Effects of self-contained breathing apparatus on ventricular function during strenuous exercise.

The purpose of this study was to investigate left-ventricular function during strenuous exercise with the self-contained breathing apparatus (SCBA). With the use of two-dimensional echocardiography, images of the left ventricle (LV) were acquired during sustained exercise (3 x 10 min) under two conditions: 1) SCBA, or 2) low resistance breathing valve. Twenty healthy men volunteered for the study, and in each condition subjects wore fire protective equipment. Heart rate, systolic blood pressure, cavity areas during systole and diastole (ESCA and EDCA, respectively), esophageal pressure, ventilation rate, oxygen consumption, perceived physical, thermal and respiratory distress, and core temperature were measured at regular intervals. Urine specific gravity (<1.020 g/ml) and hematological variables were used to infer hydration status. All subjects began both trials in a euhydrated state. No differences were found between conditions for heart rate, systolic blood pressure, ventilation rate, oxygen consumption, perceived distress, or any hematological variables. Peak expiratory esophageal pressure was always higher (P < 0.05), while EDCA and stroke area (SA) were significantly lower (P < 0.05) with the SCBA. ESCA, end-systolic transmural pressure (ESTMP), and LV contractility (ESTMP/ESCA) were similar between conditions. Sustained exercise with fire protective equipment resulted in significant reductions in EDCA, ESCA, and SA from the start of exercise, which was associated with a 6.3 +/- 0.8% reduction in plasma volume, an increase in core temperature (37.0 +/- 0.4 to 38.8 +/- 0.3 degrees C), and a significant increase in heart rate (146.9 +/- 2.1 to 181.7 +/- 2.4 beats/min) throughout exercise. The results from this study support research by others showing that increased intrathoracic pressure reduces LV preload (EDCA); however, the novelty of the present study is that when venous return is compromised by sustained exercise and heat stress, SA cannot be maintained.

Effects of high-frequency chest wall oscillation on pleural pressure and oscillated flow.

The effectiveness of high-frequency chest wall oscillation (HF-CWO) is directly related to the level of oscillated flow (osc) in the airways. We used the Vest system to investigate the effects of HFCWO on chest wall and pleural pressures and we correlated these pressures to the resultant osc. We also compared the latest HFCWO device with it predecessor. Different combinations of vest inflation pressure (background pressure) and oscillation frequency were randomly applied to 10 healthy volunteers. Chest wall pressure was determined using an air-filled bag under the vest and pleural pressure was estimated using an esophageal balloon. Reverse plethysmography was used to measure osc at the mouth and a spirometer was used to measure changes in end-expired lung volume. We found a significant correlation between chest wall and pleural pressure with approximately one-third of the chest wall pressure transmitted into the pleural space. Mean esophageal pressure remained negative at all background pressure/frequency combinations. There was a significant correlation (p<0.0001) between the esophageal pulse pressure and osc, which was highest at 15Hz regardless of the background pressure. The end-expired lung volume correlated with mean chest wall pressure. There was no significant difference between the two Vest systems. Since osc dictates the effectiveness of HFCWO and since osc is dependent on esophageal pulse pressure, which in turn is dependent on chest wall pulse pressure, it follows that the effectiveness of HFCWO is influenced by the ability to generate an effective chest wall pulse pressure.

The effects of helium-hyperoxia on 6-min walking distance in COPD: a randomized, controlled trial.

BACKGROUND: We hypothesized that breathing helium-hyperoxia (HeO2) would significantly improve 6-min walking test (6MWT) distance in COPD subjects. METHODS: This was a blinded, randomized crossover study. At visit 1, we assessed pulmonary function, exercise capacity, and 6MWT distance. Visits 2 and 3 consisted of four 6MWTs in which the following different inspired gases were used: room air (RA) by mask; 100% O2 by mask (mask O2); 100% O2 by nasal prongs (nasal O2); and 70% He/30% O2 by mask (HeO2). Walking distance, shortness of breath, leg fatigue, O2 saturation, and heart rate (HR) were assessed. RESULTS: Sixteen COPD subjects participated (mean FEV(1)/FVC ratio [+/- SD], 48 +/- 8%; mean FEV1, 55 +/- 13% predicted). Subjects walked farther when breathing HeO2 (564 m) compared to RA (497 m; p < 0.001), mask O2 (520 m; p < 0.001), or nasal O2 (528 m; p < 0.001). Despite the increased distance walked while breathing HeO2, there was no increase in shortness of breath or leg fatigue. There was desaturation when breathing RA (8%; p < 0.001) and nasal O2 (5%; p < 0.001), which was reduced when breathing HeO2 (3%; difference not significant) and mask O(2) (0%; difference not significant). There were no significant differences in HR in the four 6MWTs. CONCLUSIONS: The use of HeO2 increased 6MWT distance in COPD subjects more than either mask O2 or nasal O2 compared to RA. The increased walking distance was not associated with increased shortness of breath or leg fatigue. The results suggest that clinical benefit would be obtained by administering HeO2 during exercise, which may have significant clinical implications for the management of COPD patients.

