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Acute Exacerbation of Chronic Bronchitis

Acute bronchitis, an inflammatory condition of the bronchi, refers to a clinical syndrome whose most distinctive hallmark is the recent onset of cough, which is usually productive. This disorder, occurs more frequently in the winter, is often preceded by headache, sore throat, and coryza, and is on occasion accompanied by fever and chest discomfort. Bronchitis is usually, but not exclusively, caused by a respiratory pathogen, predominantly a virus (rhinovirus, coronavirus, adenovirus, influenza virus) and less frequently a bacterium (Mycoplasma pneumoniae, Chlamydia pneumoniae, Bordetella pertussis, Bordetella parapertussis, Legionella species, Streptococcus pneumoniae, and Haemophilus influenzae). Neither the appearance of the sputum (purulence) nor the measurement of the white cell count is a reliable indicator of the cause of the acute bronchitis (viral vs. bacterial).
When wheezing, shortness of breath, and tightness of the chest occur, the disease can resemble an acute attack of asthma. In fact, when these symptoms of bronchospasm develop, patients often display spirometric evidence of reversible airway obstruction, and these cases are referred to as “adult acute asthmatic bronchitis.” The symptoms of acute infectious bronchitis, when consisting of fever, chest discomfort, cough, and shortness of breath, can imitate those of infectious pneumonia, and chest radiography would then be required to distinguish precisely between acute bronchitis and pneumonia. The absence of fever and focal crackles suggests bronchitis rather than pneumonia.
The preponderance of evidence indicates that most healthy persons experience spontaneous resolution of bronchitis and do not sustain any sequelae. With rare exceptions (such as disease caused by influenza virus), the disease in these patients does not progress to pneumonia or cause irreversible anatomic abnormalities of the respiratory tract. In contrast, patients with HIV infection are at risk for having their disease evolve into bronchiectasis.
Neither blood nor sputum analyses appear to be indicated for the management of immunocompetent patients. There is also no convincing need to prescribe an antibiotic. For the nonpregnant patient with “presumed” influenza A bronchitis and symptoms for less than 48 hours, either amantadine (Symmetrel) or rimantadine (Flumadine) should be prescribed. Patients who experience insomnia from “bouts” of coughing can obtain symptomatic improvement from an antitussive, codeine-containing medication, and patients who have symptoms consistent with “adult acute asthmatic bronchitis” are candidates for inhaled bronchodilator therapy with albuterol. Studies have demonstrated the superiority of albuterol in comparison with erythromycin. The value of increasing fluid intake remains unknown.
Most physicians feel pressured to prescribe an antibiotic, as the public has the expectation of receiving a “magic bullet” to hasten the resolution of infection. Patients should be reassured that most infections are viral and will not respond to an antibiotic. In addition, physicians are concerned that some of these episodes of acute bronchitis are precipitated by potentially treatable organisms (M. pneumoniae, C. pneumoniae, B. pertussis), so that although there are no rapid, readily available ways, either clinical or laboratory-based, to distinguish among these etiologies, and although there are no convincing data that antibiotic treatment accelerates the resolution of symptoms of acute bronchitis caused by M. pneumoniae or C. pneumoniae, clinicians often elect to administer a course of an antimicrobial agent, such as erythromycin, clarithromycin, azithromycin, doxycycline, cefaclor, cefuroxime, loracarbef, or trimethoprim-sulfamethoxazole (TMP-SMX). That approach has no scientific foundation, adds to medical costs, fosters the emergence of resistant organisms, and contributes to drug toxicity, manifested as skin eruptions and gastrointestinal adverse events.
Many patients, with or without antimicrobial therapy, will cough for weeks. If a patient fails to improve within 4 to 5 days, efforts should be made to confirm the diagnosis, exclude alternative disorders, including pneumonia, and attempt to identify specific offending pathogens, such as B. pertussis. Patients infected with this bacterium, who serve as a reservoir of infection for nonimmune children and adults, merit antibiotic treatment (erythromycin or TMP-SMX). Pertussis is characterized by paroxysmal, nonproductive cough that worsens at night. In contrast to children, adults with pertussis do not have absolute lymphocytosis. Patients symptomatic for more than 3 weeks require additional investigations to exclude tuberculosis, drug-induced disorders, BOOP (bronchiolitis obliterans–organizing pneumonia), sarcoid chronic eosinophilic pneumonia, Wegener’s granulomatosis, and cancer.
Acute bronchitis is the most frequent lower respiratory tract illness in HIV-infected patients. These patients typically present with cough, purulent sputum, and low-grade fever. Their sputum culture often grows S. pneumoniae, H. influenzae, or Pseudomonas aeruginosa. They should receive an antibiotic. Unfortunately, however, they are prone to recurrences. When HIV-infected patients with acute bronchitis manifest cough and shortness of breath unaccompanied by purulent sputum, an effort needs to be made to distinguish this disease from roentgenographically negative Pneumocystis carinii pneumonia and tuberculosis.
Acute Exacerbation of Chronic Bronchitis
When a patient with known chronic bronchitis experiences a syndrome consisting of the abrupt development of fatigue, chest tightness, worsening cough, and dyspnea, accompanied by an increased volume and/or purulence of sputum, an “exacerbation” has occurred. Definition of the syndrome does not require all these elements to be present, and although infections precipitate some exacerbations, most are not associated with fever. An exacerbation not only produces uncomfortable and disabling symptoms, but can also result in lost work time, significant financial costs, and hospitalization. The 7.5 million Americans with chronic bronchitis are not a homogenous group. Some of these people escape exacerbations, some have one or two winter exacerbations, and others have numerous episodes each year. Certainly not all exacerbations are precipitated by an infectious event. Those organisms most frequently associated with the exacerbation of chronic bronchitis include viruses, M. pneumoniae, H. influenzae, S. pneumoniae, and Moraxella (Branhamella) catarrhalis. Limited data suggest a role for Haemophilus parainfluenzae and, rarely, C. pneumoniae.
As a general rule, there is no compelling need to analyze the blood or sputum or to obtain a chest x-ray study during the first encounter with a patient who does not appear seriously ill. A blood gas determination would be appropriate for patients experiencing insomnia, agitation, or increasing dyspnea.
For more than 50 years, physicians have prescribed antimicrobial agents to patients with chronic bronchitis experiencing an exacerbation, but the efficacy of this treatment has remained a subject of controversy. It has been difficult to assess the value of administering an antimicrobial agent to these patients because there is no precise definition of an exacerbation, not all exacerbations are caused by a bacterial infection, patients’ symptoms are often relieved by co-medications, and meaningful endpoints of treatment are difficult to identify. In addition, there are few published clinical trials, and the available investigations have some design defects. The randomized trials suggest that antibiotic treatment effects a modest but statistically significant clinical improvement. Antimicrobial agents appear to have their greatest impact in the therapy of the patient experiencing a more “severe” exacerbation—not simply an increase or change in the appearance of sputum, but both of these features plus increased shortness of breath. Antimicrobials have accelerated the rate of clinical resolution and reduced the need for additional medication, return visits, and hospitalization, and they have caused negligible toxicity.
Table 4-1 lists the macrolides, aminopenicillins, cephalosporins, carbacephem, fluoroquinolones, TMP-SMX combination, and tetracyclines that clinicians prescribe for patients experiencing an exacerbation of chronic bronchitis. There are no convincing scientific data to indicate that any one of these oral agents produces enhanced clinical resolution when compared with the others. Features of the host and antimicrobial agent that would influence drug selection include the following: patient history of drug allergy; track record of the drug; its potential to initiate untoward events or undesirable drug-drug interactions; its spectrum of activity; ease of compliance; and cost of the drug.

