䢇

Research Report
Physiologic Evidence for High-
Frequency Chest Wall Oscillation and
Positive Expiratory Pressure
Breathing in Hospitalized Subjects
With Cystic Fibrosis

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Background and Purpose. This investigation identified ventilation dis-
ўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўўў

tribution, gas mixing, lung function, and arterial blood oxyhemoglo-

bin saturation (Spo2) physiologic responses to 2 independent airway
clearance treatments, high-frequency chest wall oscillation (HFCWO)
and low positive expiratory pressure (PEP) breathing, for subjects who
had cystic fibrosis (CF) and who were hospitalized during acute and
subacute phases of a pulmonary exacerbation. Subjects. Fifteen sub-
jects with moderate to severe CF were included in this study. Methods.
Subjects performed single-breath inert gas tests and spirometry before
and immediately after HFCWO and PEP breathing at admission and
discharge. Arterial blood oxyhemoglobin saturation was monitored
throughout each treatment. Results. At admission and discharge, PEP
breathing increased Spo2 during treatment, whereas HFCWO
decreased Spo2 during treatment. Ventilation distribution, gas mixing,
and lung function improved after HFCWO or PEP breathing. Discus-
sion and Conclusion. High-frequency chest wall oscillation and PEP
breathing are similarly efficacious in improving ventilation distribu-
tion, gas mixing, and pulmonary function in hospitalized people with
CF. Because Spo2 decreases during HFCWO, people who have mod-
erate to severe CF and who use HFCWO should have Spo2 monitored
during an acute exacerbation. [Darbee JC, Kanga JF, Ohtake PJ. Phys-
iologic evidence for high-frequency chest wall oscillation and positive
expiratory pressure breathing in hospitalized subjects with cystic
fibrosis. Phys Ther. 2005;85:1278 –1289.]

Key Words: Airway clearance, Chest physical therapy, Cystic fibrosis, Gas mixing, Ventilation
distribution

Joan C Darbee, Jamshed F Kanga, Patricia J Ohtake

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1278 Physical Therapy . Volume 85 . Number 12 . December 2005

I
n people with cystic fibrosis (CF), the most com-
mon lethal inherited disease affecting people of
Caucasian ethnicity, the effective loosening and
removal of airway mucus are crucial to enhanced
life expectancy and decreased morbidity.1 Infected air-
way secretions contain proteases that destroy lung tis-
sue.2 Peripheral airways, which are less than 2 mm in
diameter, lose their stability secondary to lung tissue
destruction and tend to collapse, trapping air and
mucus.3 The collapse of smaller peripheral airways cre-
ates areas of nonhomogeneous ventilation distribution.4
As lung function continues to deteriorate, abnormalities
in ventilation distribution worsen, leading to ventilation-
weights with CPTs during8,9 and up to 24 hours after8
treatment. Thus, both HFCWO and PEP breathing are
effective at removing airway mucus; however, informa-
tion on the concomitant effects of these 2 ACTs on
ventilation distribution is scant.
To date, there have been few reports examining the
effects of ACTs on ventilation distribution or gas mixing,
even though it has been assumed that ACTs promote
improvements in ventilation distribution.7,11 Arens et al8
assessed the phase III alveolar slope during the single-
breath nitrogen (N2) washout test to discover that over-
all ventilation distribution improved equally for HFCWO

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perfusion mismatching, hypoxemia, and pulmonary
hypertension5 and eventually respiratory failure and
death.1,2,5 Respiratory failure accounts for greater than
80% of CF-related deaths in the United States.6 Under-
standably, airway clearance techniques (ACTs) are criti-
cal components of the daily regimen of care performed
by people with CF.
Putative goals of ACTs are to decrease airway obstruction
and airflow limitation and to improve ventilation distri-
bution through the mobilization and removal of airway
mucus.7 Two independent ACTs, high-frequency chest
wall oscillation (HFCWO) and positive expiratory pres-
sure (PEP) breathing, have been shown to be effective at
loosening and removing airway mucus in hospitalized
people with CF.8 –10 Mucus weight was greater after
HFCWO than after traditional airway clearance interven-
tions involving postural drainage and manual percussion
and vibration techniques (CPTs) when 29 subjects
received each intervention 3 times a day on alternating
days for 4 days.10 In contrast, mucus weights with
HFCWO8,9 and PEP breathing9 were similar to sputum
and CPT treatment groups. Recently, Darbee and col-
leagues12 showed that a single PEP breathing treatment
improved gas mixing, a measure of the extent to which
an inspired volume of gas mixes with gas already present
in the lungs, without improving ventilation distribution.
Because of the limited information regarding the effects
of HFCWO and PEP breathing on ventilation distribu-
tion, it is unclear whether one of these techniques is
more efficacious than the other. We decided to compare
the physiologic effects of HFCWO and PEP breathing on
ventilation distribution and gas mixing for people with
CF by using a single-breath inert gas technique. The
single-breath inert gas technique has the capacity to
provide information about ventilation distribution and
gas mixing. We wanted to determine the efficacy of each
airway clearance intervention and to determine whether
the physiologic effects of each intervention would differ
in subjects during an acute phase of pulmonary disease
exacerbation (within 48 hours of hospital admission)
versus a subacute phase of exacerbation (within 48 hours
of hospital discharge). For this study, we investigated a

JC Darbee, PT, PhD, is Assistant Professor, Department of Rehabilitation Sciences, Division of Physical Therapy, College of Health Sciences,
University of Kentucky, 900 S Limestone St, Lexington, KY 40536 (USA) (darbee@uky.edu). Address all correspondence to Dr Darbee.

