S137 Benralizumab is effective at reducing airway inflammation in severe asthma patients following non-response to mepolizumab associated with persistent sputum eosinophilia

Author(s):  
G Tavernier ◽  
P Aspin ◽  
LJ Holmes ◽  
L Elsey ◽  
R Niven ◽  
...  
2021 ◽  
Vol 2 ◽  
Author(s):  
Courtney Lynn Marshall ◽  
Kosovare Hasani ◽  
Neeloffer Mookherjee

Asthma is a heterogeneous respiratory disease characterized by airflow obstruction, bronchial hyperresponsiveness and airway inflammation. Approximately 10% of asthma patients suffer from uncontrolled severe asthma (SA). A major difference between patients with SA from those with mild-to-moderate asthma is the resistance to common glucocorticoid treatments. Thus, steroid-unresponsive uncontrolled asthma is a hallmark of SA. An impediment in the development of new therapies for SA is a limited understanding of the range of immune responses and molecular networks that can contribute to the disease process. Typically SA is thought to be characterized by a Th2-low and Th17-high immunophenotype, accompanied by neutrophilic airway inflammation. However, Th2-mediated eosinophilic inflammation, as well as mixed Th1/Th17-mediated inflammation, is also described in SA. Thus, existing studies indicate that the immunophenotype of SA is diverse. This review attempts to summarize the interplay of different immune mediators and related mechanisms that are associated with airway inflammation and the immunobiology of SA.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 764
Author(s):  
Shih-Lung Cheng ◽  
Kuo-Chin Chiu ◽  
Hsin-Kuo Ko ◽  
Diahn-Warng Perng ◽  
Hao-Chien Wang ◽  
...  

Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers. Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24, p = 0.0043) compared to non-exacerbators. The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300 (RR = 1.88; 95% CI, 1.26–2.81; p = 0.002) or FeNO measure ≥ 20 (RR = 2.10; 95% CI, 1.05–4.18; p = 0.0356) had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure (RR = 2.16; 95% CI, 1.47–3.18; p = < 0.0001). Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohsen Sadatsafavi ◽  
Amir Khakban ◽  
Hamid Tavakoli ◽  
Solmaz Ehteshami-Afshar ◽  
Larry D. Lynd ◽  
...  

Abstract Background Oral 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. Methods We 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. Results 21,144 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. Conclusions This 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.


2015 ◽  
Vol 8 ◽  
pp. A224
Author(s):  
Lyvia Barbosa Alves ◽  
Maria José Sartório ◽  
Faradiba Serpa ◽  
Rayane Fontoura Koch ◽  
Braga Neto ◽  
...  

2007 ◽  
pp. 74-81
Author(s):  
A. A. Visel ◽  
V. N. Seliverstov ◽  
I. Yu. Visel ◽  
V. A. Sergeev ◽  
N. M. Rakhmatullina

It is well known that efficacy of asthma treatment depends on a choice of a basic medication as well as on a delivery system. The aim of this study was a comparison of clinical efficacy of equal doses of beclomethasone dipropionate (Beclasone Eco Easi Breathe) and fluticasone propionate (Flixotide) via MDI. The study was designed as a randomized open prospective comparative trial. Findings of 26 patients with moderate and severe asthma of > 18 yrs old were analyzed, such as medical history, physical findings, spirometric and bronchodilating test results, heart beat rate and blood pressure, quality of life (QoL) using Russian version of AQLQ questionnaire. After the run-in period the patients randomly received Beclasone Eco Easi Breathe 500 to 1000 μg daily or Flixotide at the same doses for 4 weeks followed the cross-over change of the drugs for the next 4 weeks. After 1 month of the treatment, significant improvements in airflow parameters, need in short-acting β2 -agonists and QoL have been reported. After changing the drugs these effects have been maintained with no further reliable improvement. Thus, the study demonstrated similar efficacy and safety of these inhaled steroids that could be considered as being clinically equal in treatment of moderate and severe asthma.


2007 ◽  
pp. 56-59
Author(s):  
E. A. Starovoytova ◽  
S. N. Ivanov ◽  
L. M. Ogorodova

Asthma patients (n = 79, 7 to 17 years of age) were divided into 3 groups according to asthma severity: mild (n = 23), moderate (n = 24), and severe asthma (n = 32). Asthma was diagnosed according to GINA (2002). Echocardiography, ultrasound evaluation of endothelium vasomotor function and measurement of nitrite anion concentration in exhaled breathe condensate (EBC) were performed in the all patients. Right ventricle dilatation and increase in the total pulmonary vascular resistance were revealed only in patients with severe asthma compared to the control group. Increase in pulmonary artery systolic pressure was significantly higher in the severe asthma patients compared both to the control group and mild asthma patients. Increased right ventricle pressure was accompanied by endothelium dysfunction in 48.1 % (38 patients). High EBC nitrite anion concentration (12.11 ± 1.72 μmol/L) was revealed in asthmatic children compared to control group (3,34 ± 1,58 μmol/L). The results suggest that childhood asthma is associated with morphological and functional abnormalities of pulmonary hemodynamics and endothelium function depending on severity of the disease.


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