Physical Activity and Clinical and Functional

Status in COPD
Judith Garcia-Aymerich, Ignasi Serra, Federico P. Gómez, Eva Farrero,
Eva Balcells, Diego A. Rodríguez, Jordi de Batlle, Elena Gimeno, David
Donaire-Gonzalez, Mauricio Orozco-Levi, Jaume Sauleda, Joaquim Gea,
Robert Rodriguez-Roisin, Josep Roca, Àlvar G. Agustí, Josep M. Antó
and the Phenotype and Course of COPD (PAC-COPD) Study Group

Chest 2009;136;62-70; Prepublished online March 2, 2009;

DOI 10.1378/chest.08-2532
The online version of this article, along with updated information and
services can be found online on the World Wide Web at:
http://chestjournal.chestpubs.org/content/136/1/62.full.html

Chest is the official journal of the American College of Chest

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Copyright2009by the American College of Chest Physicians, 3300
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© 2009 American College of Chest Physicians
 Original Research
COPD

Physical Activity and Clinical

and Functional Status in COPD
Judith Garcia-Aymerich, MD; Ignasi Serra, BStat; Federico P. Gómez, MD;
Eva Farrero, MD; Eva Balcells, BMed; Diego A. Rodríguez, BMed;
Jordi de Batlle, BMedBiol; Elena Gimeno, PT; David Donaire-Gonzalez, PT;
Mauricio Orozco-Levi, MD; Jaume Sauleda, MD; Joaquim Gea, MD;
Robert Rodriguez-Roisin, MD, FCCP; Josep Roca, MD; Àlvar G. Agustí, MD;
and Josep M. Antó, MD; the Phenotype and Course of COPD (PAC-COPD)
Study Group*

Background: The mechanisms underlying the benefits of regular physical activity in the evolution
of COPD have not been established. Our objective was to assess the relationship between regular
physical activity and the clinical and functional characteristics of COPD.
Methods: Three hundred forty-one patients were hospitalized for the first time because of a
COPD exacerbation in nine teaching hospitals in Spain. COPD diagnosis was confirmed by
spirometry under stable conditions. Physical activity before the first COPD hospitalization was
measured using the Yale questionnaire. The following outcome variables were studied under
stable conditions: dyspnea, nutritional status, complete lung function tests, respiratory and
peripheral muscle strength, bronchial colonization, and systemic inflammation.
Results: The mean age was 68 years (SD, 9 years), 93% were men, 43% were current smokers, and
the mean postbronchodilator FEV1 was 52% predicted (SD, 16% predicted). Multivariate linear
regression models were built separately for each outcome variable and adjusted for potential
confounders (including remaining outcomes if appropriate). When patients with the lowest
quartile of physical activity were compared to patients in the other quartiles, physical activity was
associated with significantly higher diffusing capacity of the lung for carbon monoxide (DLCO)
[change in the second, third, and fourth quartiles of physical activity, compared with first quartile
(ⴙ 6%, ⴙ 6%, and ⴙ 9% predicted, respectively; p ⴝ 0.012 [for trend])], expiratory muscle
strength (maximal expiratory pressure [PEmax]) [ⴙ 7%, ⴙ 5%, and ⴙ 9% predicted, respectively;
p ⴝ 0.081], 6-min walking distance (6MWD) [ⴙ 40, ⴙ 41, and ⴙ 45 m, respectively; p ⴝ 0.006
(for trend)], and maximal oxygen uptake (V̇O2peak) [ⴙ 55, ⴙ 185, and ⴙ 81 mL/min,
respectively; p ⴝ 0.110 (for trend)]. Similarly, physical activity reduced the risk of having
high levels of circulating tumor necrosis factor ␣ (odds ratio, 0.78, 0.61, and 0.36, respec-
tively; p ⴝ 0.011) and C-reactive protein (0.70, 0.51, and 0.52, respectively; p ⴝ 0.036) in
multivariate logistic regression.
Conclusions: More physically active COPD patients show better functional status in terms of
DLCO, PEmax, 6MWD, V̇O2peak, and systemic inflammation. (CHEST 2009; 136:62–70)
Abbreviations: BMI ⫽ body mass index; CRP ⫽ C-reactive protein; Dlco ⫽ diffusing capacity of the lung for
carbon monoxide; FFMI ⫽ fat-free mass index; IC ⫽ inspiratory capacity; IL ⫽ interleukin; PAC-COPD ⫽
Phenotype and Course of COPD; Pemax ⫽ maximal expiratory pressure; Pimax ⫽ maximal inspiratory pressure;
RV ⫽ residual volume; 6MWD ⫽ 6-min walking distance; TLC ⫽ total lung capacity; TNF ⫽ tumor necrosis factor;
V̇o2peak ⫽ maximal oxygen uptake

