Bronchiectasis

Epidemiology

  • Definition: permanent dilation of bronchi and bronchioles with associated airway wall damage
  • Prevalence: bronchiectasis is found in patients of all ages, genders, and ethnic groups
    • However, older adults are mre commonly affected than youngr age groups
  • Sex: females are more commonly affected than males in North America
  • Relative Prevalence of Specific Etiologies
    • Post-infectious cases are uncommon in USA (except in Native Americans in Alaska) but are common in underdeveloped countries
    • Over 50% of bronchiectasis cases are idiopathic
    • Approximately 25-30% of bronchiectasis cases can be traced to a prior pulmonary infection
  • Association with COPD: patients with moderate-severe COPD have increased risk of bronchiectasis [MEDLINE]
    • These patients have severe airflow obstruction, isolation of a pathogenic organism from sputum, and at least one hospital admission for an exacerbation in the prior year
    • These patients also have an increased mortality rate (hazard ratio: 2.54) [MEDLINE]

Etiology

Idiopathic

  • Over 50% of all bronchiectasis cases are idiopathic

Immunodeficiency

Hypogammaglobulinemia (see Hypogammaglobulinemia)

  • Agammaglobulinemia (see Agammaglobulinemia)
    • Autosomal Recessive Agammaglobulinemia: severe hypogammaglobulinemia, antibody deficiency, and increased susceptibility to infection
    • X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia): severe hypogammaglobulinemia, antibody deficiency, and increased susceptibility to infection
      • Most cases do not present prior to 6 mo of age
  • Ataxia-Telangiectasia (see xxx)
  • B-Cell Lymphoma (see Lymphoma): due to increased catabolism of immunoglobulins
  • Biallelic Deficiency of Mismatch Repair Protein PMS2
  • Common Variable Immunodeficiency (CVID) (see Common Variable Immunodeficiency): most cases do not present until the third or fourth decade of life
  • Drug-Related Hypogammaglobulinemia: these cases probably occur in specific predisposed individuals
    • Captopril (see Captopril): may cause IgA deficiency
    • Carbamazepine (Tegretol) (see Carbamazepine): may cause IgA deficiency or reversible hypogammaglobulinemia
    • Chlorpromazine (Thorazine) (see Chlorpromazine): may cause IgA deficiency
    • Hydroxychloroquine (Plaquenil) (see Hydroxychloroquine): may cause IgA deficiency
    • Lamotrigine (Lamictal) (see Lamotrigine): may cause reversible hypogammaglobulinemia
    • Penicillamine (see Penicillamine): may cause IgA deficiency
    • Phenytoin (Dilantin) (see Phenytoin): may cause IgA deficiency or reversible hypogammaglobulinemia
    • Ramipril (Altace) (see Ramipril): may cause hypogammaglobulinemia
    • Sulfasalazine (see Sulfasalazine): may cause IgA deficiency
    • Valproic Acid (Depakote, Depakene) (see Valproic Acid): may cause IgA deficiency
  • Good Syndrome (Immunodeficiency with Thymoma) (see Thymoma)
    • Physiology: B-cell immunodeficiency syndrome
    • Clinical
  • Hyper-IgM Syndrome
    • CD40 Ligand (CD40L or CD154) Deficiency: this X-linked disorder is the etiology of most cases of Hyper-IgM syndrome
    • CD40 Deficiency
    • Activation-Induced Cytidine Deaminase (AID) Deficiency
