(Chest. 2000;117:365S-371S.)
© 2000
American College of Chest Physicians
COPD*
Early Detection and Intervention
Peter M. A. Calverley, MD
*
From the University Clinical Departments, University Hospital Aintree, Long Lane, Liverpool, United Kingdom.
Correspondence to: Peter M. A. Calverley, MD, University Clinical Departments, University Hospital Aintree, Long Lane, Liverpool L9 7AL, United Kingdom; e-mail: pmacal{at}liv.ac.uk
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Abstract
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The compelling evidence for the increasing economic and social
burden of COPD, resulting from its rising prevalence and significant
morbidity, has been reviewed in other sections of this supplement. The
impact of this disease within the United States and globally is
projected to increase irrespective of short-term medical action, but
developing successful strategies to identify the illness and reduce its
impact is essential if this growing problem is to be managed
successfully. In this article, some of the important concepts relevant
to this process are considered, and some of the present techniques used
to intervene in established COPD are reviewed.
Key Words: COPD • identification • treatment
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Introduction
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COPD
is a major cause of mortality and morbidity across the world, and the
disease burden is projected to increase in the next 20
years.1
2
The early identification and treatment of this
condition is clearly important. In an ideal world, we would be
able to define our target population clearly, identify those with
illness with a high degree of specificity and sensitivity, and then
offer effective intervention that would prevent, or at least delay, the
consequences of the illness. However, practical difficulties exist that
limit the implementation of this scheme in COPD.
|
Diagnostic Difficulties
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For many years, the lack of a satisfactory terminology has
hampered both the scientific evaluation and public understanding of
COPD. All international bodies, including the American Thoracic
Society, European Respiratory Society, and the recently developed World
Health Organization/National Heart, Lung, and Blood Institute Global
Obstructive Lung Disease Initiative, emphasize that COPD should be
defined physiologically.
Typical of these definitions is that of the British Thoracic Society:
COPD is a slowly progressive disorder characterized by airflow
obstruction (reduced FEV1 and
FEV1/FVC ratio) that does not vary markedly over
several months of observation. Most of the lung function impairment is
fixed, although some reversibility can be produced by bronchodilator
(or other) therapy.3
There is general agreement that airflow limitation in COPD is the
result of increased peripheral airways resistance, secondary to a
mixture of small airways disease and emphysema. Specific natural
histories for the individual pathologic processes have not been defined
and are unlikely to exist given the common primary insult. This is
usually tobacco smoke, although the Global Obstructive Lung Disease
Initiative has emphasized that other inhaled toxic agents can be
equally important in initiating COPD outside the developed economies.
Changes in the large airways, particularly glandular hypertrophy and
its associated cough and sputum production, are frequent, often early
findings. However, their presence is not of great significance to the
development of this illness.
The model developed by Fletcher and Peto4
to describe the
natural history of COPD has a number of strengths and limitations. It
emphasizes that disability and death are associated with a reduction of
FEV1, which declines more rapidly than normal
with age, but that it can be slowed by smoking cessation. Less commonly
appreciated is the role of inadequate lung growth, with or without a
subsequent accelerated decline in function,5
and the need
to study lung function at widely spaced points, if the rate of change
of FEV1 is to be established with confidence (Fig 1
). Moreover, the conventional interpretation that there is a discrete
difference between the 15% of individuals who develop clinical COPD
and other healthy smokers may reflect the type of statistical analysis
applied, as much as the biological effects of cigarette smoke.
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Figure 1. Rate of decline of lung function over time
expressed in absolute values against age, for four examples of smokers
with different outcomes (solid lines) and one average nonsmoker (dotted
line). Note that significant decline in lung function is possible while
the patient remains within the normal range predicted for
FEV1.4
Accurate assessment of rate of decline
is best made by measurements spaced at several-year intervals, rather
than multiple measurements over a short period. Note also that
individuals with a low FEV1 at age 25 years resulting from
poor lung growth are closer to the threshold of disability that can be
reached by relatively normal rates of lung function loss. Reprinted
with permission from Fletcher and Peto.4
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In summary, COPD is now defined physiologically, so its early detection
will require physiologic confirmation. It is easier to establish that
there is a spirometric abnormality on one occasion, preferably
confirmed by short-term bronchodilator reversibility testing, than to
calculate the rate of change of lung function over time. At present,
the need to define the pathologic abnormality in COPD precisely, using
imaging or other techniques, is still to be established, at least in
the early phase of the illness.
