Bronchiectasis in adults: Treatment of acute and recurrent exacerbations

INTRODUCTION — Bronchiectasis arises from chronic inflammation in the airways, leading to pathologic airway dilation and wall thickening. Clinically, this manifests with chronic cough and viscid daily sputum production as well as a propensity to develop recurrent upper airway infections, termed bronchiectasis exacerbations. Acute exacerbations stimulate ongoing neutrophilic airway inflammation, resulting in progressive lung damage, lung function decline, and worsened quality of life [1].

Multiple conditions may precipitate the development of bronchiectasis, but all require an initial infectious insult in combination with either impairments in airway drainage or defects in host defense. Of the multiple etiologies of bronchiectasis, only a few respond to direct treatment (eg, cystic fibrosis, certain immunodeficiencies, nontuberculous mycobacterial (NTM) infection, alpha-1 antitrypsin deficiency, and allergic bronchopulmonary aspergillosis). Instead, management of bronchiectasis is aimed primarily at treating exacerbations, controlling chronic infection and airway bleeding, reducing inflammation, and improving bronchial hygiene [1,2]. Surgical resection of affected areas may also be useful in selected patients.

The treatment of bronchiectasis exacerbations, including surgical options for refractory disease, will be reviewed here. The diagnosis and treatment of cystic fibrosis and the clinical manifestations, diagnosis, and chronic management of stable bronchiectasis in adults are discussed separately.

●(See "Cystic fibrosis: Clinical manifestations and diagnosis".)

●(See "Cystic fibrosis: Overview of the treatment of lung disease".)

●(See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

●(See "Bronchiectasis in adults: Maintaining lung health".)

DEFINITION — The diagnosis of an acute exacerbation is made exclusively by reported symptoms. Developed for research purposes (but useful in a clinical context as well), the consensus definition of bronchiectasis exacerbation is an acute clinical deterioration, requiring a change in therapy, manifesting with at least three of the following symptoms over ≥48 hours [3]:

●Cough

●Sputum volume and/or consistency

●Sputum purulence

●Breathlessness and/or exercise intolerance

●Fatigue and/or malaise

●Hemoptysis

Implied within this definition is the exclusion of other causes of clinical deterioration, such as pneumonia, anemia, pulmonary embolism, or heart failure. Although antibiotic therapies can be similar, bronchiectasis exacerbations arise from acute on chronic infection of the airways (which can sometimes extend to the lung parenchyma), while pneumonias are caused by acute infection of the lung parenchyma. Evaluation and treatment of pneumonia is discussed separately. (See "Overview of community-acquired pneumonia in adults" and "Pseudomonas aeruginosa pneumonia".)

RISK FACTORS — The most reliable predictor of future exacerbations is a prior history of exacerbations [4]. Patients with chronic Pseudomonas aeruginosa infection also have greatly increased exacerbation risk [5]. There is accumulating evidence that viral infections are important initial triggers of bronchiectasis exacerbations [6,7].

Among 1826 patients enrolled in the United States Bronchiectasis Research Registry, exacerbations were reported at baseline in 64 percent within the preceding two years [8]. Some patients appear to be "frequent exacerbators," defined as having three or more exacerbations per year, while other patients have fewer exacerbations [9]. In the nonintervention arm of one clinical trial, patients with bronchiectasis and a history of at least one exacerbation in the prior year developed an average of 1.6 exacerbations over the ensuing six months [10].

In one analysis of 21 observational studies and over 3500 patients with bronchiectasis, patients with chronic Pseudomonas infection had an average of 1.0 additional exacerbations per year (95% CI, 0.6-1.3 exacerbations/year) and a more than six-fold increased risk of hospital admission (odds ratio [OR] 6.6, 95% CI 3.2-14) [11] compared with the remainder of the cohort. In a separate cluster analysis of multiple European databases, chronic Pseudomonas infection defined a clinical phenotype that included increased inflammatory markers, more severe disease, lower quality of life, and increased risk of exacerbations [5].

Respiratory viral infections (eg, rhinovirus, influenza, and Epstein-Barr virus) may trigger exacerbations of bronchiectasis. Most studies are observational and demonstrate increased respiratory virus prevalence at times of exacerbations compared with steady state [6]. Some studies also show increased inflammatory markers during virus-associated exacerbations, lending credence to a viral role in exacerbation pathogenesis.

The role of respiratory viruses in triggering exacerbations of bronchiectasis is further supported by a prospective analysis of 147 patients from an international registry of bronchiectasis over the course of the coronavirus disease 2019 (COVID-19) pandemic [7]. During the first year of the pandemic (March 2020 to March 2021), this cohort experienced an average of 1.1 exacerbations per year, compared with 2.1 and 2.0 exacerbations per year in the preceding two years [7]. The percentage of patients with severe exacerbations requiring hospitalization was 9 percent in the pandemic year, compared with 14 and 16 percent previously. Only two patients suffered confirmed COVID-19 infections. A further retrospective cohort study of insurance databases confirmed reduced exacerbations during the first year of the pandemic in the United States [12]. Social distancing measures (eg, stay-at-home orders, mask wearing, social distancing) with reduction in viral exposures likely contributed to this dramatic decline in exacerbations.

