing an alteration in thoracoabdominal
kinematics, raising Vrcp and decreasing Vab (p Z 0.011 and
p Z 0.013) respectively. There was no significant change in
final values between procedures.
The TWT with NIV increased MV when compared to
baseline (p Z 0.013), increase Vt (p Z 0.005), but did not
influence the final values of RR, RR/Vt and ventilatory cycle
times. There was no significant change in the ventilatory
pattern in the post-test without NIV.

Discussion
Earlier studies in patients with CF showed NIV benefits in
recruiting collapsed alveolar units, improving alveolar
ventilation and oxygenation, reducing respiratory work and
air trapping [15,17,29e31]. The present study shows that
these benefits remain in a situation of cardiorespiratory
overload, such as physical exercise. The previous and
associated use of NIV prevented exercise-induced desaturation and reduced the time required to restore ventilatory
supply-demand equilibrium after the stress test, since only
on the TWT without NIV did RR remain elevated in the

Figure 4 Analysis of intra- and inter-test RR, HR and SpO2. SpO2: peripheral oxygen saturation, NIV: noninvasive ventilation.*Wilcoxon test.

Effects of NIV on treadmill 6-min WD and regional chest wall volumes in CF

Figure 5

Borgs dyspnea scale modified.

5 min post-test. These benefits associated to immediate

improvement in pulmonary function, observed by the increase in FEV1 post-test, makes NIV an instrument that
restores or strengthens the capacity of patients with CF to
engage in physical activity.
In addition to enhancing pulmonary function and peripheral oxygenation, our findings show that the use of NIV
during the TWT caused an increase in post-test Vt and MV in
children and adolescents with CF.
This assessment of changes in pulmonary volumes was
performed using OEP. In addition to evaluate the changes
in the distribution of rib cage volume by compartments,
this instrument is capable of evaluating which type of
kinematic alteration is responsible for variations in Vt
[32].
The heterogeneity of pleural pressure on the costal
surface and the different arrangement of inspiratory and
expiratory musculature in the rib cage cause different behaviors on pulmonary and thoracic mechanics in certain
situations. It is therefore important to separately assess the

Table 2

FEV1 (ml)
(%)

FVC (ml)
(%)

FEF 25e75
(L/s)
(%)

1465

mechanics of the rib cage in relation to the lungs (RCp) and

against the diaphragm (RCd) and abdomen (RCa) [33].
We observed that exercise with NIV altered thoracoabdominal kinematics, significantly increasing Vrcp and
reducing Vab. The greater expansion of the pulmonary rib
cage in detriment to the reduction of Vab demonstrates
that there was a difference in pressures acting on the rib
cage. Cala et al. [34] reports that the increase in Vt followed by this thoracoabdominal pattern occurs due to
greater recruitment of inspiratory than expiratory reserve
volume [35,36,37]. Thus, the mixed pattern of restrictive
and obstructive pulmonary impairment in CF was modified
by the use of NIV such that Vt increased as a result of
greater rib cage mobilization and a rise in its volumegenerating capacity.
MV grew after exercise associated to the use of NIV due
to increased Vt and not RR. So, instead of no statistically
difference on RR/Vt ratio, the use of NIV tends to minimize
the rapid and shallow breathing pattern after the test,
suggesting an improvement in alveolar ventilation [38].
There was no difference in ventilatory cycle variables
as measured by OEP. However, the basal duty cycle of
cystic fibrosis patients is above normal values (between 30
and 40%). Duty cycle is the Ti/Ttot ratio of the ventilatory
cycle and reflects the part of the effective diaphragm
contraction cycle. High values, such as those observed in
our sample, show a pattern of tachypnea, a decline in
exhalatory time and greater disposition to a rise in respiratory work and respiratory muscle fatigue in situations
of increased cardiorespiratory demand, such as physical
exercise [39]. Moreover, mean duty cycle values were
higher after exercise without NIV when compared to postexercise values with NIV, but without statistical
significance.
The present study shows that patients submitted to the
TWT with NIV obtained better results, underscoring the
longer walk distance and consequent enhanced functional
capacity.

