Rationale Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. Objectives To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). Methods Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV 1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. Main results 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (−2.4 units, p=0.046). Adverse events were similar between groups. Conclusions Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. Trial registration number NCT00669331.

Despite the Epworth Sleepiness Score being widely used, there are limited studies of its reliability in clinical practice. The aim of this study was to assess the reliability of the Epworth Sleepiness Score in a clinical population. The study included patients referred to Middlemore Hospital sleep service between October and November 2014, aged over 17 years, with at least two Epworth Sleepiness Score measurements at up to three different points on the diagnostic pathway: on General Practitioner referral (GP Epworth Sleepiness Score); at overnight oximetry assessment (Oximetry Epworth Sleepiness Score); and at a specialist clinic (Specialist Epworth Sleepiness Score). No treatment was administered between scores. One-hundred and thirty-three patients were included in the study. There was a median of 91 days from GP Epworth Sleepiness Score to Oximetry Epworth Sleepiness Score, and 11 days from Oximetry Epworth Sleepiness Score to Specialist Epworth Sleepiness Score. There was poor test-retest reliability between GP Epworth Sleepiness Score and Specialist Epworth Sleepiness Score; 72.4% and 17.8% of patients had an absolute difference of more than 2 and 8 Epworth Sleepiness Score points, respectively. A Bland-Altman plot of mean Epworth Sleepiness Score versus the difference between GP Epworth Sleepiness Score and Specialist Epworth Sleepiness Score demonstrated a wide scatter of data and 95% confidence interval for the difference in Epworth Sleepiness Score for an individual patient of -14 to +10. There was similar variability between GP Epworth Sleepiness Score and Oximetry Epworth Sleepiness Score. The reliability of the Epworth Sleepiness Score is unproven in clinical settings. This study shows poor test-retest reliability of Epworth Sleepiness Score, particularly between primary and secondary care, arguing against the use of Epworth Sleepiness Score for clinical decision-making or prioritisation of services without first assessing the reliability of the Epworth Sleepiness Score in the relevant clinical population.

There is an increased rate of rise in VO2 relative to work rate during exercise in patients with McArdle's disease. There is also a greater rise in catecholamines, which may be the result of a physiological response to substrate starvation, and is likely to contribute to the increase in VO2.

Combined therapy with tiotropium and long-acting beta 2 agonists confers additional improvement in symptoms, lung function and aspects of health-related quality of life (QOL) compared with each drug alone in patients with COPD. However, the efficacy of combined therapy on walking distance, a surrogate measure of daily functional activity and morbidity remains unclear. The aim was, therefore, to quantify the benefit of this therapy on the six minute walk test. Secondary outcomes included change in lung function, symptoms, the BODE index and QOL. In a double-blind, crossover study, 38 participants with moderate to severe COPD on tiotropium were randomised to receive either formoterol or placebo for 6 weeks. Following a 2-week washout period, participants crossed over to the alternate arm of therapy for a further 6 weeks. Thirty-six participants, with an average age of 64.3 years and FEV1 predicted of 53%, completed the study. Combined therapy improved walking distance by a mean of 36 metres [95% CI: 2.4, 70.1; p = 0.04] compared with tiotropium. FEV1 increased in both groups (160 mL combination therapy versus 30 mL tiotropium) with a mean difference of 110 mL (95% CI: -100, 320; p = 0.07) between groups, These findings further support the emerging advantages of combined therapy in COPD. Australian New Zealand Clinical Trials.