j appl physiol 2011 ora japplphysiol.01131
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Effect of Obesity on Respiratory Mechanics during Rest and Exercise in1
COPD23
4
Authors:5
Josuel Ora, Pierantonio Laveneziana, Karin Wadell, Megan Preston, Katherine A. Webb, Denis6
E. ODonnell.7
8
Affiliation:9
Respiratory Investigation Unit, Department of Medicine, Queens University and Kingston10
General Hospital, Kingston, Ontario, Canada.11
12
Correspondence to: Denis E. ODonnell, MD, FRCP(I), FRCP(C)13
102 Stuart Street, Kingston, Ontario, Canada K7L 2V614
E-mail: [email protected]
16
Running head: Obesity effects on exercise in COPD17
18
19
Articles in PresS. J Appl Physiol (February 24, 2011). doi:10.1152/japplphysiol.01131.2010
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ABSTRACT20
21
The presence of obesity in COPD appears not to be a disadvantage with respect to22
dyspnea and weight-supported cycle exercise performance. We hypothesized that one23
explanation for this might be that the volume-reducing effects of obesity convey mechanical and24
respiratory muscle function advantages. Twelve obese COPD (OB) (FEV1=60%predicted; body25
mass index (BMI)=321 kg/m2; meanSD) and 12 age-matched, normal-weight COPD (NW)26
(FEV1=59%predicted; BMI=232 kg/m2) subjects were compared at rest and during symptom-27
limited constant-work-rate exercise at 75% of their maximum. Measurements included28
pulmonary function tests, operating lung volumes, esophageal pressure and gastric pressure. OB29
vs. NW had a reduced total lung capacity (109 vs. 124 %predicted; p
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INTRODUCTION45
46
Obesity is increasingly recognized as an important comorbidity in patients with COPD (11,43).47
The coexistence of these two common conditions has potentially important physiological (34),48
clinical and even prognostic implications that are currently poorly understood (13).49
In patients without airway disease, obesity is associated with a restrictive ventilatory50
deficit due to reduced respiratory system compliance (4,27,36). The lower static lung volumes in51
obesity predispose to increased airway resistance and expiratory flow limitation (33,35). The52
lower resting end-expiratory lung volume (EELV) [and expiratory reserve volume (ERV)] in53
obese individuals is associated with an increased resting inspiratory capacity (IC) compared with54
lean individuals (18,33). We have suggested that this, in conjunction with dynamic increases in55
EELV during exercise towards the predicted natural relaxation volume of the respiratory system,56
may counterbalance some of the negative mechanical effects of obesity (3,33).57
The evaluation of the combined mechanical effects of mild obesity and COPD is highly58
relevant given the evidence that EELV diminishes exponentially with increasing BMI and that59
significant volume effects are seen even in the overweight range (29,18). We have recently60
reported that resting IC, symptom-limited peak oxygen uptake (VO2) and exertional dyspnea61
intensity ratings were not negatively impacted by obesity in patients with COPD (34). A recent62
retrospective analysis of a larger COPD cohort again confirmed that increased BMI was not a63
disadvantage with respect to resting IC, constant work rate cycle endurance time or dyspnea64
intensity (20). The main objective of the current study was to better understand this surprising65
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factors. Potential negative influences include increased elastic loading of the respiratory69
muscles, increased metabolic and ventilatory requirements and increased airway dysfunction and70
pulmonary resistance at the lower absolute lung volumes. Potential positive counterbalancing71
effects include improved operating length of the diaphragm at a lower EELV and increased72
driving pressure for expiratory flow due to increased static lung recoil. The current study73
extends our previous work by measuring these complex interactions in some detail. Specifically,74
