Download Chronic Obstructive Pulmonary Disease: Epidemiology, Clinical

Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease:
Epidemiology, Clinical Presentation, and
Evaluation
Radmila Choate, MPH, and David M. Mannino, MD
ABSTRACT
• Objective: To review the classification, epidemiology,
clinical presentation, and evaluation of patients with
chronic obstructive pulmonary disease (COPD).
• Methods: Review of the literature.
• Results: While smoking remains the most important
risk factor for COPD in much of the developed world,
other risk factors, including genetic factors and occupational or environmental exposures, remain important.
COPD is the third leading cause of death in the United
States. In 2011, 13.7 million adults aged ≥ 25 years
were diagnosed with COPD in the United States, and
as many as 12 million adults may have COPD that
is undiagnosed. In 2010, COPD was responsible for
an estimated 10.3 million physician office visits and
1.5 million emergency room visits and was estimated
to be the second leading cause of disability-adjusted
life years lost among the US population. COPD has
primary, secondary, and tertiary prevention strategies. The treatment of COPD has improved in recent
years, with new therapies improving patient quality
of life.
• Conclusion: COPD remains a serious public health
problem that is often underdiagnosed, particularly in its
early stages.
Key words: Chronic obstructive pulmonary disease; epidemiology; mortality; smoking; evaluation.
C
hronic obstructive pulmonary disease (COPD) is
characterized by fixed airflow obstruction with
breathing-related symptoms, such as chronic
cough, exertional dyspnea, expectoration, and wheeze [1].
These symptoms may occur in conjunction with airway
hyperresponsiveness and overlap with other chronic diseases such as asthma. Although COPD is a nonspecific
term referring to a set of conditions that develop pro172 JCOM April 2017 Vol. 24, No. 4
gressively as a result of a number of different disease
processes, it most commonly refers to chronic bronchitis
and emphysema. These conditions can be present with or
without significant physical impairment. Despite being
a very common disease and the third leading cause of
death in the United States [2], COPD often is a silent and
unrecognized disease, particularly in its early phases [3],
and may go untreated.
In this article, we review the classification, epidemiology, clinical presentation, and assessment of patients with
COPD.
Definition and Classification
Several different definitions have existed for COPD
[4–8]. The Global Initiative for Chronic Obstructive
Lung Disease (GOLD), an international collaboration of
leading experts in COPD launched in the late 90s with
a goal to develop evidence-based recommendations for
diagnosis and management of COPD [4], currently
defines COPD as “a common, preventable and treatable
disease that is characterized by persistent respiratory
symptoms and airflow limitation that is due to airway
and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases” [4].
Airflow limitation is the slowing of expiratory airflow as measured by spirometry, with a persistently low
forced expiratory volume in 1 second (FEV1) and a low
FEV1/forced vital capacity (FVC) ratio despite treatment
[8]. The GOLD definition for airflow limitation is an
FEV1/FVC ratio of less than 70% [4]. Some authorities suggest using the lower limit of normal (statistically
defined by the lower fifth percentile of a reference
From the Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public
Health, Lexington, KY.
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Clinical Review
FVC
5
Normal Values
FEV1 = 4 L
FVC = 5 L
FEV1/FVC = 0.8
Figure 1. Normal spirogram and spirogram
typical of patients with mild to moderate
COPD. Adapted from references 4 and 62.
Volume (L)
4
3
Obstructive Values
FEV1 = 1.8 L
FVC = 3.2 L
FEV1/FVC = 0.56
2
1
1
2
3
4
5
6
Time (sec)
population) for FEV1/FVC to define airway obstruction
[9]. Figure 1 depicts a spirometric tracing representative of a patient with COPD compared with a normal
tracing.
Severity of COPD has typically been determined
using the degree of lung function impairment, although
the wisdom of this approach has been questioned, with
the suggestion that other signs and symptoms, such as
arterial blood gases values, body mass index, timed walking distance, and the sensation of dyspnea, be included
in this determination [7,10]. In 2011, GOLD introduced
as assessment system that categorized patients into 4
groups (ABCD) based on a composite measure of their
symptoms, airflow obstruction, and exacerbation history [11]. Their 2017 guideline refined this assessment
tool and separated spirometric grades from the “ABCD”
groupings. Figure 2 details the current recommended
approach. Group A is defined as low risk, low symptom
burden, Group B as low risk, higher symptom burden,
Group C as high risk, low symptom burden, and Group
D as high risk, higher symptom burden [4]. This revised
approach emphasizes the significance of patient’s symptoms and exacerbation history in directing COPD treatment recommendations, and importance of spirometry
in assessing clinical outcomes [4]. There are different
pharmacological treatment recommendations for each
category.
