Bronchiectasis in adults: Maintaining lung health

INTRODUCTION — Bronchiectasis is a condition 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 impaired 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, reducing inflammation, and improving bronchial hygiene [1,2]. Surgical extirpation of affected areas may be useful in selected patients with focal disease.

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 chronic pulmonary infection" and "Clinical manifestations and diagnosis of bronchiectasis in adults".)

NONPHARMACOLOGIC THERAPIES

Avoidance of lung irritants — We advise patients to avoid exposure to respiratory irritants as much as possible. In particular, we strongly encourage cessation of smoking tobacco and vaping. Other irritants, such as smoke from indoor fires and occupational exposures (eg, cleaning agents, dust, fumes), should also be avoided. (See "Overview of smoking cessation management in adults" and "Vaping and e-cigarettes" and "Trigger control to enhance asthma management", section on 'Irritants (including cigarette smoke)'.)

Airway clearance therapy — We suggest that all patients with bronchiectasis utilize regular physiotherapy to clear airway secretions (table 1) [2-4]. 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 [4,5]. Based on clinical experience, airway clearance techniques (also known as bronchial hygiene) improve cough [6] and help 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 1) [7]. 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 [8]. Patient education in the ambulatory setting may enhance adherence [9]. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Chest physiotherapy'.)

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 [10]. 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.

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. We use nebulized hypertonic saline in selected patients, but do not use inhaled mannitol or mucolytic agents such as acetylcysteine and Dornase alpha. (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'.)

●Nebulized hypertonic saline – Nebulized hypertonic (6 to 7 percent) saline has been studied as a mucokinetic therapy [11,12]. 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 [13]. 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 or isotonic saline daily for 12 months [14]. No between group differences were found in exacerbation rates, quality of life, forced expiratory volume in one second (FEV₁), or sputum colonization.

Nebulized hypertonic saline is beneficial in patients with cystic fibrosis who are age six or older. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Inhaled airway clearance agents'.)

●Inhaled 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 noncystic fibrosis bronchiectasis [12,15]. 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 [15]. 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 noted in 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 (SGRQ). A post hoc reanalysis of this trial and a prospective analysis of 333 patients followed in a Scottish registry showed that patients with the highest symptom burden (by SGRQ) had increased time to first exacerbation and fewer exacerbations with mannitol compared with placebo, while patients with lower symptom burden did not benefit [16]. This is the first study that suggests clinical trials should focus on symptom burden (cough, sputum production, dyspnea).

Dry powder mannitol for inhalation is approved in many countries but not in the United States for bronchoprovocation testing and to improve mucus clearance. 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 (acetylcysteine, Dornase alpha) – Studies of mucolytic agents have yielded variable results [17]. 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 [18].

Aerosolized Dornase alfa (recombinant deoxyribonuclease, also called DNase), which breaks down DNA (a major gelatinous product of neutrophils), improves pulmonary function (FEV₁) and reduces hospitalizations in patients with CF [19], but is not effective in non-CF-related bronchiectasis and is potentially harmful [20]. (See "Role of mucoactive agents and secretion clearance techniques in 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.

Pulmonary rehabilitation — Pulmonary rehabilitation is efficacious in chronic obstructive pulmonary disease (COPD), and a few small studies support a benefit in patients with bronchiectasis [21]. The benefits are similar to COPD with comparable improvements in validated scoring questionnaires and numbers of patients completing a program [22].

We generally offer participation in pulmonary rehabilitation to patients with impaired exercise capacity, similar to the guidelines for COPD [23]. (See "Pulmonary rehabilitation".)

Maintaining fitness may actually be associated with reduced bronchiectasis. A secondary analysis of young individuals participating in a fitness study was performed at 25 years. Fitness was defined as duration of time on a standard treadmill program. Women and men with the highest level of fitness had the least incidence of bronchiectasis on chest CT (but no chest CT at baseline 25 years earlier) and reduced cough and phlegm compared with individuals with lower levels of fitness [24].

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 [25]. The role of nutritional support in bronchiectasis needs further study. (See "Malnutrition in advanced lung disease".)

