382 Clinical Pharmacist December 2010 Vol 2

Chronic obstructive pulmonary disease is an incurable

SUMMARY
CLINICAL FOCUS

condition affecting millions of people worldwide.

Chronic obstructive pulmonary disease (COPD) is a
term used to describe a group of airways diseases

COPD that are not fully reversible. COPD accounts for a

large amount of morbidity and mortality and is
expected to become the third leading cause of death

clinical features worldwide by 2030.

The symptoms of COPD include breathlessness,
chronic cough and regular sputum production.

and diagnosis
Diagnosis should take these symptoms into account,
in addition to exposure to risk factors such as
cigarette smoke. The severity of COPD can be
assessed using spirometry. Mortality may be better
predicted using other measures.
By Hasanin Khachi, DipClinPharm, MRPharmS, Neil
Barnes, FRCP, and Sotiris Antoniou, MSc, MRPharmS
genetics and gender) and “environmental factors” (such as

T
he term chronic obstructive pulmonary disease
(COPD) was first coined by William Briscoe in 1965.1
It is an umbrella term used to describe a group of
airways diseases that are not fully reversible, are
predominantly caused by smoking and affect patients over
35 years of age.2 COPD is a progressive, life-threatening
condition that affects millions of people within the UK and
worldwide. An understanding of the risk factors, symptoms
and diagnostic measures are required to be able to manage
this progressive disease effectively. Details of the
pathophysiology of COPD can be found in Box 1 (p384).
COPD is often undiagnosed — it is estimated that only
900,000 out of three million people who have COPD in
England have been diagnosed.3 Globally, COPD is
currently the fourth leading cause of death and the World
smoking and occupational exposure).2,7
Smoking Tobacco smoke has been implicated in the
development of chronic bronchitis and emphysema since
the 1960s.8 Tobacco smoke has numerous pulmonary
effects, which include the release of destructive proteolytic
enzymes from inflammatory cells in the lung, oxidative
stress and inactivation of a1-antitrypsin (see Box 1, p384).
Although it has been estimated that 15–20% of smokers
develop COPD, recent evidence suggests that the actual
proportion is 50%.9 The risk of COPD developing in
smokers is dose related and is affected by the age at which
smoking started and the total pack-years smoked:

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Health Organization estimates that, by 2030, COPD will
become the third leading cause of death.4,5
In England and Wales, one person dies every 20
minutes as a result of COPD. It accounts for 1.4 million
GP consultations and over 30,000 deaths in the UK each
year.5 COPD is the second most common cause of
emergency admissions to hospital and the fifth largest
cause of readmissions into hospital.6 COPD results in over
one million hospital bed days in England.6 In the UK,
direct care costs associated with COPD amount to £3bn
per year, and the overall cost is £6.6bn annually.6

Risk factors
The risk factors for COPD are not completely
understood — epidemiological studies have identified
associations rather than cause and effect relationships.
It is hypothesised that the risk of developing COPD is
due to an interaction between “host factors” (such as

Hasanin Khachi is highly specialist respiratory

pharmacist, Neil Barnes is consultant respiratory
physician and Sotiris Antoniou is principal
pharmacist for cardiac and respiratory medicine, all
at Barts and The London NHS Trust.
E: hasanin.khachi@bartsandthelondon.nhs.uk
 Vol 2 December 2010 Clinical Pharmacist 383

Number of cigarettes number of years

´ Figure 1: Graph showing effect of smoking and smoking cessation on lung function

CLINICAL FOCUS
Total pack years = smoked per day of smoking
20 100% Never smoked or
not susceptible to

Lung function (percentage of FEV1 value at age 25 years)

smoke
Environmental exposure to tobacco smoke is also
associated with reduced lung function. Maternal smoking
has been shown to affect lung development in utero and is 75%
linked with reduced lung function among offspring in Susceptible
adulthood.10,11 Passive smoking is also associated with smoker
Stopped at age 45 years
reduced lung function, although this association is not as
strong. The effect of smoking and smoking cessation on
50%
lung function is illustrated in Figure 1.

