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Association of body mass index with exercise cardiopulmonary responses in lung function-matched patients with chronic obstructive pulmonary disease
Care of Patients with Pulmonary Disorders
Association of body mass index with exercise cardiopulmonary responses in lung function-matched patients with chronic obstructive pulmonary disease Chou-Chin Lan, MD, PhDa,b, Chiu-Ping Su, MSNc, Lih-Lih Chou, MSNc, Mei-Chen Yang, MDa,b, Chor-Shen Lim, MDa,b, Yao-Kuang Wu, MDa,b,* a
Division of Pulmonary Medicine, Buddhist Tzu-Chi General Hospital, Taipei Branch, Xindian City, Taipei, Taiwan, Republic of China b School of Medicine, Tzu-Chi University, Hualien, Taiwan, Republic of China c Institute of Head Nurse, Department of Nursing, Buddhist Tzu Chi General Hospital Taipei Branch, Xindian City, Taipei, Taiwan, Republic of China
article info
abstract
Article history: Received 1 October 2011 Revised 10 February 2012 Accepted 11 February 2012 Online 14 March 2012
Background and Objectives: Lung function is traditionally used to define the severity of chronic obstructive pulmonary disease (COPD). However, this does not exclude other factors. This study investigated the influence of body mass index (BMI) on exercise responses and quality of life in patients with COPD matched for values of forced expiratory volume in 1 second (FEV1).
Keywords: Chronic obstructive pulmonary disease Body mass index Exercise capacity Health-related quality of life
Methods: Underweight, normal-weight, and overweight patients with COPD, matched for FEV1, were studied. All patients were evaluated by spirometry, a cardiopulmonary exercise test, respiratory muscle strength, and, St. George’s Respiratory Questionnaire (SGRQ). Results: The baseline characteristics and mean FEV1 of the 3 groups were similar (P > .05). Respiratory muscle strengths and SGRQ scores were lowest in underweight patients (P < .05). In terms of exercise response, the lowest oxygen uptake at anaerobic threshold and peak exercise, the highest ventilatory equivalent, and the lowest oxygen pulse were evident in underweight patients (P < .05). Conclusions: Underweight patients with COPD had lower respiratory muscle strength, impaired exercise capacity, earlier anaerobic metabolism, ineffective ventilation, and poorer quality of life. Cite this article: Lan, C.-C., Su, C.-P., Chou, L.-L., Yang, M.-C., Lim, C.-S., & Wu, Y.-K. (2012, JULY/AUGUST). Association of body mass index with exercise cardiopulmonary responses in lung function-matched patients with chronic obstructive pulmonary disease. Heart & Lung, 41(4), 374-381. doi:10.1016/ j.hrtlng.2012.02.010.
Chou-Chin Lan and Chor-Shen Lim were responsible for study conception and design. Chou-Chin Lan, Chiu-Ping Su, and Lih-Lih Chou acquired the data. Chou-Chin Lan and Mei-Chen Yang were responsible for the analysis and interpretation of the data. Chou-Chin Lan drafted the manuscript. Yao-Kuang Wu was responsible for critical revision. Yao-Kuang Wu provided statistical expertise. Yao-Kuang Wu provided general supervision. * Corresponding author: Yao-Kuang Wu, MD, Division of Pulmonary Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, 289 Jianguo Road, Xindian City, Taipei County 23142, Taiwan, Republic of China. E-mail address: [email protected] (Y.-K. Wu). 0147-9563/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.hrtlng.2012.02.010
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The prevalence of underweight status among patients with chronic obstructive pulmonary disease (COPD) is about 20% to 40%.1 Underweight patients with COPD often demonstrate poor clinical condition, compared with nonunderweight patients.2-4 Limited exercise capacity and functional impairment are key features of COPD,5 and malnutrition leads to further exercise limitations and functional impairment in underweight patients with COPD.6,7 In addition, underweight patients with COPD often have poor health-related quality of life (HRQL).8 Schols et al showed that survival was reduced by almost half in COPD patients with cachexia, and that the differences in survival were not attributable to differences in severity according to spirometric criteria.4 Therefore, the issue of body mass index (BMI) in COPD is important. Although some studies involved BMIs in COPD, the number of such studies is limited.8,9 Those studies reported on COPD patients with different BMIs, although the subjects were not matched in terms of lung function, and the influence of airway obstruction in these studies cannot be ignored.8,9 In addition, these studies focused on exercise capacity and HRQL in patients with COPD.8,9 The exercise response and overall influence of BMI in patients with COPD are not fully understood. Therefore, further studies about BMI in patients with COPD are necessary. We studied the exercise capacity and HRQL of lung function-matched patients with different BMIs. We further analyzed their ventilator and circulatory responses to exercise, to investigate whether BMI influences exercise responses in patients with COPD. Understanding more about the association of BMI and COPD may help in clinical management. Thus, we aimed to investigate the association of BMI with: (1) resting pulmonary function and respiratory muscle strength, (2) symptoms and HRQL, (3) exercise capacity, (4) ventilatory responses during exercise, and (5) circulatory responses during exercise.
Methods Patient Selection We retrospectively analyzed 309 patients with COPD receiving cardiopulmonary exercise tests (CPETs) from August 2008 to March 2011. These patients with COPD were classified into underweight (BMI, <20 kg/m2), normal-weight (BMI, 20 to 25 kg/m2), and overweight (BMI, >25 kg/m2), according to previous studies.10,11 In our study, the inclusion criteria comprised: (1) diagnosis and severity of COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging of the disease;12 (2) no occurrence of COPD exacerbations for at least 3 months; and (3) ability of the patient to mobilize independently. The exclusion
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criteria comprised: (1) an exacerbation of COPD within 12 weeks of an exercise test; (2) a history of pneumoconiosis, bronchiectasis, pulmonary tuberculosis, primary pulmonary hypertension, pulmonary embolism, interstitial lung disease, malignancies, hepatic abnormalities, congestive heart failure, or recent surgery; (3) orthopedic impairment that would influence the exercise test; and (4) participation in pulmonary rehabilitation in the preceding 12 months. After applying the inclusion and exclusion criteria, 131 patients with COPD were enrolled in our analysis. Twenty-five of these 131 patients were underweight. The patients of normal weight and the overweight patients, matched for forced expiratory volume in 1 second (FEV1), were selected for further analysis. Therefore, 75 patients, matched for FEV1, were included, with 25 patients in each weight group. The research protocol was approved by the Ethics Committee of Buddhist Tzu-Chi General Hospital. Signed, informed consent was obtained from all patients.
Measurements Physiological parameters at rest were assessed according to spirometry and respiratory muscle strength, ie, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). The HRQL was assessed by the validated Chinese version of the St. George’s Respiratory Questionnaire (SGRQ).13 Physiological parameters during exercise were assessed by CPETs.
Resting Pulmonary Function Test and Ventilatory Muscle Strength Pulmonary function tests were performed using spirometry (Medical Graphics Corporation, St. Paul, MN), following the standards of the American Thoracic Society.14 The best flow-volume loop was used in the final data analysis. We assessed MIP and MEP using a standard mouthpiece and a direct dial pressure gauge (Respiratory Pressure Meter, Micro Medical Corporation, Rochester, United Kingdom). We measured MIP at the residual volume, and MEP was measured at total lung capacity. The highest value from at least 3 maneuvers was recorded.15
Health Status and Symptom Assessment The SGRQ is a self-administered questionnaire designed to measure the influence of chest disease on HRQL.13,16,17 The responses to its 50 items can be aggregated into an overall score, with 3 subscores for symptoms (8 items), activity (16 items), and impact (26 items). Responses are weighted and scores are calculated by dividing the summed weights by the maximum possible weight.13,16,17 Scores on the SGRQ range from 100 (worst possible health status) to 0 (best
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possible status), and higher scores indicate a poorer health status. The SGRQ was reported to be valid and reliable in patients with COPD, asthma, and bronchiectasis.13,16,17 Ratings of perceived exertion were reported by patients at rest and at the end of exercise tests on a 10-point Borg scale for dyspnea.
