chronic obstructive pulmonary disease: epidemiology, … · · 2017-03-21172 jcom april 2017 vol....

172 JCOM April 2017 Vol. 24, No. 4 www.jcomjournal.com

ChroniC obstruCtive Pulmonary Disease

ABSTRACT• Objective: To review the classification, epidemiology,

clinical presentation, and evaluation of patients withchronicobstructivepulmonarydisease(COPD).

• Methods:Reviewoftheliterature.• Results: While smoking remains the most important

riskfactorforCOPDinmuchofthedevelopedworld,otherriskfactors,includinggeneticfactorsandoccupa-tional or environmental exposures, remain important.COPDisthethirdleadingcauseofdeathintheUnitedStates. In2011,13.7millionadultsaged ≥ 25 yearswerediagnosedwithCOPDintheUnitedStates,andas many as 12 million adults may have COPD thatis undiagnosed. In 2010, COPD was responsible foran estimated 10.3 million physician office visits and1.5millionemergencyroomvisitsandwasestimatedtobe thesecond leadingcauseofdisability-adjustedlifeyears lost among theUSpopulation.COPDhasprimary, secondary, and tertiary prevention strate-gies.ThetreatmentofCOPDhasimprovedinrecentyears, with new therapies improving patient qualityoflife.

• Conclusion: COPD remains a serious public healthproblemthatisoftenunderdiagnosed,particularlyinitsearlystages.

Key words: Chronic obstructive pulmonary disease; epidem-

iology; mortality; smoking; evaluation.

Chronic 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 dis-eases such as asthma. Although COPD is a nonspecific term referring to a set of conditions that develop pro-

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, epidemiol-ogy, clinical presentation, and assessment of patients with COPD.

Definition and ClassificationSeveral 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 signifi-cant exposure to noxious particles or gases” [4].

Airflow limitation is the slowing of expiratory air-flow 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 authori-ties suggest using the lower limit of normal (statistically defined by the lower fifth percentile of a reference

Chronic Obstructive Pulmonary Disease: Epidemiology, Clinical Presentation, and EvaluationRadmila Choate, MPH, and David M. Mannino, MD

From the Department of Preventive Medicine and Environ-mental Health, University of Kentucky College of Public Health, Lexington, KY.

www.jcomjournal.com Vol. 24, No. 4 April 2017 JCOM 173

population) for FEV1/FVC to define airway obstruction [9]. Figure 1 depicts a spirometric tracing representa-tive 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 walk-ing 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 his-tory [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 symp-toms and exacerbation history in directing COPD treat-ment 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, acknowledg-

ing that there is frequently overlap between these disease entities [12,13]. The GOLD definition of COPD does not differentiate between chronic bronchitis and emphy-sema 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 COPDThe 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 pul-monary 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 age-adjusted 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

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Figure 1. Normalspirogramandspirogramtypical of patients with mild to moderateCOPD.Adaptedfromreferences4and62.

Volu

me

(L)

Time (sec)

1

2

3

4

5

FVC

5 642 31

Normal ValuesFEV1=4LFVC=5LFEV1/FVC=0.8

Obstructive ValuesFEV1=1.8LFVC=3.2LFEV1/FVC=0.56



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 bronchi-tis?” 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 epi-sodes of acute bronchitis. The finding that “chronic bron-chitis” 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

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 pre-valence of obstruction from 20.9% to 14.0% [19]. How-ever, 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 clinic-based 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

Figure 2. 2017refinedGOLDABCDAssessmentTool.CAT=COPDAssessmentTest,an8-itemquestionnairedesignedtoquantifytheimpactofCOPDonhealthstatus.mMRC=ModifiedMedicalResearchCouncilDyspneaScale.Scalerangesfrom0(Ionlygetbreathlesswithstrenuousexercise)to4(IamtoobreathlesstoleavethehouseorIambreathlesswhendressing).Reprintedfromreference4.

