Clinical course of COPD The progressive nature of chronic obstructive pulmonary

Ten Minute Tutorial
Natural History of COPD
The characteristic symptoms of COPD are chronic and
progressive cough, increased sputum production and
dyspnoea (breathlessness) on exertion.2 Dyspnoea
leads to reduced activity, deconditioning of the muscles
and further inactivity.1 As the symptoms worsen, the
patient’s quality of life (QoL) and functional health will
also deteriorate: patients may feel increasingly isolated as
they may become unable to carry out everyday activities.
This can result in patients suffering from anxiety and
depression. Exacerbations (the acute onset of sustained
worsening of symptoms requiring additional medical
attention), become more likely as the disease progresses.3
Chronic cough and sputum production precede the
development of airflow limitation by many years. This
pattern offers a unique window of opportunity to identify
smokers and others at risk of COPD, and intervene
when the disease is not yet a major health problem. The
progression of COPD has historically been assessed
using changes in airflow obstruction, especially FEV1.
Natural history of COPD: Fletcher & Peto Curve 1977
Concepts relating to the natural history of chronic
obstructive pulmonary disease (COPD) arise most
importantly from the classic study of Fletcher, Peto and
colleagues which remains the landmark reference for
the natural history of COPD.4 They performed an eightyear prospective study of working men in London and
developed the much reproduced diagram, frequently
termed the “Fletcher-Peto curve” (Figure 1). This
schematic diagram continues to form the basis for
understanding the progression of this disorder.
Figure 1 illustrates the relationship between long-term
cigarette smoking, decline in lung function (FEV1) and life
expectancy, and suggests slower decline in lung function
during the earlier stages of the disease.4 However, not
all patients will follow the same clinical course outlined
in the Fletcher-Peto curve, and clinical factors other
than airflow limitation that are relevant to COPD natural
history (e.g. cough, dyspnoea and QoL measures) remain
undefined within the curve.
FEV1 % value at age 25 years
Never smoked
- non-susceptible
at 45
at 65
Age (years)
Figure 1. Effects of smoking and smoking cessation on decline in lung
function (Fletcher-Peto curve) reproduced with permission (Fletcher &
Peto, 1977).4
Natural history of COPD: current evidence
Recent studies have suggested that FEV1 decline may
in fact be greater during earlier rather than later stages
of disease.5–7 This is reflected in the recently published
modified curve (Figure 2),8 which includes data from
the Framingham study (healthy non-smokers aged
13-80 years followed for 26 years with standardised
spirometry)10 and various large trials where there was a
faster decline in GOLD stage I-II than stage III-IV groups
(susceptible smokers).5-7 The implication of this new
data is that early detection is critical to preserve lung
function by interventions such as smoking cessation.
Earlier detection allows treatment of symptoms by
pharmacological interventions and improving outcomes
with pulmonary rehabilitation.
FEV1 % value at age 25 years
Clinical course of COPD
The progressive nature of chronic obstructive pulmonary
disease (COPD) is so fundamental that it is included in
the definition adopted in the Global Initiative for Chronic
Obstructive Lung Disease (GOLD) guidelines. According
to GOLD, COPD is a disease state ‘characterized by
airflow limitation that is not fully reversible. The airflow
limitation is usually both progressive and associated
with an abnormal inflammatory response of the lungs to
noxious particles or gases’.1
Never smoked
Early smoking
Late smoking
Age (years)
Figure 2. Modified Fletcher-Peto curve redrawn by Jones & Østrem to
incorporate findings of recent advances in the natural history of COPD
including FEV1 decline data from the UPLIFT study demonstrating
greater annual rate of FEV1 decline during early stages of disease
(Adapted with permission of the editors, Primary Care Respiratory Journal)8
Clinical implications of early lung decline in COPD
Patients with early lung decline may be missed as
most COPD patients remain undiagnosed or are
diagnosed in a late stage of the disease, even though
they are smokers or have a smoking history (Table 1).8
Under-diagnosis or misdiagnosis of COPD can mean
that patients remain untreated, or that they receive
inappropriate or suboptimal treatment, leading to poor
Table 1. Reasons for underdiagnosis/misdiagnosis and undertreatment
of COPD and potential solutions. Adapted with permission from Jones
& Ostrem 20118
Underdiagnosis Physician lack
of symptom
