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Inthe

Clini

cIn the ClinicChronicObstructivePulmonary

DiseaseScreening page ITC4-2Diagnosis page ITC4-3

Treatment page ITC4-5

Practice Improvement page ITC4-13

Tool Kit page ITC4-14

Patient Information page ITC4-15

CME Questions page ITC4-16

Section EditorsDeborah Cotton, MD, MPHDarren Taichman, MD PhDSankey Williams, MD

Physician WriterMichael R. Littner, MD

The content ofIn the Clinic is drawn from the clinical information and education

resources of the American College of Physicians (ACP), including PIER (Physicians

Information and Education Resource) and MKSAP (Medical Knowledge and Self-

Assessment Program). Annals of Internal Medicine editors develop In the Clinic

from these primary sources in collaboration with the ACPs Medical Education and

Publishing divisions and with the assistance of science writers and physician writ-

ers. Editorial consultants from PIER and MKSAP provide expert review of the con-

tent. Readers who are interested in these primary resources for more detail can

consult http://pier.acponline.org, http://www.acponline.org/products_services/

mksap/15/?pr31, and other resources referenced in each issue ofIn the Clinic.

CME Objective: To review current evidence for the screening, diagnosis, treatment

and practice improvcment of chronic obstructive pulmonary disease.

The information contained herein should never be used as a substitute for clinical

judgment.

2011 American College of Physicians

wnloaded From: http://annals.org/ by Jose Roel on 09/12/2012


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Which patient populations are atrisk?Patients younger than 35 years rarelyget COPD because susceptible indi-

viduals develop the disease only afterinhalational exposure to causativeagents of sufficient intensity and du-ration. An estimated 80% to 90% ofCOPD is due to cigarette smoking.A risk of 15% for clinically signifi-cant COPD among smokers is com-monly cited, but this may be an un-derestimate (6). The effect ofenvironmental, or second-hand,smoke in the development ofCOPD is less clear (7, 8). Genetic

factors clearly play a role in suscepti-bility to COPD, the best definedbeing emphysema related to

1-

antitrypsin deficiency.

COPD is a common cause of mor-bidity and mortality worldwide.Unlike the sharp reduction in deathfrom heart disease, there has been analmost 100% increase in age-adjust-ed mortality from COPD between1970 and 2002. As of 2006, COPDwas the fourth-leading cause of

death in the United States, account-ing for 5.1% (124 583) of all deaths.In 2000, the number of deaths fromCOPD in women was equal to thatin men. Although COPD deathscontinue to represent a large propor-tion of deaths from all causes, recenttrends suggest that the incidence ofnew cases is decreasing and mortalityrates may have peaked (9).

Should clinicians screenasymptomatic patients?Screening asymptomatic patientsfor COPD with spirometry is not

supported by convincing evidence.The U.S. Preventive Services TaskForce and the Global Initiativefor Obstructive Lung Disease(GOLD) (1, 10) recommendagainst screening for COPD inthe general population. On theother hand, epidemiologic evi-dence suggests that one half of thecurrent population with COPDhas not been identified (7), andpatients who smoke or have other

risk factors may have COPDwithout being symptomatic.

A potential benefit of early detec-tion is the opportunity to motivatepatients to stop smoking, but datato support this are conflicting.Some studies show that simply in-forming patients that they have ab-normal spirometry does not lead tosmoking cessation, while other datasuggest that providing patients withan estimate of their lung age iseffective (11,12).

Some professional organizationsrecommend a case-finding ap-proach in patients with symptomswho present with risk factors, suchas smoking and age older than 35years. For example, the updated2009 GOLD guidelines suggestthat clinicians perform spirometry

2011 American College of Physicians ITC4-2 In the Clinic Annals of Internal Medicine 5 April 2011

1. Global Initiative forChronic ObstructiveLung Disease. Ac-cessed at www.gold-copd.org on 4 De-cember 2010.

2. American ThoracicSociety. COPD Guide-lines. Accessed atwww.copd-ats-ers.org/copddoc.pdf

on 20 November2010.

3. Department of Veter-ans Affairs and De-partment of Defense.COPD Guidelines. Ac-cessed atwww.healthquality.va.gov/Chronic_Ob-structive_Pul-monary_Disease_COPD.asp on 27 Novem-ber 2010.

4. National Institute ofClinical Excellence.Management ofchronic obstructivepulmonary disease inadults in primary andsecondary care. Ac-cessed at http://guid-ance.nice.org.uk/CG101/Guidance/pdf/English on 26 Novem-ber 2010.

5. Salvi SS, Barnes PJ.Chronic obstructivepulmonary disease innon-smokers. Lancet.2009;374:733-43.[PMID: 19716966]

6. Rennard SI, Vestbo J.COPD: the dangerousunderestimate of15%. Lancet. 2006;367:1216-9.[PMID: 16631861]

7. Mannino DM, BuistAS. Global burden of

COPD: risk factors,prevalence, and fu-ture trends. Lancet.2007;370:765-73.[PMID: 17765526]

8. Eisner MD, An-thonisen N, CoultasD, et al. Committeeon NonsmokingCOPD, Environmentaland OccupationalHealth Assembly. Anofficial American Tho-racic Society publicpolicy statement:Novel risk factors andthe global burden ofchronic obstructivepulmonary disease.Am J Resp Crit Care

Med 2010;182:693-718,[PMID: 20802169]

9. Chronic ObstructivePulmonary DiseasePrevalence and Mor-tality. Accessed at theUnited States Enviro-mental ProtectionAgency at http://cf-pub.epa.gov/eroe/in-dex.cfm?fuseac-tion=detail.viewInd&lv=list.listByAlpha&r=216638&subtop=381on 4 December 2010.

Chronic obstructive pulmonary disease (COPD) is a treatable, preventa-ble, and partially reversible disease characterized by progressive airflowobstruction documented by spirometry; it is associated with an abnor-

mal inflammatory response of the lungs to noxious particles or gases (14).

Between 10% and 20% of COPD in the United States is estimated to becaused by occupational or other exposure to chemical vapors, irritants, andfumes. However, a recent review suggested that the percentage of patientswith COPD who never smoked is 25% in the United States and may vary

worldwide between about 15% ( Japan) and 48% (South Africa), withhigher rates in women (5). More information is needed to determine therole of inhaled irritants other than cigarette smoke, such as those found inoutdoor air pollution, and with indoor products of biomass fuels, such aswood-burning stoves.

Screening



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2011 American College of PhysiciansITC4-3In the ClinicAnnals of Internal Medicine5 April 2011

to look for COPD in patients withsymptoms, such as chronic coughand sputum production or short-ness of breath (1). The United

Kingdoms National Institute forClinical Excellence and the Veter-ans Affairs COPD guidelines havesimilar recommendations (3, 4).

10. U.S. Preventive Serv-ices Task Force.Screening for Chron-ic Obstructive Pul-monary Disease Us-ing Spirometry: U.S.Preventive Services

Task Force Recom-mendation State-ment. Ann InternMed. 2008.148:535-43. [PMID: 18316746]

11. Wilt TJ, NiewoehnerD, Kim C, et al. Useof spirometry forcase finding, diagno-sis, and manage-ment of chronic ob-structive pulmonarydisease (COPD). Evid

Rep Technol Assess(Summ). 2005:1-7.[PMID: 16238364]

12. Parkes G, Greenhal-gh T, Griffin M, DentR. Effect on smokingquit rate of tellingpatients their lungage: the Step2quitrandomised con-trolled trial. BMJ2008;336:598-600.[PMID: 18326503]

13. Celli BR, Cote CG,Marin JM, et al. Thebody-mass index,airflow obstruction,dyspnea, and exer-cise capacity indexin chronic obstruc-

tive pulmonary dis-ease. N Engl J Med.2004;350:1005-12.[PMID: 14999112]

14. Bestall JC, Paul EA,Garrod R, et al. Use-fulness of the Med-ical Research Coun-cil (MRC) dyspnoeascale as a measureof disability in pa-tients with chronicobstructive pul-monary disease.