our objective was to determine the effect of obesity on ventilatory mechanics and respiratory75
muscle function during rest and exercise in patients with COPD. Our hypothesis was that76
obesity in COPD would be associated with increased static lung recoil pressure, a reduced77
EELV, a preserved or enhanced IC, increased intra-abdominal pressure and improved78
diaphragmatic function during exercise. These obesity-related physiological differences would79
ensure that neuromechanical uncoupling of the respiratory system and the associated exertional80
dyspnea are not further amplified when compared with normal weight COPD patients. To test81
this hypothesis, we compared dyspnea ratings, operating lung volumes, breathing pattern,82
respiratory pressure-derived measurements at rest and during symptom-limited constant work83
rate cycle exercise in obese and normal weight patients with moderate to severe COPD.84
85
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METHODS86
87
Subjects88
We studied 12 subjects with mild obesity (OB) (BMI 30.0-34.9 kg/m2) and 12 age-matched89
normal-weight subjects (NW) (BMI 18.5-24.9 kg/m2). Subjects were clinically stable men or90
women, 55-85 years of age, with a clear diagnosis of COPD (FEV1/FVC
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DL; SensorMedics, Yorba Linda, CA) according to recommended standards (1,21,24,46). Static111
lung compliance (CLst) and static lung recoil pressure (PLst) were also measured (Vmax229d;112
SensorMedics) (15). Measurements were expressed as percentages of predicted normal values113
(5,7,8,9,16,19,26); predicted inspiratory capacity (IC) was calculated as predicted TLC minus114
predicted FRC.115
Symptom-limited exercise tests were conducted on an electrically braked cycle ergometer116
(Ergometrics 800S; SensorMedics) with a cardiopulmonary exercise testing system (Vmax229d;117
SensorMedics) as previously described (30). Incremental tests consisted of a 1-min warm-up of118
loadless pedaling followed by 1-min increments of 10 W each. CWR tests consisted of a 1-min119
warm-up followed by an increase in work rate to 75% of the maximal incremental work rate;120
endurance time was defined as the duration of loaded pedaling. Measurements included: breath-121
by-breath cardiopulmonary and metabolic parameters; intensity of dyspnea (breathing122
discomfort) and leg discomfort rated using the 10-point Borg scale (6); operating lung volumes123
derived from IC maneuvers (31); esophageal pressure (Pes)- and gastric pressure (Pga)-derived124
respiratory mechanical measurements collected continuously with an integrated data-acquisition125
setup (30). Exercise parameters were compared with the predicted normal values of Jones (17).126
Peak VO2 was standardized as a percentage of the predicted normal value corrected for ideal127
body weight (47). Ventilation (VE) was compared with the maximal ventilatory capacity128
(MVC) estimated by multiplying the measured FEV1 by 35 (14).129
130
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Sniff and cough maneuvers were performed pre-exercise at rest and immediately at end-exercise134
to obtain maximum values for Pes (Pes,sniff), Pdi (Pdi,sniff) and Pga (Pga,cough) (1).135
The tidal swing (Pes,tidal) and the inspiratory swing (Pes,insp) were defined as the136
amplitude of the Pes waveform during tidal breathing and during inspiration, respectively.137
Accepted formulae were used to calculate: total lung resistance (RL); dynamic lung compliance138
(CLdyn); the pressure-time product of the respiratory (PTPes), diaphragm (PTPdi) and expiratory139
muscles (PTPga); and the tension-time index of the diaphragm (TTIdi) and the inspiratory140
muscles (TTIes) (1,45). Activation of the expiratory muscles was evaluated by measurement of141
the expiratory gastric rise (Pga,rise) and the peak expiratory Pga (Pga,exp) during tidal breathing142
(48). End-expiration (EE) was the beginning of the inspiratory effort from the Pes waveform.143
Dynamic intrinsic positive end-expiratory pressure (PEEPi) was measured as the negative144