Effects of changes in lung volume on oscillatory flow rate during high-frequency chest wall oscillation.

BACKGROUND: The effectiveness of high-frequency chest wall oscillation (HFCWO) in mucolysis and mucous clearance is thought to be dependant on oscillatory flow rate (Fosc). Therefore, increasing Fosc during HFCWO may have a clinical benefit. OBJECTIVES: To examine effects of continuous positive airway pressure (CPAP) on Fosc at two oscillation frequencies in healthy subjects and patients with airway obstruction. METHODS: Five healthy subjects and six patients with airway obstruction underwent 12 randomized trials of HFCWO (CPAP levels of 0 cm H2O, 2 cm H2O, 4 cm H2O, 6 cm H2O, 8 cm H2O and 10 cm H2O at frequencies of 10 Hz and 15 Hz) within a body plethysmograph, allowing measurements of changes in lung volume. Fosc was measured by reverse plethysmography using a 20 L isothermic chamber near the mouth. At the end of each randomized trial, an inspiratory capacity manoeuvre was used to determine end-expiratory lung volume (EELV). RESULTS: EELV increased significantly (P<0.05) with each level of CPAP regardless of oscillation frequency. Fosc also significantly increased with CPAP (P<0.05) and it was correlated with EELV (r=0.7935, P<0.05) in obstructed patients but not in healthy subjects (r=0.125, P=0.343). There were no significant differences in perceived comfort across the levels of CPAP. CONCLUSIONS: Significant increases in Fosc with CPAP-induced increases in lung volume were observed, suggesting that CPAP may be useful as a therapeutic adjunct in patients who have obstructive airway disease and who require HFCWO.

Cost analysis of intensive glycemic control in critically ill adult patients.

STUDY OBJECTIVES: To assess the effect of an intensive glycemia management protocol on the cost of care of a heterogeneous population of critically ill adult patients. DESIGN: Economic analysis of a 1,600-patient "before-and-after" study of intensive glycemia management. SETTING: Fourteen-bed mixed medical-surgical adult ICU of a university-affiliated community teaching hospital. PATIENTS: Eight hundred consecutive admissions to the ICU prior to the institution of an intensive glucose management protocol were compared to the first 800 patients admitted to the ICU following institution of the protocol. INTERVENTIONS: Cost data were analyzed using the comprehensive database of the ICU as well as other hospital data repositories. MEASUREMENTS AND RESULTS: The ICU database was used to quantify the major components of the cost of care. The analysis includes costs associated with ICU and non-ICU patient days, ventilator days, and laboratory, pharmacy, and radiology services. Comparing the baseline and treatment periods, there were decreases in patient days in the ICU; ventilator days; total laboratory, pharmacy and radiology costs; and post-ICU hospital length of stay. The net annualized decrease in costs during the treatment period was USD 1,339,500, or USD 1,580 per patient. CONCLUSIONS: The institution of a program to intensively monitor glucose levels and treat even modest hyperglycemia in the ICU was associated with substantial cost savings. This finding, in conjunction with the previously demonstrated improvement in mortality and morbidity, strongly supports the adoption of this intervention as a standard of care in the ICU.

The effects of body mass index on lung volumes.

