772

CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Regular physical activity reduces hospital admission
and mortality in chronic obstructive pulmonary
disease: a population based cohort study
J Garcia-Aymerich, P Lange, M Benet, P Schnohr, J M Antó...............................................................................................................................
Thorax 2006;61:772–778. doi: 10.1136/thx.2006.060145

See end of article forauthors’ affiliations.......................
Correspondence to:
Dr J Garcia-Aymerich,
Respiratory andEnvironmental HealthResearch Unit, Institut
Municipal d’InvestigacióMèdica (IMIM), Doctor
Aiguader 80, E-08003Barcelona, Spain;
jgarcia@imim.es
Received 7 February 2006
Accepted 10 May 2006
Published Online First
31 May 2006.......................

C

Background: Information about the influence of regular physical activity on the course of chronic
obstructive pulmonary disease (COPD) is scarce. A study was undertaken to examine the association
between regular physical activity and both hospital admissions for COPD and all-cause and specificmortality in COPD subjects.
Methods: From a population-based sample recruited in Copenhagen in 1981–3 and 1991–4, 2386
individuals with COPD (according to lung function tests) were identified and followed until 2000. Selfreported regular physical activity at baseline was classified into four categories (very low, low, moderate,and high). Dates and causes of hospital admissions and mortality were obtained from Danish registers.
Adjusted associations between physical activity and hospital admissions for COPD and mortality wereobtained using negative binomial and Cox regression models, respectively.
Results: After adjustment for relevant confounders, subjects reporting low, moderate or high physicalactivity had a lower risk of hospital admission for COPD during the follow up period than those whoreported very low physical activity (incidence rate ratio 0.72, 95% confidence interval (CI) 0.53 to 0.97).
Low, moderate and high levels of regular physical activity were associated with an adjusted lower risk of
all-cause mortality (hazard ratio (HR) 0.76, 95% CI 0.65 to 0.90) and respiratory mortality (HR 0.70, 95%
CI 0.48 to 1.02). No effect modification was found for sex, age group, COPD severity, or a background of
ischaemic heart disease.
Conclusions: Subjects with COPD who perform some level of regular physical activity have a lower risk ofboth COPD admissions and mortality. The recommendation that COPD patients be encouraged tomaintain or increase their levels of regular physical activity should be considered in future COPD
guidelines, since it is likely to result in a relevant public health benefit.

hronic obstructive pulmonary disease (COPD), with aprevalence in adults of 6–7%,1 is one of the main causesof morbidity and a leading cause of death worldwide.2
Reducing admissions to hospital due to COPD exacerbations
is a prime aim in the management of the disease3 4 because of
its high economic and social costs.5 Currently only oxygentherapy, some bronchodilators and glucocorticoids, andinfluenza vaccinations are considered effective in improving
the course of the disease—either by reducing the frequency of
hospital admission for COPD or mortality.3 4 In a previous
study conducted in a cohort of 346 patients with moderate tosevere COPD followed up for 1 year in Barcelona, Spain,
subjects with COPD who reported physical activity equivalent
to walking at least 1 hour/day had a lower risk of admission
for a COPD exacerbation than those who reported physicalactivity equivalent to walking only 20 minutes/day or less.6
The finding was considered important because of its
potentially significant beneficial impact and its implications
with regard to reducing health costs.7 Indeed, among thecurrent internationally recognised COPD guidelines, only
those produced by the British Thoracic Society8 recommendthat COPD patients be encouraged to increase their levels of
regular physical activity, a recommendation which as yet is
not evidence-based. From a public health point of view, andconsidering the large amount of health benefits associatedwith the practice of physical activity,9 the possibility thathigher levels of regular physical activity such as walking or
cycling could be associated with an improvement in thecourse of COPD is worthy of further investigation. The lack of
research on the influence of regular physical activity on the

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natural history of COPD is in contrast to that existing forother chronic diseases such as type 2 diabetes10 or cancer11 12
in which higher levels of physical activity (equivalent towalking 3–5 hours/week) have even been related to a reduced
risk of death from the chronic disease in question.13 In thepresent study we examined the association between regularphysical activity and both hospital admission due to COPD
and all-cause and specific mortality in a large prospective
cohort study of COPD subjects sampled from the general
population in Copenhagen and followed up for a mean of
12.0 years. The study is part of the Copenhagen City Heart
Study (CCHS) which has already provided relevant information about the course of COPD.14–16

