INTRODUCTION Bronchiectasis is a syndrome of chronic cough and daily viscid sputum

production associated with airway dilatation and bronchial wall thickening. Multiple conditions
are associated with the development of bronchiectasis, but all require an infectious insult and
usually also impairment of drainage, airway obstruction, and/or a defect in host defense.
Of the broad spectrum of causes of noncystic fibrosis bronchiectasis, only a few respond to
direct treatment (eg, certain immunodeficiencies, nontuberculous mycobacterial infection,
allergic bronchopulmonary aspergillosis). Instead, treatment of bronchiectasis is aimed at
controlling infection and improving bronchial hygiene [1,2]. Surgical extirpation of affected areas
may be useful in selected patients.
The treatment of bronchiectasis will be reviewed here. The diagnosis and treatment of cystic
fibrosis and the clinical manifestations and diagnosis of bronchiectasis are discussed
separately. (See "Cystic fibrosis: Clinical manifestations and diagnosis" and "Cystic fibrosis:
Overview of the treatment of lung disease" and "Cystic fibrosis: Antibiotic therapy for lung
disease" and "Clinical manifestations and diagnosis of bronchiectasis in adults".)
TREATING THE UNDERLYING DISEASE For most causes of bronchiectasis, treatment of
the underlying disease is not possible, as the bronchiectasis is a manifestation of scarring that
resulted from a prior injury or infection (eg, severe pneumonia, pertussis in childhood) or a
result of an ongoing problem with secretion clearance that does not have a specific treatment
(eg, primary ciliary dysfunction). However, some disease processes can be controlled to
prevent further scarring. The evaluation and diagnosis of the underlying causes of
bronchiectasis are discussed separately (table 1 and table 2 andtable 3). (See "Clinical
manifestations and diagnosis of bronchiectasis in adults".)
Examples of disease processes in which specific therapies may prevent progression of
bronchiectasis include the following:
While nontuberculous mycobacterial infection can be an opportunistic
infection in a patient with bronchiectasis, it can also be a primary cause
of bronchiectasis. It is usually treated directly to prevent further lung
injury. (See "Overview of nontuberculous mycobacterial infections in HIV-
negative patients" and "Treatment of nontuberculous mycobacterial
infections of the lung in HIV-negative patients".)
Certain primary immunodeficiencies can be treated with immunoglobulin
purified from pooled human plasma given intravenously (IVIG) or
subcutaneously (SCIG). The use of these preparations is discussed
separately. (See "Immune globulin therapy in primary
immunodeficiency".)
Treatment of recurrent aspiration due to swallowing difficulties or severe
gastroesophageal reflux with aspiration may help prevent progression of
bronchiectasis. (See "Diagnosis and treatment of oropharyngeal
dysphagia" and"Approach to refractory gastroesophageal reflux disease
in adults".)
Allergic bronchopulmonary aspergillosis, in which central bronchiectasis
is caused by an inflammatory response to aspergillus colonization of the
airway, is treated with glucocorticoids and antifungal agents.
(See "Allergic bronchopulmonary aspergillosis", section on 'Treatment'.)
While unproven, it is hoped that treating the underlying disease will
prevent progression of bronchiectasis due to rheumatic or other
inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel
disease, and sarcoidosis. (See "Overview of lung disease associated
with rheumatoid arthritis", section on 'Bronchiectasis' and "Pulmonary
complications of inflammatory bowel disease", section on 'Airway
involvement' and "Treatment of pulmonary sarcoidosis with
glucocorticoids".)
Patients with symptomatic bronchiectasis due to tracheobronchomegaly
may benefit from placement of a stent or tracheobronchoplasty to
maintain airway patency and improve secretion clearance. (See 'Airway
stabilization for tracheobronchomegaly' below and "Tracheomalacia and
tracheobronchomalacia in adults", section on 'Treatment'.)
TREATMENT OF ACUTE EXACERBATIONS Deciding when a patient has an acute
exacerbation depends upon symptomatic changes rather than any specific laboratory feature.
Acute bacterial infections are usually heralded by increased production of sputum that is more
viscous with darker color, often accompanied by lassitude, shortness of breath, and pleuritic
chest pain. Systemic complaints such as fever and chills are generally absent. Sputum is
obtained for gram stain and culture prior to antibiotic administration. A chest radiograph is
performed in patients with respiratory distress or systemic complaints to exclude the possibility
of pneumothorax or pneumonia.
The colonizing bacterial flora in patients with bronchiectasis is slightly different from that seen
with chronic bronchitis. Frequently isolated pathogens in bronchiectasis include Haemophilus
influenzae, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa (especially
mucoid types), and, less frequently, Streptococcus pneumoniae [3,4]. The likelihood of resistant
organisms tends to increase with the number of prior courses of antibiotics. The presence of P.
aeruginosa, particularly if the patient has had prior courses of anti-pseudomonal agents, often
necessitates hospital admission for intravenous antibiotics.
Outpatient treatment Most afebrile, clinically stable patients with an exacerbation of
bronchiectasis can be treated as outpatients. The initial selection of an oral antibiotic for an
exacerbation of bronchiectasis is generally based on previous sputum bacteriology results, the
history of success or failure of prior regimens, and the presence of allergy to antimicrobial
agents.
