Evidence Report/Technology Assessment: Number 121
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Introduction / Methods / Results / Discussion / Availability of Full Report / References
Authors: Wilt TJ, Niewoehner D, Kim C, Kane RL, Linabery A,
Tacklind J, MacDonald R, Rutks I
Chronic Obstructive Pulmonary Disease
(COPD) is manifested by chronic cough, sputum
production, wheezing and, in later stages,
dyspnea, poor exercise tolerance, and
signs/symptoms of right-sided heart failure.
Symptomatic COPD affects more than 5 percent
of the adult population, is the fourth leading
cause of death, and the twelfth leading cause of
morbidity in the United States.1,2 In more than 80
percent of cases, cigarette smoking is causally
linked to the development of COPD. Smoking
status should be assessed in all adults, and
smokers should be advised to abstain from
COPD is diagnosed in symptomatic
individuals through spirometric testing that
demonstrates irreversible airflow obstruction.3
Spirometry for case-finding diagnosis and
management of all adults with persistent
respiratory symptoms or having a history of
exposure to pulmonary risk factors has been
recommended in primary care settings for all
current and former smokers as well as never
smokers who have persistent respiratory
symptoms or have history of exposure to other
COPD risk factors.
This report was prepared to provide
objective evidence and recommendations to
inform the work of the American Thoracic
Society (ATS), in collaboration with the
American Academy of Family Physicians, the
American College of Physicians, and the
American Academy of Pediatrics Spirometry Task
Force in clarifying usage of spirometry as part of
the management of COPD.
literature review was undertaken to address four
- What is the prevalence of COPD and airflow obstructions in various adult populations as defined by:
- Clinical examination?
- Can use of spirometry lead to increased smoking cessation rates?
- Does the effectiveness of COPD-specific therapies to improve clinically relevant outcomes vary based on baseline severity or change in spirometry?
- Is prediction of future COPD status based on spirometry, with or without clinical indicators, more accurate than prediction based on clinical indicators alone?
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Articles published in the English language from
1966 to May 2005 were identified by searching
MEDLINE® and the Cochrane Database.
Because the individual questions addressed
different areas, the search strategies, types of
eligible studies, populations, interventions, and
outcomes varied. Emphasis was placed on studies
that assessed outcomes from adults in primary
care or population-based settings who had or were
at risk for COPD according to race, gender, age,
smoking, symptom, and spirometric status. Children or individuals with asthma, or alpha-1 antitrypsin disease were
excluded. Ten cohort studies4-13 were included to estimate
COPD/airflow obstruction prevalence and diagnostic accuracy.
Seven randomized controlled trials (RCT)14-20 met inclusion
criteria for smoking cessation studies, 52 RCT21-72 and four
meta-analyses of RCT73-76 were included for assessment of
COPD-specific therapies, and five cohort studies were included
The main outcomes according to question
- Prevalence of airflow obstruction as determined by spirometry and clinical examination according to race, gender, age, smoking, and symptom status and previous diagnosis of COPD.
- Long-term sustained smoking abstinence rates among smokers randomized to receive results of spirometry alone or in combination with other interventions compared to controls.
- Exacerbations, hospitalizations, mortality, and respiratory health status according to type of treatment; baseline symptom status and FEV1; acute change in FEV1 or slope in FEV1 over time.
- Independent prognostic value of airflow obstruction as
determined by spirometric stage to predict future COPD
status (stage and symptoms).
Data were used to estimate the number of adults according
to smoking status that would require symptom and spirometric
assessment and subsequent treatment to prevent COPD
exacerbations, reduce mortality or hospitalizations, and improve
smoking cessation or respiratory health status.
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More than one-third of the adult U.S. population reported
respiratory symptoms compatible with symptomatic COPD.
Compared to clinical examination, spirometry plus clinical
examination improves diagnostic accuracy of clinically
significant disease in adults who report respiratory symptoms
Based on the National Health and
Nutrition Examination Survey (NHANES) III results, 12.8
percent of adults report a current or past diagnosis of
obstructive lung disease (emphysema, chronic bronchitis, or
asthma). However, only 17.4 percent of adults reporting a
diagnosis of chronic bronchitis or emphysema (COPD) had
1987-ATS defined low lung function suggesting that many of
these individuals have normal lung function. Fewer than half of
individuals reporting a diagnosis of chronic bronchitis or
emphysema stated that they were bothered by shortness of
breath. Based on gender, age, and smoking status, between 40
and 80 percent of NHANES III participants with low lung
function as determined by spirometry in the absence of
bronchodilator testing reported no prior clinical diagnosis of
COPD. However, there were no data regarding prevalence or
type of respiratory symptoms in this group.
