Stability of the Blood Eosinophilic Phenotype in Stable and Exacerbated COPD

      Background

      There is controversy regarding the use of blood eosinophil levels as a biomarker of exacerbation risk and responsiveness of patients to inhaled corticosteroids (ICS).

      Methods

      Patients in stable COPD with Gold Initiative for Chronic Obstructive Lung Disease airflow obstruction grades II to IV were enrolled in an observational multicenter trial. Concordance was defined as blood eosinophil values persistently lower than or persistently higher than the absolute cutoff points of 150 cells/μL and 300 cells/μL, or the percentage cutoff points of 2%, 3%, and 4%. Discordance was obtained when the blood eosinophil values varied between any two visits. ICS treatment data were recorded at one time point at the inclusion of the study.

      Results

      A total of 210 patients with 2,059 visits were included in the study. Seventy percent of the patients were male, and 36% were current smokers; their average age was 67.7 ± 9.4 years, and 81% were receiving ICS at the start of the study. Assessing eosinophil levels over time (median, 7 days [4; 12]), irrespective of exacerbation or hospitalization, there was a discordance of 77%, 60%, and 42% when using the 2%, 3% and 4% cutoffs, respectively. This outcome changed to 34.5%, 24%, and 17.2% discordance when only using two visits for the analysis. The discordance was similar when using absolute eosinophil values. Patients in a stable state had higher discordant values than patients with mild/moderate exacerbations. The same was seen in patients hospitalized for other illnesses compared with patients hospitalized for severe exacerbation of COPD. Discordancy was high regardless of whether patients were taking ICS at the beginning of the study period.

      Conclusions

      These study data suggest that blood eosinophil levels present significant variability throughout the course of COPD, and a single measurement may therefore not be a reliable predictor of ICS response.

      Key Words

      Abbreviations:

      AECOPD ( acute exacerbations of COPD), ICS ( inhaled corticosteroids)
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      References

        • Crim C.
        • Calverley P.M.A.
        • Anderson J.A.
        • et al.
        Pneumonia risk with inhaled fluticasone furoate and vilanterol in COPD patients with moderate airflow limitation: the SUMMIT trial.
        Respir Med. 2017; 131: 27-34
        • Kew K.M.
        • Seniukovich A.
        Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease.
        Cochrane Database Syst Rev. 2014; 10: CD010115
        • Morjaria J.B.
        • Rigby A.
        • Morice A.H.
        Inhaled corticosteroid use and the risk of pneumonia and COPD exacerbations in the UPLIFT study.
        Lung. 2017; 195: 281-288
        • Price D.
        • Yawn B.
        • Brusselle G.
        • Rossi A.
        Risk-to-benefit ratio of inhaled corticosteroids in patients with COPD.
        Prim Care Respir J. 2013; 22: 92-100
        • Pascoe S.
        • Locantore N.
        • Dransfield M.T.
        • Barnes N.C.
        • Pavord I.D.
        Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials.
        Lancet Respir Med. 2015; 3: 435-442
        • Barnes N.C.
        • Sharma R.
        • Lettis S.
        • Calverley P.M.A.
        Blood eosinophils as a marker of response to inhaled corticosteroids in COPD.
        Eur Respir J. 2016; 47: 1299-1303
        • Chapman K.R.
        • Hurst J.R.
        • Frent S.M.
        • et al.
        Long-term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in COPD Patients (SUNSET): a randomized, double-blind, triple-dummy clinical trial.
        Am J Respir Crit Care Med. 2018; 198: 329-339
        • Watz H.
        • Tetzlaff K.
        • Wouters E.F.M.
        • et al.
        Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids: a post-hoc analysis of the WISDOM trial.
        Lancet Respir Med. 2016; 4: 390-398
        • Vedel-Krogh S.
        • Nielsen S.F.
        • Lange P.
        • Vestbo J.
        • Nordestgaard B.G.
        Blood eosinophils and exacerbations in chronic obstructive pulmonary disease—the Copenhagen general population study.
        Am J Respir Crit Care Med. 2016; 193: 965-974
        • Turato G.
        • Semenzato U.
        • Bazzan E.
        • et al.
        Blood eosinophilia neither reflects tissue eosinophils nor worsens clinical outcomes in chronic obstructive pulmonary disease.
        Am J Respir Crit Care Med. 2018; 197: 1216-1219
        • Mandal J.
        • Roth M.
        • Costa L.
        • et al.
        Vasoactive intestinal peptide for diagnosing exacerbation in chronic obstructive pulmonary disease.
        Respiration. 2015; 90: 357-368
        • Boeck L.
        • Mandal J.
        • Costa L.
        • Roth M.
        • Tamm M.
        • Stolz D.
        Longitudinal measurement of serum vascular endothelial growth factor in patients with chronic obstructive pulmonary disease.
        Respiration. 2015; 90: 97-104
        • Stolz D.
        • Leeming D.J.
        • Kristensen J.H.E.
        • et al.
        Systemic biomarkers of collagen and elastin turnover are associated with clinically relevant outcomes in COPD.
        Chest. 2017; 151: 47-59
        • Singh D.
        • Kolsum U.
        • Brightling C.E.
        • et al.
        Eosinophilic inflammation in COPD: prevalence and clinical characteristics.
        Eur Respir J. 2014; 44: 1697-1700
        • Hamad G.A.
        • Cheung W.
        • Crooks M.G.
        • Morice A.H.
        Eosinophils in COPD: how many swallows make a summer?.
        Eur Respir J. 2018; 51
        • Roche N.
        • Chapman K.R.
        • Vogelmeier C.
        • et al.
        Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. Data from the FLAME Trial.
        Am J Respir Crit Care Med. 2017; 195: 1189-1197
        • Oshagbemi O.A.
        • Burden A.M.
        • Braeken D.C.W.
        • et al.
        Stabililty of blood eosinophils in patients with chronic obstructive pulmonary disease and in control subjects, and the impact of sex, age, smoking and baseline counts.
        Am J Respir Crit Care Med. 2017; 195: 1402-1404
        • Schleich F.
        • Corhay J.L.
        • Louis R.
        Blood eosinophil count to predict bronchial eosinophilic inflammation in COPD.
        Eur Respir J. 2016; 47: 1562-1564
        • Kolsum U.
        • Donaldson G.C.
        • Singh R.
        • et al.
        Blood and sputum eosinophils in COPD; relationship with bacterial load.
        Resp Res. 2017; 18: 88