    • Uracil-Nucleoside-Glycosylase (UNG) Deficiency
  • Immunodeficiency–Centromeric Instability–Facial Anomalies (ICF) Syndrome: normal B-cell counts with agammaglobulinemia
  • Jacobsen Syndrome (Hemizygous Deletion of Part of the Long Arm of Chromosome 11)
  • Immunosuppression
    • Autologous Hematopoietic Stem Cell (HSCT) (Bone Marrow Transplant, BMT) (see Hematopoietic Stem Cell Transplant)
    • Azathioprine (Imuran) (see Azathioprine)
    • Belimumab (Benlysta) (See Belimumab): anti-B cell monoclonal antibody
    • Chemotherapy
    • Corticosteroids (see Corticosteroids)
      • Patients taking ≥12.5 mg prednisone for at least 1 year are at increased risk of hypogammaglobulinemia
      • Patients with hypogammaglobulinemia due to corticosteroid usually retain specific antibody responses: therefore, they are not usually candidates for immunoglobulin replacement therapy
    • Gold (see Gold)
    • Mycophenolate Mofetil (Cellcept) (see Mycophenolate Mofetil): may cause hypogammaglobulinemia
    • Rituximab (Rituxan) (see Rituximab)
    • Tyrosine Kinase Inhibitors
  • Isolated IgA Deficiency (see Isolated IgA Deficiency): few reported cases of bronchiectasis (although these were probably due to undetected IgG deficiencies): most common primary immunodeficiency syndrome (occurs in 1:600 persons)
  • Lymphoproliferative Malignancy
    • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia): commonly associated with hypogammaglobulinemia and infection
    • Multiple Myeloma (see Multiple Myeloma): antibody deficiency with normal total IgG levels (due to contribution of the paraprotein to the total IgG level and due to tumor cells altering normal regulatory T cells, impairing B-cell maturation)
  • Myelodysplastic Syndrome (see Myelodysplastic Syndrome)
  • Myotonic Dystrophy: increased catabolism of immunoglobulins
  • Nephrotic Syndrome (see Nephrotic Syndrome)
  • Prematurity in Infants: premature infants delivered before the third trimester usually lack adequate maternal immunoglobulin and may also more rapid metabolize the IgG that they have received
  • Protein-Losing Enteropathy: intestinal lymphangiectasia, etc
    • Diagnosis
      • IgG levels are typically affected more than IgM or IgA levels (however, the levels of IgG, IgM, and IgA may all be decreased in severe protein-losing enteropathy)
      • Hypoalbuminemia (see Hypoalbuminemia)
    • Clinical
      • Edema: usually
  • Selective IgG Subclass Deficiency (see Selective IgG Subclass Deficiency): decrease in one or more of the four classes of IgG with normal total IgG is most common type associated with bronchiectasis
  • Severe Burns (see Burns): increased catabolism of immunoglobulins
  • Severe Combined Immunodeficiency (SCID) (see Severe Combined Immunodeficiency)
    • Epidemiology: xxx
  • Specific Antibody Deficiency (SAD)/Specific Polysaccharide Antibody Deficiency (SPAD) (see Specific Antibody Deficiency): poor serological response to polysaccharide antigens (with normal levels of immunoglobulins and IgG subclasses) and normal responses to protein antigens
  • Steinert’s Disease
  • Transcobalamine Deficiency
  • Trisomy 18
  • Wiskott-Aldrich Syndrome