JF Kanga, MD, is Professor of Pediatrics and Chief, Division of Pediatric Pulmonology, Department of Pediatrics, School of Medicine, University
of Kentucky.

PJ Ohtake, PT, PhD, is Associate Professor, Department of Rehabilitation Sciences, University at Buffalo, The State University of New York, Buffalo,
NY. Dr Ohtake is supported by grants from the American Lung Association and the Interdisciplinary Research and Creative Activities
Fund–University at Buffalo (IRCAF).

Dr Darbee provided concept/idea/research design, data collection, project management, fund procurement, and facilities/equipment. Dr Darbee
and Dr Ohtake provided writing and data analysis. Dr Kanga provided subjects. Dr Darbee and Dr Kanga provided institutional liaisons. The
authors thank Hill-Rom, of St Paul, Minn, for supplying The Vest airway clearance system for this study.

Approval for this investigation was granted by the University of Kentucky Medical Institutional Review Board.

This study was funded by a grant from the Medical Center Research Fund at the University of Kentucky.

This research was presented as a platform presentation at the Combined Sections Meeting of the American Physical Therapy Association; February
23–27, 2005; New Orleans, La.

This article was received August 23, 2004, and was accepted May 24, 2005.

Physical Therapy . Volume 85 . Number 12 . December 2005 Darbee et al . 1279


Table 1.
Demographics of Participants (8 Male, 7 Female)
Characteristic X SD
Age (y) 17.5 4.2
Height (cm) 159 9 and immediately after HFCWO or PEP breathing treat-
Weight (kg) 46.6 6.9
Body mass index (kg/m2) 18.3 2.0
group of subjects who had moderate to severe obstruc-
tive disease and who were undergoing treatment for an
acute exacerbation of their CF-related lung infections.
Therefore, the purpose of this investigation was to
examine the physiologic effects of HFCWO and PEP
breathing on ventilation distribution, gas mixing, lung
volume, expiratory airflow, and arterial blood oxyhemo-
globin saturation (Spo2) for subjects with CF at hospital
admission and discharge.
Method
Subjects
From a pool of 196 subjects who had CF and who were
monitored at the University of Kentucky Cystic Fibrosis
Center, 112 subjects experienced 232 hospitalizations
for treatment of pulmonary exacerbations during the
18-month study period. Experimental procedures were
explained to 41 subjects who had CF, who were admitted
to the University of Kentucky Medical Center Hospital,
and who met study inclusion criteria. Fifteen subjects
with CF documented by a sweat test13 agreed to partici-
pate and were enrolled in the study.
Subjects were eligible to participate if they were being
hospitalized for treatment of an acute exacerbation of
their CF-related chronic obstructive lung disease, were
able to perform lung function testing according to
standard guidelines,14 were at least 7 years of age, and
were regarded as medically stable by their primary CF
physician. Subjects who had a history of pneumothorax
were excluded for safety reasons related to breathing
against resistance. No subjects were on prescribed day-
time oxygen use at the time of the study. All subjects
performed HFCWO on an outpatient basis 1 to 3 times
daily before admission, and no subjects performed daily
PEP breathing. All subjects who had CF and who were
admitted to the hospital for treatment of pulmonary
exacerbations performed HFCWO 3 times daily whether
or not they were study participants.
Subject characteristics at study entry are shown in Table
1. Informed consent was obtained from all study volun-
teers and from parents (for subjects younger than 18
years of age) before participation.
1280 . Darbee et al
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Experimental Protocol
Each subject visited the lead author’s pulmonary labora-
tory located in the College of Health Sciences at the
University of Kentucky on 4 separate days. Single-breath
inert gas tests and spirometry were performed before
ments to assess ventilation distribution, gas mixing, and
lung function on 2 separate successive days within 48
hours of hospital admission and again on 2 separate
successive days within 48 hours of hospital discharge.
Because most subjects are discharged at the end of their
intravenous antibiotic treatment, we were able to iden-
tify the likely discharge date and used the 2 days before
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discharge to study the subjects in the subacute phase.
Subjects were assigned to treatment order by numbering
them consecutively, 1 through 15, at study entry. On the
basis of a coin toss at admission, subject 1 and all
odd-numbered subjects were randomly assigned to per-
form HFCWO on day 1 and PEP breathing on day 2, and
even-numbered subjects performed PEP breathing on
day 1 and HFCWO on day 2. At discharge, subjects
received treatment in the order opposite the treatment
order at admission. Three subjects were discharged
while continuing to receive intravenous antibiotics. For
these 3 subjects, final testing was performed within 48
hours of the time at which intravenous antibiotics were
discontinued. Subjects received an average of 10 days
(range⫽7–14) of intravenous antibiotics. The average
length of hospital stay was 11 days (range⫽9 –15).
Interventions
For HFCWO, a model 103 Vest airway clearance system*
was used while subjects were seated upright in a chair.15
Subjects were fitted with a nonstretch, vinyl-coated poly-
ester inflatable vest, which was worn over the entire
thorax as shown in Figure 1. The vest was closed at the
front with 3 buckles and fit snugly when subjects inhaled
to total lung capacity (TLC).15 Two ports, located on the
front panels of the vest, were connected to the air-pulse
generator via 2 large-bore tubes. The air-pulse generator
consisted of an air blower that delivered air pressure to
the inflatable vest and a rotary valve that produced
alternating positive and zero pressures.15 During treat-
ment, the vest was inflated so that a background air
pressure was created when the setting of 5 was selected
from a scale ranging between 1 and 10 (arbitrary units).
A middle range for background pressure was selected
because, although the volume of inspired air during
spontaneous breathing has been shown to be higher
during high background pressure than during low back-
ground pressure, high background pressure is known to
lower end-expiratory lung volume (EELV) more than
low background pressure for the same oscillation fre-
* Hill-Rom, 1020 West County Rd F, St Paul, MN 55126.
Physical Therapy . Volume 85 . Number 12 . December 2005

