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(Chest. 2004;125:2075-2082.)
© 2004 American College of Chest Physicians

Effect of Heliox Breathing on Dynamic Hyperinflation in COPD Patients*

Matteo Pecchiari, MD; Andrea Pelucchi, MD; Emanuela D’Angelo, MD; Antonio Foresi, MD; Joseph Milic-Emili, MD and Edgardo D’Angelo, MD

* From the Istituto di Fisiologia Umana I (Drs. Pecchiari and Edgardo D’Angelo), Dipartimento di Pediatria (Dr. Emanuela D’Angelo), Università di Milano, Milan, Italy; Servizio di Fisiopatologia Respiratoria (Drs. Pelucchi and Foresi), Ospedale di Sesto San Giovanni, Sesto San Giovanni, Milan, Italy; and Meakins-Christie Laboratories (Dr. Milic-Emili), McGill University, Montreal, QC, Canada.

Correspondence to: Edgardo D’Angelo, MD, Istituto di Fisiologia Umana I, via Mangiagalli 32, 20133 Milan, Italy; e-mail: edgardo.dangelo{at}unimi.it


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background and objective: Patients with COPD exhibit increased inspiratory work and dyspnea due to dynamic hyperinflation caused by expiratory flow limitation. Helium-oxygen mixtures (ie, heliox) have been used in treating these patients on the assumption that, by lowering airway resistance, they might be beneficial.

Methods: In 22 patients with COPD, the presence of expiratory flow limitation was assessed with patients in the sitting and supine positions using the negative expiratory pressure technique, and the effects of heliox (80% He, 20% O2) on breathing pattern, expiratory flow limitation, and dynamic hyperinflation, evaluated from the change in inspiratory capacity (IC), were measured at rest and were compared with those due to inhaled salbutamol.

Results: During air breathing, 13 patients experienced flow limitation while in the sitting position and 18 experienced flow limitation while in the supine position. Neither heliox nor salbutamol therapy changed the breathing pattern in any of the patients, regardless of posture and the presence or absence of expiratory flow limitation. However, in both positions IC increased significantly in most flow-limited patients after bronchodilator administration, but not after heliox administration.

Conclusions: Since heliox had no effect on dynamic hyperinflation, the use of this gas mixture, which is costly and cumbersome, does not appear to be beneficial in stable patients with COPD breathing at rest.

Key Words: breathing pattern • bronchodilator • density dependence • expiratory flow limitation • negative expiratory pressure technique • respiratory mechanics


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
In healthy individuals at rest, the end-expiratory lung volume (ie, functional residual capacity [FRC]) corresponds to the relaxation volume of the respiratory system (ie, the lung volume at which the elastic recoil pressure of the respiratory system is zero).1 Pulmonary hyperinflation, which is defined as an increase in FRC above the predicted normal range, may be due to increased relaxation volume as a result of the loss of lung recoil (eg, emphysema) and/or dynamic hyperinflation. The latter occurs whenever the expiratory flow is impeded (eg, increased airway resistance) and/or the duration of expiration is insufficient to allow the lungs to deflate to the relaxation volume prior to the next inspiration (eg, increased breathing frequency). Expiratory flow also may be reduced by other mechanisms, such as persistent contraction of the inspiratory muscles during expiration and expiratory narrowing of the glottic aperture. In patients with COPD, dynamic hyperinflation is due mainly to tidal expiratory flow limitation (ie, the inability to increase expiratory flow by further increasing transpulmonary pressure at that lung volume). Most healthy subjects do not exhibit expiratory flow limitation even during maximal exercise. In contrast, in patients with COPD tidal expiratory flow limitation and concurrent dynamic hyperinflation may be present even at rest, and may play a central role in causing dyspnea and exercise intolerance.234 In these patients, bronchodilator administration decreases dynamic hyperinflation, with a concurrent increase in exercise performance and a decrease of dyspnea.45678 In hypoxemic COPD patients, however, oxygen administration also can reduce dynamic hyperinflation by lowering the pulmonary ventilation.

