Asthma as a Risk Factor for Invasive Pneumococcal Disease

Talbot, Thomas R.; Hartert, Tina V.; Mitchel, Ed; Halasa, Natasha; Arbogast, Patrick G.; Poehling, Katherine A.; Schaffner, William; Craig, Allen S.; Griffin, Marie R.

doi:10.1056/nejmoa044113

Cited by 351 publications

(315 citation statements)

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“…People with asthma have increased susceptibility to streptococcal infections, [13][14][15] increased carriage of bacterial pathogens identified by culture 16 and molecular techniques, 17 and impaired interferon and type 1 T helper cell responses to bacterial polysaccharides. 18,19 Viral infection impairs antibacterial innate immune responses 20 and increases bacterial adherence to bronchial epithelium.…”

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confidence: 99%

Azithromycin for Acute Exacerbations of Asthma

et al. 2016

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IMPORTANCEGuidelines recommend against antibiotic use to treat asthma attacks. A study with telithromycin reported benefit, but adverse reactions limit its use.OBJECTIVE To determine whether azithromycin added to standard care for asthma attacks in adults results in clinical benefit. DESIGN, SETTING, AND PARTICIPANTSThe Azithromycin Against Placebo in Exacerbations of Asthma (AZALEA) randomized, double-blind, placebo-controlled clinical trial, a United Kingdom-based multicenter study in adults requesting emergency care for acute asthma exacerbations, ran from September 2011 to April 2014. Adults with a history of asthma for more than 6 months were recruited within 48 hours of presentation to medical care with an acute deterioration in asthma control requiring a course of oral and/or systemic corticosteroids.INTERVENTIONS Azithromycin 500 mg daily or matched placebo for 3 days. MAIN OUTCOMES AND MEASURESThe primary outcome was diary card symptom score 10 days after randomization, with a hypothesized treatment effect size of −0.3. Secondary outcomes were diary card symptom score, quality-of-life questionnaires, and lung function changes, all between exacerbation and day 10, and time to a 50% reduction in symptom score. RESULTSOf 4582 patients screened at 31 centers, 199 of a planned 380 were randomized within 48 hours of presentation. The major reason for nonrecruitment was receipt of antibiotics (2044 [44.6%] screened patients). Median time from presentation to drug administration was 22 hours (interquartile range, 14-28 hours). Exacerbation characteristics were well balanced across treatment arms and centers. The primary outcome asthma symptom scores were mean (SD), 4.14 (1.38) at exacerbation and 2.09 (1.71) at 10 days for the azithromycin group and 4.18 (1.48) and 2.20 (1.51) for the placebo group, respectively. Using multilevel modeling, there was no significant difference in symptom scores between azithromycin and placebo at day 10 (difference, −0.166; 95% CI, −0.670 to 0.337), nor on any day between exacerbation and day 10. No significant between-group differences were observed in quality-of-life questionnaires or lung function between exacerbation and day 10, or in time to 50% reduction in symptom score. CONCLUSIONS AND RELEVANCEIn this randomized population, azithromycin treatment resulted in no statistically or clinically significant benefit. For each patient randomized, more than 10 were excluded because they had already received antibiotics.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01444469

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Azithromycin for Acute Exacerbations of Asthma

et al. 2016

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“…There is little published evidence that standard bacterial infections are important in the aetiology of asthma exacerbations; 14 however, patients with asthma have increased susceptibility to respiratory bacterial infections, [15][16][17] increased carriage of pathogenic respiratory bacteria identified by culture 18 and molecular techniques, 19 and impaired interferon responses to bacterial polysaccharides. 20 In addition, viral infection impairs innate responses that are important in antibacterial immunity 21 and increases bacterial adherence to bronchial epithelial cells.…”

Section: Aetiology Of Asthma Exacerbationsmentioning

confidence: 99%

A randomised, double-blind, placebo-controlled study to evaluate the efficacy of oral azithromycin as a supplement to standard care for adult patients with acute exacerbations of asthma (the AZALEA trial)

et al. 2016

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Declared competing interests of authors: Sebastian L Johnston has received institutional funding for a clinical trial and consultant compensation from Centocor, Sanofi Pasteur, GlaxoSmithKline and Synairgen; institutional funding for a research grant and consultant compensation from Chiesi, Boehringer Ingelheim and Novartis; and consultant compensation from Grünenthal. He is also a shareholder in Synairgen and has nine relevant licensed patents and one relevant patent pending. Christopher Brightling has received institutional grants and consultant compensation from GlaxoSmithKline, AstraZeneca, Boehringher Ingleheim, Novartis, Chiesi and Roche/Genentech. Dave Singh has received grants and personal fees from Almirall, AstraZeneca, Boehringher Ingleheim, Chiesi, GlaxoSmithKline, Glenmark, Johnson & Johnson, Merck, NAPP, Novartis, Pfizer, Takeda, Teva, Theravance and Verona, and personal fees from Genentech and Skyepharma. Bernard Higgins has taken the role of local principal investigator for multicentre studies funded by Novartis and Roche. Christopher Corrigan has received a grant and personal fees for attendance at scientific conferences and payments for lectures from Allergy Therapeutics; a grant and personal fees from Novartis for research collaborations and consultancy not connected with the current research; a grant for attendance at scientific conferences from Stallergenes, Boehringer Ingelheim and Diagenics; and personal fees from AstraZeneca for speaking at conferences. Rekha Chaudhuri reports a grant and personal fees for attendance at scientific conferences and advisory board meetings: Novartis Pharmaceuticals, Astra-Zeneca, Teva and GlaxoSmithKline. Published October 2016 DOI: 10.3310/eme03080This report should be referenced as follows:Johnston SL, Szigeti M, Cross M, Brightling C, Chaudhuri R, Harrison T, et al. A randomised, double-blind, placebo-controlled study to evaluate the efficacy of oral azithromycin as a supplement to standard care for adult patients with acute exacerbations of asthma (the AZALEA trial). Efficacy Mech Eval 2016;3(8). This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www.publicationethics.org/). Efficacy and Mechanism EvaluationEditorial contact: nihredit@southampton.ac.ukThe full EME archive is freely available to view online at www.journalslibrary.nihr.ac.uk/eme. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www.journalslibrary.nihr.ac.uk Criteria for inclusion in the Efficacy and Mechanism Evaluation journalReports are published in Efficacy and Mechanism Evaluation (EME) if (1) they have resulted from work for the EME programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors. EME programmeThe Efficacy and Mechanism Evaluation (EME) programme was set up in 2008 as part of the National Institute for Health Research (NIHR) and the Medical Research Council (MRC) coordinated strategy for clinical trials. The EME pro...

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“…The updated recommendations ( ３ ) in 2010 include the following changes from 1997 ACIP recommendations: 1) the indications for which PPV23 vaccination is recommended include smoking (12) and asthma (13,14) , and 2) routine use of PPV23 is no longer recommended for Alaska natives or American Indians aged below 65 years unless they have medical or other indications for PPV23 (15) .…”

Section: Pneumococcal Pneumoniamentioning

confidence: 99%