Bron Quit Is
Bron Quit Is
Bron Quit Is
18 (2004) 919937
* Corresponding author.
E-mail address: ralphg@medicine.ucsf.edu (R. Gonzales).
0891-5520/04/$ - see front matter 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.idc.2004.07.001
920 E. Aagaard, R. Gonzales / Infect Dis Clin N Am 18 (2004) 919937
Viral bronchitis
Respiratory viruses seem to cause or serve as a copathogen in most cases of
acute bronchitis in epidemiologic studies. The specic viruses most frequently
associated with acute bronchitis, in order of frequency of occurrence, are
inuenza, parainuenza, respiratory syncitial virus (RSV), coronavirus,
adenovirus, and rhinoviruses.
Recent studies have demonstrated the importance of RSV as the etiology
of ARIs in adults [35,36]. The impact of RSV is greatest in the elderly,
particularly those living in long-term care facilities, and those with underlying
heart and lung disease and malignancy [37]. Infection among exposed adults is
common, with attack rates approaching 50%, particularly in households with
children infected with RSV and in institutional settings [24,37]. Most young
and middle-aged adults develop asymptomatic or mildly symptomatic disease,
often closely resembling inuenza [38]. RSV can be associated with more
severe clinical disease and signicant morbidity, even in otherwise healthy
adults [24]. This morbidity seems to be in part secondary to induced airway
hyperreactivity.
In the elderly and institutionalized, lower respiratory illness with RSV is
common, with most studies reporting rates of pneumonia and death from
10% to 20% and 2% to 5%, respectively [37]. One report of an outbreak on
a geriatrics ward found intense coughing and fever in 96% of patients,
productive cough in 64%, and evidence of bronchopneumonia in 40% [39].
In this study, it is unclear whether RSV or secondary bacterial infection
caused these pneumonias.
Human metapneumovirus (hMPV), a paramyxovirus [33,40], has
emerged recently as an important cause of lower respiratory tract illness
and acute bronchitis. Human MPV has been detected in children, adults, the
elderly, and the immunocompromised in the Netherlands, Australia, North
America, the United Kingdom, and Finland [4145]. In one study, hMPV
was second only to RSV as a cause of respiratory tract illness presenting to
a university hospital in the Netherlands [45].
Similar to RSV, hMPV is primarily an illness of the winter months, most
commonly causing signicant illness in young children and immunocom-
promised and elderly individuals. Studies suggest that 25% to 50% of
hMPV-positive patients who have signicant respiratory tract illness have
underlying disease [46,47]. Among otherwise healthy adults, hMPV likely
causes predominantly mild respiratory illness, but may cause a small but
signicant portion (approximately 3%) of acute respiratory illness requiring
medical attention [4648].
Bacterial bronchitis
When microbiologic studies are performed on select patients who have
uncomplicated acute bronchitis in nonoutbreak settings, less than 10% of
922 E. Aagaard, R. Gonzales / Infect Dis Clin N Am 18 (2004) 919937
the elderly because they may present with atypical manifestations of pneu-
monia (and without vital sign or examination abnormalities) [107].
Conversely, during the inuenza season many patients will have fever or
tachycardia but not pneumonia. As a result, chest radiography often is
overused in the elderly and during inuenza season. In settings where chest
radiography is not available readily (eg, many private oce practices or rural
locations), patients who have cough illness (particularly elderly) may be
prescribed antibiotics to safeguard against missing a case of pneumonia.
Procalcitonin
Recent studies of procalcitonin in serum also have shown levels to
distinguish bacterial from viral illnesses [118,119]. Early procalcitonin assays
had a limited functional assay sensitivity (0.30.5 lg/L), and therefore were
not accurate for the diagnosis of early or localized infections [120,121]. A
newer assay with improved functional sensitivity (0.06 lg/L) has become
available in Europe, however. One recent study adopting a test-based
clinical algorithm with this rapid procalcitonin testing among adults
admitted to the hospital with lower respiratory tract infection demonstrated
a large reduction in antibiotic use, and equivalent outcomes [122].
E. Aagaard, R. Gonzales / Infect Dis Clin N Am 18 (2004) 919937 925
which were likely unnecessary [141]. The cost of these excess prescriptions
was estimated at $726 million. Similar high rates of inappropriate antibiotic
use are seen in Europe [142]. In addition, the result of antibiotic resistance
on antibiotic selection and clinical outcomes further increases health care
costs [143].
If they dont work, why are antibiotics so frequently prescribed for acute
bronchitis?
Physician education likely reects a small component of inappropriate
antibiotic use. Evidence suggests that physicians and patients are more likely
to believe that antibiotics are appropriate if purulent secretions are present
[144,145], despite signicant evidence to the contrary. Physician specialty
and level of training also are associated with antibiotic prescriptions for
ARIs. Family medicine physicians are more likely to prescribe antibiotics to
children with ARIs than pediatricians [146]. Also, providers that are further
from medical school graduation and practicing in rural areas are more likely
to prescribe antibiotics [147].