Cardiopulmonary Exercise Test All patients performed an incrementally progressive, symptom-limited exercise test on an electromagnetically braked cycle ergometer, in accordance with published guidelines (Lode Corival, Groningen, The Netherlands).18,19 The test consisted of measurements during 2 minutes of rest, followed by 2 minutes of unloaded pedaling and a ramp increase of load (increments of 10 watts/minute1) to maximal workload. Expired gas was analyzed breath-by-breath or in terms of oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), tidal volume (VT), and endtidal PCO2 (PETCO2), using the MedGraphics cardiopulmonary diagnostic system (Breeze suite 6.1, Medical Graphics Corporation). Heart rate (HR) was monitored continuously by 12-lead electrocardiography (ECG), and hemoglobin saturation was determined by pulse oximetry (SpO2). Blood pressure (BP), including systolic (SBP) and diastolic (DBP), were recorded at rest and after each 2 minutes of exercise. Patients were strongly encouraged to achieve their point of maximal exercise, until they could no longer continue because of severe dyspnea, leg fatigue, chest pain with ischemic ECG changes, a fall in SBP of 20 mm Hg from the highest value during the test, hypertension (SBP, 250 mm Hg systolic; DBP, 120 mm Hg), severe desaturation with SpO2 of 80%, sudden pallor, or faintness. The onset of anaerobic threshold (AT) was determined from a plot of VCO2 vs. VO2 (V-slope method), as previously reported.18,19 The ventilatory equivalent for CO2 (VEQ) was determined as the ratio of VE/VCO2 at AT. The oxygen pulse (O2P) was calculated as the ratio of VO2/ HR, and the respiratory exchange ratio (RER) as the ratio of VCO2/VO2.18,19 Peak VO2 and work rate (watts) were regarded as exercise capacity.20,21 Changes in VE, VT, respiratory rate (RR), and VEQ during exercise were regarded as ventilator responses during exercise, and changes in O2P, HR, and blood pressure (BP) during exercise were regarded as circulatory responses to exercise.20,21
Statistical Analysis All measurements are expressed as means standard deviations (SDs). Comparisons of parameters among the 3 groups were performed using one-way analysis of variance, followed by the Scheffe´ multiple comparison test. The Pearson c2 test was used to compare gender among the three groups. P < .05 was considered statistically significant. All statistical analyses were performed using SPSS for Windows (version 18.0, SPSS, Inc., Chicago, IL).
Results Anthropometric and Spirometric Data of the 3 COPD Groups The clinical characteristics and lung function of all patients with COPD are shown in Table 1. The mean BMI was 18.4 1.6 kg/m2 in underweight patients, 22.6 1.4 kg/m2 in normal-weight patients, and 27.6 2.4 kg/m2 in overweight patients (P < .001). The 3 groups demonstrated similar results regarding airflow obstruction (FEV1, forced vital capacity [FVC], and FEV1/ FVC) and age. The mean FEV1 was 50.0% 21.7% of the predicted value in underweight patients, 48.0% 18.3% of the predicted value in normal-weight patients, and 52.8% 19.9% of the predicted value in overweight patients (P > .05). The MIP and MEP were significantly lower in underweight patients compared with normalweight and overweight patients (both P < .05). However, no differences were evident in MIP and MEP between the normal-weight and overweight patients.
HRQL and Dyspnea in the 3 COPD Groups HRQL and Dyspnea are shown in Table 2. The SGRQ analysis showed that SGRQ total and impact scores were significantly higher in underweight patients compared with normal-weight and overweight patients (P < .05). The SGRQ scores of symptoms and activity were also higher in underweight patients, but without statistical significance (P > .05). The SGRQ scores (symptoms, impact, activity, and total) were similar in normal-weight and overweight patients (P > .05). The scores for dyspnea Borg scales at rest and at peak exercise were similar in the 3 groups (P > .05).
VO2 and VCO2 at Rest, AT, and Peak Exercise in the 3 COPD Groups Exercise capacity and AT are shown in Table 3. The VO2 at rest was similar in the 3 COPD groups (P > .05). However, the VO2 at AT or peak exercise was significantly lower in the underweight patients than in the normal-weight and overweight patients (P < .05). The VCO2 exhibited a trend similar to that of VO2. The RER at rest or at peak exercise was similar in the 3 groups (P > .05). The maximal workload was significantly lower in the underweight than in the normal-weight and overweight patients (P < .05).
Ventilator Response at Rest, AT, and Peak Exercise in the 3 COPD Groups Parameters of ventilatory response are shown in Table 4. The VT at rest or at peak exercise was lowest in underweight patients, although this did not reach not statistical significance (P ¼ .135 for VT at rest; P ¼ .296 for VT at peak exercise). The RR at rest was highest in underweight
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Table 1 e Baseline characteristics, pulmonary function, and respiratory muscle strength of underweight, normal-weight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value Gender (male/female) Age (years) BMI (kg/cm2) Weight (kg) Height (cm) FEV1/FVC (%) FEV1 (L) FEV1 (% predicted) FVC (L) FVC (% predicted) MVV (L/minute) MIP (cm H2O) MEP (cm H2O)
19/6 69.2 11.0 18.4 1.6y 47.4 7.3y 161.5 10.3 49.0 12.5 1.07 .49 50.0 21.7 2.19 .78 80.0 23.1 40.5 19.1 53.6 17.8 94.5 27.7
21/4 68.4 8.3 22.6 1.4* 59.4 7.5* 161.8 8.8 45.7 10.7 1.06 .48 48.0 18.3 2.31 .82 83.3 22.6 40.4 18.8 71.0 28.7* 119.3 44.7*
21/4 71.3 7.3 27.6 2.4*,y 71.9 10.5*,y 161.2 8.2 52.1 11.8 1.09 .51 52.8 19.9 2.07 .71 79.4 23.9 40.6 21.4 71.0 8.3* 116.8 40.4*
P ¼ .704 P ¼ .512 P < .000 P < .000 P ¼ .973 P ¼ .158 P ¼ 0.978 P ¼ .696 P ¼ .549 P ¼ .815 P ¼ .999 P ¼ .018 P ¼ .048
BMI, body mass index; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; MVV, maximum voluntary ventilation. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients. y P < 0.05, vs. normal-weight patients.
patients (P < .05). However, the RR at peak exercise was similar in the 3 groups (P > .05). The VE at rest and at peak exercise was also similar in the 3 groups (P > .05). The SpO2 and PETCO2 at rest, AT, and peak exercise were also similar in the 3 groups (P > .05). The VEQ was highest in underweight patients (P < .05).
Circulatory Response at Rest, AT, and Peak Exercise in the 3 COPD Groups Parameters of circulatory response are shown in Table 5. The O2P at peak exercise was significantly lower in underweight patients (6.0 1.4 mL beat1) than in normal-weight (7.3 1.9 mL beat1) or overweight (8.5 1.9 mL beat1) patients (P < .05). The HR at rest, AT, and peak exercise was similar in the 3 groups (P > .05). The SBP, DBP, and mean BP (MBP) at rest were similar in the 3 groups (P > .05). However, at peak exercise, the SBP was lowest in underweight patients (P < .05), whereas DBP and MBP lacked statistical significance (P ¼ .565 for DBP; P ¼ .101 for MBP).