Figure 1.
Vest airway clearance system used to deliver high-frequency chest wall
oscillations. Note the air compressor connected by tubing to the vest.
quency.16 In addition, there were no differences in the
volumes of expired air between the low and the high
background pressure settings during spontaneous
breathing for the same oscillation frequency.16
Oscillation frequency was set at 10 Hz for the initial 15
minutes and was increased to 15 Hz during the last 15
minutes of treatment.16 Oscillation frequencies of 10
and 15 Hz were selected because these 2 frequencies
were previously identified to generate peak airflow dur-
ing spontaneous breathing for subjects with CF.16 We
limited the oscillation frequency to 15 Hz because
airflow during spontaneous tidal volume breathing,
which is the movement of air in and out of the lungs
during resting, has been shown to decrease during expira-
tion as oscillation frequency increases beyond 15 Hz.16
A hand-foot switch, controlled by the subjects, activated
and deactivated oscillations. Every 5 minutes, subjects
deactivated the oscillations, inhaled to TLC, activated
the oscillations at 10 or 15 Hz, and performed a forced
expiratory maneuver to a low lung volume, which
resulted in coughing, in order to clear airway secretions.
Each subject determined how many forced expiratory
maneuvers, followed by coughing, were necessary in
order to clear airway secretions at each 5-minute inter-
val. Six cycles consisting of 5 minutes of treatment
followed by forced expiratory maneuvers and coughing
were completed by all subjects.
Physical Therapy . Volume 85 . Number 12 . December 2005
Low PEP was generated by breathing through a face
mask fitted with a 1-way valve, an expiratory resistor, and
a pressure manometer17 as shown in Figure 2. During
low-PEP breathing, a resistor with an internal diameter
that provided a steady PEP of 10 to 20 cm H2O during
expiration, while the subject was breathing through the
PEP mask, was used.12,17 On the basis of clinical obser-
vations made by the lead author, low PEP as opposed to
high PEP (⬎20 cm H2O) was selected for use in the
present study because high-PEP breathing is not well
tolerated and cannot easily be performed by people
experiencing an acute pulmonary exacerbation. The
pressure manometer provided visual feedback so that a
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steady PEP of 10 to 20 cm H2O was maintained during
tidal exhalations and exhalations were slightly active.12,17
Expiratory resistor internal diameters and mean sus-
tained expiratory pressures generated during low-PEP
breathing for each subject are shown in Table 2. Subjects
breathed against the expiratory resistance for 8 breaths,
removed the PEP mask, and were encouraged to per-
form a forced expiratory maneuver to a low lung volume,
which resulted in coughing, in order to clear airway
secretions. Each subject determined how many forced
expiratory maneuvers, followed by coughing, were nec-
essary in order to clear airway secretions. A total of 8 to
10 cycles consisting of 8 breaths were performed over 30
minutes.
Subjects inhaled an aerosolized solution containing
0.5 mL of albuterol and normal saline by using a PARI
Master nebulizer† during the HFCWO and PEP breath-
ing treatment interventions. The nebulizer was inter-
faced with the inspiratory port of the one-way valve
during PEP breathing so that the aerosol was inhaled
through the PEP mask.18,19 Subjects held the nebulizer
in their hand during HFCWO treatment. Nebulized
albuterol was administered during both ACTs in an
effort to duplicate treatments routinely performed by
our subjects during hospitalizations and at home. Sub-
jects at our CF center perform bronchodilator therapy
during HFCWO treatment.
Measurements
The distribution of ventilation (phase III N2 slope data
expressed as percentages of predicted values) and gas
mixing (dilution index values expressed at an absolute
lung volume [DIvl]) were measured by use of a single-
breath inert gas test20 in accordance with standard
guidelines.21 Subjects were prompted to perform a slow
inhalation of a test gas mixture containing 5% helium
(He), 5% sulfur hexafluoride (SF6), and 90% oxygen
gases, from residual volume (RV) to TLC, followed by a
slow controlled expiration back to RV. Figure 3 shows
the distribution of ventilation depicted by single-breath
†
PARI Respiratory Equipment Inc, 7493 Whitepine Rd, Richmond, VA 23237.
Darbee et al . 1281
 ўўўўўўўўўўўўўўўўўўўўўў
washout curves of exhaled N2 gas concentrations plotted
against exhaled lung volume for a subject without CF
(top panel) and a subject with CF (bottom panel).

A regression test was performed on the N2 data versus

the lung volume data between the onset of phase III and
the onset of phase IV of the single-breath curve.20 The
slope of the regression line represented the N2 /volume
slope of phase III, which served as a measure of the
uniformity of the distribution of ventilation and which
was the result of incomplete gas mixing.20,22 The closer
the phase III slope was to horizontal, the more uniform
was the distribution of ventilation. Upward sloping of the

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line away from horizontal represented an increase in the
phase III slope and a poorer distribution of ventilation.
Phase III alveolar slope data for expired N2 were
expressed as percentages of predicted values.23 The
greater the percentage of the predicted value for the N2
slope, the poorer the distribution of ventilation.

