Bronchitis
Marie M. Budev and Herbert P. Wiedemann
Based on Laennecs work,1 the CIBA symposium proposed that
chronic bronchitis was to be defined as chronic or recurrent exces-
sive mucus secretion in the bronchial tree manifested clinically by
cough and expectoration of no other origin, and that bronchitis
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found in chronic obstructive pulmonary disease (COPD) should be
distinguished from that of nuisance bronchitis or Laennecs catarrh
by the presence of airflow limitation.2,3 Chronic bronchitis and
emphysema often have similar causes (tobacco use) and often occur
together. As a result, the umbrella term of chronic obstructive pul-
monary disease is often used synonymously to describe both clinical
entities.4,5 The disabling and debilitating nature of COPD is often
punctuated by intermittent acute bacterial exacerbations of chronic
S E C T I O N 12
bronchitis (ABECB) that contribute greatly to the morbidity and the
overall diminished quality of life in these patients. In fact, bacterial
exacerbations are the leading cause of death in COPD.6
DEFINITION
The definition of bronchitis is one that remains largely subjective and
has few rare objective correlates. The American Thoracic Society
defines chronic bronchitis as the presence of chronic productive
cough for 3 months in each of the 2 successive years in a patient in
whom other disease states that can cause similar symptoms have been
excluded.7 The most commonly used definition of an ABECB is a
subjective increase in dyspnea, increased sputum volume, or
increased sputum purulence. Anthonisen and colleagues attempted
to stratify the severity of an ABECB based on these very symptoms.8
According to the Anthonisen severity scale, type I (severe) episodes
of ABECB have all three clinical findings, and type II (moderate)
exhibit two clinical findings. Type III exacerbations (mild) have one
of the clinical findings plus one of the following: an upper respiratory
tract infection in the past 5 days, fever without any other apparent
cause, increased cough or wheezing, or a 20% increase in the respira-
tory rate or heart rate above baseline.9 In many guidelines, this
scale is used to assess the severity of an exacerbation and direct
management.
PREVALENCE AND EPIDEMIOLOGY
The worldwide prevalence of chronic bronchitis and ABECB is likely
to be underestimated due to the variability in the definition of
COPD. Traditionally, it has been believed that chronic bronchitis is
a major component in 85% of patients with COPD.10 In the United
States alone, more than 16 million people are affected with COPD,
and it is estimated that more than 12 million of those suffer from
chronic bronchitis symptoms.7 Acute exacerbations in more than
50% of cases of chronic bronchitis and COPD, particularly those
meeting the Anthonisen criteria, are likely the result of infectious
pathogenic bacteria. Overall, these exacerbations occur more often
in smokers than in nonsmokers. After an acute exacerbation, many
patients experience a decrease in quality of life, and subsequently
more than 50% of patients are readmitted with an ABECB more than
once in the following 6 months. Therefore, one of the main goals of
therapy in managing COPD is to reduce the number and severity of
exacerbations.
Acute exacerbations of chronic bronchitis and COPD are the
main causes of medical visits and hospitalizations, resulting in eco-
nomic costs in excess of $5 billion yearly. In one prospective series,
the costs of treating COPD and ABECB were found to be almost
twice those reported for asthma. The prevalence of COPD, and thus
1018 www.expertconsult.com
the prevalence of ABECB, continues to rise as the population ages,
and it is the only leading cause of death for which the mortality rate
is currently increasing.5,7
PATHOLOGY AND PATHOPHYSIOLOGY
The pathologic lesions of chronic bronchitis involve morphologic
changes in both the large and small airways. In patients with chronic
bronchitis, these airways contain a marked presence of inflammatory
cells with a predominance of monocytes, lymphocytes, and CD8+
cells as well as neutrophils in the airway lumen. In the large airways,
inflammation leads to metaplasia of both the columnar and goblet
cells that line the epithelium. In addition, there is an increase in the
size of the mucus-secreting glands in smooth muscle, connective
tissue in the bronchial wall, and degeneration of the airway cartilage.
Evidence is emerging that ABECBs are associated with increased
airway inflammation. There appears to be a clear association between
the degree of inflammation and the severity and frequency of the
exacerbations. Bronchoalveolar lavage (BAL) specimens taken
during ABECB show increases in the absolute number and percent-
age of neutrophils. Levels of interleukin 8 (IL-8), a potent neutrophil
chemotactic factor, leukotriene B4, and myeloperoxidase (MPO) all
have been found to be increased during ABECB. In addition, cyto-
kine levels in BAL fluid have been noted to be higher during ABECB.
In a normal patient, the respiratory tree is sterile. In a stable
chronic bronchitis patient, the sputum produced is usually mucoid
and scant. Even in this quiescent period, however, cultures of sputum
can yield potentially pathogenic bacteria in 25% to 50% of cases.
Organisms including nontypeable Haemophilus influenzae, Morax-
ella catarrhalis, and Streptococcus pneumoniae have been found to be
the predominant organisms in early studies. Once these bacteria
colonize the lower airway, they can directly cause airway inflamma-
tion and impaired mucociliary clearance, perpetuating a vicious
circle of impairing local defenses.
Bacteria have been isolated from the sputum in approximately
60% of ABECB cases. The most common organisms isolated include
H. influenzae, Haemophilus parainfluenzae, S. pneumoniae, and
M. catarrhalis (Box 1). The contributions of these four organisms can
depend on the severity of underlying airway disease. A number of
studies have found more virulent organisms in the airways of severe
chronic bronchitis patients with acute exacerbations, including
Staphylococcus aureus, Pseudomonas species, and members of the
Enterobacteriaceae family. In general, during ABECB, many of the
same bacteria that are found in the airways during clinically stable
periods are present but at higher colony counts. The role of atypical
pathogens such as Mycoplasma and Chlamydia species seem to follow
three separate mechanisms in ABECB. First, infection with Chla-
mydia pneumoniae infection at an early age can make airways more
susceptible to effects of irritants such as cigarette smoke and can
increase the risk of chronic bronchitis later in life. Second, both these
species can cause ABECB themselves. Last, atypical organisms and
viruses can cause a primary infection that can lead to severe lower
airway inflammation, enabling a secondary increase in bacterial pro-
liferation that can lead to an exacerbation.
DIAGNOSIS
The clinical diagnosis of ABECB traditionally uses some combination
of the original three Anthonisen criteria: increased cough, dyspnea,
or increased sputum purulence from baseline. There are no