Occupational dusts and chemicals Occupational

Disability
dusts and chemicals have been recognised as co-factors for
developing COPD and there is a relationship between the 25%
degree of lung impairment and the intensity and duration Stopped at age
65 years
of exposure. Examples of implicated substances include
Death
organic and inorganic dusts, chemicals and fumes.2,12 A
survey involving almost 10,000 adult patients showed that 0%
occupational exposure caused 19.2% of COPD cases, with 25 50 75 Age (years)
31.1% having never smoked.13 This is consistent with
American Thoracic Society estimates of occupational
exposure accounting for 10–20% of all COPD cases.14,15 ● Infection: a history of tuberculosis and childhood
infections have both been associated with reduced
Indoor air pollution The burning of open fires of wood, lung function and airflow obstruction that
animal dung, coal and agricultural residues (eg, for predisposes to COPD in later life.7,21 The
cooking and heating) can lead to high levels of indoor air development of pneumonia before two years of age
pollution in poorly ventilated dwellings. The global has been shown to result in a mean loss in FEV1 of
population at risk of this form of COPD is three billion, 0.65L in males, and twice that figure when
with women in parts of the Middle East, Africa and Asia at associated with lifelong smoking22
particular risk.16 This COPD risk factor currently causes ● Socioeconomic status: the risk of developing
10–20% of all cases worldwide and results in two million COPD is inversely associated with affluence.23
deaths each year.17 Reasons are multifactorial and include greater
smoking prevalence, poorer housing and poorer
Genetics The best documented “host factor” for the nutrition23
development of COPD is the recessive, hereditary ● Nutrition: a diet rich in fruit and vegetables is
deficiency of a1-antitrypsin (Box 1, p384). Predominantly associated with a reduced risk of COPD24
affecting people of northern European origin, a1- ● Asthma: the presence of asthma in adults results in a
antitrypsin deficiency results in the early and accelerated 12-fold increased risk of developing COPD.25
development of panlobular emphysema in smokers and Approximately 20% of asthmatics develop signs of
non-smokers, with the risk in smokers increasing irreversible airway limitation26
exponentially.18 Worldwide, a1-antitrypsin deficiency
accounts for only a small number COPD cases.2, 19 Symptoms
COPD is characterised primarily by the presence
Other risk factors Other risk factors for the breathlessness, chronic cough and sputum production.