deflection in Pes from EE to the onset of inspiratory flow (46) and corrected (PEEPi,corr) by145
subtracting Pga,rise (28). The ventilatory muscle recruitment (VMR) index was determined as146
the slope of the line between points of zero flow at end-expiration (EE 0flow) and end-147
inspiration (EI0flow) for the Pga-Pes plots (Pga/Pes): negative slopes represent increased148
contribution by the diaphragm, more positive slopes represent increased contribution by149
inspiratory muscles of the ribcage and the expiratory muscles (23).150
151
Statistical Analysis152
Results are expressed as meansSD unless otherwise specified. A p
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(i.e., rest, a standardized exercise time of 2-min, peak exercise) meant that an uncorrected p157
value of
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RESULTS163
164
Twelve COPD patients with mild obesity (OB) and 12 age-, gender- and FEV1-matched normal-165
weight (NW) COPD patients were studied (Table 1). Chronic activity-related dyspnea was of166
moderate degree (i.e., shortness of breath while walking or climbing stairs) and largely similar167
across groups. Measurements of work rate, VO2 and VE at the peak of incremental cycle168
exercise were also similar across groups. The presence of the following comorbidities was169
balanced between groups: controlled hypertension (n= 6 OB, 5 NW), hypercholesterolemia (6170
OB, 4 NW), diabetes mellitus type 2 (2 OB, 2 NW), and stable ischemic heart disease (2 OB, 2171
NW). Chest CT scans done clinically were available for evaluation of emphysema in 6 NW and172
10 OB subjects: emphysema was present in all 6 (4 mild, 2 moderate) of these NW subjects and173
in 8 (3 mild, 5 moderate-severe) out of the 10 OB subjects.174
175
Pulmonary Function and Static Respiratory Mechanical Measurements176
Resting pulmonary function and respiratory mechanical measurements are summarized in Table177
2. Compared with NW, OB had a significantly (p
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between 10-40 W. Within each group, the peak VO2 and VE were similar for the incremental188
(Table 1) and CWR (Table 3) cycle tests.189
Cardiopulmonary responses to the CWR exercise test are summarized in Table 3 and190
shown in Figure 1. The CWR work rate (5316 and 5429 watts) and exercise endurance time191
(6.02.1 and 5.73.5 min) were similar in OB and NW, respectively. At the end of the CWR192
test, both groups stopped when they reached a critical ventilatory reserve: VE/MVC >85% and193
a reduced IRV
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Respiratory muscle/mechanical measurements are provided in Table 4. Pressure-derived211
measurements were largely similar in the OB and NW groups at rest, except expiratory and end-212
expiratory Pes and Pga were significantly (p
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(partial r=0.711), IRV%prTLC (partial r=0.707), VT/IC (partial r=0.710) and tidal Pes/Pes,sniff234
(partial r=0.678). PTPes/min (partial r=0.873), tidal Pes/Pes,sniff (partial r=0.665) and VT/IC235
(partial r=0.841) increased in direct proportion (p
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DISCUSSION239
240
The main findings of this study are as follows: 1) at rest, static lung volumes were lower, while241
PLst and Pga were higher in the OB compared with the NW groups; 2) exercise performance was242
not diminished in the obese; 3) despite lower absolute operating lung volumes, pulmonary243
resistance during exercise was not increased in OB; 4) ventilatory muscle recruitment patterns244
were broadly similar in the two groups apart from minor delays early in exercise in the increase245
in the VMR index determined from Pga/Pes plots (i.e., diaphragmatic de-recruitment) in the246
obese; and 5) resting IC, effort-displacement ratios and dyspnea/VE plots during exercise were247
not significantly affected by the presence of mild obesity.248
Patients in the two COPD groups were well matched for smoking history, severity of249