Other risk factors are under investigation. Sputum neutrophil elastase is an emerging biomarker candidate that correlates with increased future exacerbation risk and antibiotic responsiveness, but testing is not yet widely available [13,14]. Air pollution may also increase the risk of exacerbations, particularly ones in which a particular pathogen is not identified [15]. One study has suggested that relative immunoglobulin G2 (IgG2) subclass deficiency may be associated with increased exacerbation risk [16]. Patients with stable bronchiectasis and either high depression scores or a high symptom burden identified using validated questionnaires (Hospital Anxiety and Depression Scale [HADS] or Quality of Life Bronchiectasis Respiratory Symptom Scale [Qol-B-RSS], respectively) had an increased risk of an exacerbation in the ensuing year. [17,18].

PRESENTATION AND INITIAL EVALUATION — Most patients with recurrent exacerbations have a recognizable change in respiratory and systemic symptoms that typify a new exacerbation. Evaluation of exacerbations is focused on excluding other causes of worsening symptoms and identifying the specific pathogen(s) involved.

Presenting symptoms and signs — Acute bacterial infections are usually heralded by increased production of sputum that is more viscous and darker in color than baseline. This altered sputum production may be accompanied by shortness of breath, pleuritic chest pain, or hemoptysis. Despite the infectious nature of the process, fever and chills are frequently absent; fatigue and malaise are common [3].

Lung examination may be normal or may reveal crackles, rhonchi, low-pitched or polyphonic wheezes, or midinspiratory squeaks. High-pitched expiratory wheezes may also be heard, particularly in patients with concomitant asthma or COPD.

Identifying pathogens — All patients presenting with an acute bronchiectasis exacerbation should have a Gram stain and sputum culture prior to antibiotic therapy. Prompt sputum culture helps identify the causal organism and allows adjustment of initial therapy based on antibiotic susceptibility. Because exacerbations of bronchiectasis can be triggered by respiratory viral infections, we send nasal secretions for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing depending on local disease patterns.

The bacterial flora in bronchiectasis is slightly different from that seen in chronic bronchitis. Frequently isolated pathogens include Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa (especially mucoid types), Stenotrophomonas maltophilia, and, less frequently, Streptococcus pneumoniae [19-21]. The likelihood of resistant organisms tends to increase with the number of prior courses of antibiotics.

Assessing for concomitant pneumonia — Complaints of fever, chills, night sweats, or severe breathlessness should prompt a chest radiograph to evaluate for pneumonia. Bronchiectasis patients with pneumonia may notice more systemic symptoms or localized chest pain than they typically experience with other exacerbations.

For patients with fever ≥38°C, tachypnea, tachycardia, hypotension, altered mental status, or respiratory distress, we assess resting and ambulatory oximetry, order a complete blood count and differential, and obtain routine chemistries including (blood urea nitrogen) BUN and creatinine to further assess exacerbation severity. Arterial blood gases may also be drawn when the presentation raises concern for respiratory failure (eg, respiratory distress, altered mental status). Most of these patients require initial inpatient management. (See 'Defining severity and site of care' below.)

Treatment for pneumonia in bronchiectasis patients must consider the likelihood of resistant pathogens but otherwise adheres to standard treatment strategies. (See "Overview of community-acquired pneumonia in adults" and "Pseudomonas aeruginosa pneumonia".)

MANAGEMENT OF INFECTION — The mainstay of therapy for bronchiectasis exacerbations is antimicrobial treatment. Prompt management of acute infection with appropriately targeted therapies decreases inflammation and additional structural lung damage, thereby preventing disease progression. Optimal antibiotic selection and tailoring based on sensitivities allow control of exacerbations while minimizing the development of highly resistant pathogens.

Defining severity and site of care — Most acute exacerbations arise from low-grade infections of the upper airways that can be managed in the outpatient setting. However, certain high-risk features or practical considerations may prompt inpatient management. These include evidence of severe infection, concern for patient frailty, need for intravenous therapy, difficulties with adherence, active hemoptysis, and outpatient treatment failure (table 1) [22].

Approach to outpatient antibiotic therapy, for low-risk patients — Most afebrile, clinically stable patients with an exacerbation of bronchiectasis can be treated with an oral antibiotic. The initial antibiotic regimen for acute exacerbations of bronchiectasis is tailored to prior sputum cultures and sensitivities, when possible, rather than chosen empirically. Additional factors in antibiotic selection include determining whether to use oral or parenteral administration, the history of success or failure of prior regimens, and the presence of allergy or intolerance to antimicrobial agents. There is no role for inhaled antibiotics as sole agents during an acute exacerbation.

Initial antibiotic selection — The initial antibiotic selection is guided by any sputum culture results obtained within the past 12 to 24 months as well as prior patient experience.

●No recent sputum culture data available – For those without culture information, a fluoroquinolone (eg, levofloxacin, moxifloxacin) is a reasonable, broad spectrum therapeutic option.

