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Tratamento de bronquiectasias em adultos
Autor: Alan F Barker, MD
Editores de Seção: James K Stoller, MD, MS, Talmadge E King, Jr, MD
Editor adjunto: Helen Hollingsworth, MD
Todos os tópicos são atualizados conforme novas evidências se tornam disponíveis e nosso processo de revisão por
pares está completo.
Revisão de literatura atualizada até: maio de 2019. | Este tópico foi atualizado pela última vez em: 03 de
dezembro de 2018.
INTRODUÇÃO
Bronquiectasia é uma síndrome de tosse crônica e produção diária de escarro visceral associada
à dilatação das vias aéreas e espessamento da parede brônquica. Múltiplas condições estão
associadas ao desenvolvimento de bronquiectasias, mas todas requerem um insulto infeccioso e
geralmente também comprometimento da drenagem, obstrução das vias aéreas e / ou um defeito
na defesa do hospedeiro.
Do amplo espectro de causas de bronquiectasia de fibrose não-cística, apenas algumas
respondem ao tratamento direto (por exemplo, certas imunodeficiências, infecção micobacteriana
não tuberculosa, aspergilose broncopulmonar alérgica). Em vez disso, o tratamento das
bronquiectasias visa controlar a infecção, reduzir a inflamação e melhorar a higiene brônquica [
1,2 ]. A extirpação cirúrgica das áreas afetadas pode ser útil em pacientes selecionados.
O tratamento de bronquiectasias será revisto aqui. O diagnóstico e tratamento da fibrose cística e
as manifestações clínicas e diagnóstico de bronquiectasias são discutidos separadamente. (Veja
"Fibrose Cística: manifestações clínicas e diagnóstico" e "Fibrose Cística: Visão geral do
tratamento da doença pulmonar" e "Fibrose Cística: Antibioticoterapia para infecção pulmonar
crônica" e "Manifestações clínicas e diagnóstico de bronquiectasia em adultos" .)
TRATANDO A DOENÇA SUBJACENTE
Para a maioria das causas de bronquiectasia, o tratamento da doença subjacente não é possível,
pois a bronquiectasia é uma manifestação de cicatrização resultante de uma lesão ou infecção
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https://www.uptodate.com/contents/cystic-fibrosis-overview-of-the-treatment-of-lung-disease?search=bronchiectasis&topicRef=1435&source=see_link
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anterior (por exemplo, pneumonia grave) ou um resultado de um problema contínuo com
secreção. depuração que não tem um tratamento específico (por exemplo, disfunção ciliar
primária). No entanto, alguns processos de doença podem ser controlados para evitar novas
cicatrizes. A avaliação e o diagnóstico das causas subjacentes da bronquiectasia são discutidos
separadamente ( tabela 1 e tabela 2 e tabela 3 ). (Veja "Manifestações clínicas e diagnóstico de
bronquiectasia em adultos" .)
Exemplos de processos de doenças nos quais terapias específicas podem impedir a progressão
de bronquiectasias incluem os seguintes:
Embora a infecção micobacteriana não tuberculosa possa ser uma infecção oportunista em
um paciente com bronquiectasia, ela também pode ser uma causa primária de
bronquiectasia. Geralmente é tratado para prevenir mais lesões pulmonares. (Veja "Resumo
das infecções por micobactérias não tuberculosas em pacientes HIV-negativos" e
"Tratamento da infecção pulmonar por complexo Mycobacterium avium em adultos" .)
●
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 "Oropharyngeal
dysphagia: Clinical features, diagnosis, and management" 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 "Treatment of 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: Initial therapy 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'.)
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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 [71]. (See
"Pneumococcal vaccination in adults", section on 'Approach to vaccination'.)
PULMONARY REHABILITATION
Pulmonary rehabilitation is efficacious in chronic obstructive pulmonary disease (COPD), and a
few small studies support a benefit in patients with bronchiectasis.
We generally offer participation in pulmonary rehabilitation to patients with impaired exercise
capacity, similar to the guidelines for COPD. (See "Pulmonary rehabilitation".)
Nutritional supplementation may provide additional benefit beyond that of pulmonary rehabilitation
in patients with bronchiectasis. In a randomized trial of 30 well-nourished patients with
bronchiectasis participating in a 12 week rehabilitation program, the group receiving a high-protein
nutrition supplement enriched with hydroxyl-beta-methylbutyrate (may have anti-catabolic and
anti-inflammatory effects) resulted in greater improvement in certain parameters of strength and
physical functioning (QOL-B questionnaire), compared with the group participating in pulmonary
rehabilitation alone [75]. The role of nutritional support in bronchiectasis needs further study. (See
"Nutritional support in advanced lung disease".)
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
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 [72].
●
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 [73]. The addition of specific inspiratory muscle training extended the
improvement in exercise capacity another three months.
●
In a randomized trial of 85 patients participating in an eight-week exercise training program,
improvements were noted in symptoms and on a shuttle and six-minute walk distances [74].
At 12 months after completion of the exercise program, the walk distance improvements were
not sustained, but the patients who had participated in the exercise program experienced
fewer exacerbations.
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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 eliminate 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:
Outcomes — Surgical case series have shown low operative mortality (https://www.uptodate.com/contents/treatment-of-drug-resistant-pulmonary-tuberculosis-in-adults?search=bronchiectasis&topicRef=1435&source=see_link
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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. 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 [83]. However, if embolization is unsuccessful and bleeding
persists, surgical resection may be necessary [79]. (See "Massive hemoptysis: Initial
management", section on 'Control the bleeding and correct coagulopathy'.)
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 [84]. (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 in other diagnostic groups
[85]. As an example, 54 patients with bronchiectasis underwent bilateral lung transplantation in the
United Kingdom between 1997 and 2007 [85]. 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: An overview"
and "Lung transplantation: General guidelines for recipient selection".)
Survival on the waiting list appears better for patients with non-cystic fibrosis (CF) bronchiectasis
than for those with CF bronchiectasis. In an analysis of the United Network for Organ Sharing
database, between 1987 and 2007, 180 patients with non-CF bronchiectasis, who were on the
transplant waiting list but were not transplanted, experienced a 75 percent five-year survival on the
waitlist, compared with 40 percent for the 1932 patients with CF [86]. Further study is needed to
determine whether these findings should affect decisions about listing for lung transplantation.
