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Research Reports |
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{at}uky.edu)
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)
Address all correspondence to Dr Darbee
Submitted August 23, 2004;
Accepted May 24, 2005
 | Abstract |
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Key Words: Airway clearance • Chest physical therapy • Cystic fibrosis • Gas mixing • Ventilation distribution
| Introduction |
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 TopAbstract Introduction MethodResultsDiscussionConclusionReferences |
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Putative goals of ACTs are to decrease airway obstruction and airflow limitation and to improve ventilation distribution through the mobilization and removal of airway mucus.7 Two independent ACTs, high-frequency chest wall oscillation (HFCWO) and positive expiratory pressure (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 interventions 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 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, information 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 overall ventilation distribution improved equally for HFCWO and CPT treatment groups. Recently, Darbee and colleagues12 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 distribution, 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 group of subjects who had moderate to severe obstructive 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 oxyhemoglobin saturation (Spo2) for subjects with CF at hospital admission and discharge.
| Method |
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TopAbstractIntroductionMethodResultsDiscussionConclusionReferences |
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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 daytime 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 volunteers and from parents (for subjects younger than 18 years of age) before participation.
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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 perform 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 polyester 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 treatment, 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 background pressure, high background pressure is known to lower end-expiratory lung volume (EELV) more than low background pressure for the same oscillation frequency.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
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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 interval. Six cycles consisting of 5 minutes of treatment followed by forced expiratory maneuvers and coughing were completed by all subjects.
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 observations 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 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 sustained 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 perform 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. A total of 8 to 10 cycles consisting of 8 breaths were performed over 30 minutes.
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during the HFCWO and PEP breathing treatment interventions. The nebulizer was interfaced 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. Subjects 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 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).
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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 obtained by simple spirometry according to standard methods14 by use of a MedGraphics PC SpiroCard interfaced with the Office Medic software program
and a computer. The measurements were expressed as percentages of predicted values.24,25
Noninvasive, continuous-pulse oximetry (Nellcor N-200
) was performed with a finger probe attached to the right index finger to estimate Spo2. Arterial blood oxyhemoglobin saturation was measured before treatment, continuously throughout treatment, and for several minutes after treatment until heart rate and Spo2 stabilized. Arterial blood oxyhemoglobin saturation measurements were obtained during both ACTs because HFCWO-induced decreases in EELV have the potential to decrease Spo2,16 and low-PEP breathing has the potential to increase Spo2 during and after treatment.12,17
Data Analysis
To ensure that this study had adequate power, a power analysis was conducted. The results of the power analysis indicated that for a large effect size at an alpha level of .05, the study required 15 subjects per treatment group.
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 discharge, a 3-way repeated-measures analysis of variance was performed (treatment [HFCWO or PEP breathing] x time [before or after treatment] x hospital status [admission or discharge]) with time and hospital status as the repeated variables (Statistica 6.1 software package||). 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 treatment 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 |
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TopAbstractIntroductionMethodResultsDiscussionConclusionReferences |
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The airway clearance treatments at admission and discharge 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 HFCWO and the PEP breathing treatments at either admission or discharge (Tab. 3).
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 discharge 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 ventilation distribution homogeneity, were not different before either airway clearance treatment (Tab. 4, Fig. 4).
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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 improvements 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).
Effects of Airway Clearance on SpO2 at Hospital Admission and Discharge
Arterial blood oxyhemoglobin saturation 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).
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| Discussion |
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TopAbstractIntroductionMethodResultsDiscussionConclusionReferences |
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Effects on SpO2
The most striking difference between the HFCWO and the PEP breathing treatments was the observation that the HFCWO treatment was associated with decreases in Spo2 during treatment, whereas the PEP breathing treatment produced modest, but significant, increases in Spo2 during treatment (Fig. 6). When subject Spo2 values are 94% or above, values that correspond to partial pressures for oxygen in the low to middle 70s, as we observed in our study subjects, the decreases in Spo2 with HFCWO are likely to be clinically insignificant. However, the observed decreases in Spo2 may be important to note, because the lower a subject's pretreatment Spo2, the more likely desaturation will occur and the more likely the subject will experience hypoxia during HFCWO treatment.
Among reports of HFCWO use by subjects 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 exacerbation in both the CPT and the HFCWO groups, but there were no differences in Spo2 between the 2 treatment interventions.8 Interestingly, at enrollment, our subjects had less central and peripheral airway obstruction than subjects in the study of Arens et al,8 as indicated by the percentages of the predicted FEV1 (
±SD: 55±21 versus 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 percent predicted N2 slope values (±SD: 914±567) in the present study compared with the percent predicted N2 slope values in the study of Arens et al8 (±SD: 601±75).
Improvements in Spo2 during low-PEP breathing in the present study were similar to improvements in Spo2 reported by other authors.17 Arterial blood oxyhemoglobin saturation increased after a 20-minute low-PEP breathing treatment, peaked at 35 minutes after treatment, and never dropped below baseline for a group of subjects who had CF and who had considerably more central airway obstruction, as indicated by an FEV1 that was 34% of the predicted value,17 than the subjects in our study, who had an FEV1 that was 55% of the predicted value.
Different Mechanisms Leading to Improved Ventilation Distribution and Gas Mixing
Although there were no differences between the effects of the HFCWO and PEP breathing treatments on ventilation distribution and gas mixing in our study, there were differences in the underlying physiologic mechanisms of the 2 treatments that led to the improvements, and these differences warrant further discussion. The decreases in the phase III alveolar slopes after both airway clearance treatments resulted from more complete gas mixing and led to improvements in ventilation 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 ventilation 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 ventilation 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 accompany 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 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 reductions in EELV to 90% of baseline pre-HFCWO values. Although reductions in EELV were observed, no deterioration in Spo2 occurred during or after HFCWO treatment because the subjects were breathing 50% supplemental oxygen.16 The authors speculated, however, that hypoxia could occur for subjects with CF during a 30-minute HFCWO treatment while breathing room air 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 exhaled during the prolonged expiration.12,35 This additional 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 treatment 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 concentrations throughout the lungs due to poorly ventilated regions before treatment. During PEP breathing treatment, 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 pulmonary function testing and airway clearance treatment interventions, reflects only the efficacy of an ACT. We believe that deep breathing, coughing, and the prolonged, forceful exhalations performed during pulmonary 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, ventilation distribution, and gas mixing, which are physiologically 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 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 similarly 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 a major confounding variable.
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TopAbstractIntroductionMethodResultsDiscussionConclusionReferences |
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| Footnotes |
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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.
* Hill-Rom, 1020 West County Rd F, St Paul, MN 55126. 
PARI Respiratory Equipment Inc, 7493 Whitepine Rd, Richmond, VA 23237.
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.
|| StatSoft Inc, 2300 E 14th St, Tulsa, OK 74104.
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TopAbstractIntroductionMethodResultsDiscussionConclusionReferences |
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