Abstract
Stair climbing is associated with dynamic pulmonary hyperinflation and the development of severe dyspnea in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess whether (i) continuous positive airway pressure (CPAP) applied during stair climbing prevents dynamic hyperinflation and thereby reduces exercise-induced dyspnea in oxygen-dependent COPD-patients, and (ii) the CPAP-device and oxygen tank can be carried in a hip belt. In a randomised cross-over design, oxygen-dependent COPD patients performed two stair-climbing tests (44 steps): with supplemental oxygen only, then with the addition of CPAP (7 mbar). The oxygen tank and CPAP-device were carried in a hip belt during both trials.
Eighteen COPD patients were included in the study. Although all patients could tolerate stair climbing with oxygen alone, 4 patients were unable to perform stair climbing while using CPAP. Fourteen COPD patients (mean FEV1 36 ± 14% pred.) completed the trial and were analyzed. The mean flow rate of supplemental oxygen was 3 ± 2 l/min during stair climbing. Lung hyperinflation, deoxygenation, hypoventilation, blood lactate production, dyspnea and the time needed to manage stair climbing were not improved by the application of CPAP (all p > 0.05). However, in comparison to climbing with oxygen alone, limb discomfort was reduced when oxygen was supplemented with CPAP (p = 0.008).
In conclusion, very severe COPD patients are able to carry supporting devices such as oxygen tanks or CPAP-devices in a hip belt during stair climbing. However, the application of CPAP in addition to supplemental oxygen during stair climbing prevents neither exercise-induced dynamic hyperinflation, nor dyspnea.
Introduction
Exercise limitation is a significant burden for patients with chronic obstructive pulmonary disease (COPD) (Citation1). In particular, dynamic hyperinflation (DH) of the lungs during exercise is one of the factors that can reduce exercise capacity by increasing dyspnea during exertion (Citation2,3). DH has been established as the primary cause of the reduced physical activity experienced by COPD patients on a daily basis (Citation4). Furthermore, the common daily obstacle of stair climbing is, in comparison to walking, associated with prolonged DH and an increase in exercise-related dyspnea in COPD patients (Citation5). Therefore, reducing DH to facilitate stair climbing is of major interest.
Continuous positive airway pressure (CPAP) has been shown to benefit COPD patients because it promotes an increase in inspiratory capacity at rest (Citation6) by reducing residual volume and airway resistance (Citation7). Previous studies have investigated the effect of CPAP during exercise in COPD patients by applying an extrinsic PEEP in order to overcome the intrinsic PEEP; this, in turn, leads to a reduction in DH (Citation8). CPAP application during exercise also helps to maintain oxygenation and decrease the pressure-time integral of the respiratory muscles, thereby lowering muscle oxygen-consumption and resulting in a reduction of breathlessness (Citation9). Since these particular studies used ergometric exercise programs, it is most likely that the CPAP device was placed beside the ergometer; however, this is not practical in a real-life setting, since patients need to carry medical devices during their daily activities in order to maintain their mobility. Previous work has shown that carrying a ventilator and oxygen tank on a rollator during walking leads to improvements in dyspnea and exercise-related deoxygenation in COPD patients with chronic hypercapnic respiratory failure (Citation11), whereas such improvements are not seen when the devices are carried in a backpack (Citation12). However, it is worth noting that rollators restrict patients from managing obstacles such as stairs. For this reason, the optimal setting for transporting medical devices during exercise in patients with severe COPD remains to be determined.
Therefore, the aim of this study was to assess (i) whether CPAP prevents DH and thereby reduces exercise-induced dyspnea in advanced COPD patients with hypoxemic respiratory failure by improved oxygenation and respiratory muscle unloading, as shown in previous studies, and (ii) to assess the feasibility of carrying a CPAP device and an oxygen tank in a hip belt during stair climbing.