The use of helium-oxygen mixtures (usually 80% He and 20% O2 [also called heliox]) for the treatment of COPD was introduced in 1935 by Barach.9 If during air breathing the flow within the airways is not laminar, airway resistance should decrease using heliox mixtures.10 While Grapé et al11 found a significant decrease in pulmonary resistance with heliox, Wouters et al12 found no change in total respiratory resistance. Also controversial is the effect of heliox on dynamic hyperinflation. Grapé et al11 found no significant reduction in FRC with heliox, while Swidwa et al13 found a substantial fall in FRC. This discrepancy may reflect differences in the response to heliox in the COPD populations studied. Indeed, Meadows et al14 found that only half of their COPD patients exhibited an increase of maximal expiratory flows (MEFs) with heliox therapy (ie, the density dependence of MEF). Similarly, controversial results have been found in mechanically ventilated COPD patients.1516 Therefore, it is still unclear whether and when heliox administration is beneficial.

In COPD patients who exhibit tidal expiratory flow limitation and dynamic hyperinflation at rest, heliox breathing would be expected to increase MEF with a concomitant decrease of dynamic hyperinflation, if the flow-limiting segment is located in the central airways where the wave-speed mechanism dominates.17 In contrast, if the flow-limiting segment is located in the peripheral airways, the viscous flow-limiting mechanism should prevail.17 Hence, heliox should have no effect on MEF and dynamic hyperinflation. To test this, we have assessed in stable COPD patients, in both the sitting and supine positions, the effect of heliox breathing on tidal expiratory flow limitation, dynamic hyperinflation, and breathing pattern. Moreover, we have studied the effects of salbutamol administration in order to compare the benefits of this bronchodilator with those of heliox in the same patients.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Twenty-two stable COPD patients (one woman) with a mean (± SE) age of 71 ± 1 years were studied. Patients had no other cardiopulmonary diseases, and had not experienced an upper respiratory tract infection during the previous month. No patient was being treated with oral ß2-agonists, theophylline, or systemic corticosteroids, or had received inhaled short-acting ß2-agonistic or anticholinergic drugs for 8 h or long-acting ß2-agonists for 24 h before the study. The study was approved by the local ethics committee, and informed consent was obtained from all patients.

Pulmonary function was assessed with standard methods and procedures.18 The severity of chronic dyspnea was assessed with the modified Medical Research Council (MRC) scale.1 Spirometric measurements were performed using a body plethysmograph (Autobox 2800; SensorMedics; Yorba Linda, CA). Reference values were those of the European Coal and Steel Community.18 Oxygen and carbon dioxide partial pressure in arterial blood were measured with a blood gas analyzer (ABL 520; Radiometer; Copenhagen, Denmark).

Patients were investigated in the afternoon (1) while breathing air, (2) 10 min after equilibration with heliox, and (3) while breathing air before and 20 min after two inhalations of salbutamol (200 µg each) through a metered-dose inhaler. Measurements were carried out first seated and next supine. Procedures 1 and 2 were performed in random order.

The assessment of expiratory flow limitation was done by the negative expiratory pressure (NEP) method.2 Subjects, wearing a noseclip, breathed quietly through a flanged mouthpiece, a heated pneumotachograph (3830A; Hans Rudolph; Kansas City, MO) connected to a differential pressure transducer (± 2 cm H2O) [MP45; Validyne; Northridge, CA], and a two-way valve (model 2630; Hans Rudolph). The expiratory and inspiratory ports of the valve were connected to a Venturi device and a shutter (AeroMech Devices; Almonte, ON, Canada), respectively. The Venturi device was connected via a solenoid valve (AeroMech Devices) to a high-pressure source, and a regulator allowed for a preset pressure (–5 cm H2O) at the airway opening that was measured with a pressure transducer (± 10 cm H2O) [MP45; Validyne]. The shutter was connected through a three-way stopcock to the ambient air or to a large plastic bag containing humidified heliox at ambient temperature and pressure. The patient was unaware of the gas mixture he was breathing. The dead space of the equipment was 60 mL, and its resistance (cm H2O/s/L) was 0.73 ± 2.11 for air breathing and 0.53 ± 0.47 for heliox breathing. The pneumotachograph, calibrated with a 1-L syringe filled with air or heliox, was linear over the experimental flow range. Pressure and flow signals were amplified, low-pass filtered at 50 Hz, digitized at 100 Hz by a 16-bit AD converter (Direct Physiologic Recording System; Raytech Instruments; Vancouver, BC, Canada). The digitized data were stored on a computer and subsequently were analyzed (LabVIEW Software; National Instruments; Austin, TX).