Other

Infection

  • Adenovirus-Type 7 (see Adenovirus)
  • Allergic Bronchopulmonary Aspergillosis (ABPA) (see Allergic Bronchopulmonary Aspergillosis)
    • Typically produces upper lobe bronchiectasis (mainly apical and posterior segments)
  • Influenza Virus (see Influenza Virus)
    • Studies have shown transient nasal epithelial ciliary loss and dynein arm abnormalities in children during viral URI (influenza/ parainfluenza/ etc)
  • Measles Virus (see Measles Virus)
  • Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex)
  • Mycobacterium Tuberculosis (see Tuberculosis)
    • Epidemiology: bronchiectasis may occur following primary tuberculosis or reactivation tuberculosis
    • Diagnosis: tuberculosis typically produces upper lobe bronchiectasis (mainly in the apical and posterior segments)
  • Necrotizing Pneumonia and Pulmonary Gangrene (see Necrotizing Pneumonia and Pulmonary Gangrene)
  • Pertussis (see Pertussis)
  • Recurrent Aspiration Pneumonia (see Aspiration Pneumonia): bronchiectasis probably results from combined injury from infection and gastric acid

Inhalation Injury

Other


Physiology

  • General Features
    • Destruction of muscular and elastic components of medium-sized bronchial walls by mediators released by neutrophils (elastase) and monocytes (cytokines) -> >2 mm dilatation of medium-sized bronchi
    • Damage to peribronchial alveolar tissue: diffuse peribronchial fibrosis, squamous metaplasia of bronchial epithelium, and obliteration of distal bronchi and bronchioles
    • Impaired tracheobronchial clearance of secretions (shown by radiolabelled aerosol studies): predisposes to bacterial airway colonization and infection
  • Specific Role of Infection
    • It is not clear whether mycobacterial infection is a cause or a consequence of bronchiectasis [MEDLINE]
    • Pseudomonas infection appears to be asscoiated with more severe disease and cystic bronchiectasis
    • Mycobacterium Avium-Intracellulare (MAI) infection appears to be associated with nodular bronchiectasis (especially in the right middle lobe and lingula), mucous plugging of airways, and “tree in bud” small airway impaction

Reversibility of Bronchiectasis

  • May resolve after even years of observation in some cases (especially in areas of atelectasis due to previous pneumonia), although generally is believed to be permanent

Location

  • Can be diffuse or localized
  • Posterior-basal segments: most commonly involved
  • Bilateral LL involvement occurs in 33% of cases/ unilat-eral LL involvement occurs in left and right lungs with equal frequency/ 50% of patients with LLL involvement also have lingular involvement
  • RML is more commonly affected than RUL
  • UL involvement most common in posterior and apical segments (and is usually due to Allergic Bronchopulmonary Aspergillosis and Tuberculosis) (see xxxx and xxxx)

Pathologic Classification (Reid)

  • There is no epidemiologic or etiologic significance to this classification
    • Cylindrical: consistent widening of segments
    • Varicose: local constrictions in cylindrical segments (resembling varicsoe veins)
    • Saccular/Cystic: dilatation increases toward lung periphery (forming sacs)

Diagnosis

Arterial Blood Gas (ABG) (see Arterial Blood Gas)

  • Mild Hypoxemia with Normocapnia/Hypocapnia: hypoxemia is due to intrapulmonary shunt and V/Q mismatch)
    • Hypercapnia: uncommon and is seen only in advanced cases or in those patients with superimposed COPD

Sputum Gram Stain and Culture

  • Classic 3-Layered Sputum
    • Top: frothy watery layer
    • Middle: turbid mucopurulent layer
    • Bottom: purulent opaque layer (bottom layer may also contain Dittrich’s plugs and/or yellow or white concretions)
  • Culture

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)

  • Most Studies are Flawed, Since Concurrent Chronic Obstructive Pulmonary Disease (COPD) Cannot Be Excluded
    • However, Many Cases of Bronchiectasis Manifest Obstruction)
  • Features
    • FEV1: usually decreased
    • FEF25-75: may be decreased:
    • Mild restriction: may be seen in some cases (especially if underlying disease decreases volumes)
    • DLCO: may be decreased

Bronchoscopy (see Bronchoscopy)

  • Airways may appear wider on visual examination
  • Useful to evaluate for sources of hemoptysis, rule out foreign bodies, etc.
  • TBB: not usually performed

Chest X-Ray (CXR)/Chest CT Patterns (see xxxx and xxxx)

  • Cylindrical: tram-tracks
  • Varicose: toothpaste lines
  • Cystic: cysts that may contain fluid

High-Resolution Chest CT (HRCT) (see High-Resolution Chest CT)

  • Considered the gold standard imaging modality
  • Sensitivity: 84%
  • Specificty: 82%
  • Bronchial wall thickening and dilatation

Bronchography

  • No longer used

Serum Alpha-1 Antitrypsin (see Serum Alpha-1 Antitrypsin)

Immunoglobulin Levels (see xxxx)

  • To rule out immunodeficiency

Sweat Chloride Test (see Sweat Chloride Test)

Electron Microscopic Exam of Sperm or Respiratory Epithelium (Via Nasal Biopsy)

  • To Rule Out Ciliary Disorder

Clinical Manifestations

Otolaryngologic Manifestations

Recurrent/Chronic Rhinosinusitis

  • Epidemiology
    • Nasal/Sinus Disease May Be Seen in Association with Bronchiectasis Related to B-Cell Dysfunction Disorders

