Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance. METHODS AND ANALYSIS: We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance. ETHICS AND DISSEMINATION: Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians. TRIAL REGISTRATION NUMBER: ACTRN12619000564156.

Glucose tolerance during pulmonary exacerbations in children with cystic fibrosis.

BACKGROUND: Patients with Cystic Fibrosis (CF) are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability. METHODS: Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well. RESULTS: Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77). At the follow up OGTT, 8 of 9 (89%) remained within their respective glucose tolerance status groupings. CONCLUSION: The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.

Australian epidemic strain pseudomonas (AES-1) declines further in a cohort segregated cystic fibrosis clinic.

AIM: To evaluate changes in prevalence of an epidemic strain of Pseudomonas aeruginosa (AES-1, Australian epidemic strain, type 1) in a paediatric cystic fibrosis (CF) centre practising cohort segregation, to describe the patients' clinical characteristics at acquisition and observe mortality rates. METHODS: Cohort segregation was introduced in our paediatric CF clinic January 2000. The prevalence of AES-1 was analysed in 1999, 2002 and 2007. Age at acquisition, lung function, presence of bronchiectasis, hospitalisations, prior P. aeruginosa infection and mortality rates were collected. AES-1 infection was determined by pulse-field-gel-electrophoresis (PFGE) on airway specimen cultures taken three monthly. RESULTS: The prevalence of AES-1 declined from 21% in 1999 to 14% in 2002 (risk difference 7% (95% CI 1,13) p=0.0256) and to 6% in 2007 (risk difference 8% (95% CI 3,13) p=0.0018). New acquisitions after the introduction of cohort segregation were uncommon (10 by 2002 and another 7 by 2007) with a declining incidence of 3.3 cases/year (1999 to 2002) compared to 1.4 cases/year (2002 to 2007). Twenty-two of 32 (69%) deaths between 1999 and 2007 occurred in patients infected with AES-1. CONCLUSION: Cohort segregation has been associated with reductions in the prevalence of AES-1 in our CF clinic. Mortality was higher in patients infected with AES-1 than other organisms.