I activity
n patients with COPD, a higher level of physical
reduces the number of hospital admissions
due to exacerbations,1–3 as well as all-cause and respi-
ratory mortality.2 Previous studies4 –9 have found asso-
ciations between physical activity and phenotypical
traits potentially underlying these effects, such as dys-
pnea, lung function, body weight and composition,
muscle function, cardiac function, exercise capacity,
and/or systemic inflammation. However, most of these
studies included a small number of patients4 – 6,8 and/or

62 Original Research

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© 2009 American College of Chest Physicians
those with only severe COPD,6,7 in whom a reduced
physical activity level may be the consequence of the
disease and previous hospitalizations.3 A true effect
could be potentially inferred from pulmonary rehabil-
itation programs, which include exercise training and
From the Centre for Research in Environmental Epidemiology
(Drs. Garcia-Aymerich, Serra, and Antó, and Mr. Donaire-
Gonzalez), Barcelona, Spain; the Municipal Institute of Medical
Research (Drs. Balcells and Orozco-Levi), Hospital del Mar,
Barcelona, Spain; Centro de Investigación Biomédica en Red
Epidemiologia y Salud Pública (CIBERESP) [Dr. de Batlle],
Barcelona, Spain; Servei de Pneumologia (Drs. Gómez,
Rodríguez, and Rodriguez-Roisin, and Ms. Gimeno), Hospital
Clínic, Institut D’Investigacions Biomèdiques August Pi i Sunyer,
Universitat de Barcelona, Barcelona, Spain; Centro de Investi-
gación Biomedica en Red de Enfermedades Respiratorias (Drs.
Gea and Roca), Recinte Hospital Joan March, Bunyola, Spain;
Servei de Pneumologia (Dr. Sauleda), Hospital Universitari Son
Dureta, Palma de Mallorca, Spain; Servei de Pneumologia (Dr.
Farrero), Hospital Universitari de Bellvitge, L’Hospitalet de
Llobregat, Llobregat, Spain; and Fundació Caubet-Cimera (Dr.
Agustí), Recinte Hospital Joan March, Bunyola, Spain.
*A list of Centers and Members of the PAC-COPD Study Group
is located in the Appendix.
All authors have contributed to (1) conception and design of the
study; (2) analysis and interpretation of data; (3) writing the
article or revising it critically for important intellectual content;
and (4) final approval of the version to be published. Drs.
Garcia-Aymerich, Serra, and Antó performed the statistical anal-
ysis and interpreted the results. Dr. Garcia-Aymerich prepared
the first draft of the article. Dr. Garcia-Aymerich had full access
to all of the data in the study, and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
This research was supported by Fondo de Investigación Sanitaria
(FIS PI052292) and Spanish Society of Pneumology and Thoracic
Surgery (SEPAR 2004/136). Judith Garcia-Aymerich has a re-
searcher contract from the Instituto de Salud Carlos III (CP05/
00118), Ministry of Health, Spain. Jordi de Batlle had a predoc-
toral fellowship from the Instituto de Salud Carlos III (FI05/
01022), Ministry of Health, Spain. Diego A. Rodríguez has a long
term research fellowship from the European Respiratory Society
(2006/191). The PAC-COPD Study is funded by grants from
Fondo de Investigación Sanitaria (FIS PI020541), Ministry of
Health, Spain; Agència d’Avaluació de Tecnologia i Recerca
Mèdiques (AATRM 035/20/02), Catalonia Government; Spanish
Society of Pneumology and Thoracic Surgery (SEPAR 2002/137);
Catalan Foundation of Pneumology (FUCAP 2003 Beca Marià
Ravà); Red RESPIRA (RTIC C03/11); Red RCESP (RTIC
C03/09), Fondo de Investigación Sanitaria (PI052486); Fondo de
Investigación Sanitaria (PI052302); Fundació La Marató de TV3
(No. 041110); DURSI (2005SGR00392); and an unrestricted
educational grant from Novartis Farmacèutica, Spain. Centro de
Investigacíon Biomedica en Red Epidemiologia y Salud Pública
(CIBERESP) and CIBERES are funded by the Instituto de
Salud Carlos III, Ministry of Health, Spain. No involvement of
funding sources in study design; in the collection, analysis, and
interpretation of data; in the writing of the report; nor in the
decision to submit the article for publication. Researchers are
independent from funders.
The authors have reported to the ACCP that no significant
conflicts of interest exist with any companies/organizations whose
products or services may be discussed in this article.
Manuscript received October 23, 2008; revision accepted January
23, 2009.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/site/misc/reprints.xhtml).