●Recent sputum culture with sensitive organisms – For patients whose sputum cultures do not show beta-lactamase-positive H. influenzae or Pseudomonas, reasonable initial antibiotic choices include either amoxicillin 500 mg three times daily or doxycycline 100 mg twice daily based on typical colonization and local antibiotic resistance patterns. Alternatively, other antibiotics with a similar spectrum of coverage may be used. (See 'Identifying pathogens' above.)

●Recent sputum culture with nonpseudomonal beta-lactamase-positive organism – In the presence of Moraxella catarrhalis or beta-lactamase producing H. influenzae, oral antibiotic choices include amoxicillin-clavulanate, a second or third generation cephalosporin, doxycycline, or a fluoroquinolone [23]. (See "Moraxella catarrhalis infections", section on 'Treatment' and "Epidemiology, clinical manifestations, diagnosis, and treatment of Haemophilus influenzae", section on 'Directed treatment'.)

●Prior sputum-growing Pseudomonas – Regardless of antibiotic sensitivity, Pseudomonas aeruginosa infections are highly virulent and associated with a poor prognosis. The presence of sputum Pseudomonas aeruginosa is associated with increased death, exacerbations, and hospital admissions [5,11,24,25]. Exacerbations in patients with chronic Pseudomonas infection should be treated aggressively with antibiotics based on known sensitivities alongside close monitoring to assess for treatment failure. Inhaled antibiotics have not been found to be useful in the setting of acute exacerbations.

In the absence of known resistance to quinolones, the usual initial antibiotic choice is ciprofloxacin, 500 to 750 mg twice daily [23]. However, if the patient has had prior courses of ciprofloxacin, quinolone resistance often necessitates administration of intravenous antibiotics. Examples include piperacillin-tazobactam, a 4^th generation cephalosporin (cefepime or ceftazidime), an aminoglycoside (tobramycin favored, but never as monotherapy), a carbapenem (meropenem or imipenem), or aztreonam.

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 has been studied, but it has not been found to be helpful. For example, in one 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 [26]. The addition of inhaled TS to ciprofloxacin did not improve clinical outcomes compared with ciprofloxacin alone, although there was a marked reduction in sputum Pseudomonas density in the TS plus ciprofloxacin group. Wheezing was more common with inhaled TS.

Although current data do not suggest utility in the acute setting, certain aerosolized antibiotics may be helpful for exacerbation prophylaxis. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Inhaled antibiotics'.)

Duration of therapy — The optimal duration of therapy is not well defined. Engaging patients in shared decision making surrounding acute treatment is important for maintaining a therapeutic alliance. For patients who rarely experience exacerbations, we agree with expert groups who favor a treatment duration of 10 to 14 days [27,28]. Patients with more frequent exacerbations often form strongly held opinions regarding antibiotic therapy.

European Respiratory Society (ERS) guidelines 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]. The same guideline panel suggested that patients with mild symptoms, milder baseline disease, sensitive nonpseudomonal pathogens, or a rapid return to baseline state may benefit from shorter courses, although evidence to support this is lacking [2]. These factors play a role in our shared decision making with patients.

Tailoring therapy — We do not usually tailor oral antibiotics to new sputum culture results if the patient is improving on their current regimen [22]. For patients who are failing to improve, however, we switch to appropriate coverage for the newly isolated organisms. In addition, we generally narrow home intravenous regimens to the most effective and efficient therapies with the fewest side effects based on current susceptibilities.

Assessing treatment failure — Most outpatients who receive effective antibiotic therapy notice some improvement in their symptoms within 72 hours. Failure to improve or worsening systemic symptoms (eg, fevers, chills, malaise) should prompt re-evaluation of therapy, including a repeat chest radiograph and sputum culture [22]. In patients whose initial culture demonstrates suboptimal antibiotic selection based on the isolate, switching to an alternative outpatient regimen is reasonable if there are no new high-risk clinical features (table 1). (See 'Defining severity and site of care' above.)

For patients with new high-risk clinical features or without an explanation for treatment failure, we frequently transition to intravenous antibiotic therapy in a hospital. (See 'Patients admitted after failed outpatient therapy' below.)

Approach to inpatient therapy — Some patients with acute bronchiectasis exacerbations requiring intravenous antibiotic therapy begin treatment in the hospital setting. Selection of antibiotic therapy otherwise depends on the indication for inpatient treatment (table 1).

Patients with severe infection — Patients with bronchiectasis demonstrating evidence of severe infection, sepsis, or impending respiratory failure should receive broad-spectrum intravenous antibiotics covering both Pseudomonas and methicillin-resistant Staphylococcus aureus (MRSA) while awaiting culture data. Typical regimens use vancomycin or linezolid for MRSA and an antipseudomonal penicillin, third generation cephalosporin, carbapenem, or aztreonam for Pseudomonas. Those with known chronic pseudomonal infection should receive antibiotics based on recent susceptibilities; we prefer up-front dual-agent therapy (eg, addition of a fluoroquinolone or aminoglycoside to one of the options listed above) pending culture results.

Once the patient has stabilized and results of initial cultures are available, the antibiotic regimen can be narrowed to a sensitive antibiotic with the fewest side effects. For patients with resistant organisms such as P. aeruginosa or requiring intravenous antibiotics, we prefer a 14-day course [23].

