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Chronic Cough Due to ChronicBronchitis

ACCP Evidence-Based Clinical Practice Guidelines

Sidney S. Braman, MD, FCCP

Background:Chronic bronchitis is a disease of the bronchi that is manifested by cough and sputumexpectoration occurring on most days for at least 3 months of the year and for at least 2 consecutiveyears when other respiratory or cardiac causes for the chronic productive cough are excluded. Thedisease is caused by an interaction between noxious inhaled agents (eg, cigarette smoke, industrialpollutants, and other environmental pollutants) and host factors (eg, genetic and respiratoryinfections) that results in chronic inflammation in the walls and lumen of the airways. As the diseaseadvances, progressive airflow limitation occurs, usually in association with pathologic changes ofemphysema. This condition is called COPD. When a stable patient experiences a sudden clinicaldeterioration with increased sputum volume, sputum purulence, and/or worsening of shortness ofbreath, this is referred to as an acute exacerbation of chronic bronchitisas long as conditions otherthan acute tracheobronchitis are ruled out. The purpose of this review is to present the evidence forthe diagnosis and treatment of cough due to chronic bronchitis, and to make recommendations that

will be useful for clinical practice.Methods:Recommendations for this section of the review were obtained from data using a NationalLibrary of Medicine (PubMed) search dating back to 1950, performed in August 2004, of theliterature published in the English language. The search was limited to human studies, using thesearch terms cough, chronic bronchitis, and COPD.Results:The most effective way to reduce or eliminate cough in patients with chronic bronchitis andpersistent exposure to respiratory irritants, such as personal tobacco use, passive smoke exposure, and

workplace hazards is avoidance. Therapy with a short-acting inhaled-agonist, inhaled ipratropiumbromide, and oral theophylline, and a combined regimen of inhaled long-acting -agonist and aninhaled corticosteroid may improve cough in patients with chronic bronchitis, but there is no provenbenefit for the use of prophylactic antibiotics, oral corticosteroids, expectorants, postural drainage, orchest physiotherapy. For the treatment of an acute exacerbation of chronic bronchitis, there isevidence that inhaled bronchodilators, oral antibiotics, and oral corticosteroids (or in severe cases IVcorticosteroids) are useful, but their effects on cough have not been systematically evaluated. Therapy

with expectorants, postural drainage, chest physiotherapy, and theophylline is not recommended.Central cough suppressants such as codeine and dextromethorphan are recommended for short-termsymptomatic relief of coughing.Conclusions: Chronic bronchitis due to cigarette smoking or other exposures to inhaled noxiousagents is one of the most common causes of chronic cough in the general population. The mosteffective way to eliminate cough is the avoidance of all respiratory irritants. When cough persists

despite the removal of these inciting agents, there are effective agents to reduce or eliminate cough.(CHEST 2006; 129:104S115S)

Key words: acute exacerbation of COPD; chronic bronchitis; chronic cough; cigarette cough; COPD; cough phlegmsyndrome; mucous hypersecretion

Abbreviations:GOLDGlobal Initiative for Chronic Obstructive Lung Disease; IL interleukin

Chronic bronchitis is a cough phlegm syndrome.The term was introduced into the medical liter-

ature early in the 19th century and was recognized as

an inflammatory disease of the airways.1 However,no accepted definition of this term was establisheduntil the mid-20th century following the develop-

104S Diagnosis and Management of Cough: ACCP Guidelines

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ment of the British Medical Research Council Re-spiratory Questionnaire on Respiratory Symptoms.Based on responses to epidemiologic surveys, theterm chronic bronchitis was defined as a disease ofthe bronchi that manifested by cough and sputumexpectoration occurring on most days for at least 3months of the year and for at least 2 consecutiveyears when other pulmonary or cardiac causes forthe chronic productive cough are excluded.24 In1958, a group of international experts participating inthe Ciba Foundation Guest Symposium, proposed adefinition of chronic bronchitis as a condition ofsubjects with chronic or recurrent excessive mucoussecretion in the bronchial tree.4 Because earlierstudies suggested that chronic mucous hypersecre-tion did not cause airflow obstruction, evidence ofairflow limitation was not incorporated into theseearlier definitions. In 1986, chronic bronchitis andemphysema were acknowledged in an American

Thoracic Society statement5

as the two main compo-nents of COPD, which became a preferred term forboth diagnoses. Evidence of expiratory flow limita-tion that did not change markedly over time wasincluded in the definition of COPD.

