Uncomplicated Acute Bronchitis

The most frequent reason that persons in the U.S. visit ambulatory care physicians is cough, after general medical examination and progress visit. Bronchitis (acute or not otherwise specified) is the most frequent diagnosis given to these patients (1). In 1997, an estimated 30 million ambulatory visits for cough led to more than 12 million diagnoses of bronchitis. For most of these illnesses, acute bronchitis is the most accurate diagnosis. It applies to otherwise healthy adults with an acute respiratory illness lasting 1 to 3 weeks with cough as the prominent feature and in whom pneumonia has been excluded. Throughout the developed world, the diagnosis of acute bronchitis has become synonymous with antibiotic treatment. On average, 70% to 90% of office visits for acute bronchitis result in treatment with antibiotics. Yet, evidence-based reviews and meta-analyses of randomized, controlled trials conclude that routine antibiotic treatment does not provide major clinical benefit in adults with acute bronchitis. Lack of antibiotic treatment benefit should be expected because most cases of acute bronchitis have a viral cause. With the goal of improving the management of and curbing excess antibiotic use in adults with acute bronchitis, we describe recent developments in the pathophysiology, evaluation, and treatment of uncomplicated acute bronchitis and discuss the impact of efforts to reduce prescription of antibiotics for this illness. Methods A substantial portion of the literature review, analysis, and interpretation for this review was done during development of Principles of Appropriate Antibiotic Use for Adults with Acute Respiratory Tract Infections, a project supported in part by the Centers for Disease Control and Prevention. This paper provides a more expansive review of acute bronchitis in adults than do the Principles, which are intended primarily to be used as practice recommendations. The funding source had no role in collection, analysis, or interpretation of data or in the decision to submit this paper for publication. Studies of diagnosis, etiology, and treatment of acute bronchitis were retrieved from MEDLINE by using Medical Subject Heading and keyword searches for cough, bronchitis, and acute respiratory infection. Studies dated back to 1966 and were limited to those done in adult humans. Bibliographies from appropriate articles and textbook chapters on acute bronchitis were also searched for relevant studies. Studies identified from formal literature reviews in recently published meta-analyses of antibiotic treatment of acute bronchitis formed the basis for reviewing the efficacy of antibiotic treatment. Etiologic studies used to estimate incidence or prevalence of bacterial infections were excluded if they were conducted during known outbreaks or epidemics of that pathogen (for example, Chlamydia pneumoniae outbreaks in university settings) or in hospitalized persons, those referred to specialists for care, or those with chronic lung disease. Pathophysiology Definition The taxonomy currently used for diagnosis of acute respiratory infections is based primarily on the anatomic correlate of the predominant clinical feature of the illness (2). Hence, acute bronchitis is the acute or subacute onset of a cough illness lasting less than 2 to 3 weeks, with or without phlegm production, that is frequently accompanied by other upper respiratory tract and constitutional symptoms (2, 3). It has been proposed that cough persisting longer than 3 weeks be referred to as persistent or chronic cough but not chronic bronchitis, since this term has been defined by the American Thoracic Society to refer to patients with daily cough and sputum production for at least 3 months, for 2 consecutive years, and in the absence of any other disease that might account for daily productive cough (4). Diagnostic considerations in adults with persistent cough differ greatly from those in adults with a cough illness lasting less than 3 weeks. Postnasal drip, asthma, and gastroesophageal reflux disease account for more than 75% of cases in adults with cough lasting at least 3 weeks and a negative chest radiograph (5). This review focuses on uncomplicated acute bronchitis, as opposed to acute bronchitis in patients with underlying lung or heart disease, immunosuppression, or bacterial superinfection. Acute bronchitis in patients with documented emphysema or chronic bronchitis, for example, is usually considered a distinct clinical entity (acute exacerbation of chronic bronchitis) with unique etiologic and treatment issues. Because patients with heart disease (particularly congestive heart failure) or immunosuppression have been routinely excluded from pathophysiology and treatment studies of acute bronchitis, the generalizability of the findings to patients with these comorbid conditions is unknown. Bacterial superinfection after an acute viral respiratory infection (such as bacterial pneumonia or