Infection control — Communicability and cross-infection with respiratory pathogens (eg, Pseudomonas aeruginosa, Burkholderia cepacia, methicillin-resistant Staphylococcus aureus [MRSA]) are important concerns in CF (see "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Infection prevention and control'). Data regarding cross-infection risk among patients with noncystic fibrosis bronchiectasis are limited, but suggest that the risk is low [26]. An expert panel has offered guidelines regarding contact precautions and hand hygiene in specialty clinics and group meetings and urged further research [26].

TREATING THE UNDERLYING DISEASES AND COMORBIDITIES

Underlying diseases that need treatment — 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) 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 2 and table 3 and table 4). (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

Examples of disease processes for which specific therapies may prevent or delay progression of bronchiectasis include the following:

●Nontuberculous mycobacterial infection – While nontuberculous mycobacterial infection can be an opportunistic infection in a patient with bronchiectasis, it can also be a primary cause of bronchiectasis [27-29]. The diagnosis and treatment are described separately. (See "Overview of nontuberculous mycobacterial infections" and "Treatment of Mycobacterium avium complex pulmonary infection in adults".)

●Primary immunodeficiency – Certain primary immunodeficiencies, such as common variable immunodeficiency, can be treated with immune globulin, intravenously (IVIG) or subcutaneously (SCIG). The use of these preparations is discussed separately. (See "Immune globulin therapy in inborn errors of immunity".)

In addition, caution is required when deciding which vaccinations are safe to administer to patients with primary immunodeficiency (table 5). (See "Immunizations in patients with inborn errors of immunity".)

●Recurrent aspiration – 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 (ABPA) – In ABPA, central bronchiectasis is caused by an inflammatory response to aspergillus colonization of the airway and is treated with glucocorticoids and antifungal agents. (See "Treatment of allergic bronchopulmonary aspergillosis", section on 'Treatment'.)

●Immune diseases – Immune diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, granulomatosis with polyangiitis (GPA), and sarcoidosis, are sometimes associated with bronchiectasis. A retrospective review of patients from a multi-center rheumatology clinic with RA and bronchiectasis (by chest CT) suggested that patients treated with rituximab had fewer exacerbations and longer survival over 10 years than those treated with TNF inhibitors [30]. (See "Overview of pleuropulmonary diseases associated with rheumatoid arthritis", section on 'Bronchiectasis' and "Pulmonary complications of inflammatory bowel disease", section on 'Airway involvement' and "Treatment of pulmonary sarcoidosis: Initial approach".)

●Sinus disease – Among causes of bronchiectasis, several affect both the upper and lower airways (eg, primary ciliary dysfunction, immune deficiency, GPA, eosinophilic granulomatosis with polyangiitis) and the sinus disease contributes to symptom burden and flares of bronchiectasis. Many patients with bronchiectasis have accompanying rhinosinus disease (infections, polyps) and post-nasal drainage. Treatment of infected sinuses may improve control of bronchiectasis. In a nonrandomized 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 compared with the medication alone group. The forced expiratory volume in one second (FEV₁) was unchanged at six months in both groups [31]. (See "Microbiology and antibiotic management of chronic rhinosinusitis" and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)

●Tracheomalacia and tracheobronchomegaly – Patients with symptomatic bronchiectasis due to tracheobronchomegaly (eg, Mounier-Kuhn syndrome) or tracheomalacia, may benefit from placement of a stent or tracheobronchoplasty to maintain airway patency and improve secretion clearance [32]. (See "Tracheomalacia in adults: Treatment and prognosis".)

Treatment of comorbid disease — Patients with bronchiectasis have a median of four comorbidities [33,34]. Comorbidities that contribute to mortality and risk of hospitalization include malignancy, chronic obstructive pulmonary disease (COPD), cognitive impairment, inflammatory bowel disease, chronic liver disease, iron deficiency anemia, peripheral vascular disease, diabetes mellitus, asthma, pulmonary hypertension, and ischemic heart disease [34]. In particular, we review spirometry and chest computed tomography for evidence of COPD and asthma as the symptoms overlap and exacerbations of COPD and asthma can mimic exacerbations of bronchiectasis and occur concurrently. (See "Acute exacerbations of asthma in adults: Home and office management" and "Acute exacerbations of asthma in adults: Emergency department and inpatient management" and "COPD exacerbations: Management".)