The recently published Global Initiative forChronic Obstructive Lung Disease (GOLD) guide-lines,6 sponsored by the National Heart, Lung, BloodInstitute and the World Health Organization, pro-vides a definition of COPD that differs from previ-ous consensus statements. It does not incorporatethe terms chronic bronchitis and emphysema into

the definition, as does the American Thoracic Soci-ety statement. Instead, it defines COPD as a diseasestate that is characterized by airflow obstruction thatis no longer fully reversible and is usually progres-sive. The disease is caused by an interaction betweennoxious inhaled agents (eg, cigarette smoke, indus-trial pollutants, and other environmental pollutants)and host factors (eg, genetic factors and respiratoryinfections) that results in chronic inflammation in thewalls and lumen of the airways. The pathology ofCOPD, as well as the symptoms, the pulmonaryfunction abnormalities, and complications all can be

explained on the basis of the underlying inflamma-tion. While the GOLD document6 does not specifi-cally include chronic bronchitis and emphysema inthe definition of COPD, it is clear that they areconsidered to be the predominant causes. For in-stance, GOLD defines the earliest stage of COPD,stage 0, by evidence of chronic cough and sputum

expectoration in the absence of airflow obstructionon pulmonary function testing, not using the termchronic bronchitis.6 Because chronic cough and spu-tum expectoration are common in all stages ofCOPD, the use of the traditional definition ofchronic bronchitis as cough and sputum expectora-tion occurring on most days for at least 3 months ofthe year and for at least 2 consecutive years is most

appropriate. Recommendations for this section ofthe review were obtained from data obtained using aNational Library of Medicine (PubMed) search dat-ing back to 1950, performed in August 2004, of theliterature published in the English language. Thesearch was limited to human studies, using thesearch terms cough, chronic bronchitis, andCOPD.

Recommendations

1. Adults who have a history of chronic coughand sputum expectoration occurring on mostdays for at least 3 months and for at least 2consecutive years should be given a diagnosis ofchronic bronchitis when other respiratory orcardiac causes of chronic productive cough areruled out. Level of evidence, low; net benefit,substantial; grade of recommendation, B

2. The evaluation of patients with chroniccough should include a complete history re-garding exposures to respiratory irritants in-cluding cigarette, cigar, and pipe smoke; pas-

sive smoke exposures; and hazardousenvironments in the home and workplace. Allare predisposing factors of chronic bronchitis.Level of evidence, low; net benefit, substantial;grade of recommendation, B

Epidemiology

Over the past decade there has been increasinginterest in the pathogenesis and management ofCOPD as it has been recognized that the disease is

having a major worldwide impact.6 In the UnitedStates, estimates from national interviews taken bythe National Center for Health Statistics,7 haveshown that 16 million people are afflicted withCOPD; about 14 million are thought to have chronicbronchitis, while 2 million have emphysema.7 It hasbeen suggested that these statistics underestimatethe prevalence of COPD by as much as 50%, asmany patients underreport their symptoms and theirconditions remain undiagnosed. On the other hand,the accuracy of a self-reported diagnosis of chronicbronchitis and a physician-confirmed diagnosis of

Reproduction of this article is prohibited without written permissionfrom the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).Correspondence to: Sidney S. Braman, MD, FCCP, Division ofPulmonary and Critical Care Medicine, Rhode Island Hospital, 595Eddy St, Providence, RI 02903; e-mail: [email protected]

www.chestjournal.org CHEST / 129 / 1 / JANUARY, 2006 SUPPLEMENT 105S


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chronic bronchitis have been questioned.8 Using alongitudinal population study, patients were sur-veyed for self-reported chronic bronchitis or physi-cian-diagnosed chronic bronchitis. The survey askedabout symptoms of chronic cough and sputum pro-duction and the timing of these symptoms. Seven-teen percent of current smokers, 12.4% of formersmokers, and 6% of never-smokers met the criteria

for chronic bronchitis. The vast majority of people(88.4%) who reported a self-reported or physician-confirmed diagnoses of chronic bronchitis did notmeet the standard criteria. The overdiagnosis ofchronic bronchitis by patients and physicians may bevery common. Because the termbronchitis is oftenused as a common descriptor for a nonspecific andself-limited cough, many patients assume that theyhave had chronic bronchitis. In the Third NationalHealth and Nutrition Examination Survey, usingsurveys, physical examinations, and pulmonary func-tion testing, more accurate prevalence estimates

have been made. Using World Health Organizationdefinitions, it has been shown that 23.6 million adults(13.9% of the adult population) have COPD.9,10

Chronic bronchitis is among the most frequentcauses of cough found in community surveys.11

