Intern Emerg Med DOI 10.1007/s11739-013-0989-8
IM - ORIGINAL
Clinical characteristics and lung function in chronic obstructive pulmonary disease complicated with impaired peripheral oxygenation Ming-Lung Chuang • I-Feng Lin
Received: 19 February 2013 / Accepted: 21 August 2013 Ó SIMI 2013
Abstract During exercise testing, patients with chronic obstructive pulmonary disease (COPD) often present with ventilatory limitations and various combinations of impaired peripheral oxygenation (IPO) to the exercising muscles. The entities of IPO include anemia, circulation impairment and deconditioning. COPD-IPO is not widely accepted as being a subgroup of COPD. Therefore, the aim of this study was to evaluate the clinical features of COPDIPO patients. Forty-seven COPD patients underwent cardiopulmonary exercise testing. COPD-IPO was identified when all IPO variables had abnormal values. The patients who did not meet the COPD-IPO criteria were defined as the NIPO group. The variables with abnormal values included _ 2 ) \85 % predicated, anaerobic peak oxygen uptake (VO _ 2 -work rate slope \8.6 _ 2max pred, VO threshold \40 %VO ml/watt, oxygen pulse \80 %pred, and ventilatory equivalents for O2 and CO2 at nadir ([31 and [34, respectively). Anthropometrics, biochemistry, and lung function were compared between the groups. Forty-six COPD patients were enrolled after excluding one patient who had technical difficulties in performing the exercise tests. Despite FEV1 M.-L. Chuang (&) Division of Pulmonary Medicine and Department of Critical Care Medicine, Chung Shan Medical University Hospital, #110, Section 1, Chien-Kuo North Road, South District, Taichung 40201, ROC Taiwan e-mail:
[email protected] M.-L. Chuang School of Medicine, Chung Shan Medical University, Taichung 40201, ROC Taiwan I.-F. Lin Institute and Department of Public Health, National Yang Ming University, Taipei, ROC Taiwan e-mail:
[email protected]
and FVC being similarly reduced (p = NS) between the groups, the COPD-IPO (n = 13, 28 %) patients had lower body mass index and were taller, and had impaired diffusing capacity and larger total lung capacity and air-trapping (all p \ 0.05). We concluded that COPD patients with all six variables having abnormal values are a unique subgroup and that identification of these patients is worthwhile for further investigations and management such as exercise training and nutritional supplements. Keywords Phenotype Anthropometrics Biochemistry Cardiopulmonary exercise testing Introduction Patients with chronic obstructive pulmonary disease (COPD) may develop impaired peripheral oxygenation (IPO) to exercising muscles [1], which indicates that the oxygen flow to the mitochondria is impaired. In contrast to hypoxemia resulting from respiratory pathophysiology, the mechanisms of IPO include anemia, peripheral vascular diseases, secondary pulmonary hypertension, coexisting congestive heart failure, deconditioning and mitochondrial myopathy. In addition to lung impairment from COPD causing symptoms, IPO may further compromise the quality of life and survival of patients with COPD. Maximum incremental cardiopulmonary exercise testing (CPET) has been used to detect COPD-IPO based on abnormal gas-exchange variables [1]. The variables include _ 2max ) \85 % of predicted maximum oxygen uptake (VO _ VO2max , anaerobic threshold (AT) \40 % of predicted _ 2max , oxygen uptake-work rate slope (DVO _ 2 =DWR) \ VO _ 8.6 ml/watt, oxygen pulse (O2P: VO2max /heart rate) at peak exercise \80 % predicted, and increased ventilatory
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equivalents for oxygen and carbon dioxide at AT or nadir (V_ E =O2 [ 31 and V_ E =CO2 [ 34) [1, 2]. These variables are obtained noninvasively and are always available during CPET. Although the existence of COPD-IPO has been advocated [1], it is not widely accepted as a subgroup of COPD [3]. We hypothesized that patients with COPD-IPO can be detected by CPET, and that COPD-IPO is a unique group based on clinical characteristics, blood cell and biochemistry levels, and imaging studies compared to patients with minor or no IPO (NIPO group). This study emphasizes the importance of IPO variables in patients with COPD, and provides clinicians with clues to recognize this subgroup thereby benefiting the patients by further differentiating the co-morbidities and management such as comprehensive pulmonary rehabilitation including exercise training [4].