Expired He, N2 , and SF6 concentrations were expressed

as DIVL12,20,22 to determine whether there were any
changes in expired gas concentrations after treatment.
Higher DIVL for He, N2, and SF6 gases after treatment
than before treatment would indicate improved mixing
of the inspired test gas with gas already present in the
lungs.

Vital capacity and expiratory flow measurements were

Figure 2.
Positive expiratory pressure mask fitted with a one-way valve, an obtained by simple spirometry according to standard
expiratory resistor, and a pressure manometer. methods14 by use of a MedGraphics PC SpiroCard inter-
faced with the Office Medic software program‡ and a
computer. The measurements were expressed as per-
Table 2. centages of predicted values.24,25
Expiratory Resistor Internal Diameters (IDs) and Mean Sustained
Expiratory Pressures (SEPs) Generated During Low Positive Expiratory
Pressure (PEP) Breathing Noninvasive, continuous-pulse oximetry (Nellcor N-200§)
was performed with a finger probe attached to the right
Admission Discharge index finger to estimate Spo2. Arterial blood oxyhemo-
Subject Resistor ID SEP Resistor ID SEP
globin saturation was measured before treatment, con-
No. (mm) (H2O) (mm) (H2O) tinuously throughout treatment, and for several minutes
after treatment until heart rate and Spo2 stabilized.
1 2.5 20 2.0 20 Arterial blood oxyhemoglobin saturation measurements
2 2.0 18–20 2.0 20
3 2.0 15–18 2.0 20
were obtained during both ACTs because HFCWO-
4 2.0 18–20 2.0 18–20 induced decreases in EELV have the potential to
5 2.0 18–20 1.5 18–20 decrease Spo2,16 and low-PEP breathing has the poten-
6 2.0 20 2.0 20 tial to increase Spo2 during and after treatment.12,17
7 1.5 20 1.5 20
8 1.5 20 1.5 20
9 1.5 15 1.5 18
Data Analysis
10 1.5 18 1.5 18–20 To ensure that this study had adequate power, a power
11 2.0 20 1.5 20 analysis was conducted. The results of the power analysis
12 1.5 10 1.5 15 indicated that for a large effect size at an alpha level of
13 2.0 15 2.0 20 .05, the study required 15 subjects per treatment group.
14 1.5 20 1.5 20
15 1.5 18 1.5 20

‡
Medical Graphics Corp, 350 Oak Grove Pkwy, St Paul, MN 55127.
§
Mallinckrodt Inc, a division of Nellcor-Puritan Bennet Co, 675 McDonnel Blvd,
Hazelwood, MO 63042.

1282 . Darbee et al Physical Therapy . Volume 85 . Number 12 . December 2005


Figure 3.
(Top) Single-breath nitrogen (N2) washout curve generated by a subject
without cystic fibrosis (CF). The arrow pointing right indicates the
absolute expired N2 concentration. Phase I represents extreme upper-
airway dead-space gas. Phase II, marked by the sudden increase in N2
gas concentration, represents a mixture of dead space and alveolar
gas. Phase III represents the alveolar gas plateau, which is horizontal to
the x-axis when the expired N2 gas concentration becomes consistent,
indicating that equal amounts of N2 are being emptied from lung units
and that the distribution of ventilation is homogeneous. Under normal
physiologic conditions, the N2 concentration changes minimally as long
as the distribution of ventilation is uniform. In this case, the slight upward
phase III slope indicates some nonuniformity in the distribution of
ventilation. Phase IV marks the sudden onset of an increase in N2 gas
concentration as small, oxygen-rich airways close. (Bottom) Single-
breath nitrogen (N2) washout curve generated by subject with
CF-related obstructive lung disease. Note the rising phase III alveolar
slope for the subject, for whom the expired N2 concentration changes,
indicating nonuniformity in the distribution of ventilation. Also note
during phase IV the sudden and sharp increase in the N2 concentration,
as indicated by the downward-pointing arrow, as small airways close.
Physical Therapy . Volume 85 . Number 12 . December 2005
Group means and standard deviations were calculated
for demographic data, for percentages of predicted
N2 /volume slope data, for DIVL for He, N2 , and SF6 , for
Spo2 , and for percentages of predicted forced vital
capacity (FVC), forced expiratory volume in 1 second
(FEV1), and forced expiratory flow between 25% and
75% vital capacity (FEF25%–75%) at study enrollment. To
determine acute changes during treatment sessions and
differences in treatment at hospital admission and dis-
charge, a 3-way repeated-measures analysis of variance
was performed (treatment [HFCWO or PEP breathing]
⫻ time [before or after treatment] ⫻ hospital status
[admission or discharge]) with time and hospital status
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as the repeated variables (Statistica 6.1 software pack-
age㛳). Analysis of Spo2 data was performed as for the
other variables, with the exception that because Spo2 was
measured continuously throughout the airway clearance
treatment, the high and low Spo2 values during treat-
ment were identified, thus yielding 4 levels for time
(before, high, low, and after) but 2 levels for the other
variables. Significant F ratios were followed up with
Tukey honestly significant difference post hoc methods to
identify specific differences. Significance was set at a P
value of ⬍.05.
Results
Effects of Airway Clearance on Pulmonary Function at
Hospital Admission and Discharge
Pulmonary function was measured before and after
airway clearance treatments at admission to and dis-
charge from the hospital (Tab. 3). At admission to the
hospital, pulmonary function values measured before
airway clearance treatments were not different on the 2
testing days (Tab. 3).
Airway clearance treatments were associated with
changes in FVC and FEV1. Specifically, a significant
interaction between time and hospital status was
observed for FVC. This interaction demonstrated that
both HFCWO and PEP breathing resulted in average
improvements in FVC of 13% (P⬍.0002) during the
acute stage of exacerbation (admission) but not during
the subacute stage (discharge) (Tab. 3). A significant
main effect of time was observed for FEV1 , indicating
that during both the acute stage of exacerbation and the
subacute stage, HFCWO and PEP breathing treatments
resulted in improvements in FEV1 (P⬍.0002) (Tab. 3).
The airway clearance treatments at admission and dis-
charge had no effect on FEV1 /FVC and FEF25%–75%.
Additionally, there were no differences in the responses
of any of the pulmonary function measures between the
㛳
StatSoft Inc, 2300 E 14th St, Tulsa, OK 74104.
Darbee et al . 1283
 ўўўўўўўўўўўўўўўўўўўўўў
Table 3.
Lung Function at Admission and Dischargea

