Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease

Pavord, Ian; Chanez, Pascal; Criner, Gerard J.; Kerstjens, Huib A. M.; Korn, Stephanie; Lugogo, Njira L; Martinot, Jean-Benoît; Sagara, Hironori; Albers, Frank C.; Bradford, Eric; Harris, Stephanie; Mayer, Bhabita; Rubin, David B.; Yancey, Steven W.; Sciurba, Frank C.

doi:10.1056/nejmoa1708208

Cited by 447 publications

(386 citation statements)

References 27 publications

Supporting

Mentioning

361

Contrasting

Unclassified

Order By: Relevance

“…45,46 In the studied group, a higher use of inhaled corticosteroids was present in the group with fixed-AO, which could be the result of more severe asthma or a disease less respondent to corticosteroid treatment. This appears to be supported by studies in both asthma and COPD, where anti-IL 5 treatment seems to result in improvement of lung function.…”

Section: Discussionmentioning

confidence: 89%

Fixed airflow obstruction relates to eosinophil activation in asthmatics

Mogensen

Alving

Dahlén

et al. 2018

Clin Experimental Allergy

View full text Add to dashboard Cite

Background: Some asthmatics develop irreversible chronic airflow obstruction, for example, fixed airflow obstruction (fixed-AO). This is probably a consequence of airway remodelling, but neither its relation to inflammation nor which asthma biomarkers can be clinically useful are elucidated. We hypothesized that the presence of type 2 inflammation relates to fixed-AO. Objectives:To evaluate the presence of four markers for type 2 inflammation in fixed airflow obstruction among asthmatics.Methods: This was a cross-sectional study of 403 participants with asthma, aged 17-75 years, from three Swedish centres. Fixed airflow obstruction was defined as forced expiratory volume during the first second (FEV 1 ) over forced vital capacity (FVC) being below the lower limit of normal (LLN). The following type 2 inflammation markers were assessed: exhaled nitric oxide (FeNO), serum periostin, serum eosinophil cationic protein (S-ECP), and urinary eosinophil-derived neurotoxin (U-EDN).Results: Elevated U-EDN (values in the highest tertile, ≥65.95 mg/mol creatinine) was more common in subjects with fixed-AO vs. subjects without fixed-AO: 55% vs. 29%, P < 0.001. Elevated U-EDN related to increased likelihood of having fixed-AO in both all subjects and never-smoking subjects, with adjusted (adjusted for sex, age group, use of inhaled corticosteroids last week, atopy, early-onset asthma, smoking history, and packyears) odds ratios (aOR) of 2.38 (1.28-4.41) and 2.51 (1.04-6.07), respectively. In a separate analysis, having both elevated S-ECP (>20 μg/L) and U-EDN was related to having the highest likelihood of fixed-AO (aOR (95% CI) 6.06(2.32-15.75)). Elevated serum periostin or FeNO did not relate to fixed-AO. Conclusions and clinical relevance:These findings support that type 2 inflammation, and in particular eosinophil inflammation, is found in asthma with fixed-AO.This could indicate a benefit from eosinophil-directed therapies. Further longitudinal studies are warranted to investigate causality and relation to lung function decline.

show abstract

Section: Discussionmentioning

confidence: 89%

Fixed airflow obstruction relates to eosinophil activation in asthmatics

Mogensen

Alving

Dahlén

et al. 2018

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

“…Anti‐IL5 biological treatment is consistently beneficial in asthma and is now a licensed therapy. However, the response to anti‐IL5 and IL‐5R monoclonal antibodies in COPD has been disappointing with benefits related to the intensity of the blood eosinophil count as seen in asthma but the magnitude of response greatly reduced . Thus, both the epithelial gene expression profile and response to T2‐directed biological therapies differ between eosinophilic asthma and COPD.…”

Section: Discussionmentioning

confidence: 99%

Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma

George

Taylor

Esteve‐Codina

et al. 2019

Allergy

View full text Add to dashboard Cite

Background Whether the clinical or pathophysiologic significance of the “treatable trait” high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma. Methods Subjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U‐BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U‐BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/μL as a cut‐off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values). Results There were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U‐BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts. Conclusion Despite shared “treatable traits” between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.

show abstract

“…In a recently published study on patients with COPD with an eosinophilic phenotype, mepolizumab (a monoclonal antibody directed against interleukin-5) was associated with a lower annual rate of moderate to severe exacerbations compared to placebo [68]. This was especially true for patients with higher blood eosinophil counts at screening.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Exacerbations of COPD

2018

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. While COPD is a mainly chronic disease, a substantial number of patients suffer from exacerbations. Severe exacerbations are related to a significantly worse survival outcome. This review summarises the current knowledge on the different aspects of COPD exacerbations. The impact of risk factors and triggers such as smoking, severe airflow limitation, bronchiectasis, bacterial and viral infections and comorbidities is discussed. More severe exacerbations should be treated with β-agonists and anticholinergics as well as systemic corticosteroids. Antibiotic therapy should only be given to patients with presumed bacterial infection. Noninvasive ventilation is indicated in patients with respiratory failure. Smoking cessation is key to prevent further COPD exacerbations. Other aspects include choice of pharmacotherapy, including bronchodilators, inhaled corticosteroids, phosphodiesterase-4 inhibitors, longterm antibiotics and mucolytics. Better education and self-management as well as increased physical activity are important. Influenza and pneumococcal vaccination is recommended. Treatment of hypoxaemia and hypercapnia reduce the rate of COPD exacerbations, while most interventional bronchoscopic therapies increase exacerbation risk within the first months after the procedure.

show abstract

Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease

Cited by 447 publications

References 27 publications

Fixed airflow obstruction relates to eosinophil activation in asthmatics

Fixed airflow obstruction relates to eosinophil activation in asthmatics

Blood eosinophil count and airway epithelial transcriptome relationships in COPD versus asthma

Exacerbations of COPD

Contact Info

Product

Resources

About