Box 1 Responsible Bacteria in Acute Exacerbations of Chronic
Bronchitis
Common Bacterial Pathogens (30%-50%)
Haemophilus influenza
Haemophilus parainfluenzae
Streptococcus pneumoniae
Moraxella catarrhalis
Less-Common Bacterial Pathogens (10%-15%)
Pseudomonas aeruginosa
Enterobacteriaceae
Other gram-negative bacilli
Staphylocccus aureus
Other gram-positive cocci
Atypical Pathogens (<5%-15%)
Chlamydia pneumoniae
Mycoplasma pneumoniae
characteristic laboratory or radiographic tests that can confirm the
diagnosis of ABECB.
Some clinicians have proposed major and minor criteria; the
major criteria consist of the original Anthonisen criteria and the
minor criteria consist of wheezing, sore throat, cough, and symptoms
of the common cold, including nasal congestion or discharge. They
define an ABECB as the presence of at least two major symptoms or
one major symptom and one minor symptom for at least 2 consecu-
tive days.
There are no characteristic physical findings in ABECB. Some
have suggested that severe exacerbations may be associated with body
temperatures greater than 38.5 C, although this is highly controver-
sial. Chest radiographs are not helpful in making the diagnosis of
ABECB, but they can indicate pneumonia or other diagnoses, such
as congestive heart failure. The exception to this is a patient present-
ing to the emergency department or being hospitalized where routing
chest x-rays have revealed abnormalities that led to changes in man-
agement (16% to 21% of cases). Sputum Gram stain and culture have
a limited role in diagnosing ABECB due to frequent colonization of
airways in chronic bronchitis patients. Sputum analysis should be
reserved for patients with frequent exacerbations or in patients with
purulent sputum in whom there is a suspicion of more virulent or
resistant bacteria. Spirometry during an acute exacerbation has little
value, but it is important to know the pre-exacerbation state forced
expiratory volume in 1 second (FEV1) as a predictor of an adverse
outcome of ABECB.
TREATMENT
Therapy should be directed toward three major goals: relief of symp-
toms, prevention of transient loss of pulmonary function (can lead
to hospitalization), and reassessment of the disease in an attempt to
reduce the risk of any further exacerbations. Patients should be
removed from any further airway irritants including dust, pollutants,
and cigarette smoke. Pharmacologic therapy should be aimed at
decreasing the work of breathing, decreasing airway inflammation,
lowering the bacterial burden of the lower airways, and treating
resulting hypoxia.
The role of antimicrobial therapy in the treatment of ABECB
remains controversial despite numerous therapeutic trials of antibi-
otics for more than 50 years. Most comparative trials have found
equivalence in the use of antimicrobials. Differences in study end
points, differences in patient groups studied, and variations in anti-
biotics used have made the comparison of these studies difficult. Not
all antibiotics used to treat ABECB have the same spectrum of activ-
ity or pharmacokinetic properties. Therefore, numerous factors
should be considered when selecting an antimicrobial agent.
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Bronchitis 1019
Antibiotics should have both in vitro and in vivo activities against
the most commonly associated pathogens implicated in ABECB,
including H. influenzae, S. pneumoniae, and M. catarrhalis. In certain
subgroups of patients with severe obstructive disease, coverage might
need to be extended to include other pathogens such as S. aureus,
Pseudomonas aeruginosa, species in the family Enterobacteriaceae,
and atypical pathogens. Special attention should be paid to local and
regional resistance profiles for the major bacterial pathogens. For
example, at the Cleveland Clinic Foundation, the resistance rate of