HFCWO PEP Breathing

Admission Discharge Admission Discharge
Pre Post Pre Post Pre Post Pre Post
Parameter X SD X SD X SD X SD X SD X SD X SD X SD

FVC (% predicted) 70 18 77b 21 79 20 83 19 66 18 77b 21 79 20 80 19

b b
FEV1 (% predicted) 54 20 60 22 66 26 69 24 56 21 60b 23 64 24 66b 25
FEV1/FVC 0.68 0.15 0.67 0.13 0.70 0.14 0.71 0.12 0.67 0.13 0.67 0.13 0.69 0.14 0.70 0.15
FEF25%–75% (% predicted) 38 32 40 35 47 37 47 37 37 27 37 29 45 36 48 38
a

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HFCWO⫽high-frequency chest wall oscillation, PEP⫽low positive expiratory pressure, Pre⫽before treatment, Post⫽after treatment, FVC⫽forced vital capacity,
FEV1⫽forced expiratory volume in 1 second, FEF25%–75%⫽forced expiratory flow between 25% and 75% vital capacity.
b
Significant change between pretreatment and posttreatment values.

Table 4.
Single-Breath Dataa

HFCWO PEP Breathing

Admission Discharge Admission Discharge
Pre Post Pre Post Pre Post Pre Post
Parameter X SD X SD X SD X SD X SD X SD X SD X SD

N2 slope 922 631 843b 564 759 660 680b 571 906 522 822b 500 755 605 705b 554
(% predicted)
b
DIVL for He 3.6 1.3 3.8b 1.2 3.7 1.5 4.0b 1.4 3.4 1.0 3.8 1.4 3.7 1.5 3.9b 1.5
b b b
DIVL for N2 3.2 1.4 3.5 1.1 3.4 1.4 3.6 1.3 3.1 1.0 3.5 1.3 3.4 1.4 3.7b 1.4
b b b b
DIVL for SF6 3.6 1.5 3.9 1.3 3.8 1.6 4.3 1.7 3.4 1.1 3.9 1.5 3.9 1.8 4.1 1.6
a
HFCWO⫽high-frequency chest wall oscillation, PEP⫽low positive expiratory pressure, Pre⫽before treatment, Post⫽after treatment, N2⫽nitrogen, DIvl⫽dilution
index values expressed at an absolute lung volume, He⫽helium, SF6⫽sulfur hexafluoride.
b
Significant change between pretreatment and posttreatment values.

HFCWO and the PEP breathing treatments at either clearance treatment during both the acute exacerbation
admission or discharge (Tab. 3). stage and the subacute stage (Tab. 4, Fig. 4).

Effects of Airway Clearance on Ventilation Distribution
and Gas Mixing at Hospital Admission and Discharge
Ventilation distribution and gas mixing were measured
before and after airway clearance treatments during
both the acute stage (admission to the hospital) of
exacerbation and the subacute stage (just before dis-
charge from the hospital) (Tab. 4, Figs. 4 and 5). At
admission to and discharge from the hospital, the values
for N2 slope, which provides an index of overall ventila-
tion distribution homogeneity, were not different before
either airway clearance treatment (Tab. 4, Fig. 4).
A main effect of time was observed for N2 slope, indicat-
ing that treatment with either HFCWO or PEP breathing
at both admission and discharge was associated with a
reduction in N2 slope (P⫽.011) (Tab. 4, Fig. 4). This
reduction indicates that ventilation was more uniformly
distributed throughout the lungs after either airway
The DIVL for the 3 test gases (He, N2 , and SF6) measure
how well an inspired test gas mixes with gas already
present in the lungs. At admission to and discharge from
the hospital, the DIVL for He, N2 , and SF6 were not
different before either airway clearance treatment
(Tab. 4, Fig. 5).
There were main effects of time for the DIVL for He, N2 ,
and SF6 (Tab. 4, Fig. 5). This finding indicates that
treatment with either HFCWO or PEP breathing at both
admission and discharge was associated with improve-
ments in gas mixing. The DIVL for He, N2 , and SF6
increased, on average, 8% (P⬍.0004), 9% (P⬍.0002),
and 10% (P⬍.0003), respectively (Tab. 4, Fig. 5).