METHODS
Study design and population
The CCHS involves the study of an ongoing prospective
cohort of adults recruited from the general population, withrepeated examinations every 5–10 years. A random age
stratified sample of the general population aged 20 years ormore was drawn from the Copenhagen Population Register
as of 1 January 1976 and a first examination (n = 14 223)
took place in 1976–8. At the second examination 5 years later(1981–3), the cohort was supplemented with a new sample ofsubjects aged 20–24 years (total n = 12 698). In the third
examination (1991–4) the sample was supplemented with
Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1,forced expiratory volume in 1 second; FVC, forced vital capacity

Physical activity in COPD subjects

773

20–49 year old subjects (total n = 10 135).17 18 The institutional review board and Danish regional ethics committees
approved the research protocol. Participants gave written
informed consent.
Since the first CCHS examination provided limited
information about regular physical activity, for the present
study we selected all participants included in the second
examination (1981–3) together with the complementary
sample of the third CCHS examination (1991–4). Of these
15 563 subjects, 2386 met the criteria for COPD and were
included in the present analysis. COPD was defined on thebasis of lung function test results including forced expiratory
volume in 1 second (FEV1) and forced vital capacity (FVC) as
the presence of airway obstruction (FEV1/FVC (70%) andclassified according to the degree of airway obstruction:3 4
mild (FEV1 >80%), moderate (FEV1 ,80% and >50%),
severe (FEV1 ,50% and >30%), and very severe (FEV1,30%). Subjects who, in addition to COPD, reported having
suffered asthma (n = 268) were initially included, although alater sensitivity analysis excluded this group. The date ofparticipation in the second CCHS examination or—in those
newly recruited from the third CCHS examination, the dateof participation in the third CCHS examination—wasconsidered the start of the follow up period. Subjects were
followed up either to the time of death or to 28 December
2000, with a mean of 12 years follow up (range 0.5–20 years)
providing a total of 28 747 person years.

Lung function parameters (FEV1 and FVC) were measured
at the second CCHS examination with an electronic
spirometer (Model N403; Monaghan, Littleton, CO, USA)
which was calibrated daily with a 1 litre syringe and weekly
against a water sealed Godard spirometer. At the third
examination a dry wedge spirometer (Vitalograph,
Maidenhead, UK), calibrated daily with a 1 litre syringe,
was used. At each examination three sets of values wereobtained and at least two measurements differing by lessthan 5% had to be produced. The highest measurements of
FEV1 and FVC were used in the analyses as absolute values
and as percentage of predicted values, using internallyderived reference values based on a subsample of healthy
never smokers.25 Information about hospital admissions(dates and diagnoses on discharge) both before the startand during follow up was obtained from the National Patient
Register which covers all Danish hospitals and is administered by the National Board of Health. COPD admission was
defined as any admission classified as ICD-8 codes 490-492 or
ICD-10 codes J40–J44 for the main diagnosis. Data on deaths
and the causes thereof were obtained from the Danish
National Board of Health. Cause of death was definedaccording to the following ICD codes for the immediate
cause of death: COPD deaths 490–492 (ICD-8) or J40-J44(ICD-10); respiratory deaths 460-519 (ICD-8) or J00-J99(ICD-10), and cardiovascular deaths 390–458 (ICD-8) or I00I99 (ICD-10).

Measurements
Identical methods were applied in the second and third CCHS
examinations and have been previously described indetail.17 18 For the present analysis only the measurementsof physical activity and other independent variables obtainedat the start of the follow up period were used. A selfadministered questionnaire on regular physical activity overthe previous 12 months, current smoking and alcohol
consumption, socioeconomic factors (sex, age, education,
marital status, cohabitation, income), current symptoms(dyspnoea,19 sputum, chest pain, leg pain and intermittent
claudication), a diagnosis of co-morbidity at any time
(asthma, ischaemic heart disease, myocardial infarction,
stroke, diabetes), and health service use over the previous
12 months was completed and checked by the CCHS staff.
Blood pressure, plasma cholesterol, glucose concentrations,and body mass index were also measured. Clinical records
were reviewed to obtain information about co-morbidity.
Physical activity was measured using a questionnaireoriginally developed by Saltin and Grimby20 which discriminates between sedentary persons and their more active
counterparts with respect to maximal oxygen uptake,21 andhas been widely used to describe the effects of physicalactivity on health outcomes in similar types of populations.22 23 Physical activity variables included physical activity
at work, physical activity during leisure time, jogging, cycling
in winter, and cycling in summer. The level of physicalactivity was classified as previously reported:24 (1) low:
engaging in light physical activity such as walking or biking
for less than 2 hours/week; (2) moderate: engaging in lightphysical activity for 2–4 hours/week; and (3) high: engaging
in light physical activity for more than 4 hours/week or inmore vigorous activity for any frequency. As we havepreviously reported differences in the risk of hospital
admission for COPD between subjects who reported low
levels of physical activity and those who reported very low
physical activity,6 in the present analysis the ‘‘low’’ category
was split into very low physical activity (corresponding tothose who reported mainly sitting during work, no activity
during leisure time, and no jogging or cycling) and low levelsof physical activity for the remaining subjects.

