Inhaled heparin in cystic fibrosis

Cystic fibrosis (CF) is characterised by inspissated airway secretions and chronic endobronchial infection associated with exuberant neutrophilic inflammation. Unfractionated heparin may be mucolytic and has demonstrated a number of anti-inflammatory properties; however, further safety data are needed in these subjects who are at risk of airway bleeding. The current study aimed to assess the medium-term safety and tolerability of moderately high-dose inhaled heparin in CF adults and to explore possible in vivo mucolytic and anti-inflammatory outcomes. A randomised, double-blind, placebo-controlled crossover study of twice daily inhalation of 50,000 IU of heparin for 2 weeks was undertaken in CF adults, with a 1-week washout period. Eighteen subjects were randomised and 14 (mean±SD age 23±7.8 yrs and percentage-predicted forced expiratory volume in one second 52.1±15.56%) completed the study protocol. Heparin neither affected blood coagulation parameters nor resulted in any increase in adverse events. Heparin inhalation had no significant effect upon forced expiratory volume in one second, symptoms of sputum clearance or sputum inflammatory markers. The current pilot study demonstrated no evidence of improved sputum clearance with 50,000 IU of inhaled heparin given twice daily to adult cystic fibrosis subjects. However, inhaled heparin was safe and the future evaluation of larger doses over a longer period may be warranted

Long-term, low-dose erythromycin in bronchiectasis subjects with frequent infective exacerbations

Background: Macrolide antibiotics are increasingly prescribed for subjects with non-cystic fibrosis (CF) bronchiectasis, an empiric extension of their proven efficacy in CF. Widespread, injudicious use of long-acting macrolides, particularly azithromycin, risks significantly increasing population antimicrobial resistance. Methods: In an attempt to power a definitive randomised-controlled trial (RCT), an uncontrolled evaluation of the impact of long-term, low-dose oral erythromycin therapy upon pulmonary exacerbation frequency in non-CF bronchiectasis subjects was performed. Adult bronchiectasis subjects with at least 2 infective exacerbations in the preceding 12 months were followed for 12 months following commencement of prophylactic oral erythromycin 250 mgs daily. The co-primary outcome measures, comparing the 12 month erythromycin and pre-erythomycin periods, were numbers of infective exacerbations and days of antibiotic therapy for infective exacerbations. Results: In the 24 evaluable subjects completing a minimum of 12 months of therapy, erythromycin was associated with halving of both the median (range) annual number of infective exacerbations (2 (0-8) vs 4 (2-11), 95% CI 1.5 to 3.5, p < 0.0001) and annual days of antibiotic use (21 (0-78) vs 44 (15-138), 95% CI 18 to 40, p < 0.0001) compared with the preceding 12 month period. Conclusions: Low-dose erythromycin may have a robust effect upon exacerbation frequency in non-CF bronchiectasis subjects with frequent exacerbations and this warrants proceeding to a definitive intervention study. These data have enabled powering of an RCT of long-term, low-dose erythromycin, which is now underway and also incorporates bronchoscopic evaluation for pathophysiologic data