Influence of Reliance on Historical Blood Eosinophil Counts on ICS Prescribing by GOLD 2019 Thresholds in COPD

Summary

Blood eosinophils are a type of white blood cell that helps fight infection. They have a number of different functions but are primarily involved in numerous inflammatory processes. They are recruited from the blood into sites of inflammation.

In patients with COPD, higher blood eosinophil count (BEC) predicts a greater reduction in moderate and severe exacerbations in response to inhaled corticosteroid (ICS) therapy. The Global Initiative for Chronic Obstructive Lung Disease strategy (GOLD 2019) recommends the use of BEC to guide ICS therapy and states that eosinophil levels above 300 cells/μL can help identify responders, guiding initial dual therapy, with "little or no effect at a BEC \< 100 cells/μL". The National Institute for Health and Care Excellence (NICE) COPD 2018 guideline states that a higher BEC is associated with ICS response, but does not specify a threshold. Earlier research studies have suggested that at lower levels of BEC the harm of ICS due to pneumonia is greater than the benefit of severe exacerbation reduction.

Patients with COPD can have "flare ups" of their disease known as exacerbations. Blood eosinophils play a critical role in assessing severity of these exacerbations and guiding management. The association between BEC and reduction in exacerbation frequency is based on BEC measured when the patient is clinically stable. Transient low eosinophil count (eosinopenia with BEC \< 50 cells/μL) during severe exacerbation is extremely common. In the Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial Fibrillation (DECAF) score derivation and validation studies combined, eosinopenia was present on admission in 1,340 of 2,645 severe exacerbations of COPD (ECOPD) and is associated with longer length of stay, higher in-hospital and one year mortality. Although eosinophilic COPD exacerbations occur, overall BEC during moderate or severe exacerbation is lower than stable state.

In ECOPD managed in critical care low BEC is associated with higher rate of septic shock and mortality. BEC are also suppressed during other acute illnesses, notably sepsis. Failure to recognise that BEC are often suppressed during acute illness compared to stable state may lead to ICS therapy being inappropriately withheld. The effect of exacerbation and other acute illnesses on eosinophils is under-appreciated. Both NICE and GOLD guidelines fail to mention whether BEC should be prospectively measured when patients are stable (reflecting RCT evidence), or if reliance on historical values is acceptable.

In routine practice some clinicians rely on previous BECs to avoid a delay in treatment decisions. A number of these historical counts will have been taken during illness, underestimating the patients' stable-state BEC. Conversely, COPD is associated with other medical conditions, and BEC may be requested for reasons other than acute illness. Using the highest BEC from multiple measures in the previous 24 months may therefore better agree with stable state counts.

The primary aim of this trial is to assess the reliability of using BEC over the preceding 24 months to assess COPD eosinophil phenotype at both GOLD thresholds. The primary outcome will be based on using the highest of at least three BEC. Secondary outcomes include a) the level of agreement between baseline stable state BEC and both mean and the highest BEC over the preceding 24 months, b) the influence of the number of BEC measures available and c) the effect of limiting the time frame from 24 months to the previous 12 months.

BEC is associated with disease severity, providing further evidence that COPD eosinophil phenotype may change over time. As an exploratory analysis, periods of sustained change in eosinophil phenotype will be sought, and the relationship between eosinophil phenotype and patient characteristics and certain medication will be assessed.

The investigators will also assess the relations between the dependent variables stable state absolute eosinophil and basophil counts and both eosinophil to basophil and neutrophil to lymphocyte ratios and the following clinical outcomes: a) moderate and severe exacerbations and b) mortality. Some of these variables have previously been shown to be related to disease severity and mortality.

Conditions

• Chronic Obstructive Pulmonary Disease

Interventions

OTHER

Blood Eosinophil counts - comparing historical with stable state

Comparing historical blood eosinophil counts over 24 months to stable state eosinophil count.

Sponsors & Collaborators

• Newcastle-upon-Tyne Hospitals NHS Trust

  collaborator OTHER

• Northumbria Healthcare NHS Foundation Trust

  lead OTHER

Principal Investigators

• Stephen Bourke, MBCHb, PhD · Northumbria Healthcare NHS Foundation Trust

Eligibility

Min Age

35 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-10-26

Primary Completion

2023-04-30

Completion

2023-10-31

Countries

• United Kingdom

Study Locations