Statistical analysis
Kaplan-Meier curves and log rank tests of both COPD
admission and mortality were performed after stratifying bylevels of regular physical activity. In multivariate analysis,
physical activity categories were a priori combined into ‘‘very
low’’ and ‘‘low, moderate or high’’ levels according to theresults of a previous study.6
For the study of the association between physical activity
and COPD admission, the use of Poisson regression26 was
ruled out because of the presence of overdispersion in ourdata and a high proportion of subjects not experiencing
hospital admission. Instead, zero-inflated negative binomial
regression with the number of COPD admissions as theoutcome was used since it takes into account individuals
more prone to repeated admission and provides moreconservative confidence intervals and p values.27 In addition,
Cox proportional hazards regression, modelling time fromrecruitment to first event, was used with COPD admission
and mortality (all-cause, respiratory and cardiovascular) as
the outcomes, checking the proportionality of multivariate
models.
Among the variables detailed above, those considered as
potential confounders of the association between physicalactivity and COPD admission or mortality were tested andwere maintained in the final multivariate models if they wereindependently associated both with the outcome andexposure (p,0.05) or if they modified the risk ratio estimate
for any of the remaining covariates (>5% change).28 Finalmodels were built keeping the most parsimonious model thatstill explains the data.
The final multivariate models for both COPD admission
and mortality were stratified according to sex, age, COPD
severity, and history of ischaemic heart disease. If differencesin the risk estimate were found, interaction terms among
variables where effect modification was plausible were tested
for. For the sensitivity analyses, the final models foradmission and mortality were run excluding subjects with
self-reported asthma, those who had never smoked, andthose less than 40 years of age. The analysis was performed
using Stata release 8.0 (StataCorp, College Station, TX, USA).

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774

Garcia-Aymerich, Lange, Benet, et al

Table 1 Baseline characteristics of 2386 COPD subjects recruited from the general
population in Copenhagen, Denmark

Sex, n (%)
Mean (SD) age (years)
Education (mean (SD) years at school)
Low income, n (%)Mean (SD) BMI (kg/m2)
Ischaemic heart disease, n (%)`
Asthma, n (%)`
Dyspnoea, n (%)`
0 (no dyspnoea)
1 (dyspnoea in effort)
2 (dyspnoea walking)3 (dyspnoea at rest)
Sputum, n (%)Smoking, n (%)
Never
ExCurrent
COPD severity (GOLD stages), n (%)1
I: Mild (FEV1 >80%)
II: Moderate (FEV1 ,80% and >50%)
III: Severe (FEV1 ,50% and >30%)
IV: Very severe (FEV1 ,30%)
Any medical visit to any doctor in previous
year, n (%)**

All subjects*(n = 2386)

Women(n = 1100)

Men(n = 1286)

59.5 (10.9)
8.3 (1.9)946 (40.9)
24.9 (4.2)
634 (26.6)
268 (11.8)

1100 (46.1)
59.3 (10.8)
8.3 (1.8)
498 (47.8)
24.2 (4.5)
249 (22.6)
131 (12.5)

1286 (53.9)
59.7 (11.0)
8.4 (2.0)448 (35.2)
25.6 (3.8)
385 (29.9)
137 (11.3)

978 (41.1)
841 (35.4)
240 (10.1)
318 (13.4)
939 (39.4)

421 (38.5)
410 (37.5)
119 (10.9)
144 (13.1)
381 (34.7)

557 (43.4)
431 (33.6)
121 (9.4)
174 (13.6)
558 (43.5)