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ADDRESSING SINUS DISEASE
Since many patients have accompanying rhinosinus disease (infections, polyps) and post-nasal
drainage, attention to the sinus disease might be palliative. In a non-randomization study of 161
patients with rhinosinusitis and bronchiectasis, there was an improvement in clinical symptoms,
numerical scoring systems, and reduced exacerbations in the sinus endoscopic surgery group as
compared to the medication alone group. The FEV was unchanged at six months in both groups
[87]. (See "Chronic rhinosinusitis: Management" and "Microbiology and antibiotic management of
chronic rhinosinusitis".)
PROGNOSIS
Long term outcome studies of bronchiectasis are limited. A few studies have examined the
frequency of exacerbations, hospitalizations, comorbidities, and mortality, and also the rate of lung
function decline among patients with bronchiectasis [22,51,88-93].
1
Exacerbations – In the aerosol recombinant DNAse study, 349 patients experienced an
average of one pulmonary exacerbation every six to eight months [51]. One-third of these
episodes were severe enough to require hospitalization.
●
Severity and prognosis – Scoring systems have been proposed to help guide assessment
of prognosis and identify patients who frequently exacerbate [92,94]. The Bronchiectasis
Severity Index (BSI) was derived from 608 bronchiectasis patients at a center in Scotland and
validated in 597 patients from other centers in the United Kingdom and Europe [92].
Predictors of hospitalizations included previous hospitalization, high dyspnea index, low
forced expiratory volume in one second (FEV ), presence of Pseudomonas in sputum, and
more extensive involvement (>3 lobes) on high resolution computed tomography (HRCT).
Mortality correlated with older age, low FEV , previous hospitalization, and three or more
exacerbations in the year before study.
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1
1
The FACED score (FEV , Age, Colonization with pseudomonas, Extended involvement on
chest CT, and Dyspnea) was developed in 397 patients of a multicenter cohort of 819 patients
from Spain [94]. The ability of the scoring system to predict five year all-cause mortality was
validated in the remaining patients of the same cohort.
1
The BSI and FACED were evaluated retrospectively over 19 years regarding mortality
estimates in 91 patients followed at the Royal Brompton Hospital, London. Both scores gave
equally reliable mortality estimates at five years with the FACED slightly superior at 15years
[95]. Regarding other clinical outcomes, in a further analysis of 1612 subjects from seven
European cohorts, the BSI more accurately predicted exacerbations, hospitalizations,
respiratory symptoms, and quality of life than the FACED score [96].
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The most recent approach to help estimate exacerbations and survival utilizes the cluster
analysis approach as studied in asthma and COPD. Daily sputum production and the
presence of Pseudomonas or other potential infectious pathogens in sputum culture were the
main features linked to QOL, inflammatory markers, and clinical outcome at three years [10].
Hospitalization and mortality – Small studies have described mortality rates of 16 to 20
percent over five years, increasing with ICU hospitalization and comorbidity. Two retrospective
series assessed outcomes of patients with bronchiectasis admitted to an ICU for respiratory
failure for the first time [88,97]. A report of 48 patients from France found 19 percent mortality
in the ICU and 40 percent mortality at one year [88]. 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 [97]. Severe
hypoxemia and higher APACHE II scores were worse prognostic factors. (See "Noninvasive
ventilation in acute respiratory failure in adults".)
●
In 2013, analysis from the Intensive Care National Audit and Research Centre in the United
Kingdom included 121 ICU admissions for bronchiectasis or 0.1 percent of all ICU
admissions. Mortality was 29 percent (18 percent for COPD in same survey) with a median
ICU length of stay of three days and hospital stay of 12 days [98].
In a series of 245 patients with bronchiectasis followed in Belgium between 2006 and 2013,
mortality was 20 percent, increasing to 55 percent among those with COPD [99]. The cause
of death was mainly respiratory (58 percent).
Lung function decline – Patients with bronchiectasis have a mean annual decline in forced
expiratory volume in one second (FEV ) of 50 to 55 mL per year [22]. 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 is most accelerated
when Pseudomonas colonization, frequent exacerbations, or increased inflammatory markers
(eg, C-reactive protein) exist.
●
1
1
Pulmonary vascular disease – An observational study evaluated 94 patients with
bronchiectasis using echocardiography [89]. 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 ), low diffusing capacity of carbon
monoxide (DLCO), hypercarbia, and hypoxemia. Only 15 percent of patients had evidence of
left ventricular dysfunction.
●
1
Cardiovascular morbidity – Respiratory tract infections are associated with increased
cardiovascular events (CV: myocardial infarction, stroke) [100]. In an audit of patients with
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FUTURE DIRECTIONS
Experts from the United States [104] and Europe [105] have suggested that research priorities in
bronchiectasis should include epidemiology, pathogenesis, and management [105]. (See "Exhaled
nitric oxide analysis and applications", section on 'Bronchiectasis and cystic fibrosis'.)
bronchiectasis from primary care practices in the United Kingdom, an increase in CV events
was noted in the first 90 days after a respiratory infection (incidence rate ratio [IRR] 1.56, 95%
CI 1.20-2.02) with the greatest relative risk in the first three days (IRR 2.73, 95% CI 1.41-
5.27), compared with the individual’s baseline risk [101]. In a separate study, bronchiectasis
was an independent risk factor for coronary artery disease and stroke after adjustment for
age, sex, smoking, and other known risk factors for CV [102]. Further study is needed to
determine the optimal management of these potential comorbidities.
Cancer – A study of cancer in hospitalized patients from Taiwan (National Health Insurance
Research database) suggested a significantly increased risk of hematologic malignancies and
cancers of the lung and esophagus among patients with bronchiectasis compared with an
age, time interval, and presence of COPD diagnosis control group [103]. However,
information about cigarette smoking, family factors, or environmental factors were not
available in the database to enable adjustment for these variables.
●
Culture-independent microbial gene surveys – Culture-independent microbial gene
surveys of airway secretions from individuals with non-cystic fibrosis bronchiectasis have
identified a broader array of microbial species, including anaerobic bacteria that are not
identified by routine culture. In these studies, greater bacterial diversity was associated with
better clinical parameters, including a higher forced expiratory volume in one second (FEV )
and fewer symptoms, suggesting that low diversity may reflect overgrowth by pathogenic
bacteria such as P. aeruginosa. Identification of these organisms does not have direct
implication for therapy [106]. 
