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嗜酸性粒细胞性气道炎症和高反应性作为慢性阻塞性肺疾病的表型以及吸入性糖皮质激素的效用

Eosinophil Inflammation and Hyperresponsiveness in the Airways as Phenotypes of COPD, and Usefulness of Inhaled Glucocorticosteroids.

作者信息

Kume Hiroaki, Hojo Masayuki, Hashimoto Naozumi

机构信息

Department of Respiratory Medicine, Rinku General Medical Center, Izumisano, Japan.

Department of Respiratory Medicine and Allergology, Faculty of Medicine, Kindai University, Osakasayama, Japan.

出版信息

Front Pharmacol. 2019 Jul 25;10:765. doi: 10.3389/fphar.2019.00765. eCollection 2019.

Abstract

The differential diagnosis in persistent airway limitation is sometimes not so clear in older adults. Airway eosinophilia and airway hyperresponsiveness may develop in some cases with chronic obstructive lung disease (COPD), independent of asthma. However, little is known about clinical significance of these phenotypes of COPD in detail. This clinical study was designed to examine prevalence of airway eosinophilia and airway hyperresponsiveness in COPD who have no symptom and no past history of asthma, and to examine involvement of these pathophysiological features of asthma in the management and therapy for COPD. Sputum examination qualitative and quantitative procedures was performed in stable COPD (GOLD 1-3). When sputum eosinophils were qualitatively (≥+) or quantitatively assessed (≥3%), ciclesonide (inhaled glucocorticosteroids) was added on bronchodilators. In cases with FEV ≥ 70% of predicted values, acetylcholine provocation test was examined for assessment of airway hyperresponsiveness. Therapeutic effect was evaluated using spirometry and COPD assessment test (CAT). Sputum eosinophils were observed in 65 (50.4%) of 129 subjects using qualitative analysis; in contrast, lower grade (>0%) and higher grade (≥3%) were observed in 15 (20.3%) and 25 (33.8%) of 74 subjects using quantitative analysis. Airway hyperresponsiveness developed in 46.9% of these subjects with sputum eosinophils. Exacerbations occurred much more frequently in lower-grade airway eosinophilia without ciclesonide than in higher-grade airway eosinophilia with ciclesonide. Airway hyperresponsiveness significantly increased frequency of exacerbations in COPD with both lower and higher grade in airway eosinophilia. Addition of ciclesonide to indacaterol markedly improved lung function (FEV, IC), CAT score, and reliever use in these subjects with airway eosinophilia determined by qualitative analysis. However, ciclesonide was less effective in improving these values in subjects with airway hyperresponsiveness than in those without airway hyperresponsiveness. Airway eosinophilia and airway hyperresponsiveness are complicated with 25-50% of COPD that have no symptom and history for asthma. These phenotypes of COPD are closely related to symptom stability and reactivity to glucocorticosteroids. These phenotypes may play key roles for advancement of the management and therapy of this disease.

摘要

在老年人中,持续性气道受限的鉴别诊断有时并不那么明确。在一些慢性阻塞性肺疾病(COPD)病例中,气道嗜酸性粒细胞增多和气道高反应性可能会出现,与哮喘无关。然而,关于COPD这些表型的临床意义,目前还知之甚少。这项临床研究旨在检查无症状且无哮喘病史的COPD患者气道嗜酸性粒细胞增多和气道高反应性的患病率,并研究哮喘的这些病理生理特征在COPD管理和治疗中的作用。对稳定期COPD(GOLD 1 - 3级)患者进行痰液检查(包括定性和定量检查)。当痰液嗜酸性粒细胞定性检查(≥ +)或定量评估(≥3%)时,在支气管扩张剂基础上加用环索奈德(吸入性糖皮质激素)。对于FEV≥预测值70%的患者,进行乙酰甲胆碱激发试验以评估气道高反应性。使用。使用肺量计和慢性阻塞性肺疾病评估测试(CAT)评估治疗效果。采用定性分析,在129名受试者中有65名(50.4%)观察到痰液嗜酸性粒细胞增多;相比之下,采用定量分析,在74名受试者中,分别有15名(20.3%)和25名(33.8%)观察到较低等级(>0%)和较高等级(≥3%)的痰液嗜酸性粒细胞增多。在这些痰液嗜酸性粒细胞增多的受试者中,46.9%出现了气道高反应性。在未使用环索奈德的低等级气道嗜酸性粒细胞增多患者中,急性加重的发生频率比使用环索奈德的高等级气道嗜酸性粒细胞增多患者高得多。气道高反应性显著增加了气道嗜酸性粒细胞增多等级较低和较高的COPD患者的急性加重频率。对于经定性分析确定有气道嗜酸性粒细胞增多患者,在茚达特罗基础上加用环索奈德可显著改善肺功能(FEV、IC)、CAT评分和缓解药物的使用情况。然而,与无气道高反应性的患者相比,环索奈德在改善有气道高反应性患者的这些指标方面效果较差。25% - 50%无症状且无哮喘病史的COPD患者合并有气道嗜酸性粒细胞增多和气道高反应性。COPD的这些表型与症状稳定性和对糖皮质激素的反应性密切相关。这些表型可能在该疾病管理和治疗的进展中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f8/6676333/d988dc3e4b39/fphar-10-00765-g001.jpg

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