Etiology

In developed countries, cigarette smoking is re-sponsible for 85 to 90% of cases of chronic bronchitisand COPD. Cigarette smoke is composed of a

complex mixture of 400 particles and gases; thespecific etiologic role of each of these constituentshas not been established. Many studies10,1214 haveconfirmed the association of cigarette smoking,chronic cough, and low lung function. The incidenceof chronic bronchitis is directly proportional to thenumber of cigarettes smoked. Other risk factors forchronic mucus hypersecretion that have been iden-tified are increasing age, male gender, childhoodrespiratory infections, frequent lower respiratorytract infections, occupational exposures, and asthma.Pipe and cigar smoking are also risk factors for both

complications even in the absence of former ciga-rette smoking.10 The prevalence of chronic cough inthe Third National Health and Nutrition Examina-tion Survey was reported15 in subjects without air-flow obstruction and in those with undiagnosedairway obstruction. Cough was found in 9.3% ofsubjects and sputum production was found in 8.3%of subjects without airflow obstruction. The studyalso confirmed the observation that these symptomsare more common in subjects with more severeairflow obstruction. In those subjects with mildairflow obstruction, cough was found in 16.0% of

those surveyed and sputum production in 17%. Withsevere airflow obstruction, using the GOLD stagingcriteria, the prevalence of cough increased to 49% ofpatients, and sputum production was found in 39.5%of patients.

The identification of chronic cough and sputumproduction due to occupational exposures is notcommonly made by clinicians; yet, it has been esti-

mated that in as many as 15% of patients withchronic bronchitis and COPD, occupational expo-sure is the cause.16 There are a number of epidemi-ologic associations of workplace hazards and chronicbronchitis. The diagnosis is usually made by findinga history of exposure in individuals who have noother identifiable cause of cough. This is oftendifficult because many workers are smokers or areexposed to second-hand smoke. Other workers, suchas those exposed to organic dusts, may present withchronic cough and a history of asthma-like symptomswithout airway eosinophilia, reversible airflow ob-

struction, or bronchial hyperresponsiveness.17 Thisoccurs with chronic exposure to cotton (byssinosis),jute, hemp, flax, sisal, wood, and various grains.There is a growing body of literature that hasdemonstrated that specific occupational exposuresare associated with the symptoms of chronic bron-chitis and, at times, airflow obstruction,1821 whichare comparable to moderate cigarette smoking.22

The list of agents includes the following: coal; man-ufactured vitreous fibers; oil mist; cement; silica;silicates; osmium; vanadium; welding fumes; organicdusts; engine exhausts; fire smoke; and second-hand

cigarette smoke.23While the prevalence of passive smoke exposure in

the workplace has been decreasing as laws banningsmoking in public places have been established, it isstill a problem in many communities around theworld. Often, nonsmokers are exposed to cigarettesmoke in the home environment as well. Involuntaryexposure to tobacco smoke is strongly associatedwith chronic cough and sputum production, even inyoung adults who have been screened for other riskfactors. The risk increases significantly with an in-creasing duration of daily exposure.24 Another im-

portant exposure in the home environment thatincreasingly has been recognized as a cause ofchronic bronchitis and fixed airflow obstruction inunderdeveloped countries is exposure to the fumesof cooking fuels, especially in enclosed spaces withpoor ventilation.

Recommendation

3. Smoke-free workplace and public placelaws should be enacted in all communities.



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Level of evidence, expert opinion; net benefit, sub-stantial; grade of recommendation, E/A

Pathology and Pathophysiology

The inflammatory mechanisms of chronic bronchi-tis and COPD have been extensively reviewed.2528

Structural changes of the airways have been de-scribed in otherwise healthy smokers even as youngas 20 to 30 years old. BAL studies in such subjectshave shown an increase in the number of neutrophilsand macrophages; both play an important role inperpetuating the inflammatory process of chronicbronchitis. Bronchial biopsy specimens from formersmokers show inflammatory changes that are similarto those in the active smoker, suggesting that inflam-mation may persist in the airway once established. Anumber of extracellular signaling proteins called

cytokines are important in the pathogenesis ofCOPD because they are thought to mediate thetissue damage and repair that are induced by ciga-rette smoking. Increased quantities of certain proin-flammatory cytokines including interleukin (IL)-8,IL-1, IL-6, and tumor necrosis factor-, and theantiinflammatory cytokine IL-10 have been found inthe sputum of smokers with chronic bronchitis, andeven further increased quantities of these cytokineshave been found during acute exacerbations.

Other structural changes in the airways of smokersinclude mucus gland hyperplasia, bronchiolar

edema, smooth muscle hypertrophy, and peribron-chiolar fibrosis. These changes result in a narrowingof the small airways ( 2 mm). There is a progressiveworsening of pathologic changes when smokers withmild COPD and smokers with more severe diseaseare compared.29

Neurogenic mechanisms may play an amplifyingrole in the pathogenesis of chronic bronchitis.30

Sensory airway nerves contain tachykinins such assubstance P, neurokinin A, and neurokinin B that arereleased in the airways in association with inflamma-tion. These tachykinins have been found in the

sputum of patients with chronic bronchitis and areknown to augment airway secretions.

