Oral Corticosteroids Tapering in Severe Asthma.
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ABSTRACT:
SUBMITTER: Boulet LP
PROVIDER: S-EPMC8017580 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
Oral Corticosteroids Tapering in Severe Asthma.
Boulet Louis-Philippe LP Godbout Krystelle K
American journal of respiratory and critical care medicine 20210401 7
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Project description:BackgroundSevere asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment.MethodsIn a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile.ResultsAt enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients.ConclusionThese data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.
| S-EPMC7424982 | biostudies-literature
Project description:BackgroundOral corticosteroids are important components of pharmacotherapy in severe asthma. Our objective was to describe the extent, trends, and factors associated with exposure to oral corticosteroids (OCS) in a severe asthma cohort.MethodsWe used administrative health databases of British Columbia, Canada (2000-2014) and validated algorithms to retrospectively create a cohort of severe asthma patients. Exposure to OCS within each year of follow-up was measured in two ways: maintenance use as receiving on average ≥ 2.5 mg/day (prednisone-equivalent) OCS, and episodic use as the number of distinct episodes of OCS exposure for up to 14 days. Trends and factors associated with exposure on three time axes (calendar year, age, and time since diagnosis) were evaluated using Poisson regression.Results21,144 patients (55.4% female; mean entry age 28.7) contributed 40,803 follow-up years, in 8.2% of which OCS was used as maintenance therapy. Maintenance OCS use declined by 3.8%/calendar year (p < 0.001). The average number of episodes of OCS use was 0.89/year, which increased by 1.1%/calendar year (p < 0.001). Trends remained significant for both exposure types in adjusted analyses. Both maintenance and episodic use increased by age and time since diagnosis.ConclusionsThis population-based study documented a secular downward trend in maintenance OCS use in a period before widespread use of biologics. This might have been responsible for a higher rate of exacerbations that required episodic OCS therapy. Such trends in OCS use might be due to changes in the epidemiology of severe asthma, or changes in patient and provider preferences over time.
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Project description:Introduction: Respiratory distress accounts for approximately 14% of all pediatric emergency medical services (EMS) encounters, with asthma being the most common diagnosis. In the emergency department (ED), early administration of systemic corticosteroids decreases hospital admission and speeds resolution of symptoms. For children treated by EMS, there is an opportunity for earlier corticosteroid administration. Most EMS agencies carry intravenous (IV) corticosteroids; yet given the challenges and low rates of EMS pediatric IV placement, oral corticosteroids (OCS) are a logical alternative. However, previous single-agency studies showed low adoption of OCS. Therefore, qualitative study of OCS implementation by EMS is warranted.Methods: This study's objective was to explore uptake and implementation of OCS for pediatric asthma treatment through semi-structured interviews and focus groups with EMS clinicians. We thematically coded and analyzed transcripts using the domains and constructs of the Consolidated Framework for Implementation Research (CFIR) to identify barriers and facilitators that most strongly influenced OCS implementation and adoption by EMS clinicians.Results: We conducted five focus groups with a total of ten EMS clinicians from four EMS systems: one urban region with multiple agencies that hosted two focus groups, one suburban agency, one rural agency, and a mixed rural/suburban agency. Of the 36 CFIR constructs, 31 were addressed in the interviews. Most constructs coded were in the CFIR domains of the inner setting and characteristics of individuals, indicating that EMS agency factors as well as EMS clinician characteristics were impactful for implementation. Barriers to OCS adoption included unfamiliarity and inexperience with pediatric patients and pediatric dosing, and lack of knowledge of the benefits of corticosteroids. Facilitators included friendly competition with colleagues, having a pediatric medical director, and feedback from receiving EDs on patient outcomes.Conclusion: This qualitative focus group study of OCS implementation by EMS clinicians for the treatment of pediatric asthma found many barriers and facilitators that mapped to the structure of EMS agencies and characteristics of individual EMS clinicians. To fully implement this evidence-based intervention for pediatric asthma, more education on the intervention is required, and EMS clinicians will benefit from further pediatric training.
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Project description:Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab's effects on restoration of corticosteroid sensitivity via PP2A activation; thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance.
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Project description:Patients with asthma are treated in primary healthcare facilities (PHCFs) in Taiwan, where the asthma control status associated with acute exacerbation (AE) and use of oral corticosteroids (OCS) and short-acting β2-agonist (SABA) inhalers remains unclear. A cross-sectional, close-ended, face-to-face questionnaire survey invited board-certified physicians who treat adult asthma patients in PHCFs. The contents of the questionnaire included three parts: rescue OCS to treat AE, regular OCS for asthma control, and AE-related adverse outcomes. There were 445 out of 500 physicians who completed the questionnaire, with 61% of them being non-pulmonologists. A substantial proportion of asthma patients needed rescue OCS or regular OCS each month, or ≥3 canisters of SABA inhalers per year. Approximately 86% of physicians reported their patients with ≥2 AE-related unscheduled visits to clinics or emergency departments in the past year. A total of 41% of physicians reported their patients receiving intubation or intensive care in the past year. A total of 92% of physicians prescribed rescue OCS ≤ 40 mg/day. A total of 92% of physicians prescribed rescue OCS for a duration of ≤7 days for AEs. A total of 85% of physicians prescribed regular OCS ≤ 10 mg/day for asthma control. This is the first study to present the perceptions of asthma-treating physicians on the use of OCS in PHCFs. In summary, 31% of physicians reported ≥ 6% of their patients needed OCS for asthma control and 41% of physicians reported their patients with adverse outcomes in the past year. Thus, the need to improve asthma control in Taiwan is suggested by our study results.
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Project description:Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12 years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA. As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ≥7.5 mg·day-1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ≤5 mg·day-1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering. The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ≤5 mg·day-1, if adrenal insufficiency prevented further reduction, both sustained over ≥4 weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed. PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.
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| PRJEB11495 | ENA