Discussion Lung function is traditionally used to define the severity of COPD according to the GOLD criteria.12 However, this did not exclude the possibility that other factors such as BMI may affect exercise capacity and HRQL. The present study showed that BMI exerted an influence on COPD, independent of the degree of airway obstruction. This finding implies that low exercise capacity, respiratory muscle weakness, and poor HRQL are related not only to impaired lung function but also to low BMI. The influence of BMI on exercise capacity, AT, O2P, and HRQL should therefore be addressed. We think this study is important because
it analyzed more comprehensive measurements compared with previous studies. In addition, the patients in our study were lung function-matched, unlike the case in previous studies. The limitation of peak exercise capacity with functional impairment is an essential feature in patients with COPD.5 The relationship between lung function and exercise capacity is evident, becaus it represents lung parenchymal damage.22 As seen in our study, the relationship between BMI and exercise capacity is also important. Previous studies showed a correlation between BMI and exercise capacity.5,7 However, those studies did not perform lung function matching in their patients. Underweight patients with COPD demonstrated a lower exercise capacity and poorer HRQL, and the FEV1 was also lower in these underweight patients.5,7 The influence of airway obstruction could not be disregarded in those studies.5,7 The findings in the present study with lung function-matched patients support the idea that underweight status itself compromises exercise tolerance, leading to greater disability. Although the influence of BMI on exercise capacity was clearly established in previous studies, little attention has been given to its influence on HRQL. Our study contains the important finding that underweight patients with similar lung function also scored worse on the SGRQ. Even though Shoup et al found that underweight patients had a lower HRQL, the subjects in their study were not lung function-matched patients with COPD.8 In our study, we found that HRQL was poor in underweight patients with COPD, regardless of lung function. A decrease in body weight is primarily a consequence of disturbed energy balance in patients with COPD.23 Moreover, a hypermetabolic state is related to the excessive caloric expenditures dictated by the high energy requirements of respiratory muscles.24 In
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Table 2 e Health-related quality of life and dyspnea of underweight, normal-weight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value Borg dyspnea at rest Borg dyspnea at peak exercise SGRQ-total SGRQ-symptom SGRQ-activity SGRQ-impact
.2 .5 5.1 1.4 62.9 14.6 66.7 16.7 71.0 17.2 57.1 20.3
.5 .8 5.8 2.0 48.2 18.7 55.1 23.4 63.4 22.1 38.0 20.6*
.4 .6 5.3 1.9 49.1 19.5* 56.2 24.6 62.7 21.7 39.1 19.5*
P ¼ .291 P ¼ .349 P ¼ .007 P ¼ .125 P ¼ .289 P ¼ .002
COPD, chronic obstructive pulmonary disease; SGRQ, St. George’s Respiratory Questionnaire. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients.
Table 3 e Exercise capacity, anaerobic threshold, and respiratory exchange ratio of underweight, normalweight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value VO2 at rest (mL/minute) VO2 at AT (mL/minute) VO2 at peak exercise (mL/minute) VO2 at peak exercise (%) VCO2 at rest (mL/minute) VCO2 at AT (mL/minute) VCO2 at peak exercise (mL/minute) RER at rest RER at peak exercise WR (watts)
269.1 34.8 510.0 115.0y 727.3 182.5 48.2 18.9 240.7 38.4 492.5 117.8 779.1 241.5 .89 .09 1.06 .14 44.7 19.4
263.6 45.9 621.0 119.8* 927.1 251.4* 57.2 15.6* 240.5 38.4 593.0 108.3* 1028.2 295.7* .92 .11 1.08 .10 61.7 26.7*
272.0 52.4 719.8 131.4*,y 1052.1 284.8* 71.2 29.4* 246.5 38.7 671.7 102.9* 1089.5 298.4* .92 .10 1.04 .11 67.2 23.5*
P P P P P P P P P P
¼ .796 ¼ .000 ¼ .000 ¼ .002 ¼ .822 ¼ .000 ¼ .000 ¼ .472 ¼ .428 ¼ .003
AT, anaerobic threshold; COPD, chronic obstructive pulmonary disease; RER, respiratory exchange ratio; VCO2, carbon dioxide output; VO2, oxygen uptake; WR, work rate. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients. y P < 0.05, vs. normal-weight patients.
addition, COPD is recognized as a disease of systemic inflammation.25-27 Systemic inflammation and oxidative stress are likewise potential mechanisms for the catabolic state resulting in the development of underweight status.25-27 Malnutrition and caloric deprivation are therefore common consequences in patients with COPD, and often lead to muscle atrophy, contributing to respiratory and peripheral muscle weakness.28,29 The loss of diaphragm muscle force was also reported.30 Therefore, a lower BMI may imply a greater severity of disease, even with the same lung function. A lower peak O2P and earlier anaerobic metabolism (lower AT) during exercise was evident in underweight patients in the present study. Invasive hemodynamic measurements during the exercise test were not performed. However, on the basis of the Fick equation, the lower O2P during exercise suggests a lower stroke volume, arteriovenous oxygen difference, or both.18 In underweight patients, a depletion of cardiac muscle mass decreases the stroke volume.31 A low body mass also exerts negative effects on muscle aerobic capacity.7 Both lower stroke volume and negative muscle aerobic capacity lead to earlier anaerobic metabolism during exercise.31 Earlier anaerobic metabolism and lower stroke volume in underweight
patients will lead to earlier lactic acid production during exercise, and lactemia during exercise imposes additional respiratory stimuli, increases ventilation, and heightens dyspnea.32,33 As such, a lower O2P and earlier anaerobic metabolism are factors causing a lower exercise capacity in underweight patients. These factors, together with the additional burdens of airway obstruction, deconditioning, and respiratory and peripheral muscle weakness, lead to limitations in exercise capacity. Underweight and nonunderweight patients with COPD exhibited similar HRs and BPs at rest in this study. However, SBP at peak exercise was significantly lower in underweight patients, implying a lower BP response during exercise. The SBP was labile and changed more rapidly during exercise, and this finding may explain the significant difference in SBP as opposed to DBP, which was slow to respond to exercise. As exercise intensity increases, the reflex control of the distribution of cardiac output causes changes in BP and systemic vascular resistance.34 Although the net result is systemic vasodilatation with a fall in systemic vascular resistance during exercise, SBP typically rises progressively with the increase in cardiac output.19 If BP does not increase with exercise, a cardiac limitation
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Table 4 e Ventilatory responses during exercise in underweight, normal-weight, and overweight patients with COPD Underweight Normal weight Overweight P value (n ¼ 25) (n ¼ 25) (n ¼ 25) VE at rest (L/minute) VE at AT (L/minute) VE at peak exercise (L/minute) RR at rest (breaths/minute) RR at peak exercise (breaths/minute) VT at rest (mL) VT at peak exercise (mL) VEQ SpO2 at rest (%) SpO2 at peak exercise (%) dSpO2 (peak rest) (%) PETCO2 at rest (mm Hg) PETCO2 at peak exercise (mm Hg) dPETCO2 (peak rest) (mm Hg)
12.2 2.8 18.3 4.1 29.4 10.0 21.2 4.5 33.5 7.2 588.8 142.9 907.9 318.3 41.8 6.9 96.2 2.6 93.2 4.5 2.9 3.5 33.7 5.8 38.0 8.3 4.3 5.1
11.6 3.2 19.7 5.5 32.4 11.8 17.6 4.2* 31.2 7.0 680.6 196.3 1056.8 363.3 37.3 6.0* 96.0 2.1 93.0 3.3 3.0 2.4 33.5 5.8 40.2 7.3 6.7 4.8
12.0 3.6 20.7 4.7 33.6 14.1 19.7 4.2 33.4 8.0 615.0 149.7 1012.2 347.0 34.5 5.0* 95.9 1.9 92.6 4.1 3.2 2.9 36.8 5.4 42.6 7.0 5.9 4.8
P ¼ .795 P ¼ .236 P ¼ .450 P ¼ .017 P ¼ .471 P ¼ .135 P ¼ .296 P ¼ .000 P ¼ .906 P ¼ .866 P ¼ .929 P ¼ .081 P ¼ .103 P ¼ .189
COPD, chronic obstructive pulmonary disease; dPETCO2, difference of PETCO2 at peak exercise and rest; dSpO2, difference of SpO2 at peak exercise and rest; PETCO2, end-tidal PCO2; RR, respiratory rate; SpO2, oxygen saturation; VE, minute ventilation; VEQ, ventilatory equivalent for carbon dioxide; VT, tidal volume. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients.