Materials and methods
The study protocol was approved by the Institutional Review Board for Human Studies at the Albert-Ludwigs University Freiburg (Germany), and was performed in accordance with the ethical standards laid down in the latest version of the Declaration of Helsinki (Citation13). Written informed consent was obtained from all participants. The trial was registered at the German Clinical Trials Register (Trial Registration number: DRKS00000710).
Patients
Oxygen-dependent, non-hypercapnic COPD patients (stage IV according to GOLD criteria (Citation14)) with a history of smoking were included in the study (see ). All patients received optimal medical therapy in addition to long-term oxygen therapy according to GOLD guidelines (Citation15). Medication was not altered for the present study. Patients were excluded from the study if they showed signs of: (i) acute exacerbation (increasing cough, purulent sputum, elevated leukocytes or C-reactive protein >5 mg/dl, pulmonary infiltrates on chest X-ray, need for antibiotic treatment), (ii) other pulmonary disorders (e.g., asthma, restrictive chest disease), (iii) cardiac disease (>WHO class II), and (iv) neuromuscular diseases, or if they had orthopedic limitations to stair climbing.
Table 1. Demographic data and lung function parameters at baseline (n = 14)
Measurements
Bodyplethysmography (MasterLab, Viasys, Hoechberg, Germany) was performed according to current guidelines and recommendations (Citation16,17) and normal values were calculated according to Matthys et al. (Citation32). The following parameters were each assessed according to current recommendations (Citation18): respiratory drive, as determined by mouth occlusion pressure 0.1 s after inspiration (P0.1); peak global inspiratory muscle strength (PImaxpeak) derived from residual volume; and sniff nasal pressure (Sniff Pna) at functional residual capacity. All pressures and airflows were recorded with a differential pressure transducer (ZAN 400, nSpire Health, Oberthulba, Germany) and pneumotachograph (ZAN100, nSpire, Oberthulba, Germany).
Furthermore, spirometric measurements prior to and after stair climbing were assessed using a portable device (ZAN100, nSpire, Oberthulba, Germany). Ratings of perceived exertion (dyspnea and limb discomfort) were assessed by a modified Borg scale (Citation19). Blood gases (cobas b221, Roche, Grenzach, Germany) and blood lactate (Super GL, Hitado Diagnostic Systems, Moehnensee, Germany) were measured from blood samples taken from the arterialized ear lobe (Finalgon, Boehringer Ingelheim, Ingelheim, Germany).
Study design
In a randomized cross-over design (Citation20), two stair-climbing trials (44 steps each) were performed with supplemental oxygen in the (i) presence and (ii) absence of CPAP, in accordance with a previous trial by our group, which investigated stair climbing in COPD patients (Citation5). The oxygen flow-rate was customized to the levels used by the patient during exercise at home (previously established by oxygen titration in the 6-minute walking test), while the CPAP level was set to 7 cmH2O. Trials were performed with at least 3 hours of rest between each session, since a previous study showed that the effect of CPAP in COPD after cessation of treatment lasted approximately 30 min (Citation7).
A battery-powered CPAP device (Point with Powerpack, Hoffrichter GmbH, Schwerin, Germany) and the oxygen tank (Helios Marathon, Puritan-Bennett/Covidien, Dublin, Ireland) were carried in a hip belt (Lowe Alpin, Treviso, Italy) during both trials to ensure equal loads (4.3 kg in total) (). CPAP was administered to all patients via a full face mask of the appropriate size (S, M, or L) (Mirage Quattro, ResMed, Martinsried, Germany). At the baseline time point, bodyplethysmographic measurements and assessment of respiratory muscle strength were performed.
Figure 1. A COPD patient using CPAP in addition to supplemental oxygen during stair climbing. The oxygen tank and CPAP device are transported in a commercially available hip belt.
