Reproducibility and stability of severe asthma research program (SARP) clinical cluster phenotypes in SARP3

Moore, Wendy C.; Li, Xingnan; Li, Huashi; Castro, Mario; Erzurum, Serpil C.; Fahy, John V.; Israel, Elliot; Jarjour, Nizar N.; Levy, Bruce D.; Bacharier, Lenoard; Fitzpatrick, Anne M.; Gaston, B.; Ly, Ngoc P.; Myers, Ross; Ramratnam, Sima; Phipatanakul, Wanda; Teague, W. Gerald; Mauger, David T.; Wenzel, Sally; Meyers, Deborah A.; Bleecker, Eugene R.

doi:10.1183/13993003.congress-2016.oa3033

Cited by 4 publications

(4 citation statements)

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“…Large cohort studies of patients with asthma and severe asthma have been carried out in Europe 8,9 and the United States, 10 providing invaluable insight into patient characteristics and asthma phenotypes. There is comparatively less data in non-Western populations.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Proportion and Healthcare Utilisation of Adult Patients with Uncontrolled Severe Asthma versus Non-Severe Asthma Seen in a Southeast Asian Hospital-Based Respiratory Specialist Clinic

Tay

Wong

Ihsan

et al. 2017

Ann Acad Med Singap

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Introduction: Understanding the burden of uncontrolled severe asthma is essential for disease-targeted healthcare planning. There is a scarcity of data regarding the proportion, healthcare utilisation and costs of patients with uncontrolled severe asthma in Asia. This study aimed to plug the knowledge gap in this area. Materials and Methods: Consecutive patients with asthma managed in our respiratory specialist clinic were evaluated prospectively. Healthcare utilisation comprising unscheduled asthma-related primary care visits, emergency department (ED) visits and hospital admissions were obtained from the national health records system. We defined uncontrolled severe asthma as poor symptom control (Asthma Control Test score <20); 2 or more asthma exacerbations requiring ≥3 days of systemic corticosteroids in the previous year; 1 or more serious asthma exacerbation requiring hospitalisation in the previous year; or airflow limitation with pre-bronchodilator forced expiratory volume in 1 second (FEV1) <80% predicted despite high dose inhaled corticosteroids and another controller medication. Results: Of the 423 study participants, 49 (11.6%) had uncontrolled severe asthma. Compared to non-severe asthma, patients with uncontrolled severe asthma were older and more likely to be female and obese. They had a median of 2 (interquartile range: 0 to 3) exacerbations a year, with 51% having ≥2 exacerbations in the past 12 months. They were responsible for 43.9% of the hospital admissions experienced by the whole study cohort. Mean annual direct asthma costs per patient was S$2952 ± S$4225 in uncontrolled severe asthma vs S$841 ± S$815 in non-severe asthma. Conclusion: Approximately 12% of patients with asthma managed in a hospital-based respiratory specialist clinic in Singapore have uncontrolled severe asthma. They account for a disproportionate amount of healthcare utilisation and costs. Healthcare strategies targeting these patients are urgently needed. Key words: Cost, Exacerbations, Singapore

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Section: Introductionmentioning

confidence: 99%

Comparison of the Proportion and Healthcare Utilisation of Adult Patients with Uncontrolled Severe Asthma versus Non-Severe Asthma Seen in a Southeast Asian Hospital-Based Respiratory Specialist Clinic

Tay

Wong

Ihsan

et al. 2017

Ann Acad Med Singap

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“…The predominance of sputum eosinophilia in the inflammatory patterns of severe asthmatic subphenotypes is confirmed in the unsupervised hierarchical cluster analysis of the Severe Asthma Research Program cohort where cluster 4 of severe asthmatics was associated to atopic disease and reversible severe reductions in pulmonary function, while cluster 5 was characterized mainly by later-onset disease and airflow limitations that remain with a FEV1 < 80% predicted [71].…”