Analysis intra- and inter-test of spirometric variables, with and without NIV.

Before
After
Before
After
Before
After
Before
After
Before
After
Before
After

TWT without NIV (n Z 13)

TWT with NIV (n Z 13)

Median (IR)

Intra-test
p-valuea

Median (IR)

Intra-test
p-valuea

Inter-test
p-valueb

1.03
1.01
63
61
1.75
1.74
78
74
0.74
0.67
38
36

e
0.906
e
0.608
e
0.834
e
0.844
e
0.834
e
0.583

1.14
1.18
54
67
1.84
1.67
76
83
0.8
1.15
53
58

e
0.036
e
0.289
e
0.208
e
0.074
e
0.75
e
0.197

0.724
0.362
0.762
0.579
1.00
0.88
1.00
0.579
0.418
0.243
0.511
0.204

(0.83e1.7)
(0.85e1.68)
(40.5e76.5)
(40.5e76)
(1.31e2.31)
(1.23e2.24)
(64.5e94)
(59.5e94)
(0.43e1.87)
(0.47e1.83)
(18e85)
(23.5e90)

(0.96e1.61)
(1e1.84)
(44e82)
(50e82)
(1.4e1.91)
(1.35e2.4)
(62.5e98)
(60.5e102.5)
(0.65e2.05)
(0.64e2.19)
(31e99.5)
(34e103.5)

TWT: treadmill walk test, NIV: noninvasive ventilation, FEV1: forced expiratory volume in the first second, FVC: forced vital capacity,
FEF 25e75: forced expiratory flow between 25 and 75% of FVC. IR: interquartile range, ml: milliliters, L: liters, s: seconds.
a
Wilcoxon test.
b
ManneWhitney test.

1466

C.A. Lima et al.

Figure 6 Analysis of variation in rib cage volume by OEP. NIV: noninvasive ventilation, Vrcp: pulmonary rib cage volume, Vrca:
abdominal rib cage volume, Vab: abdominal volume. *Wilcoxon test.

The multisystem etiology of CF and the complex physiopathology of pulmonary impairment highlight the importance of assessing the impact of NIV not only in pulmonary
function, but also in functional capacity. The ability to
engage in physical exercise, when objectively determined,
is a more effective marker of the prognosis and quality of
life in this population, which can be improved with a
rehabilitation program even when the pulmonary impairment of the disease cannot be altered [29,30].
There was a significant increase in walk distance on the
TWT when it was performed with ventilatory assistance.
Our findings suggest that improved peripheral oxygenation
and pulmonary function, caused by the use of NIV at two
pressure levels, reduced the overload imposed on ventilatory muscles and increases the functional capacity of patients with CF. Accordingly, the use of NIV proved to be a
necessary means of ventilatory support to supply the

Table 3

increased ventilatory demand and increase the functional

capacity of this group of patients [12,14].
Similar results were found in patients with cardiopathies
and chronic obstructive pulmonary disease, but are new in
patients with cystic fibrosis in any age group [40,41].
A limiting factor of our study was the inability to assess
the impact of NIV on ventilatory pattern, as measured by
OEP during the test. This is due to the positive thoracic
pressure exerted by NIV in cardiopulmonary interaction,
modifying hemodynamics and blood volume in the chest
and abdomen of individuals. These alterations in blood
volume likely interfere in the assessment of total and rib
cage compartment volumes [42].
Furthermore, Borgs scale was difficult for the children
to understand, limiting the validity of our results with
respect to this variable. The young age and poor schooling
level of the population, as well as the low socioeconomic

Analysis of volumes and ventilatory pattern by intra- and inter-test OEP.