BACKGROUND: Obesity is a major health issue in North America, and the trend is for obesity to be a more important medical issue in the future. Since obesity can cause respiratory symptoms, many obese people are referred for pulmonary function tests (PFTs). It is well known that obesity causes decreases in lung volumes, but there has never been a large study showing the correlation between body mass index (BMI) and the various lung volumes. DESIGN: We collected PFT results from 373 patients sent for lung function testing who had normal values for airway function but a wide range of BMIs. SETTING: The PFTs were done in two accredited outpatient laboratories. RESULTS: There were significant linear relationships between BMI and vital capacity and total lung capacity, but the group mean values remained within the normal ranges even for morbidly obese patients. However, functional residual capacity (FRC) and expiratory reserve volume (ERV) decreased exponentially with increasing BMI, such that morbid obesity resulted in patients breathing near their residual volume. An important finding was that the greatest rates of change in FRC and ERV occurred in the overweight condition and in mild obesity. At a BMI of 30 kg/m2, FRC and ERV were only 75% and 47%, respectively, of the values for a lean person with a BMI of 20 kg/m2. CONCLUSIONS: We showed that BMI has significant effects on all of the lung volumes, and the greatest effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. Our results will assist clinicians when interpreting PFT results in patients with normal airway function.

Does fitness level modulate the cardiovascular hemodynamic response to exercise?

Subjects with greater aerobic fitness demonstrate better diastolic compliance at rest, but whether fitness modulates exercise cardiac compliance and cardiac filling pressures remains to be determined. On the basis of maximal oxygen consumption (VO2max), healthy male subjects were categorized into either low (LO: VO2max=43+/-6 ml.kg-1.min-1; n=3) or high (HI: VO2max=60+/-3 ml.kg-1.min-1; n=5) aerobic power. Subjects performed incremental cycle exercise to 90% Vo(2max). Right atrial (RAP) and pulmonary artery wedge (PAWP) pressures were measured, and left ventricular (LV) transmural filling pressure (TMFP=PAWP-RAP) was calculated. Cardiac output (CO) and stroke volume (SV) were determined by direct Fick, and LV end-diastolic volume (EDV) was estimated from echocardiographic fractional area change and Fick SV. There were no between-group differences for any measure at rest. At a submaximal workload of 150 W, PAWP and TMFP were higher (P<0.05) in LO compared with HI (12 vs. 8 mmHg, and 9 vs. 4 mmHg, respectively). At peak exercise, CO, SV, and EDV were lower in LO (P<0.05). RAP was not different at peak exercise, but PAWP (23 vs. 15 mmHg) and TMFP (12 vs. 6 mmHg) were higher in LO (P<0.05). Compared with less fit subjects, subjects with greater aerobic fitness demonstrated lower LV filling pressures during exercise, whereas SV and EDV were either similar (submaximal exercise) or higher (peak exercise), suggesting superior diastolic function and compliance.

Effect of acute increases in pulmonary vascular pressures on exercise pulmonary gas exchange.

The purpose of this study was to determine the effect of acute increases in pulmonary vascular pressures, caused by the application of lower-body positive pressure (LBPP), on exercise alveolar-to-arterial PO2 difference (A-aDO2), anatomical intrapulmonary (IP) shunt recruitment, and ventilation. Eight healthy men performed graded upright cycling to 90% maximal oxygen uptake under normal conditions and with 52 Torr (1 psi) of LBPP. Pulmonary arterial (PAP) and pulmonary artery wedge pressures (PAWP) were measured with a Swan-Ganz catheter. Arterial blood samples were obtained from a radial artery catheter, cardiac output was calculated by the direct Fick method, and anatomical IP shunt was determined by administering agitated saline during continuous two-dimensional echocardiography. LBPP increased both PAP and PAWP while upright at rest, and at all points during exercise (mean increase in PAP and PAWP 3.7 and 4.0 mmHg, respectively, P<0.05). There were no differences in exercise oxygen uptake or cardiac output between control and LBPP. Despite the increased PAP and PAWP with LBPP, A-aDO2 was not affected. In the upright resting position, there was no evidence of shunt in the control condition, whereas LBPP caused shunt in one subject. At the lowest exercise workload (75 W), shunt occurred in three subjects during control and in four subjects with LBPP. LBPP did not affect IP shunt recruitment during subsequent higher workloads. Minute ventilation and arterial PcO2 were not consistently affected by LBPP. Therefore, small acute increases in pulmonary vascular pressures do not widen exercise A-aDO2 or consistently affect IP shunt recruitment or ventilation.