Before and immediately after stair climbing, several parameters were concurrently assessed by two experienced physicians in the following sequence: blood lactate, forced expiratory volume in 1 s, vital capacity, and inspiratory capacity. Inspiratory capacity was consistently measured from end expiratory lung volume to total lung capacity after at least three normal breaths on the spirometer (Citation17). All measurements prior to and after stair climbing were performed with the same mobile spirometry unit, which was immediately transported to the finishing point of the climb following initial measurements. All patients performed a standardized stair climbing protocol in each trial, which was previously established by our group (Citation5).
Statistics
Data were analyzed using SigmaPlot 11.2 for Windows (SSI, San Jose, CA, USA). Data are presented as mean ± standard deviation (SD) after testing for normal distribution (Kolmogorov-Smirnov test). For normally distributed data, the 95% Confidence Interval (95%CI) of the mean is given where appropriate. In case of non-normally distributed data, median and interquartile ranges are given. Comparisons between stair climbing with CPAP plus supplemental oxygen and stair climbing with oxygen alone were performed using the paired t-test /Wilcoxon signed rank test for normally- /non-normally-distributed data. Statistical significance was assumed with a p-value of <0.05.
Results
Eighteen COPD patients were recruited. All patients were able to perform stair climbing with supplemental oxygen only while simultaneously carrying the oxygen tank and the CPAP device in the hip belt (). Four patients withdrew from the study due to the development of claustrophobia, or the need for rescue medication (inhaled β2-agonists) while using CPAP. Hence, the 14 patients (9 male, 5 female) who completed the trial were analyzed. Demographic data, lung function parameters and measurements of respiratory muscle strength are given in . Three patients received oral steroids (prednisolone-equivalent ranging 1–10 mg/day) and four patients received oral theophylline (range 250–375 mg/day). Inhalable drugs were used as follows: long acting β2-agonists (n = 14), inhalable steroids (n = 11), inhalable anticholinergics (n = 13). Two patients were already familiar with CPAP for the treatment of obstructive sleep apnea. All patients quit active smoking.
The mean flow rate for supplemental oxygen was 2.6 ± 1.6 l/min. Blood gases, spirometric measurements, blood lactate, blood pressure and heart rate before stair climbing did not differ between the two study sessions (all p > 0.05). Stair climbing with supplemental oxygen alone resulted in deoxygenation, exercise-induced hypercapnia, lung hyperinflation and increased blood lactate levels, as well as an increase in limb discomfort, dyspnea, heart rate and blood pressure (all p < 0.05) (). However, these physiological changes, except for limb discomfort, were not ameliorated by the addition of CPAP to supplemental oxygen (). Furthermore, the time needed for stair climbing did not differ between stair climbing with oxygen (44 seconds, interquartile range 35/46) and stair climbing with CPAP plus supplemental oxygen (44 seconds, interquartile range 39/52) (p = 0.403).
Table 2. Dyspnea, limb discomfort, blood lactate values, circulatory parameters, blood gases and lung function parameters before and after stair climbing with supplemental oxygen
Table 3. Comparison of physiological changes (Δ) occurring during stair climbing with oxygen alone or with oxygen supplemented by CPAP
Discussion
The present study is the first to investigate the application of CPAP in COPD patients in the real-life setting of stair climbing, and demonstrates that carrying medical devices in a hip belt is tolerated by COPD patients. However, the addition of CPAP to supplemental oxygen neither prevents exercise-induced DH, nor improves exercise-induced dyspnea.
Previous studies have shown that the way in which a supporting device is carried during exercise is crucial: in hypercapnic COPD patients during walking, the transportation of medical devices on a rollator and concurrent application of non-invasive ventilation significantly improved dyspnea, oxygenation and walking distance (Citation11). In contrast, carrying the devices in a backpack only improved oxygenation, but not dyspnea or walking distance (Citation12).
Therefore, it is not only the type of medical device that is used for exercise assistance, but also the mode of device transport, that appears to be of major importance. This is supported by a previous study showing that the simple use of a rollator leads to an improvement in walking distance in COPD patients (Citation21). This might be explained by the fact that bracing the arms on the rollator creates a forward-leaning position that promotes activation of respiratory accessory muscles (Citation21,22). However, since rollators can only be used on flat terrain, stair climbing is not possible.