230 (9.7)459 (19.3)
1692 (71.0)

174 (15.9)
184 (16.8)
737 (67.3)

56 (4.3)
275 (21.4)
955 (74.3)

833 (35.1)
1095 (46.1)
354 (14.9)
94 (3.9)
1871 (78.8)

363 (33.1)
521 (47.6)
166 (15.2)
45 (4.1)
911 (83.2)

470 (36.7)
574 (44.8)
188 (14.7)
49 (3.8)960 (74.9)*The numbers do not always add up to 2386 as some values are missing for certain variables: 11 in education, 5 incohabitation, 72 in income, 12 in BMI, 117 in asthma, 9 in dyspnoea, 5 in sputum, 5 in smoking, 10 in lungfunction, and 10 in visits to doctors.
Low household income was defined as income lower than 4000 Danish kroner per month.
`Ischaemic heart disease and asthma were self-reported and obtained from medical records. Dyspnoea was self19
reported and categorised according to the Modified British Medical Research Council questionnaire.
Sputum was considered present if subjects answered positively to the question ‘‘Do you usually bring up phlegm
from your chest in the morning or during the day?’’.
3
1COPD severity was classified according to GOLD stages.
**Any medical visit to any doctor in previous year includes visits to the general practitioner, specialist, emergency
room or private doctor.

Table 2 Regular physical activity in 2386* COPD subjects recruited from the general population in Copenhagen, Denmark
according to COPD severity (GOLD stages)

Physical activity at work
Mainly sitting
Sitting and standing
Walking & lifting
Heavy activity
Physical activity during leisure time
Light activity ,2 h/week and no heavy activity
Light activity 2–4 h/week and no heavy activity
Light activity .4 h/week and/or heavy activity,4 h/week
Heavy activity .4 h/week
Jogging
Cycling winter (hours/week)
No
,0.5
0.5–1
1–2
.2
Cycling summer (hours/week)
No
,0.5
0.5–1
1–2
.2
Physical activity summary score
Very low
Low
ModerateHigh

All subjects(n = 2386)

GOLD I:
Mild(n = 833)

GOLD II:
Moderate(n = 1095)

GOLD III:
Severe(n = 354)

GOLD IV:
Very severe(n = 94)824 (40.0)
763 (37.0)
392 (19.0)
83 (4.0)280 (38.7)
254 (35.1)
156 (21.6)
33 (4.6)

365 (37.9)
376 (39.0)
182 (18.9)
41 (4.2)

129 (43.7)
111 (37.6)
48 (16.3)
7 (2.4)44 (61.1)
20 (27.8)
6 (8.3)2 (2.8)0.003

540 (22.7)
1073 (45.2)
713 (30.0)

123 (14.8)385 (46.4)
296 (35.7)

246 (22.6)
506 (46.4)
318 (29.2)

124 (35.2)
143 (40.6)
82 (23.3)

42 (45.2)
37 (39.8)
14 (15.0),0.00149 (2.1)
39 (1.6)

26 (3.1)
20 (2.4)

20 (1.8)
17 (1.6)

3 (0.9)2 (0.6)

0 (0)
0 (0)

1839 (77.5)
224 (9.5)
180 (7.6)
97 (4.1)
31 (1.3)

582 (70.4)
108 (13.1)
79 (9.5)
41 (4.9)
17 (2.1)

865 (79.4)
85 (7.8)
79 (7.3)
49 (4.5)
11 (1.0)299 (84.9)
25 (7.1)
19 (5.4)
6 (1.7)3 (0.9)83 (89.2)
6 (6.5)3 (3.2)
1 (1.1)0 (0),0.0011481 (62.5)
273 (11.5)
291 (12.3)
195 (8.2)
131 (5.5)429 (51.9)
124 (15.0)
136 (16.4)
86 (10.4)
52 (6.3)705 (64.7)
114 (10.4)
122 (11.2)
90 (8.3)
59 (5.4)

260 (74.0)
29 (8.2)
29 (8.2)
17 (4.8)
17 (4.8)

78 (84.8)
6 (6.5)3 (3.2)2 (2.2)3 (3.3),0.001219 (9.2)
294 (12.4)
1089 (45.8)
773 (32.6)

45 (5.4)
69 (8.3)
389 (46.9)
327 (39.4)

97 (8.9)138 (12.7)
511 (46.9)
344 (31.5)

54 (15.3)
65 (18.5)
148 (42)85 (24.2)

20 (21.5)
20 (21.5)
39 (41.9)
14 (15.1),0.001

p value(x2 test)

0.068

Values are presented as n (%).
*The numbers do not always add up to 2386 as some values are missing for certain variables: 324 in physical activity at work, 11 in physical activity during leisuretime, 8 in jogging, 15 in cycling in winter, 15 in cycling in summer, and 10 in lung function (GOLD stage).