Methods
obtained from each participating subject. The Institutional Review Board of the hospital approved the study (IRB CMRP No. 443 and CSHRP No. 11144). Protocols and measurements Oxygen-cost diagram and leisure activity History taking included oxygen-cost diagram (OCD) measurement and leisure activity score. The OCD was used as a scale for daily activities assessed by the patients themselves. The patients were asked to indicate a point on the OCD, a 100-mm long vertical line with every-day activities listed alongside the line spaced according to the oxygen requirement associated with performing each task, above which they thought their breathlessness limited them [6]. The distance from the zero point was measured and scored. Leisure activity was coded 1–4 according to hours of activity per week: 1 = B 1 h; 2 = 1–3 h; 3 = 3–6 h; 4 = B 6 h [7]. A thorough physical examination was completed before the exercise testing.
Study design Chest radiography To identify the COPD-IPO subgroup, we enrolled COPD patients with exertional dyspnea or leg fatigue who underwent symptom-limited CPET. All patients were enrolled from medical center hospitals in Taiwan. They were divided into two groups based on the aforementioned IPO variables, into those with all variables having abnormal values (IPO group) and those not meeting the IPO criteria (NIPO group). Variables of interest were then compared between the groups.
A chest radiograph was obtained within one month of enrollment in the study. The hila-thoracic ratio [36 %, cardiac-thoracic ratio, and diameter of the anterior descending pulmonary artery [1.8 cm on a standing posterior-anterior chest radiograph were measured [8]. The chest radiographs were evaluated by two pulmonologists who were blinded to the clinical information, and the average values were recorded for analysis.
Subjects
Two-dimensional echocardiography
A diagnosis of COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines [5] Adult COPD patients with exertional dyspnea or leg fatigue who underwent symptom-limited incremental CPET to identify IPO were enrolled. All patients were clinically stable with no significant changes in medication regimen for one month prior to undergoing the tests. Patients were excluded if they had significant comorbidities including electrolyte imbalance, uncontrolled hypertension, congestive heart failure, renal failure, diabetes mellitus, or had participated in any physical training program during the course of this study. Patients with COPD may have polycythemia or anemia. To avoid rejecting too many subjects from the study and thereby generalizing the study to COPD patients, we also enrolled patients with mild anemia (i.e., hemoglobin [10 gm/dL). Congestive heart failure was diagnosed by history and twodimensional echocardiography. Informed consent was
Two-dimensional echocardiography was performed by an experienced cardiologist who was blinded to the clinical data, lung function and CPET reports. Parasternal, apical and subcostal studies were conducted as reported previously [9, 10]. The definition of cor pulmonale was as follows: in apical four-chamber view, an end-diastolic right ventricle area (EDRV)[15 cm2, and end-systolic right-ventricle area (ESRV) [10 cm2; in subcostal four-chamber view, an EDRV [13 cm2 and ESRV [8 cm2; in long and short axes views, the presence of paroxysmal intraventricular septum (IVS) with right ventricle enlargement, and right ventricle free wall thickness [4 mm at an end-diastolic phase between the tricuspid annulus and the papillary muscle.
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Pulmonary function testing Forced expired volume in one second (FEV1), total lung capacity (TLC), and residual volume (RV) were measured
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with a pressure-sensitive body plethysmography (6200 Autobox DL, Yorba Linda, CA, USA) at body temperature, ambient atmospheric pressure, and fully saturated (BTPS). The best of three technically satisfactory readings was used [11–13]. All of the lung function data were obtained after inhaling 400 lg of fenoterol HCl. The diffusing capacity for carbon monoxide (DLCO) was measured by the singlebreath technique [14]. Direct maximum voluntary ventilation (MVV) was performed and calculated from a 12-second maneuver of rapid and deep breathing as recommended for patients with COPD [15]. Simple volume calibration was conducted with a 3-L syringe before each test. Maximum inspiratory pressure (MIP) at the mouth, indicating inspiratory muscle strength, was measured at RV with a nose clip in place and a forceful inspiratory maneuver leading to a sustained maximal effort for the best 1–3 s was calculated, followed by natural release upon fatigue (Micro Medical RPM, Rochester, Kent, UK). Maximum expiratory pressure (MEP), indicating expiratory muscle strength at the mouth, was measured at TLC. MIP and MEP were both performed three times, with a suitable 1-min recovery period between efforts. The best result was recorded for analysis. Blood cell and biochemical analyses Blood cell and biochemical analyses were conducted within one month before entrance to the study. Biochemical analysis included albumin, globulin, creatinine, electrolytes, glucose, cholesterol, triglyceride, aspartate and alanine aminotransferase, and bilirubin. Maximum cardiopulmonary exercise testing