The presence of a gel-like mucus in the airways ofhealthy people is essential for normal mucociliaryclearance. The mucus is eliminated by the action ofmucociliary clearance to the hypopharynx, where it isswallowed and rarely noticed. Normally, about 500mL of sputum is produced each day, and it is usuallynot noticed. Smokers with chronic bronchitis pro-duce larger amounts of sputum each day, as much as100 mL/d more than normal. This results in coughand sputum production. The excess mucus occurs as

a result of an increase in the size and number of thesubmucosal glands and an increase in the number ofgoblet cells on the surface epithelium. Mucous glandenlargement and hyperplasia of the goblet cells are,therefore, the pathologic hallmark of chronic bron-chitis. Goblet cells are normally absent in the smallairways, and their presence there (often referred toas mucous metaplasia) is important to the develop-ment of COPD. In the larger airways in patients withchronic bronchitis, there is a reduction in the serousacini of the submucosal glands. This depresses localdefenses to bacterial adherence, because theseglands are known to produce microbial deterrentssuch as lactoferrin, antiproteases, and lysozyme.Other epithelial alterations that are seen in patientswith chronic bronchitis are a decrease in the numberand length of the cilia, and squamous metaplasia.The mucociliary abnormalities of chronic bronchitiscause the formation of a continuous sheet or blanket

of mucus lining the airways instead of the discreetdeposits of mucus seen in normal airways. Thepooling of secretions also may occur. This providesan additional cause of bacterial growth, which in turncauses a release of toxins that are further damagingto the cilia and epithelial cells. Bacterial exoproductsare known to stimulate mucus production and slowciliary beating, to impair immune effector cell func-tion, and to destroy local Igs. This cycle is especiallyseen in current smokers, as opposed to former smokers.

Based on these extensive observations regardingthe pathogenesis of chronic bronchitis, it is recog-nized that the cause of cough in patients with chronicbronchitis is multifactorial. Airway inflammation andexcessive bronchial secretions are likely to activatethe afferent limb of the cough reflex.31 There isevidence that the cough receptors are heightened inpatients with chronic bronchitis as it has been dem-onstrated that capsaicin induced cough is in-creased.32 When airflow obstruction is present, itoften leads to an ineffective cough as a result ofdecreased expiratory flow,33 and this coupled withimpaired mucociliary clearance results in the further

retention of secretions and a vicious cycle of chronicrecurrent coughing.34,35 Even in the absence ofairflow obstruction and with a short smoking history,impaired mucociliary clearance has been shown inyoung smokers. This occurs because of abnormalclearance in the small airways. Patients with ad-vanced disease and evidence of airway obstructionhave mucus retention in the small peripheral airwaysand larger central airways.36,37 This cycle is furtherworsened during episodes of acute viral and bacterialinfections, which are common in patients withchronic bronchitis.38



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Airway Infection/Acute Exacerbation of

Chronic Bronchitis

Patients with chronic bronchitis have a greaterfrequency of acute respiratory infections than thosewithout bronchitis, and with symptoms of an acuteupper respiratory infection they are more likely tohave signs of infection in the lower airways than are

healthy control subjects.39 During these attacks orexacerbations, cough and sputum production in-crease and the sputum may become purulent. Theexacerbations may also cause worsening shortness ofbreath; therefore, clinicians should be aware thatother conditions such as heart failure and pulmonaryembolism could mimic an acute exacerbation ofchronic bronchitis. While there is no uniformlyaccepted definition of an acute exacerbation ofchronic bronchitis, most have acknowledged that thiscondition is due to a sudden deterioration in the

condition of a stable patient with symptoms ofincreased sputum volume, sputum purulence, and/orworsening of shortness of breath due to acute tra-cheobronchitis. An exacerbation is often preceded bysymptoms of an upper respiratory tract infection. Animportant element of this definition is that causes ofrespiratory deterioration other than acute tracheo-bronchitis, such as pneumonia, pulmonary embo-lism, exacerbation of bronchiectasis, pneumothorax,and congestive heart failure, are excluded. Evidenceof a viral infection is found in approximately onethird of episodes. Common viral infections in the

outpatient setting are rhinovirus, coronavirus, influ-enza B, and parainfluenza.40,41 Viral respiratory in-fections predispose the airways to bacterial superin-fection because they interfere with mucociliaryclearance, impair bacterial killing by pulmonary mac-rophages, and increase the risk of aspirating secre-tions containing bacteria from the upper airways.Whether bacterial overgrowth or infection alone, inthe absence of acute viral infection, is the cause of anacute exacerbation of chronic bronchitis has beencontroversial. During stable periods, many patients

with chronic bronchitis, and especially current smok-ers, are colonized with bacteria such as Streptococ-cus pneumoniae, Moraxella catarrhalis, and Hae-mophilus influenzae, and these same organisms havebeen found in patients during an acute exacerbation.However, the molecular typing of sputum isolateshas shown that acute exacerbations of COPD arefrequently associated with a new strain of a preexist-ing organism. This supports a causative role forbacteria in the acute exacerbations of COPD.42