Correspondence to: Judith Garcia-Aymerich, MD, Centre for Re-
search in Environmental Epidemiology (CREAL), Doctor Aiguader
88, 08003 Barcelona, Catalonia, Spain; e-mail: jgarcia@creal.cat
DOI: 10.1378/chest.08-2532
www.chestjournal.org
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© 2009 American College of Chest Physicians
physical activity advice. Indeed, a review10 of rehabili-
tation programs showed a positive impact on dyspnea,
muscle function, and exercise capacity. However, be-
cause most rehabilitation programs include multiple
components, it is difficult to isolate the effects of
physical activity. So far, therefore, the mechanisms
underlying the beneficial effects of regular physical
activity on COPD have not been elucidated.11
The Phenotype and Course of COPD (PAC-COPD)
Project12 is a prospective multicenter study aimed at
investigating the phenotype heterogeneity of COPD in
a cohort of patients recruited during their first hospital
admission due to an episode of exacerbation of the
disease. The design of the project allows the study of
the role of physical activity on COPD phenotypes.
Accordingly, the present study assesses the association
between physical activity and a wide number of clinical
and functional characteristics, including dyspnea, body
weight and composition, lung function, respiratory and
peripheral muscle strength, exercise capacity, bronchial
colonization, and systemic inflammation. Understand-
ing the relationship between physical activity and dif-
ferent COPD phenotypic traits will help clarify how
physical activity plays its role in COPD and facilitate
the design of targeted interventions.
Materials and Methods
Design
The study was a cross-sectional analysis nested in a longitudinal
cohort study of COPD patients.
Participants
A total of 341 subjects hospitalized for the first time because of
a COPD exacerbation between January 2004 and March 2006 in
nine teaching hospitals in Spain were included in the study. The
recruitment process and definitions of exacerbation, first hospital
admission, and COPD are detailed in an online supplement. The
protocol was approved by the ethics committees of all the
participating hospitals, and written informed consent was ob-
tained from all subjects.
Variables and Instruments of Measurement
At recruitment (first hospitalization because of a COPD exac-
erbation), information about sociodemographic factors, comor-
bidities, and lifestyle was obtained. Physical activity in the 4
weeks prior to exacerbation was assessed using the Yale physical
activity questionnaire13 in its Spanish version validated for elderly
subjects.14 The questionnaire includes frequency, intensity, and
duration of a wide list of activities involving energy expenditure.
It allows for the calculation of the following: (1) weekly time
devoted to physical activities; (2) weekly energy expenditure in
physical activity, computed according to intensity codes for each
physical activity15; and (3) individual indexes to reflect the
following specific activity dimensions: vigorous activity, leisurely
walking, moving, standing, sitting, and a final index (the sum of
the previous five).
CHEST / 136 / 1 / JULY, 2009 63
 At least 3 months after the hospital admission and under stable Table 1—Physical Activity During 4 Weeks Previous to
conditions, the respiratory phenotype of patients was widely the Exacerbation in 341 COPD Patients Recruited at
studied, including functional limitation resulting from dyspnea, Their First Hospital Admission for a COPD
nutritional status (ie, body mass index [BMI] and fat-free mass Exacerbation
index [FFMI]), complete lung function16 –19 (FEV1, FVC, in-
spiratory capacity [IC], residual volume [RV], total lung capacity Total (n ⫽ 341)
[TLC], diffusing capacity of the lung carbon monoxide [Dlco],
Variables Mean (SD) Median (P25–P75)
Pao2, PAco2, and alveolar-arterial pressure difference), maximal
inspiratory pressure (Pimax) and maximal expiratory pressure Time spent in physical activity,
(Pemax),20,21 handgrip, exercise capacity (6-min walking distance h/wk
[6MWD], and maximal oxygen uptake [V̇o2peak] by incremental Domestic 11.1 (13.8) 6.9 (2–15.5)
cycle ergometry),22–24 bronchial colonization,25,26 and levels of At work
serum inflammatory biomarkers (tumor necrosis factor [TNF]-␣, All subjects 9.6 (21.3) 0 (0–0)