TWT without NIV (n Z 13)

Vt (L)
MV (L)
RR (ipm)
Ttot (s)
Ti (s)
Te (s)
Duty
cycle (%)
RR/Vt
(ipm/L)

Before
After
Before
After
Before
After
Before
After
Before
After
Before
After
Before
After
Before
After

TWT with NIV (n Z 13)

Median (IR)

Intra-test
p-value

Median (IR)

Intra-test
p-valuea

Inter-test
p-valueb

0.31
0.33
7.354
8.185
23.8
25.3
2.5
2.4
1.06
0.99
1.47
1.38
43.1
43.3
80.0
75.2

e
0.162
e
0.064
e
0.638
e
0.937
e
0.753
e
0.861
e
0.463
e
0.552

0.33
0.36
7.282
8.390
23.5
21.7
2.6
2.8
1.14
1.1
1.6
1.7
41.8
39.8
73.5
61.7

e
0.005
e
0.013
e
0.463
e
0.875
e
0.552
e
0.382
e
0.116
e
0.087

1.00
0.418
0.92
0.84
0.84
0.418
0.801
0.479
0.687
0.579
0.762
0.39
0.579
0.479
0.272
0.158

(0.22e0.42)
(0.3e0.37)
(4.844e9.575)
(6.667e8.945)
(19.4e31.8)
(20.2e28.6)
(1.9e3.1)
(2.1e3)
(0.85e1.47)
(0.85e1.39)
(1.05e1.95)
(1.2e1.69)
(40.2e47.2)
(38.-45.2)
(44.4e101.4)
(57.8e98.5)

(0.23e0.39)
(0.29e0.44)
(5.712e9.465)
(6.322e9.509)
(18.3e29.5)
(19.3e27.3)
(2e3.5)
(2.2e3.1)
(0.92e1.42)
(0.93e1.23)
(1.18e1.99)
(1.31e1.98)
(39.2e46.5)
(37.9e44.7)
(54.0e101.3)
(42.4e82.6)

TWT: treadmill walk test, NIV: noninvasive ventilation, Vt: tidal volume, MV: minute volume, RR: respiratory rate, Ttot: total time, Ti:
inspiratory time, Te: expiratory time, IR: interquartile range, L: liters, s: seconds ipm: incursions per minute.
a
Wilcoxon test.
b
ManneWhitney test.

Effects of NIV on treadmill 6-min WD and regional chest wall volumes in CF

status of the sample may have been the cause of this limitation. Hook et al. [43] showed that low economic status
has an influence in a wide range of situations, including
cognitive skills, school performance, executive ability and
even physical and mental health.

Conclusion
The pulmonary impairment in cystic fibrosis patients can
increase the ventilatory demand even in performing their
activities of daily living. Dyspnea being an important
limiting factor in their functionality and quality of life.
Given the impossibility of altering the severity of pulmonary impairment, the present study proved that the
immediate use of NIV in the BiLEVEL mode improves pulmonary function, respiratory muscle strength, peripheral
oxygenation, as well as providing the ventilatory support
required to increase the functional capacity of children and
adolescents with CF.
Studies that assess the impact of NIV associated to a
pulmonary rehabilitation program on long-term functional
capacity, health gains, physical conditioning and functionality scale should be encouraged.

Conflict of interest
None declared.

References
[1] Ramsey Bonnie W. Management of pulmonary disease in patients with cystic fibrosis. N Engl J Med 1996;335:179e88.
[2] Knowles MR, Durie PR. What is cystic fibrosis? [Editorial] N Engl
J Med 2002;347:439e42.
[3] Gibson R, Burns J, Ramsey B. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir
Crit Care Med 2003;168:918e95.
[4] Mandrusiak A, Maurer C, Macdonald J, Wilson C, Watter P.
Functional capacity tests in young people with cystic fibrosis.
N Z J Phys Ther 2009;37(1):13e6.
[5] Williams M. Chest physiotherapy and cystic fibrosis: why is the
most effective form of treatment still unclear? Chest 1994;
106:1872e82.
[6] Holland A, Denehy L, Ntoumenopoulos G, Naughton M,
Wilson J. Non-invasive ventilation assists chest physiotherapy
in adults with acute exacerbations of cystic fibrosis. Thorax
2003;58:880e4.
[7] Moorcroft A, Dodd M, Webb A. Exercise testing and prognosis
in adult cystic fibrosis. Thorax 1997;52:291e3.
[8] Troosters T, Langer D, Vrijsen B, Segers, Wouters B,
Janssens W, Gosselink R, Decramer D, Dupont L. Skeletal
muscle weakness, exercise tolerance and physical activity in
adults with cystic fibrosis. Eur Respir J 2009;33:99e106.
[9] Jong W, Grevink RG, Roorda RJ, Kaptein AA, Van Der
Schans CP. Effect of a home exercise training program in patients with cystic fibrosis. Chest 1994;105:463e8.
[10] Wilkes DL, Schneiderman JE, Nguyen T, Heale L, Moola F,
Ratjen F, Coates AL, Wells GD. Exercise and physical activity in
children with cystic fibrosis. Paediatr Respir Rev 2009;10:105e9.
[11] Chermont S, Quinta
o MM, Mesquita ET, Rocha NN, No
brega AC.
Noninvasive ventilation with continuous positive airway pressure acutely improves 6-minute walk distance in chronic heart
failure. J Cardiopulm Rehabil Prev 2009;29(1):44e8.