Antibiotic prescribing behavior is associated poorly with clinicians
subjective norms and intentions, which suggests that external forces such as
patient-specic beliefs and health plan factors play a greater role [148] than
physician knowledge. Patients frequently expect to receive antibiotics for
uncomplicated acute bronchitis [149,150] and patients or parents who expect
antibiotics are more likely to receive them [150,151]. Communication
elements associated with antibiotic prescriptions for ARIs include patient
appeals to specic life circumstances (eg, a pressing social engagement),
identication of a previous positive experience with antibiotic use [81], or
being labeled as having acute bronchitis rather than a chest cold [149].
Not surprisingly, clinicians with greater patient workloads prescribe
antibiotics for ARIs more frequently, likely reecting the perceived time it
would take to discuss the inappropriateness of antibiotic use in ARIs [152].
Other health plan factors that may contribute to prescribing behavior
include restricting formularies and practice characteristics such as payment
structure. A recent survey of physicians attitudes regarding the role of
societal risks in making antibiotic treatment decisions for individual patients
found that societal concerns about promoting antibiotic resistance ranked
below patient-centered factors such as ease of use and cost to the patient
[153].
Despite physician concerns about patient expectations, most studies nd
that satisfaction with care for ARIs is tied more closely to how much time
the physician spent explaining the illness, rather than receipt of antibiotics
[150,151,154]. Communication elements associated with high patient
satisfaction include positive responses to the following statements: the
doctor spent enough time with me; the doctor explained the illness to
me; and the doctor treated me with respect [147]. An intervention
E. Aagaard, R. Gonzales / Infect Dis Clin N Am 18 (2004) 919937 927
Bronchodilator therapy
Three randomized, controlled trials have demonstrated a consistent
benet to bronchodilator treatment [163165]. Approximately 50% fewer
patients report the presence of cough after 7 days of treatment. This benet
seems to be greatest in the subset of patients who had bronchial
hyperresponsiveness. A large trail of patients who had URI-associated
cough, but not clearly acute bronchitis, reported no benet of bronchodi-
lator treatment [166]. A meta-analysis of these studies showed no signicant
928 E. Aagaard, R. Gonzales / Infect Dis Clin N Am 18 (2004) 919937
Antitussive therapy
The eectiveness of antitussive therapy seems to depend on the cause of
cough illness. Acute or early cough caused by colds and other upper
respiratory tract infections does not seem to respond to dextromethorphan
or codeine. Cough of greater than 3 weeks duration, cough associated with
underlying lung disease, and experimentally induced cough seem to respond
to these agents. Given that the cough of acute bronchitis often lasts for 2 to
3 weeks, these agents likely have a modest impact on cough severity and
duration.
Immunomodulating therapies
Most trials of immunomodulatory (alternative) therapies have been
conducted on patients who have early symptoms of colds and nonspecic
ARIs. As a result, these data are dicult to extrapolate to patients who have
acute bronchitis, who generally present later and with more severe illness.
Vitamin C at doses exceeding 1 g/d seems to oer small but signicant
reduction in illness duration of about 0.5 day per cold episode [168]. Well-
performed clinical trials comprising mostly small studies of zinc gluconate
and zinc acetate lozenges have had mixed results [169] and their benet is
unclear. Echinacea seems to be of benet in some preparations [170], but
there is signicant heterogeneity of study design, as well as preparations
tested. Also, quality control of echinacea preparations sold to the
community is poor, with one study demonstrating that 10% of single-herb
echinacea preparations in one metropolitan area had no active ingredient,
and less than half met the quality standards described on the label [171].
A recent randomized, double-blind, placebo-controlled trial has shown the
benet of an extract of Pelargonium sidoides roots in acute bronchitis [172].
This plant extract is used commonly in Europe and Mexico. Its mechanism of
action is poorly understood, but is believed to be immunomodulatory in
nature, having been used rst in the early 1900s as a treatment for
tuberculosis. In the recent study, adult patients who had acute bronchitis of
greater than 48 hours duration and a bronchial severity score (BSS) of at least
5 points were enrolled. Patients were excluded if they were to receive or
recently had received antibiotics or had other serious illnesses. Patients were
randomized to receive active ingredient or color-, smell-, viscosity-, and taste-
matched placebo. Among patients receiving pelargonium, decrease in BSS on
E. Aagaard, R. Gonzales / Infect Dis Clin N Am 18 (2004) 919937 929
day 7 was 5.9 points compared with 3.2 points for placebo (P \ .0001).
Duration of illness (P \ .001) and inability to work (16% versus 43%, P \
.0001) were signicantly less in the pelargonium group compared with
placebo. Further studies are necessary to conrm these interesting results. In
the United States, Pelargonium sidioides is marketed under the trade name
Umcka (Natures Way, Springville, Utah).
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