airway obstruction (FEV1), distribution of comorbidities and sex representation. They showed250
comparable reduction in exercise capacity (mean peak VO2 was reduced by ~30% compared251
with predicted normal values) with severe exertional dyspnea due to limiting respiratory252
mechanical constraints. Thus, at the limits of tolerance, breathing reserve (as reflected by high253
VE/MVC and VT/IC ratios) was critically reduced in both groups. Peak symptom-limited VO2254
was similar during the incremental and CWR cycle tests in both groups. This confirms that the255
CWR cycle endurance test was indeed a maximal effort test: physiological limits were reached256
and patients expended maximal motivational effort and reported severe dyspnea.257
258
Differences in Resting Respiratory Mechanics259
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reflects the decreased chest wall and lung compliance known to be associated with obesity263
(27,36,37,40). Despite the lower lung volumes in OB, plethysmographically-determined airway264
resistance and other measures of airway obstruction were not significantly increased.265
The elastic properties of the lung were different in OB and NW. Thus, the static lung266
elastic recoil as measured by PLst and the coefficient of retraction was greater, and closer to267
values predicted for health, in OB. We believe that differences in lung elastance reflect268
independent effects of obesity in patients with the heterogeneous pathophysiology of COPD269
rather than the fortuitous selection of different clinical phenotypes of COPD in the obese and270
lean groups (i.e., airways disease versus emphysema predominant, respectively): 1) we excluded271
underweight patients with clinically overt advanced emphysema; 2) DLCO was moderately272
reduced and not significantly different across the two groups; 3) although patients in the OB273
COPD group had comparatively lower lung volumes they still had had significant lung274
hyperinflation (FRC = 130% predicted) and; 4) qualitative radiological assessments of available275
CT scans in 10/12 obese COPD patients indicated the presence of structural emphysema ranging276
from mild to moderate severity in the majority.277
Intra-abdominal pressure measured by gastric balloon (in the sitting position) in a278
subgroup of patients was consistently elevated in OB by close to 10 cmH2O compared with NW.279
This likely reflects the mass loading effects of adipose tissue on the chest wall and abdomen280
(39,41). Measures of static respiratory muscle strength (including the diaphragm) were not281
significantly higher in the obese group despite the significantly lower EELV. Lack of inter-282
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Differences in Dynamic Respiratory Mechanics and Muscle Function during Exercise286
Peak symptom-limited VO2 (expressed as a percentage of predicted based on ideal body287
weight), exercise endurance times and dyspnea intensity ratings were similar in both groups. In288
contrast to our previous study using incremental cycle exercise, the rise in VO2 and VE was not289
significantly increased in the OB versus the NW group during CWR exercise. This reflects the290
balance between the modestly increased metabolic load in OB and improved ventilatory291
efficiency in this group: ventilatory equivalent for CO2 was lower at rest and during exercise in292
OB (Figure 1). A better ventilatory efficiency is consistent with the notion that ventilation-293
perfusion relations were less disrupted in the OB patients during exercise (49). The finding of a294
lack of group differences in ventilatory responses to exercise was fortuitous with respect to the295
comparison of dynamic mechanics and respiratory muscle performance that we undertook.296
Despite the relatively lower lung volumes in OB, the ability to generate maximal tidal297
expiratory flow rates and to increase alveolar ventilation in pace with metabolic demand was not298
compromised to a greater extent in OB than in NW. Thus, the changes in PETCO2 and SpO2 from299