Although most such episodes of acute exacerbationsof chronic bronchitis are self-limited, they are asso-

ciated with substantial decrements in the quality oflife43 and impose a considerable financial burden onthe health-care system.43

Recommendation

4. Stable patients with chronic bronchitis

who have a sudden deterioration of symptomswith increased cough, sputum production, spu-tum purulence, and/or shortness of breath,which are often preceded by symptoms of anupper respiratory tract infection, should beconsidered to have an acute exacerbation ofchronic bronchitis, as long as conditions otherthan acute tracheobronchitis are ruled out orare considered unlikely.Level of evidence, expertopinion; net benefit, substantial; grade of recom-mendation, E/A

Progressive Airflow Obstruction

The role of chronic mucous hypersecretion andcough in the pathogenesis of airflow obstruction hasbeen another area of controversy. The lack of asso-ciation between chronic mucous hypersecretion andpulmonary function decline or mortality has beenreported in a number of studies.4447 Other studieshave examined this question, and have shown anassociation between chronic mucous hypersecretionand overall mortality48,49 as well as mortality from

COPD.50,51

The association between chronic mu-cous hypersecretion and the development of COPDalso has been established. Both an excessive FEV1decline and an increased rate of hospitalization havebeen shown in patients with established COPD whohave cough and excessive mucous production. It islikely that this is due to recurrent bronchial infec-tions.52,53

Comorbid Illnesses

It should always be kept in mind that when thecharacter of the cough changes for prolonged peri-ods in a patient with chronic bronchitis, the possibil-ity of bronchogenic carcinoma or another complica-tion should be considered. Prospective studies54 ofmiddle-aged cigarette smokers have shown that theincidence of lung cancer in this group is very high.

Treatment

While the most effective treatment of chroniccough due to chronic bronchitis is the avoidance of



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respiratory irritants, often patients refuse to avoidthem or find it impossible to do so because ofconditions at home or in the workplace. The use ofpharmacologic therapy at times may be helpful, butthe evidence that these agents are effective oftencomes from clinical trials that do not evaluate coughas a primary outcome. The use of these agents in thetreatment of stable patients with chronic disease and

for episodes of acute exacerbation of chronic bron-chitis will be reviewed. An American College ofChest Physicians/American College of Physicians-American Society of Internal Medicine evidence-based report55 on the treatment of acute exacerba-tions of COPD is a useful guideline.

Avoidance

The most effective means for controlling coughand sputum production in patients with chronic

bronchitis is the avoidance of environmental irri-tants. During an acute exposure to respiratory irri-tants at home or in the workplace, patients mayexperience symptoms of increased cough, sputumproduction, and shortness of breath that are similarto those of an exacerbation due to infection. Withrespect to chronic cough, several nonrandomizedtrials have studied the effect of smoking cessation onthis troubling symptom. Cough has been shown56 todisappear or markedly decrease in 94 to 100% ofpatients after smoking cessation, and in approxi-mately half of the subjects this occurred within 1

month. The Lung Health Study57

investigated theeffects of smoking cessation in smokers with mild-to-moderate airflow obstruction. It was a 5-yearrandomized prospective trial57 of intensive smokingintervention compared to a control group of smokerswho received usual care. At the end of 5 years, 22%of those in the intervention group had stoppedsmoking for the entire study period. The beneficialeffects, including a reduction of chronic cough andsputum production, occurred in the first year ofsmoking cessation. It was sustained throughout theentire study period. Ninety percent of those patients

who had chronic cough at the beginning of the studyand stopped smoking reported no cough by the endof the study. Similar findings were reported regard-ing sputum production. However, in patients withmore severe degrees of airflow obstruction chroniccough is more likely to persist despite the avoidanceof cigarettes or other respiratory irritants.

Recommendation

5. In patients with chronic cough who havechronic exposure to respiratory irritants, such

as personal tobacco use, passive smoke expo-sure, and workplace hazards, avoidance shouldalways be recommended. It is the most effectivemeans to improve or eliminate the cough ofchronic bronchitis. Ninety percent of patientswill have resolution of their cough after smok-ing cessation.Level of evidence, good; net benefit,substantial; grade of recommendation, A