Previous definitions of COPD differentiated between
chronic bronchitis, asthma, and emphysema, acknowledgwww.jcomjournal.com
ing that there is frequently overlap between these disease
entities [12,13]. The GOLD definition of COPD does
not differentiate between chronic bronchitis and emphysema but does note that although asthma and COPD
can coexist [4], the largely reversible airflow limitation
in asthma merits different therapeutic approaches than
the largely irreversible airflow limitation of COPD. The
overlap of asthma and COPD in a significant proportion
of patients has been the focus of recent work [14].
Epidemiology
Prevalence of COPD
The Behavioral Risk Factor Surveillance System (BRFSS) is
an ongoing national random-digit-dialed telephone survey
of landline and cellphone households designed to measure
behavioral risk factors for the noninstitutionalized adult
population of the US [15]. An affirmative response to the
following question was defined as physician-diagnosed
COPD: “Have you ever been told by a doctor or other
health professional that you have chronic obstructive pulmonary disease (COPD), emphysema, or bronchitis?”[16].
Based on 2011 BRFSS survey, 13.7 million adults aged
≥ 25 years were estimated to have a self-reported physician
diagnosis of COPD in the United States. The greatest ageadjusted prevalence was found to be clustered along the
Ohio River Valley and the southern states [16].
The National Health Interview Survey (NHIS) is
an annually conducted, nationally representative survey
of the civilian noninstitutionalized population aged
Vol. 24, No. 4 April 2017 JCOM 173
Chronic Obstructive Pulmonary Disease
Spirometrically
confirmed
diagnosis
Assessment of risks/
exacerbations of
symptoms
Assessment of
airflow limitation
Exacerbation
History
FEV1
(% Predicted)
Post-bronchodilator
FEV1/FVC < 0.7
GOLD 1
≥ 80
GOLD 2
50–79
GOLD 3
30–49
GOLD 4
< 30
≥ 2
or
≥ 1 leading to hospital
admission
C
D
0 or 1
(not leading to hospital
admission)
A
B
mMRC 0–1
CAT < 10
mMRC ≥ 2
CAT ≥ 10
SYMPTOMS
Figure 2. 2017 refined GOLD ABCD Assessment Tool. CAT = COPD Assessment Test, an 8-item questionnaire designed to quantify
the impact of COPD on health status. mMRC = Modified Medical Research Council Dyspnea Scale. Scale ranges from 0 (I only get
breathless with strenuous exercise) to 4 (I am too breathless to leave the house or I am breathless when dressing). Reprinted from
reference 4.
18 years and older. A positive response to one or both
of the following questions was used to define COPD:
“Have you ever been told by a doctor or other health
professional that you had emphysema?” and “During
the past 12 months, have you been told by a doctor or
other health professional that you had chronic bronchitis?” Age-adjusted COPD prevalence estimates showed
significant interyear variation during 1999–2011 period,
and were higher in women than in men with the highest
prevalence noted in 2001 for both genders [16].
The NHIS estimates for COPD have 2 important
limitations. First, these estimates depend on the proper
recognition and diagnosis of COPD by both the study
participants and their health care providers. This would
tend to bias the estimates toward counting fewer cases than
actually exist. A bias in the opposite direction, however,
is that the term chronic bronchitis in this survey is not
precisely defined and could be interpreted as recurrent episodes of acute bronchitis. The finding that “chronic bronchitis” has been reported in 3% to 4% of children supports
the presence of this potential bias. The second limitation is
that this survey is not able to validate, through physiologic
evaluation, whether airway obstruction is present or absent.
These limitations were addressed, in part, by separate
nationally representative US surveys that include an
174 JCOM April 2017 Vol. 24, No. 4
examination component, such as the National Health
and Nutrition Examination Surveys (NHANES) [17].