Patients requiring intravenous antibiotics for resistant organisms — Patients without high-risk features who require intravenous antibiotic therapy for resistant organisms should be treated based on the culture data available, with therapy tailored based on any new culture results.

●Prior sputum culture with resistant Pseudomonas – For patients with known airway infection with Pseudomonas that is resistant to oral quinolones, the initial antibiotic choice is based on the sensitivity profile from culture data and history of allergy to antibiotics. (See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Antibiotics with antipseudomonal activity'.)

It is controversial whether single or dual (eg, beta-lactam plus aminoglycoside) antibiotic therapy is preferable for flares of bronchiectasis due to Pseudomonas [22]. A meta-analysis of studies examining this question in patients with cystic fibrosis was unable to determine which course of therapy is better [29]. We typically use a single agent (eg, antipseudomonal penicillin, ceftazidime, carbapenem, or aztreonam) unless the patient appears acutely ill. (See 'Patients with severe infection' above.)

The questions of single versus dual therapy and antibiotic selection and dosing for Pseudomonas pneumonia are discussed in greater detail separately. (See "Pseudomonas aeruginosa pneumonia", section on 'Management' and "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Role of combination antimicrobial therapy'.)

Use of aminoglycoside antibiotics requires careful dosing and monitoring to avoid renal toxicity and ototoxicity. Aminoglycosides should never be used as single agents. (See "Dosing and administration of parenteral aminoglycosides".)

●Recent sputum culture or other evidence of MRSA – In hospitalized patients with MRSA in prior sputum samples, Gram-positive cocci in clusters on a current sputum Gram stain or positive MRSA colonization on nasal screening, the initial empiric regimen should include vancomycin or linezolid 600 mg every 12 hours (off-label). Vancomycin should be dosed to achieve therapeutic levels. (See "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults".)

In one study, multidrug resistant organisms were isolated in one-quarter of bronchiectasis exacerbations; of these, MRSA was the culprit organism in approximately 20 percent [30].

After culture results from the current exacerbation return, antibiotics can be narrowed to a sensitive antibiotic with the fewest side effects. For patients with resistant organisms requiring continued intravenous antibiotics, we prefer a 14-day course [23]. We engage in shared decision making regarding antibiotic duration for patients with mild disease or exacerbations who have returned to baseline and do not require continued intravenous therapy.

Patients admitted after failed outpatient therapy — The approach for patients admitted after failure of outpatient treatment depends on the local antibiotic resistance patterns, choice of outpatient antibiotics, and patient-specific culture data. For example, if the patient did not improve on an oral quinolone, coverage for resistant Pseudomonas and MRSA should be included, pending updated culture results. Care should be taken to avoid drugs in the same class as the ones that failed in the outpatient setting or antibiotics for which the patient has known resistant flora. Patients with available culture data showing new resistant organisms can be treated with antibiotics tailored to the new isolate. (See 'Assessing treatment failure' above and 'Patients requiring intravenous antibiotics for resistant organisms' above.)

Other patients — For patients with frailty, other practical difficulties with outpatient treatment, or hemoptysis (table 1), the approach to antibiotic therapy is generally the same as that used for outpatients, but it is accompanied by close monitoring to ensure adherence and assess clinical course. (See 'Approach to outpatient antibiotic therapy, for low-risk patients' above.)

Acute exacerbation due to influenza or COVID-19 — For patients who present with an exacerbation that is caused by viral infection, we begin antiviral therapy. Failure to improve despite antiviral therapy should prompt antibiotic treatment based on sputum culture results, if available. (See 'Approach to outpatient antibiotic therapy, for low-risk patients' above.)

Influenza antiviral therapy is usually indicated for patients whose exacerbation of bronchiectasis has been triggered by influenza virus, although the benefit of antiviral therapy wanes when more than 72 hours has transpired since symptom onset. The usual treatment is oral oseltamivir or baloxavir; intravenous peramivir can be used in patients who are unable to take oral medication. (See "Seasonal influenza in nonpregnant adults: Treatment".)

According to the Centers for Disease Control and Prevention (CDC), patients with bronchiectasis are at increased risk for severe COVID-19 (table 2). In general, patients with bronchiectasis exacerbations due to COVID-19 should receive antiviral therapies in either the outpatient or inpatient setting, depending on disease severity. Specific therapy for COVID-19 should be individualized based on symptoms, risk factors for severe disease, time since symptom onset, and location of care, as described separately. (See "COVID-19: Management in hospitalized adults" and "COVID-19: Management of adults with acute illness in the outpatient setting".)

Enhanced airway clearance measures — All patients with exacerbations should maintain or increase their airway clearance regimen to facilitate expectoration of excess mucus and prevention of lung collapse. Most patients with bronchiectasis are recommended for mechanical positive expiratory pressure devices, chest physiotherapy, nebulized isotonic or hypertonic saline, or other therapeutic strategies to enhance airway clearance (table 3). During exacerbations, maintaining effective airway clearance prevents atelectasis and preserves blood flow (and hence antibiotic delivery) to affected lung tissue. A detailed discussion of airway clearance strategies in bronchiectasis may be found elsewhere. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Airway clearance therapy' and "Bronchiectasis in adults: Maintaining lung health", section on 'Mucolytic agents and airway hydration'.)

