Blood eosinophilia, use of inhaled corticosteroids, and risk of COPD exacerbations and mortality

Oshagbemi, Olorunfemi A.; Franssen, Frits M.E.; Braeken, Dionne C.W.; Henskens, Yvonne; Wouters, Emiel F.M.; Zee, Anke‐Hilse Maitland‐van der; Burden, Andrea M.; Vries, Frank de

doi:10.1002/pds.4655

Cited by 17 publications

(18 citation statements)

References 39 publications

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“…28 Recently, Oshagbemi and coworkers reported retrospective observational real-world data indicating that ICS reduced mortality in COPD patients with blood eosinophilia. 29 These findings suggest that there might be COPD phenotypes in which ICS can reduce mortality. Heterogeneity of the COPD populations in this and other studies, and the existence of different, today insufficiently understood COPD phenotypes may explain the various results in different studies.…”

Section: Discussionmentioning

confidence: 96%

<p>Impact of Comorbidities and Commonly Used Drugs on Mortality in COPD – Real-World Data from a Primary Care Setting</p>

Ellingsen¹,

Johansson²,

Larsson³

et al. 2020

COPD

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Background: Life expectancy is significantly shorter for patients with chronic obstructive pulmonary disease (COPD) than the general population. Concurrent diseases are known to infer an increased mortality risk in those with COPD, but the effects of pharmacological treatments on survival are less established. This study aimed to examine any associations between commonly used drugs, comorbidities and mortality in Swedish real-world primary care COPD patients. Methods: Patients with physician-diagnosed COPD from a large primary care population were observed retrospectively, utilizing primary care records and mandatory Swedish national registers. The time to all-cause death was assessed in a stepwise multiple Cox proportional hazards regression model including demography, socioeconomic factors, exacerbations, comorbidities and medication. Results: During the observation period (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)) 5776 (32.5%) of 17,745 included COPD patients died. Heart failure (hazard ratio [HR]: 1.88, 95% confidence interval [CI]: 1.74-2.04), stroke (HR: 1.52, 95% CI: 1.40-1.64) and myocardial infarction (HR: 1.40, 95% CI: 1.24-1.58) were associated with an increased risk of death. Use of inhaled corticosteroids (ICS; HR: 0.79, 95% CI: 0.66-0.94), beta-blockers (HR: 0.86, 95% CI: 0.76-0.97) and acetylsalicylic acid (ASA; HR: 0.87, 95% CI: 0.77-0.98) was dose-dependently associated with a decreased risk of death, whereas use of long-acting muscarinic antagonists (LAMA; HR: 1.33, 95% CI: 1.14-1.55) and N-acetylcysteine (NAC; HR: 1.26, 95% CI: 1.08-1.48) were dose-dependently associated with an increased risk of death in COPD patients. Conclusion: This large, retrospective, observational study of Swedish real-world primary care COPD patients indicates that coexisting heart failure, stroke and myocardial infarction were the strongest predictors of death, underscoring the importance of timely recognition and treatment of comorbidities. A decreased risk of death associated with the use of ICS, betablockers and ASA, and an increased risk associated with the use of LAMA and NAC, was also found. Plain Language SummaryPatients with chronic obstructive lung disease (COPD) die earlier than healthy people. Having certain other diseases (for instance heart disorders) at the same time as COPD is common and known to increase the risk of death. It is not certain whether medication can improve survival or not. There is a need for deeper knowledge of the connection between other diseases, drugs and COPD deaths.

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Section: Discussionmentioning

confidence: 96%

<p>Impact of Comorbidities and Commonly Used Drugs on Mortality in COPD – Real-World Data from a Primary Care Setting</p>

Ellingsen¹,

Johansson²,

Larsson³

et al. 2020

COPD

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“…In contrast, several observational studies among COPD patients using ICS did not find an association between blood eosinophilia and reduced risk of exacerbations [ 83 , 84 ]. The lack of relationship shown in the observational studies suggests that this association may not be present within the real-world COPD population.…”

Section: Existent Type2 Biomarkers In Copdmentioning

confidence: 94%

Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

Oishi

Matsunaga

Shirai

et al. 2020

JCM

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Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD.

