Ho Chunman Germain, Milne Stephen, Li Xuan, Yang Chen Xi, Leitao Filho Fernando Sergio, Cheung Chung Yan, Yang Julia Shun Wei, Hernández Cordero Ana I, Yang Cheng Wei Tony, Shaipanich Tawimas, van Eeden Stephan F, Leung Janice M, Lam Stephen, Sin Don D
Centre for Heart Lung Innovation, St Paul's Hospital, The University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.
Division of Respiratory Medicine, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Biomedicines. 2022 Jun 15;10(6):1412. doi: 10.3390/biomedicines10061412.
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.
通过痰液或外周血检测的气道嗜酸性粒细胞增多与慢性阻塞性肺疾病急性加重(AECOPD)之间的关联并不一致。因此,我们旨在确定支气管肺泡灌洗(BAL)液中的嗜酸性粒细胞增多与临床队列中AECOPD之间的关联。我们分析了DISARM临床试验(Clinicaltrials.gov #NCT02833480)参与者基线BAL液中的细胞分类计数,并根据是否存在BAL嗜酸性粒细胞增多(占总白细胞的>1%)对参与者进行分类。我们使用负二项回归和Cox比例风险检验确定了随访1年期间BAL嗜酸性粒细胞增多与AECOPD之间的关联。63名参与者被随机分组,57名有BAL细胞分类计数数据。与无BAL嗜酸性粒细胞增多的参与者(N = 36)相比,有BAL嗜酸性粒细胞增多的参与者(N = 21)在随访年度内急性加重率显著增加(未调整发病率比(IRR)2.0,p = 0.048;调整后IRR 2.24,p = 0.04),且急性加重概率有增加趋势(未调整风险比(HR)1.74,p = 0.13;调整后HR 2.3,p = 0.1)。对于BAL中性粒细胞增多(41名参与者)、BAL淋巴细胞增多(27名参与者)或不同阈值定义(2%,N = 37;3%,N = 27;4%,N = 16)下的外周血嗜酸性粒细胞增多,未观察到这些关联。因此,BAL可能是远端肺嗜酸性粒细胞炎症的敏感标志物,可能有助于COPD的风险分层或生物标志物指导治疗。