On the other hand, carrying medical devices in a backpack may overcome obstacles such as staircases, but the abovementioned benefits of respiratory muscle activation are then hindered. Furthermore, the weight load of the backpack could negatively influence respiratory accessory muscles, which might explain the lack of physiological improvements when devices are carried in a backpack (Citation12). In the present study, medical devices were successfully placed in a commercially available hip belt that spared the thorax from constraint, thus resulting in a good tolerance level for the patient.
The present study confirms and extends previous findings that have shown stair climbing to be associated with DH, blood lactate production, dyspnea, deoxygenation, hypoventilation, and limb discomfort in COPD patients (Citation5). The lung hyperinflation experienced by COPD patients during stair climbing (Citation5) leads to abnormal breathing-mechanics which, in turn, force the termination of exercise due to breathlessness (Citation2,Citation23,Citation24); indeed, a decrease in inspiratory capacity is a reliable measure of DH in COPD patients (Citation25).
CPAP has been shown to reduce both DH and dyspnea during cycling exercise in moderate-stage COPD patients (Citation9,Citation26). This is in contrast to the present study, where the application during stair climbing of CPAP in severely-ill COPD patients was associated neither with a reduction in DH, nor with improvements in exercise-induced dyspnea. This could be explained by several factors:
First, CPAP was applied in all consecutively enrolled patients; however, it has been reported that CPAP treatment in resting COPD patients only reduces DH in a subgroup of these patients (Citation6). Furthermore, exercise-induced DH does not occur in all COPD patients (Citation27); this might explain the lack of improvement in DH in the present study, because COPD patients were consecutively enrolled without first being screened for exercise-induced DH. Therefore, screening COPD-patients for DH during exercise might be necessary to identify those who benefit most from treatment strategies that focus on exercise-induced DH.
Second, CPAP was set for all patients in the present study to a fixed pressure level of 7 cmH2O, without promoting a reduction in DH. This pressure level was chosen since a previous study using a similar cohort of COPD patients found a reduction in both intrinsic PEEP and muscle effort indices when pressure levels above 6 cmH2O were applied (Citation28). Because other studies in this area reported different outcomes using CPAP levels ranging from 4 to 11 cmH2O (Citation8–10), it remains to be determined whether there is an optimal CPAP level for reducing DH, or whether individually titrated CPAP levels aimed at maximally reducing residual volume at rest are needed for each patient.
Third, the type of exercise in the present study (stair climbing) differs from previous studies, which reported beneficial effects of CPAP in COPD patients during constant load cycling (Citation8,9). Furthermore, it has been shown that a patient's stair climbing performance cannot be predicted by his/her performance during other forms of exercise such as walking (Citation5). Therefore, it remains to be investigated whether the positive effects of CPAP applied during cycling exercise can be transferred to other types of exercise such as stair climbing or walking.
Interestingly, the development of limb discomfort during exercise was significantly reduced when stair climbing was performed with CPAP and supplemental oxygen compared to stair climbing with supplemental oxygen alone. Previous work has shown that CPAP application during exercise promotes a reduction in the work of breathing in COPD patients (Citation9), which further results in an increase in peripheral blood flow and hence better oxygenation of the peripheral muscles (Citation29). This might explain why CPAP application during stair climbing reduced limb discomfort in the present study. However, this is purely speculative since neither the work of breathing, nor peripheral muscle blood flow was assessed in the present study.
A limitation of this study is the lack of a sham CPAP trial. Conflicting recommendations exist for how sham CPAP treatment should be performed in sleep apnea trials (Citation30,31). Additionally, the pressure levels corresponding to sham CPAP during exercise have not been defined, since previous studies have reported therapeutic effects even at low CPAP levels such as 4 cm H2O (Citation8). Furthermore, measures of dynamic hyperinflation (loss of IC and IVC) in the current study only revealed trends towards significance, possibly due to the small sample size investigated.