Spirometrically confirmed diagnosis

Post-bronchodilator FEV1/FVC < 0.7

Assessment of airflow limitation

FEV1

(% Predicted)

GOLD 1

GOLD 2

GOLD 3

GOLD 4

≥ 80

50–79

30–49

<30

SYMPTOMS

C D

A B

Assessment of risks/exacerbations of

symptoms

Exacerbation History

≥ 2or

≥ 1leadingtohospitaladmission

0or1(notleadingtohospitaladmission)

mMRC0–1CAT<10

mMRC≥ 2CAT≥10


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 nonrevers-ible airflow obstruction in asthma patients [22] demon-strates that these diseases can coexist or, alternatively, that there is overlap and imprecision in the ways that these diseases are clinically diagnosed.

Morbidity and MortalityCOPD is a leading cause of disease morbidity and mor-tality in the United States. The National Center for Health Statistics (NCHS) conducts ongoing surveillance of several health indicators nationally. The NCHS col-lects physician office visit data using the National Ambu-latory Medical Care Survey [23], emergency department visit data and hospital outpatient data using the Na-tional Hospital Ambulatory Medical Care Survey [24], hospitalization data using the National Hospital Dis-charge 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 Inter-national 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 certif-

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 popula-tion [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 DifferencesSmoking-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 decreas-ing 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

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of both men and women with low lung function had un-diagnosed lung disease [3]. The current evidence is inad-equate 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.

Risk Factors and EtiologySmoking 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 impor-tant 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 vari-ous 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 middle-income countries [52,53]. Occupational exposure to fumes

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 exacerba-tion of the existing disease [53,55].

Clinical PresentationCOPD 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 limita-tion who do report symptoms, the symptoms reported most frequently include wheezing (64%) and shortness of breath (65%).

In recent years, COPD has been increasingly recog-nized 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 pres-ence 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-

Table 1.KeyIndicatorsforConsideringaDiagnosisofCOPD*

Indicator Characteristics

Dyspneathatis: Progressiveovertime

Characteristicallyworsewithexercise

Persistent

Chroniccough: Maybeintermittentandmaybeunproductive

Recurrentwheeze

Chronicsputumproduction AnypatternofchronicsputumproductionmayindicateCOPD

Recurrentlowerrespiratorytractinfections

Historyofriskfactors: Hostfactors(suchasgeneticfactors,congenital/developmentalabnormalities,etc)

Tobaccosmoke(includingpopularlocalpreparations)

Smokefromhomecookingandheatingfuels

Occupationaldusts,vapors,fumes,gasesandotherchemicals

FamilyhistoryofCOPDand/orchildhoodfactors:

Forexample,lowbirthweight,childhoodrespiratoryinfections,etc

COPD=chronicobstructivepulmonarydisease.(Reprintedfromreference4.)*ConsiderCOPDandperformspirometryifanyoftheseindicatorsarepresentinanindividualoverage40.Theseindicatorsarenotdiag-nosticthemselves,butthepresenceofmultiplekeyindicatorsincreasestheprobabilityofadiagnosisofCOPD.SpirometryisrequiredtoestablishadiagnosisofCOPD.


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 find-ings on the office-based spirometry should be followed up with diagnostic-quality spirometry, including the determi-nation of reversibility.

Some of the barriers to COPD diagnosis and sub-sequent 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 in-volving lack of awareness of early symptoms of COPD and considering them to be related to aging or smoking [59].

EvaluationThe evaluation of a patient with suspected COPD is ori-ented toward establishing the correct diagnosis and, once this has occurred, determining the extent of the impair-ment 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 under-developed regions of the world, bronchiectasis and tuber-culosis 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 fol-lowing: 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 diagnos-tic 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.

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,

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Table 2.DifferentialDiagnosisofCOPD

Diagnosis Suggestive Features*

COPD Onsetinmid-life

Symptomsslowlyprogressive

Historyoftobaccosmokingorexposuretoothertypesofsmoke

Asthma Onsetearlyinlife(ofteninchildhood)