two experienced investigators who were blinded to the clinical information using the dual method approach [2] containing a modified V-slope method [17] and the ventilatory equivalents method [18]. If there was a difference in the AT of more than 150 ml/min or an indeterminate AT was encountered, a consensus was reached after review. As symptom-limited exercise testing can be influenced by volition, it is reasonable to request all of the subjects to achieve a similar stress level when exercising. The definition of maximum exercise has been reported if any of the following are met: (1) heart rate reserve of 15 % or 15 beats/min of predicted maximum heart rate or less, with a predicted maximum heart rate of 220 - age; (2) respiratory exchange ratio of 1.09 or greater; (3) blood bicarbonate level of \21 mmol/L; (4) a drop of 4 mmol/L or more in bicarbonate level from baseline level; (5) pH of arterial blood gas at peak exercise of 7.35 or lower; or (6) a decrease in pH of arterial blood gas at peak exercise by 0.05 or more from rest [2, 18–20]. Each of these criteria represented one point, and therefore the scores of maximum exercise level ranged from 1 to 6. To avoid reaching different exercise intensities between groups, we compared their mean scores. To comply with the aforementioned maximum exercise criteria, brachial artery blood samples were collected from an arterial catheter connected to a pressure transducer within the last 15 s of each minute after the start of exercise to the peak of exercise. Whole-blood lactate concentration was analyzed (YSI, Yellow Springs, Ohio, USA). _ 2peak achieved by the patients was the symptomThe VO limited highest recorded point averaged over the last 15 s _ 2peak or VO _ 2max of loaded exercise and designated as VO _ [21]. VO2peak predicted was calculated from Hansen et al equations [22].
After acclimating to the computer-controlled electronicbrake cycle ergometer (Medical Graphics, St. Paul, MN, USA) and a 2-min rest period, each patient began a 2-min period of unloaded cycling followed by a ramp-pattern exercise test to the limit of their tolerance. Work rate was selected at a slope of 5–20 watts per minute according to pre-determined fitness based on our derived protocol formula [16]. Twelve-lead electrocardiography, heart rate, oxyhemo_ 2 (ml/min), VCO _ globin saturation, VO 2 (ml/min), minute ventilation, and blood pressure were measured. Oxyhemoglobin saturation was measured continuously using a pulse oximeter (Ohmeda, BOC Healthcare, Manchester, United Kingdom). The exercise data were averaged and reported every 15 s. Calibrations of the preVentTM pneumotachograph were performed with a 3-L syringe before each test. Zirconium O2 and infrared CO2 analyzers were calibrated with standard gases. The AT was determined by
Statistical analysis Data were summarized as mean ± standard deviation (SD) or median (interquartile). The Kolmogorov–Smirnov method was used to test the normality assumption. The unpaired t test was used to compare the means between two independent groups, and the paired t test was used to compare two related means from the same patient group. For non-normal data, the Mann–Whitney test was used. The Chi square test or Fisher exact test was used to compare the proportion of the categorical variables between the two groups. A p value of \0.05 was considered to be statistically significant, and a p value of \0.1 but more than 0.05 was considered to be marginally significant. Statistical procedures were performed using the SAS software package version 9.3 (SAS Institute Inc., Cary, NC, USA) and Microcal Origin v 4.0 (Northampton, MA, USA).
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Results Forty-six patients who performed with maximum effort and presented with ventilatory limitation were retained for final analysis after excluding one patient who had technical difficulties in performing the tests. The differences in the six variables between the two groups were highly significant (p \ 0.01–0.0001) (Fig. 1). The mean scores for maximum exercise effort for the IPO group and NIPO group were 2.2 ± 1.9 and 3.1 ± 2.3, respectively (p = NS), indicating that both groups reached a similar level of exercise intensity. The COPD-IPO patients had a lower body mass index (BMI) and were taller, more malnourished and modestly anemic compared to the NIPO patients (p \ 0.05–0.01) (Table 1). The expected daily exercise capacity was marginally lower in the patients with COPD-IPO (p = 0.09).