Thorax. 1999;54:581-6. [PMID: 10377201]

15. Pulmonary ScientificCouncil of the Inter-national Society forHeart and Lung

Transplantation. In-ternational guide-lines for the selec-tion of lungtransplant candi-dates: 2006 up-datea consensusreport from the Pul-monary ScientificCouncil of the Inter-national Society forHeart and Lung

Transplantation. JHeart Lung Trans-plant. 2006; 25:745-55. [PMID: 16818116]

airflow limitation (e.g., improvementin FEV

1after bronchodilator or glu-

cocorticosteroids) is not recom-

mended for diagnosis, differential di-agnosis with asthma, or forprediction of response to long-termtreatment with bronchodilators orglucocorticosteroids (1, 4).

Measurement of lung volume anddiffusing capacity may support thediagnosis but are not generally re-quired. Arterial blood gases andpulse oximetry are usually used todetermine whether a patient is a

candidate for long-term oxygentherapy or if chronic hypercapnia ispresent. These tests may also behelpful in further characterizing theseverity of COPD; suggesting thepresence of emphysema, and ex-cluding other lung diseases, such asrestrictive lung disease.

Spirometric measurements can alsobe used to calculate the BODE in-dex (Table 1) (13), which stands forBody mass index; Obstruction as

measured by FEV1; Dyspnea asmeasured by the Modified MedicalResearch Council dyspnea question-naire (14); and Exercise, as deter-mined by a 6-minute walk test. In-creasing BODE index is associatedwith higher risk for hospitalizationand worse long-term prognosis. It isalso used in evaluation of patients forlung transplantation (15).

When should clinicians consider adiagnosis of COPD?COPD should be considered in pa-

tients with a history of significantexposure to tobacco smoke, espe-cially when they have such symp-toms as cough, sputum production,dyspnea, and decreased exercise tol-erance. The physical examinationmay be normal. In more advanceddisease, there may be evidence ofhyperinflation, such as hyperreso-nance and distant breath sounds.Chronic bronchitis, defined as atleast 90 days of cough and sputum

production in each of 2 consecutiveyears, and emphysema, a pathologicdiagnosis suggested by hyperinfla-tion on examination and confirmedby imaging studies, are commonlyassociated with COPD. However,neither is required to make the di-agnosis.

What is the role of pulmonaryfunction testing in diagnosis?Spirometry is essential for diagnosisand classification of COPD. A post-

bronchodilator FEV1FVC ratio 80%), moderate (50%80%),severe (30%50%), or very severe(


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16. Blanco I, Gimeno E,Munoz PA, et al. He-modynamic and gasexchange effects ofsildenafil in patientswith chronic ob-

structive pulmonarydisease and pul-monary hyperten-sion. Am J Respir CritCare Med.2010;181:270-8.[PMID: 19875684]

17. Rietema H, HolverdaS, Bogaard HJ, et al.Sildenafil treatmentin COPD does notaffect stroke volumeor exercise capacity.Eur Respir J.2008;31:759-64.[PMID: 18094009]

18. Stolz D, Rasch H, Lin-ka A, et al. A ran-domised, controlledtrial of bosentan in

severe COPD. EurRespir J.2008;32:619-28.[PMID: 18448495]

19. National Asthma Ed-ucation and Preven-tion Program ExpertPanel Report3:Guidelines for theDiagnosis and Man-agement of Asthma.Accessed atwww.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf on 24December 2010.


The BODE index was validated prospec-

tively in 625 patients with COPD. The aver-

age FEV1percentage predicted varied from

39% to 47%. For each 1-point increase in

the BODE index, there was a 1.34 increase

in the hazard ratio for subsequent death

from any cause and a 1.62 increase for

death from respiratory failure (13).

What other laboratory tests

should clinicians order when

evaluating patients with COPD?

Apart from the specific pulmonaryfunction tests described previously,no other tests are routinely recom-mended in diagnosing COPD, clas-sifying its severity, or helping to de-termine prognosis. However, chestradiographs may show flattened di-aphragms and hyperlucency andcomputed tomography (CT) scan-ning may show destruction of pul-monary parenchyma in patients withemphysema. In addition, echocardio-

graphy may indicate the possibilityof cor pulmonale from pulmonaryhypertension. Treatment of such pul-monary hypertension with vasodila-tors is off-label, may not be effectivein improving exercise tolerance andreducing pulmonary arterial bloodpressure, and frequently leads to areduction in arterial oxygen hemo-globin saturation (1618).

Clinicians should consider measuringthe

1-antitrypsin level in patients

who have documented COPD withonset as early as the fifth decade of lifeor in the absence of a recognized riskfactor, such as smoking and occupa-tional dust exposure. It should also beconsidered in patients with a familyhistory of emphysema or

1-anti-

trypsin deficiency, bronchiectasis, liverdisease, or panniculitis.

Exercise testing may also be usefulin the differential diagnosis of pa-tients with dyspnea when it isunclear whether symptoms are pul-monary or cardiac in origin.

What other disorders shouldclinicians consider in patients withsuspected COPD?In the proper setting, clinicians shouldconsider any condition that producesairflow obstruction, including asthma;

bronchiectasis; cysticfibrosis; bronchiolitis; and upper air-way obstruction due to tumors of thetrachea, tracheal stenosis, tracheo-malacia, and vocal cord dysfunction.Less common diagnoses include otherpulmonary conditions that cause dys-pnea, such as interstitial lung disease;pulmonary arterial hypertension; chestwall disorders, such as kyphoscoliosis;

Table 1. The MMRC Dyspnea Severity Scale* for Calculation of the BODE Index

Severity Score Degree of Breathlessness Related to Activities

None 0 Not troubled with breathlessness except with strenuous exercise

Mild 1 Troubled by shortness of breath when hurrying or walking up a slight hill

Moderate 2 Walks slower than people of the same age due to breathlessness or has to stop for breath whenwalking at own pace on level ground

Severe 3 Stops for breath after walking approximately 100 meters or after a fewminutes on level ground

Very severe 4 Too breathless to leave the house or breathless when dressing or undressing

Variable Points on BODE Index

0 1 2 3

FEV1 (percentage predicted) 65 5064 3649 35

Distance walked in 6 min, m 350 250349 150249 149

MMRC dyspnea scale score 01 2 3 4

Body mass index >21 21

* Adapted from Veterans Affairs and Department of Defense guidelines (3). BODE = Body mass index, Obstruction,Dyspnea, and Exercise; COPD = chronic obstructive pulmonary disease; MMRC = Modified Medical Research Council.

Points for each variable are summed with a possible range from 0 to 10. Higher numbers indicate worse prognosis. Adapted from (10).



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20. Anthonisen NR,Connett JE, Kiley JP,

et al. Effects ofsmoking interven-tion and the use ofan inhaled anti-cholinergic bron-chodilator on therate of decline ofFEV1. The LungHealth Study. JAMA.1994;272:1497-505.[PMID: 7966841]

21. Anthonisen NR,Skeans MA, Wise RA,et al. The effects of asmoking cessationintervention on 14.5-year mortality: a ran-domized clinical trial.Ann Intern Med.2005;142:233-9.

[PMID: 15710956]22. Clinical Efficacy As-

sessment Subcom-mittee of the Ameri-can College ofPhysicians. Diagnosisand management ofstable chronic ob-structive pulmonarydisease: a clinicalpractice guidelinefrom the AmericanCollege of Physi-cians. Ann InternMed. 2007;147:633-8. [PMID: 17975186]


and cardiac causes. Some of these mayalso coexist with COPD.

How should clinicians distinguish

between patients with COPD and

those with asthma?

Because spirometric obstruction,cough, wheeze, and dyspnea arecommon to both COPD and asth-

ma, it is sometimes difficult todistinguish between the disorders.In general, patients with asthmadevelop symptoms at a younger

age; are less likely to be smokers;and experience symptoms intermit-tently and with more variability,which may be demonstrated bymonitoring daily peak flow (19).Those with COPD tend to haveonset of disease later in life; com-monly have chronic productivecough; have more persistent dysp-

nea; and generally have a less con-sistent response to drugs, such asinhaled corticosteroids and bron-chodilators.

physicians offices to more struc-tured programs, which typically in-clude 2 to 3 longer advice sessionsand medications, such as nicotinepreparations, bupropion, or vareni-cline. These programs are effectivein up to 30% of patients at 1 year.