ANTIBIOTICS FOR 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 [35]. Retained purulent secretions and the associated inflammatory cells and mediators are an important cause of airflow obstruction, airway injury, and exacerbations in bronchiectasis [36]. Thus, reducing the microbial load with selective use of antibiotics and clearing secretions form the cornerstone of preventive therapy.

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 performed [37]. A practical approach to antibiotic selection supported by the European Respiratory Guidelines is provided in the following sections [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 [38]. (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 computed tomography (CT), accelerated decline in pulmonary function, and increased number of hospitalizations, compared with patients colonized with Haemophilus influenzae [39,40]. For this reason, attempts are often made to reduce the burden of P. aeruginosa infection.

Macrolides

Patient selection (indications, contraindications, caveats) — For patients with bronchiectasis who have recurrent exacerbations (two to three or more per year) and do not have P. aeruginosa infection, we suggest preventive therapy with a macrolide antibiotic, in accordance with the European Respiratory Society (ERS) guidelines [2]. For patients with chronic P. aeruginosa in their sputum, inhaled anti-pseudomonal antibiotics are preferred as an initial choice (see 'Inhaled antibiotics' below). Patients who have P. aeruginosa but cannot take an inhaled antibiotic and those who continue to have exacerbations despite inhaled antibiotic may benefit from macrolide therapy as an alternative to or in addition to inhaled antibiotic. Among macrolides, we prefer azithromycin as most of the supportive data are with this agent [41].

As nontuberculous mycobacteria (NTM) are commonly isolated among patients with bronchiectasis (63 percent of patients) [29], some experts (and we agree) obtain sputum stains and cultures for mycobacteria prior to initiating long-term azithromycin therapy. Preventive monotherapy with a macrolide antibiotic is NOT initiated if NTM are identified on culture to avoid development of resistant organisms. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Azithromycin' and "Bronchiectasis in adults: Treatment of acute and recurrent exacerbations", section on 'Nontuberculous mycobacterial infection'.)

Dose and duration — For most adults, azithromycin is administered 500 mg three times weekly [42] or 250 mg once daily [43]. If gastrointestinal complaints are interfering, a dose of 250 mg three times weekly is acceptable. While clinical trials have examined durations of therapy of 6 and 12 months, we typically continue azithromycin indefinitely in patients who are tolerating it well and are having fewer exacerbations than prior to initiating therapy. Some patients will have increased cough and increased exacerbations after pausing azithromycin. For that reason we maintain it through the year unless adverse events appear.

Efficacy — Four independently performed systematic reviews and meta-analyses, which included the three large trials listed below, concluded favorable efficacy for chronic macrolide therapy in terms of reduced exacerbations (OR 0.34, 95% CI 0.22-0.54, 341 participants), sputum volume, and symptoms based on improved St. George Respiratory Questionnaire (SGRQ) scores and improved dyspnea index [41,44-46]. Daily or three times weekly use of a macrolide has also been found to be efficacious in the management of bronchiectasis due to cystic fibrosis (CF). (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 [42]. Azithromycin was associated with a decrease in exacerbations compared with placebo (0.59 per patient with azithromycin and 1.57 per patient with placebo, respectively; 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 [43]. 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 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 [47]. 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 (FEV₁) 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 [48]. Over the course of the study, erythromycin increased the proportion of macrolide-resistant oropharyngeal streptococci [47]. 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 [48].

Chronic low-dose administration of a macrolide antibiotic appears to have an effect that is not solely antimicrobial [49]. 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.

Potential adverse effects — 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 and clarithromycin", section on 'QT interval prolongation and cardiovascular events'.)

Nonmacrolide oral 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 do not have airway infection with P. aeruginosa [50]. Patients who have chronic airway infection with P. aeruginosa may be candidates for inhaled antibiotic therapy, as described below. (See 'Inhaled antibiotics' below.)

