Peter Alter MD , Henrik Watz MD , Kathrin Kahnert MD , Franziska C. Trudzinski MD , Hubert Wirtz MD , Tim Speicher , Inge Kokot , Sandra Söhler PhD , Robert Bals MD, PhD , Klaus F. Rabe MD , Emiel F.M. Wouters MD , Claus F. Vogelmeier MD , Rudolf A. Jörres PhD
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Jörres PhD","doi":"10.1016/j.chpulm.2025.100189","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Exacerbation risk of patients with COPD is thought to be influenced by type 2 inflammation, with blood eosinophil counts and fractional concentration of exhaled nitric oxide (F<span>eno</span>) as potential biomarkers.</div></div><div><h3>Research Question</h3><div>Are there different associations of blood eosinophils and Feno with exacerbation risk and severity in COPD, indicating a different role of local inflammation vs systemic factors?</div></div><div><h3>Study Design and Methods</h3><div>Data were taken from 3 visits (1.5 years apart) of the longitudinal COPD and Systemic Consequences–Comorbidities Network (COSYCONET) cohort, comprising a broad range of clinical and functional assessments. We determined the relationships between eosinophil counts and F<span>eno</span> vs exacerbations, defined either via categorization to Global Initiative for Chronic Obstructive Lung Disease group E (≥ 2 moderate or ≥ 1 severe), or as ≥ 1 severe exacerbation in the year before each visit. Analyses were performed via generalized linear models.</div></div><div><h3>Results</h3><div>The final data set included 384, 255, and 206 patients at visits 6, 7, and 8, respectively. According to the multivariable analyses, exacerbation risk defined via Global Initiative for Chronic Obstructive Lung Disease group E was associated with elevated values (≥ 25 ppb) of F<span>eno</span> (<em>P</em> = .003; OR, 1.90), but not eosinophil counts. In contrast, the risk for severe exacerbations was linked to eosinophils, but not to F<span>eno</span>. This relationship was expressed as either elevated risk with counts ≥ 100 and < 300 M/L (<em>P</em> = .017; OR, 1.98) or as reduced risk (<em>P</em> = .046; OR, 0.57) < 100 M/L. The results were robust against the inclusion of patients who actively smoke or with the comorbidity of asthma.</div></div><div><h3>Interpretation</h3><div>Our observations suggest a differential role of type 2-related biomarkers F<span>eno</span> and eosinophils for exacerbation risk and severity. F<span>eno</span> seemed superior regarding a broad range of exacerbations predominantly involving local airway events, whereas systemic eosinophils played a larger role in severe exacerbations. The findings also suggest that a low eosinophil count might indicate a low risk of severe exacerbations, whereas highly elevated counts did not play a statistical role.</div></div><div><h3>Clinical Trial Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>; No.: NCT01245933; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>","PeriodicalId":94286,"journal":{"name":"CHEST pulmonary","volume":"3 3","pages":"Article 100189"},"PeriodicalIF":0.0000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Relationship Between the Levels of Feno, Blood Eosinophils, and the Severity of Exacerbations in Patients With COPD\",\"authors\":\"Peter Alter MD , Henrik Watz MD , Kathrin Kahnert MD , Franziska C. 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Jörres PhD\",\"doi\":\"10.1016/j.chpulm.2025.100189\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Exacerbation risk of patients with COPD is thought to be influenced by type 2 inflammation, with blood eosinophil counts and fractional concentration of exhaled nitric oxide (F<span>eno</span>) as potential biomarkers.</div></div><div><h3>Research Question</h3><div>Are there different associations of blood eosinophils and Feno with exacerbation risk and severity in COPD, indicating a different role of local inflammation vs systemic factors?</div></div><div><h3>Study Design and Methods</h3><div>Data were taken from 3 visits (1.5 years apart) of the longitudinal COPD and Systemic Consequences–Comorbidities Network (COSYCONET) cohort, comprising a broad range of clinical and functional assessments. We determined the relationships between eosinophil counts and F<span>eno</span> vs exacerbations, defined either via categorization to Global Initiative for Chronic Obstructive Lung Disease group E (≥ 2 moderate or ≥ 1 severe), or as ≥ 1 severe exacerbation in the year before each visit. Analyses were performed via generalized linear models.