How should clinicians approach

drug therapy?

Inhaled medicationsincluding 2-

agonists, anticholinergics, and corti-costeroidsare the cornerstones ofpharmacotherapy for COPD andshould be considered part of anoverall treatment strategy that in-cludes smoking cessation, education,pulmonary rehabilitation, and long-term oxygen therapy (LTOT) in hy-

poxemic patients. Of these therapies,only smoking cessation convincinglyreduces the rate of decline in pul-monary function, and only smokingcessation and LTOT decrease mor-tality. The goal of treatment shouldbe symptom relief, particularly dysp-nea, prevention of exacerbations, andimprovement in long-term respira-tory health status.

What is the evidence thatsmoking cessation benefitspatients who already have COPD,and which smoking cessationinterventions are most effective?Clinicians should urge all patientswith COPD who smoke to quit and

to enroll in a smoking cessation pro-gram. There is excellent evidencethat patients with COPD who stopsmoking have a reduced rate of de-cline in pulmonary function (20)and reduced mortality (21).

In a multicenter, randomized, controlled tri-al (RCT) of an intensive smoking cessation

program that included behavioral modifi-cation and nicotine gum versus placebo,middle-aged smokers in the interventiongroup had a slower rate of decline in FEV

1

(34 mL/y) than those in the placebo group(63 mL/y) over a 5-year period(21).A follow-up study found that after 14.5 years, all-cause mortality was significantly lower inthe smoking cessation group than in theusual care group (8.83 per 1000 person-

years vs. 10.38 per 1000 person-years; P =0.03) (21).

Smoking cessation therapies rangefrom brief interventions in

Diagnosis... Clinicians should suspect COPD in patients with a smoking history orsubstantial exposure to inhaled irritants who have chronic cough, sputum, or dys-pnea. Confirm the diagnosis by spirometry with a FEV1FVC ratio < 0.70 measuredafter administration of a bronchodilator. Use the FEV1 and clinical data to deter-mine disease severity and to exclude other disorders. Consider measuring the 1-antrypsin level in patients who present with early-onset COPD or in those with acompatible family history.

CLINICAL BOTTOM LINE

Treatment



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Before therapy is initiated, it isimportant to assess the severity ofdisease by the level of FEV

1and by

asking about baseline symptoms andthe nature and frequency of exacer-bations. Validated instruments, likethe Modified Medical ResearchCouncil scale of dyspnea (Table 1),may provide additional information.

Symptoms do not necessarily corre-late with the level of FEV

1, and dys-

pnea may respond to drug therapy atany level. However, most studies ofthe effectiveness of drug therapywith endpoints of health status andfrequency of COPD exacerbationswere performed in symptomatic pa-tients with an FEV

1< 60% of the

predicted level. In view of this, theAmerican College of Physicians(ACP) recommended that long-

acting bronchodilator and inhaledcorticosteroid treatment for stableCOPD be reserved as primary ther-apy for patients who have respiratorysymptoms and an FEV

1< 60% of

predicted (22). However, these

interventions are often indicated forsymptom relief in patients with ahigher FEV

1.

What is the role of inhaledbronchodilators?

There are no data to recommendinitial use of one bronchodilator overanother, and the choice should be

based on patient preference, poten-tial side effects, and cost. Treatmentshould begin with a single bron-chodilator and step up to combina-tion bronchodilator therapy if addi-tional symptomatic relief is required(14). The Figure outlines theguidelines to step therapy from theAmerican Thoracic Society/European Respiratory Society (2)and is consistent with other recom-mendations (14).

Short-acting bronchodilators withdurations of action of 3 to 6 hoursare preferred in patients with mildCOPD, for treatment of intermit-tent symptoms, and for rescue treat-ment for breakthrough symptoms inpatients taking long-acting medica-tions. The short-acting bronchodila-tors include

2-agonists or the anti-

cholinergic agent ipratropium (Table2). Ipratropium has a slower onset ofaction but can be used for rescue asmonotherapy or in combination withalbuterol. Metered-dose inhalers, dry-powder inhalers, and nebulizers areequally effective but require patienteducation regarding proper techniqueto ensure adequate drug delivery.For example, the open-mouth tech-nique is not recommended for anyhydrofluoroalkane propellantdriveninhaler because of the slow speed ofaerosol delivery, or with anyanticholinergic metered-dose inhaler

due to the potential for pupillarydilatation.

Monotherapy with long-acting bron-chodilators significantly reduces thefrequency of exacerbations and im-proves overall respiratory health statusbut does not significantly reduce hos-pitalizations or mortality (23, 24). Posthoc analyses have suggested that a

Figure. Step therapy for patients with COPD from the American

Thoracic Society/European Respiratory Society guidelines.

23. Calverley PM, Ander-son JA, Celli B, et al.

TORCH investigators.Salmeterol and fluti-

casone propionateand survival inchronic obstructivepulmonary disease.N Engl J Med.2007;356:775-89.[PMID: 17314337]

24. Tashkin DP, Celli B,Senn S, et al. A 4-Year Trial of Tiotropi-um in Chronic Ob-structive PulmonaryDisease. N Engl JMed 2008;359:1543-54. [PMID: 18836213]

25. Celli BR, Thomas NE,Anderson JA, et al.Effect of pharma-cotherapy on rate ofdecline of lung func-

tion in chronic ob-structive pulmonarydisease: results fromthe TORCH study.Am J Respir Crit CareMed. 2008;178:332-8. [PMID: 18511702]

26. Troosters T, Celli B,Lystig T, et al.

Tiotropium as a firstmaintenance drugin COPD: secondaryanalysis of the UP-LIFT trial. Eur RespirJ. 2010;36:65-73.[PMID:20185426]

27. van Noord JA, Au-mann JL, Janssens E,et al. Comparison oftiotropium once dai-

ly, formoterol twicedaily and both com-bined once daily inpatients with COPD.Eur Respir J.2005;26:214-22.[PMID: 16055868]

28. Aaron SD, Van-demheen KL, Fer-gusson D et al;Canadian ThoracicSociety/CanadianRespiratory ClinicalResearch Consor-tium. Tiotropium incombination withplacebo, salmeterol,or fluticasone-salme-terol for treatment ofchronic obstructive

pulmonary disease:a randomized trial.Ann Intern Med.2007;146:545-55.[PMID: 17310045]

29. Puhan MA, Bach-mann LM, Kleijnen J,et al. Inhaled drugsto reduce exacerba-tions in patientswith chronic ob-structive pulmonarydisease: a networkmeta-analysis. BMCMed. 2009;7:2-15.[PMID: 19144173]



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Table 2. Drug Treatment for COPD*

Agent Dosage Side Effects Notes

Bronchodilator agentsInhaled short-acting 2 inhalations as needed, Sympathomimetic symptoms, such Generally used as needed2-agonist: up to 12 inhalations per day as tremor and tachycardia

albuterollevalbuterolmetaproterenolpirbuterol

Inhaled short-acting 2 inhalations qid, increase as Dry mouth, mydriasis on contact Approved by the FDA as maintenance

anticholinergic: tolerated with eye therapy. Not to be used with tiotropium.ipratroplum

Inhaled long-acting 18 g/d Dry mouth, mydriasis on contact Approved by the FDA as maintenanceanticholinergic: with eye therapy and to prevent COPD exacerba-

tiotropium tions. Not to be used with ipratropium

Inhaled long-acting Salmeterol, 42 g bid by MDI and Sympathomimetic symptoms, such Use as maintenance therapy. Overdose2-agonist: 50 g bid by DPI; formoterol, as tremor and tachycardia can be fatal. Not to be used to treat COPD

salmeterol 12 g bid by DPI and 20 g by exacerbations or acute bronchospasm.formoterol nebulized solution; aformoterol,aformoterol 15 g bid by nebulized solution

Oral theophylline Aim for serum levels between 5 Tachycardia, nausea, vomiting, Use as maintenance therapy.aminophylline: and 14 g/mL disturbed pulmonary function, and May also improve respiratory

generic and sleep. Overdose can be fatal with muscle function.brand name seizures and arrhythmiassustained and

short actingOral 2-agonists: Albuterol, 4 mg bid; Sympathomimetic symptoms, such Use as maintenance therapy. Rarely

albuterol metaproterenol, 5 to 10 mg tid as tremor and tachycardia used because of side effects but may bemetaproterenol to qid; terbutaline, 2.5 to 5 mg tid beneficial to patients who cannot useterbutaline inhalers.