In all cases, several NEP tests were performed at intervals of 6 to 8 breaths, with the preceding baseline expiration serving as the control. Patients were classified as non-flow-limited, if the application of NEP increased expiratory flow over the entire range of the control tidal volume (VT), or flow-limited, if the control and test expiratory flow-volume (-V) relations were superimposed, at least in part. Two to three breaths after each NEP test, the subjects inspired to total lung capacity (TLC), and then expired to residual volume for the assessment of inspiratory capacity (IC) and vital capacity (VC), and for the correct alignment of the individual tidal -V curves with respect to TLC. Changes in dynamic hyperinflation were assessed in terms of changes in IC. This approach has been shown to be reliable in COPD patients,19 and is commonly used.235678

Under all experimental conditions, the breathing pattern was measured over a 3-min period prior to the NEP tests. Minute ventilation (E) was computed as the product of respiratory frequency and inspired VT. Arterial blood samples were taken at the end of the experimental session with patients breathing air and heliox while in the supine position.

The data were presented as the mean ± SE and were compared using the paired or unpaired Student t test. The correlation between MRC score and routine spirometry measurements was examined using the nonparametric Spearman rank correlation.20 Statistical significance was taken at p ≤ 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Table 1 shows the anthropometric characteristics and baseline lung function data of seated patients, who were stratified according to the presence or absence of expiratory flow limitation while sitting. Only FEV1, FEV1/FVC ratio, and the midexpiratory phase of maximal mean expiratory flow were significantly lower in flow-limited patients. Among all of the respiratory variables studied, the only significant correlation of MRC score was with the IC percent predicted in flow-limited patients (r = –0.81; p = 0.0007) and the FEV1/FVC ratio percent predicted in non-flow-limited subjects (r = –0.74; p = 0.023).


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  		Table 1. Anthropometric and Routine Lung Function Data of COPD Patients With and Without Tidal Expiratory Flow Limitation While Sitting*

 
Following salbutamol administration, FEV1 increased by > 200 mL and 12% more than the baseline value in only three flow-limited patients and two non-flow-limited patients. The overall reversibility index ({Delta}FEV1 as percentage of baseline value) was the same for flow-limited patients (11 ± 2%) and non-flow-limited patients (10 ± 4%).

On switching to the supine posture, the VC decreased (mean decrease, –0.23 ± 0.05 L; p < 0.001) and the IC did not change in flow-limited patients, while in non-flow-limited patients IC was increased (mean increase, 0.28 ± 0.07 L; p < 0.005) and VC did not change. Significant changes in breathing pattern occurred only in flow-limited patients: relative to sitting posture, and there were decreases in both mean inspiratory flow (decrease, 0.04 ± 0.02 L/s; p < 0.05) and expiratory flow (decrease, 0.07 ± 0.02 L/s; p < 0.001), mainly because of a fall in VT.

Figure 1 shows the -V curves of five control breaths (top panels) [ie, the baseline expirations immediately preceding the NEP test breaths] and five NEP tests breaths (middle panels) in sitting flow-limited and non-flow-limited patients. In flow-limited patients, the expiratory -V curves, except for their initial part, followed a fixed trajectory, whereas in non-flow-limited patients these trajectories were more variable for control breaths and, in some cases, also for test breaths. Relative to control breaths, the application of NEP caused an immediate increase in expiratory flow, followed by some oscillations, both in flow-limited and non-flow-limited patients. This is caused by the collapse of extrathoracic airways and by an artifact due to the common-mode rejection ratio.4 These transients were eliminated, as shown in Figure 1, bottom panels, which illustrates the ensemble-averaged -V curve of control and test breaths during NEP application in flow-limited and non-flow-limited patients. In each patient, the control curve was obtained by dividing the inspiratory and expiratory duration of each breath into 50 intervals and computing the average flow and volume of all control breaths for each interval. The ensemble-averaged NEP curve was obtained by interpolating the part of the expiratory -V curves that was artifact free with a second-order polynomial function and extending it to cover the average VT span. In flow-limited patients, the ensemble-averaged control curve and test expiratory -V curve were superimposed over a substantial fraction of VT. In contrast, in non-flow-limited patients the expiratory -V curves during NEP application were above the control curves, indicating the absence of expiratory flow limitation. All patients who were flow-limited in the sitting position also were flow-limited in the supine position, which is in line with the findings of previous studies.24



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  		Figure 1. Examples of a flow-limited and non-flow-limited patient breathing air in the seated position. Top panels: -V loops during five control breaths immediately preceding the NEP test breaths. Middle panels: corresponding -V curves during the NEP test breaths, which exhibit an initial artifact (oscillations in flow) during the application of NEP. Bottom panels: ensemble-averaged control and test -V curves with the initial artifact removed. Volume is represented in liters below the TLC.