The impact of exercise training intensity on change in physiological function in patients with chronic obstructive pulmonary disease.

Pulmonary rehabilitation incorporating exercise training is an effective method of enhancing physiological function and quality of life for patients with chronic obstructive pulmonary disease (COPD). Despite the traditional belief that exercise is primarily limited by the inability to adequately increase ventilation to meet increased metabolic demands in these patients, significant deficiencies in muscle function, oxygen delivery and cardiac function are observed that contribute to exercise limitation. Because of this multifactorial exercise limitation, defining appropriate exercise training intensities is difficult. The lack of a pure cardiovascular limitation to exercise prohibits the use of training guidelines that are based on cardiovascular factors such as oxygen consumption or heart rate. Current recommendations for exercise training intensity for patients with COPD include exercising at a 'maximally tolerable level', at an intensity corresponding with 50% of peak oxygen consumption (V-O2peak), or at 60-80% of peak power output obtained on a symptom-limited exercise tolerance test. In general, it appears that higher intensity training elicits greater physiological change than lower intensity training; however, there is no consensus as to the exercise training intensity that elicits the greatest physiological benefit while remaining tolerable to patients. The 'optimal' intensity of training likely depends upon the individual goals of each patient. If the goal is to increase the ability to sustain tasks that are currently able to be performed, lower to moderate-intensity training is likely to be sufficient. If the goal of training, however, is to increase the ability to perform tasks that are above the current level of tolerance, higher intensity training is likely to elicit greater performance increases. In order to perform higher intensity exercise, an interval training model is likely required. High-intensity interval training involves significant anaerobic energy utilisation and, therefore, may better mimic the physiological requirements of activities of daily living. Also, high-intensity interval training is tolerable to patients and may, in fact, reduce the degree of dyspnoea and dynamic hyperinflation through a reduced ventilatory demand. Another factor that will determine the optimal intensity of training is the relative contribution of ventilatory limitation to exercise tolerance. If peak exercise tolerance is limited by a patient's ability to increase ventilation, it is possible that interval training at an intensity higher than peak will elicit greater muscular adaptation than an intensity at or below peak power on an incremental exercise test. More research is required to determine the optimal training intensity for pulmonary rehabilitation patients.

High-frequency chest compression: a summary of the literature.

The purpose of the present literature summary is to describe high-frequency chest compression (HFCC), summarize its history and outline study results on its effect on mucolysis, mucus transport, pulmonary function and quality of life. HFCC is a mechanical method of self-administered chest physiotherapy, which induces rapid air movement in and out of the lungs. This mean oscillated volume is an effective method of mucolysis and mucus clearance. HFCC can increase independence. Some studies have shown that HFCC leads to more mucus clearance and better lung function compared with conventional chest physiotherapy. However, HFCC also decreases end-expiratory lung volume, which can lead to increased airway resistance and a decreased oscillated volume. Adding positive end-expiratory pressure to HFCC has been shown to prevent this decrease in end-expiratory lung volume and to increase the oscillated volume. It is possible that the HFCC-induced decrease in end-expiratory lung volume may result in more mucus clearance in airways that remain open by reducing airway size. Adjunctive methods, such as positive end-expiratory pressure, may not always be needed to make HFCC more effective.

Obesity is a risk factor for dyspnea but not for airflow obstruction.

BACKGROUND: Previous research suggests that obesity is an important risk factor for asthma. However, since obesity can cause dyspnea through mechanisms other than airflow obstruction, diagnostic misclassification of asthma could partially account for this association. OBJECTIVE: To determine whether there is a relationship between obesity and airflow obstruction. METHODS: A total of 16 171 participants (17 years or older) from the Third National Health and Nutrition Examination Survey (NHANES III) were divided into 5 quintiles based on their body mass index (BMI) to determine the association between BMI quintile and risk of self-reported asthma, bronchodilator use, exercise performance, and airflow obstruction. Significant airflow obstruction was defined as a ratio less than 80% the predicted value of forced expiratory volume in 1 second to forced vital capacity adjusted for age, sex, and race. RESULTS: The highest BMI quintile (ie, the most obese participants) had the greatest risk of self-reported asthma (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.24-1.81), bronchodilator use (OR, 1.94; 95% CI, 1.38-2.72), and dyspnea with exertion (OR, 2.66; 95% CI, 2.35-3.00). Paradoxically, the highest BMI quintile had the lowest risk for significant airflow obstruction (P =.001). CONCLUSIONS: This study demonstrates that while obesity is a risk factor for self-reported asthma, obese participants are at a lower risk for (objective) airflow obstruction. Many more obese than nonobese participants were using bronchodilators despite a lack of objective evidence for airflow obstruction. These data suggest that mechanisms other than airflow obstruction are responsible for dyspnea genesis in obesity and that asthma might be overdiagnosed in the obese population.