S. pneumoniae to penicillin is 42%; in Detroit, it is as low as 5.2%.9
The major oral antimicrobials used to treat ABECB are listed in
Table 1. Antimicrobial therapy is appropriate for patients with an
S E C T I O N 12
ABECB if they fall into the Anthonisen type I or type II categories
but is not warranted in patients with a type III exacerbation. High-
risk patients, including patients who have significant pulmonary
impairment (FEV1 < 50% or lower than predicted), who have four
or more exacerbations per year, or who use supplemental oxygen or
chronic oral corticosteroids, should be treated with antibiotics
during ABECB. Due to emerging antimicrobial resistance, second-
generation macrolides and some second- and third-generation ceph-
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alosporins may be used to treat ABECB rather than traditional
first-line agents (aminopenicillins, doxycycline, trimethoprim-sulfa-
methoxazole [TMP-SMX]). A failure rate of 13% to 25% can be
expected after treatment of ABECB with a traditional first-line anti-
biotic (amoxicillin, TMP-SMX, tetracycline, erythromycin). Patients
who have structural lung disease, who chronically use corticoste-
roids, and who frequently use antimicrobials are at higher risk for
P. aeruginosa infection and should be treated with antipseudomonal
agents such as the fluoroquinolones. Patients who have been treated
in the past 3 months for ABECB and who present with a relapse or
reoccurrence of ABECB should be treated with a different class of
antibiotics.
Bronchodilator therapy, including inhaled -adrenergic agonists
(albuterol, fenoterol, metaproterenol, terbutaline) and anticholiner-
gic agents (ipratropium bromide), might improve airflow during
acute exacerbation. Although long-acting agonists in theory
provide longer symptomatic relief, these agents have not been studied
in ABECB and are not recommend at present. The choice of delivery
system-metered dose inhaler (MDI) versus nebulized bronchodila-
tors-should be determined based on cost and the patients ability to
use an MDI with a spacer. For patients already taking an oral meth-
ylxanthine, it is acceptable to continue this medication, keeping in
mind that drug interactions with certain antibiotics (ciprofloxacin,
clarithromycin) can occur and dosages need to be adjusted accord-
ingly. In patients with moderate to severe exacerbations , good evi-
dence supports treatment with oral or parenteral steroids for 5 to 14
days in general but not beyond 2 weeks. A number of randomized,
placebo-controlled trials have demonstrated that systemic steroids
lead to decreased treatment failure and shorten hospitalization rates.
The mechanism by which steroids increase recovery in ABECB is not
clear. Steroids are effective in decreasing airway edema and mucus
hypersecretion and in increasing secretory leukoproteinase inhibitor
(SLPI) in airway epithelial cells, which can have antiviral and anti-
bacterial activities. There is no defined role for inhaled steroids in
ABECB.
Supplemental oxygen should be provided carefully during an
acute exacerbation to avoid hypoxemia, with the goal of maintaining
a partial pressure of oxygen in arterial gas at or just above 60mmHg.
The decision regarding long-term need for oxygen should not be
made during an acute exacerbation, but patients should have an
ambulatory desaturation study performed before discharge from the
hospital to determine if supplemental home oxygen is needed.
Expectorants or cough suppressants can provide subjective relief, but
no evidence shows that these agents improve lung function or hasten
clinical recovery in ABECB. There is no beneficial effect of chest
physiotherapy in recovery from an ABECB. Instead, patients should
be kept adequately hydrated to decrease viscosity of mucus. There is
no evidence supporting the use of leukotriene receptor antagonists
 1020 Bronchitis