 
Effects of Heliox
Regardless of the posture, presence, or absence of expiratory flow limitation, heliox had no significant effect on VC, IC, or breathing pattern (Table 2 ). In a sitting posture, nine patients were flow-limited while breathing both air and heliox, four patients were flow-limited only while breathing air, and nine patients were non-flow-limited while breathing air and heliox. While in the supine position, 18 patients were flow-limited while breathing both air and heliox, and 4 patients were non-flow-limited while breathing air and heliox. In all patients who were flow-limited while breathing air and heliox, the expiratory -V curves of control and test breaths were essentially superimposed under both conditions (Fig 2 , top left, a, and bottom left, c), reflecting the density independence of MEF. In contrast, in the patients who were non-flow-limited while breathing air and heliox, expiratory flows with NEP were higher while breathing heliox than while breathing air, reflecting a density-dependent decrease of airway resistance (Fig 2, top right, b, and bottom right, d). A similar response was found also in the four seated patients who while breathing heliox reversed their status from flow-limited to non-flow-limited. In the supine posture, heliox, compared with air, did not significantly affect the mean arterial PO2 (71 ± 2 vs 75 ± 2 mm Hg, respectively) and PCO2 (39 ± 1 vs 40 ± 1 mm Hg, respectively).


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  		Table 2. IC and Breathing Pattern During Air or Heliox Breathing in COPD Patients Stratified According to Presence of Expiratory Flow Limitation*

 


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  		Figure 2. Examples of patients who were flow-limited during both air and heliox breathing in the seated position (top left, a) and the supine position (bottom left, c), and were non-flow-limited under both conditions in the seated position (top right, b) and the supine position (bottom right, d). Only ensemble-averaged -V curves of control and test breaths are shown for each posture during air breathing (dotted line) and heliox breathing (continuous line). Volume is represented in liters below the TLC.

 
Effects of Salbutamol
None of the 13 patients who were flow-limited in the sitting position became non-flow-limited after salbutamol administration. However, 10 of them exhibited a significant increase in IC and VC after salbutamol administration, while the breathing pattern did not change (Table 3 ). Since the breathing pattern did not change, the increase in IC was due entirely to the increase of MEFs caused by bronchodilation.


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  		Table 3. IC and Breathing Pattern Before and After Salbutamol Inhalation in COPD Patients Stratified According to Presence of Expiratory Flow Limitation*

 
After salbutamol administration, there was a leftward shift of the control -V loop in most flow-limited patients (Fig 3 , top left, a), indicating a reduction in end-expiratory volume as reflected by the increased IC. In contrast, in the non-flow-limited subjects the end-expiratory volume did not change (Fig 3, top right, b). In both flow-limited and non-flow-limited patients, however, the MEFs for a given lung volume increased, as is seen quantitatively by the vertical distance between the expiratory -V curves before and after salbutamol administration. This allowed the flow-limited patients to sustain the same ventilation before and after salbutamol administration (Table 3), but with a lower end-expiratory lung volume under the latter condition.



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  		Figure 3. Examples of patients who were flow-limited both before and after salbutamol inhalation in the seated position (top left, a) and the supine position (bottom left, c), and were non-flow-limited under both conditions in the seated position (top right, b) and the supine position (bottom right, d). Only ensemble-averaged -V curves of control and test breaths are shown for each posture before salbutamol inhalation (dotted line) and after salbutamol inhalation (continuous line). Volume is represented in liters below the TLC.