Pulmonary Manifestations

Chronic Hypoxemic, Hypercapnic Respiratory Failure (see Respiratory Failure)

  • Epidemiology
    • Chronic Hypoventilation (Hypoxemic, Hypercapnic Respiratory Failure) Typically Occurs Only in Patients with Advanced Bronchiectasis or in Those with Superimposed Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)

Cough with/without Sputum Production (see Cough): most common symptom

  • Clinical
    • “Wet Bronchiectasis”: purulent foul-smelling sputum
      • Mild: <10 mL per day
      • Moderate: 10-150 mL
      • Severe: >150 mL
    • “Dry Bronchiectasis”: some cases (especially those involving upper lobes that dependently drain) have minimal sputum

Dyspnea (see Dyspnea)

  • Epidemiology

Empyema (see Pleural Effusion-Parapneumonic)

  • Epidemiology
    • XXXXX

Hemoptysis (see Hemoptysis)

  • Epidemiology
    • More common in Dry Bronchiectasis
  • Clinical
    • Usually Mild, But May Be Massive (>250 mL/Day)
    • Rarely Fatal

Lung Abcess (see Lung Abscess)

  • xxx

Pneumothorax (see Pneumothorax)

  • Epidemiology
    • XXXXX

Pulmonary Hypertension/Cor Pulmonale (see Pulmonary Hypertension)

  • Epidemiology
    • Seen in some cases (37% of cases by 1969 study)
  • Physiology
    • Enlargement of Bronchial Arteries: due to increased flow to tissue
    • Anastomoses to Pulmonary Arteries: due to enlargement of preexisting connections and new connections
    • Total Pulmonary Arterial Flow: may be decreased in severe bronchiectasis, due to obstructive endarteritis and/or hypoxic vasoconstriction
    • Left-to-Right Intrapulmonary Shunting Occurs: due to anastomoses

Rales/Rhonchi (see Pulmonary Physical Exam)

  • xxx

Recurrent Pneumonia (see Community-Acquired Pneumonia)

  • xxx

Wheezing (see Wheezing)

  • xxxx

Rheumatologic Manifestations

Clubbing (see Clubbing)

  • Physiology
    • Correlation between augmented vascular supply in lungs and vascularity in clubbed digits of bronchiectasis patients (suggests a possible vasodilator substance that is not yet identified)

Other Manifestations


Treatment

Treatment of Hemoptysis

  • Bronchoscopy (see Bronchoscopy): to localize (may tamponade with Fogarty balloon)
  • Bronchial Artery (and Sometimes Also Pulmonary Artery) Embolization: may be required
  • Surgery: may be required in some cases for refractory hemoptysis

Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin)

  • Prevents Exacerbations in the Setting of Immunoglobulin Deficiency

Postural Drainage

  • xxx

Chest Physical Therapy (PT) (see Chest Physical Therapy)

  • xxx

Humidification

  • xxx

Surgery

  • Indications: localized bronchiectasis with recurrent infection unresponsive to antibiotics

Mucolytics

Agents

  • Coughing is Probably Superior

Agents

  • Deoxyribonuclease (DNase) (see Dornase Alfa): useful only for cystic fibrosis, as trials suggest that it has potential harmful effects in non-cystic bronchiectasis (Cochrane Database Syst Rev, 2014) [MEDLINE]
  • Bromhexine with Antibiotics: may facilitate sputum production and clearance, but long-term data and clinical outcomes are lacking
  • Erdosteine: may be a useful adjunct to physical therapy in stable patients with mucus hypersecretion, but robust longer-term trials are required
  • N-Acetylcysteine (Mucomyst) (see N-Acetylcysteine): further studies are required

Clinical Efficacy

  • xxxxx

Antibiotics

Clinical Utility

  • Antibiotic Treatment of Acute Exacerbation: antibiotics are standard therapy
  • Antibiotic Maintenance Therapy: indicated for patients with >2-3 exacerbations per year

Fluoroquinolones (see Fluoroquinolones])

  • Agents
  • Clinical Efficacy
    • During course of therapy, fluoroquinolones decrease sputum elastase, neutrophil chemotactic activity, sputum volume and purulence: however, 25% of patients relapse within 6 wks after therapy

