Lung function decline and physical activity

The burden of COPD

2

The Fletcher-Peto curve:classical model for the natural history of COPD

FE

V1

(% o

f val

ue a

t age

25)

100

25 50 75

Age (years)

Death

Smokedregularly andsusceptible toits effects

Never smokedor not susceptibleto smoke

Stopped at 45

Stopped at 65

75

50

25

0

COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second

Fletcher C, Peto R. Br Med J 1977;1:1645–8

3

New evidence challenges the concept that lung function decline accelerates over time

FEV1 declines progressively with age in continuous smokers1

Males

Females

Age (years)

A 100

75

50

25

0 10 20 30 40 50 60 70 80 90

FE

V1

(% v

alue

at a

ge 2

5)

NS

CS*

Age (years)

B 100

75

50

25

0 10 20 30 40 50 60 70 80 90

FE

V1

(% v

alue

at a

ge 2

5)

NS

CS*

Figures reproduced from Kohansal et al.1

CS = continuous smoker; FEV1 = forced expiratory volume in 1 second;NS = never smoker

1. Kohansal R et al. Am J Respir Crit Care Med 2009;180:3–102. Decramer M, Cooper CB. Thorax 2010;65:837–41

4

Lung function declines more rapidly in the early stages of COPD

Data from TORCH and UPLIFT show that decline in pulmonary function is faster in early stages of COPD1

• ~50 mL/year in GOLD stage II• ~30 ml/year in GOLD stage IV

In the ECLIPSE study, mean rates of decline in FEV1 were:2

• 35 mL/year for patients in GOLD stage II• 33 mL/year for patients in GOLD stage III• 25 mL/year for patients in GOLD stage IV

GOLD = Global Initiative for Obstructive Lung Disease; FEV1 = forced expiratory volume in 1 s

1. Decramer M, Cooper CB. Thorax 2010;65:837–412. Vestbo J et al. N Engl J Med 2011;365:1184–92

5

Limitations of the Fletcher-Peto curve More recent study shows that loss of lung function is more accelerated during the initial

stages of COPD

Range of average rates of FEV1 decline in patients with COPD, according to initial severity of airflow limitation

FE

V1

(% p

redi

cted

)

100

80

50

30

0

Stage I

Stage II

Stage III

Stage IV

∆ 40 mL/yr

∆ 47–79 mL/yr

∆ 56–59 mL/yr

∆ <35 mL/yr

The dashed segment of the line highlights any stage or part of it where consistent information is still lacking. COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second

Tantucci C, Modina D. Int J COPD 2012;7:95–9

6

Accelerated lung function decline occurs long before FEV1/FVC falls to threshold for definition of COPD

In heavy smokers with mostly normal or mildly impaired lung function:• Decline was greatest in patients with “normal” lung function1

• These patients would be classified as not having COPD

GOLD and ERS/ATS thresholds for COPD (FEV1/FVC <70% or less than lower limit of normal) miss the stage of most rapid decline2,3

Diagnosis of COPD cannot be excluded in heavy smokers when based on above-threshold lung-function test at a single time point1

ATS = American Thoracic Society; COPD = chronic obstructive pulmonary disease; ERS = European Respiratory Society; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; GOLD = Global Initiative for Obstructive Lung Disease

1. Mohamed Hoesein FA et al. Chest 2012;142:1530–82. Rabe KF et al. Am J Respir Crit Care Med 2007;176:532–553. Celli BR et al. Eur Respir J 2004;23:932–46

7

Fast decliners may be a distinct phenotype

The definition of fast decliners is not fully characterized, however, fast decliners have particular characteristics1

Fast decliners have been characterized by:• Current smoking (vs former smokers)2,3

• Bronchodilator reversibility3,4 • Emphysema3

• High levels of airway and systemic inflammatory markers, possibly due to frequent exacerbations5,6

• Higher baseline lung function3

• Low body mass index7

1. Friedlander et al. COPD 2007;4:355–842. Anthonisen et al. JAMA 1994;272:1497–5053. Vestbo et al. New Engl J Med 2011;365:1184–924. Tashkin et al. Am J Respir Crit Care Med 1996;153:1802–115. Crooks et al. Eur Respir J 2000;15: 274–806. Anzueto. Eur Respir Rev 2010; 19: 116, 113–87. Watson et al. Respir Med 2006; 100: 746–53

8

Physical activity declines as disease severity worsens

Activity declines significantly as COPD worsens in severity and is reduced even in mild COPD

12,000

10,000

8,000

6,000

4,000

2,000

0

Ste

ps p

er d

ay

GOLD classification of airflow limitation

CB 1 2 3 4

Data are mean ± 95% CI; p<0.001 for linear relationship between steps per day and GOLD stage of severity.CB = chronic bronchitis; GOLD = Global Initiative for Obstructive Lung Disease; CI = confidence interval; COPD = chronic obstructive pulmonary disease

Adapted from Watz H. Eur Respir J 2009;33:262–72

9

0

10

20

30

40

Shortness of breath and reduced exercise endurance are seen in patients with all severities of COPD

0 1 2 3 4

mMRC score

GOLD II

GOLD III

GOLD IV

Pro

po

rtio

n o

f su

bje

cts

(%)

Mean=1.3

Mean=1.8

Mean=2.3

Agusti A. Respir Res 2010;11:122.

Data are from ECLIPSE, a 3-year observational, longitudinal and controlled study of COPD patients and controls Mean=mean mMRC score or mean distance walked. mMRC, modified Medical Research Council Dyspnoea Scale.