Oral phosphodiesterase Roflumilast, 500 mcg daily Diarrhea, weight loss , nausea, Use to reduce risk for COPD exacerbations4 inhibitors influenza, insomnia, headache, in patients with severe COPD associated

backache, decreased appetite, with chronic bronchitis and a history ofdizziness exacerbations. Rofilumast is not a broncho-

dilator and is not indicated for relief ofacute bronchospasm.

Anti-inflammatory agentsInhaled corticosteroids: Maximum daily recommended Skin bruising, oral candidiasis, rarely Most effective in patients with a history

fluticasone doses of the following: adrenal suppression possibly glaucoma, of frequent exacerbations and whenbudesonide fluticasone, 880 mcg, budesonide decreased bone density, diabetes used in conjunction with long-acting

mometasone 720 mcg, mometasone, systemic hypertension, pneumonia bronchodilators. Not approved byciclesonide 880 mcg, ciclesonide, 640 mcg; and cataracts the FDA for treatment of COPD.all in divided doses.

Oral corticosteroids: Varying doses Skin bruising, adrenal suppression, Avoid use, if possible, in stable COPD.prednisone glaucoma, osteoporosis Pulmonary function improved in 10%20%prednisolone of patients. Reduce to lowest effective

indose, cluding transition to inhaledcorticosteroids, alternate day oralcorticosteroids, or both. Intravenous or oralcorticosteroids are standard therapy and areeffective for acute exacerbations.

Combination agents

Combined inhaled long- Each dose is given twice daily. See long-acting 2 agonist and Fluticasone 250 mcg/salmeterol 50 mcgacting 2-agonist and fluticasone 250 mcg/salmeterol inhaled corticosteroid Diskus is approved by the FDA asinhaled corticosteroid: 50 mcg dry powder Diskus maintenance therapy for COPD andin a single inhaler fluticasone 230 mcg/salmeterol prevention of COPD exacerbations.

42 mcg Budesonide 320/ formoterol 9 mcg MDIbudesonide 320 mcg/formoterol is aproved by FDA as maintenance

10 mcg MDI therapy for COPD. All other combinationsCombination of comparable and doses including those not listed aredoses of inhaled corticosteroids not approved by the DFDA for COPD.and long-acting 2-agonists in Combinations are not to be used forseparate inhalers treatment of acute bronchospasm.

Overdosage of combination can be fatalbecause of long-acting 2-agonist.

*COPD = chronic obstructive pulmonary disease; DPI = dry-powder inhaler; FDA = Food and Drug Administration; MDI = metered-dose inhaler; qid = fourtimes daily; tid = three times daily.



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30. Ferguson GT, Anzue-to A, Fei R, et al. Ef-fect of fluticasonepropionate/salme-terol (250/50 mi-

crog) or salmeterol(50 microg) onCOPD exacerbations.Respir Med.2008;102:1099-108.[PMID: 18614347]

31. Anzueto A, FergusonGT, Feldman G, et al.Effect of fluticasonepropionate/salme-terol (250/50) onCOPD exacerbationsand impact on pa-tient outcomes.COPD. 2009;6:320-9.[PMID: 19863361]

32. Lee TA, Wilke C, JooM, Stroupe KT, et al.Outcomes associat-ed with tiotropium

use in patients withchronic obstructivepulmonary disease.Arch Intern Med.2009;169:1403-10.[PMID:19667304]

33. Singh S, Loke YK.Risk of pneumoniaassociated withlong-term use of in-haled corticosteroidsin chronic obstruc-tive pulmonary dis-ease: a critical reviewand update. CurrOpin Pulm Med.2010;16:118-22.[PMID: 19926996]

34. Prevention and con-trol of influenza: rec-

ommendations ofthe Advisory Com-mittee on Immu-nization Practices(ACIP). MMWR MorbMortal Wkly Rep.2010;59:1102-6.[PMID: 20814406]

35. Poole PJ, Chacko E,Wood-Baker RW, etal. Influenza vaccinefor patients withchronic obstructivepulmonary disease.Cochrane DatabaseSyst Rev.2006:CD002733.[PMID: 16437444]

36. Anthonisen NR,Manfreda J, Warren

CP, et al. Antibiotictherapy in exacerba-tions of chronic ob-structive pulmonarydisease. Ann InternMed. 1987;106:196-204. [PMID: 3492164]

37. Sethi S. Infectiousexacerbations ofchronic bronchitis:diagnosis and man-agement. J Antimi-crob Chemother.1999;43 Suppl A:97-105.[PMID: 10225579]


long-acting 2-agonist (LABA) re-

duces the rate of decline of pulmonaryfunction in patients with a prebron-chodilator FEV

1 60% of predicted

(25), as did a long-acting anticholiner-gic in patients with a postbroncho-dilator FEV1 70% of predicted (26).

Approved LABAs include salme-

terol, formoterol, and aformoterol, allof which require twice-daily dosing.The only long-acting anticholinergicagent currently available is tiotropi-um, which is given once daily. Sal-meterol and tiotropium have a slowonset of action, whereas formoteroland aformoterol have a rapid onsetof action. Long-acting bronchodila-tors should never be used as rescuetherapy or in doses greater thanthose indicated on package inserts.

Oral 2-agonists have not been

well-studied in COPD. They maybe effective but are slower in onset,have more side effects (1), and aregenerally avoided.

If monotherapy is insufficient, cli-nicians should consider using in-haled combination therapy with aLABA and long-acting anticholin-ergic. Some studies show that suchcombinations may improve FEV

1

(27), but few data indicate thatcombination therapy is significantlybetter than monotherapy in allevi-ating dyspnea, improving exercisetolerance, and reducing COPDexacerbations. One study suggeststhat combination therapy withtiotropium and salmeterol improvesdisease-specific quality of life (29).

When should clinicians prescribecorticosteroids?Clinicians should consider adding

inhaled corticosteroids to regimensof inhaled long-acting bronchodila-tors in patients with moderate or se-vere COPD (usually when FEV

1is

< 50% of predicted) who remainsymptomatic or have repeated exac-erbations. When paired with aLABA, inhaled corticosteroids affordgreater improvement in pulmonaryfunction and clinical outcomes than

either agent alone (23). Post hocanalysis of one study suggested thatan inhaled corticosteroid alone orcombined with a LABA comparedwith placebo reduced the rate of de-cline of pulmonary function (25).

A meta-analysis of 26 786 patients in RCTs toNovember 2007 compared the combination

of an inhaled corticosteroid and a LABA withthe LABA alone. The combination signifi-cantly reduced the incidence of exacerba-tions in patients with an FEV

140% of pre-

dicted but not in patients with a higher FEV1

(29). Other, more recent RCTs document theefficacy of combination therapy in prevent-ing exacerbations compared with a LABAalone in patients with a prebronchodilatorFEV

1 50% predicted and a COPD exacerba-

tion in the past year (30, 31).

Combining a long-acting anticholin-ergic with a LABA plus an inhaled

corticosteroid improves quality of lifecompared with monotherapy with along-acting anticholinergic (28). Aretrospective analysis of a long-act-ing anticholinergic when used withan inhaled corticosteroid and aLABA suggested that this combina-tion reduced mortality, COPD exac-erbations, and COPD hospitaliza-tions compared with an inhaledcorticosteroid combined with aLABA. Other combinations that in-

cluded a long-acting anticholinergicand a short-acting anticholinergictogether seemed to increase mortali-ty, exacerbations, and hospitaliza-tions (32).

