Table 1– Characteristics of included trials
StudyCountryParticipantsInterventionControlStudy designOutcomes
AIR-BX1 and AIR-BX2 trials 2013, sponsored by Gilead Sciences [21, 22, 23]Belgium, France, Germany, Italy, the Netherlands, Spain, UK, USAInclusion criteria: adult patients (≥18 years) had non-CF bronchiectasis confirmed by HRCT, and had positive sputum culture for Gram-negative organisms Exclusion criteria: patients had hospitalisation within 14 days prior to the study, previous exposure to inhaled aztreonam, continuous O2 use >2 L·min−1, current treatment for non-TB mycobacterial infection or active TB infection within 1 year of enrolment or other serious medical conditionsAztreonam 75 mg via an eFlow nebuliser, three times a day, two 28-day on/off cycles AIR-BX1 (n=134) AIR-BX2 (n=136)Placebo via an eFlow nebuliser, three times a day, two 28-day on/off cycles 00AIR-BX1 (n=132) AIR-BX2 (n=138)International, multicentre, RDBPCTPrimary: mean change in QoL-B scores from baseline to day 28 Secondary: mean change in QoL-B scores from baseline to day 84, time to first exacerbation
Barker 2000 and Couch 2001, sponsored by PathoGenesis [9, 20]USAInclusion criteria: adult patients (≥18 years) had bronchiectasis diagnosed by CT, and had grossly purulent sputum containing PA ≥104 CFU·g−1 Exclusion criteria: patients had CF, ABPA, acute pulmonary process requiring medical intervention, or had received antibiotics within 2 weeks prior to the studyTobramycin 300 mg via a jet nebuliser, twice daily, 4 weeks (n=37)Placebo (1.25 mg quinine sulfate) via a jet nebuliser, twice daily, 4 weeks (n=37)Multicentre, RDBPCTPrimary: mean change in sputum PA density (log10 CFU·g−1) from baseline to week 4 Secondary: eradication of PA in sputum, clinical improvement, hospitalisation, PFT, adverse events, emergency of bacterial resistance
Drobnic 2005, no sponsor [29]SpainInclusion criteria: adult patients had bronchiectasis diagnosed by HRCT, and had ≥3 positive sputum cultures for PA during the 6 months before the study Exclusion criteria: patients had CF, tobramycin hypersensitivity, PA in sputum resistant to tobramycin, or had serum creatinine ≥1.5 mg·dL−1Tobramycin 300 mg via a jet nebuliser, twice daily, 6 months (n=30)Placebo (0.9% saline) via a jet nebuliser, twice daily, 6 months (n=30)Crossover RDBPCT, with a one-month washout periodPrimary: number of exacerbations and hospitalisations Secondary: mean change in sputum PA density, eradication of PA in sputum, use of antibiotic, PFT, markers of systemic inflammation, SGRQ, adverse events, emergence of bacterial resistance
Haworth 2014, sponsored by Profile Pharma Ltd [30]Russia, Ukraine, UKInclusion criteria: adult patients (≥18 years) had clinically stable, non-CF bronchiectasis conformed by CT, had ≥2 positive sputum cultures for PA in the preceding 12 months and a positive sputum culture for PA at the screening visit Exclusion criteria: not statedColistin 1 million IU via I-neb AAD system, twice daily, 6 months (n=73)Placebo (0.45% saline) via I-neb AAD system, twice daily, 6 months (n=71)Multicentre RDBPCTPrimary: time to first exacerbation Secondary: severity of exacerbation, mean change in sputum PA density (log10 CFU·g−1), SGRQ, adverse events, emergence of bacterial resistance
Murray 2011, supported by the Chief Scientist Office, Scotland [31]UKInclusion criteria: adult patients had clinically stable bronchiectasis diagnosed by HRCT, had chronically infected sputum, had ≥2 exacerbations in the past year, and had FEV1 >30% predicted Exclusion criteria: patients had CF, active pulmonary disorders (TB, sarcoidosis, ABPA), COPD, poorly controlled asthma, creatinine clearance <30 mL·min−1, vestibular instability, or had hypersensitivity to aminoglycosidesGentamicin 80 mg via a jet nebuliser, twice daily, 12 months (n=32)Placebo (0.9% saline) via a jet nebuliser, twice daily, 12 months (n=33)Multicentre, randomised, single-blind, placebo-controlled trialPrimary: mean change in sputum bacterial load (log10 CFU·g−1) Secondary: sputum analysis (volume, purulence, MPO, free elastase, bacterial eradication), acute exacerbation, PFT, SGRQ, LCQ, markers of systemic inflammation, adverse events, emergence of bacterial resistance
ORBIT-1 trial 2011, sponsored by Aradigm Corp. [24, 25]Australia, Canada, Germany, UK, USAInclusion criteria: adult patients (≥18 years) had clinically stable, non-CF bronchiectasis confirmed by HRCT, and had PA airway infection Exclusion criteria: patients had either changes in regimen or initiation of azithromycin, hypertonic saline, bronchodilators or oral steroids within 28 days prior to study, had received investigational drug or device within 28 days prior to study, or had any serious or active medical or psychical conditionsLiposomal ciprofloxacin 100 mg (n=30), 200 mg (n=32) via a nebuliser, once daily, 28 daysMatching placebo via a nebuliser, once daily, 28 days (n=33)International, multicentre, RDBPCTPrimary: mean change in sputum PA density (log10 CFU·g−1) from baseline to day 28 Secondary: acute exacerbations, PFT, quality of life scores, safety and tolerability