The effects of cycle racing on pulmonary diffusion capacity and left ventricular systolic function.

The purpose of this study was to examine the effects of a 20 km cycle race (TT) on left ventricular (LV) systolic and pulmonary function in 12 endurance cyclists. Spirometry, single-breath diffusion capacity (DLCO) with partitioning of membrane (DM) and capillary blood volume (Vc) components and 2-D echocardiograms were performed before and after the TT. During the TT mean oxygen consumption was 3.79 +/- 0.5 L x min(-1) (83 +/- 5.5% of VO2max) and mean blood lactate was 8.4 +/- 2.4 mM. Following the TT, spirometry values were unchanged, however, DLCO and DM were significantly (P<0.05) reduced. LV systolic function was increased (P<0.05) immediately after exercise, while end-diastolic area was decreased (P<0.05) at all points during recovery. The reduction in DM was correlated with LV systolic function following the TT. This relationship suggests a cardiovascular contribution to pulmonary diffusion impairment following exercise.

Effects of prolonged exercise to exhaustion on left-ventricular function and pulmonary gas exchange.

The purpose of this study was to simultaneously examine left-ventricular (LV) function and pulmonary gas exchange during prolonged constant-rate cycling in an attempt to explain the exercise-induced impairment in gas exchange. Eleven competitive cyclists rode their racing bicycles on a computerized cycle trainer at 25 W below the lactate threshold until exhaustion (exercise time = 2.51 +/- 0.86 h). LV systolic function was evaluated with two-dimensional echocardiography while arterial blood gases were used to assess pulmonary gas exchange. All variables were assessed concurrently before, during, and after exercise. LV function and cardiac output increased at the onset of exercise and were maintained until exhaustion. The alveolar-arterial P(O(2)) difference (A-a D(O(2))) increased within 15 min of the onset of exercise, was unchanged through to exhaustion, and returned to baseline 5 min post-exercise. Gas exchange was not related to cardiovascular function at the onset, or at end exercise. The results indicate that the widening A-aD(O(2)) during exercise is due to a readily reversible change in gas exchange function.

Effects of positive end-expiratory pressure on oscillated volume during high frequency chest compression in children with cystic fibrosis.

OBJECTIVE: To investigate the effects of positive end-expiratory pressure (PEEP) on end-expiratory lung volume (EELV) and mean oscillated volume (V(osc)) during high frequency chest compression (HFCC). DESIGN: A clinic-based prospective intervention study. SETTING: Pulmonary function laboratory, University of Alberta, Edmonton, Alberta. POPULATION: Nine children with cystic fibrosis with little or no obstructive airway disease who were selected from the outpatient Cystic Fibrosis and Pediatric Pulmonary Clinics at the University of Alberta Hospital, Edmonton, Alberta. METHODS: Each child received HFCC alone (at 10 Hz with chest wall pressure of 8 cm H2O) and HFCC plus PEEP. A closed circuit spirometry system was used to measure HFCC- and PEEP-induced changes in EELV, expressed as per cent baseline functional residual capacity (FRC) measured using helium dilution. An isothermic chamber permitted measurement of V(osc). RESULTS: HFCC caused a significant 9% decrease in EELV. Adding 2.0 +/- 0.3 cm H2O of PEEP increased EELV back to at least the FRC level. With HFCC alone, Vosc was significantly lower during spontaneous expiration than during spontaneous inspiration, but adding PEEP to HFCC increased V(osc), especially during spontaneous expiration. CONCLUSIONS: Adding PEEP during HFCC prevents the decrease in EELV and increases V(osc). Therefore, PEEP may improve HFCC-induced mucus clearance in children with cystic fibrosis.

Submaximal exercise with self-contained breathing apparatus: the effects of hyperoxia and inspired gas density.