Symptomsvarywidelyfromdaytoday

Symptomsworseatnight/earlymorning

Allergy,rhinitis,and/oreczemaalsopresent

Familyhistoryofasthma

Obesitycoexistence

Congestiveheartfailure

ChestX-rayshowsdilatedheart,pulmonaryedema

Pulmonaryfunctiontestsindicatevolumerestriction,notairflowlimitation

Bronchiectasis Largevolumesofpurulentsputum

Commonlyassociatedwithbacterialinfection

Chestradiograph/CTscansshowbronchialdilatation,bronchialwallthickening

Tuberculosis Onsetallages

ChestX-rayshowslunginfiltrate

Microbiologicalconfirmation

Highlocalprevalenceoftuberculosis

Obliterativebronchiolitis

Onsetatyoungerage,nonsmokers

Mayhavehistoryofrheumatoidarthritisoracutefumeexposure

Seenafterlungorbonemarrowtrans-plantation

CTonexpirationshowshypodenseareas

Diffusepanbron-chiolitis

PredominantlyseeninpatientsofAsiandescent

Mostpatientsaremaleandnonsmokers

Almostallhavechronicsinusitis

ChestX-rayandHRCTshowdiffusesmallcentrilobularnodularopacitiesandhyperinflation

COPD=chronicobstructivepulmonarydisease;CT=computedtomography.(Reprintedfromreference4.)*These features tend to be characteristic of the respective dis-eases, but are not mandatory. For example, a person who hasnever smoked may develop COPD (especially in the developingworldwhereotherriskfactorsmaybemoreimportantthancigarettesmoking);asthmamaydevelopinadultandeveninelderlypatients.



patients with moderate or severe COPD should be evalu-ated by a specialist [4].

Once the diagnosis of moderate or severe COPD has been established, further testing, including chest radio-graph, arterial blood gas determination, screening for α1-antitrypsin deficiency, 6-minute walk testing or exer-cise 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

may be seen as parts of multimorbidity associated with aging [60,61]. Therefore, it is advised to look for comor-bidities 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 reduc-tion of lung size, lung transplant, the phosphodiesterase

Table 3.EvaluationandWorkupofCOPD

Procedure Comments

Evaluation for all patients with suspected COPD

Historyandphysicalexamination Shouldincludethefollowing:

Exposuretoriskfactors

Pasthistoryofasthmaorallergicdisease

FamilyhistoryofCOPD

Presenceofcomorbiddiseases

Effectofdiseaseonpatient’slife,includingabilitytoworkandmentalhealthstatus

Possibilityforreducingriskfactors,especiallysmokingcessation

Assessmentofsymptoms ComprehensiveassessmentofsymptomsusingCATorCCQarerecommended

ProvidemeasuresofsymptomaticimpactofCOPD

Exacerbationhistory Rateofexacerbationsvariesbetweenpatients

MildandmoderateexacerbationsrequiretreatmentwithSABDsand/orantibiotics,oralcorticosteroids

Severeexacerbationsrequiringhospitalizationsassociatedwithpoorprognosis

Spirometry FEV1andFVCshouldbemeasured,andtheFEV1/FVCratiocalculated

OnlyaweakcorrelationbetweenFEV1,symptomsandimpairmentofpatient’shealthstatus

Additional investigations to consider:

Imaging ChestX-rayisseldomdiagnosticinCOPD,butusefultoruleoutotherdiagnoses

Computedtomographyscansmaybehelpfulinthepresenceofatypicalfindingsonthechestradiograph

Oximetryandarterialbloodgasmeasurement

Pulseoximetryisindicatedinallpatientswithclinicalsignsofrespiratoryfailureorrightheartfailure

Bloodgasesshouldbemeasuredifperipheralarterialoxygensaturationis<92%

α1-Antitrypsindeficiencyscreening IndicatedinpatientswhodevelopCOPDatayoungage(<45years)orwhohaveastrongfamilyhistoryofCOPD

Exercisetestingandassessmentofphysicalactivity

Powerfulindicatorofhealthstatusimpairmentandpredictorofprognosis

Usefulforassessingdisability,riskofmortality,andeffectivenessofpulmonaryrehabilitation

Lungvolumesanddiffusingcapacity Notessentialtopatientmanagement,butassistincharacterizingtheseverityofCOPD

CAT=COPDassessmenttest;CCQ=COPDControlQuestionnaire;COPD=chronicobstructivepulmonarydisease;FEV1=forcedexpira-toryvolumein1second;FVC=forcedvitalcapacity;SABD=shortactingbronchodilators.(Reprintedfromreference4.)


inhibitor roflumilast and chronic treatment with antibiot-ics 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 smok-ing. 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 diagnos-ing the disease is important in combating the disease.

Corresponding author: David M. Mannino, MD, Depart-ment of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, 111 Wash-ington 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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