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Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity? Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry. Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV 1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels. Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

Background The airway epithelium plays a central role in wound repair and host defense and is implicated in the immunopathogenesis of asthma. Whether there are intrinsic differences between the synthetic capacity of epithelial cells derived from subjects with asthma and healthy control subjects and how this mediator release is modulated by antiinflammatory therapy remains uncertain. We sought to examine the synthetic function of epithelial cells from different locations in the airway tree from subjects with and without asthma and to determine the effects of antiinflammatory therapies upon this synthetic capacity. Methods Primary epithelial cells were derived from 17 subjects with asthma and 16 control subjects. The release of 13 cytokines and chemokines from nasal, bronchial basal, and air-liquid interface differentiated epithelial cells before and after stimulation with IL-1β, IL-1β and interferon-γ, or Poly-IC (Toll-like receptor 3 agonist) was measured using MesoScale discovery or enzyme-linked immunosorbent assay, and the effects of prednisolone and an inhibitor of nuclear factor κ-B2 (IKK2i) were determined. Results The pattern of release of cytokines and chemokines was significantly different between nasal, bronchial basal, and differentiated epithelial cells but not between health and disease. Stimulation of the epithelial cells caused marked upregulation of most mediators, which were broadly corticosteroid unresponsive but attenuated by IKK2i. Conclusion Synthetic capacity of primary airway epithelial cells varied between location and degree of differentiation but was not disease specific. Activation of epithelial cells by proinflammatory cytokines and toll-like receptor 3 agonism is attenuated by IKK2i, but not corticosteroids, suggesting that IKK2i may represent an important novel therapy for asthma.