Baseline sputum eosinophil + neutrophil subgroups’ clinical characteristics and longitudinal trajectories for NHLBI Severe Asthma Research Program (SARP 3) cohort

Hastie, Annette T.; Mauger, David T.; Denlinger, Loren C.; Coverstone, Andrea M.; Castro, Mario; Erzurum, Serpil C.; Jarjour, N.N.; Levy, Bruce D.; Meyers, Deborah A.; Moore, Wendy C.; Phillips, Brenda R.; Wenzel, Sally E.; Fahy, John V.; Israel, Elliot; Bleecker, Eugene R.; Investigators, Nhlbi Sarp

doi:10.1016/j.jaci.2020.01.039

Cited by 30 publications

(24 citation statements)

References 9 publications

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“…Inflammatory subtype of sputum may thus predict prognosis, as reflected by future need of ICS, of individual patients. These results have been repeated and confirmed by a series of evidence from Severe Asthma Research Program (SARP) (63,64). They consistently demonstrated that mixed granulocytic subtype is the most refractory inflammatory subtype, characterized by the lowest lung function, worse asthma control, increased symptoms, greater healthcare requirements, and further loss in lung function, suggesting cell to cell interaction or overlapping inflammatory pathways (63,64).…”

Section: Inflammatory Subtype and Future Maintenance Therapy/ Controlmentioning

confidence: 76%

Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

Niimi

2021

J Thorac Dis

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The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, and approximately 30% to 50% of people with chronic cough have eosinophilic airway inflammation, the presence of which can be confirmed by sputum eosinophilia or elevated exhaled nitric-oxide levels. Cough variant asthma (CVA) is a phenotype of asthma which lacks wheezing or dyspnea, and consistently one of the most common causes of chronic cough worldwide. CVA and non-asthmatic eosinophilic bronchitis (NAEB) shares common feature such as chronic dry cough, eosinophilic inflammation, and development of chronic airflow obstruction (CAO) and asthma in a subset of patients. The distinctive characteristic of these conditions is the presence of airway hyperresponsiveness in CVA but not in NAEB. Coughing is responsive to bronchodilators such as beta-agonists in CVA, but such feature has not been clarified in NAEB. Inhaled corticosteroids (ICSs) are the first-line treatment, and leukotriene receptor antagonists are also effective, in patients with both CVA and NAEB. This review will give an outline of clinical and physiological features, and prognosis and its determinants of CVA and EBNA. Further, the rationale and evidence, despite limited, for the need of long-term treatment will be discussed. The development of airway remodeling due to mechanical stress to the airways exerted by long-standing coughing will also be discussed.

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Section: Inflammatory Subtype and Future Maintenance Therapy/ Controlmentioning

confidence: 76%

Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

Niimi

2021

J Thorac Dis

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“…Despite this, therapeutics specifically targeting neutrophils, even in patients with neutrophilic inflammation, have not shown efficacy ( 103 – 105 ). Given the common observation of combined increases in lung eosinophils and neutrophils with more severe disease, it is conceivable that targeting both cells may be more important ( 44 , 106 ).…”

Section: Integrating Clinical Molecular and Therapeutic Phenotypes To Understand Mechanismsmentioning

confidence: 94%

“…Longitudinal SARP data suggest that children with severe asthma, which is EOA by definition, may resolve their severe asthma, with high blood eosinophils being the best predictor of remission ( 13 ). Exacerbation-associated asthma, at least before T2 biologic intervention, appears to be a consistent characteristic of a poorly defined phenotype or poorly defined phenotypes, with baseline blood eosinophil concentrations, elevations of both eosinophils and neutrophils in sputum, and plasma IL-6 concentrations all being predictive of exacerbation-prone disease ( 40 , 44 ). Elevations in both sputum eosinophils and neutrophils have also been associated with greater lung-function decline ( 44 ).…”