Antibiotics

The use of antibiotics for treatment of an acuteexacerbation of chronic bronchitis is recommendedas it has been shown to shorten the course of theillness. The use of antibiotics is most effective inpatients with purulent sputum and in those with agreater severity of illness that includes all three ofthe cardinal symptoms (ie, increased cough; in-creased sputum volume; and increased dys-

pnea55,58,59) and in those with more severe airflowobstruction at baseline.60 An opinion expressed bythe US Food and Drug Administration61 in Novem-ber 2002 suggested that the randomized placebo-controlled trials of antibiotic therapy for the acuteexacerbation of chronic bronchitis that have beenconducted over the past 40 years have been meth-odologically flawed and that a definitive decisionregarding antibiotic use cannot be reached. How-ever, based on a metaanalysis of nine studies,58

which included randomized controlled trials, therapywith antibiotics is recommended, especially in those

patients with more severe illness. The effect thatantibiotics have on cough during an acute exacerba-tion of COPD has been investigated. There is nosignificant effect on cough clearance or cough fre-quency when compared to therapy with a placebo.60

On the other hand, older trials62 studying the use-fulness of prophylactic therapy with antibiotics toreduce the frequency and/or severity of attacks haveshown a small but statistically significant effect inreducing the number of days of illness during anacute exacerbation of chronic bronchitis. However,therapy with antibiotics is currently not recom-

mended for stable patients with chronic bronchitisbecause of concerns about antibiotic resistance andthe potential side effects of the drugs.

Recommendations

6. In stable patients with chronic bronchitis,there is no role for long-term prophylactic ther-apy with antibiotics.Level of evidence, low; bene-fit, none; grade of recommendation, I

7. In patients with acute exacerbations of



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chronic bronchitis, the use of antibiotics is rec-ommended; patients with severe exacerbationsand those with more severe airflow obstructionat baseline are the most likely to benefit. Levelof evidence, fair; net benefit, substantial; grade ofrecommendation, A

Bronchopulmonary Hygiene

The use of bronchopulmonary hygiene physicaltherapy for chronic bronchitis recently has been thesubject of review.63 The clinical benefits of posturaldrainage and chest percussion have not been proven,and their use in stable patients with chronic disease63

or during an acute exacerbation of chronic bronchi-tis55 cannot be recommended.

Recommendations

8. In stable patients with chronic bronchitis,the clinical benefits of postural drainage andchest percussion have not been proven, andthey are not recommended. Level of evidence,fair; net benefit, conflicting; grade of recommenda-tion, I

9. In patients with an acute exacerbation ofchronic bronchitis, the clinical benefits of pos-tural drainage and chest percussion have notbeen proven, and they are not recommended.Level of evidence, fair; net benefit, conflicting; grade

of recommendation, I

Bronchodilators

The effects of therapy with short-acting inhaled-agonists in patients with chronic bronchitis havebeen extensively studied,64 and have been shown toimprove pulmonary function, breathlessness, andexercise tolerance. There is some evidence thatchronic cough improves with the regular use of ashort-acting inhaled -agonist,65 but the results inthe literature are not consistent.66,67 There is no

significant improvement in sputum production withthis therapy.67,68 The long-term effects of ipratro-pium bromide therapy have been evaluated in stablepatients with chronic bronchitis. With this agent,patients coughed fewer times, and their cough wasless severe. In addition, the volume of sputumexpectorated decreased significantly.69 On the otherhand, trials70 of a once-daily regimen of inhaledanticholinergic tiotropium in patients with COPDshowed significant bronchodilatation and relief ofdyspnea when compared to placebo, but no effect oncough using diaries to assess daily symptom scores.

The use of oral theophylline for the treatment ofCOPD has declined over the last several decadesbecause of concerns over side effects, especially inelderly patients, and issues regarding interactionswith other drugs. Therapy with oral theophyllinedoes improve cough in stable patients with chronicbronchitis.71 During an acute exacerbation ofchronic bronchitis, there is good evidence that bron-

chodilator therapy improves outcomes55; however,the effect on cough has not been systematicallystudied.

Recommendations

10a. In stable patients with chronic bronchi-tis, therapy with short-acting -agonists shouldbe used to control bronchospasm and relievedyspnea; in some patients, it may also reducechronic cough.Level of evidence, good; net bene-

fit, substantial; grade of recommendation, A10b. In stable patients with chronic bronchi-

tis, therapy with ipratropium bromide shouldbe offered to improve cough. Level of evidence,fair; net benefit, substantial; grade of recommenda-tion, A

10c. In stable patients with chronic bronchi-tis, treatment with theophylline should be con-sidered to control chronic cough; careful mon-itoring for complications is necessary. Level ofevidence, fair; net benefit, substantial; grade of recom-mendation, A

11. For patients with an acute exacerbationof chronic bronchitis, therapy with short-acting-agonists or anticholinergic bronchodilatorsshould be administered during the acute exac-erbation. If the patient does not show a promptresponse, the other agent should be added afterthe first is administered at the maximal dose.Level of evidence, good; net benefit, substantial;grade of recommendation, A