development of COPD include:
● Lung growth and development: a meta-analysis has
shown a positive correlation between birth weight
and forced expiratory volume in one second (FEV1)
(see “Diagnosis” below) in adulthood7, 20
● Gender: the role of gender in the development of
COPD is unclear, although some studies have
suggested that women are more susceptible to the
effects of tobacco smoke than men. Previous studies
had shown a greater prevalence and mortality
among men than women; however more recent
studies show that in developed countries the
prevalence is now similar, probably as a result of
women living longer and their changing patterns of
smoking2
❝
However, the early stages of COPD are often
asymptomatic and it is not until patients experience
THE RISK OF COPD significant limitation that they seek medical advice.
DEVELOPING IN
SMOKERS IS DOSE Breathlessness For patients, breathlessness (dyspnoea)
RELATED AND IS is often the most concerning early symptom of COPD. It is
AFFECTED BY THE persistent and progressive, and is usually worse with
AGE AT WHICH physical exertion. As the disease progresses, breathlessness
SMOKING STARTED becomes more problematic, even with minimal exertion or
AND THE TOTAL at rest.
PACK-YEARS The Medical Research Council dyspnoea scale (see
SMOKED Box 2, p384), can be used to establish the extent of a
patient’s exertional breathlessness and can help to predict
❞ mortality in COPD.2,27 In addition to defining the degree of
dyspnoea-related disability associated with COPD, the
MRC dyspnoea scale can also be used to determine at
384 Clinical Pharmacist December 2010 Vol 2
Box 1: COPD pathophysiology
CLINICAL FOCUS
Chronic obstructive pulmonary disease (COPD) is an umbrella term
for a group of chronic respiratory diseases, including emphysema
and chronic bronchitis.
Emphysema Emphysema is a pathological process that involves
the progressive and destructive enlargement of the bronchioles,
alveolar ducts and alveolar sacs. This leads to loss of surfaces
available for gas exchange and a loss of elastic recoil in the small
airways. Elastic recoil is essential for maintaining the force of
expiration — its loss in emphysema can result in airways collapse,
especially during expiration, which in turn leads to increased
thoracic gas volume and hyperinflation in the lungs.
There are two main types of emphysema: centrilobular and
panacinar. Centrilobular emphysema is the most common form,
characterised by the destruction of bronchioles, alveolar ducts and
alveoli, and is more common in the upper lobes of lungs in cigarette
smokers and coal miners. Panacinar emphysema is less common
and is associated with deficiency of a1-antitrypsin — a protease
inhibitor that protects against lung damage. It is thought that the
presence of oestrogen, which stimulates the synthesis of protease
inhibitors such as a1-antitrypsin, confers protection in women.
Chronic bronchitis Chronic bronchitis is defined as the presence
of cough and sputum production for at least three months in each
which stage pulmonary rehabilitation would be cost-
effective and indicated (see p393 of accompanying article).
Pulmonary rehabilitation is indicated for patients
admitted to hospital following a COPD exacerbation or for
patients with an MRC score of 3 or higher.
Chronic cough Chronic cough is one of the earliest
symptoms of COPD. Cough can be productive or
unproductive and initially occurs intermittently, becoming
more frequent as the disease progresses. Unlike
breathlessness, chronic cough usually occurs at the earliest
stage of COPD and is often discounted by patients as a sign
of ageing or lack of physical fitness.
Sputum Regular production of sputum in three or more
months over two consecutive years defines the presence of
chronic bronchitis.2 However, sputum purulence in COPD
patients varies considerably (in terms of quantity and
colour, which may depend on the underlying causes of
COPD) and is difficult to evaluate accurately due to
Box 2: Medical Research Council dyspnoea scale27
GRADE DEGREE OF BREATHLESSNESS RELATED TO ACTIVITIES
1 Not troubled by breathlessness except on strenuous exercise
2 Short of breath when hurrying or walking up a slight hill
3 Walks slower than contemporaries on level ground because
of breathlessness, or has to stop for breath when walking at
own pace
4 Stops for breath after walking about 100 metres or after a
few minutes on level ground
5 Too breathless to leave the house, or breathless when
dressing or undressing
of two consecutive years.2 It is an inflammatory process that occurs
in the bronchi in response to inhaled irritants, usually due to
cigarette smoking. This results in the accumulation and
hypersecretion of mucous-secreting glands in the bronchial tree.
Viral and bacterial infections can cause worsening of symptoms
and exacerbations. Common bacterial infections can be caused by
pathogens such as Streptococcus pneumoniae, Moraxella
catarrhalis and Haemophilus influenzae.
In advanced COPD, the impairment of gas diffusion can lead to
hypoxaemia (low oxygen), hypercapnia (increased carbon dioxide)
and pulmonary hypertension, with resultant vascular remodelling,
increased right-ventricular pressure and subsequent right-ventricular
failure, known as cor pulmonale.
Peripheral oedema in cor pulmonale is mediated by the
physiological changes that occur following hypoxaemia and
hypercapnia. These include activation of the renin-angiotensin
system, salt and water retention and a reduction in renal blood flow.
Although patients with emphysema experience greater dyspnoea
than patients with bronchitis, they are better able to preserve gas
exchange (because, unlike bronchitis, the ventilation-to-perfusion
ratio is maintained) and thus are less likely to develop cor
pulomale and polycythaemia (increased red blood cells) at an early
stage.
differing patient habits with sputum (some patients will
swallow rather than expectorate). A change in colour or
volume of sputum may signify the early signs of an
exacerbation of COPD.
Other symptoms Wheeze and chest tightness can occur
at any stage of COPD, but usually occurs in severe COPD.2
More frequent “winter colds” or “winter bronchitis” and
fatigue are also common among those with COPD.
Diagnosis
A diagnosis of COPD should be considered in patients
over the age of 35 years who have a risk factor such as
smoking and who display one or more of the symptoms
described above.28 The diagnosis should take into account
the patient’s medical history and previous exposure to risk
factors for the disease. Airflow obstruction can be
measured accurately using spirometry, and this should be
performed at the time of diagnosis, with specific reference
to the following measures:2,28
● FEV1: volume of air that the patient is able to expel
in the first second (expressed in litres and as a
percentage of the predicted value)
● Forced vital capacity (FVC): total volume of air that
the patient can forcibly exhale in one breath
(expressed in litres and as a percentage of the
predicted value)
● FEV1/FVC: the ratio of FEV1 to FVC
A post-bronchodilator FEV1/FVC ratio <0.7 confirms
the presence of COPD.2,28 If the FEV1 is ³80% of
predicted, a diagnosis of COPD should only be made in
the presence of other respiratory symptoms such as
breathlessness or chronic cough.28
386 Clinical Pharmacist December 2010 Vol 2

Similarities with asthma COPD and asthma may have

CLINICAL FOCUS

some overlapping symptoms but can be distinguished

based on the patient’s history, exposure to risk factors and
spirometry results. Box 3 shows the clinical features
differentiating COPD and asthma. It is worth noting that,
in patients with chronic asthma, the distinction with
COPD is sometimes difficult to make and it is assumed
that asthma and COPD can co-exist in such patients.2

