Optimal asthma control, starting with high doses of inhaled budesonide

Abstract

The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines.The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 mg or 1,600 mg budesonide daily by Turbuhaler1 for 8 weeks (double-blind), then 1,600 mg . day -1 for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1±16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose.By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200-and 1,600-mg . day -1 starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L . min -1 , p=0.8). Subjects starting with 3,200 mg . day -1 were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of $3.92 mmol by week 16 (p=0.03). During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 mg . day -1 , p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days . week -1 , b 2 -agonist use 0.2 occasions . day -1 , and PD20 2.4 mmol).In subjects with poorly controlled asthma, a starting dose of 1,600 mg . day -1 budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation. Eur Respir J 2000; 15: 226±235.

Improvement in asthma endpoints when aiming for total control: salmeterol/fluticasone propionate versus fluticasone propionate alone

“…Although not studied in the GOAL study, a number of studies have shown that long-term treatment with ICS leads to a reduction in airway inflammation and hyper-responsiveness, and a reversal in airway remodelling. [11][12][13] In the study by Ward et al, although a reduction in inflammatory cell counts was seen after three months of treatment with fluticasone propionate, improvements in airway remodelling were not seen until 12 months of treatment. 11 The effects of ICS therapy in airway remodelling are a source of controversy and this issue requires further research.…”

Retrospective Monitoring in the Management of Persistent Asthma

“…29 However, the 61 patients in that study had poorly controlled asthma, and their expectations about monitoring were probably high. Reddel et al concluded that the context in which monitoring is undertaken may influence adherence and that the patients' perception of usefulness (and hence better adherence) may have been enhanced by visual presentation and discussion of graphed data at control visits every 8 weeks.…”

“…Reddel et al concluded that the context in which monitoring is undertaken may influence adherence and that the patients' perception of usefulness (and hence better adherence) may have been enhanced by visual presentation and discussion of graphed data at control visits every 8 weeks. 29 We believe that, in our strictly clinically oriented setting, we had an acceptable adherence rate: our overall correlation coefficient between expected and actual days of diary-card completion (completed entries) was 0.65. Moreover, 33 (39%) of the 84 patients had 100% symptom score and PEF diary-card completion, and 68% had Ն 75% completion, which might be regarded as poor in research but is reasonably good in a clinical management setting.…”

Severe refractory asthma: an update

“…There is, however, no evidence that these ultra-high doses lead to better control of asthma, improve lung function or ameliorate asthma-related quality of life [23,24]. Care givers need to realise that such high doses of inhaled steroids may be associated with systemic sideeffects in the long run including adrenal suppression, skin thinning, ecchymoses, reduced bone mineral density, glaucoma and cataract [25,26].…”