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Physical activity in COPD subjects

1.00

775

A

0.75

High
Moderate

0.50

Low
Very low0.25
p<0.0001
0.00

0

5

10

15

20

Years
1.00

B

0.75
0.50
High
Moderate
Low
Very low0.25
p<0.0001
0.00

0

5

10

15

20

Years
Figure 1 (A) Kaplan-Meier curve of time to first COPD admission
during follow up according to level of regular physical activity. (B)Kaplan-Meier curve of time to death (all-cause mortality) according tolevel of regular physical activity.

RESULTS
Description of sample and events (COPD admission,
death) during follow up
A total of 2386 subjects with COPD were included in the
study. At baseline half were men, mean age was 60 years,
mean body mass index 24.9 kg/m2, 12% reported having
suffered asthma at some time, and 71% were current smokers(table 1).
Classification of severity according to GOLD stages showeda high prevalence of mild (35%) and moderate (46%) COPD.
Very low, low, moderate, and high levels of physical activity
were reported by 9%, 12%, 46%, and 33% of subjects,
respectively (table 2). Subjects with more severe COPD hadlower levels of physical activity.
During the mean (SD) follow up period of 12.0 (5.9) years,
22% of participants had at least one hospital admission due to
COPD (median 3, interquartile range 1–5 for those with anadmission). As expected, the subjects admitted to hospitalwere older, had a higher proportion of cardiovascular disease
and asthma, performed lower levels of physical activity, andsuffered more severe COPD. The time to first COPD
admission during follow up was shorter for the subjects
with lower levels of physical activity (fig 1A).
During the follow up period 1425 subjects (60%) died.
Death from respiratory and cardiovascular diseases constituted 18% and 32% of all deaths, respectively, with 14% ofdeaths due to COPD. The subjects who died were older, had ahigher proportion of cardiovascular disease and diabetes,
performed lower levels of physical activity, and also suffered
more severe COPD. The time to death was shorter in subjects
with lower levels of physical activity (fig 1B).
Association between physical activity and both COPD
hospital admission and mortality
In the multivariate negative binomial model with the numberof COPD admissions as the outcome, subjects who reported
low, moderate, or high levels of physical activity had a lower
risk of a COPD admission than those reporting a very low
level of physical activity, after adjusting for confounders(incidence rate ratio (IRR) 0.72, 95% CI 0.53 to 0.97,
p = 0.033; table 3). Using the time to first COPD admission
as the outcome in a multivariate Cox regression modelyielded very similar results (hazard ratio (HR) 0.76, 95% CI
0.58 to 0.99, p = 0.039).
After adjusting for all relevant confounders, subjects whoreported low, moderate or high physical activity had a lower
risk of all-cause mortality (HR 0.76, 95% CI 0.65 to 0.90,
p = 0.001), death from respiratory causes (HR 0.70, 0.48 to
1.02, p = 0.060), and death from cardiovascular causes (HR0.77, 0.58 to 1.02, p = 0.065) than the group with very low
physical activity (table 4).
After stratification for sex, age, COPD stage, and history of
ischaemic heart disease, subjects who reported low, moderateor high level of physical activity had a reduced risk of both
hospital admission for COPD and death due to any cause inall subgroups of subjects than those with a very low level ofphysical activity, although statistical significance was lost in
many models, most likely due to a reduction in statisticalpower (data not shown, available from the authors).
Sensitivity analyses yielded very similar results. Afterexcluding the subjects who reported having suffered asthma
at some time, the adjusted IRR of a COPD admission for
those with low, moderate or high physical activity comparedwith those reporting very low physical activity was 0.72 (95%
CI 0.50 to 1.04, p = 0.082); correspondingly, the adjusted HR
for all-cause mortality was 0.76 (95% CI 0.63 to 0.91,