1284 . Darbee et al Physical Therapy . Volume 85 . Number 12 . December 2005

 Effects of Airway Clearance on SpO2 at
Hospital Admission and Discharge
Arterial blood oxyhemoglobin satura-
tion was measured before, during, and
after airway clearance treatments at
both admission to and discharge from
the hospital. There were no differences
in Spo2 before either treatment at
admission to and discharge from the
hospital (Fig. 6).

A significant interaction between time

and treatment was observed for Spo2.

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This interaction demonstrated that
during both the acute stage of exacer-
bation and the subacute stage, Spo2
responses differed between HFCWO
and PEP breathing airway clearance
treatments. Specifically, HFCWO
resulted in decreases in Spo2 during
treatment at both admission and dis-
charge (P⬍.00004) (Fig. 6). Immedi-
Figure 4.
Ventilation distribution depicted by the phase III alveolar nitrogen (N2) slope expressed as a ately after treatment, Spo2 returned to
percentage of predicted values for high-frequency chest wall oscillation (HFCWO) and low pretreatment levels. Conversely, airway
positive expiratory pressure (PEP) breathing interventions before treatment (Pre) and after clearance with PEP breathing at both
treatment (Post) at hospital admission and discharge. Values are means⫾SDs. *⫽significant admission and discharge was asso-
change between pretreatment and posttreatment values.
ciated with increases in Spo2 during
treatment (P⬍.00004) (Fig. 6). These
increases were not sustained after
treatment.

Discussion
In this investigation, we evaluated the
physiologic responses to 2 airway clear-
ance interventions, HFCWO and low-
PEP breathing, in subjects who had
moderate to severe CF and who
required hospitalization because of an
exacerbation of their chronic lung dis-
ease. The goal of this investigation was
to use the physiologic response data
obtained during the application of
HFCWO and low-PEP breathing to
improve the prescription of airway
clearance treatment in this patient pop-
ulation. The most important finding in
this investigation was that both the
HFCWO and the PEP breathing inter-
ventions were similarly efficacious in
improving pulmonary function, ventila-
Figure 5. tion distribution, and gas mixing in
Gas mixing for helium expressed in dilution index format for high-frequency chest wall
oscillation (HFCWO) and low positive expiratory pressure (PEP) breathing interventions before
subjects who had CF and who were
treatment (Pre) and after treatment (Post) at hospital admission and discharge. Values are experiencing an exacerbation. How-
means⫾SDs. *⫽significant change between pretreatment and posttreatment values. ever, distinct differences in the under-
lying physiologic mechanisms between
the 2 treatments were identified, and

Physical Therapy . Volume 85 . Number 12 . December 2005 Darbee et al . 1285

 ўўўўўўўўўўўўўўўўўўўўўў
more likely the subject will experience
hypoxia during HFCWO treatment.

Among reports of HFCWO use by sub-

jects with CF,8 –10,15 only Arens et al8
measured and reported subject Spo2
responses. In contrast to the findings in
the present study, improvements in
Spo2 occurred during and up to 1 hour
after treatment on days 7 and 14 of
hospitalization for a pulmonary exacer-
bation in both the CPT and the
HFCWO groups, but there were no

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differences in Spo2 between the 2 treat-
ment interventions.8 Interestingly, at
enrollment, our subjects had less cen-
tral and peripheral airway obstruction
than subjects in the study of Arens et
al,8 as indicated by the percentages of
the predicted FEV1 (X⫾SD: 55⫾21 ver-
sus 33.8⫾2.4) and FEF25%–75% (37⫾29
versus 13.5⫾2.0) values, yet the mean
Spo2 was slightly lower in our study
subjects. In addition, our study subjects
exhibited more ventilation distribution
inhomogeneity, as indicated by the per-
cent predicted N2 slope values (X⫾SD:
914⫾567) in the present study com-
pared with the percent predicted N2
Figure 6. slope values in the study of Arens et al8
Percent arterial blood oxyhemoglobin saturation (SpO2) values for high-frequency chest wall
oscillation (HFCWO) and low positive expiratory pressure (PEP) breathing interventions before
(X⫾SD: 601⫾75).
treatment (Pre), during treatment, and after treatment (Post) at hospital admission and
discharge. Note the low and high SpO2 values during each intervention. Values are Improvements in Spo2 during low-PEP
means⫾SDs. *⫽significantly different from values for HFCWO-Pre, HFCWO-High, HFCWO- breathing in the present study were
Post, and PEP-High. **⫽significantly different from values for PEP-Pre, PEP-Low, PEP-Post, and
similar to improvements in Spo2 re-
HFCWO-Low.
ported by other authors.17 Arterial blood
oxyhemoglobin saturation increased
after a 20-minute low-PEP breathing
these differences may affect clinical decision making treatment, peaked at 35 minutes after treatment, and
during prescription of an airway clearance treatment never dropped below baseline for a group of subjects
intervention in this patient population. who had CF and who had considerably more central
airway obstruction, as indicated by an FEV1 that was 34%
Effects on SpO2 of the predicted value,17 than the subjects in our study,
The most striking difference between the HFCWO and who had an FEV1 that was 55% of the predicted value.
the PEP breathing treatments was the observation that
the HFCWO treatment was associated with decreases in Different Mechanisms Leading to Improved Ventilation
Spo2 during treatment, whereas the PEP breathing Distribution and Gas Mixing
treatment produced modest, but significant, increases in Although there were no differences between the effects
Spo2 during treatment (Fig. 6). When subject Spo2 of the HFCWO and PEP breathing treatments on venti-
values are 94% or above, values that correspond to lation distribution and gas mixing in our study, there
partial pressures for oxygen in the low to middle 70s, as were differences in the underlying physiologic mecha-
we observed in our study subjects, the decreases in Spo2 nisms of the 2 treatments that led to the improvements,
with HFCWO are likely to be clinically insignificant. and these differences warrant further discussion. The
However, the observed decreases in Spo2 may be impor- decreases in the phase III alveolar slopes after both
tant to note, because the lower a subject’s pretreatment airway clearance treatments resulted from more com-
Spo2 , the more likely desaturation will occur and the plete gas mixing and led to improvements in ventilation