Table 5 e Circulatory responses during exercise in underweight, normal-weight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value O2P (mL beat1) HR at rest (beats/minute) HR at peak exercise (beats/minute) SBP at rest (mm Hg) DBP at rest (mm Hg) MBP at rest (mm Hg) SBP at peak exercise (mm Hg) DBP at peak exercise (mm Hg) MBP at peak exercise (mm Hg)
6.0 86.0 121.3 123.6 69.6 87.6 157.1 75.8 102.9
1.4 15.2 17.8 19.8 13.5 13.6 26.0 14.1 14.3
7.3 1.9* 86.5 11.3 127.1 17.2 127.0 17.4 72.6 11.3 90.7 11.4 176.0 21.9* 80.2 16.2 112.1 15.1
8.5 1.9* 86.1 12.1 123.6 14.0 126.5 16.0 69.7 11.1 88.6 10.7 169.4 26.6 79.1 14.9 109.2 16.5
P ¼ .000 P ¼ .989 P ¼ .462 P ¼ .766 P ¼ .609 P ¼ .644 P ¼ .030 P ¼ .565 P ¼ .101
COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; HR, heart rate; MBP, mean blood pressure; O2P, oxygen pulse; SBP, systolic blood pressure. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < .05, vs. control subjects.
is suggested.19 We found that underweight patients demonstrated a poor SBP response to exercise, and the lower O2P in these patients implies a lower stroke volume. Previous studies showed that malnutrition causes a decrease of left ventricular mass and systolic dysfunction with low stroke volume.35,36 Therefore, a lower SBP response during exercise occurs in underweight patients. Respiratory muscle weakness is also a cardinal feature of COPD.37 In a previous study, respiratory muscle strength was lower in more severe cases of COPD.38 However, in our present study, respiratory muscle strength was also lower in underweight patients, although they exhibited the same lung function. Respiratory muscle weakness in underweight patients with COPD involves multiple factors,
including malnutrition, muscular atrophy, and steroidinduced myopathy.37-40 Malnutrition predisposes patients to a loss of muscle mass in the diaphragm and in skeletal and respiratory muscle.39 Systemic corticosteroids are frequently used to manage COPD with acute exacerbations. However, their use was reported to have some negative consequences, including steroid myopathy of the respiratory and skeletal muscles.40 All patients in our study were stable, and none had received systemic steroids for at least 1 year. Oxidative stress and systemic inflammation lead to the damage of muscle proteins, which also contributes to diaphragm and respiratory muscle abnormalities.37 Our study revealed respiratory muscle weakness in underweight patients, accompanied by higher VEQ during exercise. The higher VEQ in our underweight
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patients implies poor ventilatory efficiency during exercise, which may be explained by respiratory muscle weakness.
Limitations of This Study This study has some limitations. First, we did not check the fat-free mass (FFM) in our patients. A reduced FFM may occur despite normal BMI.41 Second, most of these patients with COPD were male. We need to confirm our results in female patients, especially because considerable differences in body composition exist between males and female patients.42 Exercise responses may also be different between female and male patients.
Conclusions After analyzing the exercise responses of COPD patients with different BMIs, this study showed that underweight patients with COPD demonstrated lower respiratory muscle strength, impaired exercise capacity, earlier anaerobic metabolism, lower O2P, ineffective ventilation, and poor HRQL. The management of underweight patients with COPD is important. Exercise training can lead to improvements in weight gain, exercise capacity, and HRQL.
Acknowledgments This study was supported by Buddhist Tzu-Chi General Hospital grant TCRD-TPE-99-24.
References
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7. Palange P, Forte S, Onorati P, Paravati V, Manfredi F, Serra P, et al. Effect of reduced body weight on muscle aerobic capacity in patients with COPD. Chest 1998; 114:8-12. 8. Shoup R, Dalsky G, Warner S, Davies M, Connors M, Khan M, et al. Body composition and health-related quality of life in patients with obstructive airways disease. Eur Respir J 1997;10:1576-80. 9. Rabinovich RA, Ardite E, Mayer AM, Polo MF, Vilaro´ J, Argile´s JM, et al. Training depletes muscle glutathione in patients with chronic obstructive pulmonary disease and low body mass index. Respiration 2006; 73:757-61. 10. Tomoda K, Yoshikawa M, Itoh T, Tamaki S, Fukuoka A, Komeda K, et al. Elevated circulating plasma adiponectin in underweight patients with COPD. Chest 2007;132:135-40. 11. Itoh T, Nagaya N, Yoshikawa M, Fukuoka A, Takenaka H, Shimizu Y, et al. Elevated plasma ghrelin level in underweight patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:879-82. 12. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007; 176:532-55. 13. Wang KY, Chiang CH, Maa SH, Shau WY, Tarn YH. Psychometric assessment of the Chinese language version of the St. George’s Respiratory Questionnaire in Taiwanese patients with bronchial asthma. J Formos Med Assoc 2001;100:455-60. 14. American Thoracic Society. Standardization of spirometry. Am J Respir Crit Care Med 1995;152: 1107-36. 15. American Thoracic Society/European Respiratory Society. ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med 2002;166:518-624. 16. Jones PW, Quirk FH, Baveystock CM. The St. George’ Respiratory Questionnaire. Respir Med 1991;85:33-7. 17. Wilson CB, Jones PW, O’Leary C, Cole PJ, Wilson R. Validation of the St. George’s Respiratory Questionnaire in bronchiectasis. Am J Respir Crit Care Med 1997;156:536-41. 18. Wasserman K, Hansen JE, Sue DY, Stringer WW, Whipp BJ. Principles of exercise testing and interpretation: including pathophysiology and clinical applications. Philadelphia: Lippincott Williams & Wilkins; 2005. 19. American Thoracic Society, American College of Chest Physicians. ATS/ACCP statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med 2003;167:211-77. 20. Cavestri B, Wurtz A, Bart F, Nevie`re R, Aguilaniu B, Wallaert B. Cardiopulmonary exercise testing in patients with pectus excavatum. Rev Mal Respir 2010; 27:717-23. 21. Malek MH, Fonkalsrud EW, Cooper CB. Ventilatory and cardiovascular responses to exercise in patients with pectus excavatum. Chest 2003;124:870-82. 22. Wijkstra PJ, TenVergert EM, van der Mark TW, Postma DS, Van Altena R, Kraan J, et al. Relation of lung function, maximal inspiratory pressure, dyspnoea, and quality of life with exercise capacity in patients with chronic obstructive pulmonary disease. Thorax 1994;49:468-72. 23. Baarends EM, Schols AM, Pannemans DL, Westerterp KR, Wouters EF. Total free living energy
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expenditure in patients with severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155:549-54. Palange P, Galassetti P, Mannix ET, Farber MO, Manfredi F, Serra P, et al. Oxygen effect on O2 deficit and VO2 kinetics during exercise in obstructive pulmonary disease. J Appl Physiol 1995;78:2228-34. Debigare´ R, Marquis K, Coˆte´ CH, Tremblay RR, Michaud A, LeBlanc P, et al. Catabolic/anabolic balance and muscle wasting in patients with COPD. Chest 2003;124:83-9. Eid AA, Ionescu AA, Nixon LS, Lewis-Jenkins V, Matthews SB, Griffiths TL, et al. Inflammatory response and body composition in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;164:1414-8. Broekhuizen R, Wouters EF, Creutzberg EC, Schols AM. Raised CRP levels mark metabolic and functional impairment in advanced COPD. Thorax 2006;61:17-22. Nishimura Y, Tsutsumi M, Nakata H, Tsunenari T, Maeda H, Yokoyama M. Relationship between respiratory muscle strength and lean body mass in men with COPD. Chest 1995;107:1232-6. Engelen MP, Schols AM, Baken WC, Wesseling GJ, Wouters EF. Nutritional depletion in relation to respiratory and peripheral skeletal muscle function in out-patients with COPD. Eur Respir J 1994;7:1793-7. Arora NS, Rochester DF. Effect of body weight and muscularity on human diaphragm muscle mass, thickness, and area. J Appl Physiol 1982;52:64-70. Lands L, Pavilanis A, Charge TD, Coates AL. Cardiopulmonary response to exercise in anorexia nervosa. Pediatr Pulmonol 1992;13:101-7. Engelen MP, Schols AM, Does JD, Gosker HR, Deutz NE, Wouters EF. Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:1697-704. Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner CF, Wasserman K. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in