 
Similar results were found with patients in the supine position (Fig 3, bottom left, c, Table 3), in which 13 patients exhibited a significant increase in IC. Thus, salbutamol caused a reduction of dynamic hyperinflation, as reflected by increased IC, which, relative to baseline, amounted to a mean change in IC of 9.9 ± 2.5% while in the sitting position and 9.3 ± 2.4% while in the supine position (p < 0.005 for both). In six flow-limited patients the change in IC exceeded 12% in both positions (Fig 4 ). Compared to heliox breathing, IC increased significantly with salbutamol administration (0.18 ± 0.03 L; p < 0.001) in flow-limited patients both in the sitting and the supine position. In non-flow-limited patients, there were no significant changes in breathing pattern, VC, and IC (Table 3), independent of posture, and control -V loops were similar before and after salbutamol administration (Fig 3, top right, b, and bottom right, d).



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  		Figure 4. Changes in IC ({Delta}IC) after salbutamol inhalation, expressed as a percentage of control values (% baseline), in 22 COPD patients in the seated and the supine position, either flow-limited or non-flow-limited both before and after salbutamol inhalation. The dotted line indicates an IC increase of 12% relative to baseline.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Our main findings are that in all COPD patients who were flow-limited while breathing air at rest, heliox had no effect on dynamic hyperinflation, independent of posture, while, in the same flow-limited patients, salbutamol significantly increased IC in both the sitting and the supine position.

In the present COPD population, there was a high prevalence (59%) of flow limitation during air breathing while in the sitting position. There are no previous reports on the correlation of IC and FEV1/FVC ratio to MRC dyspnea score in COPD patients stratified according to the presence or absence of expiratory flow limitation. Regression analysis performed separately on flow-limited and non-flow-limited patients showed that the only significant correlation of MRC dyspnea score was with IC percent predicted in flow-limited patients and with FEV1/FVC ratio percent predicted in non-flow-limited patients, the two variables accounting for 66% and 55%, respectively, of the variance in MRC dyspnea level. This is consistent with the findings of Diaz et al3 who found that in flow-limited and non-flow-limited patients the only significant predictors of exercise tolerance were IC and FEV1/FVC, respectively.

In the absence of changes in E, breathing pattern, and MEF, heliox should have no effect on IC and, hence, on dynamic hyperinflation. This was the case in all of our patients (Table 2). It should be noted, however, that in non-flow-limited patients there was little or no dynamic hyperinflation during breathing at rest.3 Hence, heliox would not be expected to affect IC in non-flow-limited patients, as it occurs in healthy subjects.

In 9 of 13 patients who were flow-limited while breathing air in the sitting position, and in all 18 subjects who were flow-limited while breathing air in the supine position, the tidal expiratory -V relationships were essentially the same while breathing air and heliox (Fig 2), indicating that the flow-limiting segment was located in peripheral airways, where flow is limited by the viscous mechanism and, hence, MEF is independent of gas density.17 In the four patients who became non-flow-limited while breathing heliox in the sitting position, flow limitation was likely occurring in the central airways, where the wave-speed mechanism dominates, and, hence, MEF is density-dependent.17 In these patients, however, the extent of flow limitation while breathing air entailed only the last fraction of expired VT. Because of this and the variability in breathing pattern, the reversal from flow limitation to non-flow limitation had no significant effects on IC (Table 2).

In line with the findings of Grapé et al,11 heliox had no significant effect on breathing pattern and FRC, assessed in terms of the change in IC. In contrast, Swidwa et al13 observed a marked reduction in FRC while breathing heliox in the absence of changes in breathing pattern in six COPD patients. Some of those patients, however, were studied before hospital discharge for a bronchitic exacerbation or coronary artery disease, and most had an FEV1 response to bronchodilator therapy of > 20% of baseline, which is unusual for COPD patients. Also at variance with the present results, Swidwa et al13 reported a small (approximately 2 mm Hg), though significant, decrease in PaCO2 in 15 sitting COPD patients while they were breathing heliox compared to while they were breathing air. However, most of those patients were hypercapnic, while ours were normocapnic.

A comparison of MEF-volume curves while breathing air and heliox was originally used as a test for the early detection of peripheral airway obstruction.21 On this basis, only half of COPD patients studied by Meadows et al14 exhibited density-independence (ie, nonresponders), but tidal expiratory flow limitation was not assessed. Based on the results of the present study, it is possible that nonresponders were flow-limited, while the responders were non-flow-limited. It should be noted, however, that the comparison of MEF-volume curves while patients were breathing air and heliox can be misleading, unless the time course of the FVC maneuvers is standardized.22 Using the NEP technique, the time course of the control and NEP test breaths is axiomatically the same.24

The present observations also may explain the controversial results obtained with heliox breathing in symptomatic COPD patients.151623 Indeed, no beneficial effect should be expected with heliox administration in these patients if flow limitation remains located in the peripheral airways, as was the case in most stable patients in this study.

