Abstract
Rationale: Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation, little is known about its relation to daily physical activity.
Objectives: To analyze the contribution of dynamic hyperinflation, exercise tolerance, and airway oxidative stress to physical activity in patients with COPD.
Methods: In a cross-sectional study, we included 110 patients with moderate to very severe COPD. Daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients performed the 6-minute walk test, incremental exercise test with measurement of breathing pattern and operating lung volumes, and constant-work rate test at 75% of maximal work rate.
Measurements and Main Results: Using the GOLD stage and BODE index, we determined arterial blood gases, lung volumes, diffusing capacity, and biomarkers in exhaled breath condensate. Daily physical activity was lower in the 89 patients who developed dynamic hyperinflation than in the 21 who did not (n =161 [SD 70] vs. n = 288 [SD 85] VMU; P = 0.001). Physical activity was mainly related to distance walked in 6 minutes (r = 0.72; P = 0.001), o2 (r = 0.63; P = 0.001), change in end-expiratory lung volume during exercise (r = −0.73; P = 0.001), endurance time (r = 0.61; P = 0.001), and 8-isoprostane in exhaled breath condensate (r = −0.67; P = 0.001). In a multivariate linear regression analysis using VMU as a dependent variable, dynamic hyperinflation, change in end-expiratory lung volume, and distance walked in 6 minutes were retained in the prediction model (r2 = 0.84; P = 0.001).
Conclusions: Daily physical activity of patients with COPD is mainly associated with dynamic hyperinflation, regardless of severity classification.
Reduction of physical activity in patients with chronic obstructive pulmonary disease is related to exacerbations and mortality.
In patients with moderate to very severe chronic obstructive pulmonary disease, daily physical activity is mainly associated with dynamic hyperinflation.
There is limited information available about the determinant factors of physical activity in COPD. Advancing airway obstruction leads to breathlessness, which impedes daily life activities. However, the relationship between FEV1 and daily physical activity is very modest (2, 6). Therefore, it seems that the decrease in physical activity estimated in patients with COPD does not depend merely on the severity of airflow limitation, but that there are other factors contributing to the stagnation. One might be the development of dynamic hyperinflation. In patients with COPD, the breathing to higher lung volumes increases respiratory work and thus potentiates the perception of breathlessness (7), which favors a decrease in physical activity. Although the impact of dynamic hyperinflation on exercise and function is recognized (8), little specific information about its repercussions on daily physical activity is available.
It has been previously reported that the daily physical activity of patients with COPD is highly correlated with the 6-minute walk test and modestly so with o2 (2). Although there is not a general consensus about what measurement of exercise tolerance should be used in the clinical evaluation of symptomatic patients with COPD, endurance tests seem to be more sensitive in detecting improvement in exercise tolerance after pulmonary rehabilitation, and they are also better correlated with improvements in health status (9).
Recently, it has been suggested that this reduction in physical activity could be explained by the extrapulmonary effects of COPD and its comorbidities (10), but this would only justify the reduction in physical activity in a subgroup of patients. It is not known if any relationship exists between the inflammation and oxidative stress developed in the airways and the daily physical activity of patients with COPD.
The objectives of this study were to analyze the contribution of dynamic hyperinflation, exercise capacity (assessed by incremental exercise and constant work rate tests), oxidative stress, and airway inflammation to the physical activity of patients with COPD.
We included 110 consecutive patients with moderate to very severe COPD, defined as postbronchodilator FEV1/FVC <0.7 and postbronchodilator FEV1<80% predicted (11); cigarette smoking history of greater than 20 pack-years; stable condition for at least 2 months; and optimal medical therapy for at least 8 weeks.
Exclusion criteria were history of asthma or a positive bronchodilator test, clinical signs of acute heart failure, unstable or moderate-severe heart disease, hypertension, diabetes, anemia, arthritis, vascular disease, depression, neuromuscular or disabling cognitive problems, engagement in any exercise-training program in the last 3 months, and other pathologic conditions or severe pain syndromes that could affect physical activity. The study was approved by the institutional ethics committee, and each participant gave written informed consent.