12. For patients with an acute exacerbationof chronic bronchitis, theophylline should notbe used for treatment. Level of evidence, good;

net benefit, none; grade of recommendation, D

Mucokinetic Agents and Corticosteroids

There is limited evidence to justify the use ofmucokinetic agents or inhaled corticosteroids tocontrol cough in patients with chronic bronchitis.Combined therapy with a long-acting -agonist andan inhaled corticosteroid has been shown72 to reducethe exacerbation rate in patients with COPD andalso to reduce cough in long-term trials in patients



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with COPD. Therapy with inhaled corticosteroidsare recommended when airflow obstruction is severeor very severe (ie, FEV1 50%) and when there is ahistory of frequent exacerbations of chronic bronchi-tis.73,74 The beneficial effects of expectorants havenot been proven for the treatment of cough inpatients with chronic bronchitis. The oral mucolyticagent N-acetylcysteine has been studied75 in stable

patients with chronic bronchitis, and it has beenshown to improve overall symptoms and to reducethe risk of exacerbations. It is not approved for use inthe United States. The use of oral corticosteroids inpatients has been discouraged.6 There is no evidenceof benefit in stable patients with chronic bronchitis,and the well-known side effects will preclude anylong-term trials in the future.

Therapy with mucokinetic agents is not usefulduring an acute exacerbation of chronic bronchitis.55

There is considerable evidence55,76 that patients whohave an exacerbation of COPD will benefit from

systemic therapy with corticosteroids. Studies of theeffect of therapy with corticosteroids on acute exac-erbations of chronic bronchitis have not specificallyevaluated cough as an outcome.73 Treatment failureand lung function (FEV1) have been the most fre-quently assessed end points. In the largest trial,73

there was equivalence between an 8-week trial and a2-week trial of corticosteroids. Because of the signif-icant potential for side effects with these agents, a2-week trial is recommended.73

Recommendations

13. For stable patients with chronic bronchi-tis, there is no evidence that the currentlyavailable expectorants are effective and there-fore they should not be used. Level of evidence,low; net benefit, none; grade of recommendation, I

14. In stable patients with chronic bronchitis,treatment with a long-acting -agonist whencoupled with an inhaled corticosteroid shouldbe offered to control chronic cough. Level ofevidence, good; net benefit, substantial; grade of

recommendation, A15. For stable patients with chronic bronchi-

tis and an FEV1

of< 50% predicted or for thosepatients with frequent exacerbations of chronicbronchitis, inhaled corticosteroid therapyshould be offered. Level of evidence, good; netbenefit, substantial; grade of recommendation, A

16. For stable patients with chronic bronchi-tis, long-term maintenance therapy with oralcorticosteroids such as prednisone should notbe used; there is no evidence that it improvescough and sputum production, and the risks of

serious side effects are high. Level of evidence,expert opinion; net benefit, negative; grade of rec-ommendation, E/D

17. For patients with an acute exacerbationof chronic bronchitis, there is no evidence thatthe currently available expectorants are effec-tive, and therefore they should not be used.Level of evidence, low; net benefit, none; grade of

recommendation, I18. For patients with an acute exacerbation

of chronic bronchitis, a short course (10 to 15days) of systemic corticosteroid therapy shouldbe given; IV therapy in hospitalized patientsand oral therapy for ambulatory patients haveboth proven to be effective. Level of evidence,good; net benefit, substantial; grade of recommen-dation, A

Antitussive Agents

Occasionally, the cough of chronic bronchitis is sotroublesome that temporary cough suppression isrequired. When needed, codeine and dextrometho-rphan (but not pipazethate) are effective for treatingcough in patients with chronic bronchitis. Whilestudies7779 have shown that they suppress coughcounts by 40 to 60%, these studies were conductedwith very small patient populations.

Recommendation

19. In patients with chronic bronchitis, cen-tral cough suppressants such as codeine anddextromethorphan are recommended for short-term symptomatic relief of coughing. Level ofevidence, fair; benefit, intermediate; grade of evi-dence, B

Summary of Recommendations

1. Adults who have a history of chronic

cough and sputum expectoration occurringon most days for at least 3 months and for atleast 2 consecutive years should be given adiagnosis of chronic bronchitis when otherrespiratory or cardiac causes of chronicproductive cough are ruled out. Level ofevidence, low; net benefit, substantial; grade ofrecommendation, B

2. The evaluation of patients with chroniccough should include a complete historyregarding exposures to respiratory irritantsincluding cigarette, cigar, and pipe smoke;



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passive smoke exposures; and hazardousenvironments in the home and workplace.All are predisposing factors of chronic bron-chitis.Level of evidence, low; net benefit, sub-stantial; grade of recommendation, B

3. Smoke-free workplace and publicplace laws should be enacted in all commu-

nities. Level of evidence, expert opinion; netbenefit, substantial; grade of recommendation,E/A