With salbutamol administration, no flow-limited patient became non-flow-limited, independent of posture. Nevertheless, IC increased significantly (Table 3) with a concurrent decrease in dynamic hyperinflation. Since E and breathing pattern did not change, the increase in IC was due entirely to the augmented MEF (Fig 3, top left, a) due to bronchodilation. Similar results were found in previous studies58 on seated COPD patients. In one study, however, flow-limited patients exhibited a small though significant increase of ventilation with salbutamol administration.5 The reason for this discrepancy is not clear.

In COPD patients who are non-flow-limited at rest with IC within the normal limits, exercise performance is relatively well-preserved and the levels of chronic dyspnea (MRC score), as well as exertional dyspnea (Borg score), are relatively low.237 In these patients, bronchodilator administration has no significant effect on dyspnea at rest or during exercise.824 In COPD patients who are flow-limited at rest with an IC below the normal limits, the levels of chronic and exertional dyspnea are high, and exercise tolerance decreases proportionately to the reduced IC.3 Bronchodilator administration to these patients increases MEF, allowing ventilation to occur at lower lung volumes with concurrent reductions in elastic work and improvement of inspiratory muscle function.2678 As a result, there is a decrease of dyspnea at rest and during exercise, as well as an increase of exercise tolerance.678 In contrast, as shown by the present results, in COPD patients heliox has no effect on dynamic hyperinflation at rest, independent of posture and the presence or absence of flow limitation. Moreover, in the flow-limited patients MEF did not increase with heliox administration, and hence there should be little improvement during exercise.

At variance with the findings in flow-limited patients, heliox breathing in non-flow-limited subjects should improve exercise performance as a result of increased maximal flows and decreased airway resistance. The different responses to heliox of flow-limited and non-flow-limited patients may explain why the pertinent results reported in the literature for COPD patients are controversial. Two studies2526 showed a small though significant increase in peak exercise ventilation and oxygen uptake, while in two other studies2728 these variables did not change. This could be due in part to a preponderance of flow-limited patients in the last two reports or to a different methodology. In the two reports that showed no change in peak exercise ventilation and oxygen uptake with heliox breathing, ventilation was measured with a spirometer or a bag-in-box system, while in the other two studies the expired volume was measured with pneumotachographs calibrated with the inspired heliox mixture.

MEFs while breathing heliox are usually measured with a pneumotachograph that is calibrated using the inspired gas mixture. Such measurements underestimate the expiratory flow because the viscosity of the expired gas mixture is lower than the inspired mixture.29 This does not affect the assessment of expiratory flow limitation with NEP, because the control and NEP expiratory flows are measured with the same gas composition.

Although heliox does not reduce dynamic hyperinflation at rest in non-flow-limited COPD patients, it may improve their exercise performance by increasing MEF. Further exercise studies are required in COPD patients who are classified as being non-flow-limited at rest based on NEP. In such studies, dynamic hyperinflation and NEP should also be assessed during exercise.30

In conclusion, the present results indicate that in stable COPD patients the breathing of heliox had no significant effect on dynamic hyperinflation, regardless of posture and the presence or absence of expiratory flow limitation during air breathing, or on PaO2 and PaCO2 while in the supine position. In contrast, in the same COPD patients who were flow-limited while breathing air, the degree of hyperinflation was significantly reduced after salbutamol administration both in the sitting and the supine positions. Accordingly, heliox administration, which is costly and cumbersome, does not appear to be useful for reducing dynamic hyperinflation in stable COPD patients at rest.


   Footnotes
 
Abbreviations: FRC = functional residual capacity; IC = inspiratory capacity; MEF = maximal expiratory flow; MRC = Medical Research Council; NEP = negative expiratory pressure; TLC = total lung capacity; VC = vital capacity; E = minute ventilation; VT = tidal volume; -V = flow-volume

This study was supported by Ministero dell’Istruzione, dell’Università e della Ricerca Scientifica (MIUR), Rome, Italy.

Received for publication May 30, 2003. Accepted for publication December 12, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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