●
1
Investigative method of palliation for P. aeruginosa infection – Some patients with
bronchiectasis have excess immunoglobulin G2 (IgG2) specific to the bacterial O-antigen,
which (unlike other antibodies) inhibits immune killing of P. aeruginosain serum samples. Two
patients with bronchiectasis, severe respiratory insufficiency, P. aeruginosa airway infection,
and frequent exacerbations had elevated IgG2 serum levels and impaired serum killing of P.
aeruginosa [107]. Plasmapheresis sessions followed by intravenous pooled immune globulin
infusions for five days markedly improved their clinical status including reduction of days in
the hospital and average days on intravenous antibiotics assessed up to 8 to 12 months.
Cultures for P. aeruginosa remained negative for three months, IgG2 levels were lowered, and
ability to kill P. aeruginosa was improved.
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SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Bronchiectasis".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.”
The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading
level, and they answer the four or five key questions a patient might have about a given condition.
These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10 to 12 grade reading level and are best for
patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or
e-mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on “patient info” and the keyword(s) of interest.)
SUMMARY AND RECOMMENDATIONS
Enhancing treatment adherence – Bronchiectasis is a complex chronic disease that often
involves following a difficult and cumbersome management plan with multiple oral and
nebulized medications and bronchial hygiene maneuvers throughout the day. Many of the
treatments for bronchiectasis involve the use of off-label and expensive medications,
prolonged administration time, and sometimes distressing adverse effects. Adherence to
treatments involves patient-specific and treatment-related constraints. A pilot study involving a
structured interview process has begun to explore factors to enhance treatment adherence
among patients with bronchiectasis [108].
●
th th
th th
Basics topic (see "Patient education: Bronchiectasis in adults (The Basics)")●
Bronchiectasis is a syndrome of chronic cough and viscid sputum production associated with
airway dilatation and bronchial wall thickening. Exacerbations are usually caused by acute
bacterial infections. (See 'Introduction' above and 'Treatment of acute exacerbations' above.)
●
For most causes of bronchiectasis, treatment of the underlying disease is not possible.
Examples of disease processes in which specific therapies may interrupt progression of
bronchiectasis include nontuberculous mycobacterial infection, certain immunodeficiencies,
cystic fibrosis (in presence of G551D mutation), recurrent aspiration, allergic
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bronchopulmonary aspergillosis, tracheobronchomegaly, and possibly bronchiectasis
associated with rheumatic disease. (See 'Treating the underlying disease' above.)
The initial antibiotic regimen for acute exacerbations of bronchiectasis is tailored to prior
sputum cultures and sensitivities, rather than chosen empirically. Additional factors in
antibiotic selection include oral versus parenteral administration, the history of success or
failure of prior regimens, and the presence of allergy to antimicrobial agents. (See 'Treatment
of acute exacerbations' above.)
●
For outpatients with sputum cultures that do not show beta-lactamase-positive H.
influenzae or Pseudomonas, reasonable initial antibiotic choices include amoxicillin, 500
mg three times daily, or a macrolide. In the presence of beta-lactamase producing
organisms, choices include amoxicillin-clavulanate, second or third generation
cephalosporin, doxycycline, or a fluoroquinolone. (See 'Oral antibiotic treatment' above.)
•
For outpatients with multiple prior exacerbations or no recent sputum culture data, we
suggest initiation of a fluoroquinolone antibiotic (eg, levofloxacin, moxifloxacin), rather
than an alternative oral antibiotic. (Grade 2C). (See 'Treatment of acute exacerbations'
above.)
•
For hospitalized patients with an acute exacerbation, we suggest initiation of an
intravenous antibiotic with efficacy for P. aeruginosa (Grade 2B). Alternatively, for
patients who are acutely ill and have a history of growing resistant strains of P.
aeruginosa, we select two anti-pseudomonal antibiotics that have different mechanisms
of action, although the need for dual therapy is controversial. (See 'Intravenous
treatment' above.)
•
For treatment of acute exacerbations, we suggest 10 to 14 days of antibiotic therapy
rather than a shorter course (Grade 2C). Occasionally, a longer course is needed if the
patient has resistant organisms or is improved but not yet back to baseline. (See
'Treatment of acute exacerbations' above.)
•
For patients who have recurrent exacerbations, we suggest preventive therapy with a
macrolide antibiotic (Grade 2B). Our threshold for the initiation of preventive antibiotics is two
to three exacerbations within one year. We obtain sputum stains and cultures to exclude
nontuberculous mycobacterial (NTM) infection prior to initiating long-term macrolide therapy.
Alternatively, for patients with recurrent exacerbations and P. aeruginosa in their sputum, we
suggest a therapeutic trial of inhaled antibiotics. (See 'Prevention of exacerbations' above.)
●
We suggest that all patients with bronchiectasis regularly use airway clearance techniques to
help remove airway secretions (table 4) (Grade 2C). (See 'Airway clearance therapy' above.)
●
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●
Inhaled glucocorticoids should not be routinely used in patients with bronchiectasis unless
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●
Other medical therapies used in selected patients include inhaled bronchodilators,
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●
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●
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●
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●
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GRAPHICS
Evaluation of bronchiectasis-1
Category Specific examples/features Diagnostic tests
Acquired bronchial obstruction
Foreign-body
aspiration
Peanut; chicken bone; tooth; grass
inflorescence; etc
Chest imaging; flexible bronchoscopy
Tumors Laryngeal papillomatosis; airway adenoma;
endobronchial teratoma
Chest imaging; flexible bronchoscopy
Hilar adenopathy Tuberculosis; histoplasmosis; sarcoidosis PPD or IGRA; chest HRCT
COPD Chronic bronchitis Pulmonary function tests; serum alpha-1
antitrypsin level
Mucoid impaction Allergic bronchopulmonary aspergillosis;
bronchocentric granulomatosis (BG);
postoperative mucoid impaction
Total serum IgE, Aspergillus specific IgE and
IgG; Aspergillus skin test; chest imaging;
biopsy for BG
Other Relapsing polychondritis (RP);
tracheobronchial amyloidosis
Clinical syndrome of RP/cartilage biopsy;
biopsy for amyloid
Congenital anatomic defects that may cause bronchial obstruction
Tracheobronchial Bronchomalacia; bronchial cyst; cartilage
deficiency (Williams-Campbell syndrome);
tracheobronchomegaly (Mounier-Kuhn
syndrome); ectopic bronchus;
tracheoesophageal fistula
Chest CT with inspiratory and expiratory
images
Vascular Pulmonary (intralobar) sequestration;
pulmonary artery aneurysm
Chest CT imaging
Lymphatic Yellow-nail syndrome History of dystrophic, slow growing nails
PPD: purified protein derivative (tuberculin skin test); IGRA: interferon gamma release assay; COPD: chronic obstructive
pulmonary disease; RP: relapsing polychondritis; IgE: immunoglobulin E; IgG: immunoglobulin G; BG: bronchocentric
granulomatosis; CT: computerized tomography.