Spirometry, when used in primary care settings for case
finding of all adults with persistent respiratory symptoms or
having a history of exposure to pulmonary risk factors, is likely
to label a relatively large proportion of individuals as diseased
with airflow obstruction but who do not have respiratory
symptoms or whose symptoms are unlikely to affect their
Conversely, spirometry is normal in a relatively
large percentage of adults who report respiratory symptoms
including dyspnea, the respiratory symptom having the greatest
impact on quality of life. Prevalence and severity of airflow
obstruction and symptomatic COPD vary widely according to
definitions utilized and country and populations studied. The
percentage of adults having normal spirometry and no
respiratory symptoms (normal/asymptomatic) ranged from 56
to 91 percent.
Compared with previous definitions of airflow
obstruction, use of recent criteria tripled the number of adults
being labeled as "at-risk" or having "low lung function" (from
6.8 to 20 percent). Normal spirometry with chronic sputum
production ("at-risk") was present in 7.2 percent of subjects. An
additional 13.9 percent of adults had prebronchodilator
spirometrically detected airflow obstruction (mild, moderate, or
severe to very severe airflow obstruction = 7.2 percent, 5.4
percent, and 1.5 percent respectively). Prevalence was higher in
current smokers and older individuals.
The percentage of
individuals reporting respiratory symptoms increased with
airflow obstruction severity. However, one-third of individuals
with normal spirometry reported respiratory symptoms (21
percent reported shortness of breath). Some of these individuals
may have had asthma and thus might have normal spirometry
at the time of testing. Approximately, 21 percent of individuals
with severe to very-severe airflow obstruction (similar to Global
Initiative for Obstructive Lung Disease Stage 3,4) were
asymptomatic and 35 percent did not report shortness of
Smoking cessation is the most important factor in reducing
the development and/or progression of airflow obstruction and
symptomatic COPD. All adults should be asked about
smoking and current smokers encourage to quit. However,
evidence indicates that baseline symptom and spirometric status
are of limited clinical use in reliably predicting a patient's future
likelihood of quitting smoking.
Spirometric testing as a
motivational tool to improve smoking cessation rates is unlikely
to provide more than a small benefit. Results from
observational studies of spirometry are mixed. RCT of other
biomarkers used as motivational tools for smoking cessation are
generally negative. The only randomized controlled trial that
assessed the independent contribution of spirometry and
counseling on smoking cessation rates reported a nonsignificant
1 percent greater quit rate at 12 months in the group assigned
to receive spirometry plus repeat counseling compared to repeat
counseling alone (6.5 percent vs. 5.5 percent). Quit rates were
lower in the spirometry group than in participants who
received repeat counseling plus nicotine replacement therapy
Two other studies approximated an independent
effect and their results were mixed. The self-reported 6-month
point prevalent abstinence rates for the intervention group
assigned to receive spirometry in combination with advice plus
carbon monoxide values were lower than the group that
received advice alone (9 percent vs. 14 percent). The one study
that showed an improvement in smoking cessation rates
compared a 50-minute educational intervention with a group
that received the educational intervention plus a questionnaire
and discussion of symptom status, spirometric results, and
carbon monoxide levels. At 12 months, the biologically verified
point prevalent quit rates were 20 percent in the intervention
group and 6.7 percent in the control group. Four other trials
that evaluated spirometry demonstrated an improvement in
smoking cessation but all included concomitant interventions
proven to increase abstinence.
Spirometry is useful for determining at what threshold of
airflow obstruction initiation of therapy is likely to improve
clinical outcomes in adults with bothersome respiratory
symptoms. However, monitoring with spirometry to guide
additional therapy or to initiate interventions in individuals
who do not report bothersome respiratory symptoms does not
appear to be beneficial. COPD trials typically were of short
duration, they involved subjects with an established clinical
diagnosis of COPD who had moderate to severe respiratory
symptoms, frequent COPD exacerbations, and severe to very
severe baseline airflow obstruction, and they used varying
outcome definitions for exacerbations. On average,
interventions reduced the relative risk of exacerbations by 20 to
25 percent and the absolute risk by 5 to 6 percent.
improved measures of dyspnea and respiratory functional
status, although the average improvement from inhaled
bronchodilators and corticosteroids on validated health status
measures failed to achieve a predetermined level of clinical
significance. However, some individuals will notice greater and
clinically significant improvement in respiratory symptoms.