awareness and
risk factors for
for COPD
(spirometry) in at
risk patients
Perception that
COPD is self
education of
Underuse of
spirometry as
diagnostic tool
and training in
spirometry use
Patients lack
of symptom
awareness and
risk factors
Consider asking
questions about
symptoms and
general QoL
perception of
cough as ‘normal’ of smoking
status and
Inaccurate use of
Increase staff
training on
spirometry use
between COPD
and asthma
differences in
and symptoms
between COPD
and asthma
and perform
Achieving earlier diagnosis in practice
NICE suggests that in order to identify early disease,
post bronchodilator spirometry should be performed in
patients who are over 35, current or ex-smokers, and
have a chronic cough.2 The next step is to conduct
a detailed assessment of symptoms through direct
questioning and physical examination, with diagnosis
being confirmed by spirometric measurements of airflow
limitation (primarily FEV1 and FVC) (see
TMT: ‘Diagnosis of COPD’ and ‘Is it COPD or something
else?’) Traditionally the severity of disease has been
equated with the degree of airflow limitation (see Table
2 below) but NICE recommends that there should be
a multidimensional assessment of severity (using tools
such as the BODE index (Body Mass Index, Obstruction
(FEV1% predicted), Dyspnoea (MRC score), Exercise
(as measured by six-minute walking test) and the DOSE
(Dyspnoea [MRC score], Obstruction [FEV1% predicted;
Smoking status, Exacerbation frequency) score.2
Table 2. Severity of airflow obstruction (Reproduced with permission
from National Clinical Guideline Centre 2010)2
Severity of airflow
FEV1 (% predicted)*
50% – 79%
30% – 49%
Very severe
<30% (or <50% + respiratory
* Where FEV1/FVC <0.7
** If FEV1 ≥80% predicted, then the patient must be symptomatic
For those patients who are at risk and who have
potentially early disease, the International Primary Care
Respiratory Group (IPCRG) also recommends that
people over 35 years old should be evaluated for their
risk of developing or having COPD by taking a history
or using validated screening questionnaires such as the
IPCRG COPD risk evaluation questionnaire. Those who
screen positive should then be further assessed by:12,13
• P
erforming ‘case-identification’ spirometry to exclude
those with normal FEV1 and so identify those who
require more complete investigation for COPD. Those
testing positive should then undergo clinical review
and diagnostic standard spirometry
• Alternatively going directly to diagnostic spirometry
to patients who have symptoms and risk factors, or a
positive screening questionnaire, or whose screening
FEV1 is outwith normal limits.
Current guidelines are in broad agreement that COPD
treatment should follow a stepwise approach, depending on
disease severity (Figure 3).1,2 However, active risk reduction
(e.g. smoking cessation and influenza vaccination) should
also be part of the overall treatment plan.
In early stages of COPD life style changes of smoking
cessation and physical activity may affect outcome.
Very often patients do not get this information until
their disease is advanced and the best opportunities
to help are lost. Pulmonary rehabilitation is usually
reserved for people with MRC dyspnoea scale three
or above, but may also be effective in people with less
degrees of impairment.
Figure 3. NICE algorithm on use of inhaled therapies for COPD
Related Ten Minute Tutorials
A basic guide to diagnosing COPD
COPD or something else?
Spirometry and lung function
Early diagnosis: Case finding or screening?
Managing the COPD patient
What you need to know
Symptoms of COPD such as chronic cough and
sputum production precede the development of
airflow limitation by many years
Patients with early lung decline may remain
undiagnosed (and therefore untreated) leading
to poor outcomes
SABA: Short-acting ß2 agonist SAMA: Short-acting muscarinic antagonist LABA: Long-acting ß2 agonist
LAMA: Long-acting muscarinic antagonist *SABA (as required) may continue at all stages
­­—————>Offer therapy (strong evidence)
-------> Consider therapy (less strong evidence)
Reproduced with permission from: National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary
disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London:
National Clinical Guideline Centre © National Clinical Guideline Centre - Acute and Chronic Conditions 2010.
As the disease progresses and lung function declines,
regular (maintenance) treatment with one or more
long-acting bronchodilators, such as a long-acting
muscarinic antagonist (LAMA; also known as a longacting anticholinergic) or long-acting ß2-agonist (LABA),
should be introduced. In addition, for those with
FEV1<50% of predicted and exacerbations inhaled
steroids are indicated.