Sputum showing sensitive organisms For patients whose sputum
cultures do not show beta-lactamase-positiveH.
influenzae or Pseudomonas, reasonable initial antibiotic choices
include amoxicillin, 500 mg three times daily, or a macrolide, based on
the typical colonization patterns noted above. Alternatively, other
antibiotics with a similar spectrum of coverage may be used. High-dose
regimens (amoxicillin 1 gram three times daily, or 2 grams twice daily)
may be needed in patients with severe bronchiectasis who are
chronically colonized with H. influenzae, but may be difficult to tolerate
due to gastrointestinal adverse effects such as diarrhea [2]. The initial
antibiotic selection can be modified in a couple of days based on the
response to therapy and results of the sputum culture and sensitivity.
Sputum culture growing beta-lactamase-positive organism In the
presence of beta-lactamase producing H. influenzae, antibiotic choices
include amoxicillin-clavulanate, a second or third generation
cephalosporin, azithromycinor clarithromycin, doxycycline, or a
fluoroquinolone [2]. (See "Microbiology, epidemiology and treatment of
Haemophilus influenzae", section on 'Treatment'.)
Sputum culture data not available For those without culture
information, a fluoroquinolone (eg, levofloxacin,moxifloxacin) is a
reasonable, broad spectrum, therapeutic option [5].
Sputum growing sensitive Pseudomonas For patients with known
colonization with Pseudomonas, the initial antibiotic selection depends
on the sensitivity patterns of the organisms isolated. In the absence of
known resistance to quinolones, the usual choice is ciprofloxacin, 500 to
750 mg twice daily [2].

Because of the propensity of P. aeruginosa to develop resistance and
the limited of availability of oral agents, the efficacy of adding
inhaled tobramycin solution (TS) to oral ciprofloxacin was studied. In a
multicenter trial, 53 patients with known P. aeruginosa infection who
were having exacerbations of bronchiectasis were randomly assigned to
receive ciprofloxacin plus inhaled TS or ciprofloxacin plus placebo for two
weeks [6]. The addition of inhaled TS to ciprofloxacin did not improve
clinical outcomes compared to ciprofloxacin alone, although there was a
marked reduction of Pseudomonas density in the sputum of patients who
received inhaled TS plus ciprofloxacin. Wheezing was more common in
the inhaled TS plus ciprofloxacin group.

Based on current data, inhaled aerosols of antibiotics, such as TS,
cannot be recommended alone or in combination with ciprofloxacin for
acute exacerbations in bronchiectasis. Certain aerosolized antibiotics
may be helpful for prophylaxis. (See 'Inhaled antibiotics' below.)
Sputum growing resistant Pseudomonas The nonquinolone
antibiotics typically used for resistant Pseudomonasare not available
orally and require intravenous administration for a systemic effect.
Intravenous antibiotics for exacerbations due to resistant Pseudomonas
are discussed below and separately. (See 'Inpatient treatment' below
and "Treatment of Pseudomonas aeruginosa infections", section on
'Antibiotic choices'.)

As noted above, inhaled aerosols of antipseudomonal antibiotics are not
adequate treatment for exacerbations of bronchiectasis.
Duration of therapy The optimal duration of therapy is not well-
defined. Clinical experience favors a duration of 10 days for patients with
a first time or few exacerbations [5,7,8]. For patients with resistant
organisms such as P. aeruginosa, a 14 day course is preferred [2].
Sputum culture and sensitivity to help define antibiotic selection are
indicated in patients who fail to respond to the initial antibiotic, or who
have repeated symptomatic attacks over a short period of time.
Inpatient treatment Initial inpatient treatment of an exacerbation is appropriate for patients
with characteristics such as increased respiratory rate 25/minute, hypotension, temperature
38C, hypoxemia (pulse oxygen saturation <92 percent), or failure to improve after oral
antibiotics (and no facilities for home intravenous therapy) [2]. As with outpatient treatment, a
sputum sample is obtained for bacteriologic culture prior to initiation of antibiotics. Blood
cultures are obtained in patients with a fever 38C or evidence of respiratory distress.
If the reason for hospital admission is to initiate intravenous antibiotics because the patient has
known colonization withPseudomonas resistant to oral quinolones (rather than due to severity of
illness), the initial antibiotic choice is based on the sensitivity profile from culture data and
history of allergy to antibiotics.
If sputum culture data are not available, local antibiotic resistance patterns and responses to
recent antibiotics guide empiric antibiotic selection. For example, if the patient has failed an oral
quinolone, coverage for resistant Pseudomonas and methicillin resistant Staphylococcus
aureus should be included, pending updated culture results.
It is controversial whether single or dual (eg, beta-lactam plus aminoglycoside) antibiotic
therapy is preferable for flares of bronchiectasis due to Pseudomonas [2]. A meta-analysis of
studies examining this question in patients with cystic fibrosis was unable to determine which
course of therapy is better [9]. We typically use a single agent (eg, antipseudomonal penicillin
with or without a beta-lactamase inhibitor, ceftazidime, aztreonam) unless the patient appears
acutely ill such that an incipient Pseudomonas pneumonia seems possible. In the latter case,
we typically add a second agent (eg, fluoroquinolone, aminoglycoside). Aminoglycosides should
not be used as monotherapy. The question of single versus dual therapy and antibiotic selection
and dosing for Pseudomonas pneumonia are discussed in greater detail separately.
(See"Pseudomonas aeruginosa pneumonia", section on 'Treatment' and "Treatment of
Pseudomonas aeruginosa infections".)
Use of aminoglycoside antibiotics requires careful dosing and monitoring to avoid renal or
ototoxicity. (See"Aminoglycosides".)