We recorded information about alcohol consumption, smoking habits, and educational status. Patients completed the Medical Research Council dyspnea scale (MRC) (12) and the St. George's Respiratory Questionnaire (13). COPD severity was classified according to the GOLD stage (14) and the BODE index (15).
IL-6, soluble TNF-α receptor 1, and 8-isoprostane concentrations in exhaled breath condensate (Ecoscreen; Jaeger, Hoechberg, Germany) were measured by enzyme immunoassay.
Physical activity was measured over five consecutive days using an RT3 triaxial accelerometer (Stayhealthy, Monrovia, CA), as previously described (16). The device sampled movement at a rate of 10 Hz. Analog-to-digital converted data were recorded every second and added to produce 1-minute movement epochs of vector magnitude units (VMU). A more detailed description of the applied clinical methods and accelerometer measurement is contained in the online supplement.
Arterial blood gas values breathing room air were measured (Rapidpoint 405; Bayer, Munich, Germany). Spirometry, body plethysmography, and determination of diffusing capacity for carbon monoxide were performed (MasterLab Body, Jaeger) according to current recommendations (17–19). The predicted values used were those of the European Coal and Steel Community (ECSC) (20).
Two 6-minute walk tests were performed according to ATS guidelines (21). A symptom-limited incremental exercise test was conducted on a cycle-ergometer (Ergobex, Bexen, Spain) according to ATS/ACCP standards (22). Workload was increased by 15 W/min, and expired gases, ventilation, and 12-lead electrocardiogram were continuously measured (Oxycon Alpha, Jaeger). The predicted values of Jones were used (23). Anaerobic threshold was estimated using the nadir of the ventilatory equivalent and the V-slope method (22). At least two reproducible inspiratory capacity maneuvers were obtained at rest and every 2 minutes during exercise, and the mean end-expiratory lung volumes (EELV) of the three preceding breaths were determined (24). On a following day, constant work rate test at 75% of the maximum work rate was performed (7). Endurance time was defined as the duration of loaded pedaling.
Values are expressed as mean (SD), median, and interquartile range or percentage. Differences between groups were analyzed by the chi-square test, Kruskal-Wallis test, or analysis of variance. The relationships between variables were determined using Pearson's correlation and simple regression analysis using weighted least squares. Significant contributors were introduced into a stepwise multiple linear regression analysis to identify independent determinants of the physical activity. A P less than 0.05 was considered significant.
The general characteristics, pulmonary function, airway biomarkers, and exercise response parameters of the group of patients included in the study are shown in Tables 1–3. A complementary description of the patients' characteristics is given in the online supplement (Tables E1–E6).