An analysis of these data from 1988–1994 and 2007–
2012 [18] demonstrated that over 70% of people with
evidence of obstruction (based on an FEV1/FVC
< 70%) did not have a diagnosis of lung disease (COPD
or asthma). In addition, people with evidence of obstruction had a higher risk of mortality whether or not they
had diagnosed lung disease [18].
Evaluation of “reversibility” of the airway obstruction
requires the administration of bronchodilator, which is
not a part of most population-based studies. A subset of
participants in the NHANES 2007–2012 survey received
a bronchodilator, with a decrease in the estimated prevalence of obstruction from 20.9% to 14.0% [19]. However, a closer look at similar data from a study where
all people got a bronchodilator reveal that only a small
proportion of people with “reversibility” actually had a
significant response to the bronchodilator [20]. In a clinicbased study of subjects with COPD who were aged 69
years and older, 31% demonstrated reversibility, defined
as a 15% improvement (from baseline) in FVC and FEV1
following administration of an inhaled bronchodilator
[21]. In this study, subjects with more severe obstruction
were more likely to have reversibility but would also be
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Clinical Review
more likely to continue to have diminished lung function
after maximum improvement was obtained, thus being
classified as having “partial reversibility.”
The presence of significant reversibility or partial
reversibility in patients with COPD [15] and nonreversible airflow obstruction in asthma patients [22] demonstrates that these diseases can coexist or, alternatively,
that there is overlap and imprecision in the ways that
these diseases are clinically diagnosed.
Morbidity and Mortality
COPD is a leading cause of disease morbidity and mortality in the United States. The National Center for
Health Statistics (NCHS) conducts ongoing surveillance
of several health indicators nationally. The NCHS collects physician office visit data using the National Ambulatory Medical Care Survey [23], emergency department
visit data and hospital outpatient data using the National Hospital Ambulatory Medical Care Survey [24],
hospitalization data using the National Hospital Discharge Survey [25], and death data using the mortality
component of the National Vital Statistics System [26].
The following data include the number and rate of
COPD events in adults in the United States (using International Classification of Diseases, 9th Revision, Clinical
Modification [ICD-9-CM], codes 490, 491, 492 and
496) in these data sets for the most recent years available.
In 2010, COPD was responsible for an estimated 10.3
million physician office visits, with a resulting age-adjusted
rate of 494.8 per 10,000 US civilian population [16].
COPD was also responsible for an estimated 1.5 million
emergency room visits, with a resulting age-adjusted rate
of 72 visits per 10,000 population [16].
COPD is a leading cause of hospitalization in US
adults, particularly in older populations. In 2010, almost
699,000 hospitalizations, were attributed to COPD.
The age-adjusted rate of COPD hospitalizations (as the
primary cause of hospitalization) was 32.2 per 10,000
population in 2010 [16].
Deaths due to or associated with COPD have not
significantly changed since 1999. While the age-adjusted
death rate among men declined during 1999–2010
(P = 0.001), the rate among women has not changed
significantly (P = 0.127). In 2010, 63, 778 men and 69,
797 women aged ≥ 25 years died of COPD [26]. One of
the limitations of using the mortality component of the
National Vital Statistics System is that it is based on the
underlying cause of death as reported on the death certifwww.jcomjournal.com
icate; however, many decedents with COPD listed on the
death certificate have their death attributed to another
cause [27]. The significance of COPD as a contributor to
death is undefined when it is present with diseases more
likely to be attributed as the underlying cause of death,
such as myocardial infarction or lung cancer [28].
COPD is a very costly disease, with estimated direct
medical costs in 2004 of $20.9 billion. The estimated
indirect costs related to morbidity (loss of work time and
productivity) and premature mortality is an additional
$16.3 billion, for a total of $37.2 billion [29]. Because
COPD may be present but not listed as the underlying
cause of death or the primary reason for hospitalization,
these cited estimates may underestimate the true cost
of COPD. For example, in another analysis of COPD
costs in the US, the total for 2010 was estimated at
$32.1 billion [30], but could be up to $100 billion [31]
depending on the assumptions surrounding comorbid
disease.