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“…In our previous work using COPD patients from the same data source, we found similar results for moderate-to-severe and severe exacerbations. However, an important difference is the fact that in our previous study only patients with prior history of ICS use were included (29). Analyses of data from the FLAME trial reported that LABA/LAMA combination was superior to LABA/ICS combination in exacerbation reduction for relative or absolute blood eosinophil threshold (2%, !2%, 3%, <5% and <150 cells/ml subgroups), and at no threshold was LABA/ICS superior to LABA/LAMA (8).…”

Section: Discussionmentioning

confidence: 94%

Blood Eosinophil Counts, Withdrawal of Inhaled Corticosteroids and Risk of COPD Exacerbations and Mortality in the Clinical Practice Research Datalink (CPRD)

Oshagbemi

Franssen

Kraaij

et al. 2019

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Although recently introduced in the pharmacological treatment algorithm of chronic obstructive pulmonary disease (COPD), there is a need for more data supporting the use of blood eosinophil counts as a biomarker to guide inhaled corticosteroids (ICS) therapy. The aim of this study was to evaluate the risk of moderate and/or severe exacerbations and all-cause mortality in a large primary care population after withdrawal of ICS compared to continued users stratified by elevated blood eosinophil counts. In this population based cohort study, we used data from the Clinical Practice Research Datalink (CPRD) in the United Kingdom. We included subjects' aged 40 years or more who had a diagnosis of COPD. We excluded subjects with a history of asthma, pulmonary fibrosis, cardiac arrhythmia and bronchiectasis, COPD exacerbations occurring within 6 weeks prior to index date, or with a myocardial infarction within 3 months prior to index date. Continuous users were subjects who received their most recent ICS prescription within 3 months before the start of an interval. ICS withdrawals were those who discontinued ICS for more than 3 months. We evaluated the risk of moderate and/or severe exacerbations and all-cause mortality among subjects with various blood eosinophil thresholds who withdrew from ICS compared to continuous ICS users with elevated blood eosinophil levels using Cox regression analysis adjusted for potential confounders. We identified 48,157 subjects diagnosed with COPD between 1 January 2005 to 31 January 2014. Withdrawal of ICS was not associated with an increased risk of moderate-to-severe exacerbations among subjects with absolute blood eosinophil counts !0.34 Â 10 9 cells/L [adjusted hazard ratio (adj. HR) 0.72; 95% confidence interval (CI) 0.63-0.81] or relative counts ! 4.0% (adj. HR 0.72; 95% CI: 0.66-0.78). Similarly, withdrawal of ICS was not associated with an increased risk of severe exacerbations among subjects with absolute blood eosinophil !0.34 Â 10 9 cells/L (adj. HR 0.82; 95% CI: 0.61-1.10) or relative blood eosinophil counts !4.0% (adj. HR 0.80; 95% CI: 0.61-1.04). No increased risk of all-cause mortality was observed among subjects who withdrew from ICS irrespective of elevated absolute or relative blood eosinophil counts. In a real-world primary care population, we did not observe an increased risk of moderate and/or severe COPD exacerbations or all-cause mortality among subjects with eosinophilia who withdrew their use of ICS.

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Blood eosinophilia, use of inhaled corticosteroids, and risk of COPD exacerbations and mortality

Cited by 17 publications

References 39 publications

<p>Impact of Comorbidities and Commonly Used Drugs on Mortality in COPD – Real-World Data from a Primary Care Setting</p>

<p>Impact of Comorbidities and Commonly Used Drugs on Mortality in COPD – Real-World Data from a Primary Care Setting</p>

Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

Blood Eosinophil Counts, Withdrawal of Inhaled Corticosteroids and Risk of COPD Exacerbations and Mortality in the Clinical Practice Research Datalink (CPRD)

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