Total | Quartile 1 (VMU ≤ 112) | Quartile 2 (112 > VMU ≤ 170) | Quartile 3 (170 > VMU ≤ 245) | Quartile 4 (VMU > 245) | P Value* | |
|---|---|---|---|---|---|---|
| Patients, n (%) | 110 (100) | 27 (24.5) | 28 (25.4) | 28 (25.4) | 27 (24.5) | |
| Age, yr | 63 (8) | 65 (6) | 62 (8) | 62 (8) | 62 (8) | 0.48 |
| Males, n (%) | 104 (95) | 26 (96) | 26 (93) | 25 (89) | 27 (100) | 0.34 |
| BMI, kg/m2 | 27.5 (3.7) | 27.1 (3.6) | 26.7 (3.2) | 28.1 (4.4) | 28.2 (3.5) | 0.38 |
| Current smokers, n (%) | 20 (18) | 5 (20) | 6 (23) | 5 (19) | 4 (16) | 0.74 |
| Pack-years of smoking | 58 (48) | 83 (89) | 49 (12) | 48 (29) | 53 (16) | 0.21 |
| Alcohol consumption, g/d | 20 (15) | 21 (19) | 21 (14) | 19 (15) | 20 (15) | 0.93 |
| Retired or disabled, n (%) | 59 (54) | 20 (74) | 13 (46) | 14 (50) | 12 (44) | 0.10 |
| University studies, n (%) | 11 (10) | 4 (15) | 2 (7) | 3 (11) | 2 (7) | 0.87 |
| Years from diagnosis, yr | 6 (5) | 5 (4) | 9 (7) | 6 (3) | 4 (3) | 0.07 |
| Current treatment | ||||||
| SABA, n (%) | 104 (95) | 27 (100) | 27 (96) | 25 (89) | 25 (93) | 0.33 |
| LABA, n (%) | 91 (83) | 22 (82) | 24 (86) | 24 (86) | 21 (78) | 0.84 |
| Anticholinergics, n (%) | 86 (78) | 19 (70) | 25 (89) | 22 (79) | 20 (74) | 0.35 |
| Inhaled corticosteroids, n (%) | 85 (77) | 21 (78) | 23 (82) | 22 (79) | 19 (70) | 0.77 |
| Theophyllines, n (%) | 19 (73) | 4 (15) | 7 (25) | 6 (21) | 2 (7) | 0.33 |
| LTOT, n (%) | 10 (9) | 4 (15) | 4 (14) | 2 (7) | 0 (0) | 0.19 |
| MRC | 2.2 (1.0) | 2.9 (1.2) | 2.5 (1.0) | 1.8 (0.7) | 1.8 (0.8) | 0.001 |
| BODE index | 4.0 (2.1) | 5.9 (1.9) | 4.9 (1.7) | 2.9 (1.4) | 2.3 (1.4) | 0.001 |
| SGRQ-symptoms | 39.3 (20.9) | 50.8 (22.2) | 44.5 (21.3) | 29.4 (16.9) | 31.6 (14.9) | 0.001 |
| SGRQ-activity | 49.9 (18.7) | 62.2 (18.4) | 49.7 (17.7) | 47.9 (17.2) | 39.0 (14.6) | 0.001 |
| SGRQ-impact | 33.9 (19.6) | 51.3 (17.9) | 29.4 (16.3) | 24.8 (15.0) | 30.8 (18.8) | 0.001 |
| SGRQ-total | 40.2 (17.0) | 54.5 (17.5) | 38.1 (16.3) | 33.6 (12.5) | 34.4 (13.2) | 0.001 |
Total | Quartile 1 (VMU ≤ 112) | Quartile 2 (112 > VMU ≤ 170) | Quartile 3 (170 > VMU ≤ 245) | Quartile 4 (VMU > 245) | P Value* | |
|---|---|---|---|---|---|---|
| Postbronchodilator FVC, % pred | 75 (15) | 71 (14) | 70 (14) | 80 (15) | 79 (15) | 0.02 |
| Postbronchodilator FEV1, % pred | 47 (14) | 43 (13) | 42 (12) | 49 (14) | 54 (13) | 0.01 |
| Postbronchodilator FEV1/FVC | 50 (12) | 48 (13) | 49 (11) | 49 (12) | 55 (11) | 0.15 |
| FRC, % pred | 133 (37) | 143 (25) | 144 (42) | 130 (22) | 114 (28) | 0.002 |
| TLC, % pred | 108 (18) | 112 (16) | 112 (21) | 107 (13) | 99 (17) | 0.02 |
| RV/TLC, % | 57 (9) | 60 (7) | 59 (9) | 56 (9) | 52 (8) | 0.002 |
| DlCOc, % pred | 77 (28) | 61 (27) | 75 (22) | 77 (25) | 94 (23) | 0.001 |