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patients with obstructive lung disease. Am Rev Respir Dis 1991;143:9-18. Perloff D, Grim C, Flack J, Frohlich ED, Hill M, McDonald M, et al. Human blood pressure determination by sphygmomanometry. Circulation 1993;88:2460-70. Romano C, Chinali M, Pasanisi F, Greco R, Celentano A, Rocco A, et al. Reduced hemodynamic load and cardiac hypotrophy in patients with anorexia nervosa. Am J Clin Nutr 2003;77:308-12. de Simone G, Scalfi L, Galderisi M, Celentano A, Di Biase G, Tammaro P, et al. Cardiac abnormalities in young women with anorexia nervosa. Br Heart J 1994; 71:287-92. Klimathianaki M, Vaporidi K, Georgopoulos D. Respiratory muscle dysfunction in COPD: from muscles to cell. Curr Drug Targets 2011;12:478-88. Terzano C, Ceccarelli D, Conti V, Graziani E, Ricci A, Petroianni A. Maximal respiratory static pressures in patients with different stages of COPD severity. Respir Res 2008;21:8. Gosker HR, Wouters EF, van der Vusse GJ, Schols AM. Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. Am J Clin Nutr 2000;71:1033-47. Nava S, Fracchia C, Callegari G, Ambrosino N, Barbarito N, Felicetti G. Weakness of respiratory and skeletal muscles after a short course of steroids in patients with acute lung rejection. Eur Respir J 2002; 20:497-9. Schols AM, Soeters PB, Mostert R, Pluymers RJ, Wouters EF. Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease: a placebo-controlled randomized trial. Am J Respir Crit Care Med 1995;152: 1268-74. Yquel RJ, Tessonneau F, Poirier M, Moinard J, Pillet O, Manier G. Peak anaerobic power in patients with COPD: gender related differences. Eur J Appl Physiol 2006;97:307-15.
Association of body mass index with exercise cardiopulmonary responses in lung function-matched patients with chronic obstructive pulmonary disease Chou-Chin Lan, MD, PhDa,b, Chiu-Ping Su, MSNc, Lih-Lih Chou, MSNc, Mei-Chen Yang, MDa,b, Chor-Shen Lim, MDa,b, Yao-Kuang Wu, MDa,b,* a
Division of Pulmonary Medicine, Buddhist Tzu-Chi General Hospital, Taipei Branch, Xindian City, Taipei, Taiwan, Republic of China b School of Medicine, Tzu-Chi University, Hualien, Taiwan, Republic of China c Institute of Head Nurse, Department of Nursing, Buddhist Tzu Chi General Hospital Taipei Branch, Xindian City, Taipei, Taiwan, Republic of China
article info
abstract
Article history: Received 1 October 2011 Revised 10 February 2012 Accepted 11 February 2012 Online 14 March 2012
Background and Objectives: Lung function is traditionally used to define the severity of chronic obstructive pulmonary disease (COPD). However, this does not exclude other factors. This study investigated the influence of body mass index (BMI) on exercise responses and quality of life in patients with COPD matched for values of forced expiratory volume in 1 second (FEV1).
Keywords: Chronic obstructive pulmonary disease Body mass index Exercise capacity Health-related quality of life
Methods: Underweight, normal-weight, and overweight patients with COPD, matched for FEV1, were studied. All patients were evaluated by spirometry, a cardiopulmonary exercise test, respiratory muscle strength, and, St. George’s Respiratory Questionnaire (SGRQ). Results: The baseline characteristics and mean FEV1 of the 3 groups were similar (P > .05). Respiratory muscle strengths and SGRQ scores were lowest in underweight patients (P < .05). In terms of exercise response, the lowest oxygen uptake at anaerobic threshold and peak exercise, the highest ventilatory equivalent, and the lowest oxygen pulse were evident in underweight patients (P < .05). Conclusions: Underweight patients with COPD had lower respiratory muscle strength, impaired exercise capacity, earlier anaerobic metabolism, ineffective ventilation, and poorer quality of life. Cite this article: Lan, C.-C., Su, C.-P., Chou, L.-L., Yang, M.-C., Lim, C.-S., & Wu, Y.-K. (2012, JULY/AUGUST). Association of body mass index with exercise cardiopulmonary responses in lung function-matched patients with chronic obstructive pulmonary disease. Heart & Lung, 41(4), 374-381. doi:10.1016/ j.hrtlng.2012.02.010.
Chou-Chin Lan and Chor-Shen Lim were responsible for study conception and design. Chou-Chin Lan, Chiu-Ping Su, and Lih-Lih Chou acquired the data. Chou-Chin Lan and Mei-Chen Yang were responsible for the analysis and interpretation of the data. Chou-Chin Lan drafted the manuscript. Yao-Kuang Wu was responsible for critical revision. Yao-Kuang Wu provided statistical expertise. Yao-Kuang Wu provided general supervision. * Corresponding author: Yao-Kuang Wu, MD, Division of Pulmonary Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, 289 Jianguo Road, Xindian City, Taipei County 23142, Taiwan, Republic of China. E-mail address: [email protected] (Y.-K. Wu). 0147-9563/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.hrtlng.2012.02.010
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The prevalence of underweight status among patients with chronic obstructive pulmonary disease (COPD) is about 20% to 40%.1 Underweight patients with COPD often demonstrate poor clinical condition, compared with nonunderweight patients.2-4 Limited exercise capacity and functional impairment are key features of COPD,5 and malnutrition leads to further exercise limitations and functional impairment in underweight patients with COPD.6,7 In addition, underweight patients with COPD often have poor health-related quality of life (HRQL).8 Schols et al showed that survival was reduced by almost half in COPD patients with cachexia, and that the differences in survival were not attributable to differences in severity according to spirometric criteria.4 Therefore, the issue of body mass index (BMI) in COPD is important. Although some studies involved BMIs in COPD, the number of such studies is limited.8,9 Those studies reported on COPD patients with different BMIs, although the subjects were not matched in terms of lung function, and the influence of airway obstruction in these studies cannot be ignored.8,9 In addition, these studies focused on exercise capacity and HRQL in patients with COPD.8,9 The exercise response and overall influence of BMI in patients with COPD are not fully understood. Therefore, further studies about BMI in patients with COPD are necessary. We studied the exercise capacity and HRQL of lung function-matched patients with different BMIs. We further analyzed their ventilator and circulatory responses to exercise, to investigate whether BMI influences exercise responses in patients with COPD. Understanding more about the association of BMI and COPD may help in clinical management. Thus, we aimed to investigate the association of BMI with: (1) resting pulmonary function and respiratory muscle strength, (2) symptoms and HRQL, (3) exercise capacity, (4) ventilatory responses during exercise, and (5) circulatory responses during exercise.