Inhaled antibiotics — In accordance with society guidelines and systematic reviews, we suggest a therapeutic trial of inhaled antibiotics for patients with P. aeruginosa in their sputum and either three or more exacerbations per year or significant morbidity from fewer exacerbations [2,37,51,52]. Additionally, treatment with inhaled antibiotics may be reasonable for patients not infected with P. aeruginosa in whom oral antibiotic prophylaxis is contraindicated, not tolerated, or ineffective [2]. Combination therapy with an inhaled antibiotic and a macrolide is typically not useful but may be attempted if single-agent treatment has been only marginally effective. (See 'Macrolides' above.)

Our first choice for patients with >2 to 3 exacerbations/year and sputum growing a Gram negative potential pathogen is one of the commercially available inhaled tobramycin agents. For individuals who cannot tolerate tobramycin, inhaled aztreonam, colistin, or gentamicin are possible choices. Aerosolized preparations of aztreonam lysine and colistin have demonstrated benefit in CF, but not in noncystic fibrosis bronchiectasis, possibly due to methodologic issues. Inhaled aztreonam lysine is available and widely used in CF. Inhaled colistin and gentamicin are used in Europe, but commercial products are not available in the United States. No formulation of inhaled ciprofloxacin is available specifically for inhalation (see 'Ineffective agents' below).

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 FEV₁, 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'.)

●Inhaled tobramycin – Tobramycin is available for inhalation as a solution for nebulization and in a dry powder inhaler [53-58]. 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 [54].

In a systematic review, five studies (184 participants) were identified that compared nebulized tobramycin with placebo in patients with bronchiectasis and P. aeruginosa [53]. Inhaled tobramycin reduced P. aeruginosa density in sputum. Improvements in patient-important outcomes such as hospitalizations, exacerbations, and symptoms had a positive trend, but definitive conclusions were limited by variable study designs and small numbers.

A larger trial of standard-dose inhaled tobramycin versus placebo in patients with bronchiectasis and chronic P. aeruginosa infection demonstrated similar reductions in pseudomonas density (mean 1.74 Log₁₀ colony forming units/g) as well as a borderline clinically meaningful improvement in respiratory symptoms (Quality of Life-Bronchiectasis Respiratory Symptom Score; +7.9) [59]. These changes modestly diminished over additional treatment cycles. There were no statistically significant differences in lung function or exacerbation rates.

●Aerosolized aztreonam lysine – Aztreonam is a monobactam with a monocyclic beta-lactam structure. Aerosolized aztreonam lysine is used in patients with CF in whom inhaled tobramycin is not effective or not well tolerated, but it is off label in noncystic fibrosis bronchiectasis. The lysine salt formulation is used for inhalation instead of the intravenous preparation, which induces airway inflammation. The dose is 75 mg via eFlow mesh nebulizer three times daily in repeated cycles of 28 days on drug followed by 28 days off drug. Pretreatment with a bronchodilator is advised. (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'.)

In paired trials (AIR-BX1 and AIR-BX2) that included a total of 540 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 [60]. A “second” look at the data from this study showed that the individuals with higher bacterial load (all screening cultures had quantitative analysis of bacterial organisms) of the pathogenic organisms showed an improvement in the respiratory domain of the QOL-B questionnaire as compared to those with a lower bacterial load [61]. In a retrospective analysis of 440 participants in AIR-BX1 and AIR-BX2, cough and purulence (evidence by color) were significantly improved with aztreonam compared with placebo [62].

An additional clinical trial of aztreonam lysine in noncystic fibrosis bronchiectasis is in progress (NCT03696290).

●Aerosolized colistin – Inhaled colistin (colistimethate) is used to treat chronic P. aeruginosa infection in CF. In the United States, it is delivered by nebulizing an intravenous formulation (an off-label use). Outside of the United States, formulations designed for inhalation are available, either as a powder intended for suspension in liquid and nebulization, or as capsules containing a dry powder that is directly inhaled. The dose typically used in CF is 150 mg, diluted in 2 mL of sterile water and administered by nebulizer twice per day for 28 days, alternating with 28 days off treatment.

A randomized trial of inhaled colistin 1 million IU (aerosolized via I-neb) versus saline placebo was performed in 144 subjects with P. aeruginosa in their sputum (phase 2). 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) [63]. A preliminary report on a phase 3 trial (PROMIS-I) of inhaled colistin reported reduced exacerbations, prolonged time to first exacerbation, and reduced levels of P. aeruginosa in sputum [64]. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Inhaled colistin'.)