MANAGEMENT OF EXACERBATION-ASSOCIATED HEMOPTYSIS — Bleeding due to bronchiectasis is typically associated with acute infective episodes and is produced by injury to superficial mucosal neovascular bronchial arterioles. Although minor hemoptysis (blood-streaked sputum) is a frequent annoyance during exacerbations, more serious and even life-threatening bleeding may occur.

Assessing hemoptysis severity — Hemoptysis severity is frequently defined in guidelines by volume of blood expectorated and the rate of bleeding; however, asking patients to make this assessment in the outpatient setting is very difficult. Blood is also often admixed with mucus, complicating quantification. When we ask patients about bleeding quantity, we try to refer to measuring cups rather than rely on abstract estimates. In general, we prefer a slightly less precise, but more patient-friendly, classification for help with triage:

●Minimal – For patients with bronchiectasis exacerbations, hemoptysis where blood is mixed in with recognizable sputum is considered minimal. Small amounts of clot that are self-limited or occur less than twice a day also qualify.

●Active – Active bleeding involves coughing up more than a teaspoon (5 mL) of clots or frank blood more than two or three times a day with bleeding ongoing for more than a few hours.

●Life-threatening – This refers to hemoptysis that causes difficulty breathing or airway obstruction, significantly abnormal gas exchange (new hypoxemia or hypercarbia), or hemodynamic instability. Any large volume hemoptysis (eg, more than 100 mL/hour or more than 150 mL per day) should also be treated as potentially life-threatening. (See "Evaluation and management of life-threatening hemoptysis", section on 'Definition'.)

Minimal and self-limited hemoptysis — For bronchiectasis patients who present with blood in their sputum or self-limited expectoration of small amounts of blood during an exacerbation, we obtain a chest radiograph to assess for new cavitary processes or pneumonia complicating the exacerbation. For those with a stable chest radiograph, treatment of the exacerbation is generally sufficient, with further evaluation only necessary for clinical worsening. Those with new imaging findings generally require chest computed tomography (CT) to better delineate risk of further bleeding and need for additional treatment.

Active hemoptysis — For bronchiectasis patients with active bleeding, flexible bronchoscopy and chest CT with arterial contrast are complementary diagnostic tools to localize the bleeding to a lobe or segment. Once the site of bleeding is identified, local 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 greatly decrease or stop the bleeding [31].

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 (IR) service. If embolization is unsuccessful and bleeding persists, surgical resection may be necessary [32]. (See "Evaluation and management of life-threatening hemoptysis", section on 'Initial investigations'.)

Life-threatening hemoptysis — In patients with life-threatening hemoptysis, initial measures should focus on securing the airway, maintaining adequate ventilation, ensuring hemodynamic stability, and correcting any bleeding diathesis. Early bronchoscopy to identify the site of bleeding is very helpful for optimal positioning (placing the bleeding side down) and lung isolation if necessary. IR-guided techniques may be used subsequently in an attempt to achieve bleeding control. (See "Evaluation and management of life-threatening hemoptysis", section on 'Initial life-saving and supportive measures' and 'Active hemoptysis' above and "Evaluation and management of life-threatening hemoptysis", section on 'Initial investigations'.)

Patients may occasionally require urgent surgery for the management of life-threatening hemoptysis due to bronchiectasis that cannot be controlled with less invasive measures. The evaluation and management of continuing active hemoptysis is discussed separately. (See "Evaluation and management of life-threatening hemoptysis", section on 'Continued or recurrent life-threatening bleeding'.)

ADDITIONAL THERAPIES, IN CERTAIN POPULATIONS — Additional therapies for bronchiectasis exacerbation may be warranted based on the etiology of bronchiectasis, pathogen involved, or presence of comorbid disease.

Nontuberculous mycobacterial infection — While nontuberculous mycobacterial (NTM) infection can be an opportunistic infection in patients with bronchiectasis, it can also be a primary cause of bronchiectasis [8,33,34]. Mycobacterium. avium, M. intracellulare, and M. abscessus are the most frequently isolated NTM and are responsible for the greatest clinical impact. Treating exacerbations arising from progressive mycobacterial disease as routine bronchiectasis exacerbations may lead to mycobacterial antibiotic resistance and complicate future efforts at eradication. The diagnosis and treatment of mycobacterial disease are described separately. (See "Overview of nontuberculous mycobacterial infections" and "Microbiology of nontuberculous mycobacteria" and "Treatment of Mycobacterium avium complex pulmonary infection in adults".)

ABPA — Allergic bronchopulmonary aspergillosis (ABPA) is classically a cause of central bronchiectasis in patients with asthma and can also arise in patients with bronchiectasis. While acute exacerbations may be due to bacteria and should be treated appropriately, definitive treatment of ABPA involves reducing allergic inflammation and aspergillus colonization (eg, with systemic glucocorticoids, antifungal agents, and/or omalizumab) to limit progressive lung injury. Treatment of ABPA is discussed in detail separately. (See "Treatment of allergic bronchopulmonary aspergillosis".)