Table 1 Oral Antibiotics Used in the Treatment of Acute Exacerbations of Chronic Bronchitis

Antibiotic Spectrum of Activity and Resistance Pattern Comments

Penicillins
Amoxicillin No activity against atypical and beta-lactamase-producing Resistance limits use
bacteria
Penicillin resistance concerning with Streptococcus
pneumoniae
Limited activity against Enterobacteriaceae

Amoxicillin-clavulanate Activity against major pathogens More costly

No activity against atypical bacteria Gastrointestinal side effects
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Penicillin resistance concerning with S. pneumoniae

Moderate activity against Enterobacteriaceae

Cephalosporins
General Activity against major pathogens Alternative to beta-lactam agents and generally as effective
No activity against atypical bacteria

Resistance concerning with S. pneumoniae

Moderate activity against Enterobacteriaceae
S E C T I O N 12

Second Generation
Cefaclor Can be destroyed by Haemophilus influenzae and Associated with failure in patients with severe disease
Moraxella catarrhalis enzymes

Cefprozil Moderate H. influenzae activity

Cefuroxime

Loracarbef Moderate H. influenzae activity

Third Generation
Cefdinir

Cefibuten No activity against Staphylococcus aureus Poor gram-positive activity limits use
Marginal activity against S. pneumoniae

Cefixime Poor activity against S. aureus

Cefpodoxime

Macrolides
General Macrolide resistance concerning with S. pneumoniae
Active against atypical organisms
Not active against Enterobacteriaceae

Azithromycin Greatest activity against H. influenzae Short course of 3-5 days may be used

Clarithromycin Greatest activity against S. pneumoniae Alteration of taste may be an issue with bid dosing

Erythromycin Poor activity against H. influenzae Limited spectrum of activity

Tetracyclines
Doxycycline Covers major pathogens and atypical organisms Maybe an alternative to quinolones and macrolides when
S. pneumoniae resistance is common atypical coverage is needed

Minocycline Similar to doxycycline Limited spectrum of activity

Tetracycline Limited activity against major pathogens

Active against atypical bacteria

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 Bronchitis 1021

Table 1 Oral Antibiotics Used in the Treatment of Acute Exacerbations of Chronic Bronchitiscontd

Antibiotic Spectrum of Activity and Resistance Pattern Comments

Fluoroquinolones
General Active against all major pathogens, atypical pathogens,
Enterobacteriaceae, and Pseudomonas aeruginosa

Ciprofloxacin Least active against S. pneumoniae Use if P. aeruginosa coverage is required

Greatest activity against P. aeruginosa

Gatifloxacin Enhanced gram-positive activity

S E C T I O N 12
Levofloxacin

Moxifloxacin Greatest activity against S. pneumoniae

Other
Trimethoprim- Covers major pathogens Resistance limits use
sulfamethoxazole

PULMONARY
No atypical coverage
S. pneumoniae resistance is common

Adapted from Dever LL, Shashikumar K, Johanson WG: Antibiotics in the treatment of acute exacerbations of chronic bronchitis. Expert Opin Investig Drugs
2002;11:911-925.

in ABECB. In appropriate patients, noninvasive ventilation in acute Suggested Readings

exacerbations of COPD has been shown to reduce mortality, decrease
the need for intubation and mechanical ventilation, and decrease the
length of hospital and intensive care unit stay.
OUTCOMES
Hospitalization due to ABECB carries a short-term mortality rate of
approximately 4% in patients with mild to moderate disease. The
1-year mortality rate for patients with severe disease can be as high
as 46%. Many of the patients hospitalized for ABECB require subse-
quent readmissions because of persistent symptoms and often expe-
rience a temporary decrease in their functional abilities. Overall,
ABECB contributes significantly to the morbidity and the dimin-
ished quality of life experienced by people with COPD.
The COPD Guidelines Group of the Standards of Care Committee of the BTS. BTS
guidelines for the management of chronic obstructive pulmonary disease. Thorax
1997;52(Suppl 5):S1-S28.
Pauwels RA, Buist AS, Calverly PM, et al, for the GOLD Scientific Committee: Global
strategy for the diagnosis, management, and prevention of chronic obstructive pul-
monary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung
Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001;163:1256-
1276.
References
For a complete list of references, log onto www.expertconsult.com.

Summary

l AABECBs are characterized by an increase in cough,

sputum production, and dyspnea.
l Bacterial exacerbations of chronic bronchitis are the

leading cause of death in patients with chronic obstructive

pulmonary disease.
l After an ABECB, most patients experience a decrease in

quality of life, and more than one half of patients require

rehospitalization in the following 6 months.
l The most common bacteria isolated from the sputum in

approximately 60% of ABECBs are Haemophilus influenza,

Haemophilus parainfluenza, Streptococcus pneumoniae,
and Moraxella catarrhalis.
l The role of antimicrobial therapy in the treatment of mild

ABECBs remains controversial.

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