An RCT compared salmeterol plus fluticas-one with placebo, salmeterol alone, or flu-ticasone alone for a period of 3 years in6112 patients with an FEV

1< 60% of pre-

dicted. The study found that the combina-tion decreased the annual rate of moder-ate-to-severe exacerbations comparedwith either salmeterol or fluticasone alone.

A statistically signif icant effect on mortali-ty was not seen (23).

Side effects of inhaled cortico-steroids are listed in Table 2. The inci-dence of pneumonia is reported to beincreased with the use of inhaled cor-ticosteroids; a meta-analysis of RCTscomprising over 23 000 patientsshows a relative risk of pneumonia of



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38. McCrory DC, BrownC, Gelfand SE, et al.Management ofacute exacerbationsof COPD: a summaryand appraisal of

published evidence.Chest.2001;119:1190-209.[PMID: 11296189]

39. Quon BS, Gan WQ,Sin DD. Contempo-rary management ofacute exacerbationsof COPD: a systemat-ic review and meta-analysis. Chest.2008;133:756-66.[PMID: 18321904]

40. Niewoehner DE, Erb-land ML, DeupreeRH, et al. Effect ofsystemic glucocorti-coids on exacerba-tions of chronic ob-structive pulmonary

disease. Departmentof Veterans AffairsCooperative StudyGroup. N Engl J Med.1999;340:1941-7.[PMID: 10379017]

41. Hurst JR, Vestbo J,Anzueto A, Locan-tore N, et al. Suscep-tibility to exacerba-tion in chronicobstructive pul-monary disease. NEngl J Med.2010;363:1128-38.[PMID: 2084324730]


1.56 (P< 0.0001) in patients taking in-haled corticosteroids compared withthose who did not (33). Althoughsafety concerns prompted the U.S.Food and Drug Administration(FDA) to recommend against the useof LABAs without concomitant ad-ministration of inhaled corticosteroids,these recommendations did not apply

to COPD.

Oral corticosteroids should be re-served for limited periods to treatacute exacerbations of COPD. Ingeneral, ongoing use of oral corti-costeroids should be avoided instable disease because of limited, ifany, benefits and a high potentialfor side effects.

When should clinicians consider

adding oral theophylline toinhaled drug therapy?

The bronchodilator effects ofmethylxanthines, such as amino-phylline or theophylline, are rela-tively modest, and side effects, es-pecially nausea andtachyarrhythmia, are common.These drugs can be used in patientswith refractory symptoms even ifthey are receiving inhaled bron-chodilators and/or inhaled corticos-teroids. In such patients, theo-phylline can be started at a lowdose and titrated to effect, aimingfor a blood level between 5 and 14micrograms/mL (2, 3). Theo-phylline should be discontinued ifsymptoms do not improve afterseveral weeks and should not beused in treating acute exacerbationsof COPD. The narrow therapeuticwindow, multiple interactions withother medications, and potentialtoxicity necessitate frequent moni-

toring of serum drug levels.

What immunizations should

clinicians administer?The Advisory Committee on Immu-nization Practices recommends in-fluenza and pneumococcal vaccina-tions for persons who have chronicpulmonary or cardiovasculardisorders, including COPD (34).

Influenza vaccination should be ad-ministered yearly to all patients withCOPD.

In a Cochrane review of 11 RCTs, 6 of whichwere done in patients with COPD, use of in-activated influenza vaccine resulted in asignificant reduction in the total numberof exacerbations per vaccinated personcompared with those who received place-

bo (weighted mean difference, 0.37 [95%CI, 0.64 to 0.11]; P= 0.006) (35).

Adults aged 19 to 64 who smoke orwho have COPD should be givenpneumococcal vaccination once,and again after age 65 years if theprevious vaccination was givenmore than 5 years earlier. If the pa-tient was not vaccinated before age65, then a one-time vaccination isrecommended (34).

How should clinicians manageacute exacerbations?Although there is no single defini-tion of a COPD exacerbation, thecriteria shown in the Box are usedcommonly (Criteria and Classifica-tion of Acute COPD Exacerbation).

Acute exacerbations frequently de-velop after an upper respiratoryinfection. Management includesprompt recognition and may also

involve adjustment of bronchodilatorand steroid therapy, initiation ofantibiotics, and assessment of theneed for hospitalization. If pneumo-nia is suspected, a chest radiographshould be obtained for confirmation.

Clinicians should strongly considerprescribing antibiotics for patientswith a moderate or severe exacerba-tion. Exacerbations may be due tobacterial or viral infection or inhaledirritants; the inciting factor is typically

not known in usual practice, so thera-py is given for the most common bac-terial pathogens, Haemophilus influenza,Streptococcus pneumoniae, andMoraxellacatarrhalis(36, 37), taking into accountlocal bacterial resistance patterns. Sev-eral meta-analyses and systematic re-views support the utility of antibioticsin this setting because they improvepeak flow, reduce mortality, and

Criteria and Classification of

Acute COPD Exacerbation

Major criteria Increase in sputum volume

Increase in sputum purulence(generally yellow or green)

Worsening dyspnea

Additional criteria Upper respiratory infection in the

past 5 days Fever of no apparent cause

Increase in wheezing and cough

Increase in respiratory rate or heartrate 20% above baseline

Mild exacerbation = 1 major criterionplus 1 or more additional criteria

Moderate exacerbation = 2 majorcriteria

Severe exacerbation = all 3 majorcriteria

(Adapted from ref. 30)



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42. Sasaki T, NakayamaK, Yasuda H, et al. Arandomized, single-blind study of lanso-prazole for the pre-vention ofexacerbations ofchronic obstructivepulmonary disease

in older patients. JAm Geriatr Soc.2009;57:1453-7.[PMID: 19515110]

43. Sethi S, Jones PW,Theron MS, et al.Pulsed moxifloxacinfor the prevention ofexacerbations ofchronic obstructivepulmonary disease:a randomized con-trolled trial. RespirRes. 2010;11:10-22.[PMID: 20109213]

44. Seemungal TA,Wilkinson TM, HurstJR, et al. Long-termerythromycin thera-py is associated with

decreased chronicobstructive pul-monary disease ex-acerbations. Am JRespir Crit Care Med.2008;178:1139-47.[PMID: 1872343744]

45. Poole P, Black PN.Mucolytic agents forchronic bronchitis orchronic obstructivepulmonary disease.Cochrane DatabaseSyst Rev. 2010 Feb17;(2):CD001287.[PMID 20166060]


reduce treatment failure, especially inpatients with more severe exacerba-tions (38, 39).

The severity of the exacerbation, thedegree of impaired pulmonary func-tion, the history of exacerbations, andthe response to previous treatmentshould be used to guide therapy. Spu-

tum Gram stain and culture are usual-ly not initially needed to treat acuteexacerbations. Rather, the severity ofthe exacerbation and baseline pul-monary function is useful to guidetherapy. For patients with moderate orsevere exacerbations, a -lactam/-lac-tamase inhibitor, an extended-spec-trum macrolide, a second- or third-generation cephalosporin, or afluoroquinolone can be used. Mildexacerbations can be managed with a

tetracycline or trimethoprim-sulfa-methoxazole. In any case, alwaysconsider antibiotics in patients withpurulent sputum (1, 4).

Oral corticosteroids should be con-sidered in patients with moderate-to-severe acute exacerbations of COPD.Although the appropriate dose is notwell-defined, 30 to 60 mg/d for up to2 weeks is commonly used. There isgood evidence to suggest that a 6-week course of systemic steroids is no

more beneficial than a 2-weekcourse, and the longer course increas-es the risk for adverse effects (40).

A meta-analysis of 959 patients treated for

COPD exacerbations found a reduction intreatment failures with the use of systemiccorticosteroids (39).