interleukin [IL]-6, IL-8, and C-reactive protein [CRP]). Detailed Occupationally active 42.9 (24.4) 40 (40–40.2)
information about methods and procedures of the PAC-COPD subjects (n ⫽ 61)
study has been previously reported12 and is provided in the online During leisure time 14.0 (12.9) 10 (4.5–21.2)
supplement. Total 34.7 (27.6) 28.5 (13.9–45.7)
Energy expenditure in physical
activity, kcal/wk
Statistical Analysis Domestic 2,144 (2,524) 1,410 (395–2,940)
At work
Physical activity measures are presented as the mean and SD, and
All subjects 1,528 (3,520) 0 (0–0)
the median and 25th and 75th percentiles. Energy expenditure in
Occupationally active 6,855 (4,376) 6,000 (3,600–9,600)
physical activity, categorized in quartiles, was selected a priori as the
subjects (n ⫽ 61)
main exposure variable. Sociodemographic characteristics at base-
During leisure time 3,129 (3,115) 2205 (840–4,440)
line, as well as all previously detailed clinical and functional variables
Total 6,801 (5,274) 5,662 (2,940–8,933)
under stable conditions, were compared between quartiles of energy
Activity dimensions
expenditure in physical activity. A test for trend was calculated by
Vigorous activity index score 6.3 (12.6) 0 (0–5)
treating the physical activity categories as an ordinal variable in a
(0–60)
linear regression for continuous variables, or ␹2 test for trend for
Leisurely walking index 15.5 (16.8) 12 (0–24)
categorical variables. Multivariate regression models were built
score (0–48)
separately for each clinical or functional variable, with physical
Moving index score (0–15) 9.3 (3.6) 9 (6–12)
activity as the exposure, and adjusted for potential confounders
Standing index score (0–10) 5.0 (2.6) 4 (4–6)
(including remaining clinical and functional variables if appropriate).
Sitting index score (0–4) 2.6 (1.0) 2 (2–3)
Linear or logistic regression was used for continuous or categorical
Summary index score (0–137) 38.4 (21.3) 34 (20–52.5)
outcome variables, respectively.27,28 Additional information about
statistical analysis, as well as sensitivity analyses, are provided in the P25-P75 ⫽ 25th to 75th percentile.
online supplement. All analyses were performed with a statistical
software package (Stata, version 10.0; Stata Corp LP; College
Station, TX). pressure difference], or other markers of systemic
inflammation [IL-6, IL-8]).
Being in the second, third, and fourth quartile of
Results energy expenditure in physical activity, compared with
the first quartile, was related to higher levels of Dlco,
During the 4 weeks prior to exacerbation, patients Pemax, 6MWD, and V̇o2peak, and to reduced levels of
were physically active for a median duration of 29 TNF-␣ and CRP, after having adjusted for confound-
h/wk, with the main activity being a leisurely walk. ers (Fig 1). Covariates in each multivariate model were
The median energy expenditure was 5,662 kcal/wk, as follows: smoking, dyspnea, and BMI for Dlco; sex
which was lower than that observed with the same and Dlco for Pemax; sex, age, working status, dys-
questionnaire in healthy subjects of similar age13,14 pnea, postbronchodilator FEV1 percent predicted, and
(Table 1). Being younger, unmarried, occupationally TNF-␣ for 6MWD; sex, age, BMI, postbronchodilator
active, and a current smoker were associated with FEV1 percent predicted, and Dlco for V̇o2peak; sex,
higher levels of physical activity (Table 2). smoking, postbronchodilator FEV1 percent predicted,
After hospital discharge and under clinically stable and 6MWD for TNF-␣; and BMI and postbronchodi-
conditions (Table 3), higher levels of regular physical lator FEV1 percent predicted for CRP. Other potential
activity previous to the exacerbation were associated confounders (including other sociodemographic, clini-
with statistically significant higher values for BMI, cal, and functional variables) were not finally included
FEV1, FEV1/FVC ratio, IC/TLC ratio, Dlco, Pemax, because they were not related to the outcome or
6MWD, and V̇o2peak, as well as lower values for modified point estimates for physical activity. After
dyspnea, RV/TLC ratio, bronchial colonization, cir- adjusting for confounders, the associations between
culating TNF-␣ and CRP. No differences were physical activity and BMI, FEV1, FEV1/FVC ratio,
found in the remaining variables (FFMI, levels of IC/TLC ratio, RV/TLC ratio, or bronchial colonization
arterial blood gases [Pao2, PAco2, alveolar-arterial were not any more statistically significant.