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Evaluation of bronchiectasis-2
Category Specific examples/features Diagnostic tests
Immunodeficiency states
IgG deficiency Congenital (Bruton-type)
agammaglobulinemia; selective deficiency
of subclasses (IgG2, IgG4); acquired
immune globulin deficiency; common
variable hypogammaglobulinemia; "bare
lymphocyte" syndrome
Quantitative immunoglobulin levels;
immunoglobulin subclass levels; impaired
response to immunization with
pneumococcal vaccine
IgA deficiency Selective IgA deficiency ± ataxia-
telangiectasia syndrome
Quantitative immunoglobulin levels
Leukocyte
dysfunction
Chronic granulomatous disease (NADPH
oxidase dysfunction)
Dihydrorhodamine 123 (DHR) oxidation
test; nitroblue tetrazolium test; genetic
testing
Other rare humoral
immunodeficiencies
(CXCR4 mutation,
CD40 deficiency,
CD40 ligand
deficiency, and
others)
WHIM; hypergammaglobulinemia M Neutrophil count; quantitative
immunoglobulin levels
Abnormal secretion clearance
Ciliary defects of
airway mucosa
Primary ciliary dyskinesia with or without
situs inversus (Kartagener syndrome)
Nasal nitric oxide and extended panel
genetic testing. High speed videomicroscopy
analysis (HSVA, also called HSVM) and
transmission electron microscopy (TEM)
may be needed if genetic testing negative in
patient with high suspicion of ciliary
dyskinesia.
Cystic fibrosis
(mucoviscidosis)
Typical early childhood syndrome; later
presentation with predominantly
sinopulmonary symptoms
Sweat chloride; genetic testing
Young's syndrome Obstructive azoospermia with
sinopulmonary infections
Sperm count
Miscellaneous disorders
Alpha-1 antitrypsin
deficiency
Absent or abnormal antitrypsin protein
and/or decreased hepatocyte secretion into
blood
Alpha-1 antitrypsin serum level; alpha-1
antitrypsin genotyping
Recurrent
aspiration
pneumonia
Alcoholism; neurologic disorders; lipoid
pneumonia
History; chest imaging
Rheumatic disease Associated with rheumatoid arthritis and
Sjogren syndrome
Rheumatoid factor; antiSSA/antiSSB;
salivary gland MRI or biopsy
Inflammatory
bowel disease
Crohn's disease; ulcerative colitis History; lower gastrointestinal endoscopy;
colonic biopsy
Inhalation of toxic
fumes and dusts
Ammonia; nitrogen dioxide, or other irritant
gases; smoke
Exposure history; chest imaging
Chronic rejection
following organ
transplantation
Bone marrow, lung and heart lung
transplantation; associated with obliterative
bronchiolitis
History; PFT; chest CT imaging with
inspiratory and expiratory views
MRI: magnetic resonance imaging; CT: computed tomography; NADPH: reduced nicotinamide adenine dinucleotide
phosphate; PFT: pulmonary function testing; WHIM: syndrome of warts, hypogammaglobulinemia, infections, and
myelokathexis.
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Evaluation of bronchiectasis-3
Category Specific examples Diagnostic tests
Childhood
infections
Pertussis; measles History of infection
Bacterial
infections
Infections due to Staphylococcus aureus, Pseudomonas
aeruginosa
History of infection; sputum
culture
Viral
infections
Infections due to adenovirus (particularly types 7 and 21),
influenza, herpes simplex
History/serologic evidence of
infection
Other
infections
Fungal (histoplasmosis); Mycobacterium tuberculosis,
nontuberculous mycobacteria; possibly mycoplasma
Fungal culture; AFB smear and
mycobacterial culture
AFB: acid-fast bacilli.
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Airway clearance/bronchial hygiene
Technique Advantages Comment/disadvantage
Directed cough Inexpensive, simple Chest pain may limit
Regular exercise Inexpensive, strengthens
respiratory and peripheral
muscles
 
Autogenic breathing Controls breathing Requires patient cooperation
Forced expiration Helps control breathing Requires patient learning
Chest physical therapy (CPT) (postural
drainage, hand, or mechanical chest
clapping)
Most tested in cystic
fibrosis
Needs assistant, hard to position,
hypoxemia, sometimes worsens
gastroesophageal reflux
Positive expiratory pressure (PEP) Easy, inexpensive Device needs cleaning
Oscillatory PEP (eg, flutter valve
acapella device)
Easy, inexpensive, adds
vibration to airways
Deviceneeds cleaning
High frequency chest wall oscillation
vest with inflatable bladder
Extensive experience Pain may limit; need electrical outlet
High frequency chest wall oscillation
vest with mechanical oscillators
Not painful compared with
inflatable bladder
Can be mobile; small batteries in the vest;
closest to chest PT
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Contributor Disclosures
Alan F Barker, MD Consultant/Advisory Boards: Bayer [Bronchiectasis (Ciprofloxacin inhalation)]; Grifols
(Cipro liposomal); International Biophysics [Education materials]. James K Stoller, MD,
MS Grant/Research/Clinical Trial Support: Alpha-1 Foundation [Alpha-1 antitrypsin detection (Pooled human
alpha-1 antiprotease)]. Consultant/Advisory Boards: CSL Behring; Grifols; Shire [Alpha-1 antitrypsin detection
(Pooled human alpha-1 antiprotease)]; Arrowhead Pharmaceuticals [Alpha-1 antitrypsin deficiency]; Vertex;
Inhibrx; 23andMe [Alpha-1 antitrypsin deficiency]; Alpha-1 Foundation [Member, Board of Directors (Alpha-1
antitrypsin deficiency)]; American Respiratory Care Foundation [Member, Board of Directors (Respiratory
therapy issues)]. Talmadge E King, Jr, MD Nada para divulgar Helen Hollingsworth, MD Nada a revelar
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TREATMENT OF ACUTE EXACERBATIONS
Patients with bronchiectasis have a high burden of bacterial pathogens and inflammation.