Once the patient has stabilized and results of initial cultures are available, the antibiotic regimen
can be narrowed to the most effective/least toxic regimen.
Atypical pathogens Two colonizing organisms that are particularly problematic and difficult
to eradicate are Mycobacterium avium complex (MAC) and Aspergillus species.
Mycobacterium avium complex Mycobacterium avium complex (MAC) refers to infections
caused by one of two nontuberculous mycobacterial species, either M. avium or M.
intracellulare. MAC and other nontuberculous mycobacteria are often harbored in damaged lung
tissue and bronchiectatic airways. A detailed discussion about the treatment of MAC and other
nontuberculous mycobacteria in the lung is presented elsewhere. (See "Treatment of
nontuberculous mycobacterial infections of the lung in HIV-negative patients" and "Microbiology
of nontuberculous mycobacteria".)
Aspergillus species Allergic bronchopulmonary aspergillosis is a cause of central
bronchiectasis in patients with asthma and can also develop in patients with bronchiectasis due
to another cause. For patients with allergic bronchopulmonary aspergillosis and a total serum
IgE level >1000 IU/mL (>2400 ng/mL), the usual initial therapy is oralprednisone 0.5 to
1 mg/kg per day for two weeks followed by alternate day therapy tapered over three to six
months. A 16 week course of an antifungal agent, such as itraconazole or voriconazole, may be
added in patients who require substantial doses of glucocorticoids. (See "Allergic
bronchopulmonary aspergillosis", section on 'Treatment'.)
PREVENTION OF EXACERBATIONS Infection plays a major role in causing and
perpetuating bronchiectasis, so reducing the microbial load and attendant mediators is a
cornerstone of therapy [10]. A variety of suppressive or preventive antibiotic regimens have
been studied as methods to reduce the frequency of exacerbations and prevent further loss of
lung function.
One difficult issue is colonization with Pseudomonas aeruginosa, which has a propensity to
persist in damaged (eg, bronchiectatic) airways, possibly due to its ability to produce virulence
factors and to circumvent immune defenses with quorum signaling and biofilm
production. Pseudomonas can also interact adversely and directly with the airway epithelial
surface and the cystic fibrosis conductance regulator (CFTR) protein [11]. (See "Cystic fibrosis:
Genetics and pathogenesis", section on 'Chronic lung infection' and "Epidemiology and
pathogenesis of Pseudomonas aeruginosa infection", section on 'Chronic infection in cystic
fibrosis'.)
Patients colonized with P. aeruginosa have reduced quality of life indices, more extensive
bronchiectasis on CT, accelerated decline in pulmonary function, and increased number of
hospitalizations, compared to patients colonized with Haemophilus influenzae [12,13]. For this
reason, attempts are often made to eradicate P. aeruginosa infection with variable success.
Macrolides For patients with bronchiectasis who have recurrent exacerbations, we suggest
preventive therapy with a macrolide antibiotic. Our threshold for the initiation of preventive
antibiotics is two or more exacerbations within one year. Chronic low-dose administration of
macrolide antibiotics appears to have an effect that is not solely antimicrobial [14]. A variety of
alternative mechanisms have been proposed to explain the observed benefit, including
reduction of biofilm around virulent gram negative organisms such as P. aeruginosa, retardation
of neutrophilic influx, stabilization of nuclear and cellular membranes, and promotion of gastric
emptying that may reduce potential for acid reflux. Daily or three times weekly use of a
macrolide has been found to be efficacious in the management of cystic fibrosis even in patients
colonized withPseudomonas. (See "Cystic fibrosis: Overview of the treatment of lung disease",
section on 'Macrolide antibiotics'.)
Three multicenter, randomized trials have shown reduced rates of exacerbations with use of a
macrolide as compared to placebo in patients with noncystic fibrosis bronchiectasis. The trials
are small but have a consistent finding of a reduction in exacerbations.
In the Effectiveness of Macrolides in patients with Bronchiectasis
using Azithromycin to Control Exacerbations (EMBRACE) trial, 141
patients with at least one exacerbation of bronchiectasis in the prior year
were randomly assigned to take azithromycin 500 mg or placebo, orally
three times a week for six months [15]. Azithromycin was associated with
a decrease in exacerbations compared with placebo (RR 0.38, 95% CI
0.260.54). However, no significant difference was noted in lung function
or quality of life.
In the Bronchiectasis and Long-term Azithromycin treatment (BAT) trial,
83 patients with three or more exacerbations of noncystic fibrosis
bronchiectasis in the prior year were randomly assigned to take
azithromycin 250 mg or placebo daily for 12 months [16]. The median
number of exacerbations was zero in the azithromycin group and two in
the placebo group. Thirty-two placebo-treated versus 20 azithromycin-
treated individuals had at least 1 exacerbation (hazard ratio, 0.29 [95%
CI, 0.16-0.51]). However, the rate of colonization with azithromycin
resistant organisms was 88 percent in the azithromycin group and 26
percent in the placebo group. Abdominal pain and diarrhea were more
common in the azithromycin group.
The Bronchiectasis and Low-dose Erythromycin Study (BLESS)
randomly assigned 117 patients two or more exacerbations of noncystic
fibrosis bronchiectasis in the prior year to take erythromycin 250 mg or
placebo twice daily for one year [17]. Protocol defined pulmonary
exacerbations were modestly reduced in the erythromycin group (mean
1.29 versus 1.97 per patient per year, incidence rate ratio [IRR], 0.57
[95% CI 0.42-0.77]). The volume of sputum produced and rate of decline
in forced expiratory volume in one second (FEV
1
) were also decreased,
although the clinical importance of these changes appears small.