Studies have not demonstrated benefit with inhaled ciprofloxacin or inhaled gentamicin for noncystic fibrosis bronchiectasis, although inhaled gentamicin is used in some countries. Inhaled ciprofloxacin is discussed below. (See 'Ineffective agents' below.)

●Aerosolized gentamicin – Aerosolized gentamicin, prepared by diluting the intravenous preparation with saline, was assessed in 58 patients with noncystic fibrosis bronchiectasis, who were randomly assigned to use nebulized gentamicin 80 mg twice daily or normal saline placebo for a year [65]. Patients were aware of their medication assignment. The primary endpoint of reduction in sputum bacterial density was achieved in the gentamicin cohort as compared with 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 can be recommended.

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 [50]. 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 FEV₁ 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.

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.

Eradication of new isolates of Pseudomonas — The ERS guidelines suggest eradication of new P. aeruginosa infection, but note that data 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:

●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 [58]. 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 [66].

Eradication of chronic P. aeruginosa infection (present for years) is unlikely to be successful [2].

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. However, aerosol bronchodilator therapy, as used in asthma and COPD, has not been studied extensively 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 [50]. If symptoms improve on therapy, either a short- or long-acting beta-agonist is continued.

●For those lacking evidence of airway obstruction on spirometry, we typically do not initiate long-acting bronchodilators.

In an unblinded trial of patients with bronchiectasis and airway obstruction, the combination of inhaled formoterol with budesonide 640 mcg/day was compared with inhaled budesonide 1600 mcg/day alone [67,68]. 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.

In a small placebo-controlled trial of 34 patients with bronchiectasis without reversible airway obstruction, COPD, or asthma, beclomethasone-formoterol combination therapy showed no effect on cough, quality of life, dyspnea, lung function, or pulmonary exacerbations [69]. However, more adverse events (including exacerbations) and therapeutic discontinuation occurred in the ICS/LABA group.

There is little evidence to suggest that LAMAs improve patient-important outcomes in patients with bronchiectasis. One double-blind cross-over trial assessed the use of tiotropium in patients with noncystic fibrosis bronchiectasis, airflow obstruction, and a <20 pack-year smoking history [70]. Approximately half of the patients were on treatment with long-acting beta-agonist/inhaled glucocorticoid therapy, which was maintained throughout the trial. After 26 weeks, tiotropium modestly improved trough FEV₁ (treatment difference 58 mL [3.3 percent], 95% CI 23-92 mL), but failed to impact exacerbation rate, patient-centered measures of disease, or sputum neutrophil or eosinophil counts. The patients were not stratified by bronchodilator responsiveness.

Further study is needed before long-acting bronchodilators 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 that support efficacy of any of these agents in adults with stable or acute bronchiectasis, and we do not use NSAIDs or statins for this purpose. (See 'Ineffective agents' below.)

●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 adverse 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 [50,71], and ERS guidelines advise against use of inhaled glucocorticoid therapy in the absence of asthma or COPD [2]. 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 [71]. In contrast, a post hoc analysis of a study of inhaled glucocorticoids in bronchiectasis (published after the systematic review) suggested that individuals with blood eosinophils >3 percent had improved QOL by the SGRQ at the end of six months compared with those who did not use inhaled glucocorticoids or had lower eosinophil counts [72]. Similarly, a separate registry analysis of 928 patients with bronchiectasis (but not asthma or allergic bronchopulmonary aspergillosis) examined bronchiectasis outcomes according to degree of peripheral eosinophilia [73]. Inhaled glucocorticoids only showed a significant impact on exacerbations in the subgroup with peripheral eosinophil counts >300 cells/microL (n = 153), in which those taking glucocorticoids had decreased total exacerbations (1.5 versus 2.2 per year) and hospitalizations (0.7 versus 1.2 per year) compared with the entire cohort. Further study on inhaled glucocorticoids in those with elevated markers of type 2 inflammation may better define a therapeutic role for these agents in bronchiectasis.

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 [74]. 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 [75]. Adverse effects of inhaled glucocorticoids are discussed separately. (See "Major side effects of inhaled glucocorticoids".)