Another manifestation of the importance of COPD
is its effect on the burden of disease in a population
determined using disability-adjusted life-years (DALYs).
DALYs for a disease or condition are calculated as the sum
of the years of life lost due to premature mortality in the
population and the years of life lost due to disability [32].
In 2010, COPD was estimated to be the second leading
cause of DALYs lost among the North American population [33]. Worldwide, COPD is expected to move up from
being the twelfth leading cause of DALYs lost in 1990 to
the fifth leading cause in 2020 [34].
Gender Differences
Smoking-related diseases such as COPD and lung cancer
are continuing to increase among women in the United
States [35,36], while they have plateaued or are decreasing among men [27,37]. Some evidence has emerged that
compared with men at a similar level of tobacco smoking,
women may be more likely to develop COPD [38] or that
the severity of COPD in women may be increased [39–41].
In the Lung Health Study, which evaluated patients
with mild COPD, more women than men demonstrated
increased airway responsiveness, although this difference
was thought to be related to airway caliber rather than
gender [42]. Adult women are more likely to both develop
and die of asthma than are men [43–45]. In NHANES
III, whereas women reported more physician-diagnosed
COPD and asthma than men, men and women had similar
rates of decreased lung function, and a similar proportion
Vol. 24, No. 4 April 2017 JCOM 175
Chronic Obstructive Pulmonary Disease
Table 1. Key Indicators for Considering a Diagnosis of COPD*
Indicator
Characteristics
Dyspnea that is:
Progressive over time
Characteristically worse with exercise
Persistent
Chronic cough:
May be intermittent and may be unproductive
Recurrent wheeze
Chronic sputum production
Any pattern of chronic sputum production may indicate COPD
Recurrent lower respiratory tract infections
History of risk factors:
Host factors (such as genetic factors, congenital/ developmental abnormalities, etc)
Tobacco smoke (including popular local preparations)
Smoke from home cooking and heating fuels
Occupational dusts, vapors, fumes, gases and other chemicals
Family history of COPD and/ or childhood factors:
For example, low birthweight, childhood respiratory infections, etc
COPD = chronic obstructive pulmonary disease. (Reprinted from reference 4.)
*Consider COPD and perform spirometry if any of these indicators are present in an individual over age 40. These indicators are not diagnostic themselves, but the presence of multiple key indicators increases the probability of a diagnosis of COPD. Spirometry is required to
establish a diagnosis of COPD.
of both men and women with low lung function had undiagnosed lung disease [3]. The current evidence is inadequate to determine whether women who smoke are more
likely to develop COPD or have more severe COPD than
men, although this question is being studied by various
groups.
Clinical Presentation
Risk Factors and Etiology
Smoking is the dominant risk factor for the development
and progression of COPD; however, not all smokers
develop COPD, and COPD does occur in persons who have
never smoked [1], suggesting that other factors are important in the etiology of COPD. Alpha1-antitrypsin deficiency
is an important cause of COPD in a very small percentage
of cases [46]. Other undefined genetic factors certainly play
an important role in COPD development [38]. The role
of infections in both the development and progression of
COPD is receiving increased attention, including the role of
adenoviral infections in emphysema [47–49].
Occupational and environmental exposures to various pollutants (eg, particulate matter, agricultural dusts)
are also important factors in the development of COPD
[50,51]. Exposure to indoor air pollutants such as smoke
from solid biomass fuels is a major risk factor for COPD
especially among women and children in low- and middleincome countries [52,53]. Occupational exposure to fumes
COPD is heterogeneous in its presentation. Based on data
from NHANES III, 44% of patients with severe airflow
limitation (FEV1 < 50% of predicted) may not report
symptoms [3]. Among patients with severe airflow limitation who do report symptoms, the symptoms reported
most frequently include wheezing (64%) and shortness of
breath (65%).
In recent years, COPD has been increasingly recognized as a systemic illness, with effects on nutritional
status, muscle wasting, and depression [56–58]. A large
proportion of patients probably have components of
chronic bronchitis, asthma, and emphysema occurring
together. Although some of this overlap may be related
to misdiagnosis, some of it may be a measure of the presence of airflow limitation reversibility, as described above.
Better defining individuals in these groups may ultimately
help tailor better interventions.
