BackgroundThe delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery.MethodsPhase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation—after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study.ResultsDRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs −0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events.ConclusionsOnce-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population.

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis.Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study.60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g−1 (range -9.78–5.02 log10 CFU·g−1)) compared with placebo (-0.27 log10 CFU·g−1 (range -7.96–5.25 log10 CFU·g−1)); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low.Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.

To determine whether asthma alone can cause irreversible airflow obstruction 42 men and 47 women with chronic asthma (mean duration 22 (SD 13) years) without evidence of other disease likely to cause irreversible airflow obstruction were treated with theophylline orally and a beta agonist both orally and by inhalation for four weeks. After two weeks of treatment the FEV, was less than 85% of the predicted normal value (%P) in 48 patients and these individuals then received prednisolone 0*6 mg/kg/day for two weeks. Duration and severity of asthma and smoking history were quantified by questionnaire; 38 patients were current smokers or ex-smokers. FEV1 was measured at 0, 2, and 4 weeks. The mean difference between the best FEV1 during the study and the predicted normal value was 0-29 1 (p < 0.001); FEVy %P decreased with age (r = -030, p < 0.01) and with the duration (r = -0 47, p < 0.001) and severity (r = -0*55, p < 0.001) of asthma. Similar findings were noted when the results for non-smokers and those whose asthma started in adult life were analysed separately. We conclude that asthma alone can cause irreversible airflow obstruction and that the degree of obstruction is a function of the duration and severity of previous asthma. The results suggest the possibility that irreversible airflow obstruction in asthma may be preventable by minimising the degree of persistent asthma.

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Pancreatic enzyme supplementation plays an important role in incretin secretion, gastric emptying, and postprandial hyperglycemia in CF.