Gastroesophageal reflux — There is emerging concern that gastroesophageal reflux (GER) and bronchiectasis are associated [76,77]. Among patients with advanced lung disease awaiting lung transplantation, patients with bronchiectasis had the highest prevalence of GER (50 percent) [78]. 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 [79]. 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 administered annually to patients with bronchiectasis, except those unable to receive live attenuated vaccines due to immune deficiency disease (table 5). (See "Seasonal influenza vaccination in adults" and "Immunizations in patients with inborn errors of immunity".)

Pneumococcal vaccine is typically given to patients with bronchiectasis, as is recommended for patients with other chronic respiratory diseases [80]. Pneumococcal vaccination with the conjugate vaccine is recommended for patients with combined immunodeficiencies, antibody deficiency, complement deficiencies, congenital asplenia, and phagocyte disorders who are not receiving immune globulin (table 5). In a randomized trial 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 [81]. (See "Pneumococcal vaccination in adults" and "Immunizations in patients with inborn errors of immunity", section on 'Pneumococcal vaccine'.)

Ineffective agents

●Inhaled ciprofloxacin – Studies of the efficacy of inhaled ciprofloxacin have yielded mixed results, and there is no formulation that is 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 [82]. 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 [82].

•In two separate trials (identical protocols) of aerosolized liposomal ciprofloxacin (135 mg liposome encapsulated plus 54 mg of free ciprofloxacin; called ARD-3150), participants (290 in ORBIT-3 and 308 in ORBIT-4) were randomly assigned (2:1) to ciprofloxacin or placebo once daily for 48 weeks [83]. The primary endpoint, median time to first exacerbation, was significantly prolonged in the ARD-3150 group in ORBIT-4, but not in ORBIT-3 nor the pooled groups. There was no difference in adverse events between ARD-3150 and placebo.

●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 [84,85]. (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 [86]. 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) [87]. Cough as measured by the LCQ (primary endpoint) did not improve on atorvastatin. There was improvement in the SGRQ and some indices of systemic inflammation.

PHYSICIAN-PATIENT PARTNERSHIP — Bronchiectasis is a chronic disease that requires prompt responses to exacerbations and, for many patients, daily therapy at home. Partnerships between patients and the clinical team (physicians, nurses, respiratory therapists, pharmacists) are essential to the development of successful management plans and reinforcement of treatment modalities [88].

Collaborative management — We establish an active partnership with patients to identify goals that are important (eg, reducing and expectorating sputum, maintaining and improving exercise tolerance, treating bacterial infections promptly, and avoiding hospitalization) and work with them to achieve these goals. Patients are more likely to adhere to therapies that resonate with their goals when they participate in the decision-making. The physician/health care provider acts as an educator and facilitator.

The British Thoracic Society advises use of a bronchiectasis self-management plan [89,90], although formal research in support of self-management in bronchiectasis is limited. A systematic review found two trials that assessed self-management interventions for bronchiectasis; neither met the primary end-point of improved health-related quality of life.

Education and self-efficacy — Patients have a spectrum of learning styles and literacy skills, so programs should provide patients with a variety of resources to help match their individual needs. Video and electronic communication and patient-driven resources are important adjuncts to office explanations (www.bronchiectasis.me) [88]. (See 'Information for patients' below.)

The key educational topics include the meaning of the diagnosis of “bronchiectasis,” why patients develop it, what symptoms they can expect to have in the future, how they can adjust their day-to-day activities to minimize disease impact, and how best to respond to early symptoms of an exacerbation. Armed with this information, patients can develop self-efficacy and take an active role in management of their bronchiectasis.

Communication — Communication between the healthcare team and the patient is enhanced by an understanding of the individual patient’s disease experience and how they engage with information about their health. Eliciting and responding to the patient’s concerns and questions helps to build trust and providing educational resources that dovetail with the advice given by the healthcare team can increase that trust [9]. A written management plan should be prepared, reviewed, and edited over time as needed. Communication channels should be made clear (ie, phone numbers for general and emergency use, access to secure electronic messaging, names of primary caregiver and/or consultants, and resources for emergency care [emergency department, Urgent Care, etc]).