Patients receiving immunoglobulin therapy — Certain primary immunodeficiencies, such as common variable immunodeficiency, can be treated with immune globulin, intravenously (IVIG) or subcutaneously (SCIG). Patients with these conditions who have missed doses or are otherwise IgG deficient during a bronchiectasis exacerbation may benefit from receiving immune globulin treatment, although this has not been formally studied. Treatment is usually delayed for a few days after initiation of antibiotic therapy to prevent adverse reactions. The use of immunoglobulin preparations in primary immunodeficiencies is discussed separately. (See "Immune globulin therapy in inborn errors of immunity".)

Comorbid COPD or asthma — We recommend the use of oral glucocorticoids or inhaled glucocorticoids (aka, inhaled corticosteroids [ICS]) only in patients with bronchiectasis exacerbations who have comorbid asthma or chronic obstructive pulmonary disease (COPD).

Oral glucocorticoid bursts should be reserved for patients with comorbid asthma or COPD who have new or worsening wheezing that does not improve with airway clearance or a change in dyspnea. For patients with an acute exacerbation without these features, systemic glucocorticoids are avoided because they depress host immunity, promote bacterial and fungal colonization, and may perpetuate infection. Oral glucocorticoids also have other significant adverse effects that are discussed separately. (See "Acute exacerbations of asthma in adults: Home and office management", section on 'Initiation of oral glucocorticoids' and "COPD exacerbations: Management", section on 'Home oral glucocorticoid therapy' and "Major adverse effects of systemic glucocorticoids".)

We do not generally alter chronic ICS therapy during bronchiectasis exacerbations in patients with asthma or COPD. The best available evidence suggests benefits to treating eosinophilic inflammation in asthma and COPD. Furthermore, the use of ICS does not appear to increase the risk of pneumonia in patients with concomitant bronchiectasis and COPD [35]. Patients with persistent asthma should receive ICS as a controller medication, with up-titration and addition of other bronchodilators based on symptom control. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend ICS therapy in COPD based on exacerbation history and the presence of eosinophilic inflammation. (See "An overview of asthma management" and "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control" and "Stable COPD: Follow-up pharmacologic management" and "Major side effects of inhaled glucocorticoids", section on 'Lung infection'.)

OUTCOMES AFTER EXACERBATIONS — Although recovery to baseline is common after most acute exacerbations, frequent exacerbations portend a poor prognosis. Symptoms of a bronchiectasis exacerbation last for a median of 16 days, but approximately 16 percent of patients do not recover to baseline for at least one month [36]. In some patients, exacerbations lead to irreversible morbidity. Patients with three or more exacerbations per year have twice the mortality rate of those who do not experience exacerbations (hazard ratio 2.0; 95% CI 1.0–4.0), even after accounting for many potential confounding factors [4]. Similarly, exacerbations requiring hospital admission more than double the subsequent mortality risk [4].

PREVENTATIVE MEASURES — Based on the risk of clinical worsening and death associated with frequent exacerbations, much of the routine care of bronchiectasis patients is targeted at exacerbation prevention. These strategies are discussed in detail separately. (See "Bronchiectasis in adults: Maintaining lung health".)

MANAGEMENT OF REFRACTORY AND RECURRENT EXACERBATIONS — Some patients continue to have debilitating exacerbations and worsening lung function despite preventative measures. For those with localized disease, surgical resection may improve outcomes. Those with widespread bronchiectasis may be eligible for bilateral lung transplantation, but typical wait times remain long. Several promising experimental strategies to reduce exacerbations are under active investigation.

Surgical resection, in localized bronchiectasis — The goal of surgical extirpation includes removal of the most involved segments or lobes while preserving the remaining lung. 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 during lower lobe resection. At the same time, surgical resection should be complete, as residual disease left after resection has demonstrated worse outcomes in some studies [23,37].

Although empiric data are lacking, surgical intervention is usually combined with an aggressive perioperative antibiotic and bronchial hygiene regimen to reduce bacterial infection and improve drainage.

Patient selection — In general, resectional surgery is considered for disease confined to one or two lobes that is not controlled by medical therapy and results in frequent infectious episodes. Examples of disease settings where resection might be favorable include:

●Removal of destroyed lung distal to partial obstruction by a nonmetastatic tumor or the residue of a foreign body

●Recurrent infective episodes due to localized bronchiectasis not responsive to medical therapy

●Overwhelming purulent and viscid sputum production in patients with localized bronchiectasis that is unresponsive to medical therapy

●Presence of a localized bronchiectatic area suspected of harboring resistant organisms such as nontuberculous mycobacteria (NTM) [38,39] or multidrug-resistant tuberculosis (see "Treatment of Mycobacterium avium complex pulmonary infection in adults", section on 'Surgical management' and "Treatment of drug-resistant pulmonary tuberculosis in adults")

Relative contraindications include untreatable progressive etiologies of bronchiectasis (eg, primary ciliary dyskinesia, recurrent aspiration), severe lung function abnormalities, anorexia, poor exertional tolerance, or other evidence of frailty. Preoperative pulmonary rehabilitation and nutritional interventions are helpful in improving the surgical fitness of some patients [2,23].