BACKGROUND: The self-contained breathing apparatus (SCBA) used by firefighters, and other working in dangerous environments, adds an external resistance to expiration, which increases expiratory work during heavy exercise. HYPOTHESIS: Compressed air is typically used with the SCBA and we hypothesized that changing the inspired oxygen concentration and/or gas density with helium would reduce the external expiratory resistance. METHODS: On separate days, 15 men completed four 30-min bouts of treadmill exercise dressed in protective clothing and breathing the test gases through the SCBA. Four different gas mixtures were assigned in random order: [compressed air (NOX: 21% O2, 79% N2), hyperoxia (HOX: 40% O2, 60% N2), normoxic-helium (HE-OX: 21% O2, 79% He), and helium-hyperoxia (HE-HOX: 40% O2, 60% He)]. RESULTS: Compared with NOX, the two helium mixtures (but not HOX), decreased the external breathing resistance and all three gas mixtures decreased the peak expired mask pressure and the ventilatory mass moved. Both hyperoxic mixtures decreased blood lactate and the rating of perceived exertion was decreased at 30 min with HE-HOX. CONCLUSIONS: These results demonstrate that the helium-based gas mixtures, and to a lesser extent HOX, reduce the expiratory work associated with the SCBA during strenuous exercise.

Effects of the self-contained breathing apparatus on left-ventricular function at rest and during graded exercise.

The purpose of this study was to examine the effects of the self-contained breathing apparatus (SCBA) on left-ventricular (LV) function at rest and during mild- to moderate-intensity exercise, using 2-dimensional echocardiography. Twenty-three healthy male volunteers exercised on a stair-climber at work rates equivalent to 50%, 60%, 70%, and 80% of peak oxygen consumption. Esophageal pressure LV diastolic and systolic cavity areas, and myocardial areas were acquired during the final minute of each stage of exercise. As expected, the esophageal pressure response during SCBA breathing revealed significantly lower (more negative) inspiratory pressures and higher (more positive) expiratory pressures and, consequently, higher pressure swings, than free breathing (FB). End-diastolic cavity area (EDCA) and end-systolic cavity area (ESCA) were lower with the SCBA than with FB. LV contractility was higher (p < 0.05) with the SCBA, which can partially be explained by decreases in end-systolic wall stress. Therefore, the SCBA was found to decrease LV preload during moderate-intensity exercise, but did not negatively affect stroke area because of a similar reduction in ESCA.

Helium-hyperoxia: a novel intervention to improve the benefits of pulmonary rehabilitation for patients with COPD.

BACKGROUND: Helium-hyperoxia (HH) reduces dyspnea and increases exercise tolerance in patients with COPD. We investigated whether breathing HH would allow patients to perform a greater intensity of exercise and improve the benefits of a pulmonary rehabilitation program. METHODS: Thirty-eight nonhypoxemic patients with COPD (FEV(1)=47 +/- 17%(pred)) were randomized to rehabilitation breathing HH (60:40 He:O(2); n = 19) or air (n = 19). Patients cycled for 30 min, 3 days/week for 6 weeks breathing the assigned gas. Exercise intensity was prescribed from baseline, gas-specific, incremental exercise tests and was advanced as tolerated. The primary outcome was exercise tolerance assessed as a change in constant-load exercise time (CLT) following rehabilitation. Secondary outcomes were changes in exertional symptoms, health related quality of life (as assessed by the Short-form 36 and St George respiratory questionnaires), and peak oxygen consumption during an incremental exercise test. RESULTS: The HH group had a greater change in CLT following rehabilitation compared to the air group (9.5 +/- 9.1 vs 4.3 +/- 6.3 min, p < 0.05). At an exercise isotime, dyspnea was significantly reduced in both groups, while leg discomfort only decreased in the HH group. The changes in exertional symptoms and peak oxygen consumption were not different between groups. Health-related quality of life significantly improved in both groups; however, the change in St. George respiratory questionnaire total score was greater with HH (-7.6 +/- 6.4 vs -3.6 +/- 5.6, p < 0.05). During rehabilitation, the HH group achieved a higher exercise intensity and training duration throughout the program (p < 0.05). CONCLUSIONS: Breathing HH during pulmonary rehabilitation increases the intensity and duration of exercise training that can be performed and results in greater improvements in CLT for patients with COPD.