1286 . Darbee et al Physical Therapy . Volume 85 . Number 12 . December 2005

distribution. The increases in expired gas concentrations
for He, N2 , and SF6 after the treatments reflected the
improved efficiency with which an inspired gas mixture
containing a test gas mixed with gas already present in
the lungs.26
HFCWO mechanisms. Although the exact mechanism
for improvements in gas mixing and ultimately ventila-
tion distribution during HFCWO is speculative, several
theories have been suggested.27 One postulate is that
pendelluft may increase during HFCWO.28 –30 Pendelluft
is the movement of air between neighboring lung units
(the functional unit of gas exchange, which consists of
structures containing alveoli that reside distal to the end
of the terminal bronchiole) that have different time
constants.31 The time constant for a lung unit is defined as
the time required for a lung unit to empty or fill and is
equal to the product of its resistance to airflow and its
compliance.31 Thus, air movement within the lungs is
dependent on airway diameter and tissue elasticity.31
Time constants are slow when lung units have low
distensibility and high airway resistance, such as in
CF-related lung disease. Parallel lung units, present in
the same lung region, normally fill and empty at about
the same rates.31 However, in obstructive lung disease,
parallel lung units frequently fill and empty at different
rates.4,12 During HFCWO, pendelluft may increase the
recirculation of air, thereby increasing alveolar ventila-
tion for previously closed or underventilated lung
units.27,29 The results are improvements in gas mixing
and homogenization of expired gas concentrations from
these neighboring lung units.29,30
High-frequency chest wall oscillation delivered at 10 and
15 Hz has been shown to decrease functional residual
capacity (FRC) and to increase tidal volume and airflow
in subjects who were healthy16,32 and in subjects with
obstructive lung disease.16,32,33 Functional residual
capacity, or EELV (the volume of gas remaining in the
lungs at the end of expiration), decreased during
HFCWO because of the positive pressure applied over
the chest wall.16,28,32,33 End-expiratory lung volume, a
dynamic and constantly changing breath-by-breath lung
volume, is commonly elevated in subjects with chronic
obstructive pulmonary disease, such as CF secondary to
air trapping.3,34 This elevation of EELV provides an
important physiologic mechanism by which small-airway
closure is minimized and gas exchange is sustained in
subjects with chronic obstructive pulmonary disease.2
Although decreases in FRC have been shown to accom-
pany increases in tidal volume and alveolar ventilation at
low oscillation frequencies,28 HFCWO delivered at high
oscillation frequencies potentially leads to small-airway
closure and deterioration in gas exchange for subjects
who already have expiratory airflow limitations.3,16,28,34
Physical Therapy . Volume 85 . Number 12 . December 2005
During HFCWO intervention, we purposefully selected
lower oscillation frequencies, of 10 and 15 Hz, from a
range of 5 to 25 Hz, and a midrange background
pressure in order to maximize oscillated airflow16 and
oscillated tidal volume16 and to minimize reductions in
EELV.16,33 In this regard, Jones et al16 reported reduc-
tions in EELV to 90% of baseline pre-HFCWO values.
Although reductions in EELV were observed, no deteri-
oration in Spo2 occurred during or after HFCWO treat-
ment because the subjects were breathing 50% supple-
mental oxygen.16 The authors speculated, however, that
hypoxia could occur for subjects with CF during a
30-minute HFCWO treatment while breathing room air
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because of the reductions in EELV associated with
HFCWO.16 Therefore, the observed decreases in Spo2
during HFCWO treatment in the present study may be
important because the lower the subject’s pretreatment
Spo2 , the more likely desaturation is to occur.
In light of the small decreases in SpO2 during HFCWO,
it is possible that some small-airway closure occurred and
may have reduced the contribution made by small-airway
inhomogeneities to the phase III alveolar slope during
single-breath testing and caused the phase III slope to
move downward toward horizontal.28 However, the
effects of any decreases in lung volume likely were offset
by the effects of improved gas mixing during HFCWO,
which preserved gas exchange in our subjects in both
the admission and the discharge HFCWO treatment
sessions.
PEP breathing mechanisms. Low-PEP breathing also
was associated with marked improvements in ventilation
distribution (Tab. 4, Fig. 4) and gas mixing (Tab. 4,
Fig. 5), but through physiologic mechanisms different
from those of HFCWO. Improvements in gas mixing
after low-PEP breathing in the present study were similar
to findings reported previously from our laboratory.12
Our data suggest that the improvements in gas mixing
and FVC likely were attributable to a decrease in the
partial or complete obstruction of smaller, peripheral
airways. The low expired He, N2 , and SF6 concentrations
(Tab. 4, Fig. 5) and the N2 phase III alveolar slope values
(Tab. 4, Fig. 4) measured before the interventions
reflected heterogeneity of time constants within the
peripheral airways of our subjects with CF, confirming
the presence of fast and slow time constants. During 30
minutes of resistance breathing during PEP treatment,
peripheral airways were dilated, facilitating the ongoing
exhalation of RV gas.12,35 The ongoing exhalation of RV
gas generated airflow through the smaller airways12,35
and facilitated faster filling and emptying times for lung
units, but particularly for slow lung units.12,35 Gas mixing
improved because time constants for lung units, which
are dependent on airway diameter and tissue elasticity,
became faster and additional gas volume could be
Darbee et al . 1287