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© 2009 American College of Chest Physicians
Table 2—Sociodemographic Characteristics of 341 COPD Patients Recruited at Their First Hospital Admission for a
COPD Exacerbation

Energy Expenditure in Physical Activity

Total Quartile 1 Quartile 2 Quartile 3 Quartile 4

Variables (n ⫽ 341) (n ⫽ 85) (n ⫽ 85) (n ⫽ 85) (n ⫽ 86) p Value for Trend*

Male sex† 317 (93) 83 (98) 81 (95) 75 (88) 78 (91) 0.025

Age,‡ yr 67.5 (8.5) 70.5 (7.8) 69.2 (7.0) 67.2 (7.5) 63.0 (9.6) ⬍ 0.001
Married† 274 (80) 75 (88) 73 (86) 62 (73) 64 (74) 0.005
Less than primary school education† 200 (59) 51 (60) 45 (53) 48 (57) 56 (65) 0.425
Occupationally active† 61 (18) 0 (0) 5 (6) 17 (20) 39 (46) ⬍ 0.001
Low socioeconomic status (grade IV, V)† 258 (82) 68 (83) 64 (83) 64 (80) 62 (81) 0.595
Current smoker† 145 (43) 24 (28) 28 (33) 39 (46) 54 (63) 0.007
Charlson index of comorbidity (score 0–30)‡ 2.0 (1.3) 2.2 (1.5) 2.0 (1.3) 1.7 (1.1) 1.9 (1.4) 0.077
Quartile 1 ⫽ 1,650 kcal/wk; Quartile 2 ⫽ 4,060 kcal/wk; Quartile 3 ⫽ 7,404 kcal/wk; Quartile 4 ⫽ 12,240 kcal/wk. According to quartiles of energy
expenditure in physical activity; 24 values are missing for socioeconomic status.
*Tests for trend across groups: linear regression for continuous variables; ␹2 test for trend for categorical variables.
†Values are given as No. (%).
‡Values are given as the mean (SD).

Using weekly hours of physical activity instead of for the significantly lower proportion of bronchial
energy expenditure yielded almost identical results. colonization in patients who scored higher in the
The analysis of the different dimensions of physical vigorous index score (40%, 33%, and 14% of
activity did not yield additional information, except colonization in a score ⬍ 5, between 5 and 20, and

Table 3—Clinical and Functional Characteristics at Least 3 Months After Hospital Discharge and Under Stable
Conditions of 341 COPD Patients Recruited at Their First Hospital Admission for a COPD Exacerbation

Energy Expenditure in Physical Activity, kcal/wk

Total Quartile 1 Quartile 2 Quartile 3 Quartile 4

Variables (n ⫽ 341) (n ⫽ 85) (n ⫽ 85) (n ⫽ 85) (n ⫽ 86) p Value for Trend*
Severe dyspnea (MMRC 154 (46) 52 (62) 34 (40) 28 (33) 40 (47) 0.036
score 3, 4, 5)†
BMI,‡ kg/m2 28.2 (4.7) 27.5 (4.6) 27.7 (4.4) 28.6 (4.3) 28.9 (5.3) 0.023
FFMI,‡ kg/m2 19.7 (3.1) 19.8 (3.4) 19.2 (2.9) 19.5 (2.7) 20.0 (3.2) 0.524
Post-BD FEV1,‡ % 52.4 (16.2) 48.8 (16.3) 49.6 (14.8) 56.6 (16.0) 54.4 (16.6) 0.002
predicted
Post-BD FEV1/FVC,‡ % 53.4 (11.9) 51.3 (12.9) 50.5 (11.9) 56.3 (10.9) 55.4 (11.1) 0.002
IC/TLC ratio‡ 0.31 (0.10) 0.30 (0.09) 0.29 (0.09) 0.33 (0.11) 0.32 (0.09) 0.033
RV/TLC ratio,‡ % 55.5 (10.0) 57.7 (8.7) 56.8 (10.2) 54.2 (10.3) 53.7 (10.4) 0.004
Dlco,‡ % predicted 65.2 (20.7) 58.1 (19.9) 65.8 (20.6) 68.2 (19.5) 68.0 (21.6) 0.004
Pao2,‡ mm Hg 74.3 (10.6) 74.5 (10.7) 75.4 (11.1) 75.0 (9.9) 72.3 (10.7) 0.187
Paco2,‡ mm Hg 41.8 (5.3) 41.7 (5.6) 41.4 (5.2) 42.0 (4.7) 42.1 (5.8) 0.530
Pimax,‡ % predicted 64.0 (23.4) 61.3 (28.1) 61.5 (17.3) 67.7 (23.3) 64.9 (23.1) 0.169
Pemax,‡ % predicted 66.7 (22.9) 60.0 (20.6) 67.5 (24.8) 67.2 (22.0) 71.4 (23.2) 0.004
Nondominant handgrip,‡ % 103.8 (26.9) 103.8 (29.0) 105.1 (21.8) 104.7 (28.5) 101.6 (28.2) 0.593
predicted
6MWD,‡ m 442.0 (94.9) 396.5 (115.1) 445.9 (78.6) 456.2 (85.6) 466.6 (84.8) ⬍ 0.001
V̇o2peak,‡ mL/min 1,184.2 (366.9) 1,043.0 (235.1) 1,138.9 (300.4) 1,295.9 (444.6) 1,233.9 (397.5) 0.004
Bronchial colonization† 75 (33) 24 (43) 19 (33) 20 (35) 12 (22) 0.035
TNF-␣ ⱖ 0.5,†§ pg/mL 117 (35) 38 (48) 32 (38) 29 (35) 18 (21) ⬍ 0.001
CRPⱖ 3 mg/L† 187 (58) 53 (68) 51 (60) 40 (50) 43 (52) 0.023
BD ⫽ bronchodilation; MMRC ⫽ Modified Medical Research Council dyspnea scale. See Table 2 for definitions not given in the text. According
to quartiles of energy expenditure in physical activity during the 4 weeks previous to exacerbation (unadjusted analysis). Some values are missing
for certain variables: 3 in dyspnea; 12 in FFMI; 27 in IC/TLC; 27 in RV/TLC; 46 in Dlco; 11 in Pao2; 10 in Paco2; 43 in Pimax; 47 in Pemax;
13 in handgrip; 32 in 6MWD; 150 in V̇o2peak; 117 in bronchial colonization; 11 in TNF-␣; and 16 in CRP. Missing values were distributed at
random, and were mainly due to hospital logistics and patient availability (data available from the authors).
*Test for trend across groups: linear regression for continuous variables, and ␹2 test for trend for categorical variables.
†Values are given as No. (%).
‡Values are given as the mean (SD).
§Limit of detection was 0.5 for TNF-␣.