Key indicators for considering a diagnosis of COPD are
listed in Table 1. These indicators are either the presence
of symptoms (chronic cough, chronic sputum produc-
176 JCOM April 2017 Vol. 24, No. 4
and dusts remains an important cause for COPD globally
[53,54]. Exposure to outdoor air pollution is associated
with a risk of development of COPD as well as exacerbation of the existing disease [53,55].
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Clinical Review
tion, or dyspnea) or a history of smoking or exposure to
occupational dusts or chemicals. Spirometry with an
evaluation of bronchodilator response is then needed to
establish a diagnosis of COPD. Based on prior data, at
least 67% of the adult US population would have at least
1 of these indicators present [3]. The proportion of the
US population that has had pulmonary function testing is
unknown but is thought to be very low. Abnormal findings on the office-based spirometry should be followed up
with diagnostic-quality spirometry, including the determination of reversibility.
Some of the barriers to COPD diagnosis and subsequent treatment often include insufficient knowledge
and awareness about COPD especially among primary
care physicians, misdiagnosis of COPD as other respiratory
diseases such asthma, as well as patient-related barriers involving lack of awareness of early symptoms of COPD and
considering them to be related to aging or smoking [59].
Table 2. Differential Diagnosis of COPD
Diagnosis
Suggestive Features*
COPD
Onset in mid-life
Symptoms slowly progressive
History of tobacco smoking or exposure to
other types of smoke
Asthma
Symptoms vary widely from day to day
Symptoms worse at night/early morning
Allergy, rhinitis, and/or eczema also present
Family history of asthma
Obesity coexistence
Congestive heart
failure
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Chest X-ray shows dilated heart, pulmonary
edema
Pulmonary function tests indicate volume
restriction, not airflow limitation
Bronchiectasis
Large volumes of purulent sputum
Commonly associated with bacterial infection
Chest radiograph/CT scans show bronchial
dilatation, bronchial wall thickening
Evaluation
The evaluation of a patient with suspected COPD is oriented toward establishing the correct diagnosis and, once
this has occurred, determining the extent of the impairment such that therapy can be appropriately targeted.
The differential diagnosis of COPD is listed in Table 2.
While some of the other diagnoses listed are rare in the
United States (eg, diffuse panbronchiolitis, obliterative
bronchiolitis), others, such as asthma and congestive
heart failure, are quite common. In addition, in underdeveloped regions of the world, bronchiectasis and tuberculosis continue to be very important and prevalent
diseases.
Components in the evaluation of COPD are listed
in Table 3. Every patient with suspected COPD should
undergo a thorough history and physical examination.
The history should pay particular attention to the following: exposure to risk factors; past history of asthma or
allergic disease; family history of COPD; presence of
comorbid diseases; effect of disease on the patient’s life,
including ability to work and mental health status; and
possibilities for reducing risk factors, especially smoking
cessation [4]. The physical examination is rarely diagnostic in COPD because most physical abnormalities do not
occur until the advanced stages of the disease. Physical
examination findings in patients with advanced disease
include wheezing, prolonged expiration, decreased breath
sounds, and an increased anterior-posterior diameter of
the chest.
Onset early in life (often in childhood)
Tuberculosis
Onset all ages
Chest X-ray shows lung infiltrate
Microbiological confirmation
High local prevalence of tuberculosis
Obliterative bronchiolitis
Onset at younger age, nonsmokers
May have history of rheumatoid arthritis or
acute fume exposure
Seen after lung or bone marrow transplantation
CT on expiration shows hypodense areas
Diffuse panbronchiolitis
Predominantly seen in patients of Asian
descent
Most patients are male and nonsmokers
Almost all have chronic sinusitis
Chest X-ray and HRCT show diffuse small centrilobular nodular opacities and hyperinflation
COPD = chronic obstructive pulmonary disease; CT = computed
tomography. (Reprinted from reference 4.)
*These features tend to be characteristic of the respective diseases, but are not mandatory. For example, a person who has
never smoked may develop COPD (especially in the developing
world where other risk factors may be more important than cigarette
smoking); asthma may develop in adult and even in elderly patients.
