New Treatments for Early and Late COPD: Part 1, Prevention

December 31, 2006

ABSTRACT: The key factor in reducing morbidityand mortality in patients with chronicobstructive pulmonary disease (COPD)continues to be smoking cessation. Newerformulations of nicotine replacementtherapy-a nasal spray and an inhaler-provide rapid delivery of nicotine and maybe appropriate for highly dependent smokers.Bupropion has been shown to improvesmoking cessation rates, either when usedalone or with a nicotine patch. Both theinfluenza and pneumococcal vaccines arerecommended to reduce the morbidity andmortality associated with respiratory infectionsin patients with COPD.

ABSTRACT: The key factor in reducing morbidityand mortality in patients with chronicobstructive pulmonary disease (COPD)continues to be smoking cessation. Newerformulations of nicotine replacementtherapy--a nasal spray and an inhaler--provide rapid delivery of nicotine and maybe appropriate for highly dependent smokers.Bupropion has been shown to improvesmoking cessation rates, either when usedalone or with a nicotine patch. Both theinfluenza and pneumococcal vaccines arerecommended to reduce the morbidity andmortality associated with respiratory infectionsin patients with COPD.Chronic obstructive pulmonary disease(COPD) is characterized by longstandingairflow limitation that usuallyresults from emphysema or chronicbronchitis. More than 16 million Americanshave COPD, which is now thefourth leading cause of death in theUnited States. COPD is also a majorcause of morbidity and a leading contributorto hospital admissions and officevisits.1COPD is often not recognizeduntil late in its course, when lung functionis markedly reduced and the patienthas become symptomatic. Earlyrecognition and diagnosis can halt--orat least slow--the progression of thisdisease.Here we focus on prevention andearly identification of COPD; in oursecond article on page 30, we discussdrug therapy, pulmonary rehabilitation,lung volume reduction surgery,and transplantation.PREVENTION:AN OVERVIEW
Smoking cessation and abstinenceare key primary preventionstrategies for COPD. Identifying highriskgroups, including smokers andthose with a family history of prematureCOPD or alpha1-antitrypsin deficiency,facilitates early detection andinitiation of therapy (secondary prevention).Vaccination with the influenzaand pneumococcal vaccines can reducethe risk of infection and consequentmorbidity and mortality inpatients with COPD.SMOKING CESSATIONCigarette smoking is the leadingcause of COPD and promotes ongoingdeterioration of lung function. The dictum"It's never too late to quit" continuesto ring true. Smoking cessation remainsone of the only interventionsshown to reduce morbidity and mortalityin patients with COPD. In contrast,continued smoking acceleratesthe ongoing decline in lung function,increases susceptibility to respiratoryinfections and bronchoconstriction,and contributes significantly to the developmentof other comorbid diseasesin this (usually older) population.Cigar smoking is also a knownrisk factor for COPD. Between 1993and 2002, cigar consumption nearlydoubled. A cohort study with approximately18,000 men--encompassingseveral decades of follow-up--demonstratedan increased risk of COPD,coronary heart disease, upper aerodigestivetract disorders, and lung cancer in regular cigar smokers. Thiswas a dose-response effect.2During office visits, many smokersare not advised to quit or givensmoking cessation assistance. Therefore,we recommend the following forevery visit3:

  • Record tobacco-use status along withvital signs.
  • Offer simple smoking cessation adviceand assistance to current smokers("Ask, Advise, Assess, Assist").

Nicotine replacement therapy.

These therapies can help patients copewith withdrawal symptoms, such as irritabilityand early morning craving,that commonly occur in those whosmoke more than 10 cigarettes daily(

Table 1

). Exercise caution in recommendingthese products to patients with recent (within the previous 4weeks) myocardial infarction, severearrhythmias, or angina. Both the nicotinepatch and gum are available overthe-counter in the United States; thepatch is generally preferred because itis easier to use.Two alternative formulations ofnicotine replacement are the nasalspray and oral inhaler. The inhaler is a plastic rod that provides a nicotinevapor (when puffed) that may helpwith the oral fixation of smoking.These products may be considered forhighly dependent smokers and arepreferred by some patients; the deliveryof nicotine is quicker than withother forms of nicotine replacement.

Bupropion

. This antidepressanthas been shown to improve smokingcessation rates at 1 year, either whenused alone or with a nicotine patch.

