Budesonide

In severe asthma, intensive (“supratherapeutic”) doses of inhaled corticosteroids (ICS) are often used. The prevalence of supratherapeutic ICS use and its impact on corticosteroid-related comorbidities is poorly understood. We aimed to describe the prevalence of supratherapeutic ICS use in severe asthma, its relation to corticosteroid-related comorbidities, and changes in prescribed and redeemed ICS dose after 12 months of biologic therapy.

Patients from the nationwide Danish Severe Asthma Register (DSAR) receiving biologic therapy > 12 months were included. Supratherapeutic doses were defined as > 1600 µg budesonide daily. Baseline characteristics, comorbidity burden, and change in ICS use after 12 months of biologic therapy was stratified according to ICS use at baseline.

We included 652 patients in our analyses and 156 (24%) were supratherapeutic ICS users prior to initiation of biologic therapy. Supratherapeutic ICS users had a higher baseline prevalence of cataracts at 14 vs 8.1%; p = 0.025. No differences in other corticosteroid-related comorbidities were observed.No change in prevalence of prescribed supratherapeutic ICS was seen after 12 months of biologic therapy. However, a reduction in ICS adherence among supratherapeutic users was observed with 72% of patients demonstrating > 80% adherence at 12 months, compared to 83% at baseline (p < 0.001).

Supratherapeutic doses of ICS were used by almost one-fourth of the patients prior to initiation of biologic therapy and were associated with a higher prevalence of cataracts. Physician-driven ICS reduction was rare, yet supratherapeutic ICS users were found to self-regulate ICS therapy when treated with biologic therapy.

The aim of this study was twofold. First, to examine the mechanical properties (packing and flow) of a series of adhesive mixtures, consisting of two different lactose carriers and varying concentrations of budesonide, using a range of test methods. Second, to investigate if any of the test methods correlate with the dispersibility of the mixtures, i.e. the fine particle fraction and mass median aerodynamic diameter. The mechanical properties assessed included packing, shearing, permeability and compressibility. Dispersion data were generated using an impactor operated at two pressure drops (0.5 and 4 kPa). To explore correlations between the mixture properties, Principal Component Analysis and Pearson correlation were used as statistical tools. The different test methods yielded different property-drug load relationships, which can be classified into two groups: First, packing density and shearing properties, and second, permeability and compressibility. The methods in the first group produced markedly fluctuating property-drug load relationships, characterised by two distinct waves. This type of property-drug load relationship was similar to that observed in the dispersion experiments, and significant correlations were found between shearing properties and dispersibility. Thus, any correlations between mechanical and dispersion properties depend on the choice of the test method used. The underlying cause of this co-variation is the parallel effect of both the blend architecture and the structure of the adhesion layer on mechanical and dispersion properties.