Section: Clinical and Molecular Biomarkers And Phenotypingmentioning

confidence: 99%

Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes

Wenzel

2021

Am J Respir Crit Care Med

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Evaluation and effective management of asthma, and in particular severe asthma, remains at the core of pulmonary practice. Over the last 20–30 years, there has been increasing appreciation that “severe asthma” encompasses multiple different subgroups or phenotypes, each with differing presentations. Using clinical phenotyping, in combination with rapidly advancing molecular tools and targeted monoclonal antibodies (human knockouts), the understanding of these phenotypes, and our ability to treat them, have greatly advanced. Type-2 (T2)-high and -low severe asthmas are now easily identified. Fractional exhaled nitric oxide and blood eosinophil counts can be routinely employed in clinical settings to identify these phenotypes and predict responses to specific therapies, meeting the initial goals of precision medicine. Integration of molecular signals, biomarkers, and clinical responses to targeted therapies has enabled identification of critical molecular pathways and, in certain phenotypes, advanced them to near-endotype status. Despite these advances, little guidance is available to determine which class of biologic is appropriate for a given patient, and current “breakthrough” therapies remain expensive and even inaccessible to many patients. Many of the most severe asthmas, with and without T2-biomarker elevations, remain poorly understood and treated. Nevertheless, conceptual understanding of “the severe asthmas” has evolved dramatically in a mere 25 years, leading to dramatic improvements in the lives of many.

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“…Following the baseline and TA-response characterizations, some participants also came in during a subsequent exacerbation. The acute exacerbation visit was within 5 days of a subject reporting ≥2 days of increased symptoms compared with baseline and could occur any time after the subject had completed the baseline and post-TA visits and at least 6 weeks prior to the final visit [37], which was 36 months after baseline [38]. The recovery visit was 6 weeks after the acute exacerbation visit.…”

Section: Methodsmentioning

confidence: 99%

Plasma P-Selectin Is Inversely Associated with Lung Function and Corticosteroid Responsiveness in Asthma

Johansson

Grill

Barretto

et al. 2020

Int Arch Allergy Immunol

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Background: Severe asthma has multiple phenotypes for which biomarkers are still being defined. Plasma P-selectin reports endothelial and/or platelet activation. Objective: To determine if P-selectin is associated with features of asthma in a longitudinal study. Methods: Plasmas from 70 adult patients enrolled in the Severe Asthma Research Program (SARP) III at the University of Wisconsin-Madison were analyzed for concentration of P-selectin at several points over the course of 3 years, namely, at baseline (BPS), after intramuscular triamcinolone acetonide (TA) injection, and at 36 months after baseline. Thirty-four participants also came in during acute exacerbation and 6 weeks after exacerbation. Results: BPS correlated inversely with forced expiratory volume in 1 s (FEV1) and with residual volume/total lung capacity, an indicator of air trapping. BPS was inversely associated with FEV1 change after TA, by regression analysis. FEV1 did not change significantly after TA if BPS was above the median, whereas patients with BPS below the median had significantly increased FEV1 after TA. BPS was higher in and predicted assignment to SARP phenotype cluster 5 (“severe fixed-airflow asthma”). P-selectin was modestly but significantly increased at exacerbation but returned to baseline within 3 years. Conclusions: High BPS is associated with airway obstruction, air trapping, the “severe fixed-airflow” cluster, and lack of FEV1 improvement in response to TA injection. P-selectin concentration, which is a stable trait with only modest elevation during exacerbation, may be a useful biomarker for a severe asthma pheno- or endotype characterized by low pulmonary function and lack of corticosteroid responsiveness.

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Baseline sputum eosinophil + neutrophil subgroups’ clinical characteristics and longitudinal trajectories for NHLBI Severe Asthma Research Program (SARP 3) cohort

Cited by 30 publications

References 9 publications

Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes

Plasma P-Selectin Is Inversely Associated with Lung Function and Corticosteroid Responsiveness in Asthma

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