In conclusion, although severely ill, oxygen-dependent COPD patients are able to carry medical devices in a hip belt during stair climbing, physiological changes such as dynamic hyperinflation, deoxygenation, hypoventilation, blood lactate production, and dyspnea could not be ameliorated by the application of CPAP in addition to supplemental oxygen.
Declaration of Interest Statement
This study was supported by an unrestricted research grant from Philips-Respironics, (USA). The sponsors had no role in the study design, results, interpretation of the findings, or any other subject discussed in the submitted manuscript.
S. Walterspacher was supported by research grants from the German Medical Association of Pneumology and Ventilatory Support (DGP e.V., Germany) and Philips-Respironics Inc. (USA). He received travel grants from Vivisol (Germany) and Weinmann (Germany) and speaking fees from Weinmann (Germany).
D.J. Walker has received travel grants from Vivosol (Germany).
H.J. Kabitz has received travel grants from Vivosol (Germany) and Werner und Müller (Germany).
W. Windisch was reimbursed by Breas Medical AB (Sweden) for attending the annual ERS conferences between 2001 and 2005, and by Werner and Müller Medizintechnik, (Germany) for attending the annual German conferences on home mechanical ventilation between 2001 and 2007. W. Windisch received speaking fees from the following companies: Dräger Medical (Germany), Heinen und Löwenstein (Germany); Werner und Müller Medizintechnik (Germany); VitalAire (Germany); Philips-Respironics (USA); Weinmann (Germany); ResMed (Germany/Australia); MPV Truma (Germany); Covedien (France); Linde (Germany) and Siare (Italy). W. Windisch received research grants from Respironics (USA) in 2008, 2009 and 2010, respectively, and from Breas (Sweden) in 1999–2010.
M. Dreher received speaking fees or travel grants from VitalAire (Germany), ResMed (Germany), Dräger Medical (Germany), Vivisol (Germany), Weinmann (Germany) and Philips-Respironics (USA). Furthermore, he received unrestricted research grants from ResMed (Germany).
The authors are responsible for the content and the writing of this paper.
Acknowledgments
We would like to thank Dr. Sandra Dieni for helpful comments on the manuscript prior to submission. This study was supported by an unrestricted research grant from Philips-Respironics, Pittsburgh, Pennsylvania, USA.
References
- O'Donnell DE. Ventilatory limitations in chronic obstructive pulmonary disease. Med Sci Sports Exerc 2001; 33(7 Suppl):S647–655.
- Jolley CJ, Moxham J. A physiological model of patient-reported breathlessness during daily activities in COPD. Eur Respir Rev 2009; 18:66–79.
- Polkey MI. Muscle metabolism and exercise tolerance in COPD. Chest 2002; 121(5 Suppl):131S–135S.
- Garcia-Rio F, Lores V, Mediano O, Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med 2009; 180(6):506–512.
- Dreher M, Walterspacher S, Sonntag F, Exercise in severe COPD: is walking different from stair-climbing? Respir Med 2008; 102(6):912–918.
- Soares SMTP, Oliveira RARA, Franca SA, Continuous positive airway pressure increases inspiratory capacity of COPD patients. Respirology 2008; 13(3):387–393.
- Lopes AJ, Nery FP, Sousa FC, CPAP decreases lung hyperinflation in patients with stable COPD. Respir Care 2011; 56(8):1164–1169.
- O'Donnell DE, Sanii R, Younes M. Improvement in exercise endurance in patients with chronic airflow limitation using continuous positive airway pressure. Am Rev Respir Dis 1988; 138(6):1510–1514.
- Petrof BJ, Calderini E, Gottfried SB. Effect of CPAP on respiratory effort and dyspnea during exercise in severe COPD. J Appl Physiol 1990; 69(1):179–188.