Tailoring therapy to prevent futureCOPD exacerbations is difficultbecause there are several factors thatdetermine risk. The frequency of an

exacerbation in the past year has anoverall sensitivity of 43% and a speci-ficity of 87% for predicting thefrequency of an exacerbation in thefollowing year. The best predictor offuture exacerbations is 2 or more exac-erbations in the past year. Othersinclude a baseline FEV

1


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46. Decramer M, Rutten-van Mlken M,Dekhuijzen PN, et al.Effects of N-acetyl-cysteine on out-comes in chronicobstructive pul-monary disease(Bronchitis Random-ized on NAC Cost-Utility Study, BRON-CUS): a randomisedplacebo-controlledtrial. Lancet.2005;365:1552-60.[PMID:15866309]

47. Salman GF, Mosier

MC, Beasley BW, etal. Rehabilitation forpatients with chron-ic obstructive pul-monary disease:meta-analysis of ran-domized controlledtrials. J Gen InternMed. 2003;18:213-21. [PMID: 12648254]

48. Puhan MA,Scharplatz M, Troost-ers T, et al. Respirato-ry rehabilitation afteracute exacerbationof chronic obstruc-tive pulmonary dis-ease. CochraneDatabase of System-atic Reviews 2009, Is-

sue 1. Ar.No.:CD005305.DOI:10.1002/14651858. CD005305.pub2.[PMID: 19160250]

49. Guyatt GH, Nonoya-ma M, Lacchetti C, etal. A randomized tri-al of strategies forassessing eligibilityfor long-term domi-ciliary oxygen thera-py. Am J Respir CritCare Med.2005;172:573-80.[PMID: 15901604]


breathlessness and anxiety that limitactivity, and who are willing to un-dertake an intensive education andexercise program (1, 3). Most studiesinvolve patients with more severeCOPD, but patients with mild-to-moderate disease may also benefit.

A meta-analysis of 20 RCTs of 979 patients,

including studies to the year 2000, conclud-ed that pulmonary rehabilitation increasedexercise ability and health-related quality oflife and reduced dyspnea. Inspiratory muscletraining by itself was not effective. Patientswith severe COPD required a program last-ing at least 6 months to achieve benefit,while patients with mild-to-moderate COPDcould benefit from shorter programs (47).

A Cochrane collaboration analysis of 219patients to 2008 found that pulmonary re-habilitation following a COPD exacerba-tion significantly reduced future hospital

admissions and mortality and improvedhealth-related quality of life comparedwith conventional community care with-out rehabilitation. The improvement inhealth-related quality of life was wellabove the minimal important difference.In all trials, pulmonary rehabilitation im-

proved exercise capacity. No adverseevents were reported (2 studies) (48).

What other adjunctive measuresshould clinicians consider?Adjunctive therapies are used com-

monly, although little evidence sup-ports their effectiveness. Relaxationtechniques may reduce anxiety dueto shortness of breath, pursed-lipbreathing and diaphragmatic breath-ing are used to reduce shortness ofbreath, and nutritional interventionsaim to achieve ideal body weight andimprove the ability to perform dailyactivities and exercise (1, 3, 4). Chestphysiotherapy, percussion and vibra-tion, and postural drainage are usedto enhance clearance of sputum andalleviate shortness of breath, buthave limited usefulness in the ab-sence of excessive sputum productionand inadequate bronchial clearance.

When should clinicians prescribeoxygen therapy?Patients with moderate-to-severeCOPD should be periodicallyevaluated to determine whether they

need supplemental oxygen. The Boxlists criteria for initiation of long-term oxygen therapy (Criteria forInitiation of Long-Term OxygenTherapy). Measurement of PaO

2af-

ter 30 minutes of breathing room airis the most accurate clinical standardfor initiating therapy. Pulse oximetrycan be used to qualify patients for

long-term oxygen therapy and to ad-just oxygen flow rates after the initialdiagnosis and over time. Inexpensivepulse oximeters allow patients toself-adjust the rate of oxygen flow,provided the patient is instructed inthe use of the oximeter and keepsSaO

2above and near 90%. This ap-

proach can also be useful for patientsto titrate oxygen flow at differentaltitudes.

When long-term oxygen therapy isindicated, it should be used for atleast 15 hours and ideally 24 hours aday. Patients should have an initialfollow-up within 3 months and year-ly thereafter to guide subsequentoxygen therapy (49). However, thecriteria of the Centers for Medicare& Medicaid Services do not general-ly require follow-up assessment if thequalifying PaO

2was 55 mm Hg or

less or the qualifying SaO2was 88%

or less (50).In patients who do not qualify forcontinuous therapy, oxygen thera-py can be used to reduce dyspneaduring exercise in persons withexertional desaturation (51, 52)and during sleep in those who de-saturate at night (52). However, itis unclear whether the use of noc-turnal oxygen in patients withoutdaytime hypoxemia has benefits inmortality, health-related quality of

life, or daytime function (52, 53).

In a Cochrane review, meta-analysis of 6RCTs showed that long-term home oxy-

gen therapy improved survival in a select

group of patients with COPD and severehypoxemia (arterial PaO

2< 55 mm Hg

[8.0 kPa]). Home oxygen therapy did not

improve survival in patients with mild-to-moderate hypoxemia or in those with

only arterial desaturation at night(53).

Criteria for Initiation of

Long-Term Oxygen Therapy

Room air PaO2

no greater than 55mm Hg or between 56 to 59 mmHg with cor pulmonale or signs oftissue hypoxia, such aspolycythemia; or an SaO

2no

greater than 88%, or 89% withcor pulmonale and/or signs oftissue hypoxia;

Nocturnal hypoxemia with anSaO

2no greater than 88% (use

oxygen only at night); or

Exercise hypoxemia with a PaO2

55 mm Hg or less or an SaO2

88% of less (use oxygen onlywith exertion).



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When should clinicians referpatients to a pulmonologist?Clinicians should consider referringpatients with COPD to a pulmonolo-gist when there is diagnostic uncer-tainty or when patients are not re-sponding well to treatment. Table 3lists referral recommendations adaptedfrom professional society guidelines.

Patients with COPD have a 2.7- to4.7-fold increase in the risk forpostoperative pulmonary complica-tions depending on the severity ofCOPD and the type, location, andurgency of the surgical procedure.Patients undergoing thoracic andupper abdominal procedures are atgreatest risk. Patient-related risk fac-tors include age, American Societyof Anesthesiologists class, and ciga-

rette smoking (54).A systematic review of interventionsto reduce postoperative pulmonarycomplications after noncardiothoracicsurgery found that some are effectivein preventing atelectasis, pneumonia,and respiratory failure. These includeearly ambulation, lung expansion ma-neuvers, such as incentive spirometry,deep breathing exercises, and continu-ous positive airway pressure. Teachingpatients about lung expansion maneu-

vers increases efficacy. Data that favoruse of nasogastric tubes, epiduralanesthesia and analgesia, laparoscopicoperations, and enteral nutrition inter-ventions are less clear-cut (54, 55).

When should clinicians considersurgical therapies?Lung-volume reduction surgeryLung-volume reduction surgeryinvolves resection of up to 30% ofdiseased or nonfunctioningparenchyma to allow the remain-ing lung to function more effi-ciently. It may be considered in

patients with COPD who havecompleted a pulmonary rehabilita-tion program and meet the follow-ing criteria: 1) evidence of bilateralemphysema on CT scan; 2) post-bronchodilator total lung capacityand residual volume > 150% and100% of predicted, respectively; 3)maximum FEV

1no greater than

45% of predicted; and 4) room airPaCO

2no more than 60 mm Hg

and a PaO2

of at least 45 mm Hg.

Patients with an FEV1 20% ofpredicted and either homogenousemphysema on CT scan or carbonmonoxidediffusing capacity20%of predicted should not be consid-ered for lung-volume reductionsurgery as they are unlikely tobenefit and have a high risk forperioperative mortality (56).

In patients with COPD who meetspecific clinical criteria, lung-volumereduction surgery increases the

chance for improved exercisecapacity, lung function, dyspnea, andquality of life but does not improveoverall survival compared with med-ical therapy alone. In a subgroup of

Table 3. When to Consider Referral to a Pulmonary Specialist*

Disease onset before 40 years of age

Frequent exacerbations (2 or more per year) despite adequate treatment

Rapidly progressive course of disease (decline in FEV1, progressive dyspnea, decreased exercise tolerance, unintentional weight loss)

Severe COPD (FEV1


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50. Centers for Medicare& Medicaid Services.Evidence of medicalnecessity oxygenclaims. Accessed atwww.cms.hhs.gov/transmittals/down-loads/r1742B3.pdfon 20 November2010.

