Additive prognostic value of blood eosinophils and exhaled nitric oxide (FeNO) to predict asthma attacks in the ORACLE patient-level meta-analysis

<bold>Tionale:</bold> In asthma, type-2 biomarkers blood eosinophil cells (BEC) and exhaled nitric oxide (FeNO) identify a higher risk and anti-inflammatory responsive phenotype. Their combined prognostic value is unclear. <bold>Aim:</bold> To assess the independent and combined prognostic relationship of BEC and FeNO with severe asthma attacks <bold>Methods:</bold> We included 6,516 participants from control arms of 22 randomised controlled trials spanning mild to severe asthma (6-12 months follow-up, the OxfoRd Asthma attaCk risk scaLE (ORACLE) patient-level meta-analysis). Baseline predictors included BEC, FeNO, Asthma Control Questionnaire-5, FEV1%, and attack history in the past 12 m. Statistical interaction between BEC and FeNO was tested continuously and categorically. <bold>Results:</bold> The multivariable rate ratio [95% CI] for the interaction term log<sub>10</sub>(BEC)×log<sub>10</sub>(FeNO) was 1.39 [1.01-1.91], indicating that BEC and FeNO have additive prognostic value (Fig. 1A). The very type-2 inflammatory status (BEC ≥ 0.3×10<sup>9</sup>/L & FeNO ≥ 50 ppb) was the most predictive modifiable risk factor across asthma severities (Fig. 1B). <bold>Conclusion:</bold> Type-2 biomarkers BEC and FeNO are independent and additive risk factors for asthma attacks. ORACLE shows potential for a prediction model centred on biomarkers to support clinical decision-making. <bold>Prospero:</bold> CRD42021245337; <bold>Funding:</bold> NIHR, QRHRN, FRQS, APQ, SAB, LUF <fig><object-id>erj;64/suppl_68/PA1205/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa1205
Primary Topic
Chronic Obstructive Pulmonary Disease (COPD) Research
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article
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article

Additive prognostic value of blood eosinophils and exhaled nitric oxide (FeNO) to predict asthma attacks in the ORACLE patient-level meta-analysis

Guy Brusselle, C.A. Celis-Preciado, Jacob K. Sont, Neil A. Martin et al.
Chronic Obstructive Pulmonary Disease (COPD) Research
article

Additive prognostic value of blood eosinophils and exhaled nitric oxide (FeNO) to predict asthma attacks in the ORACLE patient-level meta-analysis

Guy Brusselle, C.A. Celis-Preciado, Jacob K. Sont, Neil A. Martin, Jonathan Corren, Nicola A. Hanania, Sanjay Ramakrishnan, Mario Castro, Timothy Hinks, Fleur L. Meulmeester, Emilio Santoro, Jo Hardy, Christopher Edward Brightling, Annette Laugerud, D. J. Jackson, Richard Beasley, Michael Wechsler, Cécile Holweg, Sarah Diver, Simon Couillard, Xavier Jaumont, Ian Pavord, Ewout W. Steyerberg, Megan E Hardin, Deborah Clarke, Chris Compton
article en

Abstract

<bold>Tionale:</bold> In asthma, type-2 biomarkers blood eosinophil cells (BEC) and exhaled nitric oxide (FeNO) identify a higher risk and anti-inflammatory responsive phenotype. Their combined prognostic value is unclear. <bold>Aim:</bold> To assess the independent and combined prognostic relationship of BEC and FeNO with severe asthma attacks <bold>Methods:</bold> We included 6,516 participants from control arms of 22 randomised controlled trials spanning mild to severe asthma (6-12 months follow-up, the OxfoRd Asthma attaCk risk scaLE (ORACLE) patient-level meta-analysis). Baseline predictors included BEC, FeNO, Asthma Control Questionnaire-5, FEV1%, and attack history in the past 12 m. Statistical interaction between BEC and FeNO was tested continuously and categorically. <bold>Results:</bold> The multivariable rate ratio [95% CI] for the interaction term log<sub>10</sub>(BEC)×log<sub>10</sub>(FeNO) was 1.39 [1.01-1.91], indicating that BEC and FeNO have additive prognostic value (Fig. 1A). The very type-2 inflammatory status (BEC ≥ 0.3×10<sup>9</sup>/L & FeNO ≥ 50 ppb) was the most predictive modifiable risk factor across asthma severities (Fig. 1B). <bold>Conclusion:</bold> Type-2 biomarkers BEC and FeNO are independent and additive risk factors for asthma attacks. ORACLE shows potential for a prediction model centred on biomarkers to support clinical decision-making. <bold>Prospero:</bold> CRD42021245337; <bold>Funding:</bold> NIHR, QRHRN, FRQS, APQ, SAB, LUF <fig><object-id>erj;64/suppl_68/PA1205/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

AstraZeneca (United Kingdom) (GB), North Bristol NHS Trust (GB), Université de Sherbrooke (CA), University of Leicester (GB), University of California, Los Angeles (US), The University of Western Australia (AU), Baylor College of Medicine (US), GlaxoSmithKline (United Kingdom) (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Leiden University Medical Center (NL), Ghent University Hospital (BE), National Jewish Health (US), University of Oxford (GB), AVEO Oncology (United States) (US), Acentech (United States) (US), Prognos (Switzerland) (CH), University of Kansas Medical Center (US), Medical Research Institute of New Zealand (NZ), Science Oxford (GB), University of Colorado Denver (US)
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Chronic Obstructive Pulmonary Disease (COPD) Research
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