Outcomes — Overall, surgical outcomes are favorable in the select group of patients receiving surgical resection. Surgical case series have shown low 30-day mortality (<2 percent) and resolution or improvement of symptoms in the majority of patients [32,40-44]. The following studies illustrate typical reports:

●In the largest study from the past two decades, 790 patients (mean age 47 years) were followed for a mean of four years following lung resection (segmentectomy, lobectomy, pneumonectomy) [41]. Mortality at 30 days was 1.1 percent. Seventy-five percent of patients became asymptomatic or were improved, while 15 percent were unimproved or worse.

●In another large case series, 134 patients (mean age 48 years) were followed for a mean of six years [32]. Thirty-day mortality was 2 percent and 89 percent of patients improved.

Postoperative complications include empyema, hemorrhage, prolonged air leak, and poorly expanding lung due to persistent atelectasis or suppuration. In selected patients, video-assisted thoracoscopic surgery (VATS) segmentectomy or lobectomy may allow fewer complications and shorter hospitalizations than thoracotomy. However, the presence of pleural adhesions may require conversion to an open procedure [23,42].

Lung transplantation — After bilateral orthotopic lung transplantation, the survival advantage gained by patients with bronchiectasis is comparable with that seen in other diagnostic groups, including cystic fibrosis [45,46]. According to the Organ Procurement and Transplant Network (OPTN) database maintained by the United Network for Organ Sharing (UNOS), 407 patients with noncystic fibrosis bronchiectasis underwent lung transplantation in the United States between 1992 and 2019 [47]. The mean age was 47 years, and the median transplant list waiting time was 254 days. The median survival time posttransplant was 5.5 to 6.0 years. Poor lung function (forced expiratory volume in one second [FEV₁] <30 percent), severe secondary pulmonary hypertension, recurrent massive hemoptysis, or intensive care unit (ICU) admissions requiring noninvasive or invasive ventilation are among the indications for transplant referral [23]. (See "Lung transplantation: An overview" and "Lung transplantation: General guidelines for recipient selection".)

Experimental approaches — Experts from the United States [48] and Europe [49,50] have suggested that research priorities in bronchiectasis should include epidemiology, pathogenesis, and management [49]. Active areas of research on management and prevention of refractory exacerbations include:

●Investigative methods for palliation of P. aeruginosa infection – Some patients with bronchiectasis have excess IgG2 specific to the bacterial O-antigen, which (unlike other antibodies) inhibits immune killing of P. aeruginosa in serum samples. One study examined the impact of treatment targeting these antibodies in two patients with bronchiectasis, severe respiratory insufficiency, P. aeruginosa airway infection, and elevated IgG2 serum levels [51]. Plasmapheresis sessions followed by intravenous pooled immune globulin infusions for five days markedly improved patient clinical status by reducing time spent in the hospital and days on intravenous antibiotics over the next 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.

●Elastase inhibitors – Excess activation of neutrophil serine proteases (NSPs) is thought to contribute to perpetuation of inflammation and lung destruction in bronchiectasis, raising the possibility that an inhibitor of NSP activation (eg, brensocatib; INS1007) might reduce the rate of exacerbations. In a phase 2 trial (WILLOW), 256 participants who had at least two exacerbations in the prior year were treated with brensocatib 10 mg daily, brensocatib 25 mg daily, or placebo for 24 weeks [52]. Over the course of the trial, 42 exacerbations occurred in the 25 mg brensocatib group, 34 in the 10 mg brensocatib group, and 54 in the placebo group. The time to first exacerbation was prolonged with brensocatib compared with placebo (adjusted hazard ratio approximately 0.6 in both groups, 95% CI 0.35-0.99). Overall, brensocatib was reportedly well tolerated; headache and dyspnea were common side effects that occurred more often in the 25 mg group than with placebo, but the numbers were small.

●Treatment based on eosinophilic endotype – Multiple studies are investigating differential treatment of patients with bronchiectasis who demonstrate eosinophilic inflammation. In a post-hoc analysis of a placebo-controlled trial examining inhaled fluticasone in obstructive lung diseases, patients with bronchiectasis and elevated blood eosinophils who received fluticasone demonstrated improved respiratory qualities of life [53]. In a separate observational study, 21 patients with bronchiectasis underwent a trial of anti-eosinophilic biologic therapy based on peripheral eosinophilia >300 cells/microL and refractory exacerbations despite aggressive management [54]. Twelve patients received an interleukin (IL)-5 antagonist (mepolizumab) and nine received an IL-5-alpha receptor antagonist (benralizumab). After six months of therapy, there were significant improvements in FEV₁ and respiratory quality of life, as well as a trend towards reduced exacerbation frequency, compared with pretreatment assessment.

●Microbiome assessment – Culture-independent microbial gene surveys of airway secretions from individuals with noncystic fibrosis bronchiectasis have identified a broader array of microbial species, including anaerobic bacteria, that are not identified by routine culture [55] and can remain relatively stable over long periods of time [56].