51. Bradley JM, ONeill B.Short-term ambula-

tory oxygen forchronic obstructivepulmonary disease.Cochrane DatabaseSyst Rev.2005:CD004356.[PMID: 16235359]

52. Cranston JM, Crock-ett AJ, Moss JR, et al.Domiciliary oxygenfor chronic obstruc-tive pulmonary dis-ease. CochraneDatabase Syst Rev.2005:CD001744.[PMID: 16235285]

53. Lewis CA, FergussonW, Eaton T, et al. Iso-lated nocturnal de-saturation in COPD:

prevalence and im-pact on quality oflife and sleep. Tho-rax. 2009;64:133-8.[PMID: 18390630]

54. American College ofPhysicians. Preopera-tive pulmonary riskstratification for non-cardiothoracic sur-gery: systematic re-view for theAmerican College ofPhysicians. Ann In-tern Med.2006;144:581-95.[PMID: 16618956]

55. Ferreira IM, Brooks D,Lacasse Y, et al. Nu-tritional supplemen-

tation for stablechronic obstructivepulmonary disease.Cochrane DatabaseSyst Rev.2005:CD000998.[PMID: 15846608]

56. Fishman A, MartinezF, Naunheim K, et al.A randomized trialcomparing lung-vol-ume-reduction sur-gery with medicaltherapy for severeemphysema. N EnglJ Med.2003;348:2059-73.[PMID: 12759479]

57. Berger RL, DeCampMM, Criner GJ, and

Celli BR. Lung vol-ume reduction ther-apies for advancedemphysema: an up-date. Chest.2010;138:407-17.[PMID: 20682529]

58. United Network forOrgan Sharing. Theorgan procurementand transplantationnetwork. Accessedat http://optn.trans-plant.hrsa.gov/ar2009/ on 20 November2010.


patients with upper lobe emphysemaand low exercise capacity, lung-vol-ume reduction surgery may improvesurvival, but definitive long-termdata are not yet available (56).

More recently, endobronchial ap-proaches to reduce lung volume bycreating atelectasis of emphysematous

portions of the lung are in develop-ment. These may include one-wayvalves, introduction of biologic mate-rials, or creation of nonanatomicalpathways to decompress hyperinflatedportions of the lung (57). None ofthese approaches is approved by theFDA as of 4 December 2010.

Lung transplantation

COPD disease-specific guidelinesfor candidate selection for lung

transplantation include patients witha BODE index of 7 to 10 and atleast 1 of the following: 1) history ofhospitalization for an exacerbation

associated with acute hypercapnia(PCO

2> 50 mm Hg); 2) pulmonary

hypertension, cor pulmonale, or bothdespite oxygen therapy; and 3) FEV

1

< 20% of predicted and either acarbon monoxidediffusing capacity< 20% of predicted or homogenousdistribution of emphysema (15).

Successful lung transplantation re-sults in improved pulmonary func-tion, exercise capacity, quality of life,and possibly survival (2). Actuarialsurvival following single lung trans-plantation for patients with COPDis approximately 83%, 60%, and 43%at 1, 3, and 5 years, respectively.Double-lung transplantation survivalis similar or slightly higher (58). By5 years after lung transplantation,the prevalence of chronic allograft

rejection (obliterative bronchiolitis),the leading cause of long-term mor-bidity and mortality, is as high as50% to 70% among survivors (59).

Treatment... All patients with COPD who smoke should be urged to stop and to en-ter a smoking cessation program. Patients who have symptoms, such as dyspnea,can be treated with inhaled -agonists or anticholinergic agents alone or in combi-nation. The greatest benefit from treatment with long-acting bronchodilators isachieved in patients with an FEV1 < 60% of predicted, and benefits include im-proved health status and reduced COPD exacerbations. These benefits may be en-hanced with the addition of an inhaled corticosteroid. Acute exacerbations shouldbe treated by optimizing bronchodilator therapy and adding systemic corticosteroids

and/or antibiotics when clinically indicated. All patients should be encouraged toexercise. Pulmonary rehabilitation should be offered to patients with moderate-to-severe COPD to improve dyspnea and health status. Continuous long-term oxygentherapy is recommended for patients with hypoxemia. Eligible patients should beevaluated for lung-volume reduction surgery or lung transplantation.

CLINICAL BOTTOM LINE

PracticeImprovement2007 (3); the National Institute of

Clinical Excellence, updated in 2010

(4); and the ACP, published in 2007(22). The first 4 present a comprehen-sive approach to the diagnosis andmanagement of COPD and draw in-formation and evidence from a varietyof sources, including RCTs; cohortstudies; casecontrol studies; recom-mendations from public policy organi-zations, such as the Advisory Com-mittee on Immunization Practices;

What do professionalorganizations recommend with

regard to prevention, screening,diagnosis, and treatment?Guidelines from professional organi-zations include those from the GlobalInitiative for Chronic ObstructiveLung Disease, updated in 2009 (1);the American Thoracic Society/Euro-pean Respiratory Society, updated in2005 (2); the Veterans Affairs andDepartment of Defense, updated in



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59. Heng D, Sharples LD,McNeil K, et al. Bron-chiolitis obliteranssyndrome: inci-dence, natural histo-ry, prognosis, andrisk factors. J Heart

Lung Transplant.1998;17:1255-63.[PMID: 9883768]

60. 2010 PQRI MeasuresList.Accessed athttps://www.cms.gov/PQRI/Down-loads/2010_PQRI_Measures-List_111309.pdf on 4December 2010.

In

theClinic

Tool KitIn the Clinic

ChronicObstructivePulmonaryDisease

PIER Moduleshttp://pier.acponline.org/physicians/diseases/d631/d631.htmlPIER modules on chronic obstructive pulmonary disease (COPD),

smoking cessation, and preoperative pulmonary risk assessment from theAmerican College of Physicians (ACP). PIER modules provide evidence-based, updated information on current diagnosis and treatment in anelectronic format designed for rapid access at the point of care.

Patient Informationwww.acponline.org/fcgi/pierpi.pl?module=d153

Access the Patient Information material on the following page forduplication and distribution to patients.

www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.htmlwww.nlm.nih.gov/medlineplus/tutorials/copd/htm/index.htmwww.nlm.nih.gov/medlineplus/spanish/tutorials/copdspanish/htm/index.htmInformation on COPD from National Institutes of Healths

MedlinePLUS, including an interactive tutorial in English and Spanish.

www.acponline.org/patients_families/diseases_conditions/copd/http://copd.acponline.org/www.acponline.org/fcgi/pierpi.pl?module=d153Information for patients on COPD from the ACP, plus access to theACPs COPD Portal and HEALTH TIPS patient handout.

www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_WhatIs.htmlInformation on COPD, in question and answer format, from the National

Heart, Lung, and Blood Institute.

Clinical Guidelineswww.annals.org/content/147/9/633.longDiagnosis and management of stable COPD from the ACP in 2007.www.healthquality.va.gov/Chronic_Obstructive_Pulmonary_Disease_COPD

.aspManagement of COPD from the U.S. Department of Veterans Affairs in

2007.http://guidance.nice.org.uk/CG101/NICEGuidance/pdf/EnglishManagement of COPD in adults in primary and secondary care from the

British National Institute for Health and Clinical Excellence in 2010.http://goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=996Global strategy for the diagnosis, management, and prevention of COPD

from the Global Initiative for Chronic Obstructive Lung Disease in 2008.

Quality-of-Care Guidelineswww.annals.org/content/148/7/529.full

Advises against screening for COPD using spirometry from the U.S.Preventive Services Task Force in 2008.

5 April 2011Annals of Internal MedicineIn the ClinicITC4-14 2011 American College of Physicians

and expert opinion. The ACP guide-lines are based almost solely on RCTs(22). Although most guidelines sug-gest treating patients with COPDwhen they become symptomatic, thecontribution of the ACP meta-analy-sis and guideline is to emphasize thatthe evidence indicates that inhaleddrug therapy is most effective in pa-

tients in whom FEV1 is < 60%predicted.