Pulmonary function testing is a critical part of the
evaluation of suspected COPD. Whereas most patients
with COPD can be managed by a primary care physician,
Vol. 24, No. 4 April 2017 JCOM 177
Chronic Obstructive Pulmonary Disease
Table 3. Evaluation and Workup of COPD
Procedure
Comments
Evaluation for all patients with suspected COPD
History and physical examination
Should include the following:
Exposure to risk factors
Past history of asthma or allergic disease
Family history of COPD
Presence of comorbid diseases
Effect of disease on patient’s life, including ability to work and mental health status
Possibility for reducing risk factors, especially smoking cessation
Assessment of symptoms
Comprehensive assessment of symptoms using CAT or CCQ are recommended
Provide measures of symptomatic impact of COPD Exacerbation history
Rate of exacerbations varies between patients
Mild and moderate exacerbations require treatment with SABDs and/or antibiotics, oral corticosteroids
Severe exacerbations requiring hospitalizations associated with poor prognosis
Spirometry
FEV1 and FVC should be measured, and the FEV1/FVC ratio calculated
Only a weak correlation between FEV1, symptoms and impairment of patient’s health status
Additional investigations to consider:
Imaging
Chest X-ray is seldom diagnostic in COPD, but useful to rule out other diagnoses
Computed tomography scans may be helpful in the presence of atypical findings on the chest radiograph
Oximetry and arterial blood gas measurement
Pulse oximetry is indicated in all patients with clinical signs of respiratory failure or right heart failure
Blood gases should be measured if peripheral arterial oxygen saturation is < 92%
α1-Antitrypsin deficiency screening
Indicated in patients who develop COPD at a young age (< 45 years) or who have a strong
family history of COPD
Exercise testing and assessment of
physical activity
Powerful indicator of health status impairment and predictor of prognosis
Lung volumes and diffusing capacity
Not essential to patient management, but assist in characterizing the severity of COPD
Useful for assessing disability, risk of mortality, and effectiveness of pulmonary rehabilitation
CAT = COPD assessment test; CCQ = COPD Control Questionnaire; COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 second; FVC = forced vital capacity; SABD = short acting bronchodilators. (Reprinted from reference 4.)
patients with moderate or severe COPD should be evaluated by a specialist [4].
Once the diagnosis of moderate or severe COPD has
been established, further testing, including chest radiograph, arterial blood gas determination, screening for
α1-antitrypsin deficiency, 6-minute walk testing or exercise oxymetry may be indicated based on the patient’s
history and/or clinical findings. Data from computed
tomography scans are useful in some advanced cases.
Prognosis of COPD is often influenced by presence of
various comorbidities including extrapulmonary, such as
osteoporosis, metabolic syndrome, and depression that
178 JCOM April 2017 Vol. 24, No. 4
may be seen as parts of multimorbidity associated with
aging [60,61]. Therefore, it is advised to look for comorbidities in COPD patients with any severity of airflow
obstruction and treat them accordingly [4].
Therapy for COPD targets reducing risk factors, improv
ing symptoms, and decreasing the risk of exacerbations [10].
Interventions include smoking cessation, vaccinations,
decreasing exposures to occupational and environmental
pollutants, pulmonary rehabilitation, bronchodilators, and
corticosteroids. Select patients with advanced COPD may
benefit from other interventions, such as surgical reduction of lung size, lung transplant, the phosphodiesterase
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Clinical Review
inhibitor roflumilast and chronic treatment with antibiotics such as macrolides.
Conclusion
COPD is a common disease that is a leading cause of
morbidity and mortality, both in the United States and
worldwide. Most cases of COPD are attributable to smoking. Although its incidence among men has plateaued, it
continues to increase among women. COPD, particularly in
its early stages, is under-diagnosed in the United States. An
increased awareness among physicians of the prevalence of
mild COPD and the importance of spirometry in diagnosing the disease is important in combating the disease.
Corresponding author: David M. Mannino, MD, Department of Preventive Medicine and Environmental Health,
University of Kentucky College of Public Health, 111 Washington Avenue, Lexington, KY 40536, [email protected].
Financial disclosures: Dr. Mannino has received fees from
GlaxoSmithKline, Novartis, AstraZeneca, Sunovion, and
Boehringer Ingelheim for advisory board services.
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