Biologic Therapy and Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 100-114 ◽  
Author(s):  
Ravi Viswanathan ◽  
William Busse
Keyword(s):  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Clinical Characteristics ◽  
Biologic Therapy ◽  
Severe Disease ◽  
Asthma Patient ◽  
Clinical Heterogeneity ◽  
Patient Responsiveness

AbstractAlthough airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest.

scholarly journals Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option?

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Michael E. Wechsler ◽  
Chris E. Brightling
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Human Monoclonal Antibody ◽  
Unmet Need ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Uncontrolled Asthma ◽  
Asthma Exacerbations

Abstract Despite treatment with standard-of-care medications, including currently available biologic therapies, many patients with severe asthma have uncontrolled disease, which is associated with a high risk of hospitalization and high healthcare costs. Biologic therapies approved for severe asthma have indications limited to patients with either eosinophilic or allergic phenotypes; there are currently no approved biologics for patients with eosinophil-low asthma. Furthermore, existing biologic treatments decrease exacerbation rates by approximately 50% only, which may be because they target individual, downstream elements of the asthma inflammatory response, leaving other components untreated. Targeting an upstream mediator of the inflammatory response may have a broader effect on airway inflammation and provide more effective asthma control. One such potential target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine released in response to multiple triggers associated with asthma exacerbations, such as viruses, allergens, pollutants and other airborne irritants. Mechanistic studies indicate that TSLP drives eosinophilic (including allergic) inflammation, neutrophilic inflammation and structural changes to the airway in asthma through actions on a wide variety of adaptive and innate immune cells and structural cells. Tezepelumab is a first-in-class human monoclonal antibody that blocks the activity of TSLP. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma across the spectrum of inflammatory phenotypes, and improved lung function and asthma control. Phase 3 trials of tezepelumab are underway. NAVIGATOR (NCT03347279), a pivotal exacerbation study, aims to assess the potential efficacy of tezepelumab further in patients with a broad range of severe asthma phenotypes, including those with low blood eosinophil counts. SOURCE (NCT03406078) aims to evaluate the oral corticosteroid-sparing potential of tezepelumab. DESTINATION (NCT03706079) is a long-term extension study. In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.

scholarly journals Saudi Arabian real-life experience with biologic therapy in severe asthma

2021 ◽  
Vol 16 ◽  
Author(s):  
Safwat Eldaboussi ◽  
Ahmed Qabil ◽  
Ahmed Lotfi ◽  
Amgad Awad ◽  
Eman Abdel Salam ◽  
...  
Keyword(s):  
Observational Study ◽  
Asthma Control ◽  
Severe Asthma ◽  
Eosinophil Count ◽  
Biologic Therapy ◽  
Blood Eosinophil ◽  
Blood Eosinophil Count ◽  
Asthma Exacerbations ◽  
Percent Improvement

Background: Severe asthma (SA) is a common health problem associated with increased morbidity and mortality and high medical costs. Biological therapies have emerged in recent decades as promising treatment options for patients with high type 2 (T2) SA. This retrospective observational study from Saudi Arabia aimed to investigate the effects of additional biologics therapy on reducing oral corticosteroid (OCS) consumption, frequency of asthma exacerbations, improvement in lung function, and asthma control.Methods: This multicenter observational study enrolled a cohort of 97 patients from Mach 2019 to February 2021. Outcomes of anti-IgE, anti-IL5/IL5R, and anti-IL4R therapies in severe type 2 asthma were recorded and analyzed in terms of number of exacerbations (emergency visits or hospitalizations required), asthma symptoms, and use of oral corticosteroids, blood eosinophil count, asthma control according to GINA classification, and FEV1 before and during biologic therapy.Results:  Ninety-seven patients were included in the analysis The mean age was 46.7±14.1 years, and 69.1% of them were female. The average duration of biological treatment was 16.4±6.8 months. At the time of data collection, the four biologic therapies reduced the exacerbation rate per year from 82/97 (84.5%) to 14/97 (14.4%) with a percent improvement of 83% from 2.9 per year in the year before biologic treatment to 1.6 per year (p<0.001). OCS was reduced from 75/97 (77.3%) to 10/97 (10.3%) for a percent improvement of 86.7%, and the average OCS dose decreased from 7.12 mg to 6.8 mg. Mean blood eosinophil count also decreased after biologic therapy from 750.5±498.5 to 188.0±122.4 cells/μl, most significant result achieved with benralizumab, and mean FEV1 improved from 59.0±12.9% to 76.0±10.2%, most significant result achieved with omalizumab.  ll patients had uncontrolled asthma before biologics therapy, but asthma control improved by 91.8% after treatment.Conclusions: Biologic as add-on therapy for high T2 SA was found to reduce asthma exacerbations, systemic glucocorticoid doses, and SA symptoms.

scholarly journals Airway inflammation in severe asthmatics with acid gastro-oesophageal reflux

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216304
Author(s):  
Nicole Tanner ◽  
Sejal Saglani ◽  
Albert M Li ◽  
Andrew Bush ◽  
Louise Fleming
Keyword(s):  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Systemic Inflammation ◽  
Childhood Asthma ◽  
Host Defence ◽  
Oesophageal Reflux ◽  
Epithelial Integrity ◽  
The Relationship

The relationship between childhood asthma and gastro-oesophageal reflux (GOR) is contentious. Recent studies in adult asthmatics suggest that GOR is associated with worse control and differences in sputum proteomics related to epithelial integrity, systemic inflammation and host defence. We assessed 127 children with severe asthma undergoing bronchoscopy and pH study. There were no differences in asthma control or measures of airway inflammation or remodelling when those with acid GOR were compared with those without. These results suggest that acid GOR is not an important comorbidity in paediatric severe asthma.