| pH | 7.41 (0.02) | 7.40 (0.02) | 7.41 (0.02) | 7.40 (0.03) | 7.41 (0.02) | 0.33 |
| PaO2, mm Hg | 67.2 (9.6) | 64.0 (8.7) | 64.3 (8.6) | 68.3 (6.9) | 71.0 (6.6) | 0.01 |
| PaCO2, mm Hg | 40.3 (5.0) | 41.8 (5.5) | 40.4 (5.8) | 40.2 (3.5) | 38.7 (5.1) | 0.27 |
| Hemoglobin, g/dl | 15.4 (1.5) | 15.5 (1.4) | 15.1 (1.4) | 16.2 (1.7) | 14.7 (1.3) | 0.12 |
| IL-6 in EBC, pg/ml | 3.3 (5.3) | 2.1 (3.3) | 6.3 (7.8) | 1.9 (3.2) | 1.7 (2.5) | 0.04 |
| sTNFR 1 in EBC, pg/ml | 3.3 (6.7) | 4.0 (5.4) | 4.4 (10.4) | 1.0 (1.0) | 3.2 (4.7) | 0.59 |
| 8-isoprostane in EBC, pg/ml | 39.8 (26.2) | 58.9 (20.3) | 45.6 (23.8) | 33.6 (23.0) | 11.1 (7.1) | 0.001 |
Total | Quartile 1 (VMU ≤ 112) | Quartile 2 (112 > VMU ≤ 170) | Quartile 3 (170 > VMU ≤ 245) | Quartile 4 (VMU > 245) | P Value* | |
|---|---|---|---|---|---|---|
| 6MWD, m | 314 (125) | 199 (82) | 263 (76) | 377 (117) | 416 (83) | 0.001 |
| ΔBorg/distance, 1,000/m | 7.8 (8.7) | 13.2 (10.2) | 6.1 (3.3) | 6.4 (5.2) | 5.0 (2.6) | 0.001 |
| W peak, w | 59 (24) | 48 (20) | 53 (19) | 60 (22) | 79 (20) | 0.001 |
| e peak, L/min | 38.7 (10.0) | 34.3 (9.9) | 34.6 (8.3) | 40.7 (8.5) | 47.1 (11.4) | 0.001 |
| Breathing reserve, % | 27.2 (13.4) | 29.5 (12.3) | 26.1 (12.7) | 26.2 (13.5) | 26.4 (14.7) | 0.77 |
| f peak, breaths/min | 31 (7) | 29 (6) | 30 (7) | 32 (5) | 33 (7) | 0.08 |
| VT peak, L | 1.27 (0.30) | 1.20 (0.31) | 1.17 (0.33) | 1.29 (0.34) | 1.46 (0.39) | 0.01 |
| Δe/Δco2 peak | 31.5 (7.3) | 33.2 (8.1) | 31.9 (7.5) | 31.7 (4.7) | 30.5 (7.0) | 0.57 |
| Vd/Vt peak | 0.22 (0.04) | 0.23 (0.05) | 0.22 (0.04) | 0.22 (0.04) | 0.20 (0.03) | 0.07 |
| HR peak, beats/min | 125 (18) | 122 (16) | 127 (15) | 126 (12) | 131 (17) | 0.24 |
| HRR, beats/min | 34 (16) | 36 (16) | 34 (15) | 32 (11) | 28 (12) | 0.21 |
| HR slope, L/ml/kg | 7.5 (2.2) | 8.4 (2.1) | 7.7 (1.7) | 7.1 (1.4) | 6.7 (1.8) | 0.007 |
| Δo2/HR peak, ml | 11.0 (2.9) | 9.9 (2.9) | 10.0 (2.2) | 12.1 (3.0) | 12.4 (2.5) | 0.001 |
| o2 peak, ml/min/kg | 18.1 (4.3) | 14.9 (3.3) | 16.8 (3.1) | 19.2 (3.9) | 21.7 (3.8) | 0.001 |
| o2 peak (%) | 69 (17) | 57 (16) | 65 (14) | 74 (12) | 81 (18) | 0.001 |
| o2 slope | 17.0 (5.4) | 16.4 (5.9) | 18.7 (7.7) | 15.9 (3.2) | 17.1 (3.3) | 0.29 |
| Anaerobic threshold, %o2max | 49 (14) | 41 (12) | 49 (13) | 46 (12) | 58 (15) | 0.001 |
| Minimum SpO2, % | 88 (6) | 85 (7) | 87 (7) | 89 (3) | 89 (49) | 0.01 |
| ΔEELV, L | 0.44 (0.48) | 0.83 (0.49) | 0.60 (0.29) | 0.35 (0.38) | -0.05 (0.20) | 0.001 |
| ΔEILV, L | 1.13 (0.56) | 1.43 (0.53) | 1.15 (0.42) | 1.17 (0.57) | 0.77 (0.52) | 0.001 |
| Endurance time, sec | 270 (141) | 158 (104) | 256 (110) | 301 (133) | 386 (117) | 0.001 |
Figures 1 and 2 show the individual data of the daily physical activity among patients with COPD classified according to the GOLD stage and according to the BODE index. As expected, patients with more severe COPD performed less physical activity during their everyday life.