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© 2009 American College of Chest Physicians
 Figure 1. Adjusted association between physical activity and Dlco, Pemax, 6MWD, V̇o2peak,
TNF-␣, and CRP. A multivariate linear regression model was built separately for Dlco, Pemax,
6MWD, and V̇o2peak including as covariates all potential confounders and all remaining outcomes,
until a final model with only statistically significant variables was obtained. Covariates in each final
model are smoking, dyspnea, and BMI for Dlco model; sex and Dlco for Pemax model; sex, age,
working status, dyspnea, postbronchodilator percentage of predicted FEV1, and TNF-␣ for
6MWD; and sex, age, BMI, postbronchodilator percentage of predicted FEV1, and Dlco for
V̇o2peak model. Other potential confounders (including other sociodemographic, clinical, and
functional variables) were not finally included because they were not related to the outcome nor
modified point estimates for physical activity. Dots and vertical lines represent the adjusted mean
differences and 95% confidence intervals between participants in the second, third, and fourth
quartiles of physical activity and those in the first physical activity quartile (horizontal line). A
multivariate logistic regression model was built for TNF-␣ and CRP including as covariates all
potential confounders and all remaining outcomes, until a final model with only statistically
significant variables was obtained. Covariates in each final model are sex, smoking, postbronchodi-
lator percentage of predicted FEV1, and 6MWD for TNF-␣; and BMI and postbronchodilator
percentage of predicted FEV1 for CRP. Other potential confounders (including other sociodemo-
graphic, clinical, and functional variables) were not finally included because they were not related
to the outcome or modified point estimates for physical activity. Dots and vertical lines represent
the adjusted odds ratio and 95% confidence intervals for having an elevated TNF-␣ (ⱖ 0.5 pg/mL)
or CRP (ⱖ 3 mg/L) for participants in the second, third, and fourth quartiles of physical activity
relative to those in the first physical activity quartile.

⬎ 20, respectively; p ⫽ 0.006). Several stratified Discussion

analyses were performed, yielding very similar
results to those just reported, as follows: (1) when
only retired individuals were included in the anal-
ysis (n ⫽ 280), results remained basically un-
changed; (2) in the full sample, no differences
were observed in the association between physical
activity and lung function variables after stratifica-
tion according to smoking status; and (3) in the full
sample, no differences were observed in the asso-
ciation between physical activity and colonization
or systemic inflammation variables after stratifica-
tion according to inhaled glucocorticosteroid use.
Principal Findings
Our study investigated potential relationships
between regular physical activity and several phe-
notypic expressions of COPD in a large sample of
patients recruited during their first hospital admis-
sion because of a COPD exacerbation. The main
results show that regular physical activity is related
to higher Dlco, expiratory muscle strength (Pe-
max), and exercise capacity, as well as to lower
levels of systemic inflammation, after adjusting for
confounders.