Potential benefits of earlier treatment with long
acting bronchodilators
Bronchodilator therapy is a foundation treatment for
symptomatic COPD and reduces breathlessness,
improves quality of life allowing some to maintain
physical activity.1 Data from TORCH and UPLIFT studies
suggest that long-acting bronchodilator therapy in GOLD
stage 2 and 3 may reduce the decline in lung function.5,6
Recent data from the ECLIPSE study also suggests
that there is a distinct COPD phenotype characterized
by frequent exacerbations, who may also benefit from
earlier and aggressive therapy.14 Those patients with a
history of frequent exacerbations tend to have faster
lung function decline than patients with infrequent
exacerbations.15 Results from studies suggest that
exacerbations where the patient was treated early after
onset of symptoms had a faster recovery time, compared
with exacerbations where there was a delay
in treatment.15
In conclusion, it is important for all healthcare
professionals to aim to identify early-stage COPD
patients and to initiate smoking cessation before too
much damage is done. Earlier identification allows
people with symptoms and exacerbations to receive
drug treatment to relieve their distress and life style
changes which can keep them healthier.
Early identification of COPD can result in
better long term outcomes as the decline in
lung function is faster in early stages, thus
late diagnosis means there is less to gain by
smoking cessation.
Case identification can be used to identify
patients at risk and/or those with early disease
It is important to advocate lifestyle changes
(such as smoking cessation and physical
activity) in patients with early disease.
Depending on assessment of symptoms and
exacerbations, long-acting bronchodilator and
inhaled steroids therapy should be used.
Think about…
• Are you aware of the implications of early
decline in lung function?
• How would you identify those patients at risk
of early stage disease?
• What lifestyle changes would you recommend?
• Do you understand what bronchodilator
therapies should be used and when (NICE
1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global
Strategy for the Diagnosis, Management and Prevention of COPD (updated
2009). Gig Harbor, WA, USA: December 2009. Available from: http://www.
2. National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary
disease: management of chronic obstructive pulmonary disease in adults in
primary and secondary care. London: National Clinical Guideline Centre.
3. Burge S, Wedzicha JA. COPD exacerbations: definitions and classifications.
Eur Respir J Suppl 2003;41:46s–53s.
4. Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med
J 1977;1(6077):1645–8.
5. Decramer M, Celli B, Kesten S et al. Effect of tiotropium on outcomes in
patients with moderate chronic obstructive pulmonary disease (UPLIFT):
a prespecified subgroup analysis of a randomised controlled trial. Lancet
6. Jenkins CR, Jones PW, Calverley PM, et al. Efficacy of salmeterol/fluticasone
propionate by GOLD stage of chronic obstructive pulmonary disease:
analysis from the randomised, placebo-controlled TORCH study. Respir Res
7. Beaucage F, Frémault A, Janssens W et al. FEV1 decline in COPD patients
according to severity stages. Am J Respir Crit Care Med 2008;177:A401.
Jones R, Ostrem A. Optimising pharmacological maintenance treatment for
COPD in primary care. Prim Care Respir J 2011;20(1):33-45. DOI: http:// Last accessed July 2011
Kohansal R, Martinez-Camblor P, Agusti A et al. The natural history of chronic
airflow obstruction revisited: an analysis of the Framingham offspring cohort.
Am J Respir Crit Care Med 2009;180(1):3–10.
10.Yawn B, Mannino D, Littlejohn T et al. Prevalence of COPD among
symptomatic patients in a primary care setting. Curr Med Res
11.Bednarek M, Maciejewski J, Wozniak M et al. Prevalence, severity and
underdiagnosis of COPD in the primary care setting. Thorax 2008;63(5):402–7.
12.IPCRG Opinion Sheet No 5. Early diagnosis of COPD does help! Date: 17th
November 2009
13.Price D, Crockett A, Arne M et al. Spirometry in primary care caseidentification, diagnosis and management of COPD. Primary Care Respiratory
Journal 2009 18 (3) 216–23
14.Hurst JR, Vestbo J, Anzueto A et al. Susceptibility to exacerbation in chronic
obstructive pulmonary disease. N Engl J Med. 2010 Sep 16;363(12):1128–38.
15.Wedzicha JA & Wilkinson T. Impact of chronic obstructive pulmonary disease
exacerbations on patints and payers. Proc Am Thorac Soc 2006; 3: 218–21
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SPI/SPV2940 Date of preparation: August 2011