Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial.

BACKGROUND: Tiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. METHODS: In a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of >20 pack-years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 µg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. RESULTS: 90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72-1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23-92 mL; p=0.002). Adverse events were similar under both treatments. CONCLUSIONS: Tiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

Vitamin D3 supplementation in adults with bronchiectasis: A pilot study.

Vitamin D supplementation prevents acute respiratory infections and, through modulating innate and adaptive immunity, could have a potential role in bronchiectasis management. The primary aims of this pilot study were to assess serum 25-hydroxyvitamin D (25(OH)D) levels in New Zealand adults with bronchiectasis, and their 25(OH)D levels after vitamin D3 supplementation. Adults with bronchiectasis received an initial 2.5 mg vitamin D3 oral loading dose and 0.625 mg vitamin D3 weekly for 24 weeks. The primary outcome was serum 25(OH)D levels before and after vitamin D3 supplementation. Secondary outcomes (time to first infective exacerbation, exacerbation frequency, spirometry, health-related quality of life measures, sputum bacteriology and cell counts and chronic rhinosinusitis) were also assessed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12612001222831). The initial, average 25(OH)D level was 71 nmol/L (95% confidence interval (CI): [58, 84]), rising to 218 nmol/L (95% CI: [199, 237]) at 12 weeks and 205 nmol/L (95% CI: [186, 224]) at 24 weeks. The initial serum cathelicidin level was 25 nmol/L (95% CI: [17, 33]), rising to 102 nmol/L (95% CI: [48, 156]) at 12 weeks and 151 nmol/L (95% CI: [97, 205]) at 24 weeks. Over the 24-week study period, we observed statistically significant changes of 1.11 (95% CI: [0.08, 2.14]) in the Leicester Cough Questionnaire and -1.97 (95% CI: [-3.71, -0.23]) in the Dartmouth COOP charts score. No significant adverse effects were recorded. Many New Zealand adults with bronchiectasis have adequate 25(OH)D levels. Weekly vitamin D3 supplementation significantly improved 25(OH)D levels.

Sputum procalcitonin: a potential biomarker in stable bronchiectasis.

Sputum procalcitonin is elevated in exacerbations of bronchiectasis. The primary aim of this study was to investigate whether sputum procalcitonin levels are higher in patients with stable bronchiectasis than in healthy controls. We also assessed differences in procalcitonin levels in spontaneously expectorated and induced sputum samples and their repeatability 1 week later. Participants included were aged over 18 years and either had radiologically confirmed bronchiectasis or were healthy controls. Patients with bronchiectasis were clinically stable for at least 6 weeks and had spontaneous and induced sputum collected at visit 1 and again 7 days later. Only induced sputum samples were collected from healthy controls during visit 1. Sputum procalcitonin concentrations in sputum were measured. In total, 30 patients with bronchiectasis and 15 healthy controls were enrolled in this observational study. In the pooled data from visit 1 and 2, the geometric mean procalcitonin level in induced sputum was significantly higher in the bronchiectasis group than in the healthy control group (1.5 ng·mL-1, 95% CI 1.0-2.1 ng·mL-1 versus 0.4 ng·mL-1, 95% CI 0.2-0.9 ng·mL-1; mean ratio 3.6, 95% CI 1.5-8.6; p=0.006). Mean procalcitonin level was higher in spontaneous sputum than in induced sputum at visit 1 (1.8 ng·mL-1, 95% CI 1.2-2.7 ng·mL-1 versus 1.1 ng·mL-1, 95% CI 0.7-1.8 ng·mL-1) and visit 2 (1.5 ng·mL-1, 95% CI 1.0-2.5 ng·mL-1 versus 1.2 ng·mL-1, 95% CI 0.8-1.6 ng·mL-1; p=0.001). Repeating spontaneous and induced sputum procalcitonin levels 1 week later produced similar concentrations (p=0.29, intraclass correlation coefficient (ICC)=0.76 and p=0.72, ICC=0.70, respectively). Sputum procalcitonin is increased in patients with stable bronchiectasis and has potential as a biomarker of airway inflammation and infection in bronchiectasis.