Figure 1. Individual distribution of daily physical activity (vector magnitude units, VMU) according chronic obstructive pulmonary disease (COPD) severity assessed by the GOLD criteria. Horizontal lines represent mean values (analysis of variance with post hoc multiple comparisons by the Bonferroni test).
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Figure 2. Individual distribution of daily physical activity (vector magnitude units, VMU) according to chronic obstructive pulmonary disease severity assessed by the BODE index. Horizontal lines represent mean values (analysis of variance with post hoc multiple comparisons by the Bonferroni test).
[More] [Minimize]Table 4 shows the variables significantly related with daily physical activity. In addition to symptoms and quality of life, a strong relationship was found between physical activity and exercise tolerance, assessed by the distance walked in 6 minutes, o2, and endurance time (Figures 3A–3C). In these patients, daily physical activity was also related to ventilatory response to exercise, mainly with the development of dynamic hyperinflation. The 89 patients with COPD who developed an increase in EELV during exercise performed less physical activity than the remaining 21 patients who did not experience dynamic hyperinflation (161 [SD 70] vs. 288 [SD 85] VMU; P = 0.001). Moreover, an inverse relationship was found between the change in EELV and the activity recorded by the accelerometer (Figure 3D).
Figure 3. Relationship between daily physical activity recorded by accelerometer and (A) the distance walked in 6 minutes, (B) peak oxygen uptake, (C) change in end-expiratory lung volume, (D) endurance time, and (E) 8-isoprostane level in breath exhaled condensate in patients with chronic obstructive pulmonary disease (Pearson's correlation coefficient). VMU = vector magnitude units.
[More] [Minimize]Parameter | r | 95% Confidence Interval | P Value |
|---|---|---|---|
| MRC | −0.46 | −0.59 to −0.29 | 0.001 |
| SGRQ-symptoms | −0.38 | −0.55 to −0.19 | 0.001 |
| SGRQ-activity | −0.41 | −0.57 to −0.22 | 0.001 |
| SGRQ-impact | −0.28 | −0.46 to −0.08 | 0.006 |
| SGRQ-total | −0.37 | −0.53 to −0.17 | 0.001 |
| Postbronchodilator FVC, % pred | 0.28 | 0.10 to 0.45 | 0.003 |
| Postbronchodilator FEV1, % pred | 0.38 | 0.21 to 0.53 | 0.001 |
| Postbronchodilator FEV1/FVC | 0.25 | 0.07 to 0.42 | 0.008 |
| FRC, % pred | −0.37 | −0.53 to −0.19 | 0.001 |
| TLC, % pred | −0.32 | −0.48 to −0.13 | 0.001 |
| RV/TLC, % | −0.36 | −0.52 to −0.13 | 0.001 |
| DlCOc, % pred | 0.49 | 0.31 to 0.61 | 0.001 |
| PaO2, mm Hg | 0.36 | 0.16 to 0.53 | 0.001 |
| 6MWD, m | 0.72 | 0.62 to 0.80 | 0.001 |
| ΔBorg/distance, 1,000·m−1 | −0.39 | −0.54 to −0.21 | 0.001 |
| e peak, L/min | 0.49 | 0.33 to 0.62 | 0.001 |
| f peak, breaths/min | 0.30 | 0.12 to 0.47 | 0.001 |
| Vt peak, liters | 0.25 | 0.07 to 0.42 | 0.008 |
| Vd/Vt peak | −0.23 | −0.40 to −0.04 | 0.02 |
| HRR, beats/min | −0.23 | −0.41 to −0.04 | 0.02 |
| HR slope, L/ml/kg | −0.34 | −0.49 to −0.16 | 0.001 |
| Δo2/HR peak, ml | 0.38 | 0.20 to 0.53 | 0.001 |
| o2 peak, ml/min/kg | 0.63 | 0.50 to 0.74 | 0.001 |
| o2 peak, % | 0.55 | 0.40 to 0.60 | 0.001 |
| Anaerobic threshold, %o2max | 0.48 | 0.28 to 0.63 | 0.001 |
| Minimum SpO2, % | 0.30 | 0.12 to 0.47 | 0.002 |
| ΔEELV, L | −0.73 | −0.81 to −0.63 | 0.001 |
| ΔEILV, L | −0.44 | −0.58 to −0.27 | 0.001 |
| Endurance time, s | 0.61 | 0.47 to 0.72 | 0.001 |
| Isoprostane in EBC, pg/ml | −0.67 | −0.78 to −0.51 | 0.001 |
Airway oxidative stress, evaluated by the levels of 8-isoprostane in exhaled breath condensate, was inversely related to daily physical activity (Figure 3E). Neither age, sex, smoking habit, current treatment, comorbid conditions, inspiratory capacity, desaturation during the 6-minute walk test, nor the inflammation markers in exhaled breath condensate was associated with physical activity.
