DEFINITION

The basis of the currently accepted defini-tion is the clinical symptom of chronic produc-tive cough on most days for at least 3 succes-sive months of the year over a 2 year period .All specific causes for these symptoms must beexcluded before the diagnosis can be accepted .The common differential diagnoses are tuber-culosis, carcinoma of the lung, bronchialasthma, congestive heart failure, and pulmo-nary mycoses. This chronic bronchitis of non-specific type may coexist with the diseases men-tioned or may be a consequence of them . Theestablishment of the diagnosis of chronic bron-chitis is often neglected when other overt spe-cific disease is present, although it is impor-tant to identify all diagnoses so that completetherapy can be instituted .

The exact cause of chronic bronchitis is notknown. It appears to be more common in urbanor industrial areas . A number of inhaled irri-tants appear obviously to play a role in the per-sistence or aggravation or both of the symp-toms and pathology . These include inhaledtobacco smoke, certain air pollutants, dusts,powders, and noxious fumes . Bacterial or viralinfections of the bronchopulmonary tree suchas pneumonia or acute viral tracheobronchitismay be the precipitating event or more seri-ously aggravate the course of the disease .When the diagnosis of chronic bronchitis isestablished, chronic bronchial infection is usu-ally present. All age groups are affected butover 20 per cent of adult males and about 10per cent of adult females appear to have thesymptoms of chronic productive cough . Theserious consequences of the disease are usuallynoted after the age of 40 . There are now 15,000documented deaths yearly attributed to bron-chitis and emphysema in the United States andthese diseases are second only to cardiac dis-ease as a cause of disability . Although a historyof heavy cigaret smoking is common, the dis-ease can be observed in nonsmokers .

* These studies were supported in part by a grantfrom The Council for Tobacco Research-U.S.A.

CHRONIC BRONCHITIS*By SANFORD CHODOSH, M.D., EARLE B . WEISS, M.D .,and MAURICE S. SEGAL, M.D .Tufts University School of Medicine, Boston, Massachusetts

Pathologically there is hypertrophy and hy-perplasia of the mucus-secreting bronchialglands relative to the bronchial wall thicknessand of the goblet cells of the bronchial epi-thelium. There are diffuse inflammatory changesof the bronchial epithelium with ulceration,neutrophile infiltration, loss of cilia, bacterialinvasion, and areas of squamous metaplasiawith "abnoiuial" mucus in the bronchial luminawhich may even extend to the proximal al-veoli. Many of these changes interfere withmucociliary function .

Among other things, chronic bronchitis iscalled smoker's bronchitis, simple bronchitis,purulent bronchitis, cigaret cough or morningcough. When dyspnea and/or wheezing arepresent, chronic bronchitis may be misdiag-nosed as asthma or emphysema . The recenttendency to assimilate chronic bronchitis intothe broader category of chronic obstructivelung disease is unfortunate . This detracts froma more specific pathophysiologic understand-ing of the disease process, while emphasizingonly one feature of chronic bronchitis, i .e . theairways obstruction .

SYMPTOMS

The identifying symptoms of chronic coughand expectoration may be difficult to elicitfrom the patient with early or minimal disease .The increase in severity of symptoms may begradual with the patient accepting each newincreased level as part of his normal existence .If the onset of the disease was a specific bron-chopulmonary insult, the patient is more likelyto remember the actual onset of the symptomsand be concerned by their presence . The coughis more noticeable in the morning because ofpooling of nocturnal secretions in the supineposition which are then mobilized with morn-ing activities. Lying down at night may alsoresult in cough because of the shifting of se-cretions. Wheezing is common and is charac-teristically relieved by raising sputum . Clinicaldistinction from the wheezing associated withasthma (relieved by specific medications) or

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emphysema (effort related) is possible . A back-

ROENTGENOGRAPHYground history of asthma is often obtained .Frequent and protracted chest colds or pneu-monias are common in these patients, but se-vere disease may be present without such his-tory. Severe coughing spells may lead toinsomnia, anorexia, depression, and "cough"fractures of ribs simulating pleurisy . The dysp-nea in pure chronic bronchitis may be insidiousand is probably related to obstruction of air-ways with abnormal and excessive mucus . Ma-laise, weight loss, fatigability, and retrosternalburning with cough are common in the mod-erately severe case . Chronic bronchitis is themost frequent basis for mild hemoptysis .Chronic upper respiratory disease of both al-lergic and infectious nature may be a com-monly associated or precipitating factor .