Monitoring

●Symptoms and history – Patients should be asked about dyspnea and exercise tolerance. Color, consistency, and estimated quantity of sputum should be recorded at each visit as this information is helpful when determining if a patient has an exacerbation. New or increasing hemoptysis is almost always a concern for medical attention.

Between visits, patients should record exacerbations particularly when they’ve had an emergency department visit or hospitalization, or antibiotics have been administered.

New respiratory medications including dosage and frequency should be recorded and shared. Use of airway clearance techniques should be reviewed. Personal exercise programs should be updated (walking, treadmill/cycle, etc) along with any limitations.

●Sputum culture – Sputum culture is obtained at the time of exacerbations before administration of an antibiotic and periodically at the time of office visits. A sterile sputum collection cup can be provided to the patient to obtain a first morning sample at the time of their next visit or if they have symptoms of an exacerbation.

PROGNOSIS — 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, although long-term outcomes studies are limited [20,40,91-95].

●Exacerbations – Among 1826 patients enrolled in the US Bronchiectasis Research Registry, exacerbations were reported at baseline in 64 percent within the preceding two years [29]. Some patients appear to be “frequent exacerbators” with three or more exacerbations per year, while other patients have fewer exacerbations [96]. In the EMBRACE trial described above, patients with a history of at least one exacerbation in the prior year, the exacerbation rate was 1.57 per patient over 6 months [42].

●Severity and prognosis – Scoring systems have been proposed to help guide assessment of prognosis and identify patients who frequently exacerbate [95,97]. 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 [95]. Predictors of hospitalizations included previous hospitalization, high dyspnea index, low forced expiratory volume in one second (FEV₁), presence of Pseudomonas in sputum, and more extensive involvement (>3 lobes) on high resolution computed tomography (HRCT). Mortality correlated with older age, low FEV₁, previous hospitalization, and three or more exacerbations in the year before study.

The FACED score (FEV₁, Age, Colonization with Pseudomonas, Extended involvement on chest computed tomography [CT], and Dyspnea) was developed in 397 patients of a multicenter cohort of 819 patients from Spain [97]. The ability of the scoring system to predict five-year all-cause mortality was validated in the remaining patients of the same cohort.

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 15 years [98]. 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 [99].

Another approach to estimating exacerbations and survival utilizes the cluster analysis approach as studied in asthma and chronic obstructive pulmonary disease (COPD). Daily sputum production and the presence of Pseudomonas or other potential infectious pathogens in sputum culture were the main features linked to quality of life (QOL), inflammatory markers, and clinical outcome at three years [100].

●Hospitalization and mortality – Small studies have described mortality rates of 16 to 20 percent over five years, increasing with intensive care unit (ICU) hospitalization and comorbidity. A study from the United Kingdom found that the age-adjusted mortality for adults with bronchiectasis was approximately twice that of the general population, independent of age differences [33]. Two retrospective series assessed outcomes of patients with bronchiectasis admitted to an ICU for respiratory failure for the first time [91,101]. A report of 48 patients from France found 19 percent mortality in the ICU and 40 percent mortality at one year [91]. 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 [101]. Severe hypoxemia and higher APACHE II scores were worse prognostic factors. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)

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 [102].

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 [103]. The cause of death was mainly respiratory (58 percent).

●Lung function decline – Patients with bronchiectasis have a mean annual decline in FEV₁ of 50 to 55 mL per year [40]. This is greater than normal individuals (20 to 30 mL per year), but similar to patients with COPD (approximately 60 mL per year). Among patients with bronchiectasis, the decline in FEV₁ 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 [92]. 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 FEV₁, low diffusing capacity of carbon monoxide (DLCO), hypercarbia, and hypoxemia. Only 15 percent of patients had evidence of left ventricular dysfunction.

●Cardiovascular morbidity – Respiratory tract infections are associated with increased cardiovascular events (CV: myocardial infarction, stroke) [104]. In an audit of patients with 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 [105]. 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 [106]. Serum desmosine, a marker of elastin degradation, may be a marker for cardiovascular and all-cause mortality [107]. 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 [108]. However, information about cigarette smoking, social factors, and environmental factors were not available in the database to enable adjustment for these variables.