The stepwise multiple regression model for daily physical activity only retains dynamic hyperinflation, EELV change, and distance walked during 6 minutes as independent variables (Table 5). The model that includes the three variables accounts for 84% of the explained variance in physical activity.
Unstandardized Regression Coefficients | Standardized Regression Coefficients | |||||||
|---|---|---|---|---|---|---|---|---|
| B | SE | 95% CI for B | B | P Value | R2 | R2 change | ||
| Constant | 170.22 | 37.93 | 91.95 to 248.50 | — | — | — | — | |
| 6MWD, m | 0.39 | 0.07 | 0.24 to 0.55 | 0.53 | 0.001 | 0.66 | — | |
| Dynamic hyperinflation* | −90.40 | 26.36 | −144.81 to -35.99 | −0.34 | 0.001 | 0.80 | 0.14 | |
| ΔEELV, L | −52.54 | 22.20 | −98.35 to -6.74 | −0.24 | 0.001 | 0.84 | 0.04 | |
The main finding of our study is that the reduced daily physical activity of patients with moderate-severe COPD might be partially explained by the development of dynamic hyperinflation, regardless of the severity of the disease according to the GOLD stages or BODE index. Distance walked during 6 minutes is also an independent predictor factor.
In contrast to physical activity questionnaires, which provide useful results for group estimations but may provide inaccurate results on an individual basis, the motion sensors objectively register the activity performed by a patient over a period of time (25). There are different procedures to estimate physical activity using accelerometers. One of the most common is estimating the energy expenditure of the activity performed. However, accelerometers are limited to estimating energy expenditure in daily life. The accuracy of the energy expenditure estimation is influenced by the equation chosen, and the literature provides conflicting results, with some studies suggesting underestimation and others overestimation (25–27). There is evidence that accelerometers are more accurate for the quantification of body movement than for the estimation of energy expenditure, especially in relatively inactive populations (25, 28). Another possible analysis is the distribution of daily time in activities of various intensities, although this entails a high level of variability, with a variation coefficient above 25% (2). In contrast to these approximations, the global estimate of physical activity using a single measurement could be more consistent (25). We have used an RT3 accelerometer, which is sensitive to low levels of activity, reflects the intensity and frequency of activity, and provides an output as a triaxial vector plot over time. Moreover, its cost is moderate, and, like its predecessor the Tritrac RD3, it has been used previously in patients with COPD (29–31). Previous data of our group confirm the concordance and short- and midterm reproducibility of its registers in patients with COPD, with a within-week variation coefficient of 6% and a midterm repeatability of 11.2% (16).
In our patients, less physical activity is observed as the disease increases in severity. This finding is concurrent with other studies that use the GOLD severity classification (10, 32). It has been suggested that the GOLD stages do not properly differentiate which patients with COPD are active or inactive in daily life, in contrast to the multidimensional BODE index (6). Nevertheless, our data, as those of Watz and colleagues (10), do not confirm that the BODE index severity evaluation is much superior to the GOLD classification in detecting differences in the daily physical activity of patients with moderate to very severe COPD.