rest to exercise termination were similar in both groups. It is possible that in the OB group, the300
better preserved PLst (and the attendant increased driving pressure for expiratory flow)301
compensated for the possible disadvantage with respect to airway function of breathing at lung302
volumes closer to residual volume. It is interesting to speculate that better preservation of the303
elastic properties of the lungs and in operating lung volumes seen in the obese group may lead to304
improved airway and respiratory muscle function. We could find no evidence of greater305
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is noteworthy that measured pulmonary resistance was not increased in OB despite the lower309
EELV (Figure 3). In fact, in contrast to NW, pulmonary resistance transiently but consistently310
fell slightly at the onset of exercise as EELV dynamically increased. This suggests the presence311
of a greater lung volume-dependent component in the increased resistance in OB compared with312
control.313
The static strength of the inspiratory and expiratory muscles (measured at rest) was not314
diminished at the limits of tolerance in either group. Intra-abdominal pressures were significantly315
elevated at rest and to a similar degree throughout exercise. However, the pattern of expiratory316
muscle activation (measured by Pga,rise) was similar in both groups. The pressure-time product317
and the tension-time index of the inspiratory and expiratory muscles during exercise were also318
similar.319
We were particularly interested in comparing diaphragmatic function in obese and lean320
COPD as the lower absolute lung volumes (by almost 1.0 L) and increased intra-abdominal321
pressures in OB patients could theoretically optimize the configuration (i.e., cephaloid shift) and322
length-tension relations of this muscle. However, we were unable to show any such advantages323
in the OB group other than a minor delay in the time course of de-recruitment of the diaphragm324
(and recruitment of accessory muscles) during early exercise in the OB compared with NW325
patients as indicated by analysis of the tidal Pes and Pga plots (Figure 4) (23,25). The pressure-326
time product and pattern of rise in Pdi during exercise were not different in the two groups. The327
lack of a significant between-group difference in Pga is probably related to inadequate power as328
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However, measures of CLdyn and PEEPi during exercise were not significantly different between332
groups. This contention that the elastic load is increased in obesity is supported by the finding333
that the pressure requirements to generate IC of similar magnitude at rest and serially throughout334
exercise were consistently higher in the obese patients (Figure 2B). It is noteworthy that during335
spontaneous breathing throughout exercise, tidal pressure swings (for a similar VT) relative to336
maximum were not different between the groups suggesting that the net load-capacity ratio of the337
respiratory muscles was essentially similar.338
339
Lack of Increase in Exertional Dyspnea Intensity in Obesity340
341
In contrast to our previous study (34), dyspnea/VE slopes in OB were not lower but similar to342
that of NW during exercise. This finding confirms the results reported by Laviolette et al.(20) in343
a large group of men with COPD and lung hyperinflation using a similar CWR protocol. There344
are several possible reasons for the apparent disparity between results of our two studies. 1) This345
study, unlike the previous study (n=18 per group)(34), may not have been sufficiently powered346
to detect significant differences in dyspnea between the groups. 2) The current study includes347
patients with only mild obesity (BMI 30-35 kg/m2) and more moderate airway obstruction, while348
our previous study included subjects with a greater BMI range and more severe COPD. We have349
recently reported that the volume-reducing effects of increased BMI are most pronounced in350