_ 2peak ) %pred (left Fig. 1 Scattergram of peak oxygen uptake (VO _ 2max upper panel); the ratio of anaerobic threshold and predicted VO _ 2max pred) (middle upper panel); the ratio of change of VO _ 2 (AT/VO _ and change of work rate (DVO2 =DWR) (right upper panel); Oxygen pulse (O2P) %pred (left lower panel); the ratio of minute ventilation _ 2nadir ) (middle lower panel); and the ratio of _ 2 at nadir (V_ E/VO and VO
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On physical examination, the COPD-IPO patients had a higher proportion of right ventricle heave than the NIPO patients (p = 0.002). On chest radiography, both groups had similar proportions of patients regarding the diameter of the anterior descending pulmonary artery C18 mm (Table 1, 2/13 vs. 10/33, p = NS) and the hila-thoracic ratio C36 % (6/12 vs. 19/32, p = NS). There was no difference in cardiac-thoracic ratio between the two groups (42.8 ± 6 vs. 44.7 ± 6.5 %, p = NS). Two-dimensional echocardiography revealed no significant statistical differences between the groups regarding EDRV [15 cm2 or ESRV [10 cm2 in the apical fourchamber view, or EDRV [13 cm2 or ESRV [8 cm2 in the subcostal four-chamber view, or paroxysmal IVS or the right-ventricle free wall thickness [4 mm (Table 1, all p = NS).
_ _ _ minute ventilation and VCO 2 at nadir (VE =VO2nadir ) (right lower panel) in COPD patients with impaired peripheral oxygenation (IPO) and COPD patients with no IPO (NIPO). AT was measured in 39 of 46 patients. Open square indicate average value; bars indicate standard error. * p value is shown on the top of each panel
Intern Emerg Med Table 1 Clinical characteristics, blood tests, chest radiography and twodimensional echocardiography in patients with COPD
IPO (N = 13)
NIPO (N = 33)
p value
Age, year
63.8 ± 6.4
66.1 ± 5.2
NS
Height, cm
168.6 ± 6.2
163.6 ± 6.0
0.02 NS
Weight, kg
59.2 ± 8.4
60.9 ± 12.2
Body mass index, kg/m2
20.7 ± 2.3
22.7 ± 3.8
0.04
Cigarette, packyear
39.9 ± 17.5
43.2 ± 20
NS
Oxygen-cost diagram, cm
6.4 ± 1.6
7.3 ± 1.2
0.09
Leisure activity
1.5 ± 0.9
2.1 ± 1.3
0.19*
Right ventricle heave, no./total no.
10/10
11/26
0.002
Triceps, mm
5.5 ± 2.1
6.7 ± 2.7
NS
Mid-arm, cm
27 ± 3
27.4 ± 3.6
NS
Blood tests Data are presented as mean ± SD for continuous variables, and proportions for categorical variables IPO group: patients with abnormal values of the six variables as shown in the table denoting impaired peripheral oxygenation; non-IPO group: patients who did not meet the IPO criteria * indicates between-group comparisons conducted with the Mann–Whitney U test. Oxygencost diagram: a scale for daily activities assessed by the patients themselves. For details, please refer to the text. Leisure activity: coded 1–4 according to hours of activity per week: 1 B 1 h; 2 = 1–3 h; 3 = 3–6 h; 4 C 6 h. Comparisons between groups were performed using unpairedt tests. Right ventricle heave indeterminate in 10 patients, triceps indicating the skinfold of the triceps, mid-arm indicating its circumference
Hemoglobin, gm %
14 ± 1.8
15.2 ± 1.3
0.04
Carboxyhemoglobin, gm %
1 ± 0.7
1.5 ± 0.9
0.07
Albumin, gm/L
4 ± 0.4
4.2 ± 0.3
0.06
Albumin/Globulin
1.3 ± 0.2
1.5 ± 0.3
0.02
Chest radiography, no./total no. Hila-thoracic ratio [36 %
6/12
19/32
NS
Cardiothoracic ratio, %
42.8 ± 6
44.7 ± 6.5
NS
Anterior descending pulmonary artry [1.8 cm
2/13
10/33
NS
EDRV [15 cm2
3/11
11/31
NS
ESRV [10 cm2
0/11
4/31
NS
EDRV [13 cm2
5/11
21/31
NS
ESRV [8 cm2
6/11
12/31
NS
Paroxysmal intraventricular septum
0/11
1/25
NS
Right ventricle free wall thickness [4 mm
9/11
23/31
NS
Two-dimensional echocardiography, no./total no. Apical four-chamber view
Subcostal four-chamber view
Long and short axes view, no./total no.