Treatment with antibiotics reduces the bacterial load and airway and systemic inflammatory
mediators [1]. 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, and may be
accompanied by lassitude, shortness of breath, pleuritic chest pain, or hemoptysis. Systemic
complaints such as fever and chills are generally absent [3]. 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. Sputum elastase is an emerging biomarker candidate that may herald an
exacerbation and correlate with antibiotic responsiveness [4].
Viral infection may also be a contributor to exacerbations of bronchiectasis. In a one-year study of
119 patients with bronchiectasis, polymerase chain reaction (PCR) assays identified respiratory
viral sequences (coronavirus, rhinovirus, and influenza) in nasopharyngeal and sputum samples
more frequently during exacerbations as compared with steady state [5]. In addition, inflammatory
markers were more often associated with the virus positive than virus negative states. The role of
viruses is not yet clear as there were no clinical correlates.
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 [6,7]. 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 administration of intravenous antibiotics.
Oral antibiotic treatment — Most afebrile, clinically stable patients with an exacerbation of
bronchiectasis can be treated with an oral antibiotic. 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 culture data not available – For those without culture information, a fluoroquinolone
(eg, levofloxacin, moxifloxacin) is a reasonable, broad spectrum, therapeutic option.
●
Sputum growing sensitive organisms – For patients whose sputum cultures do not show
beta-lactamase-positive H. 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
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https://www.uptodate.com/contents/levofloxacin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
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Intravenous treatment
be used. The initial antibiotic selection can be modified 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
Moraxella catarrhalis or beta-lactamase producing H. influenzae, antibiotic choices include
amoxicillin-clavulanate, a second or third generation cephalosporin, azithromycin or
clarithromycin, doxycycline, or a fluoroquinolone [8]. (See "Moraxella catarrhalis infections",
section on 'Treatment' and "Epidemiology, clinical manifestations, and treatment of
Haemophilus influenzae".)
●
Sputum growing sensitive Pseudomonas – The virulence of Pseudomonas aeruginosa in
sputum cannot be emphasized strongly enough. The presence of sputum Pseudomonas
aeruginosa is associated with increased death, exacerbations, and hospital admissions [9-
12]. For patients with known airway infection 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 [8].
●
Because of the propensity of P. aeruginosa to develop resistance and the limited 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 [13]. 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.)
Duration of therapy – The optimal duration of therapy is not well-defined. Clinical experience
favors a duration of 10 to 14 days for patients with a first time or few exacerbations [14,15].
The European Respiratory Society (ERS) guidelines released in 2017 suggest a 14-day
course of antibiotics based on expert consensus, although they note that shorter and longer
durations have not been directly compared [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.
●
Sputum growing resistant Pseudomonas – The nonquinolone antibiotics typically used for
resistant Pseudomonas require intravenous administration. Intravenous antibiotics for
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https://www.uptodate.com/contents/azithromycin-drug-information?search=bronchiectasis&topicRef=1435&source=see_linkhttps://www.uptodate.com/contents/clarithromycin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/doxycycline-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/treatment-of-bronchiectasis-in-adults/abstract/8
https://www.uptodate.com/contents/moraxella-catarrhalis-infections?sectionName=TREATMENT&search=bronchiectasis&topicRef=1435&anchor=H1052224713&source=see_link#H1052224713
https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-treatment-of-haemophilus-influenzae?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/treatment-of-bronchiectasis-in-adults/abstract/9-12
https://www.uptodate.com/contents/ciprofloxacin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/treatment-of-bronchiectasis-in-adults/abstract/8
https://www.uptodate.com/contents/tobramycin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/ciprofloxacin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/treatment-of-bronchiectasis-in-adults/abstract/13
https://www.uptodate.com/contents/ciprofloxacin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
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exacerbations due to resistant Pseudomonas are discussed below and separately. (See
"Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on
'Antibiotics with antipseudomonal activity'.)
Hospitalization – Initial inpatient treatment of an exacerbation is appropriate for patients with
characteristics such as increased respiratory rate ≥25/minute, hypotension, temperature
≥38˚C, hypoxemia (pulse oxygen saturation 1000 IU/mL (>2400 ng/mL), the usual initial therapy is oral prednisone 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 "Treatment of allergic bronchopulmonary
aspergillosis", section on 'Treatment'.)
PREVENTION OF EXACERBATIONS
Frequent exacerbations are the strongest predictor of future exacerbations and are associated
with increased hospitalizations, reduced quality of life, and increased mortality [17]. Retained
purulent secretions and the associated inflammatory cellsand mediators are an important cause
of airflow obstruction, airway injury, and exacerbations in bronchiectasis [18]. Thus, reducing the
microbial load with selective use of antibiotics and clearing secretions form the cornerstone of
preventive therapy. For patients who have recurrent exacerbations (eg, two to three or more per
year), we suggest long-term antibiotic therapy with a macrolide or inhaled antibiotic depending on
the sputum culture results, as described below, in accordance with the European Respiratory
Society guidelines [2].
While there are insufficient data to advocate routine use of mucolytic agents or airway hydration
therapies in patients with bronchiectasis, we suggest that all patients with bronchiectasis receive
regular chest physiotherapy.
Antibiotics — 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.
Studies that would guide the choice of oral versus inhaled antibiotics in this setting have not been
Airway clearance – Inpatient therapy should include attention to airway clearance
techniques, as described below (table 4). (See 'Airway clearance therapy' below.)
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https://www.uptodate.com/contents/microbiology-of-nontuberculous-mycobacteria?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/prednisone-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/itraconazole-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/voriconazole-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/treatment-of-allergic-bronchopulmonary-aspergillosis?sectionName=TREATMENT&search=bronchiectasis&topicRef=1435&anchor=H1410588617&source=see_link#H1410588617
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https://www.uptodate.com/contents/treatment-of-bronchiectasis-in-adults/abstract/2
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performed [19]. One practical approach to antibiotic selection supported by the European
Respiratory Guidelines is provided [2].