S100A8/A9: a mediator of severe asthma pathogenesis and morbidity?This article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba.

2009 ◽  
Vol 87 (10) ◽  
pp. 743-755 ◽  
Author(s):  
Andrew J. Halayko ◽  
Saeid Ghavami
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Protein Complex ◽  
Airway Remodeling ◽  
Severe Disease ◽  
S100 Protein ◽  
Future Research ◽  
Inhaled Steroids ◽  
Molecular Pattern ◽  
125Th Anniversary

Nearly 12% of children and 6% of adults in Canada have been diagnosed with asthma. Although in most patients symptoms are controlled by inhaled steroids, a subpopulation (∼10%) characterized by excessive airway neutrophilia, is refractory to treatment; these patients exhibit severe disease, and account for more than 50% of asthma health care costs. These numbers underscore the need to better understand the biology of severe asthma and identify pro-asthma mediators released by cells, such as neutrophils, that are unresponsive to common steroid therapy. This review focuses on a unique protein complex consisting of S100A8 and S100A9. These subunits belong to the large Ca2+-binding S100 protein family and are some of the most abundant proteins in neutrophils and macrophages. S100A8/A9 is a damage-associated molecular pattern (DAMP) protein complex released in abundance in rheumatoid arthritis, inflammatory bowel disease, and cancer, but there are no definitive studies on its role in inflammation and obstructive airways disease. Two receptors for S100A8/A9, the multiligand receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4), are expressed in lung. TLR4 is linked with innate immunity that programs local airway inflammation, and RAGE participates in mediating fibroproliferative remodeling in idiopathic pulmonary fibrosis. S100A8/A9 can induce cell proliferation, or apoptosis, inflammation, collagen synthesis, and cell migration. We hypothesize that this capacity suggests S100A8/A9 could underpin chronic airway inflammation and airway remodeling in asthma by inducing effector responses of resident and infiltrating airway cells. This review highlights some key issues related to this hypothesis and provides a template for future research.

scholarly journals Comparing Patient Characteristics, Clinical Outcomes, and Biomarkers of Severe Asthma Patients in Taiwan

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 764
Author(s):  
Shih-Lung Cheng ◽  
Kuo-Chin Chiu ◽  
Hsin-Kuo Ko ◽  
Diahn-Warng Perng ◽  
Hao-Chien Wang ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Clinical Characteristics ◽  
Linear Models ◽  
Patient Characteristics ◽  
Emergency Department Visits ◽  
Receiver Operating Characteristic Curves ◽  
Increased Risk ◽  
Significant Difference ◽  
Asthma Patients ◽  
Patients At Risk

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.

scholarly journals Analysis of clinical characteristics of severe pertussis in infants and children: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caiying Wang ◽  
Huimin Zhang ◽  
Yanlan Zhang ◽  
Lin Xu ◽  
Min Miao ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Characteristics ◽  
Severe Disease ◽  
Severe Pneumonia ◽  
Infants And Children ◽  
Critically Ill Children ◽  
Young Infants ◽  
Incidence And Mortality ◽  
Increasing Trend ◽  
Medical University

Abstract Background The incidence of pertussis shows an increasing trend in recent years, but some clinicians often lack sufficient understanding of the clinical characteristics and risk factors for severe pertussis, and more effective measures should be taken to reduce the incidence and mortality of pertussis in young infants Methods A retrospective study was conducted, and 184 infants and children with pertussis who had been hospitalized in the Department of Pediatrics of Beijing Ditan Hospital affiliated with Capital Medical University from January 2016 to December 2017 were included. Clinical data of the patients were collected and the clinical characteristics were statistically analyzed Results Among the 184 patients, 41.85% were infants < 3 months of age, and 65.22% of the total patients were not vaccinated against pertussis. There were 22 critically ill children, among whom 4 died, and compared with mild cases, they had a higher proportion of children younger than 3 months of age and infants not vaccinated against pertussis (63.64% vs. 38.89% and 100% vs. 60.49%, respectively); a higher proportion of children with severe pneumonia (100% vs. 0%); higher leukocyte count(× 109/L , 35.80 ± 20.53 vs 19.41 ± 8.59); and a higher proportion of children with severe hyperleukocytosis (18.18% vs. 0%, respectively) (P<0.05) Conclusions 1. Infants aged <3 months not vaccinated for pertussis appear more likely to become infected and have more severe disease. 2. Severe pneumonia and hyperleukocytosis are the main mechanisms underlying severe pertussis.

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