Reversibility testing If COPD diagnosis is in doubt,

reversibility testing can help to distinguish the presence of
COPD or another underlying respiratory disease such as
asthma. Since COPD is characterised by airflow
obstruction that is not fully reversible,28 reversibility
testing using an inhaled bronchodilator (eg, salbutamol)

Scott Camazine | Science Photo Library

can be used to distinguish between COPD and asthma.
Minor degrees of reversibility have no prognostic value,
but a marked post-bronchodilator response greater than
400ml suggests the presence of asthma.28

Severity
The severity of COPD can be classified according to the
patient’s FEV1 compared with predicted values (see
below). However, it should be borne in mind that severity
based on FEV1 may not always correspond to the degree
of symptom control and exacerbation rates.
Disease severity is an indicator of prognosis. The five-
year survival of patients with mild COPD is 78% for men
and 72% for women.29 This reduces to 30% and 24%,
respectively, for patients with severe disease.29
Unsurprisingly, the economic impact of COPD also
correlates with severity, with the annual cost for a patient
Coloured X-ray of the lungs of a patient with chronic obstructive pulmonary disease
with mild COPD estimated at £120 compared with over
£3,000 for a patient with severe COPD.5
According to the National Institute for Health and
Clinical Excellence and the Global Initiative for Chronic
Obstructive Lung Disease, patients with a post-
bronchodilator FEV1/FVC ratio below 0.7 can be
classified as follows:2,28

Box 3: Differences between asthma and COPD28 ● FEV1 ³80%: stage 1 (mild)
FEATURES COPD ASTHMA ● FEV1 50–79%: stage 2 (moderate)
● FEV1 30–49%: stage 3 (severe)
Smoker or ex-smoker Nearly all Possibly
● FEV1 <30%: stage 4 (very severe)
Symptoms under age 35 years Rare Often
Chronic productive cough Common Uncommon Some studies have found that an index known as
“BODE” is a better predictor of exacerbations, hospital
Breathlessness Persistent and Variable admission and mortality than FEV1.30–32 BODE is an
progressive
acronym for:
Night-time waking with Uncommon Common
breathlessness or wheeze ● Body mass index
Significant diurnal or day-to-day Uncommon Common ● Obstruction (degree of airway obstruction):
variability of symptoms measured as a percentage of predicted FEV1
● Dyspnoea: measured using a modified MRC
dyspnoea scale
Box 4: The BODE index28 ● Exercise tolerance: measured with a six-minute
VARIABLE POINTS ON THE BODE INDEX walk test
0 1 2 3
The BODE index is a 10-point scoring system, with a
FEV1 (% of ³65 50–64 36–49 £35 higher score corresponding with a higher likelihood for
predicted) poor patient outcomes. (Box 4 shows how points on the
Distance walked in ³350 250–349 150–249 £149 BODE index are allocated.) The updated NICE guidelines
six minutes (m) suggest that the BODE index should be used to assess the
Modified Medical 0–1 2 3 4 prognosis of all patients. The BODE index can be modified
Research Council to a “BOD” index if there is difficulty carrying out an
dyspnoea scale exercise tolerance test.
The severity of COPD will also guide treatment (see
Body mass index >21 £21 — —
accompanying article, p390).