Erythromycin increased the proportion of macrolide-resistant
oropharyngeal streptococci.
The impact of adverse effects, such as gastrointestinal symptoms, hepatotoxicity, decreased
hearing, and increased bacterial resistance, will need ongoing review and attention. In addition,
macrolide antibiotics are associated with the potential for prolongation of the QT interval.
Clinicians should assess the risk of torsades de pointes when considering a macrolide for long-
term treatment in patients at risk for cardiovascular events. Patients at particular risk include
those with existing QT interval prolongation, hypokalemia, hypomagnesemia, significant
bradycardia, bradyarrhythmias, uncompensated heart failure, and those receiving certain
antiarrhythmic drugs. (See "Azithromycin, clarithromycin, and telithromycin", section on 'QT
interval prolongation'.)

In order to avoid development of nontuberculous mycobacteria that are macrolide resistant,
some experts (and we agree) obtain sputum stains and cultures for nontuberculous
mycobacterial (NTM) infection prior to initiating long-term azithromycintherapy. Preventive
monotherapy with a macrolide antibiotic is NOT initiated if NTM are identified on culture.
(See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Macrolide
antibiotics' and 'Mycobacterium avium complex'above.)
Daily suppressive nonmacrolide antibiotics Daily oral nonmacrolide antibiotic treatment
has been studied in small case series, but not randomized trials. As an example, among 10
patients treated with ciprofloxacin (500 to 1500 mg/day in two to three divided doses) for at least
90 days, symptomatic improvement occurred in seven [18]. A major concern with long-term
quinolone suppressive therapy is the development of resistant strains of P. aeruginosa [2].
Based on clinical experience, we usually reserve daily suppressive nonmacrolide antibiotic
regimens (eg, amoxicillin 500 mg twice daily,doxycycline 100 mg twice daily) for patients with
three or more exacerbations a year who are not candidates for long-term macrolide
administration and are not colonized with P. aeruginosa [2]. Patients who are colonized with P.
aeruginosa may be candidates for inhaled antibiotic therapy, as described below.
Inhaled antibiotics The role of inhaled antibiotics in noncystic fibrosis bronchiectasis is
unclear. Inhaled antibiotics (eg,tobramycin, gentamicin) have been investigated primarily in
patients with cystic fibrosis when P. aeruginosa is present in the respiratory secretions. Benefits
in these patients include reduced sputum Pseudomonas density, improved FEV
1
, and
decreased hospitalizations. Inhaled antibiotics may also play a role in the management of some
patients with noncystic fibrosis bronchiectasis and Pseudomonas colonization, but no agent is
approved for this purpose by the US Food and Drug Administration (FDA). (See "Cystic fibrosis:
Antibiotic therapy for lung disease", section on 'Inhaled antibiotics'.)
Studies of inhaled antibiotics in noncystic fibrosis bronchiectasis include the following:
Aerosolized tobramycin The use of aerosolized tobramycin has been
studied in patients with noncystic fibrosis bronchiectasis [19-22]. One trial
randomly assigned 74 patients with non-CF bronchiectasis and
bacteriologic evidence of P. aeruginosa infection to receive aerosolized
tobramycin (300 mg, twice daily) or aerosolized placebo for 28 days [19].
Patients in the treatment group demonstrated a 10,000-fold reduction
in Pseudomonas density, but no change in FEV
1
as compared to
controls.

In a six month crossover study of aerosolized tobramycin versus placebo
in 30 patients, there was no difference in the exacerbation rate, but the
number of hospitalizations and duration of hospital stay were modestly
reduced during the tobramycin phase [23]. Of concern, four patients in
the tobramycin group and one in the placebo group died during the
study.

In a small, uncontrolled study, aerosolized tobramycin (300 mg, twice
daily) was administered to 41 patients with non-CF bronchiectasis and a
history of P. aeruginosa infection. The protocol alternated two weeks of
treatment with two weeks without therapy for a total of 12 weeks [20].
Treatment was associated with a decrease in symptoms and
improvements in health-related quality of life (QOL). However, 10 of 41
patients (24 percent) were unable to complete the protocol because of
side effects (cough, wheezing, worsened dyspnea), and two of the
patients who completed the trial acquired tobramycin-resistant P.
aeruginosa.
Aerosolized gentamicin Aerosolized gentamicin, prepared by diluting
the intravenous preparation with saline, was assessed in 58 patients with
non-CF bronchiectasis, who were randomly assigned to use nebulized
gentamicin 80 mg twice daily or normal saline placebo for a year [22].
Patients were aware of their medication assignment. The primary
endpoint of reduction in sputum bacterial density was achieved in the
gentamicin cohort as compared to no reduction in the saline group.
Thirty-one percent of the gentamicin cohort had complete eradication
of Pseudomonas at the end of 12 months. Favorable secondary
endpoints in subjects taking gentamicin included reduction in
exacerbations and improved patient outcomes by analysis of two
questionnaires. However, no differences were seen in the 24 hour
sputum volume or in spirometric parameters. In addition, the sputum
bacterial density was no longer different from control at the three month
follow-up visit. Further study is needed before routine use of nebulized
intravenous gentamicin in these patients.
