No abstract

Background: Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. Methods: This question was explored in a pre-specified analysis of a 52week, open-label, randomized, parallel-group trial in patients with mild asthma receiving only reliever inhalers, comparing salbutamol 200µg asneeded, maintenance budesonide 200µg twice-daily with salbutamol as needed, and budesonide/formoterol 200/6µg as-needed. Outcomes were compared between patients with blood eosinophils of <0.15, 0.15-<0.3 and ≥0.3x109/L; FeNO of <20, 20-50 and >50ppb; and a composite score based on both. Results: The proportion of patients randomised to as-needed salbutamol having a severe exacerbation increased progressively with increasing blood eosinophil sub-group (4.1%, 6.5% and 19.5%; p=0.014). There were no significant interactions between either biomarker and the effect of as-needed budesonide/formoterol compared with as-needed salbutamol for either exacerbations or severe exacerbations. However, there were significant interactions between blood eosinophil sub-groups and the effect of maintenance budesonide compared with as needed salbutamol for exacerbations (p<0.001) and severe exacerbations (p<0.001). Maintenance budesonide was more effective than as-needed salbutamol in patients with eosinophils ≥0.3x109/L for exacerbations (odds ratio 0.13; 95% CI 0.05-0.33) and severe exacerbations (0.11; 0.03-0.45). This was not the case for eosinophils <0.15x109/L (odds ratio for exacerbations 1.15; 0.51-1.28 and severe exacerbations 5.72; 0.97-33.6). There was no consistent interaction between treatment response and FeNO or the composite score. Conclusions: In patients with mild asthma the effects of as-needed budesonide/formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts.

Pharyngitis (sore throat) is usually caused by viral infections; therefore, antibiotics are generally not warranted. Flurbiprofen 8.75 mg spray (maximum five doses/day, for three days) provides effective symptomatic relief. ABSTRACTBackground: Viral infections cause most cases of pharyngitis (sore throat); consequently, antibiotics are generally not warranted. However, a treatment targeting pain and inflammation, e.g. a topical non-steroidal anti-inflammatory spray, may be helpful for patients. Objective: To evaluate the efficacy and safety of flurbiprofen 8.75 mg spray. Methods: This randomised, double-blind, parallel group study was conducted at six communitybased clinical research centres in Australia and two in New Zealand. Adults with sore throat due to upper respiratory tract infection (onset four days) took one dose of flurbiprofen (n ¼ 249) or placebo spray (n ¼ 256); after six hours, they could re-dose every three-six hours as required, for three days (max. five doses/day). The primary endpoint was the area under the change from baseline curve in throat soreness from zero-two hours (AUC 0-2h ). The change from baseline in other sore throat symptoms also assessed efficacy. Results: The mean AUC 0-2h for throat soreness was significantly greater with flurbiprofen spray (À1.82; 95% CI: À1.98 to 1.65) compared with placebo (À1.13; 95% CI: À1.27 to 0.99) (P < 0.0001). Significantly greater reductions from baseline were observed with flurbiprofen spray compared with placebo from the first time-points assessed (five minutes for throat soreness/difficulty swallowing, 20 minutes for sore throat pain intensity and 30 minutes for swollen throat) for up to six hours (P < 0.05 for all). There was no significant difference in adverse events between treatment groups during the three-day study. Conclusion: Flurbiprofen spray provides rapid and long-lasting relief from sore throat symptoms, and is well-tolerated over three days.

Symptom-driven low-dose inhaled corticosteroid–formoterol is safe and effective in mild asthma and has been recommended as one of the preferred treatment regimens at steps 1 and 2 in the 2019 update of the Global Initiative for Asthma. However, there are no data on patient preferences for this regimen.A subgroup of participants in the PRACTICAL study (ACTRN12616000377437), a randomised controlled trial comparing symptom-driven budesonide–formoterol with maintenance budesonide plus as-needed terbutaline completed a survey on treatment preferences, satisfaction, beliefs and experience at their final study visit.306 (75%) out of 407 eligible participants completed the survey. Regimen preference was strongly associated with randomised treatment, as were preferences for and beliefs about preventer inhaler use. Combination preventer and reliever as-needed therapy was preferred by 135 (90%, 95% CI 85.2–94.8%) out of 150 who were randomised to as-needed budesonide–formoterol, and by 63 (40%, 95% CI 32.7–48.1%) out of 156 who were randomised to maintenance budesonide. By contrast, twice-daily preventer inhaler with a reliever inhaler as required was preferred by 15 (10%) out of 150 of those randomised to as-needed budesonide–formoterol and 93 (60%) out of 156 of those randomised to maintenance budesonide. Satisfaction with all study inhalers was high. Of patients randomised to as-needed budesonide–formoterol 92% (n=138) were confident using it as a reliever at the end of the study.Although most participants preferred the regimen to which they had been randomised, this association was much stronger for those randomised to budesonide–formoterol as needed, indicating that most patients preferred as-needed corticosteroid–formoterol therapy if they had experienced it.

Flurbiprofen spray provides rapid, long-lasting and clinically meaningful relief from sore throat (ANZCTR: ACTRN12612000457842).