those with severe COPD (29). We postulate, therefore, that the effects of obesity on operating351
lung volumes would be greater and more consistent in a sample of patients with higher BMI and352
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in this study (CWR) was different from that used in our previous study (incremental). 4)356
Relatively small sample sizes in both studies can potentially result in greater variability in357
physiological responses within and between studies (low power).358
The relationship between dyspnea intensity and VE during exercise in COPD reflects the359
extent of the underlying mechanical abnormalities and respiratory muscle function. Thus,360
manipulations of the mechanical load by bronchodilators in COPD patients have been shown to361
consistently affect this relationship; dyspnea is diminished at a given VE (38). The finding that362
dyspnea/VE plots were similar in obese and lean COPD groups bolsters the argument that the363
net balance between intrinsic mechanical loading of the respiratory muscles and their maximal364
force-generating capacity was similar. We have previously argued that the IC is an important365
predictor of dyspnea intensity in COPD (31). The smaller the IC, the more VT encroaches during366
exercise on the upper reaches of the respiratory systems sigmoidal pressure-volume curve where367
there is widening disparity between central neural drive and the mechanical response of the368
respiratory system, i.e., neuromechanical uncoupling. Despite the difference in absolute lung369
volumes, the dynamic IC and IRV were similar throughout exercise in both groups so it is not370
surprising that the relationship between contractile respiratory muscle effort and VT displacement371
(i.e., effort-displacement ratio) and corresponding dyspnea intensity ratings were also similar.372
Moreover, by correlative analysis, previously established contributory factors to dyspnea373
intensity which included indices of mechanical constraints on tidal volume expansion (VT/IC,374
IRV) and increased respiratory effort (pressure-time product, Pes/Pes,sniff) were similar across375
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Limitations379
Our patients had mild to moderate increases in BMI and the results may not be applicable to380
patients with morbid obesity. Accurate measurements of body composition and adipose tissue381
distribution were not available to confirm and quantify the extent of obesity. However, recent382
reports suggest that mechanical derangements of obesity are more closely correlated with383
increasing BMI than with fat distribution patternsper se (2,44). We believe that the changes in384
static lung volumes and resting respiratory mechanics in higher BMI group are consistent with385
the presence of significant obesity. We may have underestimated the mechanical consequences386
in the OB group as measures of chest wall compliance were not available. Estimates of fat-free387
mass were higher in subsets of OB than in NW which raises the possibility that increased skeletal388
muscle strength played a role in maintaining exercise performance in the former. Our studies389
were conducted using cycle ergometry, thus, our results may have been different had we used390
treadmill where the metabolic load is known to be greater.391
392
In conclusion, increased BMI was shown to have consistent effects on static lung recoil393
pressure and on operating lung volumes and ventilatory efficiency during exercise, all of which394
were potentially advantageous. There were small but consistent improvements in pulmonary395
resistance and diaphragmatic function early in exercise in OB that were not seen in NW. In396
obesity, the lower EELV did not compromise airway function likely because of the preservation397
of static lung recoil pressure driving expiratory flow. Furthermore, the increased elastic loading398
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lack of greater respiratory discomfort or exercise curtailment in obese COPD patients402