Inhaled aztreonam Aztreonam is a monobactam with a monocyclic
beta-lactam structure. As inhalation of the intravenous preparation of
aztreonam induces airway inflammation, a lysine salt formulation was
developed for inhalation. In patients with cystic fibrosis
and Pseudomonas airway colonization, inhaled aztreonam 75 mg 3 times
daily (at least 4 hours apart) for 28 days improved FEV
1
, decreased
sputum Pseudomonas density, and delayed time to need for intravenous
or other inhaled antipseudomonal antibiotics compared with placebo. All
of the studies have used a particular mesh nebulizer for administration of
aztreonam, called the Altera eFlow. Preliminary evidence suggests that
inhaled aztreonam is not beneficial in noncystic fibrosis bronchiectasis.
(See "Cystic fibrosis: Antibiotic therapy for lung disease", section on
'Inhaled aztreonam lysine' and "Delivery of inhaled medication in adults",
section on 'Mesh nebulizers'.)
All of the inhaled antibiotics have the potential to cause bronchospasm, so the first treatment is
generally administered in a supervised setting with spirometry before and 15 and 30 minutes
after the test dose [2]. If a patient is going to develop bronchospasm, it will usually occur during
the first treatment. Albuterol should be immediately available for inhalation should
bronchospasm develop. Subsequently, pretreatment with an inhaled beta-agonist
bronchodilator can be given to those patients who develop mild bronchoconstriction. For those
whose FEV
1
decreases by >15 percent or >200mL after antibiotic inhalation, we generally do
not administer further doses [2].
Patients treated with inhaled antibiotics should be assessed for medication-related adverse
effects (eg, throat irritation or pain, abnormal taste sensation, cough, chest discomfort) and
development of resistant organisms.
Other inhaled antibiotics are under investigation for noncystic fibrosis bronchiectasis,
including colistin and both dry powder and dual-release (contains free and liposomal drug)
preparations of ciprofloxacin [24,25]. (See "Cystic fibrosis: Antibiotic therapy for lung disease",
section on 'Inhaled colistin'.)
Intermittent intravenous antibiotics Intermittent intravenous antibiotics are not part of
routine care of patients with stable bronchiectasis. In the absence of an acute exacerbation,
administration of intravenous antibiotics should be reserved for patients with resistant
organisms (such as Pseudomonas) being prepared for major surgery, such as resection of a
bronchiectatic region of lung or another procedure during which pulmonary function may be
compromised.
Mucolytic agents and airway hydration A variety of agents, such as nebulized hypertonic
saline solution, mannitol, and mucolytic agents, have been developed to help patients clear their
airways of secretions. Among these therapies, some evidence favors hypertonic saline, but the
other therapies have not been proven to be beneficial in noncystic fibrosis bronchiectasis. In
contrast, nebulized hypertonic saline and dornase alfa are beneficial in cystic fibrosis.
Avoidance of dehydration is logical, but of unproven benefit. (See "Role of mucoactive agents in
the treatment of COPD" and "Cystic fibrosis: Overview of the treatment of lung disease", section
on 'Agents to promote airway secretion clearance'.)
Nebulized hypertonic saline Nebulized hyperosmolar agents,
including hypertonic (6 to 7 percent) saline andmannitol, have been
studied as mucokinetic therapies [26]. Their mechanism of action is
thought to be related to improved mucus rheology, increased ciliary
motility, and enhanced cough clearance. Another possibility, suggested
by in vitro data, is that low mucus salinity rather than under hydration
contributes to mucus retention, which is counteracted by hypertonic
saline [27]. We use hypertonic saline in patients with tenacious or
copious phlegm to augment expectoration, based on clinical experience.

The efficacy of nebulized hypertonic saline (6 percent) was examined in
40 patients with noncystic fibrosis bronchiectasis who were randomly
assigned to treatments with hypertonic saline or isotonic saline daily for
12 months [28]. No between group differences were found in
exacerbation rates, quality of life, FEV
1
, or sputum colonization.
Nebulized mannitol Mannitol is a hyperosmolar agent that is thought
to hydrate airway secretions, which might theoretically improve mucus
clearance. However, further study is needed to determine whether
inhaled mannitol improves patient important outcomes such as
exacerbations or antibiotic use. Aerosol dry powder mannitol is not an
approved drug in the United States.

A randomized trial of aerosolized dry powder mannitol 320 mg (231
patients) versus placebo (112 patients) twice daily for three months
found no difference in quality of life [29]. A lower daily sputum weight was
noted in the placebo group, but this was attributed to greater antibiotic
usage in that group, rather than to an effect of mannitol inhalation.

Changes in airway osmolarity caused by mannitol inhalation can lead to
mast cell mediator release and bronchoconstriction in patients with
asthma. Thus, mannitol use can only be considered in patients with
bronchiectasis who do not have asthma or have a negative mannitol
provocation test. (See "Bronchoprovocation testing", section on
'Mannitol'.)
Mucolytic agents Studies of mucolytic agents have yielded variable
results. As an example, acetylcysteine, a mucolytic agent that cleaves
disulfide bonds in glycoproteins, has not demonstrated clear benefit
among patients with cystic fibrosis (CF), and there are no well-designed
studies in non-CF-related bronchiectasis [30].

Aerosolized dornase alpha (recombinant deoxyribonuclease, also
called DNase), which breaks down DNA (a major gelatinous product of
neutrophils), improves pulmonary function (FEV
1
) and reduces
hospitalizations in patients with CF [31], but is not effective in non-CF-
related bronchiectasis and is potentially harmful [32]. (See "Role of
mucoactive agents in the treatment of COPD".)