Tricuspid regurgitation, no./total no.
7/11
22/32
NS
Pulmonary regurgitation, no./total no.
0/11
2/32
NS
The COPD-IPO patients had larger TLC, RV/TLC, functional residual capacity (FRC), and lower DLCO %pred (all p \ 0.005–0.05, Table 2), while both groups had similarly reduced spirometric data, direct MVV, MIP and MEP (all p = NS, Table 2).
Discussion The main findings of this study are that using the six noninvasive variables relevant to impaired peripheral oxygen flow to exercising muscles, a specific group of patients with COPD can be identified. The COPD-IPO patients had a lower BMI, were taller and more
malnourished, anemic and had larger lung volumes, more air-trapping, and lower diffusing capacity [23, 24]. However, FVC and FEV1 were similarly reduced in both IPO and NIPO groups. Wasserman et al. reported that IPO may compromise patients with COPD [1]. The results of the current study _ 2peak , AT, VO _ 2 /work-load slope, clearly showed that VO _ 2 and V_ E =VCO _ O2Ppeak, and V_ E =VO 2 at nadir as a whole were strikingly different between the two groups (Fig. 1). This indicates that the six variables can be used as a panel for identifying COPD-IPO. Even though this particular group of patients has not yet been advocated as a phenotype of COPD [3], they are quite different from the severity categories of A, B, C, and D raised recently by the GOLD
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Intern Emerg Med Table 2 Lung function testing of the patients with COPD (mean ± SD)
Group
IPO (N = 13)
Non-IPO (N = 33)
p value
FVC (L)
2.54 ± 0.66
2.46 ± 0.69
NS
FEV1 (L)
1.22 ± 0.42
1.15 ± 0.61
NS
52 ± 17
49 ± 15
NS
FEV1/FEV1pred (%) For definition of grouping, please refer to Table 1 IPO impaired peripheral oxygenation, FVC forced vital capacity, FEV1 forced expired volume in one second, DLCO diffusing capacity for carbon monoxide Comparisons between groups were performed using unpairedt tests * indicates between-group comparisons conducted with the Mann–Whitney U test
FEV1/FVC (%)
47 ± 23
50 ± 11
NS
Direct maximum voluntary ventilation (L/min)
35.2 ± 17.2
36.7 ± 17.1
NS 0.04
Total lung capacity (TLC) (L)
6.99 ± 1.07
6.26 ± 0.87
TLC/TLCpred (%)
143 ± 19
131 ± 20
0.07
Residual volume (RV) (L)
4.35 ± 0.97
3.5 ± 69
0.005*
56 ± 0. 9
0.05
Functional residual capacity (FRC) (L)
RV/TLC (%)
5.34 ± 0.1
4.51 ± 0.79
0.02
DLCO (ml/min/mm Hg)
13.5 ± 5.1
16.9 ± 5.4
0.06
DLCO/DLCOpred (%)
54 ± 20
76 ± 19
0.003
Maximum inspiratory pressure (cm H2O)
62 ± 18
71 ± 19
NS
Maximum expiratory pressure (cm H2O)
96 ± 26
107 ± 21
NS
committee [25]. Further studies with a larger population are warranted to confirm our findings. FEV1 has been used as a marker of COPD severity [5]. We found that in both IPO and NIPO groups FVC and FEV1 were similarly reduced. However, CPET could further identify the unique COPD-IPO subgroup with strikingly different findings from the NIPO subgroup in BMI, hemoglobin, albumin/globulin ratio, TLC, air-trapping, and DLCO. Although the 6-min walk test has been widely used in the evaluation of patients with COPD, it cannot be used to identify the subgroup of patients with IPO [26]. We suggest that CPET is a comprehensive tool that should be added to the evaluation of the complexity of COPD. Based on CPET results, clinicians can further arrange other tests to differentiate the co-morbidities such as hyperinflation or cardiovascular impairment and take action on further management such as exercise training or nutritional supplements. It has been reported that patients with COPD presenting predominantly with emphysema are slimmer and have larger lung volumes, lower diffusing capacity and weaker diaphragms [27, 28]. The physiological characteristics of our study subjects are similar to patients with emphysema, except for similar MIP values between both groups (p = NS). We, therefore, speculate that our patients with COPD-IPO probably had emphysema. However, further studies such as high-resolution chest computed tomography to evaluate emphysema are necessary to confirm this. Nevertheless, the six variables are physiologically related to larger lung volumes with air-trapping and lower diffusing capacity. It was recently reported that underweight-matched FEV1 patients with COPD have lower exercise capacity, AT and ventilatory muscle strength, and poorer ventilatory
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62 ± 0. 9