sepsis, particularly with influenza infection) should be considered when patients with acute bronchitis develop clinical signs of pneumonia. However, this complication is very uncommon in otherwise healthy adults. In a large study of pneumonia and influenza-associated deaths during influenza epidemics, 95% of deaths occurred in adults with a chronic medical condition (mostly chronic heart and lung disease), and 68% occurred in adults older than 65 years of age (6). Etiology Respiratory viruses, particularly influenza, appear to cause the large majority of cases of uncomplicated acute bronchitis in which an agent is identified by means of culture, antibody serology, or polymerase chain reaction (7-11). No isolated pathogen is also a frequent finding; it probably represents viral infections for which studies did not perform appropriate analyses. Under selected circumstances, noninfectious causes of uncomplicated acute bronchitis, such as cough-variant asthma or allergic or occupational exposures, should also be considered. The viruses most frequently associated with uncomplicated acute bronchitis are those that produce primarily lower respiratory tract disease (influenza B, influenza A, parainfluenza, and respiratory syncytial virus) and those that more commonly produce upper respiratory tract symptoms (coronavirus, adenovirus, and rhinoviruses). Increased attention has been given to respiratory syncytial virus as a cause of uncomplicated acute bronchitis in adults, particularly elderly persons. Infection with respiratory syncytial virus among exposed adults is common (with attack rates approaching 50%), particularly in households with children infected with respiratory syncytial virus and in institutional settings (12). Most young and middle-aged adults infected with respiratory syncytial virus develop asymptomatic or mildly symptomatic disease, including bronchitis, although respiratory syncytial virus can be associated with more severe clinical disease in otherwise healthy adults. In contrast to young adults, respiratory syncytial virus infection in elderly persons (age>60 years) more frequently leads to symptomatic lower respiratory tract disease. For example, a report of an outbreak of respiratory syncytial virus on a geriatrics ward found that 96% of persons reported intense coughing and fever, 64% developed a productive cough, and 40% had evidence of bronchopneumonia (13). Whether bronchopneumonia was actually due to respiratory syncytial virus or to bacterial superinfection was not examined. When microbiological studies are performed in unselected patients with uncomplicated acute bronchitis in nonoutbreak settings, fewer than 10% will have evidence of acute bacterial infection. To date, only Bordetella pertussis, Mycoplasma pneumoniae, and Chlamydia pneumoniae have been clearly established as causes of acute bronchitis. There is no evidence that Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis cause acute bronchitis in adults without underlying lung disease; studies that found an association between these encapsulated bacteria and acute bronchitis failed to distinguish between colonization and acute infection (14). However, these bacteria are important causes of superinfections after acute viral respiratory illnesses (15). The discovery that C. pneumoniae infection can cause acute bronchitis is relatively new (16). This discovery rejuvenated speculation that a bacterial pathogen, and therefore antibiotic treatment, may in fact play a significant role in uncomplicated acute bronchitis. Several reports of outbreaks of C. pneumoniae cited attack rates exceeding 50% among families (17, 18) and 25% among students (19). However, surveillance studies have reported a much lower range of incidence rates, reflecting the seasonal, geographic, and epidemic nature of C. pneumoniae infection (20-25). Evidence that B. pertussis and B. parapertussis cause uncomplicated acute bronchitis in previously immunized adults is also fairly new. Although immunity after natural infection with pertussis appears to be lifelong (26), immunity conferred by childhood immunization begins to wane after as little as 3 years and is usually absent after 10 to 12 years. Attack rates as high as 100% have been reported among adult and adolescent household contacts of infected children (27). Infection in previously immunized adults appears to take a more benign course (28). Mechanism of Disease Manifestations Synthesis of the literature suggests that the clinical features of uncomplicated acute bronchitis develop in sequential phases. The acute phase of infection results from direct inoculation of the tracheobronchial epithelium by the infectious virus, leading to cytokine release and inflammatory cell activation. This phase is characterized by variable constitutional symptoms, such as fever, myalgias, and malaise, that last 1 to 5 days depending on the infectious agent. For example, uncomplicated acute bronchitis due to rhinovirus may pre