4,5

Treatment is typically started 1 weekbefore the quit date at a dosage of150 mg/d for 3 days, then 150 mgtwice daily for 7 to 12 weeks. TheTreating Tobacco Use and Dependence(

TTUD

) guidelines advocatemaintenance therapy for up to 6months

3

; however, a clinical trialshowed that extending treatment withbupropion to 52 weeks improved1-year abstinence rates by approximately13%.

6

Major side effects areheadache and insomnia. Exercisecaution in recommending this medicationto patients with a history ofseizures.

Clonidine

. Oral or transdermaladministration of this centrally actingantihypertensive agent can diminishwithdrawal symptoms (such as cravingand anxiety) and improve cessationrates in severely addicted smokers.Use of this agent is limited by a highincidence of side effects, such as sedation, dry mouth, and dizziness (23% to92%; median, 71%), compared withplacebo (4% to 61%; median, 10%).

3

Thesedation may be useful in those withextreme agitation and anxiety thatis unrelieved by nicotine replacementtherapy.Clonidine may be used in additionto, or in place of, nicotine replacement.Overall, it is considered secondlinetherapy and should be reservedfor those with severe nicotine dependenceand withdrawal symptoms inwhom nicotine replacement therapy orbupropion has failed.

3

It is best usedfor short-term therapy (3 to 10 weeks).Frequently, many attempts aremade before smoking cessation is successful.If one modality fails, encouragepatients to try another. Combination therapy may be beneficial in difficultcases.

Resources for patients.

Smokingcessation rates vary considerably butare highest when behavioral and supportivetherapies are combined withnicotine replacement and/or treatmentwith bupropion. The key to success isclose follow-up and support during thequitting period. Self-help resources areavailable through the American LungAssociation (800-LUNG-USA [800-586-4872], www.lungusa.org), the AmericanCancer Society (800-227-2345,www.cancer.org), and the AmericanHeart Association (800-242-8721, www.americanheart.org).Some pharmaceutical companiesoffer telephone-based support that canhelp reduce the need for face-to-face encounters. The bottom line is thatany method of smoking cessation canbe successful--and with supportivecounseling, quit rates can be doubled(from 15% to 30%) at 6 months.

3,7,8

VACCINATIONS


Influenza vaccine.

Influenza virustype A and B epidemics usually beginearly in the winter and end in thespring. The virus (particularly type A)mutates rapidly. A new formulation ofthe influenza vaccine is prepared eachyear and should be administered tohigh-risk persons, such as those withchronic lung disease. The risk of morbidityand mortality from acute respiratoryinfection is very high in patientswith

COPD

and can be reducedthrough vaccination.Nevertheless, recent surveys bythe CDC have shown that vaccination rates in high-risk groups are as low as30%. To ensure immunization compliance,it is essential to incorporate vaccinationsinto a standardized chartingor care plan formula. Yearly influenzavaccinations are also recommendedfor health care workers and householdcontacts of patients with

COPD

.

Pneumococcal vaccine

.

Streptococcuspneumoniae

is the most commoncause of pneumonia in all agegroups and is responsible for considerablemorbidity and mortality, particularlyin patients with

COPD

. A multivalentpolysaccharide antigen vaccineagainst

S

pneumoniae

provides immunityagainst the common

S

pneumoniae

strains. The pneumococcal vaccine isrecommended for high-risk patientsand those older than 65 years (

Table2

).

9

Antibody titers wane with time,and reimmunization or booster injections with the vaccine are recommendedafter 6 years. The vaccine hasbeen shown to reduce mortality inhigh-risk groups by 50%. Studies haveindicated that side effects are minimal,with no systemic side effects and onlymild to moderate local symptoms in25% of patients.