Systemic hydration Maintenance of euvolemia with oral liquids is a
logical, although unstudied, approach to avoiding inspissation of
secretions. There is no evidence that hydration beyond euvolemia
provides any benefit.
Chest physiotherapy We suggest that all patients with bronchiectasis receive regular chest
physiotherapy. Bronchiectasis is the prototypical disease for which secretion loosening
combined with enhanced removal techniques should be salutary, although large population and
long-term studies of efficacy are lacking [33]. Based on clinical experience, chest physiotherapy
(also known as bronchial hygiene) helps to remove the tenacious secretions and mucous plugs
that frequently complicate bronchiectasis.
Most studies have been small, uncontrolled, short-term, and without patient-important
endpoints. However, one trial assessed the efficacy of an oscillatory positive expiratory
pressure (PEP) device used for three months [34]. Twenty patients who were not practicing
chest physiotherapy were randomly assigned to PEP twice daily versus no device, in a
crossover design. The primary endpoint was the Leicester Cough Questionnaire (LCQ);
secondary end-points included changes in sputum volume, spirometry, exercise capacity,
exacerbation frequency, and sputum microbiology. After three months of using oscillatory PEP,
a significant improvement in the LCQ, a reduction in sputum volume, and an improved exercise
capacity were noted. No change was found in spirometric parameters, exacerbation frequency,
or sputum microbiology.
Numerous chest physiotherapy techniques and devices exist to loosen viscid secretions
mechanically; the most popular are listed in the table (table 4) [35,36]. Some of the techniques
and devices have been popularized by patients and clinicians, despite a paucity of good data.
The choice of a technique or device should be based upon patient comfort, cost, and the
patient's ability to use the technique or device with minimal interference to their lifestyle and
minimal detriment to coexisting medical conditions. (See "Cystic fibrosis: Overview of the
treatment of lung disease", section on 'Chest physiotherapy'.)
OTHER MEDICAL THERAPIES Other potential, but less well-studied, therapies for
bronchiectasis, include inhaled bronchodilators, anti-inflammatory medications, anti-
gastroesophageal reflux therapies, and immunization.
Bronchodilators Airway reactivity, presumably due to transmural inflammation, is often
present in patients with bronchiectasis. Aerosol bronchodilator therapy, as used in asthma and
COPD, may be appropriate but has not been studied rigorously in bronchiectasis.
When deciding whether to prescribe a bronchodilator for bronchiectasis, we usually assess
airflow obstruction on spirometry before and after bronchodilator. For those patients with
bronchodilator reversibility, we typically initiate a trial of a short-acting beta agonist [2]. If
symptoms improve on therapy, either a short or long-acting bronchodilator is continued.
In a 12 month randomized trial of 40 patients with noncystic fibrosis bronchiectasis, the
combination of inhaled formoterolwith budesonide 640 mcg/day was compared with inhaled
budesonide 1600 mcg/day alone [37]. The formoterol group experienced improved dyspnea,
coughing, and health related quality of life (HRQL) based on a questionnaire (St. George's
Respiratory Questionnaire [SGRQ]-Spanish version) without alteration in sputum pathogens or
an increase in adverse effects. Further study is needed before long-acting beta-adrenergic
agonists are used routinely in patients with bronchiectasis who lack wheezing or reversible
airflow limitation.
Antiinflammatory medications Since inflammation and neutrophilic mediator release play a
major role in bronchiectasis, antiinflammatory agents such as oral or inhaled glucocorticoids
and nonsteroidal anti-inflammatory agents (NSAIDs) might theoretically be beneficial. However,
there are no large randomized trials upon which to make recommendations regarding the
efficacy of any of these agents in adults with stable or acute bronchiectasis.
We reserve systemic glucocorticoids for acute exacerbations of bronchiectasis that are
accompanied by wheezing suggestive of concomitant asthma or allergic bronchopulmonary
aspergillosis. In other patients, systemic glucocorticoids are avoided because they depress host
immunity, promote bacterial and fungal colonization, and may perpetuate infection. In addition,
oral glucocorticoids have other significant adverse effects that are discussed separately.
(See "Major side effects of systemic glucocorticoids".)
Current evidence is insufficient to support routine inhaled glucocorticoid therapy for patients with
bronchiectasis but without concomitant asthma [2,38]. Several small trials in noncystic fibrosis
bronchiectasis suggested that inhaled glucocorticoids might improve lung function and dyspnea,
while reducing cough, sputum production, and the need for beta-agonist rescue [39-41].
However, a meta-analysis of six placebo-controlled trials with a total of 278 subjects did not find
a significant difference in spirometry, exacerbation rate or sputum volume [38].
Inhaled glucocorticoids have potential adverse effects to keep in mind. As an example, patients
with bronchiectasis may have underlying adrenal insufficiency that can be exacerbated by
inhaled glucocorticoid use [42]. Adverse effects of inhaled glucocorticoids are discussed
separately. (See "Major side effects of inhaled glucocorticoids".)
Oral ibuprofen is occasionally used to reduce airway inflammation in children aged 6 to 13 with
cystic fibrosis, but data are insufficient to support a role for nonsteroidal anti-inflammatory
agents (NSAIDs) in adult noncystic fibrosis bronchiectasis [43]. (See "Cystic fibrosis: Overview
of the treatment of lung disease", section on 'Ibuprofen'.)
