Article Figures & Tables
Tables
Cause Mean incidence Supporting diagnostic features Diagnostic investigations Cystic fibrosis 0.6%–2.7% Younger age (< 45 yr); history of malabsorption; history of pancreatitis; history of Pseudomonas aeruginosa infection, Staphylococcus aureus infection, nontuberculous mycobacterial infection; history of male infertility Sweat chloride assessment; CFTR genetic analysis as per guidelines (specialist centre referral) Alpha1-antitrypsin deficiency 0.6%–11.3% Evidence of emphysema; obstructive pattern on spirometry; panniculitis Serum alpha1-antitrypsin level; phenotyping in those with low serum levels Primary ciliary dyskinesia 2.0%–10.3% History of chronic upper respiratory tract problems, otitis media, male infertility; abnormal ciliary beat pattern ± frequency on nasal brushings Measurement of nasal nitric oxide levels; ciliated epithelial biopsy (specialist centre referral) Allergic bronchopulmonary aspergillosis 0.9%–7.8% History of asthma; peripheral blood eosinophils > 500 cells/μL; positive Aspergillus fumigatus IgG or positive precipitins; sputum culture of A. fumigatus; fleeting infiltrates on chest radiograph or CT chest; proximal bronchiectasis on CT chest scan Total IgE > 500 IU/mL; positive A. fumigatus–specific IgE or immediate reaction on skin-prick testing Autoimmune/connective tissue diseases (typically rheumatoid arthritis, SLE) 1.8%–31.1% History or clinical signs of connective tissue disease ± vasculitis Rheumatoid factor; anti-CCP; other investigations pertinent to suspected diagnosis from clinical review Inflammatory bowel diseases 1.0%–3.0% History or clinical signs of ulcerative colitis or Crohn disease Specialist gastrointestinal review; positive pathological features on colonoscopy Congenital malformations 0.2%–0.6% Williams–Campbell syndrome (bronchomalacia); Mounier-Kuhn syndrome (tracheobronchomegaly) and lung sequestration Typically diagnosed on chest CT Aspiration 0.2%–11.3% History of reflux; history of aspiration Various modalities available: video fluoroscopic swallow study; upper gastrointestinal endoscopy; ambulatory esophageal manometry; pH studies; flexible endoscopic evaluation of swallow Humoral immunodeficiency 1.1%–16.0% History of recurrent infections Serum immunoglobulins levels (IgG, IgA and IgM); specific antibody responses to pneuomococcal, Haemophilus influenzae B and tetanus antigens Postinfectious* 29.0%–42.0% History or radiologic evidence of previous infection (e.g., frequently, pneumonia, Bordetella pertussis, Mycobacterium tuberculosis, nontuberculous mycobacteria) Idiopathic* 26.0%–53.0% Other causes excluded Other causes excluded Note: CCP = cyclic citrullinated peptide; CFTR = cystic fibrosis transmembrane conductance regulator; CT = computed tomography, Ig = immunoglobulin, SLE = systemic lupus erythematosus.
↵* This review focuses predominantly on the management of these 2 causes of bronchiectasis.
- Box 2: Presenting signs and symptoms of bronchiectasis
Symptoms at presentation (2), (16) Signs at presentation (2), (16) Cough (90.2%–96.0%) Normal examination Sputum (75.0%) Clubbing (2.0%–3.0%) Excessive sputum volume ([mean ± SD] 38 ± 34 mL) Crackles (69.9%–73.0%) Hemoptysis (26.0%–51.2%) Wheeze (21.0%–34.0%) Dyspnea (60.0%) Chest pain (19.0%–46.3%) Recurrent chest infections ([mean ± SD] 2.4 ± 1.6/yr) Note: SD = standard deviation.
Study design (year) Intervention Patients Outcome Retrospective analysis (2015) (39) 3-wk pulmonary rehabilitation program n = 108
-Mean age 71 yr
-Mean FEV1 76% of predictedSignificant improvement in exercise capacity; significant improvement in reported dyspnea Predictors of efficacy: male, FEV1/FVC < 70% and > 2 exacerbations/yr Randomized single-blind trial (2014) (37) 8 wks of exercise training and review of airway clearance technique v. control n = 85
-Minimum of 2 exacerbations/yr
-Medical Research Council Dyspnea Scale score ≥ 1
-Mean FEV1 74% of predicted
-Mean age 63–65 yrSignificant improvement in exercise capacity; less reported dyspnea and fatigue; improvement in exercise capacity, reported dyspnea and fatigue was not sustained at follow-up; fewer exacerbations in the subsequent 12 mo with a longer time to first exacerbation Randomized controlled pilot study (2012) (40) 8-wk pulmonary rehabilitation program and twice-daily chest physiotherapy v. twice-daily chest physiotherapy n = 30
-Regularly expectorating sputum
-Limited exercise capacity due to bronchiectasis
-Already practicing chest physiotherapy ≥ x 4/wk
-Mean FEV1 72%–76% of predicted
-Mean age 64 yrSignificant improvement in exercise capacity and HRQL with both pulmonary rehabilitation and chest physiotherapy v. chest physiotherapy alone; no improvements in spirometry, respiratory muscle function or inflammatory markers in either group Retrospective study (2011) (41) 6- or 8-wk pulmonary rehabilitation program v. patients with COPD in same program n = 95
-Mean FEV1 66.5% of predicted (24.2)
-Mean age 68.6 (9.8) yrSignificant improvement in exercise capacity in both groups; significant improvement in HRQL in both groups Randomized controlled trial (2005) (42) 8-wk pulmonary rehabilitation program v. 8-wk pulmonary rehabilitation program and inspiratory muscle training v. control n = 32
-FEV1 64%, 54% and 69% of predicted respectively per group
-Mean age 63.1, 57.3, 62.9 yr respectively per groupSignificant improvement in exercise capacity in both intervention groups v. control; improvements sustained only at 3-mo follow-up in the group that also had inspiratory muscle training Note: COPD = chronic obstructive pulmonary disease, FEV1 = forced expiratory volume in the first second, FVC = forced vital capacity, HRQL = health-related quality of life.