</div></div><div><h3>Results</h3><div>The final data set included 384, 255, and 206 patients at visits 6, 7, and 8, respectively. According to the multivariable analyses, exacerbation risk defined via Global Initiative for Chronic Obstructive Lung Disease group E was associated with elevated values (≥ 25 ppb) of F<span>eno</span> (<em>P</em> = .003; OR, 1.90), but not eosinophil counts. In contrast, the risk for severe exacerbations was linked to eosinophils, but not to F<span>eno</span>. This relationship was expressed as either elevated risk with counts ≥ 100 and < 300 M/L (<em>P</em> = .017; OR, 1.98) or as reduced risk (<em>P</em> = .046; OR, 0.57) < 100 M/L. The results were robust against the inclusion of patients who actively smoke or with the comorbidity of asthma.</div></div><div><h3>Interpretation</h3><div>Our observations suggest a differential role of type 2-related biomarkers F<span>eno</span> and eosinophils for exacerbation risk and severity. F<span>eno</span> seemed superior regarding a broad range of exacerbations predominantly involving local airway events, whereas systemic eosinophils played a larger role in severe exacerbations. The findings also suggest that a low eosinophil count might indicate a low risk of severe exacerbations, whereas highly elevated counts did not play a statistical role.</div></div><div><h3>Clinical Trial Registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>; No.: NCT01245933; URL: <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span></div></div>\",\"PeriodicalId\":94286,\"journal\":{\"name\":\"CHEST pulmonary\",\"volume\":\"3 3\",\"pages\":\"Article 100189\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CHEST pulmonary\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S294978922500056X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CHEST pulmonary","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S294978922500056X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Relationship Between the Levels of Feno, Blood Eosinophils, and the Severity of Exacerbations in Patients With COPD
Background
Exacerbation risk of patients with COPD is thought to be influenced by type 2 inflammation, with blood eosinophil counts and fractional concentration of exhaled nitric oxide (Feno) as potential biomarkers.
Research Question
Are there different associations of blood eosinophils and Feno with exacerbation risk and severity in COPD, indicating a different role of local inflammation vs systemic factors?
Study Design and Methods
Data were taken from 3 visits (1.5 years apart) of the longitudinal COPD and Systemic Consequences–Comorbidities Network (COSYCONET) cohort, comprising a broad range of clinical and functional assessments. We determined the relationships between eosinophil counts and Feno vs exacerbations, defined either via categorization to Global Initiative for Chronic Obstructive Lung Disease group E (≥ 2 moderate or ≥ 1 severe), or as ≥ 1 severe exacerbation in the year before each visit. Analyses were performed via generalized linear models.
Results
The final data set included 384, 255, and 206 patients at visits 6, 7, and 8, respectively. According to the multivariable analyses, exacerbation risk defined via Global Initiative for Chronic Obstructive Lung Disease group E was associated with elevated values (≥ 25 ppb) of Feno (P = .003; OR, 1.90), but not eosinophil counts. In contrast, the risk for severe exacerbations was linked to eosinophils, but not to Feno. This relationship was expressed as either elevated risk with counts ≥ 100 and < 300 M/L (P = .017; OR, 1.98) or as reduced risk (P = .046; OR, 0.57) < 100 M/L. The results were robust against the inclusion of patients who actively smoke or with the comorbidity of asthma.
Interpretation
Our observations suggest a differential role of type 2-related biomarkers Feno and eosinophils for exacerbation risk and severity. Feno seemed superior regarding a broad range of exacerbations predominantly involving local airway events, whereas systemic eosinophils played a larger role in severe exacerbations. The findings also suggest that a low eosinophil count might indicate a low risk of severe exacerbations, whereas highly elevated counts did not play a statistical role.
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