One difficult issue is chronic infection 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 [20]. (See "Cystic fibrosis: Genetics and
pathogenesis", section on 'Chronic lung infection' and "Epidemiology, microbiology, and
pathogenesis of Pseudomonas aeruginosa infection", section on 'Chronic infection in cystic
fibrosis'.)
Patients with chronic P. aeruginosa infection have reduced quality of life indices, more extensive
bronchiectasis on CT, accelerated decline in pulmonary function, and increased number of
hospitalizations, compared with patients colonized with Haemophilus influenzae [21,22]. For this
reason, attempts are often made to reduce the burden of P. aeruginosa infection.
Macrolides — For patients with bronchiectasis who have recurrent exacerbations (two to three
or more per year) and do not have P. aeruginosa infection, have P. aeruginosa but cannot take an
inhaled antibiotic, or continue to have exacerbations despite inhaled antibiotic, we suggest
preventive therapy with a macrolide antibiotic, in accordance with the ERS guidelines [2]. Chronic
low-dose administration of a macrolide antibiotic appears to have an effect that is not solely
antimicrobial [23]. 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.
(See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Azithromycin'.)
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.
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 [24]. Azithromycin was associated with a
decrease in exacerbations compared with placebo (RR 0.38, 95% CI 0.26–0.54). 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 [25]. The median
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https://www.uptodate.com/contents/epidemiology-microbiology-and-pathogenesis-of-pseudomonas-aeruginosa-infection?sectionName=Chronic+infection+in+cystic+fibrosis&search=bronchiectasis&topicRef=1435&anchor=H8&source=see_link#H8
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Three independently performed systematic reviews and meta-analyses, which included the three
large studies above, concluded favorable efficacy in terms of reduced exacerbations (OR 0.34,
95%CI 0.22-0.54, 341 participants) [28], sputum volume, and symptoms based on improved St.
George Respiratory Questionnaire (SGRQ) scores and improved dyspnea index [29,30].
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 and
cardiovascular events'.)
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 azithromycin therapy. Preventive monotherapy with a
macrolide antibiotic is NOT initiated if NTM are identified on culture. (See 'Mycobacterium avium
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 one
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 with two or more exacerbations of noncystic fibrosis bronchiectasis in the prior year
to take erythromycin 400 mg or placebo twice daily for one year [26]. 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 ) were also decreased, although the clinical importance of these changes appears
small. A follow-up study of the sputum microbiota of the 44 subjects in the erythromycin group
showed that reduced exacerbations occurred predominantly among subjects with initial
dominance of Pseudomonas in their sputum [27]. Over the course of the study, erythromycin
increased the proportion of macrolide-resistant oropharyngeal streptococci [26]. In addition,
those subjects with Haemophilus as the primary sputum pathogen had an increased presence
of Pseudomonas and reduced presence of Haemophilus after being on erythromycin for a
year [27].
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complex' above and "Cystic fibrosis: Overview of the treatment of lung disease", section on
'Azithromycin'.)
Daily suppressive nonmacrolide antibiotics — Daily oral nonmacrolide antibiotic treatment
has been studied in small case series, but not randomized trials. 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 [8].
Patients who have chronic airway infection with P. aeruginosa may be candidates for inhaled
antibiotic therapy, as described below.
Inhaled antibiotics — The role of inhaled antibiotics in noncystic fibrosis bronchiectasis
continues to evolve. Two society guidelines and a systematic review suggest a therapeutic trial of
inhaled antibiotics in patients with three or more exacerbations per year or significant morbidity
from fewer exacerbations and P. aeruginosa in their sputum; this is in accord with our practice
[2,15,31].
Inhaled antibiotics (eg, tobramycin, aztreonam, colistin) 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 forced expiratory volume
in one second (FEV ), and decreased hospitalizations. Inhaled antibiotics may 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 chronic pulmonary infection", section on 'Inhaled
antibiotics'.)
Studies of inhaled antibiotics in noncystic fibrosis bronchiectasis have yielded mixed results [31-
35]. The greatest experience is with inhaled tobramycin, which is generally the first choice among
these options. Studies of inhaled ciprofloxacin are promising, but no inhaled formulation is
available. No commercial formulation of inhaled gentamicin is available. Inhaled colistin has been
used in Europe, but no commercial product is available. Inhaled aztreonam is available and widely
used in cystic fibrosis, although studies in bronchiectasis are disappointing. 
1
Aerosolized tobramycin – Tobramycin is available for inhalation as a solution for nebulization
and in a dry powder inhaler. The usual dose for nebulization is 300 mg/5 mL every 12 hours in
repeated cycles of 28 days on the drug followed by 28 days off. The powdered form is dosed
112 mg (4 capsules of 28 mg each) every 12 hours in the same 28 day repeated cycles.
●
The use of aerosolized tobramycin has been studied in patients with noncystic fibrosis
bronchiectasis [32,33,35]. One trial randomly assigned 74 patients with non-cystic fibrosis
(CF) bronchiectasis and bacteriologic evidence of P. aeruginosa infection to receive
aerosolized tobramycin (300 mg, twice daily) or aerosolized placebo for 28 days [32]. Patients
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https://www.uptodate.com/contents/amoxicillin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/doxycycline-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
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https://www.uptodate.com/contents/tobramycin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/aztreonam-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/colistin-colistimethate-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/cystic-fibrosis-antibiotic-therapy-for-chronic-pulmonary-infection?sectionName=Inhaled+antibiotics&search=bronchiectasis&topicRef=1435&anchor=H16&source=see_link#H16https://www.uptodate.com/contents/treatment-of-bronchiectasis-in-adults/abstract/31-35
https://www.uptodate.com/contents/tobramycin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/ciprofloxacin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/gentamicin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/colistin-colistimethate-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/aztreonam-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/tobramycin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/tobramycin-drug-information?search=bronchiectasis&topicRef=1435&source=see_link
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in the treatment group demonstrated a 10,000-fold reduction in Pseudomonas density, but no
change in FEV as compared to controls.1
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 [33]. 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.
Inhaled ciprofloxacin – The efficacy of inhaled ciprofloxacin in preventing exacerbations has
been examined in phase III trials. Results are mixed, and the formulation is not licensed for
clinical use.
