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. 2018 Nov 6:13:3669-3676.
doi: 10.2147/COPD.S179425. eCollection 2018.

Blood eosinophils: a biomarker of COPD exacerbation reduction with inhaled corticosteroids

Salman H Siddiqui  1   2 , Ian D Pavord  3   4 , Neil C Barnes  5   6 , Alessandro Guasconi  7 , Sally Lettis  8 , Steven Pascoe  9 , Stefano Petruzzelli  7
Affiliations

Blood eosinophils: a biomarker of COPD exacerbation reduction with inhaled corticosteroids

Salman H Siddiqui et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Background: Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS). We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD.

Methods: The studies assessed ICS/long-acting β2 agonist (LABA) combinations vs LABA alone. Using data from each study, we modeled COPD exacerbation rates, predose FEV1, and St George's Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0-1,000 eosinophils/µL in FORWARD, 0-993 eosinophils/µL in Dransfield).

Results: In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts. In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/µL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm. In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/µL, and from 0.56 to 1.75 per year in the LABA-only arm. Change in FEV1 was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV1 was observed at higher eosinophil levels in the Dransfield studies. ICS/LABA led to greater improvements in St George's Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with ≥67 eosinophils/µL.

Conclusion: Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction. Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations.

Keywords: COPD; FEV1; ICS; lung function.

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Conflict of interest statement

Disclosure SHS has received grants from the Chiesi Onulus scheme to study small airways and is on the international steering board for the Chiesi-sponsored ATLANTIS trial; in the past 5 years, SHS has received honoraria for attending advisory panels with Roche, AstraZeneca, Boehringer Ingelheim, and GSK and performed consultancy for Owlstone Nanotech and Mundipharma; SHS has also received honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, GSK, and Novartis. IDP has received honoraria in the past 5 years for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, and GSK and a payment for organizing an educational event from AstraZeneca; he has received honoraria for attending advisory panels with Almirall, Genentech, Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Merck Sharp & Dohme, Schering-Plough, Novartis, Dey Pharma, Napp Pharmaceuticals, and RespiVert; he has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, and Napp Pharmaceuticals. NCB is employed by GSK and holds GSK stocks. SL is employed by GSK and holds GSK stocks. AG is employed by Chiesi. SPa is employed by GSK and holds GSK stocks. SPe is employed by Chiesi. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A) Predicted exacerbation rates by baseline blood eosinophils for the FORWARD study; (B) predicted annual exacerbation rates by baseline blood eosinophils for the Dransfield studies. Note: The shaded areas indicate the 95% CI. Abbreviations: BDP, beclomethasone dipropionate; FF, fluticasone furoate; FOR, formoterol; VI, vilanterol.
Figure 2
Figure 2
(A) Predicted change from baseline in trough FEV1 by baseline blood eosinophils in the FORWARD study at week 48; (B) predicted change from baseline in trough FEV1 by baseline blood eosinophils in the Dransfield studies at week 52. Note: The shaded areas indicate the 95% CI. Abbreviations: BDP, beclomethasone dipropionate; FF, fluticasone furoate; FOR, formoterol; VI, vilanterol.
Figure 3
Figure 3
Predicted change from baseline in SGRQ total score at week 48 by baseline blood eosinophils in the FORWARD study. Note: The shaded areas indicate the 95% CI. Abbreviations: BDP, beclomethasone dipropionate; FOR, formoterol; SGRQ, St George’s Respiratory Questionnaire.
See this image and copyright information in PMC

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