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Detection Strategies in COPD
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Most COPD patients are still first identified when they present to
the hospital with an exacerbation. Those requiring intensive care are
clearly at an advanced state of their illness, with > 30% dying 1
year after admission.6
Delaying diagnosis and assessment
until this point in the illness remains unacceptable. In developing a
more useful approach, however, several dilemmas arise.
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Defining the Population To Be Screened
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Symptoms vs Lung Function: Although the presence of cough and
sputum production, whether mucoid or purulent, is not a
specific predictor for the subsequent development of COPD, the converse
is not necessarily true, namely that COPD does not develop in people
with these symptoms. There are now data7
8
suggesting that
sputum production will predict hospitalization and may even contribute
somewhat to the decline in FEV1 of patients with
established COPD. The assessment of large patient cohorts in COPD
intervention studies has shown that many are symptomatic, whether they
are investigated in Europe9
or in North
America10
). (Table 1
However, most patients do not attribute particular significance to
these symptoms, which often worsen during periods of upper respiratory
tract infection. Studies of patients with early-onset airways
obstruction in The Netherlands have found surprisingly little
relationship between the presence of these symptoms and regular
cigarette smoking.11
Individuals complaining of
troublesome lower respiratory tract infections who seek medical help
are much more likely to be suffering from COPD.12
Review
of the family physicians’ case records may prove a cost-effective way
of identifying people who have required one or more courses of
antibiotics during the winter, and who may be at greatest risk of this
illness.
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Table 1. Prevalence of Significant Symptoms in Middle-aged
Patients (n = 1,277) Who Continue To Smoke but Who Are Not Under
Medical Review*
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Targeted or Global Screening?
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If resource utilization was no object, it would be sensible to
screen large numbers of otherwise healthy individuals for the presence
of COPD. Some data about the utility of this approach to early
detection has come from the National Health and Nutrition Examination
Surveys reviewed elsewhere in this supplement, and from
operational studies in family practice in Holland (the Detection,
Interaction and Monitoring of COPD and Asthma Project). This project
sought new cases of airflow limitation defined by
FEV1 criteria and/or symptoms and/or
bronchodilator reversibility in a random population of 1,749 Dutch
people aged between 25 and 70 years.13
Sixty-six percent
participated in the initial survey, and of these, 1,155 subjects (52%)
met the generous criteria for possible airways disease. Further
follow-up is offered to the subpopulation over 2 years, to identify
those showing the accelerated decline of lung function seen in 12.5%
of the original population. Surprisingly, smoking state was a poor
screening tool, possibly reflecting the inclusion of significant
numbers of asthmatic subjects who are also known to show decline in
lung function with time.14
The cost of this exercise
ranges from approximately $500 to $1,000 per patient detected,
depending on how rigorous the chosen disease definition was. This is
relatively modest compared with other screening
programs,15
but calculation of the true cost-effectiveness
is not yet possible, given the lack of intervention studies in
populations defined in this way. What is clear is that these people are
less symptomatic than those seeking medical help, and are likely to be
identified at an earlier stage of their illness.16
In practice, there is still a reluctance to undertake screening
spirometry, although other population studies have shown that impaired
lung function is not only a good way of identifying early COPD, but
also detects patients with the highest risk of overall mortality and
death from ischemic heart disease (Fig 2
).17
These population data demonstrate that the highest
incidence of the disease by far is found in smokers (Fig 3
), suggesting that a series of different cost options could be developed
depending on how large a percentage of the total population of early
COPD was to be identified. Not every individual developing COPD is
going to have abnormal spirometry results at a given age, but their
identification as smokers and subsequent recall 3 to 5 years later to
repeat their spirometry does increase the chances of detecting early
disease, and also maximizes the opportunity for successful smoking
cessation.