●
In the first of two identical randomized trials, RESPIRE 1, 416 subjects with
bronchiectasis were assigned to a dry powder formulation of ciprofloxacin 32.5 mg twice
daily for 14 days on/off, 28 days on/off, or placebo [36]. Ciprofloxacin in the 14 day on/off
regimen resulted in a significantly prolonged time to first exacerbation median time >336
versus 186 days (hazard ratio 0.53, 97.5% CI 0.36–0.80) and reduced frequency of
exacerbations compared with placebo in the 14 day on/off regimen (incidence rate ratio
0.61, 97.5% CI 0.40–0.91), but not the 28 day on/off regimen [36].
•
In the second trial of 521 subjects, RESPIRE 2, inhaled ciprofloxacin prolonged the time
to first exacerbation in both the 14 and 28 days on/off arms but statistical significance
was not achieved [37].
•
In a separate trial (combined two identical protocols) of aerosolized liposomal
ciprofloxacin (150 mg liposome encapsulated plus 60 mg of free ciprofloxacin) in 582
subjects, there was no significant difference in median time to first exacerbation between
the ciprofloxacin and placebo arms. However, the ciprofloxacin arm had a significant
reduction in the annual frequency of exacerbations [38].
•
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 [34]. 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
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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 [8]. If a patient is likely 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 decreases by >15 percent
or >200 mL after antibiotic inhalation, we generally do not administer further doses.
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.
Eradication of new isolates of Pseudomonas aeruginosa — Chronic airway infection with
Pseudomonas aeruginosa is associated with poor outcomes (eg, greater decline in lung function
and more frequent exacerbations) in adults with bronchiectasis [21,22]. The European Respiratory
Society (ERS) guidelines suggest eradication of new P. aeruginosa infection, but note that data
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 can be recommended.
Aerosolized 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 via eFlow nebulizer. In
paired trials that included a total of 274 patients with bronchiectasis and positive respiratory
cultures for Gram negative organisms, inhaled aztreonam did not result in clinically significant
improvement in respiratory quality of life after four weeks, despite some benefit being
demonstrated in separate studies of patients with cystic fibrosis and Pseudomonas airway
colonization [39]. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection",
section on 'Inhaled aztreonam lysine' and "Delivery of inhaled medication in adults", section
on 'Mesh nebulizers'.)
●
Aerosolizedcolistin – A randomized trial of inhaled colistin 1 million IU (aerosolized via I-neb)
versus saline placebo was performed in 144 subjects with Pseudomonas aeruginosa in their
sputum. Each subject received two weeks of intravenous anti-pseudomonal antibiotics for an
exacerbation before enrollment. The median time to first exacerbation was not significantly
different (p = 0.11) in the colistin subjects (165 days) compared with the placebo subjects (111
days). Secondary endpoints that favored colistin were improved QOL and reduced bacterial
sputum density of Pseudomonas (similar to most other aerosol antibiotic trials [40]. (See
"Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Inhaled
colistin'.)
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are limited [2]. Other experts, including ourselves do not use eradication regimens in this setting
due to the small number of patients studied and unclear benefit.
Studies in support of eradication of new P. aeruginosa isolates include the following:
Eradication of chronic P. aeruginosa infection (present for years) is unlikely to be successful [2].
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. Nebulized hypertonic saline and Dornase alfa are beneficial in cystic
fibrosis. (See "Role of mucoactive agents and secretion clearance techniques in COPD" and
"Cystic fibrosis: Overview of the treatment of lung disease", section on 'Inhaled airway clearance
agents'.)
In a randomized trial, 35 patients with new P. aeruginosa isolation were assigned to
ceftazidime and tobramycin intravenously followed by nebulized tobramycin 300 mg twice
daily or placebo for three months [41]. Twelve months later, 54 percent of the eradication
group and 29 percent of the placebo group were free of P. aeruginosa in sputum cultures. The
eradication group had fewer exacerbations, hospital admissions, and hospital days during
follow-up.
●
A retrospective study of 30 patients who underwent eradication therapy with a variety of
regimens had a reduction in exacerbation frequency following eradication, but only 54 percent
were free of P. aeruginosa after a median follow-up of 26 months [42].
●
Nebulized hypertonic saline – Nebulized hypertonic (6 to 7 percent) saline has been studied
as a mucokinetic therapy [43,44]. The 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 [45]. Based on
clinical experience, we use hypertonic saline in patients with tenacious or copious phlegm to
augment expectoration.
●
The efficacy of nebulized hypertonic saline (6 percent) was examined in 40 patients with
bronchiectasis who were randomly assigned to treatments with hypertonic saline or isotonic
saline daily for 12 months [46]. No between group differences were found in exacerbation
rates, quality of life, FEV , or sputum colonization.1
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Airway clearance therapy — We suggest that all patients with bronchiectasis receive regular
therapy to clear airway secretions (table 4). 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 [52]. Based on clinical experience,
airway clearance techniques (also known as bronchial hygiene) improve cough [53] and help
Nebulized mannitol – Mannitol is a hyperosmolar agent that is thought to hydrate airway
secretions, which might improve mucus clearance. However, clinical trials have failed to meet
primary efficacy end-points in bronchiectasis, and the available evidence does not suggest
benefit for inhaled mannitol in non-cystic fibrosis bronchiectasis [44,47]. As an example, a
multicenter trial (the largest therapeutic trial in bronchiectasis) randomly assigned 461
patients to inhale dry powder mannitol 400 mg or mannitol 50 mg (control) twice daily for 52
weeks [47]. The low dose of mannitol was used as the negative control as it has the same
taste and sensation characteristics as the full dose, but was ineffective in a prior dose-ranging
study. The exacerbation rate was not significantly reduced by mannitol 400 mg (RR 0.92, 95%
CI 0.78-1.08). Modest, but significant improvements were notedin time to first exacerbation
(165 versus 124 days for mannitol and control, respectively, p = 0.021), days of antibiotics to
treat exacerbations, and quality of life by St. George’s Respiratory Questionnaire.
●
Aerosol dry powder mannitol is not approved for use in bronchiectasis in the United States.
The dry powder formulation of mannitol for bronchoprovocation testing is available in many
countries, but not the United States. While adverse events are not generally more frequent
with mannitol than with placebo, 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 [48]. 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 [49].