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© 2009 American College of Chest Physicians
Strengths and Weaknesses of the Study
Present results may identify the mechanisms that
mediate the beneficial effects of physical activity on
COPD. Compared with previous reports, the clear
strengths of our study are as follows: (1) the adjust-
ment for potential confounders and a wide range of
outcomes as covariates; (2) the design that excludes
the possibility that physical activity might have been
reduced as a result of previous hospital admissions;
and (3) the large number of patients included and
the large variability of severity of their disease.
A potential limitation is the cross-sectional design,
so the direction of the associations cannot be estab-
lished. However, the dose-response pattern of some
of the associations is evidence against reverse causa-
tion as an explanation for the present results.29 A
questionnaire was used to measure physical activity,
which had been validated in elderly Spanish subjects
against an accelerometer.14 In addition, a pilot
study30 with nine COPD patients conducted in our
area showed moderate concordance between the ques-
tionnaire and the physical activity monitor (SenseWear
Pro Armband; Body Media Inc; Pittsburgh, PA).
Although the questionnaires are subject to misclas-
sification (ie, subjects who report being active are
really inactive, and vice versa) and poor accuracy at
the individual level, they are considered appropriate
for identifying group differences.31 In any case, this
misclassification leads to an underestimation of the
effects of physical activity.32 Several measures, in-
cluding the training of interviewers and rigorous
quality control, were taken into consideration to
ensure that patients reported physical activity previ-
ous to the exacerbation. Finally, the male predomi-
nance in our study, which is in agreement with
COPD gender distribution in Spain,33 did not allow
us to identify whether or not the associations be-
tween physical activity and COPD traits could differ
according to gender.
Comparison With Previous Studies and
Interpretation
Physical activity was associated with a higher
Dlco after adjusting for confounders, which is a
new finding in COPD patients. The observed asso-
ciation is consistent with the recently reported34 high
correlation coefficient between Dlco and lower
limb activity in COPD patients, as well as with
previous data35 on higher Dlco values in athletes
compared with sedentary individuals. Moreover, al-
though a decreased Dlco has been observed36
immediately after strenuous exercise, this reduction
is lower in most trained subjects. Altogether, these
findings indicate that physically active individuals
have better pulmonary circulation due to their train-
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© 2009 American College of Chest Physicians
ing. In the case of COPD patients, the present data
allow us to hypothesize that the attenuation of the
decline in Dlco, probably indicating a more effi-
cient pulmonary gas exchange and oxygen transport
to peripheral tissues, could be one of the mecha-
nisms explaining the previously reported1–3 benefits
of physical activity on COPD.
Physical activity was related also to better Pemax.
Although this is consistent with the finding of in-
creased Pemax after an exercise program in patients
with chronic air flow limitation,37 it is unlikely that
regular physical activity places sufficient specific load
on the respiratory muscles to increase respiratory
muscle strength.38 In addition, our study showed no
differences in Pimax or in handgrip strength. It
could be hypothesized that the benefits of regular
physical activity on respiratory muscles are mediated
through systemic effects, including reduction of sys-
temic inflammation, which would potentially atten-
uate muscle dysfunction.
In agreement with previous cross-sectional stud-
ies,6,8 a strong association between physical activity
and exercise capacity was found, both for 6MWD
and V̇o2peak. Further, it is well established that
pulmonary rehabilitation improves exercise capaci-
ty,10 even after a COPD admission.39 Most likely,
therefore, regular physical activity in COPD contrib-
utes to maintaining aerobic performance by prevent-
ing both cardiovascular and muscular decondition-
ing. A clinically relevant contribution of this study,
however, is that associations were found with daily
life activities rather than with the planned exercise
activities that characterize rehabilitation programs.
In experimental animals and in healthy individu-
als, moderate levels of exercise reduce the circulat-
ing levels of a number of inflammatory markers,
including TNF-␣ and CRP, among others.40 – 42 In
patients with advanced COPD, rehabilitation pro-
grams also appear to reduce exercise-induced oxidative
stress.43– 45 In keeping with these findings, we
observed that physical activity was related to lower
risk of high levels of circulating TNF-␣ and
CRP ⱖ 3 mg/L.
Interestingly, the subset of patients with highest
energy expenditure in physical activity showed a
lower prevalence of bronchial colonization, as did
those with the highest vigorous index scores. This
finding is in keeping with the reported association
between moderate exercise and a lower risk of upper
respiratory tract infections both in humans46,47 and
animals.48 Therefore, it could be hypothesized that if
regular physical activity is indeed associated with a
reduction in airway bacterial load, this could explain
why most active COPD patients are less prone to
hospitalizations because of exacerbations of the dis-
ease,1–3 a contention that may need further research.
CHEST / 136 / 1 / JULY, 2009 67
 The lack of association between regular physical
activity and some other clinically important domains
of COPD is also worth mentioning. First, the study
did not find an association between physical activity