Blue lips and nails, enlargement of the ter-minal phalanges, swelling of the legs, or dysp-nea at rest is usually a late symptom of chronicbronchitis, but ;'nterestingly may be the chiefcomplaint that first brings the patient to thephysician's attention .

PHYSICAL EXAMINATION

Abnormal physical findings in the chest maybe absent or minimally present even in mod-erately severe cases, and this discrepancy mustnot be interpreted as a denial of the historypresented. Positive signs are almost all refer-able to bronchial secretions . Roughened breathsounds, coarse rales, and rhonchi may be notedon inspiration, or expiration ; they are oftenbasilar and transient, and may clear completelywith cough. Decreased to absent breath soundsrelated to secretions also may be of a spottyand migratory nature . Wheezing may be notedon inspiration or expiration, but expiration fre-quently is prolonged. Such findings are usuallyexaggerated during acute exacerbations ofbronchitis . Palpation of the chest may reveallocal tenderness over a recently fractured ribor callous formation . In more advanced dis-ease, the patient may be plethoric or have adusky cyanosis and have cardiac findings ofcor pulmonale. Overt clubbing is not com-monly observed in pure chronic bronchitis (al-though the nail beds are often soft) and shouldmake one suspicious of other disease, e .g. ab-scess, carcinoma, or bronchiectasis . Whenbronchial asthma or emphysema is concomi-tantly present, the physical findings may berelated to the multiple disease processes .

In minimal chronic bronchitis the chest x-rayfindings are often normal. However, occasion-ally one sees thickening of bronchial walls andcrowding of bronchial structures in the lowermedial zones . In cross section such bronchi ap-pear as distinct circles of density with air in-side and out . A longitudinal section showsthickened parallel walls with air contrast . In-trabronchial beading or rosary effects may beproduced by the irregularly piled-up mucusinterspersed with air pockets . In addition, tinyair "diverticulae" extend out of the lumen andinto the wall representing dilated mucus glandducts. These bronchial findings become morecommon as the disease becomes more severe .The vasculature is preserved or more pro-nounced than normal. The finding of dimin-ished or tapered vessels suggests associatedemphysema. A scalloped diaphragmatic borderor localized areas of fibrosis represent healedparenchymal processes which are commoncomplications of bronchitis . Laminographymay define some of these abnormalities . Bron-chography demonstrates the extent to whichthe bronchial mucus glands are involved andmucosal thickening related to edema or hyper-plasia. The beading, reduced numbers of pe-ripheral bronchi, and overt cutoffs of the largerbronchi due to secretions may be surprising intheir extent. Fusiform and cylindrical dila-tions are consistent with bronchitis and do notdenote bronchiectasis . Fluoroscopy is of littlevalue, but may reveal patterns of regional ven-tilation or signs of early pulmonary hyperten-sion by the prominence of hilar pulmonaryartery pulsations .

LABORATORY STUDIES

The peripheral blood examination is oflimited value . The white blood cell count isusually normal even during an acute infectiousexacerbation . A mild shift to the left of theneutrophilic cells is often the only indicationof increased turnover . The sedimentation rateis more often normal than increased . Increasedhematocrit and hemoglobin occur with hy-poxia, but may not correlate with the degree .With advanced stages, a decrease in Pa02which is further decreased with exercise, andan elevation of PaCO2 are present. The pH willvary depending on the degree of renal com-pensation and concurrent therapy (diuretics) .Hypochloremia often accompanies chronic re-

spiratory acidosis. A lower hemoglobin thanexpected should lead one to search for a causefor blood loss, since bleeding peptic ulcer isvery common in this group of patients .