Table 4-1. Antimicrobial agents

TMP-SMX and doxycycline appear to be appealing drugs. They inhibit the growth of the majority of bacteria incriminated in the exacerbation of chronic bronchitis. Additionally, they are an appropriate selection for penicillin-allergic patients, can be taken twice a day, and are relatively safe and inexpensive compounds with an established track record. However, some patients experience hypersensitivity reactions (fever, rash) or gastrointestinal untoward events with TMP-SMX, and there is a risk for interaction when it is coadministered with warfarin, cyclosporine, phenytoin, methotrexate, or oral hypoglycemic agents. In addition, older patients are at greater risk for TMP-SMX–induced blood dyscrasias and hyperkalemia. Doxycycline has a potential to cause gastrointestinal toxicity. This antibiotic has also produced esophageal ulcerations and strictures (particularly in elderly patients) and, rarely, hepatitis, rashes, and photosensitivity. The drug should not be prescribed for patients who are taking antacids, ferrous sulfate, or cimetidine. Treatment with either of these compounds can be restricted to approximately 1 week.
Ancillary treatment consists of encouraging smoking cessation. The use of a bronchodilator, such as ipratropium or a b-adrenergic sympathomimetic agent, may confer some additional benefit. The value of drinking copious fluids or taking an expectorant is undocumented. Patients usually improve clinically within 4 days and achieve complete resolution of the exacerbation within 2 weeks.
When a patient fails to demonstrate any improvement within 5 days, the clinician should consider the following: incorrect diagnosis (perhaps pneumonia, neoplasm, or congestive heart failure); noncompliance; inappropriate antimicrobial selection (organism resistant to the medication prescribed); diminished antimicrobial bioavailability (concomitant administration of iron, antacids, didanosine, and multivitamins with zinc decreases the absorption of tetracyclines and fluoroquinolones); and excessive bronchospasm and bronchial secretions.
Patients with chronic bronchitis are candidates for an annual immunization with influenza vaccine, as well as pneumococcal vaccine, although the value of pneumococcal vaccine for these patients is controversial. Another potential preventive measure is to offer the patient antibiotic prophylaxis with an agent such as tetracycline, ampicillin, amoxicillin, or TMP-SMX prescribed once a day either four times a week or every day during the winter. The published scientific data are very “soft” here, however. Antibiotic prophylaxis should be restricted to the patient who experiences four or more exacerbations per year.
Researchers have recently examined the role of oral immunization with bacterial extracts as an approach to stimulating respiratory tract immune defenses and reducing exacerbations of chronic bronchitis. Limited data suggest that this approach may have some merit. The basis for oral immunization is that stimulation of gut-associated lymphoid tissue can prime bronchial tube-associated lymphoid tissue, presumably through cell traffic between these two systems. (R.A.G.)
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Fever is not a common manifestation of the exacerbation.
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Antibiotics should not be routinely prescribed to healthy adults who experience acute bronchitis.
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An attempt to identify the infectious causes of the exacerbation of chronic bronchitis.


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