The physical activity that a subject does throughout his/her daily life can be influenced by many factors. Aside from physical capabilities, there are psychological, behavioral, social, and personality aspects that determine whether a person's lifestyle is more or less active. However, in debilitating chronic diseases such as COPD, the magnitude of the physical limitations can essentially condition the amount of activity performed.
In our patients, the multiple linear regression analysis identified dynamic hyperinflation and distance walked during 6 minutes as independent, significant predictors of physical activity in moderate-very severe patients. Although the relationship between physical activity and FEV1 and the FEV1/FVC coefficient (2, 6, 10, 29) is average, other data suggest the possible repercussions of the ventilatory limitations to exercise on the physical activity of patients with COPD. In patients with moderate-severe COPD, maximal voluntary ventilation, which reflects the ventilatory reserve available to respond to the increased physiological demand during exercise, is better correlated to different variables concerning physical activity in daily life than FEV1 (6). The FEV1 levels of our patients show a modest relation with the change in EELV during exercise (r = 0.38), and it is not an independent predictor for physical activity. It is well known that the development of dynamic hyperinflation makes patients breathe at larger operational volumes, which results in an increase in respiratory effort, greater neuromechanical dissociation, and a greater perception of dyspnea (7, 33). In our patients, the increase in EELV during exercise showed a directly proportional relation with the intensity of dyspnea as evaluated by the MRC scale (r = 0.31; P = 0.001). This increase in respiratory discomfort could justify the limitation that many patients with moderate-severe COPD experience when performing a large part of their daily physical activity. At the same time, dynamic hyperinflation contributes to the weakness and fatigue of the respiratory muscles (33) and promotes deconditioning, and patients therefore enter into a vicious circle. The inactivity contributes to a further worsening of the physical condition of the patient and to even more dyspnea. This configures a cycle of inactivity, deconditioning, and dyspnea that can cause the disease to worsen and progress (34). We also cannot rule out the contribution of dynamic hyperinflation to cardiac limitations. Recently, it has been described that hyperinflation is associated with lower oxygen pulse and exercise capacity in patients with severe COPD (35), supporting an interaction between hyperinflation and decreased cardiac function that may contribute to exercise limitation in these patients. This could justify the absence of cardiac variables in our prediction model.
The affected daily physical activity is not justified by dynamic hyperinflation alone. Our data show that the distance walked during 6 minutes also is a contributing factor. The 6-minute walk test evaluates the global responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic and peripheral circulation, blood, neuromuscular units, and muscle metabolism. In fact, the relationship between the distance walked in 6 minutes and V̇o2 has been widely reported (36, 37). Although the 6-minute walk test does not evaluate the causes or mechanisms of exercise limitation, it provides information that may be a better index of the patient's ability to perform daily activities than V̇o2 (38–40).
We have detected an inversely proportional relationship between the levels of 8-isoprostane in exhaled breath condensate and the physical activity performed (Figure E4). The relation between the intensity of the lipid peroxidation in the airways, the severity of COPD evaluated by the BODE index, and physical activity could be interpreted as a cause or a consequence of physical inactivity. Although it is well known that a sedentary lifestyle can be related to a higher level of systemic oxidative stress (41), its repercussions on the airways is not as clear. However, in our multiple regression model, the level of local oxidative stress is not retained as an independent variable. This circumstance could be explained by its supposed dependence on dynamic hyperinflation. It has been recently reported that the alveolar epithelial cells submitted to stretching due to pulmonary overdistension produce more reactive oxygen species (42).
There are several limitations to our study. Because it is a cross-sectional study, it cannot establish a causal relationship, but instead one of association. The COPD patient sample that we have studied is not representative of the population; in addition, the exclusion of comorbidities limits its extrapolation to the entire patient population of this disease. Finally, the accelerometer used is subject to a possible vibration artifact and gives no feedback to the wearer.
In conclusion, our data suggest that dynamic hyperinflation might be related to the physical activity performed by patients with moderate to very severe COPD. In future studies, it would be important to establish whether the correction of dynamic hyperinflation with therapeutic intervention would be accompanied by an increase in the daily physical activity of these patients.
The authors acknowledge the excellent technical assistance provided by A. Alvarez. P. Librán, A. Pérez, and C. Suárez.
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