August 4, 2014

The impact of azithromycin therapy on the airway microbiota in asthma

  • Research letter
Open Access
  1. Dominick Shaw3
+Author Affiliations
  1. 1Department of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, UK
  2. 2Department of Ecology and Evolution, Imperial College, London, UK
  3. 3Department of Respiratory Medicine, University of Nottingham, Nottingham, UK
  4. 4Institute of Pharmaceutical Science, Kings College London, London, UK
  1. Correspondence toDr Kenneth Bruce, King's College London, Molecular Microbiology Research Laboratory, Institute of Pharmaceutical Science, 150 Stamford Street, London SE1 9NH, UK;kenneth.bruce@kcl.ac.uk
  • Received 15 September 2013
  • Revised 5 November 2013
  • Accepted 6 November 2013
  • Published Online First 28 November 2013

Introduction

There is interest in the use of macrolide antibiotics in asthma. Macrolides have been shown to improve airway hyper-responsiveness (AHR) and measures of airway inflammation.1 The degree of AHR may relate to the microbiota present in the airways,2 with a recent study reporting that patients with asthma with a significant improvement in AHR following treatment with clarithromycin had a higher bacterial diversity prior to treatment.3 To our knowledge, the impact on the asthmatic airway microbiota of an antibiotic has not been reported and we therefore set out to establish if macrolide therapy was associated with a change in airway microbiota in asthma.

Methods

Five adult patients with moderate/severe asthma (British Thoracic Society step 4–5) (see online supplementary table S1) and no evidence of respiratory infection or bronchiectasis underwent bronchoscopy before and after 6 weeks of daily 250 mg azithromycin therapy. Patients had consented to the study (REC 11/EM/0062). Saline washings of the right upper lobe were obtained following standard procedure, DNA was isolated from the samples (see online supplementary …
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Risk Factors for Chronic and Recurrent Otitis Media–A Meta-Analysis



PLoS One. 2014; 9(1): e86397.
Published online Jan 23, 2014. doi:  10.1371/journal.pone.0086397
PMCID: PMC3900534
Yan Zhang,1 Min Xu,1,* Jin Zhang,1 Lingxia Zeng,1 Yanfei Wang,1,2,3 and Qing Yin Zheng1,2,3
Franklin D. Lowy, Editor
Author information ► Article notes ► Copyright and License information ►

Abstract

Risk factors associated with chronic otitis media (COM) and recurrent otitis media (ROM) have been investigated in previous studies. The objective of this study was to integrate the findings and determine the possible risk factors for COM/ROM based on our meta-analysis. A comprehensive search of electronic bibliographic databases (PubMed, Embase, CNKI and Wanfang database) from 1964 to Dec 2012, as well as a manual search of references of articles, was performed. A total of 2971 articles were searched, and 198 full-text articles were assessed for eligibility; 24 studies were eligible for this meta-analysis. Regarding risk factors for COM/ROM, there were two to nine different studies from which the odds ratios (ORs) could be pooled. The presence of allergy or atopy increased the risk of COM/ROM (OR, 1.36; 95% CI, 1.13–1.64; P = 0.001). An upper respiratory tract infection (URTI) significantly increased the risk of COM/ROM (OR, 6.59; 95% CI, 3.13–13.89; P-0.00001). Snoring appeared to be a significant risk factor for COM/ROM (OR, 1.96; 95% CI, 1.78–2.16; P-0.00001). A patient history of acute otitis media (AOM)/ROM increased the risk of COM/ROM (OR, 11.13; 95% CI, 1.06–116.44; P = 0.04). Passive smoke significantly increased the risk of COM/ROM (OR, 1.39; 95% CI, 1.02–1.89 P = 0.04). Low social status appeared to be a risk factor for COM/ROM (OR, 3.82; 95% CI, 1.11–13.15; P = 0.03). Our meta-analysis identified reliable conclusions that allergy/atopy, URTI, snoring, previous history of AOM/ROM, Second-hand smoke and low social status are important risk factors for COM/ROM. Other unidentified risk factors need to be identified in further studies with critical criteria.
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Tiotropium in asthma: a systematic review

REVIEW


         
Authors Befekadu E, Onofrei C, Colice GL
Published Date February 2014 Volume 2014:7 Pages 11—21
Received 12 December 2013, Accepted 15 January 2014, Published 27 February 2014
Elizabeth Befekadu,1 Claudia Onofrei,1 Gene L Colice1,2
1MedStar Washington Hospital Center, Washington, DC, USA; 2The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

Introduction: The objective of this paper is to systematically review the existing evidence of the effectiveness and safety profile of a long-acting inhaled muscarinic antagonist as add-on therapy in patients with asthma that is uncontrolled despite inhaled corticosteroid (ICS) use.
Methods: With the assistance of two experienced research librarians, we searched Ovid MEDLINE/PubMed (1946 to September 12, 2013), the Cochrane Library review, and the TRIP database. The key search terms were “tiotropium and asthma.” The search was limited to human data published in English. Included in the systematic review were all randomized controlled trials that evaluated the efficacy of tiotropium in patients with asthma. The clinical trials had to be at least 4 weeks in duration and to provide adequate information on clinically appropriate end points in asthma care (eg, change in lung function, exacerbation rates, and/or ICS dosing). Data on patient characteristics, study design, outcome measures, concomitant asthma medication, and adverse events were extracted from the full text of each included individual study. Marked heterogeneity of study design precluded statistical pooling of results for a meta-analysis. Consequently, only descriptive summaries of outcomes are provided.
Results: Our database search retrieved 149 citations. We found five randomized controlled trials in humans that met our criteria for inclusion in the systematic review. We also found two open-label uncontrolled trials that were considered in the discussion. Each of the five included studies met the Consolidated Standards of Reporting Trials criteria for a well-designed randomized trial.
Discussion: The five clinical studies included in this systematic review focused on evaluating the efficacy of tiotropium as add-on therapy to ICS or ICS in combination with a long-acting inhaled β2-agonist (LABA) in patients with uncontrolled moderate to severe persistent asthma. Tiotropium maintained lung function when ICSs were tapered and when an LABA was discontinued. Tiotropium improved lung function when added to ICS alone or ICS–LABA combination therapy. In the only trial to have compared the addition of tiotropium with doubling the dose of ICS, tiotropium provided significantly superior results. In trials in which the addition of tiotropium was compared with salmeterol, the beneficial effects of these two bronchodilators were similar. No safety concerns were found with use of tiotropium as add-on therapy.
Conclusion: Tiotropium may have a beneficial role in moderate to severe persistent asthma despite use of an ICS or ICS and LABA. Use of tiotropium as add-on therapy poses no safety concerns.

Keywords: tiotropium, asthma, lung, inflammation, inhaled corticosteroid, LABA, LAMA 
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Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g3009 (Published 13 May 2014)Cite this as: BMJ 2014;348:g3009


    Rik J B Loymans    , general practitioner1, 
  3. Armin Gemperli, assistant professor234, 
  4. Judith Cohen, general practitioner1,
  5. Sidney M Rubinstein, senior researcher5, 
  6. Peter J Sterk, professor6, 
  7. Helen K Reddel, research leader7, 
  8. Peter Jüni, professor2, 
  9. Gerben ter Riet, associate professor1
    Author affiliations
  1. Correspondence to: R J B Loymans r.j.loijmans@amc.nl
  • Accepted 14 April 2014

Abstract

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma.
Design Systematic review and network meta-analysis using Bayesian statistics.
Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate.
Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome.
Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy.
Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.
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