1467

[12] Lima E, Cruz C, Santos F, Gomes-Neto M, Bittencourt H, Reis F,

et al. Suporte Ventilato
rio na Capacidade Funcional de
Pacientes com Insuficie
ncia Cardaca: Estudo Piloto. Arq Bras
Cardiol 2011;96(3):227e32.
[13] Keilty, Ponte J, Fleming TA, Moxham J. Effect of inspiratory
pressure support on exercise tolerance and breathlessness in
patients with severe stable chronic obstructive pulmonary
disease. Thorax 1994;49:990e4.
[14] Van t Hul R, Gosselink P, Hollander Z, Postmus P, Kwakkel G.
Acute effects of inspiratory pressure support during exercise
in patients with COPD. Eur Respir J 2004;23:34e40.
[15] Serra A, Polese G, Braggion C, Rossi A. Non-invasive proportional assist and pressure support ventilation in patients with
cystic fibrosis and chronic respiratory failure. Thorax 2002;57:
50e4.
[16] Wedzicha J, Muir J-F. Noninvasive ventilation in chronic
obstructive pulmonary disease, bronchiectasis and cystic
fibrosis. Eur Respir J 2002;20:777e84.
[17] Fauroux B, Boule
M, Lofaso F, Ze
rah F, Cle
ment A, Harf A,
Isabey D. Chest physiotherapy in cystic fibrosis: improved
tolerance with nasal pressure support ventilation. Pediatrics
1999;103(32).
[18] Peter JV, Moran JL, Phillips-Hughes J. Effect of non-invasive
positive pressure ventilation (NIPPV) on mortality in patients
with acute cardiogenic pulmonary oedema: a meta-analysis.
Lancet 2006;367:11155e63.
[19] Fauroux B, Roux E, Ravilly S, Bellis G, Clement A. Long term
noninvasive ventilation in patients with cystic fibrosis. Respiration 2008;76:168e74.
[20] Ferreira HC, Santos FB. Aspectos Gerais da Ventilac
a
o na
oinvasiva. Rev Cient HCE 2008;02.
[21] AARC guideline: intermittent positive pressure breathing.
Respir Care 2003;48(5).
[22] ATS statement: guidelines for six-minute walk test. Am J
Respir Crit Care Med 2002;166:111e7.
[23] Camarda S, Tebexreni A, Pa
faro C, Sasai F, Tambeiro V,
Juliano Y, Barros Neto T. Comparison of maximal heart rate
using the prediction equations proposed by Karvonen and
Tanaka. Arq Bras Cardiol 2008;91(5):311e4.
[24] Camargo VM, Martins BCS, Jardim C, Fernandes CJC,
Hovnanian A, Souza R. Validation of a treadmill six-minute walk
test protocol for the evaluation of patients with pulmonary
arterial hypertension. J Bras Pneumol 2009;35(5):423e30.
[25] Lenssen AF, Wijnen LCAM, Vankan DG, Van Eck BH,
Berghmans DP, Roox GM. Six-minute walking test done in a
hallway or on a treadmill: how close do the two methods
agree? Eur J Cardiovasc Prev Rehabil 2010;17(6):713e7.
[26] Granton JT, Kesten S. The acute effects of nasal positive
pressure ventilation in patients with advanced cystic fibrosis.
Chest 1998;113:1013e8.
[27] American Thoracic Society. Standardisation of spirometry. Eur
Respir J 2005;26:319e38.
[28] WHO Multicentre Growth Reference Study Group. WHO child
growth standards: length/height-for-age, weight-for-age,
weight-for-length, weight-for-height and body mass index-forage: methods and development. Geneva: World Health Organization; 2006. 312 pp.
[29] Reisman J, Schneiderman J, Walker Corey M. The role of an
organized exercise program in cystic fibrosis. A three year
study. Pediatr Pulmonol 1995;252.
[30] Bradley J, Mcalister O, Elborn S. Pulmonary function, inflammation, exercise capacity and quality of life in cystic fibrosis.
Eur Respir J 2001;17(4):712e5.
[31] Placidi G, Cornacchia M, Polese G, Zanolla L, Assael B,
Braggion C. Chest physiotherapy with positive airway pressure: a pilot study of short-term effects on sputum clearance
in patients with cystic fibrosis and severe airway obstruction.
Respir Care 2006;51(10):1145e53.