Study design (year) Patients Intervention Outcome Crossover study (1999) (44) 19 1 session ACBT with head-down tilt v. 1 session without No difference in sputum weight, spirometry Randomized crossover study (2002) (45) 17 4 wk of ACBT v. 4 wk of Flutter* No difference in sputum weight, dyspnea score, spirometry Randomized prospective study (2007) (46) 30 Flutter* v. ACBT v. ACBT and postural drainage, all assessed over 1 wk Greater sputum weight with ACBT and postural drainage Randomized crossover study (2016) (47) 31 3 nonconsecutive sessions over 7 d of autogenic drainage v. slow expiration with glottis open in lateral position v. temporary positive expiratory pressure No difference in sputum expectoration during 24-h posttreatment period; cough severity score improved for all groups Randomized trial (2013) (48) 30 Twice-daily sessions administered 5 d/wk for 15 d of traditional chest physiotherapy (various techniques) v. high-frequency chest wall oscillation (using the Vest Airway Clearance System) v. no physiotherapy Both treatment groups were superior to no physiotherapy for dyspnea scores, lung function and sputum production; high-frequency chest wall oscillation Note: ACBT = active cycle of breathing technique.
↵* The Flutter is an oscillating positive expiratory pressure device. (44)– (46)
Study (year) Treatment Study duration Number of patients Patient characteristics Significant results and outcomes BAT study (2013) (65) 250 mg daily azithromycin v. placebo 12-mo treatment
90-d run-out83 ≥ × 3 exacerbations/yr ≥ 1 sputum culture with pathogens in preceding yr With azithromycin v. placebo:
-Fewer exacerbations (0[0 – 1] v. 2[1 – 3])
-Improvement in FEV1% predicted (+1.03% v. −0.1%)
-Improved HRQL
-Well tolerated, despite increased relative risk of diarrhea
-Increased macrolide resistance: 35% in 8 patients at baseline increased to 88% in 20 patients v. 26% in 22 patientsBLESS study (2013) (66) 400 mg twice daily erythromycin v. placebo 48-wk treatment
4-wk washout117 ≥ × 2 exacerbations/yr With erythromycin v. placebo:
-Fewer exacerbations (76 v. 114)
-Significant reduction in 24-h sputum weight (−5.4 g v. −1.7 g reduction)
-Less decline in postbronchodilator FEV1% predicted (−1.6% v. −4.0%)
-Increased macrolide resistance: 27.7% v. 0.04%
-Well tolerated; 28.8% v. 25.9% reporting AEsEMBRACE study (2012) (67) 500 mg azithromycin 3 times per wk v. placebo 6-mo treatment
6-mo follow-up141 ≥ × 1 exacerbation/yr With azithromycin v. placebo:
-62% relative reduction in exacerbation rate during treatment and 42% annually
-Annually, longer time to first exacerbation 239 (190–331) d v. 85 (52–113) d
-Well tolerated, with 59 reported AEs v. 65
-No macrolide resistance testing performedNote: AE = adverse event, FEV1 = forced expiratory volume in the first second, HRQL = health-related quality of life.
Antibiotic class and agent Study design Dose and duration Patients Main findings Monobactam: aztreonam (68) Two multicentre, double-blind, randomized placebo-controlled trials 75 mg daily 4 weeks on, 4 weeks off for 16 weeks v. placebo Followed with 4-week open label Study 1: n = 266
Study 2: n = 274
Criterion: Chronic sputum colonization with gram-negative pathogens (but not exclusively Haemophilus influenzae)No improvement in respiratory symptoms; time to first exacerbation not prolonged; more treatment-related adverse events; more discontinuations with treatment than placebo Polymyxin: colistin (69) Multicentre, randomized, double-blind, placebo-controlled trial 1 million IU twice daily v. placebo for 6 months n = 144
Criterion: chronic sputum colonization with Pseudomonas aeruginosaReduced sputum bacterial density; increased time to first exacerbation; improved HRQL Quinolone: ciprofloxacin (70) Multicentre, randomized, double-blind, placebo-controlled trial Dual-release liposomal ciprofloxacin 150/60 mg 28 days on, 28 days off v. placebo for 24 weeks n = 42
Criterion: Chronic sputum colonization with P. aeruginosaReduced sputum bacterial density; fewer exacerbations; well tolerated Quinolone: ciprofloxacin (71) Multicentre, randomized, double-blind, placebo-controlled trial Dry powder inhaled ciprofloxacin 32.5 mg twice daily for 28 days n = 124
Criterion: Chronic sputum colonization with any pathogenReduced sputum bacterial density; improved sputum purulence; 35% pathogen eradication Aminoglycoside: gentamicin (72) Randomized, single-blind controlled trial 80 mg nebulized twice daily v. placebo for 12 months with 3-month follow-up n = 60
Criterion: Chronic sputum colonization with any pathogenReduced sputum bacterial density; 30.8% Pseudomonas eradication and 92.8% eradication in other pathogens; reduced airways inflammation; improved exercise capacity; improved HRQL; fewer exacerbations; increased time to first exacerbation; treatment effects not sustained during follow-up Note: HRQL = health-related quality of life, IU = international units.