Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate

Respirology ◽  
2001 ◽  
Vol 6 (3) ◽  
pp. 237-246 ◽  
Author(s):  
Norbert Berend ◽  
Bruce Kellett ◽  
Neil Kent ◽  
Peter D. Sly ◽  
Keyword(s):  
Fluticasone Propionate ◽  
Asthma Control ◽  
Severe Asthma ◽  
High Dose

scholarly journals Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215168
Author(s):  
David J Jackson ◽  
John Busby ◽  
Paul E Pfeffer ◽  
Andrew Menzies-Gow ◽  
Thomas Brown ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Symptom Control ◽  
Unmet Need ◽  
High Dose ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Exacerbation Rate ◽  
The Uk ◽  
Blood Eosinophils

BackgroundThe UK Severe Asthma Registry (UKSAR) is the world’s largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids.MethodsDemographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL).ResultsAge (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)).ConclusionsThe UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure.

scholarly journals First analysis of the Severe Paediatric Asthma Collaborative in Europe registry

2020 ◽  
Vol 6 (4) ◽  
pp. 00566-2020
Author(s):  
Norrice M. Liu ◽  
Karin C.L. Carlsen ◽  
Steve Cunningham ◽  
Grazia Fenu ◽  
Louise J. Fleming ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Suboptimal Control ◽  
High Dose ◽  
Asthma Control Test ◽  
European Respiratory Society ◽  
Paediatric Asthma ◽  
Global Initiative For Asthma ◽  
Global Initiative ◽  
Long Acting

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe.Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination.Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic.We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching.

Schweres Asthma: Vergleich einer Typ-2-Biomarkerstrategie mit einem Symptom-basierten Algorithmus zur Steuerung der Kortisondosis

2021 ◽  
pp. 1-2
Author(s):  
Sebastian Böing
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Patient Choice ◽  
Control Group ◽  
High Dose ◽  
Life Questionnaire ◽  
Strategy Group ◽  
Corticosteroid Dose ◽  
Increased Risk ◽  
Secondary Outcomes

<b>Background:</b> Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom-risk-based algorithm (control). <b>Methods:</b> We did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at 12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed. <b>Findings:</b> Patients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n = 240) or to the control group (n = 61). 28.4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18.5% of patients in the control group (adjusted odds ratio [aOR] 1.71 [95% CI 0.80–3.63]; p = 0.17). In the per-protocol (PP) population (n = 121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30.7% of patients) compared with the control group (5.0% of patients; aOR 11.48 [95% CI 1.35–97.83]; p = 0.026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose. <b>Interpretation:</b> Biomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low. <b>Funding</b>: This study was funded, in part, by the Medical Research Council UK.

scholarly journals Efficacy of antiinflammatory therapy in patients with severe asthma and cold air-provoked bronchial hyperresponsiveness

2018 ◽  
Vol 28 (5) ◽  
pp. 576-583 ◽  
Author(s):  
A. B. Pirogov ◽  
A. G. Prikhod’ko ◽  
D. A. Gassan ◽  
T. A. Mal’tseva ◽  
V. P. Kolosov ◽  
...  
Keyword(s):  
Fluticasone Propionate ◽  
Asthma Control ◽  
Severe Asthma ◽  
Combined Therapy ◽  
Bronchial Hyperresponsiveness ◽  
Sputum Eosinophil ◽  
Partial Control ◽  
Cold Air ◽  
Antiinflammatory Therapy ◽  
Neutrophil Number