●
Aerosolized Dornase alfa (recombinant deoxyribonuclease, also called DNase), which breaks
down DNA (a major gelatinous product of neutrophils), improves pulmonary function (FEV )
and reduces hospitalizations in patients with CF [50], but is not effective in non-CF-related
bronchiectasis and is potentially harmful [51]. (See "Role of mucoactive agents and secretion
clearance techniques in COPD".)
1
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.
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patients to expectorate the tenacious secretions and mucous plugs that frequently complicate
bronchiectasis.
Numerous airway clearance techniques and devices exist to loosen viscid secretions
mechanically; the most popular are listed in the table (table 4) [52]. The choice of a technique or
device should be based upon, frequency and tenacity of phlegm, 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 [54]. (See "Cystic fibrosis: Overview of the
treatment of lung disease", section on 'Chest physiotherapy'.)
ELTGOL is an airway clearance technique that involves slow expiration in the lateral posture with
the glottis opened, 15 minutes for each lung [55]. In a randomized trial, 44 participants with
bronchiectasis were assigned to ELTGOL or placebo (upper limb stretching) exercises twice daily
for one year [56]. Participants in the ELTGOL group had increased sputum volume during the
intervention and 24 hours later (approximately 12 versus 0 mL) at the start and end of the study,
fewer exacerbations (p = 0.042), and significant improvement in quality of life and Leicester cough
questionnaire, but no improvement in the six-minute walk test.
Oscillatory positive expiratory pressure (PEP) devices combine PEP with high frequency
oscillations to loosen respiratory secretions and move them toward the mouth. Each treatment
involves 6 to 10 cycles of a deep inhalation, two to three second breath hold, exhalation through
the device which creates oscillations, and coughing. In a systematic review of nine studies (213
participants), daily oscillatory PEP for four weeks was associated with improved health, compared
with breathing exercises without a device, but no difference was noted in amount of sputum
expectorated, breathlessness, or lung function compared with other airway clearance therapies
[57]. The overall quality of evidence was deemed to be low. Further study is needed to determine
whether oscillatory PEP has benefits over other airway clearance therapies during exacerbations
or with long-term use.
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 [8]. If symptoms improve on
therapy, either a short or long-acting bronchodilator is continued. 
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In a 12 month randomized, unblinded trial of 40 patients with noncystic fibrosis bronchiectasis and
chronic airflow limitation (but not asthma or chronic obstructive pulmonary disease [COPD]), the
combination of inhaled formoterol with budesonide 640 mcg/day was compared with inhaled
budesonide 1600 mcg/day alone [58,59]. The formoterol group experiencedimproved 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. A meta-analysis failed to find any additional randomized trials utilizing
a combined long-acting beta agonist and inhaled glucocorticoid [59]. Further study is needed
before long-acting beta-adrenergic agonists are used routinely in patients with bronchiectasis who
lack wheezing or reversible airflow limitation.
Anti-inflammatory medications — Since inflammation and neutrophilic mediator release play a
major role in bronchiectasis, anti-inflammatory agents such as oral or inhaled glucocorticoids,
nonsteroidal anti-inflammatory agents (NSAIDs), and statins 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.
Oral glucocorticoids – 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".)
●
Inhaled glucocorticoids – Current evidence is insufficient to support routine inhaled
glucocorticoid therapy for patients with bronchiectasis but without concomitant asthma or
COPD [8,60]. A systematic review of seven randomized trials with a total of 380 participants
did not find a significant difference in spirometry, exacerbation rate, or sputum volume
between patients using inhaled glucocorticoids and those on placebo [60]. ERS guidelines
also advise against use of inhaled glucocorticoid therapy in the absence of asthma or COPD
[2].
●
Inhaled glucocorticoids have potential adverse effects. A registry study found that inhaled
glucocorticoid use was associated with a greater likelihood of Pseudomonas aeruginosa
infection (adjusted odds ratio 1.8 [95% CI 1.24-2.6]), although it is not possible to determine
causality from the available data [61]. A separate study found evidence of adrenal
insufficiency in 48 percent of patients with bronchiectasis who were taking inhaled
glucocorticoids and in 23 percent of those not using inhaled glucocorticoids [62]. Adverse
effects of inhaled glucocorticoids are discussed separately. (See "Major side effects of inhaled
glucocorticoids".)
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Gastroesophageal reflux — There is emerging concern that gastroesophageal reflux (GER) and
bronchiectasis are associated [67]. Among patients with advanced lung disease awaiting lung
transplantation, patients with bronchiectasis had the highest prevalence of GER (50 percent) [68].
In a retrospective series of 81 patients with bronchiectasis from a single center in Ireland, 36
percent had a hiatal hernia and 62 percent had symptomatic GER. Although there was no
predilection for a single lobe to be involved with bronchiectasis, bronchiectasis severity scores
were higher or more severe in the hiatal hernia subjects [69]. 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
bronchiectasis. 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 [70]. 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
NSAIDs – 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 oral or inhaled
NSAIDs in adult noncystic fibrosis bronchiectasis [63,64]. (See "Cystic fibrosis: Overview of
the treatment of lung disease", section on 'Ibuprofen'.)
●
Statins – Statins have anti-inflammatory properties, but preliminary data do not support a role
in bronchiectasis unless the patient has another indication for statin therapy. In a pilot, single-
center study, 60 subjects with stable, mild bronchiectasis were administered atorvastatin 80
mg or placebo daily for six months [65]. Scores on the Leicester Cough Questionnaire (LCQ)
were significantly improved by 1.5 units (1.3 units is minimum clinically important difference)
in the atorvastatin group as compared with -0.7 units in the placebo group. Adverse events
including headache, leg pain, and diarrhea were more frequent in the atorvastatin group.
●
In a randomized, crossover study of 32 patients with severe bronchiectasis and chronic
Pseudomonas aeruginosa in their sputum, 27 completed the six-month trial (three months on
atorvastatin 80 mg daily or placebo) [66]. Cough as measured by the LCQ (primary endpoint)
did not improve on atorvastatin. There was improvement in the St. George’s Respiratory
Questionnaire and some indices of systemic inflammation.
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https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-gastroesophageal-reflux-in-adults?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/medical-management-of-gastroesophageal-reflux-disease-in-adults?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/seasonal-influenza-vaccination-in-adults?search=bronchiectasis&topicRef=1435&source=see_link
https://www.uptodate.com/contents/treatment-of-bronchiectasis-in-adults/abstract/70