Gastroesophageal reflux There is emerging concern that gastroesophageal reflux (GER)
and bronchiectasis are associated [44]. Among patients with advanced lung disease awaiting
lung transplantation, patients with bronchiectasis had the highest prevalence of GER (50
percent) [45]. As a result, gastric acid suppression (eg, H2 blocker, proton pump inhibitor) is
used in patients with symptomatic GER or those with two or more exacerbations in a year. The
role of diagnostic testing (eg, esophageal pH monitoring, manometry, esophagram, or upper
endoscopy) is uncertain. We typically pursue diagnostic testing or additional anti-reflux
measures in patients with persistent symptoms or frequent, unexplained exacerbations.
(See"Clinical manifestations and diagnosis of gastroesophageal reflux in adults" and "Medical
management of gastroesophageal reflux disease in adults".)
Immunizations Data are limited regarding immunization guidelines for individuals with
chronic respiratory diseases. Seasonal influenza vaccine is typically administered annually to
patients with bronchiectasis, as for other chronic respiratory diseases. (See "Seasonal influenza
vaccination in adults".)
Despite limited data in bronchiectasis, pneumococcal vaccine is typically given to patients with
bronchiectasis, as is recommended for patients with other chronic respiratory diseases [46]. In a
prospective randomized study of 167 adults with chronic respiratory diseases including 20 with
probable bronchiectasis, the group receiving both influenza and pneumococcal vaccines had
significantly reduced numbers of acute infectious exacerbations during the first, but not second
year of the study as compared to the group receiving the influenza vaccine alone [47].
(See "Pneumococcal vaccination in adults", section on 'Approach to vaccination'.)
PULMONARY REHABILITATION Pulmonary rehabilitation is efficacious in COPD, and a
few small studies support a benefit in patients with bronchiectasis. In a trial that randomly
assigned 30 patients with bronchiectasis to pulmonary rehabilitation plus chest physiotherapy or
chest physiotherapy alone, the pulmonary rehabilitation group had greater improvements in
exercise tolerance and health related quality of life [48]. In a trial of 32 patients with
bronchiectasis, an eight week exercise rehabilitation program improved the distance traveled
during a walk test and endurance capacity, compared to a control group [49]. The addition of
specific inspiratory muscle training extended the improvement in exercise capacity another
three months.
We generally offer participation in pulmonary rehabilitation to patients with moderate-to-severe
airflow limitation on pulmonary function testing, similar to the guidelines for COPD.
(See "Pulmonary rehabilitation in COPD".)
SURGERY The combination of impaired defense mechanisms and recurrent infection often
results in diffuse bronchiectasis affecting multiple lobes of the lung. In the setting of diffuse
bronchiectasis, there is little opportunity for surgical cure, other than bilateral lung
transplantation. Nevertheless, there is a role for surgery in some patients to remove particularly
diseased segments or to control massive hemoptysis. Goals are conservative, aiming to control
specific disease manifestations rather than cure or elimination of all areas of bronchiectasis.
Resection of bronchiectatic lung The immediate goal of surgical extirpation includes
removal of the most involved segments or lobes with preservation of nonsuppurative or
nonbleeding areas. Middle and lower lobe resections are most often performed. The superior
segment of the lower lobe may be involved to a lesser extent and can frequently be salvaged
when considering lower lobe resection. Surgical intervention is often combined with an
aggressive antibiotic and bronchial hygiene regimen to reduce bacterial infection and improve
drainage.
Major indications The major indications and goals for resectional surgery in bronchiectasis
include:
Removal of destroyed lung partially obstructed by a tumor or the residue
of a foreign body
Reduction in acute infective episodes in patients with frequent
exacerbations due to localized bronchiectasis
Reduction in overwhelming purulent and viscid sputum production in
patients with bronchiectasis confined to one or two lobes and
unresponsive to medical therapy
Elimination of bronchiectatic airways subject to uncontrolled hemorrhage
when other measures fail (see 'Management of hemoptysis' below)
Removal of an area suspected of harboring resistant organisms such as
MAC [50] or multidrug resistant tuberculosis [51] (see "Treatment of
nontuberculous mycobacterial infections of the lung in HIV-negative
patients", section on 'Surgical management' and "Diagnosis, treatment,
and prevention of drug-resistant tuberculosis", section on 'Surgery')
Outcomes Surgical case series have shown low operative mortality (<2 percent) and
resolution or improvement of symptoms in the majority of patients selected to receive surgery
[49,52-55]. The following studies illustrate typical outcomes that follow surgical resection:
In the largest study from the past two decades, 790 Chinese patients
(mean age 47 years) were followed for a mean of four years following
lung resection (segmentectomy, lobectomy, pneumonectomy) [52].
Mortality at 30 days was 1.1 percent. Seventy-five percent of patients
became asymptomatic or were improved, while 15 percent were
unimproved or worse.
In a study from the United States, 134 patients (mean age 48 years)
were followed for a mean of six years [53]. Mortality was 2 percent and
89 percent of patients improved.
Postoperative complications include empyema, hemorrhage, prolonged air leak, and poorly
expanding remaining lung due to persistent atelectasis or suppuration. In selected patients,
video-assisted thoracoscopic surgery (VATS) segmentectomy or lobectomy may be possible
and allow fewer complications and shorter hospitalizations. Pleural adhesions may require
conversion to thoracotomy [54].
Management of hemoptysis Bleeding due to bronchiectasis is often associated with acute
infective episodes and is produced by injury to superficial mucosal neovascular bronchial
arterioles. Urgent surgery is occasionally required for the management of life-threatening
hemoptysis (>600 mL/day) due to bronchiectasis that cannot be controlled with less invasive
measures. The evaluation and management of massive hemoptysis is discussed separately.