Orriols 1999, no sponsor [32]SpainInclusion criteria: adult patients had bronchiectasis diagnosed by bronchography, CT or both, had ≥3 positive sputum cultures for PA during the year prior to study, and had been treated at least once with oral ciprofloxacin in the past 3 months because of exacerbation Exclusion criteria: patients had CF, immunodeficiency, enzymatic deficiency, congenital disease, hypersensitivity or bacterial resistance to β-lactams or aminoglycosides, or had kidney failureTobramycin 100 mg + Ceftazidime 1000 mg via a jet nebuliser, twice daily, 12 months (n=8)Symptomatic treatment with oxygen, bronchodilators and corticosteroids (n=9)Randomised, open-label, controlled trialMicrobiological study (bacterial eradication) of sputum, hospitalisation, use of antibiotic, PFT, adverse events, emergence of bacterial resistance
Serisier 2013, sponsored by Aradigm Corp. [33]Australia, New ZealandInclusion criteria: adult patients had clinically stable bronchiectasis diagnosed by CT, PA airway infection, and had ≥2 exacerbations requiring antibiotic therapy in the preceding 12 months Exclusion criteria: patients had CF, ABPA, or pulmonary non-TB mycobacterial infectionDRCFI (liposomal ciprofloxacin 150 mg + free ciprofloxacin 60 mg) via PARI LC sprint nebuliser, once daily, three treatment cycles of 28 days “on” inhaled therapy, 28 days “off” (n=20)Matched placebo (liposomal 15 mg or 0.9% saline) via PARI LC sprint nebuliser, once daily, three treatment cycles of 28 days “on” inhaled therapy, 28 days “off” (n=22)International, multicentre, RDBPCTPrimary: mean change in sputum PA density (log10 CFU·g−1) from baseline to day 28 Secondary: eradication of PA in sputum, acute exacerbation, PFT, 6MWT, SGRQ, adverse events and tolerability, emergence of bacterial resistance
Tabernero 2014, no sponsor [28]SpainInclusion criteria: adult patients had non-CF bronchiectasis diagnosed by HRCT, had chronic PA airway infection after an acute exacerbation admission and appropriate antimicrobial therapy Exclusion criteria: not statedColistin 1 million IU via a nebuliser, twice daily, 1 year (n=20)Conventional therapy, 1 year (n=19)Randomised, open-label, controlled trialPrimary: need for hospital readmissions Secondary: sputum microbiology, clinical symptoms, PFT, adverse events
TR02-107, 2009, sponsored by Insmed Inc. [26, 27]Bulgaria, Greece, Hungary, India, Serbia, UkraineInclusion criteria: adult patients (≥18 years) had non-CF bronchiectasis diagnosed by HRCT, had chronic PA airway infection, had SaO2 ≥90% while breathing room air, and were able to produce ≥0.5 g sputum Exclusion criteria: patients had CF, ABPA, aspiration of foreign body, pulmonary TB or non-TB mycobacterial infection, history of lung transplantation, FEV1 <50% predicated, use of any type of antibiotics within 4 weeks prior to the study, evidence of biliary cirrhosis with portal hypertensionArikace (liposomal amikacin) 280 mg or 560 mg, via an eFlow nebuliser, once daily, 28 days (n=44)Matched placebo (liposomes in 1.5% saline) via an eFlow nebuliser, once daily, 28 days (n=20)International, multicentre, RDBPCTPrimary: adverse events Secondary: mean change in sputum PA density, acute exacerbation, hospitalisation, PFT, SGRQ
Wilson 2013, sponsored by Bayer Pharma AG [11]Australia, Germany, Spain, Sweden, UK, USAInclusion criteria: adult patients (≥18 years) had non-CF bronchiectasis diagnosed by HRCT, had ≥2 exacerbations requiring systemic antibiotics or ≥1 hospitalisation for intravenous antibiotics in the previous 12 months, had stable disease in the preceding 30 days, and were able to produce sputum (≥5 mL) that was culture positive for potential respiratory pathogens Exclusion criteria: patients had active non-TB mycobacterial infection, recent significant haemoptysis, use of nebulised antibiotics as maintenance treatment, or use of systemic antibiotics for exacerbation within 4 weeks before randomisationCiprofloxacin 32.5 mg via dry powder for inhalation, twice daily, 28 days (n=60)Matching placebo via dry powder for inhalation, twice daily, 28 days (n=64)International multicentre, RDBPCTPrimary: mean change in sputum bacterial load (log10 CFU·g−1) from baseline to day 28 Secondary: acute exacerbation, hospitalisation, sputum analysis (bacterial eradication, volume, colour), PFT, markers of systemic inflammation, SGRQ, adverse events, emergence of bacterial resistance
  • CF: cystic fibrosis; HRCT: high-resolution computed tomography; TB: tuberculosis; RDBPCT: randomised, double-blind, placebo-controlled trial; QoL-B: quality of life-bronchiectasis; CT: computed tomography; PA: Pseudomonas aeruginosa; ABPA: allergic bronchopulmonary aspergillosis; PFT: pulmonary function test; SGRQ: St George’s Respiratory Questionnaire; FEV1: forced expiratory volume in 1 s; COPD: chronic obstructive pulmonary disease; MPO: myeloperoxidase; LCQ: Leicester Cough Questionnaire; DRCFI: dual release ciprofloxacin for inhalation; 6MWT: 6-min walk test; SaO2: arterial oxygen saturation.