1468
[32] Aliverti A, Cala SJ, Duranti R, Ferrigno G, Kenyon M, Pedotti A,
Scano G, Sliwinski P, Macklem Peter T, Yan S. Human respiratory muscle actions and control during exercise. J Appl
Physiol 1997;83(4):1256e69.
[33] Aliverti A, Stevenson N, Dellaca
` R, Lo. Mauro M, Pedotti A,
Calverley PMA. Regional chest wall volumes during exercise in
chronic obstructive pulmonary disease. Thorax 2004;59:210e6.
[34] Cala SJ, Kenyon CM, Ferrigno G, Carnevali P, Aliverti A,
Pedotti A, Macklem PT, Rochester DF. Chest wall and lung
volume estimation by optical reflectance motion analysis. J
Appl Physiol 1996;81(6):2680e9.
[35] Tobin MJ, Perez W, Guenther SM, Lodato RF, Dantzker DR.
Does rib cage-abdominal paradox signify respiratory muscle
fatigue? J Appl Physiol 1987;63(2):851e60.
[36] Kenyon CM, Cala SJ, Yan S, Aliverti A, Scano G, Duranti R,
Pedotti A, Macklem PT. Rib cage mechanics during quiet
breathing and exercise in humans. J Appl Physiol 1997;83(4):
1242e55.
[37] Mayer OH, Clayton Sr RG, Jawad AF, Mcdonough JM, Allen JL.
Respiratory inductance plethysmography in healthy 3- to 5year-old children. Chest 2003;124(5):1812e9.

C.A. Lima et al.

[38] Wilkens H, Weingard B, Lo. Mauro A, Schena E, Pedotti A,
Sybrechtand GW, Aliverti A. Breathing pattern and chest wall
volumes during exercise in patients with cystic fibrosis, pulmonar fibrosis and COPD before and after lung transplantation. Thorax 2010;65:808e14.
[39] Klawitter PF, Clanton TL. Tension-time index, fatigue and
energetics in isolated rat diaphragm: a new experimental
model. J Appl Physiol 2003;96(1):89e95.
[40] Barbas CSV, Bueno MAS, Amato MBP, Hoelz C, Junior MR.
Interac
a

ao Meca
o Cardiopulmonar Durante a Ventilac
nica.
Rev Soc Cardiol 1998;8(3):406e19.
[41] Wittmer VL, Simo
es GM, Sogame LC, Vasquez EC. Effects of
continuous positive airway pressure on pulmonary function
and exercise tolerance in patients with congestive heart
failure. Chest 2006;130(1):157e63.
[42] Duke GJ. Cardiovascular effects of mechanical ventilation.
Critical Care Resusc 1999;1:388e99.
[43] Hook CJ, Lawson GM, Farah MJ. Status Socioecono
mico e
Desenvolvimento das Func

oes Executivas. Enciclope

dia sobre
o Desenvolvimento na Primeira Infa
ncia; 2013.