Gentamicin (Nebulized) (see Gentamicin)

  • Clinical Efficacy
    • Randomized Trial of Nebulized Gentamicin in Non-Cystic Bronchiectasis (Am J Respir Crit Care Med, 2011 ) [MEDLINE]
      • Regular long-term nebulized gentamicin 80 mg BID decreased sputum bacterial density, airway inflammation, and exacerbations (with no change in FEV1 or FVC)
      • Treatment needs to be continuous for ongoing efficacy
    • Systematic Review and Meta-Analysis of Inhaled Antibiotics in Bronchiectasis in Adults (Lancet Respir Med, 2019) [MEDLINE]: n = 2,597 (16 trials)
      • Inhaled antibiotics are well tolerated, reduce bacterial load, and achieve a small but statistically significant reduction in exacerbation frequency without clinically significant improvements in quality of life in patients with bronchiectasis and chronic respiratory tract infections

Tobramycin (Tobi) (see Tobramycin)

  • Clinical Efficacy
    • Systematic Review and Meta-Analysis of Inhaled Antibiotics in Bronchiectasis in Adults (Lancet Respir Med, 2019) [MEDLINE]: n = 2,597 (16 trials)
      • Inhaled antibiotics are well tolerated, reduce bacterial load, and achieve a small but statistically significant reduction in exacerbation frequency without clinically significant improvements in quality of life in patients with bronchiectasis and chronic respiratory tract infections
      • The mean reduction of colony forming units per g of sputum with inhaled antibiotics was -2·32 log units (95% CI -3·20 to -1·45; p<0·0001). Bacterial eradication was increased with inhaled antibiotic therapy (odds ratio [OR] 3·36, 1·63 to 6·91; p=0·0010). Inhaled antibiotics significantly reduced exacerbation frequency (rate ratio 0·81, 0·67 to 0·97; p=0·020). Time to first exacerbation was significantly prolonged with inhaled antibiotics (hazard ratio 0·83, 0·69 to 0·99; p=0·028). The proportion of patients with at least one exacerbation decreased (risk ratio 0·85, 0·74 to 0·97; p=0·015). There was a significant reduction in the frequency of severe exacerbations (rate ratio 0·43, 0·24 to 0·78; p=0·0050). The scores for neither the Quality of Life Bronchiectasis questionnaire nor St George’s Respiratory Questionnaire improved above the minimal clinically important difference. The relative change in FEV1 was a deterioration of 0·87% predicted value (-2·00 to 0·26%; p=0·13). Other efficacy endpoints were reported in only few studies or had few events. There was no difference in treatment-emergent adverse effects (OR 0·97, 0·67 to 1·40; p=0·85) or bronchospasm (0·99, 0·66 to 1·48; p=0·95). Emergence of bacterial resistance was evident at the end of the treatment period (risk ratio 1·91, 1·46 to 2·49; p<0·0001).

Macrolides (see Macrolides)