fundamentally reflects the fact that, regardless of differences in absolute lung volumes, the403
resting IC was similar to the lean group. Thus, breathing pattern, the dynamic performance of the404
respiratory muscles and effort-displacement ratios were remarkably similar throughout exercise405
in lean and obese COPD patients.406
407
ACKNOWLEDGEMENTS: The authors wish to acknowledge Yuk-Miu Lam, PhD408
(Department of Community Health & Epidemiology, Queens University) for providing his409
statistical expertise.410
GRANTS: Canadian/OntarioThoracic Society Grant-in Aid411412
DISCLOSURES: The authors have no conflicts of interest related to this manuscript to report.413
414
415
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544
545
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TABLE 1. Subject characteristics546
NW (n=12) OB (n=12)
Male, n (%) 6 (50) 6 (50)
Age, yrs 68 8 68 4
Height, cm 169 13 167 9
Weight, kg 67.3 12.0 90.3 12.1 *
Weight, % of ideal 95 8 131 5 *
Body mass index, kg/m2
23.4 1.8 32.2 1.2 *
Smoking history, pack-yrs 61 35 68 54
COPD duration, yrs 8 6 10 10
Baseline Dyspnea Index,focal score 0-12:
Magnitude of Effort 0-4
Magnitude of Task 0-4
Functional Impairment 0-4
6.7 1.2
2.4 0.5
1.9 0.3
2.3 0.8
6.2 0.8
1.8 0.4 *
1.8 0.5
2.6 0.7
Medical Research Council
dyspnea scale, 1-5 2.4 0.7 2.7 0.8
Peak incremental work rate,
watts (% predicted maximum)
71 36
(56 20)
70 19
(59 21)
Peak incremental VO2, L/min
(% predicted maximum)
1.14 0.58
(73 19)
1.18 0.31
(71 18)
Peak incremental VE, L/min (%
estimated MVC)
43.7 24.1
(95 15)
39.2 8.6
(92 18)
Values are means SD.547
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TABLE 2. Pulmonary function and static respiratory mechanical measurements556
NW OB
FEV1, L (%predicted) 1.33 0.64 (59 17) 1.26 0.21 (60 13)
FVC, L (%predicted) 3.10 1.18 (95 16) 2.80 0.60 (92 20)
FEV1/FVC,% 42 8 47 12
PEFR, L/s (%predicted) 4.4 1.4 (68 16) 4.4 0.7 (73 16)
FEF50, L/s (%predicted) 0.5 0.4 (12 8) 0.5 0.2 (14 6)
TLC, L (%predicted) 7.44 1.97 (124 15) 6.35 1.66 (109 30 *)IC, L (%predicted) 2.24 0.86 (81 18) 2.18 0.35 (84 15)
FRC, L (%predicted) 5.20 1.37 (158 27) 4.18 1.51 (130 38 *)
RV, L (%predicted) 3.83 1.04 (170 43) 3.42 1.29 (154 53)
RV/TLC, % 52 11 52 9
ERV, L (%predicted) 1.37 0.69 (134 50) 0.76 0.42 * (80 38 *)
sRaw, cmH2Os (%predicted) 22.5 9.3 (544 218) 21.5 11.8 (512 270)
DLCO, mL/min/mmHg (%predicted) 13.9 6.5 (75 26) 14.6 5.0 (67 20)
DLCO/VA, mL/min/mmHg/L
(%predicted)2.86 0.69 (77 16) 3.45 0.88 (93 23)
MIP, cmH2O (%predicted) -67 22 (89 30) -76 16 (108 38)
MEP, cmH2O (%predicted) 121 28 (75 17) 125 46 (77 24)CLst, L/cmH2O 0.37 0.13 0.29 0.12
PLst, cmH2O (%predicted) 21.3 5.9 (77 37) 27.4 8.1 * (97 25)
Coefficient of retraction, cmH2O/L 3.1 1.4 4.5 1.5 *
Sniff Pes, cmH2O -64 18 -65 11
Sniff Pdi, cmH2O 114 27 127 25
Cough Pga, cmH2O 137 66 177 69
Values are means SD with percentage of the predicted normal value in parentheses.557
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TABLE 3. Measurements during CWR exercise at 75% of incremental peak work rate566
567
Rest 2 min PeakNW OB NW OB NW OB
Dyspnea, Borg 0.2 0.4 0.3 0.6 2.7 2.3 2.8 1.8 6.6 2.8 6.8 2.2
Leg discomfort, Borg 0.2 0.6 0.3 0.6 2.8 2.0 2.9 1.1 6.1 3.2 6.6 2.4
Work rate, watts 0 0 54 29 53 16 54 29 53 16
VO2, L/min 0.22 0.10 0.290.10 0.82 0.30 0.93 0.20 1.10 0.47 1.19 0.30
VCO2, L/min 0.18 0.08 0.240.08 0.69 0.27 0.77 0.18 1.04 0.44 1.16 0.33Heart rate, beats/min 77 9 85 13 106 18 113 21 127 19 120 15
SpO2, % 95.5 1.4 95.1 1.8 94.3 2.3 92.3 2.8 93.6 3.4 93.8 3.6
VE, L/min 11.1 3.4 12.1 3.2 27.9 8.3 27.5 3.9 41.7 16.7 40.2 9.3
PETCO2, mmHg 35 4 36 5 39 5 41 6 39 7 41 7
VT, L 0.61 0.12 0.66 0.18 1.14 0.37 1.03 0.16 1.22 0.36 1.15 0.23
TI/TTOT 0.38 0.06 0.36 0.05 0 .4 0 0.06 0.39 0.03 0.41 0.06 0.38 0.03
Peak tidal expiratory
flow, L/s0.60 0.21 0.72 0.16 1.29 0.36 1.57 0.34 1.98 0.69 2.20 0.63
IC, L 2.37 0.77 2.20 0.37 1.84 0.76 1.79 0.38 1.63 0.57 1.66 0.36
IC from rest, L 0 0 -0.53 0.26 -0.46 0.32 -0.74 0.40 -0.59 0.29
