title: Systematic review of the dry powder inhalers colistimethate sodium and tobramycin in cystic fibrosis.
abstract: This systematic review evaluated evidence for two dry powder formulations, colistimethate sodium and tobramycin, for the treatment of chronic Pseudomonas aeruginosa in cystic fibrosis, as part of the UK national recommendation process for new technologies. Electronic bibliographic databases were searched in May 2012 (MEDLINE, MEDLINE in-Process, EMBASE, Cochrane Library databases, CINAHL, Web of Science, Conference Proceedings Citation Index and BIOSIS Previews). Relevant outcomes included rate and extent of microbial response (e.g. sputum density of P. aeruginosa), lung function (e.g. forced expiratory volume in 1 s (FEV1)), frequency, severity of acute exacerbations and adverse events. Three trials were included, and both dry powder formulations were reported to be non-inferior in the short term to nebulised tobramycin for FEV1. However, long-term follow-up data were missing and the effect on exacerbation rates was not always reported. Whilst short-term results showed that both dry powder drugs were non-inferior to nebulised tobramycin, there was no long-term follow-up and no phase 3 trials compared nebulised and dry powder colistimethate sodium. The use of FEV1 as the primary end-point may not accurately represent changes in lung health. This review illustrates the difficulty in assessing new technologies where the evidence base is poor.
authors.affiliation: School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, 2 Department of Gastroenterological and Hepatological Medicine, Sheffield Children's Hospital, Sheffield Children's NHS Foundation Trust, Sheffield, 3 Adult Cystic Fibrosis Unit, Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, and 4 Paediatric and Adult Regional Cystic Fibrosis Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Lesley
authors.initials: L
authors.lastname: Uttley
authors.forename: Sue
authors.initials: S
authors.lastname: Harnan
authors.forename: Anna
authors.initials: A
authors.lastname: Cantrell
authors.forename: Chris
authors.initials: C
authors.lastname: Taylor
authors.forename: Martin
authors.initials: M
authors.lastname: Walshaw
authors.forename: Keith
authors.initials: K
authors.lastname: Brownlee
authors.forename: Paul
authors.initials: P
authors.lastname: Tappenden
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D018450:Disease Progression; D058995:Dry Powder Inhalers; D019317:Evidence-Based Medicine; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology; D011208:Powders; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D012107:Research Design; D013997:Time Factors; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D011208:Powders; C004691:colistinmethanesulfonic acid; D014031:Tobramycin; D003091:Colistin