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- Bafadhel, Mona, et al.
(author)
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Acute Exacerbations of Chronic Obstructive Pulmonary Disease : Identification of Biologic Clusters and Their Biomarkers
- 2011
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 184:6, s. 662-671
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Journal article (peer-reviewed)abstract
- Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Objectives: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Methods: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed "pauciinflammatory." Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1 beta, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83-0.95); serum CXCL10, 0.83 (95% CI, 0.70-0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78-0.93), respectively. Conclusions: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1 beta, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
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| 2. |
- Bafadhel, Mona, et al.
(author)
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Blood Eosinophils to Direct Corticosteroid Treatment of Exacerbations of Chronic Obstructive Pulmonary Disease A Randomized Placebo-Controlled Trial
- 2012
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 186:1, s. 48-55
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Journal article (peer-reviewed)abstract
- Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. Objectives: Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. Methods: Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and <= 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms. Measurements and Main Results: There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04). Conclusions: The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.
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| 3. |
- Mogensen, Ida
(author)
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Inflammation in asthma: relation to symptomatology, exacerbations and lung function
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Asthma is an inflammatory disease in the airways. It is characterized by respiratory symptoms such as wheezing, variable airflow obstruction and impaired lung function development. A better understanding of the underlying inflammation is crucial in order to treat and prevent asthma symptoms and lung function deterioration.We have evaluated six inflammatory markers in relation to asthma symptoms, asthma attacks, and lung function measures (fixed airflow obstruction (FAO) and lung function development over time) in five investigations. The markers (elevated levels) were fraction of exhaled NO (FeNO) (elevated ≥25ppb), serum eosinophil cationic protein (S-ECP) (≥20 µg/L), blood eosinophils (B-Eos) (≥300 cells/µL), urinary eosinophil derived neurotoxin (U-EDN) (≥65.95mg/mol creatinine), serum periostin (S-periostin) ( ≥74μg/L), and blood neutrophils (B-Neu) (≥5,100 cells/µL). The studied populations consisted of mainly adults (except in Paper II) and included asthmatics from the Swedish part of the Global Allergy and Asthma European Network survey (Papers I and III), the American National Health and Nutrition Examination Survey (Papers II and IV), the Uppsala part of the European Community Respiratory Health Survey I-III, the Vlagtwedde and Vlaardingen study, and the Rotterdam study, the latter two from the Netherlands (Paper V). All study populations were population based, and the asthmatics included had mainly mild to moderately severe asthma.The main findings are that simultaneously elevated FeNO and S-ECP are associated with more reported asthma symptoms and attacks, and elevated FeNO and B-Eos are associated with lower lung function, suggesting a value in measuring both local (FeNO) and systemic (S-ECP, B-Eos) inflammation in asthma. Eosinophil inflammation (elevated U-EDN and S-ECP) was associated with FAO in asthma, while the other type-2 markers FeNO and S-periostin were not. Elevated B-Eos was further associated to lower lung function measures in a general population, and a faster lung function decline in asthmatics. FeNO was more often elevated in asthmatics, but was difficult to robustly associate to a specific disease characteristic. B-Neu was associated to FAO in participants with current smoking or pronounced smoking history.In conclusion, asthma with elevated markers for eosinophil inflammation was associated to worse morbidity and lung function development in comparison with asthmatics without elevated markers for eosinophil inflammation. These results indicate ongoing eosinophil inflammation in asthma as closely associated to disease activity and the absence of eosinophil inflammation to less morbidity.
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