The American Journal of Managed Care October 2004
Acute Exacerbation of Chronic Bronchitis: A Primary Care Consensus Guideline
Objective: To develop consensus on appropriate treatment for acute exacerbation of chronic bronchitis (AECB).
Characteristics and Etiology: Patients with chronic bronchitis have an irreversible reduction in maximal airflow velocity and a productive cough on most days of the month for 3 months over 2 consecutive years. An AECB is characterized by a period of unstable lung function with worsening airflow and other symptoms. Most (80%) cases of AECB are due to infection, with half due to aerobic bacteria. The remaining 20% are due to noninfectious causes such as environmental factors or medication nonadherence.
Management: Supportive care should be provided to all patients, which might include removal of irritants, use of a bronchodilator, oxygen, hydration, use of a systemic corticosteroid, and chest physical therapy. Antibacterial treatment should be reserved for patients with at least 1 key symptom (ie, increased dyspnea, sputum production, sputum purulence) and 1 risk factor (ie, age ¡Ý 65 years, forced expiratory volume in 1 second <50% of the predicted value, ¡Ý4 AECBs in 12 months, 1 or more comorbidities). A newer macrolide, extended-spectrum cephalosporin, or doxycycline is appropriate for an exacerbation of moderate severity, and high-dose amoxicillin/clavulanate or a respiratory fluoroquinolone should be used for a severe exacerbation. There has been increasing antibacterial resistance by the 3 most prevalent pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis).
Conclusion: Although all AECB patients should receive supportive care, only patients with at least 1 key symptom and 1 risk factor should receive antibiotic therapy.
(Am J Manag Care. 2004;10:689-696)
Chronic bronchitis is a subset of disease within the broader category of chronic obstructive pulmonary disease (COPD), which is characterized by a chronic, predominantly irreversible reduction in maximal airflow velocity. Chronic bronchitis, emphysema, asthma, and to a lesser extent bronchiectasis comprise the majority of COPD (Figure 1). Chronic bronchitis is a disease process identified clinically as the presence of a productive cough on most days of the month for 3 months over 2 consecutive years.1 It occurs in the absence of other causes of chronic cough such as tuberculosis or lung cancer. An acute exacerbation of chronic bronchitis (AECB) is a distinct event superimposed on chronic bronchitis and is characterized by a period of unstable lung function with worsening airflow and other symptoms. The average number of episodes of AECB per year is reported to range from 1.5 to 3.2-4
IMPACT OF ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS
The overall rate of emergency department visits for chronic bronchitis increased 28% between 1992 and 2000. The rate of visits rose more significantly for African Americans than Caucasians. The rate increased in all age groups, particularly in persons aged 55 to 64 years; in fact, the rate in this group now approaches the rate in persons aged 65 years or older (Figure 2).5 Needless to say, the health and socioeconomic consequences are enormous. A retrospective analysis of Medicare and other databases involving more than 280 000 patients with AECB showed that the total cost of treatment in 1994 was approximately $1.6 billion.6 Outpatient care accounted for only $40 million (2.5% of the total cost) or approximately $70 per visit. This clearly demonstrates that hospitalization due to AECB accounts for the vast majority of total expenditures. A more recent report found the cost of inpatient hospitalization for AECB ranged from $6285 to $6625.7
The impact on families and informal caregivers also is substantial because they provide an average of 5.1 hours per week of informal care to patients with emphysema or chronic bronchitis.8 Undoubtedly, the impact is even greater during the period when a patient with chronic bronchitis has an episode of AECB.
The purpose of the initial clinical assessment of patients with AECB is twofold. First, it should serve to determine whether the worsening respiratory status is due to a concomitant disease or a trigger for an acute exacerbation. Second, it should determine the severity of illness so as to guide management and predict prognosis.
The diagnosis of AECB generally is made on clinical grounds. Many factors must be assessed during the history, physical examination, and workup (Table 1).9-11 Although acute exacerbations generally result from bacterial or viral infections, 20% of cases have a noninfectious cause.12 Exposure to allergens, pollutants, or cigarette smoke must be considered, and the importance of that exposure must be assessed.
A change from baseline in 1 or more chronic symptoms generally indicates worsening disease. Such symptoms include shortness of breath, increased sputum production, increased sputum purulence, cough, and increased sputum tenacity. The first 3 of these symptoms¡ªshortness of breath, increased sputum production, and increased sputum purulence¡ªare particularly helpful to determine the severity of the exacerbation.4,13 Patients with only 1 of these 3 symptoms generally are considered to have a mild acute exacerbation; those with 2 of the 3 symptoms, a moderate acute exacerbation; and those with all 3 symptoms, a severe acute exacerbation (Table 2). Clinically, increased dyspnea, cold symptoms, and sore throat are associated with a viral exacerbation, whereas an exacerbation characterized by increased sputum production or purulence, and associated with neutrophilic inflammation, is likely to be bacterial in nature.3,14,15 In fact, evolving evidence indicates that some markers of inflammation, such as interleukin-6, interleukin-8, tumor necrosis factor-alpha, neutrophil elastase, and serum fibrinogen, may be useful to distinguish bacterial from nonbacterial AECB, as well as the bacterial etiology.14 Although the measurement of these inflammatory markers is limited to the research setting at present, their use in clinical practice is possible in the near future.