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" and "Society guideline links: Primary ciliary dyskinesia" and "Society guideline links: Hemoptysis".)

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^th to 6^th 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^th to 12^th 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.)

●Basics topic (see "Patient education: Bronchiectasis in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Bronchiectasis is a syndrome of chronic cough and viscid sputum production associated with airway dilation and bronchial wall thickening. Exacerbations are usually caused by acute bacterial infections. (See "Bronchiectasis in adults: Treatment of acute and recurrent exacerbations".)

●Physician-patient partnership – Bronchiectasis is a chronic disease that requires prompt responses to exacerbations and, for many patients, daily therapy at home. Partnerships between patients and the clinical team (physicians, nurses, respiratory therapists, pharmacists) are essential to the development of successful management plans and reinforcement of treatment modalities. We establish an active partnership with patients to identify goals that are important to them and work with them to develop a management plan to achieve these goals. (See 'Physician-patient partnership' above.)

●Nonpharmacologic therapies

•Airway clearance – We suggest that all patients with bronchiectasis regularly use airway clearance techniques to help remove airway secretions (Grade 2C). Airway clearance techniques are listed in the table (table 1). (See 'Airway clearance therapy' above.)

•Mucolytic therapy and airway hydration – There are insufficient data to advocate routine use of nebulized hypertonic saline, inhaled mannitol, or acetylcysteine in patients with bronchiectasis. We use hypertonic saline in patients with viscid sputum or frequent exacerbations. Use of inhaled dornase (DNase) has not been shown to be beneficial as a mucolytic agent in noncystic fibrosis bronchiectasis and may be deleterious. (See 'Mucolytic agents and airway hydration' above.)

•Pulmonary rehabilitation – We offer pulmonary rehabilitation to patients with moderate-to-severe airflow limitation on pulmonary function testing. (See 'Pulmonary rehabilitation' above and "Pulmonary rehabilitation".)

●Evaluation of underlying diseases – We evaluate for underlying diseases (eg, nontuberculous mycobacterial infection, immunodeficiency, cystic fibrosis, recurrent aspiration, allergic bronchopulmonary aspergillosis, tracheobronchomegaly, rheumatic disease) for which specific therapy may interrupt progression of bronchiectasis. (See 'Underlying diseases that need treatment' above.)

●Antibiotics for prevention of exacerbations

•Patients without chronic Pseudomonas – For patients who have recurrent exacerbations and do not have Pseudomonas aeruginosa infection, 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. (See 'Macrolides' above.)

•Patients with chronic Pseudomonas – For patients with three or more exacerbations per year, or significant morbidity from fewer exacerbations, and P. aeruginosa in their sputum, we suggest a therapeutic trial of inhaled tobramycin (Grade 2C). Treatment with inhaled tobramycin may also be reasonable for patients not infected with P. aeruginosa in whom oral antibiotic prophylaxis is contraindicated, not tolerated, or ineffective. (See 'Inhaled antibiotics' above.)

Patients who experience bronchospasm with a test dose of inhaled antibiotic require premedication with a short-acting bronchodilator (eg, a beta-agonist). (See 'Inhaled antibiotics' above.)

•Patients who have P. aeruginosa but cannot take an inhaled antibiotic may benefit from macrolide therapy as an alternative. (See 'Patient selection (indications, contraindications, caveats)' above.)

●Avoidance of glucocorticoids – Inhaled glucocorticoids should not be routinely used in patients with bronchiectasis unless they are indicated for control of concomitant asthma or COPD. Systemic glucocorticoids should be reserved for acute exacerbations with wheezing suggestive of asthma or COPD and should accompany antibacterial therapy. (See 'Anti-inflammatory medications' above.)

●Other medical therapies – Inhaled bronchodilators, medications to reduce gastroesophageal reflux, and immunization are appropriate in selected patients. For patients with bronchiectasis and reversible airflow limitation on spirometry, we suggest a trial of inhaled beta-adrenergic agents (Grade 2C). (See 'Other medical therapies' above.)

●Prognosis – The prognosis of bronchiectasis is influenced by the underlying disease process, frequency of exacerbations, and comorbidities, but overall, the age-adjusted mortality is increase compared with the general population. (See 'Prognosis' above.)