exhaled during the prolonged expiration.12,35 This addi-
tional exhaled gas volume led to the increased FVC. We
attribute the improvements in Spo2 after PEP breathing
to improvements in gas mixing, in which a larger volume
of an inspired gas mixture containing a test gas mixed
with a smaller volume of gas already present in the
lungs.12,22
Decreases in the phase III alveolar slopes for N2 gas
indicated that there were improvements in ventilation
distribution after PEP breathing treatment. This finding
was different from findings reported previously from our
laboratory.12 Previously, phase III alveolar slopes for He
gas were not found to be different after 20 minutes of
PEP breathing.12 We attribute this finding to the high
diffusivity of He, which permitted the gas to diffuse into
poorly ventilated regions before PEP breathing treat-
ment and therefore minimized our ability to measure
any changes in ventilation distribution that might have
occurred as a result of the PEP breathing treatment. In
the present study, we used heavier, resident N2 gas
which, in contrast to He gas, had unequal concentra-
tions throughout the lungs due to poorly ventilated
regions before treatment. During PEP breathing treat-
ment, airways were opened and N2 gas likely diffused
into previously closed regions as a result of breathing
against positive pressure.12,35 The improvements in the
homogeneity of ventilation distribution were reflected
by the decreased N2 phase III alveolar slopes after PEP
breathing treatment.
Role of Sputum Collection in Studies of Airway Clearance
Treatments
Sputum collection was not performed in this study.
Based on our previous findings,12 we do not believe that
sputum collection, within the context of repeated pul-
monary function testing and airway clearance treatment
interventions, reflects only the efficacy of an ACT. We
believe that deep breathing, coughing, and the pro-
longed, forceful exhalations performed during pulmo-
nary function testing facilitated the loosening and
removal of sputum, which led to the cumulative
increases in sputum amounts observed during control,
low-PEP, and high-PEP conditions in our previous
study.12 We believe that, in the evaluation of an airway
clearance treatment, it is important to consider other
indexes reflecting airway clearance, such as Spo2 , venti-
lation distribution, and gas mixing, which are physiolog-
ically meaningful and have important implications for
physical therapist clinical practice.
Limitations
In the present study, the subjects used bronchodilator
therapy during both airway clearance treatments.
Because PEP breathing transmits a back pressure to the
airways, it is conceivable that the administration of the
1288 . Darbee et al
ўўўўўўўўўўўўўўўўўўўўўў
bronchodilator will be altered during this treatment and
thus may affect results. However, a previous study that
examined the effect of PEP breathing on the delivery of
metered-dose inhaled albuterol showed that there were
no differences in total drug dosages with PEP breathing
and without PEP breathing.18 Additionally, in another
study,19 an inhaled bronchodilator was administered
with PEP breathing and without PEP breathing; the
authors found that peak expiratory flow increased simi-
larly with the administration of the bronchodilator with
PEP breathing and without PEP breathing.19 These
findings suggest that the administration of albuterol with
PEP breathing or without PEP breathing is unlikely to be
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a major confounding variable.
Conclusion
The results of this investigation indicated that both
HFCWO and low-PEP breathing airway clearance inter-
ventions were similarly efficacious in improving pulmo-
nary function, ventilation distribution, and gas mixing
for subjects who had CF and who were experiencing an
acute exacerbation of their pulmonary disease. These
improvements in ventilation distribution and gas mixing
were associated with small, yet significant, increases in
Spo2 during PEP breathing. Alternatively, the use of
HFCWO was associated with improvements in ventila-
tion distribution and gas mixing and small decreases in
Spo2. These findings led to our recommendation that,
for people who have moderate to severe CF-related lung
disease and who are experiencing an acute exacerbation
requiring hospital admission, it is essential to monitor
Spo2 during airway clearance treatments. People who
have low pretreatment Spo2 levels could desaturate to
unacceptable levels during HFCWO therapy. These indi-
viduals may benefit from the use of low-PEP breathing
therapy during an acute exacerbation of their lung
disease. Both HFCWO and low-PEP breathing interven-
tions were associated with improvements in ventilation
distribution and gas mixing. Therefore, we recommend
either HFCWO or low-PEP breathing for people stable
CF-related lung disease because, once the acute lung
infection has been treated and lung function improves,
it may be possible to maintain Spo2 at acceptable levels
with either treatment and still experience the benefits of
improved gas mixing. For people in whom HFCWO
results in desaturation and who find that low-PEP breath-
ing is too fatiguing to perform during the early stages of
treatment for an acute exacerbation, CPT may be indi-
cated because it has been shown that CPT and low-PEP
breathing are equally effective at secretion removal in
subjects with CF.9 For people with stable lung function,
both HFCWO and low-PEP breathing are associated with
similar improvements in pulmonary function, ventila-
tion distribution, and gas mixing; thus, patient prefer-
ence should be considered in the prescription of a
specific airway clearance treatment.
Physical Therapy . Volume 85 . Number 12 . December 2005
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