Table 3 Crude and adjusted associations between level of physical activity and numberof COPD admissions in COPD subjects (zero-inflated negative binomial regression)

Physical activity (combined)
Very low
Low/moderate/highPhysical activity (categories)
Very low
Low
ModerateHighp for linear trendn*

Crude IRR
(95% CI)p value

Adjusted IRR(95% CI)p value

219
2155

1
0.63 (0.46 to 0.86)

0.004

1
0.72 (0.53 to 0.97)

0.033

219
294
1089
772

1
0.73 (0.49 to 1.08)
0.63 (0.45 to 0.88)
0.57 (0.40 to 0.82)

0.113
0.006
0.002
0.002

1
0.77 (0.53 to 1.14)
0.68 (0.49 to 0.93)
0.76 (0.53 to 1.08)

0.192
0.018
0.121
0.104

IRR, incident rate ratio; CI, confidence interval.
*The number of subjects may be lower in the multivariate models as some values are missing for certain variables(see tables 1 and 2). One subject was excluded from the zero-inflated negative binomial regression model forrecording 65 COPD admissions during follow up (outlier value).
Multivariate model adjusted for sputum and FEV1 in the count component, and for age, ischaemic heart disease,smoking habit, sputum, visits to doctor, and FEV1 in the zero-inflated component of the zero-inflated negative
binomial regression.

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0.001,0.0001,0.0001,0.001

10.84 (0.58 to 1.23)
0.73 (0.54 to 0.98)
0.81 (0.59 to 1.11)

0.372
0.035
0.194
0.195

p = 0.003). After excluding never smokers, the adjusted IRR
of a COPD admission was 0.70 (95% CI 0.52 to 0.96,
p = 0.026) and the adjusted HR of all-cause mortality was
0.76 (95% CI 0.64 to 0.90, p = 0.001). After excluding subjects
less than 40 years of age, the adjusted IRR of a COPD
admission was 0.72 (95% CI 0.53 to 0.98, p = 0.037) and theadjusted HR of all-cause mortality was 0.77 (95% CI 0.65 to
0.91, p = 0.002).
Given the results of the bivariate analysis (figs 1A and B),
all analyses were run taking together those reporting a very
low or low level of physical activity (n = 513) as the reference
category, providing an adjusted IRR for a COPD admission of
0.80 (95% CI 0.64 to 1.01, p = 0.065) and the following
adjusted HRs for mortality: all-cause 0.71 (95% CI 0.63 to
0.80, p,0.001), respiratory causes 0.71 (95% CI 0.53 to 0.95,
p = 0.021), and cardiovascular causes 0.82 (95% CI 0.66 to
1.03, p = 0.084).

10.55 (0.38 to 0.79)
0.47 (0.36 to 0.63)
0.45 (0.34 to 0.61)

DISCUSSION*The number of subjects may be lower in the multivariate models as some values are missing for certain variables (see tables 1 and 2).
Each row is a multivariate model adjusted for sex, age, income, BMI, smoking, glucose, systolic blood pressure, and FEV1.
`Each row is a multivariate model adjusted for sex, age, BMI, myocardial infarction, asthma, sputum, smoking, asthma6smoking interaction, and FEV1.
1Each row is a multivariate model adjusted for sex, age, income, ischaemic heart disease, myocardial infarction, stroke, smoking, glucose, systolic blood pressure and FEV1.

0.622
0.028
0.142
0.072
1
0.89 (0.55 to 1.44)
0.64 (0.43 to 0.95)
0.72 (0.46 to 1.12)
0.089,0.001,0.001,0.001
10.68 (0.44 to 1.06)
0.41 (0.28 to 0.59)
0.31 (0.21 to 0.46)
0.744,0.001,0.001,0.0011
1.04 (0.84 to 1.27)
0.73 (0.61 to 0.86)
0.72 (0.59 to 0.86)
0.009,0.001,0.001,0.00110.77 (0.63 to 0.94)
0.52 (0.44 to 0.61)
0.48 (0.40 to 0.57)

10.77 (0.58 to 1.02),0.00110.47 (0.36 to 0.62)
10.70 (0.48 to 1.02),0.00110.40 (0.29 to 0.57)
0.001
10.76 (0.65 to 0.90)

p valuep value,0.001
10.53 (0.45 to 0.62)

HR (95% CI)
p valueHR (95% CI)
HR (95% CI)

HR (95% CI)