Few studies reported information on hospitalizations, but in
those that did reduction was 4 to 7 percent. Mortality was
similar between treatment and control groups, though there
were relatively few events and the available information cannot
rule out an improvement with long term inhaled treatment.
Information related to the effectiveness of short-acting inhaled
medications used for acute symptomatic rescue therapy was not
Benefits from interventions are mostly limited to reduction
in exacerbations in patients having activity-limiting respiratory
symptoms and severe to very-severe airflow obstruction (FEV1
<50 percent predicted). Five large studies of greater than 1-year
duration (one assessing a short-acting anticholinergic and four
evaluating inhaled corticosteroids) found little to no
improvement in respiratory outcomes among subjects with
mild to moderate airflow obstruction or those with normal
airflow but having chronic sputum production ("at risk"
Analysis of one of these studies that enrolled a
subgroup of individuals that had mild to moderate airflow
obstruction but denied respiratory symptoms demonstrated
that ipratropium did not prevent development of symptoms at
3 years of followup. Subgroup analysis of other studies
indicated that treatment benefit was almost exclusively confined
to adults with bothersome respiratory symptoms and severe to
very-severe airflow obstruction.
Five additional comparative
studies of long-acting inhaled b-agonists and corticosteroids
indicated that combination therapy was similar to
monotherapy regarding exacerbations (ARR 1-2 percent) and
mortality (ARR 0-1 percent). Combination therapy with short- or
long-acting beta-agonists plus anticholinergics was not
superior to anticholinergics alone but did reduce exacerbations
versus short-acting beta-agonists (ARR = 6 percent). Adverse
effects of inhaled interventions during the study followup
periods were generally mild but included bone loss, thrush, dry
mouth, and serious cardiovascular events. About 50 percent of
subjects remained compliant with therapy. Withdrawals from
therapy were greater in subjects assigned to placebo than to
Studies have not examined the value of spirometry to
monitor need for additional therapy or to identify candidates
for treatment among patients who do not report symptoms. It
is unlikely to be beneficial because data indicated that:
- Clinical improvement was not associated with an individual's spirometric response to therapy.
- Treatments other than smoking cessation did not alter the rate of spirometric decline over time.
- There was wide intra-individual variation in spirometric decline.
- Higher doses of inhaled interventions or combination therapy were not superior to lower doses or to monotherapy.
- Interventions were not effective in asymptomatic individuals or those with mild to moderate airflow obstruction.
Based on NHANES III results if all "at risk" adults (i.e.,
smokers and ex-smokers regardless of symptom status as well as
never smokers with persistent respiratory symptom) undergo an
office-based spirometric test then nearly two-thirds of the adult
population, approximately 110 million adults, would receive
- If a primary care clinic was comprised of 10,000 adults
with similar demographic, smoking, symptom, and
spirometric status as NHANES III respondents then
6,588 would undergo spirometric testing, 129 (1.3
percent) would be potential candidates for COPD therapy
and 7 (0.08 percent) would have reductions in
exacerbations (i.e., an estimated 1,010 current smokers,
960 former smokers, and 2,043 never smokers would
undergo spirometric and respiratory assessment to identify
candidates for treatment consisting of an inhaled
bronchodilator or corticosteroid to prevent an individual
from having one or more exacerbations).
- If subjects with moderate airflow obstruction (FEV1 50-80 percent predicted; approximately Global Initiative for
Obstructive Lung Disease Stage 2) benefit to a similar
magnitude as severe to very severe airflow obstruction,
then 529 adults (5.3 percent) would be candidates for
treatment and 32 adults (0.3 percent) would benefit from
having at least one exacerbation prevented compared with
placebo. Approximately 76 (0.8%) would report a
clinically noticeable improvement in respiratory health
status. Reserving testing and treatment for individuals
with respiratory symptoms (especially dyspnea, exercise
intolerance, or exacerbations) would maintain benefits.
- If spirometry was targeted to individuals with dyspnea,
regardless of smoking status, the number needed to screen
and treat for severe to very severe airflow obstruction
would be 475.