(See "Overview of massive hemoptysis" and "Massive hemoptysis: Initial management".)
For most patients with hemoptysis complicating bronchiectasis, flexible bronchoscopy and chest
CT are complementary diagnostic tools to localize the bleeding to a lobe or segment [56]. Once
the site of bleeding is identified, bronchoscopic techniques such as balloon tamponade, topical
application of a vasoconstrictive or coagulant agent, laser therapy, electrocautery, argon plasma
coagulation, and cryotherapy may be able to stop the bleeding. If bronchoscopic techniques to
control bleeding are unsuccessful or are not available, the next step is usually arteriographic
embolization of bleeding sites (typically from a bronchial artery) by an interventional radiology
service. Bronchial artery embolization successfully stops pulmonary hemorrhage in more than
85 percent of attempted embolizations. Bronchial artery embolization preserves lung tissue and
often eliminates the need for surgery [57]. However, if embolization is unsuccessful and
bleeding persists, surgical resection may be necessary [53]. (See "Massive hemoptysis: Initial
management", section on 'Control the bleeding'.)
Airway stabilization for tracheobronchomegaly For patients with tracheobronchomegaly
(eg, Mounier-Kuhn syndrome), tracheal stabilizing procedures, such as proximal stents or
tracheobronchoplasty, may enhance clearance of airway secretions and improve pulmonary
function [58]. (See "Tracheomalacia and tracheobronchomalacia in adults", section on
'Treatment'.)
Lung transplantation Patients with suppurative lung disease were initially considered poor
candidates for lung transplantation due to the potential persistence of infection that might
worsen during prolonged immunosuppression. However, with bilateral lung transplantation, the
survival advantage of transplantation is now thought to be comparable to that of other
diagnostic groups [59]. As an example, 54 patients with bronchiectasis underwent bilateral lung
transplantation in the United Kingdom between 1997 and 2007 [60]. The mean age was 50 and
the median transplant list waiting time was 309 days. The median survival time for transplant
recipients was eight years. In comparison, 59 patients died while on the waiting list. (See "Lung
transplantation: General guidelines for recipient selection".)
PROGNOSIS Long term outcome studies of bronchiectasis are limited. However, a few
studies have examined the frequency of exacerbations, hospitalizations, and mortality and also
the rate of lung function decline among patients with bronchiectasis [13,32,61-64].
Exacerbations In the aerosol recombinant DNAse study, 349 patients
experienced an average of one pulmonary exacerbation every six to
eight months [32]. One-third of these episodes were severe enough to
require hospitalization.
Hospitalization and mortality A retrospective cohort study identified 842
patients with bronchiectasis from the National Hospital Discharge
Registry in Finland and followed those patients for 8 to 12.9 years [61].
The number of hospitalizations per patient varied widely (range 1 to 51),
with a mean of 2.2 episodes per patient. There were 239 deaths (28
percent of patients), mostly related to respiratory complications.

There is limited information regarding the prognosis of patients with
bronchiectasis and respiratory insufficiency admitted to an intensive care
unit. Two retrospective series assessed outcomes of patients with
bronchiectasis admitted to an ICU for respiratory failure for the first time
[62,65]. A report of 48 patients from France found 19 percent mortality in
the ICU and 40 percent mortality at one year [62]. In a series of 57
patients from Singapore, an overall hospital mortality of 26 percent was
reported with no difference whether the patients received noninvasive
ventilation or intubation with mechanical ventilation [65]. Severe
hypoxemia and higher APACHE II scores were worse prognostic factors.
(See "Noninvasive positive pressure ventilation in acute respiratory
failure in adults".)
Lung function decline Patients with bronchiectasis have a mean annual
decline in forced expiratory volume in one second (FEV
1
) of 50 to 55 mL
per year [13]. This is greater than normal individuals (20 to 30 mL per
year) and similar to patients with COPD (approximately 60 mL per year).
Among patients with bronchiectasis, the decline in FEV
1
is most
accelerated when Pseudomonas colonization, frequent exacerbations, or
increased inflammatory markers (eg, C-reactive protein) exist.
Pulmonary vascular disease An observational study evaluated 94
patients with bronchiectasis using echocardiography [63]. There was
evidence of pulmonary hypertension (defined as an estimated systolic
pulmonary artery pressure >40 mmHg) in 33 percent of patients and right
ventricular systolic dysfunction in 13 percent. Both abnormalities were
more common among patients with cystic bronchiectasis. Right
ventricular dysfunction correlated with a low forced expiratory volume in
one second (FEV
1
), low diffusing capacity of carbon monoxide (DLCO),
hypercarbia, and hypoxemia. Only 15 percent of patients had evidence
of left ventricular dysfunction.
FUTURE DIRECTIONS Methods for noninvasive detection of tissue injury and impending or
existing bronchiectasis are being sought. Bronchoalveolar lavage, while helpful diagnostically
for some respiratory diseases, is probably too invasive for ongoing management of
bronchiectasis. Exhaled breath condensates (for H
2
O
2
and NO) require specialized equipment
and preliminary results have been conflicting. (See "Exhaled nitric oxide analysis", section on
'Bronchiectasis, cystic fibrosis, and sarcoidosis'.)
Analysis of induced sputum for inflammatory cell constituents and biomarkers (eg, 8-
isoprostane) is an emerging methodology that may hold promise for assessing disease activity
[66]. Measuring sputum biomarkers with high throughput technology is another possible method
for quantifying inflammation in airway diseases including bronchiectasis [67].
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