0

10

20

30

40

0

10

20

30

40

0

10

15

20

25

Distance walked (m)

Pro

po

rtio

n o

f su

bje

cts

(%)

Mean=405

Mean=356

Mean=289

0

10

15

20

25

0

25

5

5

10

15

20

5

>0–3

0>3

0–90

>90–

150

>150

–210

>210

–270

>270

–330

>330

–390

>390

–450

>450

–510

>510

–570

>570

–630

>630

–690

>690

–750

>750

–810

n=954

n=911

n=296

10

Functional limitations of COPD are at least as great in young patients as in older patients

In the Confronting COPD study, functional limitations imposed by COPD on persons of <65

years were equal to or greater than those aged >65 years in sports and recreation, social

activities, household chores, sex life and family activities

• Only in normal physical exertion did significantly fewer persons aged <65 yrs (55.7%) than >65 yrs

(62.3%) report being significantly limited as a result of their condition (p<0.05)

0

10

20

30

40

50

60

70

A B C D E F G

Su

bje

cts

lim

ited

(%

)

Key

A = Sports and recreation

B = Normal physical

C = Social

D = Sleep

E = Household chores

F = Sex life

G = Family exertion

*p<0.05 <65 years

≥65 years

COPD = chronic obstructive pulmonary disease

Rennard S et al. Eur Respir J 2002;20:799–805

11

COPD limits the amount of work individuals are able to perform

In the COPD Uncovered study, 70% of COPD patients were no longer working

• Of these 26% reported giving up work because of COPD

• Mean age for those retiring early was 58.33 years (range 45–68 years)

Of those who continued to work, WPAI scores showed:• Impairment with regular activities was more marked than overall work

loss and impaired work activity levels

• ‘Presenteeism’ more of a problem than absenteeism

COPD = chronic obstructive pulmonary disease; WPAI = Work Productivity and Activity Impairment

Fletcher et al. BMC Public Health 2011;11:612

12

Shortness of breath/inactivity downward spiral

Patients avoid shortness of breath by becoming less active, leading to a shortness of breath/inactivity downward spiral

Patient becomes more sedentary to avoid activity producing shortness of breath

(decreases activity)1

Shortness of breathwith activities

De-conditioning aggravates shortness of breath; patients

adjust by reducing activity further1

Figure adapted from Reardon JZ Am J Med 2006.2

1. ZuWallack R COPD 2007;4:293–72. Reardon JZ et al. Am J Med 2006;119(10 Suppl 1):32–72

13

Health status and physical activity are predictors of survival in COPD

Prognostic research in COPD has established several assessments beyond airflow limitation1

Physical activity is the strongest predictor of all-cause mortality in patients with COPD1,2,3

• It has been speculated that physical inactivity leads to dysregulated cellular and molecular circuitry, which directly contributes to multiple chronic health disorders4

Impaired health status has also been shown to be a strong predictor of mortality in COPD5,6

COPD = chronic obstructive pulmonary disease

1. Waschki et al. Chest. 2011;140:331–422. Garcia-Aymerich  et al. Thorax 2006;619:772–83. ZuWallack RL. Monaldi Arch Chest Dis 2003;59:230–34. Booth et al. J Appl Physiol 2002;931:3–305. Oga et al. Am J Respir Crit Care Med 2003;1674:544–96. Halpin et al. Respir Med 2008;102:1615–24

14

Pulmonary rehabilitation and patient education

Exercise training is a cornerstone of pulmonary rehabilitation and significantly improves muscle function1

• Improved exercise endurance is associated with a number of positive outcomes - Reduced hyperinflation (which may reduce shortness of breath)2

- Improved overall pulmonary function2

- Improved health-related quality of life2

• Exercise training may also:- Reduce the risk of hospital readmission3

- Reduce mortality3

Patient education programmes may also improve health status and reduce healthcare resource utilization4

• Reduced risk of hospital admission4

• Improved SGRQ total score, and improved ‘Activity’ and ‘Impact’ sub-scale scores4

SGRQ = St George’s Respiratory Questionnaire.

1. Nici L, et al. Am J Respir Crit Care Med 2006;173:1390–413.2. Yoshimi K, et al. J Thorac Dis 2012;4:259–64.3. Puhan MA, et al. Respir Res 2005;6:54.4. Bourbeau J, et al. Arch Intern Med 2003;163:585–91.

15

Conclusions

Patients with mild/moderate COPD show different rates of lung function decline depending on smoking status and presence of respiratory symptoms1

• Lung function decline is faster during the initial stages of COPD2

Physical inactivity is present in the early stages of COPD3,4

• Activity continues to decline as COPD worsens5

• Physical activity is the strongest predictor of all-cause mortality in patients with COPD6–8

COPD impairs functional abilities and limits ability to work9,10

Early intervention in COPD may interrupt the downward spiral of symptoms and activity limitation11,12

Pulmonary rehabilitation (exercise training) improves muscle function and may reduce hospital admissions and mortality13,14

COPD = chronic obstructive pulmonary disease

1. de Marco R. Am J Respir Crit Care Med 2009;180;956–63; 2. Tantucci C, Modina D. Int J COPD 2012;7:95–9; 3. Walz H et al. Am J Respir Crit Care Med 2008;177:743–51; 4. Decramer M, Cooper CB. Thorax 2010;65:837–41; 5. Walz H. Eur Respir J 2009;33:262–72;6. Waschki et al. Chest. 2011;140:331–42; 7. Garcia-Aymerich  et al. Thorax 2006;619:772–8; 8. ZuWallack RL. Monaldi Arch Chest Dis 2003;59:230–3;9. Rennard S et al. Eur Respir J 2002;20:799–805; 10. Fletcher et al. BMC Public Health 2011;11:612;11. Reardon JZ et al. Am J Med 2006;119(10 Suppl 1):32–72; 12. ZuWallack R COPD 2007;4:293–7; 13. Nici L et al. Am J Respir Crit Care Med 2006;173:1390–413; 14. Puhan MA et al. Respir Res 2005;6:54