These estimates assume individuals with airflow obstruction
and respiratory symptoms have COPD as the cause of their
symptoms and that effective detection by clinical examination
and treatment would not have occurred without spirometry.
Based on 2004 Red Book prices, the annual long-acting inhaled
drug costs would be over $4.5 billion to treat the estimated 4
percent of adults with dyspnea and severe to very-severe airflow
obstruction (n=4,630,000). If combination therapy was
routinely used instead of monotherapy, effectiveness would be
similar but drug costs would be considerably higher. Compared
to diagnosis and treatment based on clinical examination alone,
spirometry may reduce the number of symptomatic individuals
who are diagnosed with, and treated for, COPD but do not
have airflow obstruction of severity that is likely to benefit from
Spirometry provides independent prognostic value regarding
respiratory symptoms, morbidity, and mortality, though level of
dyspnea is a better predictor of symptom progression and
mortality. Baseline spirometry predicts rate of spirometric
decline over time in male smokers. Spirometric levels may be
useful as a guide for initiation of inhaled medications and
pulmonary rehabilitation among individuals having disabling
respiratory symptoms, especially frequent exacerbations.
Subjects with chronic sputum production and normal
spirometry (Stage GOLD 0 condition) are not at increased risk
for developing airflow obstruction compared to individuals
without chronic sputum production, and more than half of
these subjects do not have chronic sputum production after 10
years of followup.
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Spirometry in addition to clinical examination improves
COPD diagnostic accuracy compared to clinical examination
alone and it is a useful diagnostic tool in individuals with
symptoms suggestive of possible COPD. The primary benefit
of spirometry is to identify individuals who might benefit from
pharmacologic treatment in order to improve exacerbations.
These include adults with symptomatic, severe to very severe
airflow obstruction. In individuals where a diagnosis of asthma
is suspected bronchodilator responsiveness, testing may be
The evidence does not support widespread use of
spirometry in primary care settings for all adults with persistent
respiratory symptoms or having a history of exposure to
pulmonary risk factors for case-finding, improving smoking
cessation rates, monitoring the clinical course of COPD, or
adjusting COPD interventions.
Routine spirometric testing in primary care settings is likely
to result in considerable testing and treatment costs, resource
utilization, and health care personnel time. It might reduce the
number of individuals being labeled as having COPD or
receiving disease-specific treatment in the absence of severe to
very-severe airflow obstruction. However, it is likely to label a
large number of individuals (many not reporting bothersome
respiratory symptoms or having nondisabling symptoms) as
diseased who would not benefit from testing or treatment.
Treatment effectiveness (beyond short acting medications used
for "acute rescue therapy") is largely limited to reducing
exacerbations among subjects who have bothersome dyspnea,
frequent exacerbations, and severe to very-severe airflow
obstruction. Nearly all the benefit from treatment could be
obtained by reserving spirometry for those having activity
limiting respiratory symptoms and targeting therapy to those
who have reached a spirometric threshold of airflow obstruction
of approximately a FEV1 less than 50 percent predicted.
Spirometric response to therapy or change over time has not
been shown to be associated with clinical outcomes, nor does it
appear to be beneficial in modifying therapy. Future studies
should be conducted to determine:
- If spirometry improves smoking cessation rates.
- If treatment effectiveness in established COPD varies according to an individual's baseline or followup spirometric value.
- If treatment benefits individuals with airflow obstruction and moderate to no reported respiratory
- If therapy improves the rate of decline of FEV1.
Spirometry provides independent prognostic value for
predicting respiratory and overall morbidity and mortality.
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Availability of Full Report
The full evidence report from which this summary was taken
was prepared for the Agency for Healthcare Research and
quality (AHRQ) by the Minnesota Evidence-based Practice
Center, under Contract No. 290-02-0009. Printed copies may be
obtained free of charge from the AHRQ Publications
Clearinghouse by calling 800-358-9295. Requesters should ask
for Evidence Report/Technology Assessment No. 121, Use of
Spirometry for Case Finding, Diagnosis, and Management of
Chronic Obstructive Pulmonary Disease (COPD) (AHRQ Publication No. 05-E017-2).
The Evidence Report is also online on the National Library of Medicine Bookshelf, or can be downloaded as a PDF File (4.8 MB) with Appendixes in PDF (6 MB) or as Zipped PDF Files (6.2 MB) [Plugin Software Help].
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AHRQ Publication Number 05-E017-1
Current as of August 2005