What measures do stakeholdersuse to evaluate the quality of carefor patients with COPD?The Centers for Medicare & Medi-caid Services issued specifications for

measures for the 2010 PhysiciansQuality Reporting Initiative (60). Ofthese measures, 2 relate to COPD.The first measure evaluates the per-centage of patients age 18 years orolder with a diagnosis of COPDwho had spirometry evaluation doc-umented in the measurement year.The second measure evaluates the

percentage of patients age 18 yearsor older with a diagnosis of COPD,an FEV

1FVC ratio < 0.70, and

such symptoms as dyspnea, cough,sputum, or wheezing who were pre-scribed an inhaled bronchodilator.



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In the Clinic

Annals of Internal Medicine

PatientIn

formation

THINGS YOU SHOULDKNOW ABOUT COPD

What is chronic obstructivepulmonary disease (COPD)? It is a lung disease that makes it hard to breathe.

Most people with COPD have both emphysema andchronic bronchitis.

Emphysema damages the walls between the lungsair sacs and causes the air sacs to lose elasticity.This leads to shortness of breath.

Chronic bronchitis inflames the lungs airways andcauses them to become clogged with mucus. Thismakes breathing hard, and causes a chronic coughwith mucus.

Who gets COPD? It is most common in cigarette smokers.

It can also occur in persons exposed to lung irritantslike air pollution, chemical fumes, second-handsmoke, or dust.

A rare genetic condition called 1-antitrypsin defi-

ciency makes some people vulnerable to lung dam-age from lung irritants.

It is usually diagnosed in middle-aged or olderadults.

What are the symptoms? Coughing up large amounts of mucus. Wheezing. Shortness of breath. Chest tightness.

Symptoms develop slowly and often worsen overtime. When severe, symptoms may make routine activities,

like walking, difficult.

How is it diagnosed? Your doctor will listen to your chest with a stetho-

scope and ask about your symptoms, medical histo-ry, and possible causes of COPD.

The doctor may order a test called spirometry. Youblow into a machine called a spirometer that meas-ures how well your lungs are functioning.

Other tests may include a chest x-ray or CT scan,which can reveal signs of COPD, and an arterialblood gas test, which measures the level of oxygenin your blood.

How is COPD treated? Smoking cessation is the most effective treatment. Medications can improve breathing, including bron-

chodilators, corticosteroids, antibiotics, and theo-phylline.

Supplemental oxygen therapy increases the level ofoxygen in blood.

Your doctor may enroll you in a pulmonary rehabili-tation program, which teaches patients skills for liv-ing with COPD.

In severe cases, a surgery called lung-volume reduc-tion can improve breathing by removing damagedtissue from the lungs. Rarely, patients may receivelung transplants.

For More Information

www.lungusa.org/lung-disease/copd/

Information for patients on COPD, including information onlifestyle changes, management tools, and support groups, fromthe American Lung Association.

www.cancer.gov/cancertopics/factsheet/tobacco/cessationInformation on quitting smoking, including how to get help,

from the National Cancer Institute.

www.alpha-1foundation.org/publications/Publications from the Alpha-1 Foundation, including education

brochures titled What Is Alpha-1 Antitrypsin Deficiency? andWhat Does It Mean To Be an Alpha-1 Carrier?



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CME Questions

5 April 2011Annals of Internal MedicineIn the ClinicITC4-16 2011 American College of Physicians

Questions are largely from the ACPs Medical Knowledge Self-Assessment Program (MKSAP, accessed at

http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/

to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.

1. A 72-year-old woman is evaluated forfatigue and decreased exercise capacity.The patient has severe chronicobstructive pulmonary disease (COPD),

which was first diagnosed 10 years ago,and was hospitalized for her secondexacerbation 1 month ago. She is aformer smoker, having quit 5 years ago.She has no other significant medicalproblems. Her medications are albuterolas needed, an inhaled corticosteroid, along-acting bronchodilator, and oxygen2 L/min by nasal cannula.

On physical examination, vital signs arenormal. Breath sounds are decreased, andthere is 1+ bilateral pitting edema.Spirometry done 1 month ago showed an

FEV1 of 28% of predicted, and blood gasesmeasured at that time (on supplementaloxygen) showed pH 7.41, PCO

243 mm Hg,

and PO264 mm Hg; DLCo is 30% of

predicted. There is no nocturnal oxygendesaturation. Chest radiograph at this timeshows hyperinflation. CT scan of the chestshows homogenous distribution ofemphysema.

Which of the following would be the mostappropriate management for this patient?

A. Lung transplantation

B. Lung volumereduction surgery

C. Nocturnal assisted ventilationD. Pulmonary rehabilitation

2. A 65-year-old woman is evaluated in afollow-up examination for dyspnea,chronic cough, and mucoid sputum; shewas diagnosed with COPD 3 years ago.The patient has a 40-pack-year history ofcigarette smoking, but quit smoking 1year ago. She is otherwise healthy, andher only medication is inhaled albuterolas needed.

On physical examination, vital signs are

normal. Breath sounds are decreased, butthere is no edema or jugular venousdistention. Spirometry shows an FEV1 of62% of predicted and an FEV1/FVC ratioof 65%. Chest radiograph shows mildhyperinflation.

Which of the following is the mostappropriate therapy for this patient?

A. Add a long-acting inhaled

bronchodilator

B. Add an inhaled corticosteroidC. Add an oral corticosteroid

D. Add theophylline and montelukastE. Continue current albuterol therapy

3. A 60-year-old man is evaluated duringroutine follow-up in November. Thepatient has severe COPD, with dyspneaon minimal exertion and a chroniccough. He has a 40-pack-year history ofcigarette smoking, but he quit smoking 3years ago. His medications are albuterolas needed, inhaled corticosteroids, and

tiotropium.On physical examination, the patient isafebrile, blood pressure is 140/88 mmHg, pulse rate is 90/min, and respirationrate is 20/min. Oxygen saturation withthe patient at rest and breathing ambientair is 86%. Jugular venous distention anda loud P

2are present. The chest is

hyperinflated and breath sounds arediminished. There is 1+ pedal edema.

Hemoglobin concentration is 16.5 g/dL(165 g/L). Arterial blood gases show pH7.35, PCO

255 mm Hg, and PO

255 mm Hg

on ambient air. Spirometry shows an FEV1of 25% of predicted. Chest radiographshows hyperinflation but no infiltrates.

Which of the following is the mostappropriate therapy for this patient?

A. Continuous oxygen

B. Nocturnal oxygenC. Oxygen as neededD. Oxygen during exercise

4. A 70-year-old woman is evaluated for a6-month history of fatigue, unintentionalweight loss of 4.4 kg (10 lb), increase in

chronic cough with sputum production,and decreased exercise capacity. Thepatient has a 40-pack-year history ofcigarette smoking but stopped smoking10 years ago when COPD was diagnosed.She has no other symptoms and reports

no abdominal pain, nausea, vomiting,diarrhea, or change in bowel habits. Hermedications are albuterol as needed, aninhaled corticosteroid, and salmeterol.

She has been on stable dosages of thesedrugs for 18 months. Age- and sex-appropriate cancer screening tests done6 months ago were normal. On physicalexamination, her temperature is 37.5C(99.5F), blood pressure is 128/76 mmHg, pulse is 94/min and regular,respiration rate is 16/min, and BMI is 20.Heart sounds are distant, and breathsounds are diminished bilaterally. Thereare no abdominal masses ororganomegaly and no peripheral edema.Laboratory studies yield the followingresults: hemoglobin, 15 g/dL (150 g/L);

albumin, 3.0 g/dL (30 g/L); creatinine ,0.8 mg/dL (70.7 mol/L); and thyroid-stimulating hormone , 2.0 U/mL(2.0 mU/L).

Spirometry shows an FEV1of 40% of

predicted and an FEV1/FVC ratio of 45%.

Chest radiograph shows hyperinflation.

Which of the following is the most likelyreason for this patients weight loss?

A. Breast cancerB. Cervical cancer

C. Colon cancer

D. COPD

annals epoc

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