Methods Patient Selection We retrospectively analyzed 309 patients with COPD receiving cardiopulmonary exercise tests (CPETs) from August 2008 to March 2011. These patients with COPD were classified into underweight (BMI, <20 kg/m2), normal-weight (BMI, 20 to 25 kg/m2), and overweight (BMI, >25 kg/m2), according to previous studies.10,11 In our study, the inclusion criteria comprised: (1) diagnosis and severity of COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging of the disease;12 (2) no occurrence of COPD exacerbations for at least 3 months; and (3) ability of the patient to mobilize independently. The exclusion
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criteria comprised: (1) an exacerbation of COPD within 12 weeks of an exercise test; (2) a history of pneumoconiosis, bronchiectasis, pulmonary tuberculosis, primary pulmonary hypertension, pulmonary embolism, interstitial lung disease, malignancies, hepatic abnormalities, congestive heart failure, or recent surgery; (3) orthopedic impairment that would influence the exercise test; and (4) participation in pulmonary rehabilitation in the preceding 12 months. After applying the inclusion and exclusion criteria, 131 patients with COPD were enrolled in our analysis. Twenty-five of these 131 patients were underweight. The patients of normal weight and the overweight patients, matched for forced expiratory volume in 1 second (FEV1), were selected for further analysis. Therefore, 75 patients, matched for FEV1, were included, with 25 patients in each weight group. The research protocol was approved by the Ethics Committee of Buddhist Tzu-Chi General Hospital. Signed, informed consent was obtained from all patients.
Measurements Physiological parameters at rest were assessed according to spirometry and respiratory muscle strength, ie, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). The HRQL was assessed by the validated Chinese version of the St. George’s Respiratory Questionnaire (SGRQ).13 Physiological parameters during exercise were assessed by CPETs.
Resting Pulmonary Function Test and Ventilatory Muscle Strength Pulmonary function tests were performed using spirometry (Medical Graphics Corporation, St. Paul, MN), following the standards of the American Thoracic Society.14 The best flow-volume loop was used in the final data analysis. We assessed MIP and MEP using a standard mouthpiece and a direct dial pressure gauge (Respiratory Pressure Meter, Micro Medical Corporation, Rochester, United Kingdom). We measured MIP at the residual volume, and MEP was measured at total lung capacity. The highest value from at least 3 maneuvers was recorded.15
Health Status and Symptom Assessment The SGRQ is a self-administered questionnaire designed to measure the influence of chest disease on HRQL.13,16,17 The responses to its 50 items can be aggregated into an overall score, with 3 subscores for symptoms (8 items), activity (16 items), and impact (26 items). Responses are weighted and scores are calculated by dividing the summed weights by the maximum possible weight.13,16,17 Scores on the SGRQ range from 100 (worst possible health status) to 0 (best
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possible status), and higher scores indicate a poorer health status. The SGRQ was reported to be valid and reliable in patients with COPD, asthma, and bronchiectasis.13,16,17 Ratings of perceived exertion were reported by patients at rest and at the end of exercise tests on a 10-point Borg scale for dyspnea.
Cardiopulmonary Exercise Test All patients performed an incrementally progressive, symptom-limited exercise test on an electromagnetically braked cycle ergometer, in accordance with published guidelines (Lode Corival, Groningen, The Netherlands).18,19 The test consisted of measurements during 2 minutes of rest, followed by 2 minutes of unloaded pedaling and a ramp increase of load (increments of 10 watts/minute1) to maximal workload. Expired gas was analyzed breath-by-breath or in terms of oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), tidal volume (VT), and endtidal PCO2 (PETCO2), using the MedGraphics cardiopulmonary diagnostic system (Breeze suite 6.1, Medical Graphics Corporation). Heart rate (HR) was monitored continuously by 12-lead electrocardiography (ECG), and hemoglobin saturation was determined by pulse oximetry (SpO2). Blood pressure (BP), including systolic (SBP) and diastolic (DBP), were recorded at rest and after each 2 minutes of exercise. Patients were strongly encouraged to achieve their point of maximal exercise, until they could no longer continue because of severe dyspnea, leg fatigue, chest pain with ischemic ECG changes, a fall in SBP of 20 mm Hg from the highest value during the test, hypertension (SBP, 250 mm Hg systolic; DBP, 120 mm Hg), severe desaturation with SpO2 of 80%, sudden pallor, or faintness. The onset of anaerobic threshold (AT) was determined from a plot of VCO2 vs. VO2 (V-slope method), as previously reported.18,19 The ventilatory equivalent for CO2 (VEQ) was determined as the ratio of VE/VCO2 at AT. The oxygen pulse (O2P) was calculated as the ratio of VO2/ HR, and the respiratory exchange ratio (RER) as the ratio of VCO2/VO2.18,19 Peak VO2 and work rate (watts) were regarded as exercise capacity.20,21 Changes in VE, VT, respiratory rate (RR), and VEQ during exercise were regarded as ventilator responses during exercise, and changes in O2P, HR, and blood pressure (BP) during exercise were regarded as circulatory responses to exercise.20,21
Statistical Analysis All measurements are expressed as means standard deviations (SDs). Comparisons of parameters among the 3 groups were performed using one-way analysis of variance, followed by the Scheffe´ multiple comparison test. The Pearson c2 test was used to compare gender among the three groups. P < .05 was considered statistically significant. All statistical analyses were performed using SPSS for Windows (version 18.0, SPSS, Inc., Chicago, IL).
Results Anthropometric and Spirometric Data of the 3 COPD Groups The clinical characteristics and lung function of all patients with COPD are shown in Table 1. The mean BMI was 18.4 1.6 kg/m2 in underweight patients, 22.6 1.4 kg/m2 in normal-weight patients, and 27.6 2.4 kg/m2 in overweight patients (P < .001). The 3 groups demonstrated similar results regarding airflow obstruction (FEV1, forced vital capacity [FVC], and FEV1/ FVC) and age. The mean FEV1 was 50.0% 21.7% of the predicted value in underweight patients, 48.0% 18.3% of the predicted value in normal-weight patients, and 52.8% 19.9% of the predicted value in overweight patients (P > .05). The MIP and MEP were significantly lower in underweight patients compared with normalweight and overweight patients (both P < .05). However, no differences were evident in MIP and MEP between the normal-weight and overweight patients.
HRQL and Dyspnea in the 3 COPD Groups HRQL and Dyspnea are shown in Table 2. The SGRQ analysis showed that SGRQ total and impact scores were significantly higher in underweight patients compared with normal-weight and overweight patients (P < .05). The SGRQ scores of symptoms and activity were also higher in underweight patients, but without statistical significance (P > .05). The SGRQ scores (symptoms, impact, activity, and total) were similar in normal-weight and overweight patients (P > .05). The scores for dyspnea Borg scales at rest and at peak exercise were similar in the 3 groups (P > .05).
VO2 and VCO2 at Rest, AT, and Peak Exercise in the 3 COPD Groups Exercise capacity and AT are shown in Table 3. The VO2 at rest was similar in the 3 COPD groups (P > .05). However, the VO2 at AT or peak exercise was significantly lower in the underweight patients than in the normal-weight and overweight patients (P < .05). The VCO2 exhibited a trend similar to that of VO2. The RER at rest or at peak exercise was similar in the 3 groups (P > .05). The maximal workload was significantly lower in the underweight than in the normal-weight and overweight patients (P < .05).