Crude
Adjusted
Crude

0.060

HR (95% CI)
p valueHR (95% CI)

Physical activity (combined)
Very low
Low/moderate/highPhysical activity (categories)
Very low
Low
ModerateHighp for linear trend

Adjusted`

p value

Adjusted1
Crude

Cardiovascular mortality(n = 2386, 461 deaths)*
Respiratory mortality(n = 2386, 254 deaths)*
All-cause mortality(n = 2386, 1425 deaths)*

Crude and adjusted associations between physical activity and mortality in COPD subjects (Cox regression)
Table 4www.thoraxjnl.com

0.065

Garcia-Aymerich, Lange, Benet, et al

p value

776This 20 year follow up study of 2386 subjects with COPD
shows that, for these subjects, a level of physical activity
equivalent to walking or cycling 2 hours/week or more wasassociated with a 30–40% reduction in the risk of both
hospital admission due to COPD and respiratory mortality.
This is the first population-based cohort study showing that a
relatively small amount of physical activity may haveimportant beneficial effects on the course of COPD. To date,
only the British guidelines for COPD8 advise that COPD
patients should be encouraged to exercise (page S12), a
recommendation that so far is not evidence-based. The
present results provide robust evidence in favour of thisrecommendation and support for its consideration in future
COPD guidelines.
The results of this study are highly consistent with ourprevious observation of a reduction in COPD hospital
admissions among patients with COPD recruited fromtertiary hospitals in Barcelona who reported a level ofphysical activity equivalent to walking 1 hour daily.6 The
important environmental and climatic differences between
Copenhagen and Barcelona are likely to result in different
patterns of physical activity, reinforcing the external validityof the reported associations.
Some respiratory rehabilitation trials have shown areduced risk of COPD admission.29–31 Since the majority of
respiratory rehabilitation programs include a component of
exercise training, it could be considered that the effects
reported in our study and those reported in respiratory
rehabilitation studies are consistent. However, respiratory
rehabilitation also incorporates other pharmacological andnon-pharmacological interventions and the effect of exercise
training cannot be isolated.32 Whereas respiratory rehabilitation should be considered in specific COPD patients, ourresults suggest the convenience of incorporating the advice ofincreasing or maintaining a moderate level of physicalactivity at any medical encounter with patients with COPD
of all stages. Further interventional studies should test theefficacy and effectiveness of physical activity advice in COPD
subjects.
The mechanisms underlying the potential beneficial effects
of regular physical activity in COPD are not known, althoughsome evidence regarding muscle function, exercise capacity,and inflammation may give support to its biologicalplausibility. Physical activity improves peripheral muscle
function,33 and this has been related to reduced use of healthservices in patients with COPD.34 At the cellular level, exercise
training improves the bioenergetics of skeletal muscle in
COPD patients35 which, through a reduction in lactate
production during exercise, could reduce symptoms.36 On
the other hand, exercise capacity has been associated with aPhysical activity in COPD subjects