References
1 Petty TL. The history of COPD. International Journal of COPD 2006:1;3–14.
2 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for
the diagnosis, management, and prevention of chronic obstructive
pulmonary disease. 2008. www.goldcopd.com (accessed 29 October 2010).
3 World Health Organization. Chronic respiratory diseases. www.who.int/
respiratory/copd/burden/en/index.html (accessed 29 October 2010).
4 Hospital Episodes Statistics. Met Office health forecasts for COPD
patients. www.hesonline.nhs.uk (accessed 29 October 2010).
5 Department of Health. On the state of the public health: annual report of
the chief medical officer 2004. July 2005. www.dh.gov.uk (accessed 29
October 2010).
6 British Thoracic Society. The burden of lung disease. June 2006.
www.brit-thoracic.org.uk (accessed 29 October 2010).
7 Chapman KR, Mannino DM, Soriano JB, et al. Epidemiology and costs of
chronic obstructive pulmonary disease. European Respiratory Journal
2006;27:188–207.
8 Hoogendoorn M, Rutten-van Mölken MP, Hoogenveen RT, et al. A dynamic
population model of disease progression in chronic obstructive pulmonary
disease. European Respiratory Journal 2005;26:223–33.
9 Lundbäck B, Lindberg A, Lindström M, et al. Not 15 but 50% of smokers
develop COPD? Report from the obstructive lung disease in Northern
Sweden studies. Respiratory Medicine 2003;97:115–22.
10 Barker DJP. Chronic bronchitis. In: Mothers, babies and disease in later
life. London: BMJ Publishing Group, 1994; pp94–105.
11 Tager IB, Ngo L, Hanrahan JP. Maternal smoking during pregnancy.
Effects on lung function during the first 18 months of life. American
Journal of Respiratory and Critical Care Medicine 1995;152:977–83.
12 Isoaho R, Puoluoki H, Huhti E, et al. Prevalence of chronic obstructive
pulmonary disease in elderly Finns. Respiratory Medicine 1994;88:571–80.
13 Hnizdo E, Sullivan PA, Bang KM, et al. Association between chronic
obstructive pulmonary disease and employment by industry and
occupation in the US population: a study of data from the Third National
Health and Nutrition Examination Survey. American Journal of
Epidemiology 2002;156:738–46.
14 Trupin L, Earnest G, San Pedro M, et al. The occupational burden of
chronic obstructive pulmonary disease. European Respiratory Journal
2003;22:462–9.
15 Balmes J, Becklake M, Blanc P, et al. American Thoracic Society
statement: occupational contribution to the burden of airway disease.
American Journal of Respiratory and Critical Care Medicine
2003;167:787–97.
16 Chan-Yeung M, Ait-Khaled N, White N, et al. The burden and impact of
COPD in Asia and Africa. International Journal of Tuberculosis and Lung
Disease 2004;8:2–14.
Vol 2 December 2010 Clinical Pharmacist 389
17 Smith K. Pollution management in focus. Washington DC: The World
Bank; 1999.
CLINICAL FOCUS
18 Blanco I, de Serres FJ, Fernandez-Bustillo E, et al. Estimated numbers
and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency
in European countries. European Respiratory Journal 2006;27:77–84.
19 Sandford AJ, Weir TD, Paré PD. Genetic risk factors for chronic obstructive
pulmonary disease. European Respiratory Journal 1997;10:1380–91.
20 Lawlor DA, Ebrahim S, Davey Smith G. Association of birth weight with
adult lung function: findings from the British Women's Heart and Health
Study and a meta-analysis. Thorax 2005;60:851–8.
21 Menezes AM, Hallal PC, Perez-Padilla R, et al. Tuberculosis and airflow
obstruction: evidence from the PLATINO study in Latin America.
European Respiratory Journal 2007;(6):1180–5.
22 Shaheen SO, Barker DJP, Shiell AW, et al. The relationship between
pneumonia in early childhood and impaired lung function in late adult
life. American Journal of Respiratory Critical Care Medicine 1994;149:616–9.
23 Prescott E, Lange P, Vestbo J. Socioeconomic status, lung function and
admission to hospital for COPD: results from the Copenhagen City Heart
Study. European Respiratory Journal 1999;13:1109–14.
24 Watson L, Margetts B, Howarth P, et al. The association between diet
and chronic obstructive pulmonary disease in subjects selected from
general practice. European Respiratory Journal 2002;20:313–8.
25 Silva GE, Sherrill DL, Guerra S, et al. Asthma as a risk factor for COPD
in a longitudinal study. Chest 2004;126:5965.
26 Vonk JM, Jongepier H, Panhuysen CI, et al. Risk factors associated with
the presence of irreversible airflow limitation and reduced transfer
coefficient in patients with asthma after 26 years of follow up. Thorax
2003;58:322–7.
27 Bestall JC, Paul EA, Garrod R, et al. Usefulness of the Medical Research
Council (MRC) dyspnoea scale as a measure of disability in patients with
chronic obstructive pulmonary disease. Thorax 1999;54:581–6.
28 National Institute for Health and Clinical Excellence. Management of
chronic obstructive pulmonary disease in adults in primary and secondary
care. June 2010. www.nice.org.uk/cg101 (accessed 29 October 2010).
29 Soriano JB, Maier WC, Egger P, et al. Recent trends in physician
diagnosed COPD in women and men in the UK. Thorax 2000;55:789–94.
30 Ong KC, Earnest A, Lu SJ. A multidimensional grading system (BODE
index) as predictor of hospitalization for COPD. Chest 2005;128:3810–6.
31 Marin JM, Carrizo SJ, Casanova C, et al. Prediction of risk of COPD
exacerbations by the BODE index. Respiratory Medicine
2009;103:373–8.
32 Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow
obstruction, dyspnea, and exercise capacity index in chronic obstructive
pulmonary disease. New England Journal of Medicine
2004;350:1005–12.