Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. Methods We performed a randomised double-blind placebo-controlled trial in subjects with exacerbationprone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β 2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Results The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with noneosinophilic severe asthma (blood eosinophilia ≤200/ml): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. ClinicalTrials.gov number NCT00760838.

The benefits of drug therapy for asthma have been well established, but adherence to treatment is poor, and this might be associated with an increased risk of asthma exacerbations. The aim of this study was to review the literature on the association between adherence to asthma controller treatment and risk of severe asthma exacerbations in children and adults.A systematic literature search was performed in PubMed, Embase and Web of Science, from inception until January 2014. Studies were included if data on the association between medication adherence and severe asthma exacerbations were presented. Quality was assessed using a modified version of the Newcastle-Ottawa Scale.The search yielded 2319 unique publications, of which 23 met the inclusion criteria and underwent data extraction and quality scoring. High levels of heterogeneity across studies with regard to adherence and exacerbation measurements, designs and analysis precluded a formal meta-analysis. Although effect measures varied widely, good adherence was associated with fewer severe asthma exacerbations in highquality studies.Good adherence tended to be associated with lower risk of severe asthma exacerbations. Future studies should use standardised methodology to assess adherence and exacerbations, and should consider inhaler competence.@ERSpublications High-quality studies indicated that better adherence is associated with fewer severe asthma exacerbations

Objective To provide an overview of drug use in children in three European countries.Design Retrospective cohort study, 2000-5.Setting Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet).Participants 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands).Main outcome measure Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of “recurrent/chronic” use (three or more prescriptions a year) and “non-recurrent” or “acute” use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class.Results Three levels of drug use could be distinguished in the study population: high (>10/100 children per year), moderate (1-10/100 children per year), and low (<1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label.Conclusion This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs.

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