lower risk of hospital admission for COPD exacerbation37 anda lower risk of mortality38 39 in COPD cohorts. The extent towhich exercise capacity in COPD patients is influenced byregular physical activity and vice versa is not known,
although a cross sectional association between the two has
been reported.40 Finally, important anti-inflammatory andanti-oxidant effects have been reported both in healthy
subjects exposed to moderate levels of exercise41 42 and in
COPD patients participating in rehabilitation programs.43 44
As with any observational study, ours may be affected byseveral limitations. Since losses to follow up are the maincause of selection bias in longitudinal studies45 and only four
subjects (0.2%) were lost to follow up in our study, it isunlikely that selection will have biased the estimates of theeffects of physical activity in the course of COPD. It is most
likely that we will have measured regular physical activity
with a degree of non-differential misclassification, bothbecause of the inherent limited validity of the questionnaire
and the omission of changes in physical activity duringfollow up. In either case, the resulting effect was mostprobably a reduced estimate of the effects of physicalactivity.22 45 Given that the present study was not specificallydesigned to examine the effects of physical activity, direct
measures were not available but should be considered infuture studies. Our study was designed to test the hypothesisthat physical activity may reduce the risk of COPD admission
or respiratory related death in COPD patients, and consequently our study population included only patients with
COPD. The inclusion of a reference group without COPD
would not have been appropriate since control subjects
exposed to physical activity would not have had theopportunity of experiencing the expected effects.
We considered the possibility of dyspnoea acting as aconfounder since it was not included in the final models,even though its presence was associated with both physicalactivity and the outcomes. The inclusion of dyspnoea in the
regression models did not change the magnitude of theassociations between physical activity and COPD admission
or mortality (IRR for COPD admission 0.82, 95% CI 0.60 to
1.11; HR for mortality 0.80, 95% CI 0.68 to 0.95), with themagnitude of the potential confounding effect being virtually
null.45 In addition, since dyspnoea could also be anintermediate variable between reduced levels of physicalactivity and an increased risk of admission or mortality, andas dyspnoea was correlated with physical activity, its
inclusion in our multivariate models was avoided. We are
currently exploring the applicability of marginal structuralmodels to disentangle the individual effects of physicalactivity and dyspnoea.46
It should also be considered whether the group of subjects
who reported very low physical activity represent a specificgroup with an unhealthy lifestyle, which could partiallyaccount for an increased risk of COPD admission andmortality. However, multivariate models already included
smoking and income as covariates, and the inclusion of
alcohol consumption or other sociodemographic factors(education, marital status or cohabitation) did not change
the estimates for physical activity (results available from theauthors). Other markers of lifestyle such as diet were notavailable but should be explored in future studies.
The lack of a linear dose-response relationship between
levels of physical activity and admission to hospital or
mortality may cast some doubts on the observed estimates.
However, no clear dose-response relationship between
physical activity and health related outcomes has beenreported for hypertension, obesity, cancer, osteoporosis,
quality of life, depression and anxiety, among otherdisorders.47 Whether the lack of a clear dose-response
association is due to the real lack of a dose-response777

relationship, a lack of sensitivity in determining the dose ofphysical activity, or uncontrolled confounders is generally not
known.47 However, because the kind of dose-response
relationship is important for public health, we recommendthat this issue should be addressed in further research byusing more accurate measures of physical activity including
frequency, duration, and intensity.47
In summary, our results provide robust evidence that theperformance of regular physical activity by patients with
COPD is associated with an important reduction in the risk ofboth admission to hospital with COPD and all-cause andrespiratory mortality. The magnitude of this effect and thefact that the type of physical activity required to achieve it
can be easily recommended without the need for additional
training or specialised supervision make these findings
particularly promising. Our results provide evidence that
future COPD guidelines should consider the recommendationthat COPD patients be encouraged to maintain or increase
their levels of regular physical activity. Given that COPD is achronic disease associated with a high socioeconomic burden
and health consequences, such a measure is likely to result ina relevant public health benefit.

ACKNOWLEDGEMENTS
The authors thank Dr Jorgen Vestbo for his stimuli and advice oncommencing the study.
.....................

Authors’ affiliations

J Garcia-Aymerich, M Benet, J M Antó, Respiratory and Environmental
Health Research Unit, Institut Municipal d’Investigació Mèdica (IMIM),
Barcelona, Spain
P Lange, P Schnohr, Copenhagen City Heart Study, EpidemiologicalResearch Unit, Bispebjerg University Hospital, Copenhagen, Denmark
P Lange, Department of Cardiology and Respiratory Diseases, Hvidovre
University Hospital, Denmark
J M Antó, Department of Experimental and Health Sciences, Universitat
Pompeu Fabra, Barcelona, Spain
Funding: Supported in part by grants from the Generalitat de CatalunyaDURSI 2001/SGR/00406. JG-A and MB were respectively funded by
the Red RESPIRA Network (RTIC C03/11) and the Red RCESP Network(RTIC C03/09), from the Instituto de Salud Carlos III. The Copenhagen
City Heart Study was supported by grants from The Danish Heart
Foundation, The Danish Lung Association and Danish Medical ResearchCouncil. No part of the research presented has been funded by tobacco
industry sources. The sources of funding had no involvement in study
design and conduct; collection, management, analysis or interpretationof data; and preparation, review, or approval of the manuscript.
Competing interests: none.
JG-A, PL, PS, and JMA participated in the design of the study; PL and PS
coordinated data collection in Copenhagen; JG-A, PL, MB, and JMA
performed the statistical analysis and interpreted the results; JG-A
prepared the first draft of the paper; and all the authors contributed to
the writing of paper. JG-A had full access to all of the data in the study
and takes responsibility for the integrity of the data and the accuracy ofthe data analysis.

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