Section: Severe Eosinophilic Asthma In Cluster Analysismentioning

confidence: 74%

Eosinophilic Phenotype: The Lesson from Research Models to Severe Asthma

Guida¹,

Antonelli²

2020

Cells of the Immune System

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Eosinophilic airway inflammation is a hallmark in the pathophysiological and clinical definition of asthma. In the last decades, asthma evolved in the recognition of different phenotypes identified by natural history, clinical and physiological characteristics, and the underlying immune mechanisms. Among these phenotypes, many have been associated with eosinophilic-driven inflammation. This is the case of either early-onset allergic Th2 asthma or late-onset persistent eosinophilic asthma. Both animal models and analysis from human samples have contributed to elucidate the role of eosinophils in the asthmatic inflammatory response and the synergic role of Th2 cytokines. In severe asthma, high numbers of eosinophils can persist despite treatment with inhaled and oral corticosteroids leading to the definition of severe refractory eosinophilic asthma. The combined role of IL-4-, IL-13-and IL-5-associated pathways has focused the view over the T2-type endotypes, wherein a specific biological pathway explains the observable properties of different phenotypes and the identifiable biomarkers can predict response to monoclonal antibodies directed against a selected immune target. In the era of precision medicine and personalized therapy, both the identification of Th2 molecules and eosinophils as targets and biomarkers have become the best clue for treating and monitoring severe asthma.

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“…For example, all five of the initial SARP clinical clusters were reproducible in the subsequent SARP 3 cohort barring a slight shift toward the more severe clusters (3,4,5), as SARP-3 was enriched for severe asthma. 22 The ADEPT phenotypes were reassessed at 3, 6, and 12 months after baseline classification and the majority of the patients had stable phenotypes over 1 year. 14 To reproduce the ADEPT clusters, a subset of the U-BIOPRED cohort (US) was rephenotyped.…”

Section: Other Considerationsmentioning

confidence: 99%

Phenotyping, Precision Medicine, and Asthma

Mohan

Lugogo

2022

Semin Respir Crit Care Med

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The traditional one-size-fits all approach based on asthma severity is archaic. Asthma is a heterogenous syndrome rather than a single disease entity. Studies evaluating observable characteristics called phenotypes have elucidated this heterogeneity. Asthma clusters demonstrate overlapping features, are generally stable over time and are reproducible. What the identification of clusters may have failed to do, is move the needle of precision medicine meaningfully in asthma. This may be related to the lack of a straightforward and clinically meaningful way to apply what we have learned about asthma clusters. Clusters are based on both clinical factors and biomarkers. The use of biomarkers is slowly gaining popularity, but phenotyping based on biomarkers is generally greatly underutilized even in subspecialty care. Biomarkers are more often used to evaluate type 2 (T2) inflammatory signatures and eosinophils (sputum and blood), fractional exhaled nitric oxide (FeNO) and serum total and specific immunoglobulin (Ig) E reliably characterize the underlying inflammatory pathways. Biomarkers perform variably and clinicians must be familiar with their advantages and disadvantages to accurately apply them in clinical care. In addition, it is increasingly clear that clinical features are critical in understanding not only phenotypic characterization but in predicting response to therapy and future risk of poor outcomes. Strategies for asthma management will need to leverage our knowledge of biomarkers and clinical features to create composite scores and risk prediction tools that are clinically applicable. Despite significant progress, many questions remain, and more work is required to accurately identify non-T2 biomarkers. Adoption of phenotyping and more consistent use of biomarkers is needed, and we should continue to encourage this incorporation into practice.

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Reproducibility and stability of severe asthma research program (SARP) clinical cluster phenotypes in SARP3

Cited by 4 publications

References 0 publications

Comparison of the Proportion and Healthcare Utilisation of Adult Patients with Uncontrolled Severe Asthma versus Non-Severe Asthma Seen in a Southeast Asian Hospital-Based Respiratory Specialist Clinic

Comparison of the Proportion and Healthcare Utilisation of Adult Patients with Uncontrolled Severe Asthma versus Non-Severe Asthma Seen in a Southeast Asian Hospital-Based Respiratory Specialist Clinic

Eosinophilic Phenotype: The Lesson from Research Models to Severe Asthma

Phenotyping, Precision Medicine, and Asthma

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