and dyspnea, after adjusting for confounders. It is
well established that dyspnea limits exercise toler-
ance in COPD.10 The reduction in dyspnea after
rehabilitation programs suggests that dyspnea could
also be affected by physical activity.10 Our study
assessed the effects of regular physical activity, which
is most likely of lower intensity than that incorpo-
rated to rehabilitation programs. It is possible, there-
fore, that the lack of association between habitual
levels of physical activity and dyspnea observed in
the present study reflects a true phenomenon.
Second, it is well known that physical activity may
both reduce body weight and increase muscle mass
in the general population.49 In COPD patients, low
fat-free mass, irrespective of body weight, is a poor
prognostic indicator,50 and so changes in fat-free
mass have been proposed as mechanisms underlying
the beneficial effect of physical activity on the natu-
ral history of COPD.51,52 Our study did not show
differences in body weight or composition between
the different physical activity groups. The relatively
narrow distribution of body mass and fat-free mass,
and the smaller proportion of undernourished pa-
tients (only 18 patients [5%] with BMI ⬍ 21 kg/m2;
and 33 [10%] with FFMI ⬍ 16 kg/m2) in our study,
in comparison with others,53 may explain the absence
of an association.
Except for Dlco, the adjusted models in our
study did not show differences in results of lung
function tests (spirometry, static lung volumes, and
arterial blood gases) among physical activity groups.
By contrast, an association between physical activity
and FEV1 and FVC has been reported by previous
studies in the general population.51,52,54,55 It is likely
that the mentioned associations cannot be observed
in COPD patients given the reduced variability in
lung function parameters, in comparison to the
general population.
Clinical Implications
It has been found that a higher level of physical
activity relates to an improved COPD course in
terms of hospitalizations and mortality.1–3 The
present article goes a step further by identifying
associations between physical activity and clinically
relevant COPD traits. For most of the outcomes,
there is no minimal clinically relevant difference
defined in the literature, except for the 6MWD in
which the accepted 54-m difference56 is in agree-
ment with the one observed in our study between
the most active subjects and those inactive. There-
68
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© 2009 American College of Chest Physicians
fore, considering both the substantial benefits of
moderate physical activity in COPD and its safety (as
derived from pulmonary rehabilitation programs),10
in our opinion physical activity should be widely
recommended in patients with COPD. Further-
more, COPD guidelines should include this advice.
So far, most influential COPD guidelines do not
include the advice of physical activity16,57 or include
this advice with no references.58
Conclusions
Our study shows that higher levels of regular
physical activity in patients with COPD are associ-
ated with better functional status in terms of Dlco,
expiratory muscle strength (Pemax, exercise capacity
([6MWD], and V̇o2peak), and systemic inflammation,
after adjusting for confounders. These findings sug-
gest potential underlying mechanisms for the previ-
ously reported relation between physical activity and
hospitalizations and mortality in COPD patients, and
they may facilitate the design of targeted interven-
tions. Further randomized controlled trials would
allow an assessment and comparison of the effective-
ness of diverse therapeutic strategies to increase
physical activity in COPD patients, to maximize its
beneficial effects.
Appendix
Centers and Members of the PAC-COPD Study Group
Centre for Research in Environmental Epidemiology (CREAL),
Barcelona: Josep M Antó (principal investigator), Judith Garcia-
Aymerich (project coordinator), Marta Benet, Jordi de Batlle,
Ignasi Serra, David Donaire-Gonzalez, Stefano Guerra; Hospital
del Mar-IMIM, Barcelona: Joaquim Gea (center coordinator),
Eva Balcells, Àngel Gayete, Mauricio Orozco-Levi, Ivan Vollmer;
Hospital Clínic—Institut D’Investigacions Biomèdiques August
Pi i Sunyer (IDIBAPS), Barcelona: Joan Albert Barberà (center
coordinator), Federico P Gómez, Carles Paré, Josep Roca,
Robert Rodriguez-Roisin, Xavier Freixa, Diego A Rodriguez,
Elena Gimeno, Karina Portillo; Hospital General Universitari
Vall D’Hebron, Barcelona: Jaume Ferrer (center coordinator),
Jordi Andreu, Esther Pallissa, Esther Rodríguez; Hospital de la
Santa Creu i Sant Pau, Barcelona: Pere Casan (center coordina-
tor), Rosa Güell, Ana Giménez; Hospital Universitari Germans
Trias i Pujol, Badalona: Eduard Monsó (center coordinator),
Alicia Marín, Josep Morera; Hospital Universitari de Bellvitge,
L’Hospitalet de Llobregat: Eva Farrero (center coordinator),
Joan Escarrabill; Hospital de Sabadell, Corporació Parc Taulí,
Institut Universitari Parc Taulí (Universitat Autònoma de Barce-
lona), Sabadell: Antoni Ferrer (center coordinator); Hospital
Universitari Son Dureta, Palma de Mallorca: Jaume Sauleda
(center coordinator), Àlvar G Agustí, Bernat Togores; Hospital de
Cruces, Barakaldo: Juan Bautista Gáldiz (center coordinator),
Lorena López; Hospital General Universitari, València: José
Belda.
Original Research
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Original Research
 Physical Activity and Clinical and Functional Status in COPD
Judith Garcia-Aymerich, Ignasi Serra, Federico P. Gómez, Eva Farrero, Eva
Balcells, Diego A. Rodríguez, Jordi de Batlle, Elena Gimeno, David
Donaire-Gonzalez, Mauricio Orozco-Levi, Jaume Sauleda, Joaquim Gea,
Robert Rodriguez-Roisin, Josep Roca, Àlvar G. Agustí, Josep M. Antó and
the Phenotype and Course of COPD (PAC-COPD) Study Group
Chest 2009;136; 62-70; Prepublished online March 2, 2009;
DOI 10.1378/chest.08-2532
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