Ventilator Response at Rest, AT, and Peak Exercise in the 3 COPD Groups Parameters of ventilatory response are shown in Table 4. The VT at rest or at peak exercise was lowest in underweight patients, although this did not reach not statistical significance (P ¼ .135 for VT at rest; P ¼ .296 for VT at peak exercise). The RR at rest was highest in underweight
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Table 1 e Baseline characteristics, pulmonary function, and respiratory muscle strength of underweight, normal-weight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value Gender (male/female) Age (years) BMI (kg/cm2) Weight (kg) Height (cm) FEV1/FVC (%) FEV1 (L) FEV1 (% predicted) FVC (L) FVC (% predicted) MVV (L/minute) MIP (cm H2O) MEP (cm H2O)
19/6 69.2 11.0 18.4 1.6y 47.4 7.3y 161.5 10.3 49.0 12.5 1.07 .49 50.0 21.7 2.19 .78 80.0 23.1 40.5 19.1 53.6 17.8 94.5 27.7
21/4 68.4 8.3 22.6 1.4* 59.4 7.5* 161.8 8.8 45.7 10.7 1.06 .48 48.0 18.3 2.31 .82 83.3 22.6 40.4 18.8 71.0 28.7* 119.3 44.7*
21/4 71.3 7.3 27.6 2.4*,y 71.9 10.5*,y 161.2 8.2 52.1 11.8 1.09 .51 52.8 19.9 2.07 .71 79.4 23.9 40.6 21.4 71.0 8.3* 116.8 40.4*
P ¼ .704 P ¼ .512 P < .000 P < .000 P ¼ .973 P ¼ .158 P ¼ 0.978 P ¼ .696 P ¼ .549 P ¼ .815 P ¼ .999 P ¼ .018 P ¼ .048
BMI, body mass index; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; MVV, maximum voluntary ventilation. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients. y P < 0.05, vs. normal-weight patients.
patients (P < .05). However, the RR at peak exercise was similar in the 3 groups (P > .05). The VE at rest and at peak exercise was also similar in the 3 groups (P > .05). The SpO2 and PETCO2 at rest, AT, and peak exercise were also similar in the 3 groups (P > .05). The VEQ was highest in underweight patients (P < .05).
Circulatory Response at Rest, AT, and Peak Exercise in the 3 COPD Groups Parameters of circulatory response are shown in Table 5. The O2P at peak exercise was significantly lower in underweight patients (6.0 1.4 mL beat1) than in normal-weight (7.3 1.9 mL beat1) or overweight (8.5 1.9 mL beat1) patients (P < .05). The HR at rest, AT, and peak exercise was similar in the 3 groups (P > .05). The SBP, DBP, and mean BP (MBP) at rest were similar in the 3 groups (P > .05). However, at peak exercise, the SBP was lowest in underweight patients (P < .05), whereas DBP and MBP lacked statistical significance (P ¼ .565 for DBP; P ¼ .101 for MBP).
Discussion Lung function is traditionally used to define the severity of COPD according to the GOLD criteria.12 However, this did not exclude the possibility that other factors such as BMI may affect exercise capacity and HRQL. The present study showed that BMI exerted an influence on COPD, independent of the degree of airway obstruction. This finding implies that low exercise capacity, respiratory muscle weakness, and poor HRQL are related not only to impaired lung function but also to low BMI. The influence of BMI on exercise capacity, AT, O2P, and HRQL should therefore be addressed. We think this study is important because
it analyzed more comprehensive measurements compared with previous studies. In addition, the patients in our study were lung function-matched, unlike the case in previous studies. The limitation of peak exercise capacity with functional impairment is an essential feature in patients with COPD.5 The relationship between lung function and exercise capacity is evident, becaus it represents lung parenchymal damage.22 As seen in our study, the relationship between BMI and exercise capacity is also important. Previous studies showed a correlation between BMI and exercise capacity.5,7 However, those studies did not perform lung function matching in their patients. Underweight patients with COPD demonstrated a lower exercise capacity and poorer HRQL, and the FEV1 was also lower in these underweight patients.5,7 The influence of airway obstruction could not be disregarded in those studies.5,7 The findings in the present study with lung function-matched patients support the idea that underweight status itself compromises exercise tolerance, leading to greater disability. Although the influence of BMI on exercise capacity was clearly established in previous studies, little attention has been given to its influence on HRQL. Our study contains the important finding that underweight patients with similar lung function also scored worse on the SGRQ. Even though Shoup et al found that underweight patients had a lower HRQL, the subjects in their study were not lung function-matched patients with COPD.8 In our study, we found that HRQL was poor in underweight patients with COPD, regardless of lung function. A decrease in body weight is primarily a consequence of disturbed energy balance in patients with COPD.23 Moreover, a hypermetabolic state is related to the excessive caloric expenditures dictated by the high energy requirements of respiratory muscles.24 In
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Table 2 e Health-related quality of life and dyspnea of underweight, normal-weight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value Borg dyspnea at rest Borg dyspnea at peak exercise SGRQ-total SGRQ-symptom SGRQ-activity SGRQ-impact
.2 .5 5.1 1.4 62.9 14.6 66.7 16.7 71.0 17.2 57.1 20.3
.5 .8 5.8 2.0 48.2 18.7 55.1 23.4 63.4 22.1 38.0 20.6*
.4 .6 5.3 1.9 49.1 19.5* 56.2 24.6 62.7 21.7 39.1 19.5*
P ¼ .291 P ¼ .349 P ¼ .007 P ¼ .125 P ¼ .289 P ¼ .002
COPD, chronic obstructive pulmonary disease; SGRQ, St. George’s Respiratory Questionnaire. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients.
Table 3 e Exercise capacity, anaerobic threshold, and respiratory exchange ratio of underweight, normalweight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value VO2 at rest (mL/minute) VO2 at AT (mL/minute) VO2 at peak exercise (mL/minute) VO2 at peak exercise (%) VCO2 at rest (mL/minute) VCO2 at AT (mL/minute) VCO2 at peak exercise (mL/minute) RER at rest RER at peak exercise WR (watts)
269.1 34.8 510.0 115.0y 727.3 182.5 48.2 18.9 240.7 38.4 492.5 117.8 779.1 241.5 .89 .09 1.06 .14 44.7 19.4
263.6 45.9 621.0 119.8* 927.1 251.4* 57.2 15.6* 240.5 38.4 593.0 108.3* 1028.2 295.7* .92 .11 1.08 .10 61.7 26.7*
272.0 52.4 719.8 131.4*,y 1052.1 284.8* 71.2 29.4* 246.5 38.7 671.7 102.9* 1089.5 298.4* .92 .10 1.04 .11 67.2 23.5*
P P P P P P P P P P
¼ .796 ¼ .000 ¼ .000 ¼ .002 ¼ .822 ¼ .000 ¼ .000 ¼ .472 ¼ .428 ¼ .003
AT, anaerobic threshold; COPD, chronic obstructive pulmonary disease; RER, respiratory exchange ratio; VCO2, carbon dioxide output; VO2, oxygen uptake; WR, work rate. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients. y P < 0.05, vs. normal-weight patients.
