HE PATHOPHYSIOLOGY OF NONcystic fibrosis (CF) bronchiectasis is generally considered to be characterized by an airway inflammatory response to bacterial pathogens, and recent data provide further evidence to support this "vicious cycle" hypothesis. 1 However, studies of maintenance therapies designed to interrupt this cycle at differing points have failed to demonstrate convincing evidence of clinical efficacy, including prolonged oral antibiotics, 2 inhaled tobramycin, 3 inhaled corticosteroids, 4 and mucolytics. 5 Until recently, 6 there have arguably been no therapies with proven clinical benefit in non-CF bronchiectasis.Maintenance azithromycin was shown to reduce exacerbations in non-CF bronchiectasis 6 ; however, limitations of that study 7 included a treatment period of only 6 months and a lack of systematic evaluation for macrolide See also pp 1251 and 1295.

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL−1. Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

This trial compared the cost of an integrated home-based care model with traditional inpatient care for acute chronic obstructive pulmonary disease (COPD). 25 patients with acute COPD were randomised to either home or hospital management following request for hospital admission. The acute care at home group costs per separation ($745, n=13) were significantly lower (p<0.01) than the hospital group ($2543($ , CI95% $1766

Although heparin is used as an anticoagulant, its biologic function remains unclear. Substantial evidence exists that suggests it may modulate many aspects of immune function and inflammation. We demonstrated, in a double-blind, placebo-controlled, crossover study involving 10 allergic subjects, that a small dose of heparin (25 U/kg) administered intravenously 10 min before challenge reduced the acute cutaneous reaction to 10 allergens and histamine from a group-average sum of mean (+/- SD) wheal diameters at a baseline of 29.9 +/- 10 mm and after normal saline placebo (29.5 +/- 10.7 mm) to after heparin (14.4 +/- 10.4 mm) (p < 0.02, Wilcoxon's signed rank test). In 15 subjects with asthma and dust mite allergy, nebulized heparin 20,000 units administered in a double-blind, placebo-controlled, crossover fashion 10 min before challenge inhibited the bronchospasm induced by inhaled dust mite extract. Log2 of the provocative dose of mite extract causing a 20% fall in FEV1 at baseline was 4.1 +/- 1.5 protein nitrogen units (PNU); after normal saline it was 4.5 +/- 2.0 PNU, and after heparin it was 5.1 +/- 2.5 PNU (p = 0.04). These data suggest heparin may have an inhibitory role in acute mast-cell-mediated allergic inflammation.

Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.