Airway Eosinophilia on Bronchoalveolar Lavage and the Risk of Exacerbations in COPD

Chunman Germain Ho, Stephen Milne, Xuan Li, Chen Xi Yang, Fernando Sergio Leitao Filho, Chung Yan Cheung, Julia Shun Wei Yang, Ana I Hernández Cordero, Cheng Wei Tony Yang, Tawimas Shaipanich, Stephan F van Eeden, Janice M Leung, Stephen Lam, Don D Sin, Chunman Germain Ho, Stephen Milne, Xuan Li, Chen Xi Yang, Fernando Sergio Leitao Filho, Chung Yan Cheung, Julia Shun Wei Yang, Ana I Hernández Cordero, Cheng Wei Tony Yang, Tawimas Shaipanich, Stephan F van Eeden, Janice M Leung, Stephen Lam, Don D Sin

Abstract

The associations between airway eosinophilia, measured in sputum or peripheral blood, and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are inconsistent. We therefore aimed to determine the association between eosinophilia in bronchoalveolar lavage (BAL) fluid and AECOPD in a clinical cohort. We analyzed differential cell counts from baseline BAL fluid in participants in the DISARM clinical trial (Clinicaltrials.gov #NCT02833480) and classified participants by the presence or absence of BAL eosinophilia (>1% of total leukocytes). We determined the association between BAL eosinophilia and AECOPD over 1 year of follow-up using negative binomial regression and Cox proportional hazards test. N = 63 participants were randomized, and N = 57 had BAL differential cell counts available. Participants with BAL eosinophilia (N = 21) had a significantly increased rate of acute exacerbations (unadjusted incidence rate ratio (IRR) 2.0, p = 0.048; adjusted IRR 2.24, p = 0.04) and a trend toward greater probability of acute exacerbation (unadjusted hazard ratio (HR) 1.74, p = 0.13; adjusted HR 2.3, p = 0.1) in the year of follow-up compared to participants without BAL eosinophilia (N = 36). These associations were not observed for BAL neutrophilia (N = 41 participants), BAL lymphocytosis (N = 27 participants) or peripheral blood eosinophilia at various threshold definitions (2%, N = 37; 3%, N = 27; 4%, N = 16). BAL may therefore be a sensitive marker of eosinophilic inflammation in the distal lung and may be of benefit for risk stratification or biomarker-guided therapy in COPD.

Keywords: biomarkers; bronchoscopy; chronic obstructive pulmonary disease; eosinophilia.

Conflict of interest statement

D.D.S. reports grants from AstraZeneca during the conduct of the study; personal fees from GSK and Boehringer-Ingelheim, and grants and personal fees from AstraZeneca outside the submitted work. C.G.H., S.M., X.L., C.X.Y., F.S.L.F., A.I.H.C., C.W.T.Y., C.Y.C., J.S.W.Y., T.S., S.F.v.E. and S.L. have nothing to disclose. The sponsor had no role in the design, execution, interpretation, or writing of the study.

Figures

Figure 1
Figure 1
Relationship between eosinophilia and AECOPD events in the DISARM trial. BAL eosinophilia (>1% of total BAL leukocytes) (A), but not peripheral blood eosinophilia (>3% of total blood leukocytes) (B), was associated with a higher rate of AECOPD events (incidence rate ratio 2.0, p = 0.048 vs. 1.0, p = 0.99). Abbreviations: AECOPD, acute exacerbations of chronic obstructive pulmonary disease; BAL, bronchoalveolar lavage.
Figure 2
Figure 2
Survival analysis of the effect of eosinophilia on AECOPD events in the DISARM trial. BAL eosinophilia (A), but not peripheral blood eosinophilia (B), was associated with a non-significant increased probability of an AECOPD event (Cox proportional hazards test unadjusted hazard ratio 1.74, p = 0.13 vs. 0.77, p = 0.5). Abbreviations: AECOPD, acute exacerbations of chronic obstructive pulmonary disease; BAL, bronchoalveolar lavage.
Figure 3
Figure 3
Relationship between BAL and peripheral blood eosinophil counts at baseline in the DISARM trial. There was no correlation between eosinophil proportions in the two compartments (Spearman’s rho 0.24, p = 0.09). Abbreviations: BAL, bronchoalveolar lavage.

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Source: PubMed

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