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Figure 2. Relationship between adjusted odds ratio of death
(all causes; top) and death from ischemic heart disease
(HID; bottom) in a general population expressed by
gender and by quintile of FEV1 as a percent predicted (%
pred) within that population.17
Note that the
FEV1 is a good predictor of the increased risk of all-cause
mortality, and this is equally important in men and women. Data derived
from Hole et al.17
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Figure 3. Likelihood of an individual being a nonsmoker or
smoking > 15 cigarettes/d in relationship to their measured
FEV1 as a percent predicted. Those with the best lung
function are in quintile 5, and those with the worst are in quintile 1,
as in Figure 2
. Individuals with the worst lung function are much more
likely to be smokers than those with relatively preserved lung
function. Data derived from Hole et al.17
See Figure 2
for
abbreviation.
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Choice of Diagnostic Tests
Any successful screening program must use a diagnostic test that
is sensitive, specific, reproducible, and relatively uncomplicated to
administer. The general merits of some of the pulmonary function tests
proposed for COPD screening are listed in Table 2
. Of these, the FEV1 remains the most reliable and
best characterized. The within- and between-day reproducibility of this
measurement are independent of the initial value, and are approximately
140 mL and 170 mL, respectively.18
Even so, reproducible
spirometry requires familiarization with the test, and is at present
best performed by a trained technician. Hopefully, new computer-aided
equipment will make this relatively simple form of testing available to
less-experienced workers. Hand-held peak expiratory flowmeters have
been widely used in the management of bronchial asthma,19
and as such are familiar to family physicians. However, too little is
known about what constitutes a significant change in peak expiratory
flow in COPD populations, and individual values are unsatisfactory as
indicators of disease severity. This is because this measurement is
much more effort dependent than the FEV1, and
also because the peak flow occurs before the onset of flow limitation
due to airways collapse, and hence may overestimate lung function in an
otherwise disabled COPD patient. Other proposed measurements of
peripheral airways function in individuals with a relatively normal
FEV1 have been extensively studied. These include
the closing volume and closing capacity, the density-dependence of
expiratory flow, nitrogen and oxygen, washout testing, and the
frequency dependence of compliance. All have an excellent physiologic
rationale, work well in carefully selected individuals, and are
relatively complex and expensive to perform. None of these tests has
proven superior to the simple FEV1 in identifying
susceptible subjects in the clinical setting.
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Table 2. Relative Merits of Different Lung Function
Measurement Approaches as Tools for Population Screening for COPD*
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Thus, the early detection of COPD is difficult, and no simple test can
be applied with 100% sensitivity or specificity. However, this is not
a justification to abandon all attempts at early intervention.
Targeting groups where airflow limitation is likely, particularly
smokers with > 20–pack-years exposure and/or individuals with
relevant respiratory symptoms, especially when persistent or in need of
antibiotic treatment, will undoubtedly improve the present poor
situation with regard to early detection. Confirmation of the diagnosis
by spirometry and bronchodilator reversibility, if possible, provides a
firm basis for future care, as well as offering a simple means of
assessing the extent of disease progression.
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Interventions
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Detecting early disease is of little value unless some form of
effective intervention can be offered. This may not always prevent
progression of the illness, but can still be applied even when disease
is established, to limit its impact on the patient’s life. A range of
approaches are available, most of which are supported by substantial
clinical evidence,20
21
and these are considered briefly
below.
Removing the Cause or Stimuli
Tobacco smoking is by far the most important initiating factor in
COPD, and stopping smoking is the only intervention known to modify the
natural history of airways obstruction.10
This is reviewed
in detail elsewhere in the supplement. Environmental exposure,
including organic and coal dust, may also contribute to
COPD,22
and removing patients from such elements is likely
to be beneficial.