  • Agents
  • Clinical Efficacy
    • EMBRACE Trial (Lancet, 2012) [MEDLINE]
      • Azithromycin x 6 mo -> decreased rate of exacerbations (in patients who had at least one exacerbation in the past year)
    • BAT Trial (JAMA, 2013) [MEDLINE]: multi-center Dutch placebo-controlled study (n = 83) in non-cystic fibrosis bronchiectasis using daily azithromycin x 12 mo
      • Decreased rate of infectious exacerbations, increased rate of macrolide resistance
    • BLESS Trial (JAMA, 2013) [MEDLINE]: single-center Australian placebo-controlled study (n = 117) in non-cystic fibrosis bronchiectasis using daily erythromycin x 12 mo
      • Modest decrease in the rate of exacerbations, increased rate of macrolide resistance, decreased sputum production
    • Analysis of BLESS Trial Data (Lancet Respir Med, 2014) [MEDLINE]
      • Long-term erythromycin treatment changes the composition of respiratory microbiota in patients with bronchiectasis
      • In patients without Pseudomonas Aeruginosa airway infection, erythromycin did not significantly reduce exacerbations and promoted displacement of Haemophilus Influenzae by more macrolide-tolerant pathogens (including Pseudomonas Aeruginosa) -> these findings argue for a cautious approach to chronic macrolide use in patients without Pseudomonas Aeruginosa airway infection
    • Meta-Analysis of Long-Term Macrolides in Bronchiectasis in Adults (Lancet Resp Med, 2019) [MEDLINE]
      • Long-term macrolide treatment significantly reduces the frequency of exacerbations in patients with bronchiectasis, with similar benefits observed in all subgroups based on patient characteristics
      • This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful
      • However, downsides of long-term macrolide treatment must also be taken into account
      • Of 234 identified studies, we included three randomised controlled trials, and IPD was obtained for 341 participants. Macrolide antibiotics reduced the frequency of exacerbations (adjusted incidence rate ratio [IRR] 0·49, 95% CI 0·36 to 0·66; p<0·0001). We also found that macrolide treatment improved the time to first exacerbation (adjusted hazard ratio 0·46, 0·34 to 0·61; p<0·0001) and was associated with improved quality of life measured by the SGRQ (mean improvement 2·93 points, 0·03 to 5·83; p=0·048). Macrolides were not associated with a significant improvement in FEV1 (67 mL at 1 year, -22 to 112; p=0·14). Effect estimates in prespecified subgroup analyses revealed a reduced frequency of exacerbations in all prespecified subgroups, including a high level of benefit in patients with P aeruginosa infection (IRR 0·36, 0·18-0·72; p=0·0044) and in patients with one to two exacerbations per year (0·37, 0·16-0·88; p=0·025). Studies were rated as low risk of bias across all domains.

Penicillins (see Penicillins)

Tetracyclines (see Tetracyclines)

Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim)

  • Clinical Efficacy
    • xxxx

Other Treatments

  • Nutrition: indicated for weight loss
  • Inhaled Indomethacin (see Indomethacin): decreases bronchorrhea (anti-inflammatory)
  • Bronchodilators: terbutaline increases tracheal mucous velocity in CF patients
  • Oxygen (see Oxygen): probably useful (if required)

Prevention of Bronchiectasis


Prognosis

  • Prognosis was Previously Poor in the Pre-Antibiotic Era: however, the current prognosis is comparable to that of COPD
    • Functional Status: 77% of patients miss <2 wks of work annually

References

General

  • Saliva immunoglobulins in elite women rowers. Eur Resp J 15:5-10, 2000 [MEDLINE]
  • Thoracic manifestations of inflammatory bowel disease. Chest 131:524-532, 2007 [MEDLINE]
  • British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58 [MEDLINE]
  • Factors Associated With Bronchiectasis in Patients With COPD. Chest. 2011 Nov;140(5):1130-7 [MEDLINE]
  • The initial evaluation of adults with bronchiectasis. Clin Chest Med. 2012 Jun;33(2):219-31 [MEDLINE]
  • Bronchiectasis and nontuberculous mycobacterial disease. Clin Chest Med. 2012 Jun;33(2):283-95 [MEDLINE]
  • Prognostic Value of Bronchiectasis in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2013 Apr 15;187(8):823-31 [MEDLINE]

Treatment

  • A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2011;183:491-499 [MEDLINE]
  • Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):660-7 [MEDLINE]
  • Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA. 2013 Mar 27;309(12):1260-7 [MEDLINE]
  • Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013 Mar 27;309(12):1251-9 [MEDLINE]
  • The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial. Lancet Respir Med. 2014 Dec;2(12):988-96. doi: 10.1016/S2213-2600(14)70213-9. Epub 2014 Oct 14 [MEDLINE]
  • Mucolytics for bronchiectasis. Cochrane Database Syst Rev. 2014 May 2;5:CD001289. doi: 10.1002/14651858.CD001289.pub2 [MEDLINE]
  • Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis. Lancet Respir Med. 2019 Oct;7(10):845-854. doi: 10.1016/S2213-2600(19)30191-2 [MEDLINE]
  • The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: a systematic review and meta-analysis. Lancet Respir Med. 2019 Oct;7(10):855-869. doi: 10.1016/S2213-2600(19)30185-7 [MEDLINE]