addition, COPD is recognized as a disease of systemic inflammation.25-27 Systemic inflammation and oxidative stress are likewise potential mechanisms for the catabolic state resulting in the development of underweight status.25-27 Malnutrition and caloric deprivation are therefore common consequences in patients with COPD, and often lead to muscle atrophy, contributing to respiratory and peripheral muscle weakness.28,29 The loss of diaphragm muscle force was also reported.30 Therefore, a lower BMI may imply a greater severity of disease, even with the same lung function. A lower peak O2P and earlier anaerobic metabolism (lower AT) during exercise was evident in underweight patients in the present study. Invasive hemodynamic measurements during the exercise test were not performed. However, on the basis of the Fick equation, the lower O2P during exercise suggests a lower stroke volume, arteriovenous oxygen difference, or both.18 In underweight patients, a depletion of cardiac muscle mass decreases the stroke volume.31 A low body mass also exerts negative effects on muscle aerobic capacity.7 Both lower stroke volume and negative muscle aerobic capacity lead to earlier anaerobic metabolism during exercise.31 Earlier anaerobic metabolism and lower stroke volume in underweight
patients will lead to earlier lactic acid production during exercise, and lactemia during exercise imposes additional respiratory stimuli, increases ventilation, and heightens dyspnea.32,33 As such, a lower O2P and earlier anaerobic metabolism are factors causing a lower exercise capacity in underweight patients. These factors, together with the additional burdens of airway obstruction, deconditioning, and respiratory and peripheral muscle weakness, lead to limitations in exercise capacity. Underweight and nonunderweight patients with COPD exhibited similar HRs and BPs at rest in this study. However, SBP at peak exercise was significantly lower in underweight patients, implying a lower BP response during exercise. The SBP was labile and changed more rapidly during exercise, and this finding may explain the significant difference in SBP as opposed to DBP, which was slow to respond to exercise. As exercise intensity increases, the reflex control of the distribution of cardiac output causes changes in BP and systemic vascular resistance.34 Although the net result is systemic vasodilatation with a fall in systemic vascular resistance during exercise, SBP typically rises progressively with the increase in cardiac output.19 If BP does not increase with exercise, a cardiac limitation
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Table 4 e Ventilatory responses during exercise in underweight, normal-weight, and overweight patients with COPD Underweight Normal weight Overweight P value (n ¼ 25) (n ¼ 25) (n ¼ 25) VE at rest (L/minute) VE at AT (L/minute) VE at peak exercise (L/minute) RR at rest (breaths/minute) RR at peak exercise (breaths/minute) VT at rest (mL) VT at peak exercise (mL) VEQ SpO2 at rest (%) SpO2 at peak exercise (%) dSpO2 (peak rest) (%) PETCO2 at rest (mm Hg) PETCO2 at peak exercise (mm Hg) dPETCO2 (peak rest) (mm Hg)
12.2 2.8 18.3 4.1 29.4 10.0 21.2 4.5 33.5 7.2 588.8 142.9 907.9 318.3 41.8 6.9 96.2 2.6 93.2 4.5 2.9 3.5 33.7 5.8 38.0 8.3 4.3 5.1
11.6 3.2 19.7 5.5 32.4 11.8 17.6 4.2* 31.2 7.0 680.6 196.3 1056.8 363.3 37.3 6.0* 96.0 2.1 93.0 3.3 3.0 2.4 33.5 5.8 40.2 7.3 6.7 4.8
12.0 3.6 20.7 4.7 33.6 14.1 19.7 4.2 33.4 8.0 615.0 149.7 1012.2 347.0 34.5 5.0* 95.9 1.9 92.6 4.1 3.2 2.9 36.8 5.4 42.6 7.0 5.9 4.8
P ¼ .795 P ¼ .236 P ¼ .450 P ¼ .017 P ¼ .471 P ¼ .135 P ¼ .296 P ¼ .000 P ¼ .906 P ¼ .866 P ¼ .929 P ¼ .081 P ¼ .103 P ¼ .189
COPD, chronic obstructive pulmonary disease; dPETCO2, difference of PETCO2 at peak exercise and rest; dSpO2, difference of SpO2 at peak exercise and rest; PETCO2, end-tidal PCO2; RR, respiratory rate; SpO2, oxygen saturation; VE, minute ventilation; VEQ, ventilatory equivalent for carbon dioxide; VT, tidal volume. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < 0.05, vs. underweight patients.
Table 5 e Circulatory responses during exercise in underweight, normal-weight, and overweight patients with COPD Underweight (n ¼ 25) Normal weight (n ¼ 25) Overweight (n ¼ 25) P value O2P (mL beat1) HR at rest (beats/minute) HR at peak exercise (beats/minute) SBP at rest (mm Hg) DBP at rest (mm Hg) MBP at rest (mm Hg) SBP at peak exercise (mm Hg) DBP at peak exercise (mm Hg) MBP at peak exercise (mm Hg)
6.0 86.0 121.3 123.6 69.6 87.6 157.1 75.8 102.9
1.4 15.2 17.8 19.8 13.5 13.6 26.0 14.1 14.3
7.3 1.9* 86.5 11.3 127.1 17.2 127.0 17.4 72.6 11.3 90.7 11.4 176.0 21.9* 80.2 16.2 112.1 15.1
8.5 1.9* 86.1 12.1 123.6 14.0 126.5 16.0 69.7 11.1 88.6 10.7 169.4 26.6 79.1 14.9 109.2 16.5
P ¼ .000 P ¼ .989 P ¼ .462 P ¼ .766 P ¼ .609 P ¼ .644 P ¼ .030 P ¼ .565 P ¼ .101
COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; HR, heart rate; MBP, mean blood pressure; O2P, oxygen pulse; SBP, systolic blood pressure. P values ¼ comparisons between underweight, normal-weight, and overweight patients. * P < .05, vs. control subjects.
is suggested.19 We found that underweight patients demonstrated a poor SBP response to exercise, and the lower O2P in these patients implies a lower stroke volume. Previous studies showed that malnutrition causes a decrease of left ventricular mass and systolic dysfunction with low stroke volume.35,36 Therefore, a lower SBP response during exercise occurs in underweight patients. Respiratory muscle weakness is also a cardinal feature of COPD.37 In a previous study, respiratory muscle strength was lower in more severe cases of COPD.38 However, in our present study, respiratory muscle strength was also lower in underweight patients, although they exhibited the same lung function. Respiratory muscle weakness in underweight patients with COPD involves multiple factors,
including malnutrition, muscular atrophy, and steroidinduced myopathy.37-40 Malnutrition predisposes patients to a loss of muscle mass in the diaphragm and in skeletal and respiratory muscle.39 Systemic corticosteroids are frequently used to manage COPD with acute exacerbations. However, their use was reported to have some negative consequences, including steroid myopathy of the respiratory and skeletal muscles.40 All patients in our study were stable, and none had received systemic steroids for at least 1 year. Oxidative stress and systemic inflammation lead to the damage of muscle proteins, which also contributes to diaphragm and respiratory muscle abnormalities.37 Our study revealed respiratory muscle weakness in underweight patients, accompanied by higher VEQ during exercise. The higher VEQ in our underweight
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patients implies poor ventilatory efficiency during exercise, which may be explained by respiratory muscle weakness.
Limitations of This Study This study has some limitations. First, we did not check the fat-free mass (FFM) in our patients. A reduced FFM may occur despite normal BMI.41 Second, most of these patients with COPD were male. We need to confirm our results in female patients, especially because considerable differences in body composition exist between males and female patients.42 Exercise responses may also be different between female and male patients.
Conclusions After analyzing the exercise responses of COPD patients with different BMIs, this study showed that underweight patients with COPD demonstrated lower respiratory muscle strength, impaired exercise capacity, earlier anaerobic metabolism, lower O2P, ineffective ventilation, and poor HRQL. The management of underweight patients with COPD is important. Exercise training can lead to improvements in weight gain, exercise capacity, and HRQL.
Acknowledgments This study was supported by Buddhist Tzu-Chi General Hospital grant TCRD-TPE-99-24.
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