efficiency and quality of life [29]. The authors also reported that patients with COPD who have a low BMI would benefit more from comprehensive pulmonary rehabilitation than those who have a normal or high BMI [4]. Reduced body mass has been reported to have an independent negative effect on muscle aerobic capacity in COPD patients, and that this effect may be related to the variability in exercise tolerance among patients with comparable ventilatory limitations [30]. The COPD-IPO patients in this study also had lower BMI, exercise capacity, AT and poorer daily life activity, and are thus expected to benefit from comprehensive pulmonary rehabilitation. Although there were significant differences in hemoglobin and albumin between the groups, most of the values were similar because of the inclusion criteria of the study. Therefore, the clinical significance of the statistical difference might not be that concerned (Table 1). Right ventricle heave was more common in the COPDIPO group than in the NIPO group (p = 0.002). However, differences in the presence of secondary pulmonary hypertension diagnosed with chest radiography and twodimensional echocardiography were insignificant between the groups (Table 1, all p = NS). Although the correlation of diagnosing pulmonary hypertension in COPD with chest radiography and two-dimensional echocardiography is significant, the hila-thoracic ratio plus the diameter of right anterior descending pulmonary artery has low sensitivity and negative predictive value for identifying pulmonary hypertension [31]. Although tricuspid regurgitation velocity has been used to estimate the right ventricular systolic pressure [32], certain conditions influence the estimation of right ventricular systolic pressure such as the size and collapsibility of the inferior vena cava [33]. Further studies
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with right heart catheterization are needed to elucidate whether adding tricuspid regurgitation velocity to Danchin’s method [10] can improve the accuracy of detecting pulmonary hypertension. There are some limitations to this study. The grouping strategy of the study was not completely precise, as some of the patients in the NIPO group had abnormal values of some of the six variables relevant to IPO. A difficulty was that no patients in the study had normal values of all six variables, and therefore it would seem to be necessary to enroll more patients in future studies. If 1 in 50 patients with COPD has normal values of all six variables, 1,000 patients would be required to identify 20 with normal values of all six variables. Because some patients had abnormal values of the variables in the NIPO group, there was overlapping _ 2 and V_ E =VCO _ between the groups, especially for V_ E =VO 2 at nadir (Fig. 1). This suggests that using a panel of six variables instead of using each individual variable can identify a unique subgroup with more severity. However, we cannot exclude some minor cases of IPO being present in the NIPO group. This study is a preliminary report and further studies are needed with a larger COPD population to investigate whether a unique subgroup can be identified as in our findings. Measures of quality of life such as St. George’s Respiratory Questionnaire were not prospectively evaluated in this study, although the daily exercise capacity was evaluated with the OCD scale and weekly exercise duration was also evaluated. Further studies are needed to elucidate whether or not IPO is a prognostic indicator. It may be argued that the cost and complexity in interpreting CPET data outweigh the benefits. The cost of the test varies from country to country, however, the benefits are consistent if the interpretation and management are appropriate. Although type II errors may have occurred when comparing spirometry, anthropometrics, biochemistry, and lung volumes, the striking differences in the variables of anthropometrics, biochemistry, and lung volumes and diffusing capacity between these two groups reduce the concern. We estimated a statistical power of 0.82 for FRC, given the number of subjects in our study with a mean ± SD of 5.34 ± 1 L in the IPO group (n = 13) and 4.51 ± 0.79 L in the NIPO group (n = 33).
Conclusions This study confirms that CPET is an excellent test to identify a unique group of COPD patients with more severe impaired peripheral oxygenation who may benefit from further differentiation of co-morbidities and management
such as exercise training and nutritional supplements. Further studies with a larger patient population are needed to confirm the findings and hypotheses of this study. Acknowledgments This study was supported in part by the Chang Gung Medical Research Program (CMRP No. 443) and Chung Shan Hospital Research Program (CSHRP No. 11144, CSH-2012-C-023). The authors would like to thank professor Fen-Chiung Lin of Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C. for her excellent performing the two-dimensional echocardiography. Conflict of interest
None.
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