10

ALPHA1-ANTITRYPSINREPLACEMENT


A congenital form of emphysema,which typically occurs in youngeradults, has been linked to alpha

1

-antitrypsindeficiency. This genetic disorderis inherited in a codominant fashion(expressing alleles from both parents).Alpha

1

-antitrypsin is a proteinproduced in the liver that inhibits neutrophilelastase (a proteolytic enzymein the lung). When serum levels ofalpha

1

-antitrypsin drop below about 35% of predicted, elastase activity is notsufficiently inhibited, and there is a significantlyincreased risk of emphysema,primarily of the panacinar type.The distribution of emphysema ischaracteristically at the lung bases, asopposed to the upper lobes (as in thetypical form of "smoker's emphysema").Chronic bronchitis and, rarely,bronchiectasis may also develop.Smoking can further reduce the activityof alpha1-antitrypsin and can causeemphysema 10 to 15 years earlier thanin nonsmokers. Alpha

1

-antitrypsin deficiencymay also increase the risk ofcirrhosis and other liver disease, particularlyin younger persons.Although only a small minority ofcases of

COPD

are caused by this deficiency,it is important to identify thesecases (

Table 3

). This disorder maytypically be found in young patients,usually smokers, who demonstrate severebasilar emphysema on chest radiographs;there may also be associatedliver disease and a family history ofthe disorder.A form of purified and isolatedalpha

1

-antitrypsin protein has been approvedby the FDA for replacementtherapy. This expensive treatment requiresweekly intravenous infusion. Apulmonary consultation is appropriate(

Table 4

).Early identification of appropriatecandidates (by serum alpha

1

-antitrypsinlevel and confirmation of emphysema)may decrease the rate ofprogression of the disease; however, todate, controlled studies have not beenperformed to demonstrate this benefit.Subgroup analysis of a national Alpha

1

-Antitrypsin Deficiency Registry StudyGroup showed that the rate of declineof forced expiratory volume in 1 secondand mortality are reduced in patientswith moderate to severe COPDwho receive replacement therapy.

10

References:

REFERENCES:

1.

Pauwels RA, Buist AS, Calverley PM, et al, forthe GOLD Scientific Committee. Global strategy forthe diagnosis, management, and prevention ofchronic obstructive pulmonary disease.NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.

AmJ Respir Crit Care Med.

2001;163:1256-1276.

2.

Iribarren C, Tekawa IS, Sidney S, Friedman GD.Effect of cigar smoking on the risk of cardiovasculardisease, chronic obstructive pulmonary disease, andcancer in men.

N Engl J Med.

1999;340:1773-1780.

3.

Tobacco Use and Dependence Clinical PracticeGuideline Panel Staff and Consortium Representatives.A clinical practice guideline for treating tobaccouse and dependence: a US Public Health Servicereport.

JAMA.

2000;283:3244-3254.

4.

Jorenby DE, Leischow SJ, Nides MA, et al. A controlledtrial of sustained-release bupropion, a nicotinepatch, or both for smoking cessation.

N Engl J Med.


5.

Hurt RD, Sachs DP, Glover ED, et al. A comparisonof sustained-release bupropion and placebofor smoking cessation.

N Engl J Med.

1997;337:1195-1202.1999;340:685-691.

6.

Hays JT, Hurt RD, Rigotti NA, et al. Sustainedreleasebupropion for pharmacologic relapse preventionafter smoking cessation. A randomized, controlledtrial.

Ann Intern Med.

2001;135:423-433.

7.

Fiore MC, Bailey SC, Cohen SJ, et al.

TreatingTobacco Use and Dependence.

Rockville, Md: US Deptof Health and Human Services, Public Health Service;2000. AHRQ publication 00-0032.

8.

Watts SA, Noble SL, Smith PO, Disco M. Firstlinepharmacotherapy for tobacco use and dependence.

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2002;15:489-497.

9.

Centers for Disease Prevention and Control. Preventionof pneumococcal disease: recommendationsof the Advisory Committee on Immunization Practices(ACIP).

MMWR.

1997;46:1-24.

10.

Nichol KL, MacDonald R, Hauge M. Side effectsassociated with pneumococcal vaccination.

AmJ Infect Control.

1997;25:223-228.

11.

The Alpha

1

-Antitrypsin Deficiency RegistryStudy Group. Survival and FEV

1

decline in individualswith severe deficiency of alpha1-antitrypsin.

Am J Respir Crit Care Med.

1998;158:49-59.

12.

American Thoracic Society. Standards for thediagnosis and care of patients with chronic obstructivepulmonary disease.

Am J Respir Crit Care Med.

1995;152:S77-S121.

13.

COPD Guidelines Group of the Standards ofCare Committee of the BTS. BTS guidelines for themanagement of chronic obstructive pulmonary disease.

Thorax.

1997;52(suppl 5):S1-S28.