Although utilization of the 3 symptoms just discussed is helpful to assess the severity of the acute exacerbation, false positives and false negatives are frequent. Unfortunately, the diagnostic usefulness of a culture remains contentious because bacterial pathogens can be isolated from the sputum of patients with stable chronic bronchitis (ie, bacterial colonization) as frequently as they can from the sputum of patients with AECB.9,14,16 Interestingly, however, it has been observed that a new strain of a bacterial pathogen was isolated twice as frequently during AECB as it was during stable chronic bronchitis.17 A sputum culture may, however, be useful in certain situations such as recurrent AECB, an inadequate response to therapy, and before starting treatment with prophylactic antibiotics.12
A chest radiograph is not used to diagnose AECB, but it may be helpful in patients who have an atypical presentation and in whom community-acquired pneumonia is suspected.9 In addition, a chest radiograph is helpful to identify comorbidities that may contribute to the acute exacerbation. The presence of pulmonary edema or pulmonary infiltrate on chest radiograph is more useful than history and clinical signs and symptoms to identify patients with congestive heart failure or pneumonia, respectively.18
Assessment of oxygen saturation is important to guide therapy. Indirect evidence from several studies indicates that arterial blood gas analysis is helpful to gauge the severity of an exacerbation and to identify those patients in need of oxygen therapy, as well as those who might require mechanical ventilation.16 Although commonly used in the assessment of AECB, the benefit of pulse oximetry has not been investigated in a clinical trial.19
Although the role of spirometry in diagnosis of AECB is less clear than it is in diagnosis of COPD,16,19 evidence from 3 trials show that measurement of lung function using spirometry is valuable to assess the degree of airway obstruction.20-22 The forced expiratory volume in 1 second (FEV1) is correlated with the partial pressure of carbon dioxide (PaCO2) and pH, but not with the partial pressure of oxygen (PaO2). The FEV1 also is correlated with the relapse rate. Spirometry is available in emergency departments and increasingly in the primary care setting. The computer-assisted devices now available are relatively simple to use with appropriate training.23 Although some patients in respiratory distress are not able to perform full spirometry to assess FEV1, the use of a peak flow meter is not appropriate because the peak expiratory flow rate is not sufficiently well correlated with lung function to substitute for FEV1.18 It should be noted, however, that serial measurement of the peak expiratory flow rate with a peak flow meter might be clinically useful.19 Similarly, baseline spirometry should be undertaken in all smokers who are without symptoms at present. Not only will this help to uncover existing lung dysfunction, but it also can be helpful for comparative purposes during an acute exacerbation.
ETIOLOGY OF ACUTE EXACERBATION OF CHRONIC BRONCHITIS
The infectious and noninfectious causes of AECB have been historically difficult to quantify because of difficulty in isolating organisms, in differentiating between pathogens and colonized organisms, and in defining patients with AECB in clinical trials, to name a few reasons. A review by Sethi of the relevant literature led him to conclude that 80% of AECB cases are infectious in nature, and noninfectious causes such as environmental factors or triggers and medication nonadherence comprise the remainder.12
In cases of AECB due to infection, 3 classes of pathogens have been found: aerobic gram-positive and gram-negative bacteria, respiratory viruses, and atypical bacteria (Figure 3).12 Although the review by Sethi was not intended to rigorously quantify the incidence of specific pathogens, he observed that aerobic bacteria were found in half of patients with AECB and viruses in one third. The predominant aerobic bacteria are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.12 Pseudomonas aeruginosa and other gram-negative bacilli also are seen and appear to be more common in patients who have a severe acute exacerbation with an FEV1 of 35% or less of the predicted value.24 Infection due to multiple pathogens occurs in a small percentage of all patients with AECB and is more common in patients with a severe exacerbation.12
Viral infection is commonly associated with AECB. In 1 study, 64% of exacerbations were associated with a cold that occurred within the previous 18 days.3 This study showed that patients with a cold experienced increased dyspnea, had a higher total symptom count at presentation, and had a median symptom recovery period of 13 days. The pattern of viral pathogens is variable. One study found that a rhinovirus was identified in 58% of exacerbations, and a respiratory syncytial virus, coronavirus, or influenza A virus was found in 29%, 11%, and 9%, respectively.12 A review of 3 longitudinal studies, on the other hand, showed that influenza was the viral pathogen most frequently observed and was found in one third of patients, while parainfluenza was isolated in one quarter of patients.12 Nonetheless, these findings support the importance of preventing colds (primarily by hand washing and avoiding exposure to those with a cold) and other viral infections, and stress the value of yearly influenza immunization.
Fewer than 10% of acute exacerbations are due to an atypical bacterium. The most common atypical bacterium is Chlamydia pneumoniae, whereas Mycoplasma pneumoniae and Legionella pneumophila are seen less frequently.12
PATTERNS OF ANTIBACTERIAL RESISTANCE