The aim of this study was to assess effects of antiinflammatory therapy with leukotriene receptor antagonists (LTA) and/or combination of an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) on the clinical course and airway inflammatory patterns in patients with severe asthma and cold air-provoked bronchial hyperresponsiveness. Methods. Asthma symptoms, lung function, and spontaneous sputum cytology were assessed at baseline and after 24 weeks of the therapy. Subgroup analysis was performed for patients with sputum eosinophils < 61% and sputum neutrophils < 61%. Eosinophilic patients were treated with fluticasone propionate/salmeterol, neutrophilic patients with treated with fluticasone propionate/salmeterol plus montelukast during 24 weeks. The control of the disease was assessed using Asthma Control Test (ACT). Results. After 24-wk treatment, eosinophilic patients improves asthma control from 10.9 ± 0.5 to 19.6 ± 1.3 according to ACT questionnaire (р < 0.001), FEV1 improved from 45.9 ± 3.7% pred. to 79.2 ± 2.2% pred. (р < 0.001). Sputum eosinophil number decreased from 27.9 ± 2.1% to 7.1 ± 1.9% (р < 0.001); sputum neutrophil number decreased from 21.1 ± 2.1% to 8.7 ± 2.3% (р < 0.001). In neutrophilic patients, ACT score improved from 8.9 ± 0.6 to 15.9 ± 1.2 (р < 0.001), FEV1 improved from 42.9 ± 2.6% pred. to 72.3 ± 2.5% pred. (р < 0.001). Sputum neutrophil number decreased from 76.8 ± 3.7 to 52.2 ± 4.3 % (р < 0.001); Sputum eosinophil number decreased from 8.1 ± 0.7% to 6.2 ± 0.4% (р < 0.05). After 24 weeks of the treatment, partial control of asthma (ACT 20 -24) was achieved in 63% and 29% of patients in eosinophilic and neutrophilic groups, respectively (χ2 = 1.81; р > 0.05) after treatment. Conclusion. Adding montelukast to the combined therapy with fluticasone propionate/salmeterol in patients with severe asthma, cold air-provoked bronchial hyperresponsiveness and increased sputum neutrophils did not resulted in better control of the disease. The analysis of airway inflammatory pattern could be used as an additional marker to predict treatment efficiency.

scholarly journals The role of antifungals in the management of patients with severe asthma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
W. Garth Rapeport ◽  
Kazuhiro Ito ◽  
David W. Denning
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Alternative Therapy ◽  
Fungal Spores ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Airflow Obstruction ◽  
Therapeutic Benefit ◽  
High Dose ◽  
Dosing Regimens

Abstract In patients with asthma, the inhalation of elevated amounts of fungal spores and hyphae may precipitate the onset of asthma or worsen control to the extent of being life-threatening. Sensitisation to fungi, especially Aspergillus fumigatus, is found in 15% to 48% of asthmatics in secondary care and is linked to worse asthma control, hospitalisation, bronchiectasis and fixed airflow obstruction, irrespective of whether allergic bronchopulmonary aspergillosis (ABPA) is diagnosed. ABPA represents a florid response to the presence of Aspergillus spp. but up to 70% of patients with severe asthma exhibit sensitisation to different fungi without meeting the diagnostic criteria for ABPA. The presence of persistent endobronchial colonisation with fungi, especially A. fumigatus, is linked to significantly higher rates of radiological abnormalities, lower post-bronchodilator FEV1 and significantly less reversibility to short acting bronchodilators. The therapeutic benefit for antifungal intervention in severe asthma is based on the assumption that reductions in airway fungal burden may result in improvements in asthma control, lung function and symptoms (especially cough). This contention is supported by several prospective studies which demonstrate the effectiveness of antifungals for the treatment of ABPA. Significantly, these studies confirm lower toxicity of treatment with azoles versus high dose oral corticosteroid dosing regimens for ABPA. Here we review recent evidence for the role of fungi in the progression of severe asthma and provide recommendations for the use of antifungal agents in patients with severe asthma, airways fungal infection (mycosis) and fungal colonisation. Documenting fungal airways colonisation and sensitisation in those with severe asthma opens up alternative therapy options of antifungal therapy, which may be particularly valuable in low resource settings.

scholarly journals Risk factors for death in patients with severe asthma

2014 ◽  
Vol 40 (4) ◽  
pp. 364-372 ◽  
Author(s):  
Andréia Guedes Oliva Fernandes ◽  
Carolina Souza-Machado ◽  
Renata Conceição Pereira Coelho ◽  
Priscila Abreu Franco ◽  
Renata Miranda Esquivel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Health Care ◽  
Asthma Control ◽  
Severe Asthma ◽  
Airflow Obstruction ◽  
Care Facility ◽  
Health Care Facility ◽  
Control Program ◽  
Male Gender ◽  
Respiratory Causes

OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4). Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality.

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