Symptom Relief
In patients with established COPD, respiratory symptoms are
frequent and increase in severity as the illness progresses. Inhaled
short-acting ß-agonists and anticholinergics reduce breathlessness by
improving lung emptying and also reduce the severity of coughing.
Long-acting inhaled bronchodilators such as salmeterol improve the
individual’s health status,23
as do regular inhaled
anticholinergic drugs,24
presumably by preventing episodes
of breathlessness and/or improving exercise tolerance and the ability
to undertake daily activity. Oral theophyllines are effective at high
doses in improving exercise tolerance,25
but are limited
by their side effects, such as cardiotoxicity, headache, and nausea.
Although selected individuals show improvement in overall quality of
life with these drugs, this has not been demonstrated in an unselected
population.
Anti-inflammatories
To date, the most widely used drugs are corticosteroids, although
promising new agents such as specific phosphodiesterase 4 and
leukotriene B4 inhibitors are currently being tested
in COPD. Oral corticosteroids increase the resolution rate of COPD
exacerbations, whether given in high26
or
low27
doses. However, oral corticosteroids in clinically
stable patients may be associated with corticosteroid myopathy and an
increased mortality.28
Inhaled budesonide in asymptomatic
patients with early COPD does not modify the decline in
FEV1.29
In mild, early COPD patients
who continue to smoke, this drug increases postbronchodilator
FEV1 by approximately 60 mL, but does not affect
the rate of decline of lung function.9
The initial reports
of the Inhaled Steroids in Obstructive Lung Disease in Europe trial, in
which inhaled fluticasone was administered to patients with more
advanced COPD, confirm the small increase in postbronchodilator
FEV1, but again show no effect on the evolution
of lung function with time. However, in these patients, the frequency
of COPD exacerbations was significantly reduced, as was the rate of
decline in health status in those treated with the active
drug.30
Thus, some aspects of COPD impact can be changed
by inhaled corticosteroids, but the underlying disease process
will not be altered.
Extrapulmonary Complications
The development of persistent hypoxemia only occurs in advanced
COPD, but when it does, the use of supplementary oxygen sufficient to
raise the arterial PO2 > 60 mm Hg
for 
15 h/d prolongs life.31
32
In patients with
moderate to severe disease, exercise tolerance is limited by leg muscle
weakness as well as breathlessness,33
the former being
accompanied by specific changes in skeletal muscle
pathology.34
There are now compelling data that
participation in a program of exercise training, together with general
education and advice about breathing control—pulmonary
rehabilitation—improves exercise performance and quality of
life.35
36
The role of nutritional supplements in disease
is still to be fully established, but those people with a low body mass
index are also at increased risk of premature deaths.37
38
Prevention of Exacerbations
Apart from the recent data with inhaled corticosteroids,
influenza-related exacerbations can be prevented by appropriately timed
vaccinations, and it is probably prudent to include immunization
against pneumococci as well. Development of infection and antibiotics
is reviewed elsewhere in this supplement, but the nonspecific
immunostimulant OM-85 BV has also been reported to reduce
hospitalizations when administered prophylactically.39
Surgical Approaches
The impact of lung volume reduction surgery on the clinical care
of patients with very severe COPD has been dramatic and controversial.
In carefully selected patients, FEV1 and exercise
tolerance can be improved, but the duration of these effects and the
risks of surgery in inexperienced hands mean that considerable care is
needed in patient selection.40
Lung transplantation,
commonly using a single lung technique, can improve symptoms
dramatically, but does not increase life expectancy.41
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Conclusion
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The economic and social impact of COPD is immense, and simply
waiting until the affected individuals are noticed by the health-care
system is not an option. Changes in our attitude to cigarette smoking
and the development of effective smoking cessation strategies should
help prevent early disease progression, but even when established, much
can be done to modify the effects of the disease on the patient long
before decisions about managing the end stage of the illness arise. In
the next decade, improvements in our understanding of the continuing
inflammation that characterizes this illness, and changes in our
ability to modify it, will make early detection and intervention even
more important than they are already.
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TOP
Abstract
Introduction