In studies of the airway microbiome, greater bacterial diversity is associated with better clinical parameters, including a higher FEV₁ and fewer symptoms, suggesting that low diversity may reflect overgrowth by pathogenic bacteria such as P. aeruginosa [57]. Moreover, the clustering of organisms, particularly in association with Pseudomonas, correlates with exacerbations of bronchiectasis [58]. Antibiotic treatment reduces this clustering or the so-called interactome [59]. There may also be significant interaction between the airway and gut microbiome, with airway Pseudomonas interactions with gut Bacteroides and Saccharomyces correlating with increased exacerbations and greater radiologic and overall bronchiectasis severity [60]. Use of this technology does not yet have clinical applicability.

●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 [61].

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)")

●Basics topic (see "Patient education: Coughing up blood (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition and risk factors – Bronchiectasis exacerbations are usually caused by acute bacterial airway infection and are characterized by worsening of cough and sputum volume or purulence. Patients with a history of exacerbations or chronic pseudomonal infection are at the highest risk. (See 'Definition' above and 'Risk factors' above.)

●Evaluation – Evaluation is focused on excluding other causes and identifying the specific pathogen(s) involved. Complaints of fever, chills, or night sweats prompt evaluation for pneumonia. Sputum Gram stain and culture should be obtained prior to antibiotic administration. (See 'Presentation and initial evaluation' above.)

●Management of infection – Most acute exacerbations can be managed in the outpatient setting. However, evidence of severe infection, concern for patient frailty, need for intravenous therapy, difficulties with adherence, active hemoptysis, or outpatient treatment failure may prompt inpatient management (table 1). (See 'Defining severity and site of care' above.)

•Airway clearance – All patients with exacerbations should maintain or increase their airway clearance regimen to facilitate sputum removal and prevent lung collapse.

•Antiviral therapy – Influenza or COVID-19 antiviral therapy is usually indicated for bronchiectasis exacerbations due to these viruses, although the benefit of antiviral therapy wanes with time since symptom onset. (See 'Acute exacerbation due to influenza or COVID-19' above.)

•Empiric antibiotic therapy – The initial antibiotic regimen for acute exacerbations of bronchiectasis is tailored to prior sputum cultures and sensitivities, when available. Additional factors in antibiotic selection include oral versus parenteral administration, the history of success or failure of prior regimens, and patient drug allergies. (See 'Approach to outpatient antibiotic therapy, for low-risk patients' above.)

-No recent sputum data – For clinically stable patients without sputum culture data over the past 12 to 24 months or known prior colonization with resistant organisms, we suggest initiation of a fluoroquinolone antibiotic (eg, levofloxacin, moxifloxacin) rather than an alternative oral antibiotic (Grade 2C). (See 'Initial antibiotic selection' above.)

For patients with bronchiectasis hospitalized for severe infection or respiratory distress, we suggest broad spectrum empiric therapy with coverage of both methicillin-resistant Staphylococcus aureus (MRSA) (eg, vancomycin or linezolid) and Pseudomonas (eg, antipseudomonal penicillin, third generation cephalosporin, a carbapenem, or aztreonam) rather than narrower regimens (Grade 2C). (See 'Patients with severe infection' above.)

-Recent cultures without highly resistant organisms – For clinically stable patients with sputum cultures from the past 6 to 12 months that do not reveal antibiotic-resistant organisms, we suggest amoxicillin 500 mg three times daily or doxycycline 100 mg twice daily rather than other agents (Grade 2C). In the presence of beta-lactamase producing organisms, choices include amoxicillin-clavulanate, second or third generation cephalosporin, doxycycline, or a fluoroquinolone. Sensitive isolates of Pseudomonas can be treated with ciprofloxacin. (See 'Initial antibiotic selection' above.)

-Recent cultures with highly resistant organisms – For clinically stable patients with the most recent prior cultures growing chronic Pseudomonas aeruginosa or MRSA resistant to oral agents, we suggest initiation of an intravenous antibiotic with efficacy against prior isolates (Grade 2C). (See 'Initial antibiotic selection' above and 'Patients requiring intravenous antibiotics for resistant organisms' above.)

For patients with a history of chronic Pseudomonas infection who are hospitalized for severe infection or respiratory distress, we suggest empiric therapy with vancomycin or linezolid and two antipseudomonal antibiotics rather than vancomycin or linezolid and only one antipseudomonal antibiotic (Grade 2C). (See 'Approach to inpatient therapy' above.)

-Course of therapy – Patients who do not improve or who are on intravenous therapy should be transitioned to antibiotics tailored to sputum cultures from the current exacerbation once these are available. We typically treat acute exacerbations for 10 to 14 days. (See 'Duration of therapy' above.)

●Hemoptysis – Patients with active hemoptysis should receive chest CT and bronchoscopy to help localize and treat the site of bleeding. For patients with brisk or life-threatening hemoptysis, bronchial artery embolization or resectional surgery may be required. (See 'Management of exacerbation-associated hemoptysis' above and "Evaluation and management of life-threatening hemoptysis".)

●Refractory disease – For patients with bronchiectasis confined to one or two lobes that is not controlled by medical therapy, we suggest surgical evaluation rather than continued medical therapy alone (Grade 2C). In diffuse disease refractory to medical management, referral for lung transplantation may be appropriate. (See 'Management of refractory and recurrent exacerbations' above.)