- Keilty SE, Ponte J, Fleming TA, Effect of inspiratory pressure support on exercise tolerance and breathlessness in patients with severe stable chronic obstructive pulmonary disease. Thorax 1994; 49(10):990–994.
- Dreher M, Storre JH, Windisch W. Non-invasive ventilation during walking in patients with severe COPD: A randomized cross-over trial. Eur Respir J 2007; 5(29):930–936.
- Dreher M, Doncheva E, Schwoerer A, Preserving oxygenation during walking in severe chronic obstructive pulmonary disease: noninvasive ventilation versus oxygen therapy. Respiration 2009; 78(2):154–160.
- World Medical Association. Declaration of Helsinki (Internet). 2008 (cited 14.02.2012); Available from: http://www.wma.net/en/30publications/10policies/b3/ index.html.
- WHO/NIH. GOLD - The Global Initiative for Chronic Obstructive Lung Disease (Internet). 2011 (cited 14.02.2012); Available from: http://www.goldcopd.org/.
- Rabe KF, Hurd S, Anzueto A, Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007; 176(6):532–555.
- Wanger J, Clausen JL, Coates A, Standardisation of the measurement of lung volumes. Eur Respir J 2005; 26(3):511–522.
- Miller MR, Hankinson J, Brusasco V, Standardisation of spirometry. Eur Respir J 2005; 26(2):319–338.
- ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med 2002; 166(4):518–624.
- Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc 1982; 14(5):377–381.
- Saghaei M. Random allocation software for parallel group randomized trials. BMC Med Res Methodol 2004; 4(26):1–6.
- Probst VS, Troosters T, Coosemans I, Mechanisms of improvement in exercise capacity using a rollator in patients with COPD. Chest 2004; 126(4):1102–1107.
- Sharp JT, Drutz WS, Moisan T, Postural relief of dyspnea in severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1980; 122(2):201–211.
- Grazzini M, Stendardi L, Gigliotti F, Pathophysiology of exercise dyspnea in healthy subjects and in patients with chronic obstructive pulmonary disease (COPD). Respir Med 2005; 99(11):1403–1412.
- Stendardi L, Binazzi B, Scano G. Exercise dyspnea in patients with COPD. Int J Chron Obstruct Pulmon Dis 2007; 2(4):429–439.
- Marin JM, Carrizo SJ, Gascon M, Inspiratory capacity, dynamic hyperinflation, breathlessness, and exercise performance during the 6-minute-walk test in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 163(6):1395–1399.
- O'Donnell DE, Sanii R, Giesbrecht G, Effect of continuous positive airway pressure on respiratory sensation in patients with chronic obstructive pulmonary disease during submaximal exercise. Am Rev Respir Dis 1988; 138(5):1185–1191.
- O'Donnell DE, Webb KA. The major limitation to exercise performance in COPD is dynamic hyperinflation. J Appl Physiol 2008; 105(2):753–757.
- O'Donoghue FJ, Catcheside PG, Jordan AS, Effect of CPAP on intrinsic PEEP, inspiratory effort, and lung volume in severe stable COPD. Thorax 2002; 57(6):533–539.
- Romer LM, Polkey MI. Exercise-induced respiratory muscle fatigue: implications for performance. J Appl Physiol 2008; 104(3):879–888.
- Jenkinson C, Davies RJ, Mullins R, Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 1999; 353(9170):2100–2105.
- Farre R, Hernandez L, Montserrat JM, Sham continuous positive airway pressure for placebo-controlled studies in sleep apnoea. Lancet 1999; 353(9159):1154.
- Matthys H, Zaiss A, Theissen J, Definitionen, Soll- und Meßwerte zur Diagnose obstruktiver, restriktiver sowie gemischter Ventilationsstörungen für die klinische Lungenfunktionsdiagnostik. Atemw-Lungenkrkh. 1995; 3:21130–21138.