4. Stable patients with chronic bronchitiswho have a sudden deterioration of symp-toms with increased cough, sputum produc-tion, sputum purulence, and/or shortness ofbreath, which are often preceded by symp-toms of an upper respiratory tract infection,should be considered to have an acute ex-acerbation of chronic bronchitis, as long asconditions other than acute tracheobronchi-

tis are ruled out or are considered unlikely.Level of evidence, expert opinion; net benefit,substantial; grade of recommendation, E/A

5. In patients with chronic cough whohave chronic exposure to respiratory irri-tants, such as personal tobacco use, passivesmoke exposure, and workplace hazards,avoidance should always be recommended.It is the most effective means to improve oreliminate the cough of chronic bronchitis.Ninety percent of patients will have resolu-tion of their cough after smoking cessation.

Level of evidence, good; net benefit, substantial;grade of recommendation, A

6. In stable patients with chronic bronchi-tis, there is no role for long-term prophylactictherapy with antibiotics.Level of evidence, low;benefit, none; grade of recommendation, I

7. In patients with acute exacerbations ofchronic bronchitis, the use of antibiotics isrecommended; patients with severe exacer-bations and those with more severe airflowobstruction at baseline are the most likely tobenefit. Level of evidence, fair; net benefit,

substantial; grade of recommendation, A8. In stable patients with chronic bron-

chitis, the clinical benefits of postural drain-age and chest percussion have not beenproven, and they are not recommended. Levelof evidence, fair; net benefit, conflicting; grade ofrecommendation, I

9. In patients with an acute exacerbationof chronic bronchitis, the clinical benefits ofpostural drainage and chest percussion

have not been proven, and they are notrecommended. Level of evidence, fair; netbenefit, conflicting; grade of recommendation, I

10a. In stable patients with chronic bron-chitis, therapy with short-acting -agonistsshould be used to control bronchospasmand relieve dyspnea; in some patients, it

may also reduce chronic cough. Level ofevidence, good; net benefit, substantial; grade ofrecommendation, A

10b. In stable patients with chronic bron-chitis, therapy with ipratropium bromideshould be offered to improve cough.Level ofevidence, fair; net benefit, substantial; grade ofrecommendation, A

10c. In stable patients with chronic bron-chitis, treatment with theophylline shouldbe considered to control chronic cough;careful monitoring for complications is nec-

essary. Level of evidence, fair; net benefit, sub-stantial; grade of recommendation, A

11. For patients with an acute exacerba-tion of chronic bronchitis, therapy withshort-acting -agonists or anticholinergicbronchodilators should be administeredduring the acute exacerbation. If the pa-tient does not show a prompt response, theother agent should be added after the firstis administered at the maximal dose.Level ofevidence, good; net benefit, substantial; grade ofrecommendation, A

12. For patients with an acute exacerba-tion of chronic bronchitis, theophyllineshould not be used for treatment. Level ofevidence, good; net benefit, none; grade ofrecommendation, D

13. For stable patients with chronic bron-chitis, there is no evidence that the cur-rently available expectorants are effectiveand therefore they should not be used.Levelof evidence, low; net benefit, none; grade ofrecommendation, I

14. In stable patients with chronic bron-

chitis, treatment with a long-acting -ag-onist when coupled with an inhaled corti-costeroid should be offered to controlchronic cough. Level of evidence, good; netbenefit, substantial; grade of recommendation,A

15. For stable patients with chronic bron-chitis and an FEV

1of< 50% predicted or

for those patients with frequent exacerba-tions of chronic bronchitis, inhaled cortico-steroid therapy should be offered. Level of



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evidence, good; net benefit, substantial; grade ofrecommendation, A

16. For stable patients with chronic bron-chitis, long-term maintenance therapy withoral corticosteroids such as prednisoneshould not be used; there is no evidencethat it improves cough and sputum produc-

tion, and the risks of serious side effects arehigh. Level of evidence, expert opinion; netbenefit, negative; grade of recommendation,E/D

17. For patients with an acute exacerba-tion of chronic bronchitis, there is no evi-dence that the currently available expecto-rants are effective, and therefore theyshould not be used.Level of evidence, low; netbenefit, none; grade of recommendation, I

18. For patients with an acute exacerba-tion of chronic bronchitis, a short course (10

to 15 days) of systemic corticosteroid ther-apy should be given; IV therapy in hospital-ized patients and oral therapy for ambula-tory patients have both proven to beeffective. Level of evidence, good; net benefit,substantial; grade of recommendation, A

19. In patients with chronic bronchitis,central cough suppressants such as codeineand dextromethorphan are recommendedfor short-term symptomatic relief of cough-ing. Level of evidence, fair; benefit, intermedi-ate; grade of evidence, B

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