Production o f sputum indicates bronchopul-monary disease o f some type . The cells can beevaluated by simple examination of a wet prep-aration or a Papanicalaou stained smear. Instable chronic bronchitis there is a character-istic cytologic pattern . Numerous individualbronchial epithelial cells are exfoliated andare usually degenerated with some metaplasticchanges, and occasionally contain identifiablebacteria. These bronchial epithelial cells con-stitute 5 to 20 per cent of the total cell popu-lation and their numbers reflect the area ofbronchial mucosa involved in the process atthe time of sampling. The predominant celltype is the polymorphonuclear neutrophile (60to 90 per cent of total cells) and marked in-creases indicate an inflammatory exacerbationeven in the absence of clinical evidence. Thehistiocyte or alveolar macrophage is a verysensitive indicator of cellular responsiveness .There may be from 1 to 20 per cent present inthe stable state . A marked paucity of histio-cytes is commonly the first sign of an acute in-flammatory exacerbation. A marked increasedenotes that the cellular response is good andthis is usually followed by recovery. When thenumber of histiocytes is maintained at a highlevel in the stable state, the patient is usuallyhandling his disease well . Other cells such asmonocytes, lymphocytes, and plasma cells areusually found in small numbers. If over 2 percent of the cells are eosinophiles, one shouldsuspect an allergic component . Sputum cul-tures can be helpful in following the courseof and suggesting the antibiotic treatment ofchronic bronchitis, particularly if these cul-tures are carried out in conjunction with a care-ful gram stain analysis . Gram stains and cul-tures carried out with material that has beenshown microscopically to represent broncho-pulmonary secretion can be very useful . Theinvestigators who belittle bacteriologic exami-nation of sputum do not usually select materialon this simple criterion . Exactly what consti-tutes a pathogen in chronic bronchitis is notclear, but one can almost invariably find somebacteria in the gram stain of a bronchitic .When there are more than 30 to 50 organismsper oil immersion field, there is probably a sig-nificant bacterial infection present . The usualorganisms found are streptococci, Neisseria sp .,D. pneumoniae, diphtheroids, and Hemophilus

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influenzae . The marked predominance of H. in-fluenzae or D . pneumoniae almost always rep-resents a significant infection, although theothers should not be ignored . It is unusual tofind staphylococci to be a predominant factorin an acute exacerbation of chronic bronchitis .The role of virus infection in the stable stateof bronchitis is not clear, although acute ex-acerbations frequently appear to be triggeredby such infections .

BRONCHOSCOPIC FINDINGS

The findings are related to the extent andseverity of the mucosal inflammation and ofthe degree of hypersecretion of mucus . Red,friable, and edematous mucosa and dilatedbronchial mucus gland ducts may be seen. Abiopsy of the bronchial wall may demonstrateinflammation, areas of metaplasia, and the hy-perplasia-hypertrophy of the bronchial mucusglands. In the absence of other specific in-fectious cause or of cystic fibrosis, these find-ings are diagnostic of chronic bronchitis .

PULMONARY FUNCTION STUDIES

In early or minimal chronic bronchitis allpulmonary physiologic tests may be withinnormal limits . The abnormalities which maybe observed later in the disease reflect the par-tial and complete obstruction of bronchi dueto secretions or mucosal changes. These testsare discussed in the section on chronic pul-monary emphysema. However, one should notethat the patterns observed may not distinguishchronic bronchitis from chronic pulmonaryemphysema .

COURSE

It is important to remember that chronicbronchitis by itself can progress to cause com-plete disability and finally death . Although in-sidious progression can bring the patient tothe physician in a severe state of disability, itis clear that reversibility is possible . Patientspresenting with cor pulmonale, polycythemia,weight loss, and frequent infectious exacerba-tions may be returned to a fully active life .Those who present with early or minimal dis-ease can have a complete clinical resolution .Despite treatment, the course is unpredictable .In general, based on clinical impressions, it issafer to assume that the disease will progresswithout adequate therapy . Exactly how chronic

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pulmonary emphysema is related pathophysio- will be the outcome . The intelligent use of thelogically is not clear, but the diseases are diagnostic criteria, with particular emphasishighly related . on mild cough and sputum production, may

Clinically we suspect that the earlier chronic result in a substantial improvement in the earlybronchitis is recognized, the more favorable

detection of this disease .

Reprinted from Current Diagnosis 2Edited by Howard F . Conn, M.D. and Rex B. Conn, Jr., M.D .Published by W . B. Saunders Company, 1968

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