IRV, L 1.76 0.69 1.54 0.37 0.71 0.53 0.76 0.30 0.41 0.28 0.510.22
EELV, L 5.33 1.29 4.15 1.50 * 5.60 1.52 4.56 1.67 5.81 1.65 4.69 1.59
EELV, % pred TLC 86 14 70 20 * 93 17 78 23 97 17 80 22 *
EILV/TLC, % 77 6 75 7 91 7 87 5 94 5 92 4
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TABLE 4. Respiratory muscle/mechanical measurements571
572
Rest 2 min PeakNW OB NW OB NW OB
Pes-derived measurements (n=12 per group):
Pes,exp, cmH2O 0.2 2.1 3.0 3.0 * 8.8 6.9 11.2 6.8 11.9 4.9 15.5 11.0
Pes,insp, cmH2O -8.9 3.1 -9.1 2.1 -12.6 4.4 -13.5 4.0 -16.4 5.3 -19.3 4.8
PesEE, cmH2O -1.6 2.1 1.0 3.3 * 7.2 6.6 10.0 6.1 10.4 5.0 14.4 11.0
PesEE0flow, cmH2O -3.5 1.8 -1.8 2.8 -1.6 5.5 -0.2 3.9 -0.7 7.2 -0.6 6.7
TTIes,insp 0.0140.011 0.0240.020 0.0410.043 0.0560.048 0.0660.042 0.0640.057
PTPes, cmH2Os/min 72 33 103 30 194 90 203 49 259 56 285 53
Pga- and Pdi-derived measurements (n=8 NW, n=7 OB):
VMR (Pga/Pes) -3.4 0.9 -3.1 2.0 -0.0 0.9 -1.2 1.7 0.7 0.9 0.4 1.5
PEEPi,corr, cmH2O 1.5 2.1 2.2 2.2 6.3 4.7 8.1 8.8 7.2 11.0 10.5 14.7
Pga,rise, cmH2O 0.8 1.0 0.8 1.4 6.8 5.1 6.2 2.9 12.9 6.9 14.7 5.6
PgaEE0flow, cmH2O 6.5 6.7 16.9 4.9 * 14.0 7.5 20.3 7.3 17.7 12.6 22.9 6.1
Pga,exp, cmH2O 12.6 7.3 20.2 4.5 * 19.4 7.7 25.6 7.8 24.3 13.0 32.3. 8.5
PTPga, cmH2Os/min 59 24 70 21 152 94 151 75 243 148 292 153
Pdi,tidal, cmH2O 12.5 4.5 17.4 6.0 20.0 7.1 22.1 9.6 20.6 13.5 20.3 9.7
TTIdi,insp swing 0.0270.015 0.0390.014 0.0250.013 0.0250.010 0.0250.021 0.0170.005
PTPdi, cmH2Os/min 136 70 165 56 203 77 231 98 187 117 227 84
Values are means SD.573
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FIGURES577
Figure 1. Oxygen consumption (VO2), ventilation (VE), the ventilatory equivalent for carbon578
dioxide (VE/VCO2), inspiratory capacity (IC), tidal volume (VT) and breathing frequency (Fb)579
are shown in response to symptom-limited constant work rate cycle exercise in obese COPD580
(OB) subjects () and in normal-weight COPD (NW) subjects (). Values are means SE.581
*p
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subjects () and in normal-weight COPD (NW) subjects (). RL remained stable throughout601
exercise in NW, but decreased significantly (*p
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1.4 50 75NW
0.6
0.8
1.0
1.2
(L/min)
30
40
tion(L/min)
*
55
65
/VCO2
0.0
0.2
0.4
0 1 2 3 4 5 6 7 8
VO
0
10
0 1 2 3 4 5 6 7
V
entila
* *2535
0 1 2 3 4 5 6 7
V
Exercise time (min) Exercise time (min) Exercise time (min)
90
100
)
40
45
VC
) 35
40
in)
60
70
80
C(%predicted
20
25
30
35
T(%predicted
15
20
25
Fb
(breaths/m
500 1 2 3 4 5 6 7
I
Exercise time (min)
15
0 1 2 3 4 5 6 7
Exercise time (min)
10
0 1 2 3 4 5 6 7
Exercise time (min)
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(A) NWOB
ControlTLCNW120
130
LC
)
TLCOB
EILV90
100
110
predictedT
TLCControl
**
VT
60
70
80
volumes(%
EELV
40
50
0 20 40 60 80
Lu
ng
Ventilation (L/min)
(B)
*
min Pes (at TLC)-50
-40
inspiratoryreserve
-30
-20H2O
)
Pes,insp
id l
-10
es(c
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NW
OB12 250.5
6
8
10
cmH2
O/L/s)
10
15
20
Pi(cmH2
O)
*
0.2
0.3
0.4
(L/cmH2
O)
2
4
0 1 2 3 4 5 6 7
RL
(
0
5
0 1 2 3 4 5 6 7
PE
0.0
0.1
0 1 2 3 4 5 6 7
CL
dy
50
60
70
,sn
iff)
1.2
1.4
1.6
1.8
VT/prVC
0.20
0.25
0.30
al
10
20
30
40
estidal(%Pe
0.2
0.4
0.6
0.8
1.0
es/Pes,sniff:
0.05
0.10
0.15
TTIestid
0
0 1 2 3 4 5 6 7
Exercise time (min)
0.0
0 1 2 3 4 5 6 7
Exercise time (min)
0.00
0 1 2 3 4 5 6 7
Exercise time (min)
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-10
-H
2O) NW COPD OB COPD
(A)
-6
-4essure(cm
-2
0
ophagealp
= EI 0 flow
2 min
Peak
Rest
2 min
Peak
1 min 1 min
2
6 8 10 12 14 16 18 20 22 24 26
Es
Gastric pressure (cmH2O)
= ow
1
2(B)NW
OB
-2
-1
0
Pga
/Pes)
*
-3
MR(
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8
9
10
8
9
10 NW
OB
4
5
6
pnea
(Borg)
4
5
6
pnea
(Borg)
0
1
2
0 1 2 3 4 5 6 7
Dy
0
1
2
0 10 20 30 40 50
Dy
Exercise time (min) Ventilation (L/min)
9
10
9
10
T
LC
5
6
7
ea
(Borg)
5
6
7
8
nea
(Borg)
1
2
3Dys
pn
1
2
3Dy
sp
50 100 150 200 250 300 350
PTPes (cmH2O x s/min)
05101520253035
IRV (%pred TLC)