哮喘患者中炎症亚型与对甘露醇的气道高反应性及呼出NO相关
2009/10/15
根据痰液中是否出现嗜酸性粒细胞，哮喘可分为嗜酸细胞性哮喘和非嗜酸细胞性哮喘。最近，有建议将其分为四个炎性亚型。本试旨在验描述这些炎症亚型与气道炎症标记物和气道高反应性之间的关系。
研究纳入62例18～65岁未使用吸入糖皮质激素治疗的非吸烟成人哮喘患者，进行痰液诱导、甘露醇支气管激发试验，并检测呼出气一氧化氮水平（eNO）。根据痰液中嗜酸性粒细胞和中性粒细胞的比例，将受试对象分为下述四个炎症亚型：嗜酸细胞性哮喘（痰液嗜酸性粒细胞> 1.0%）、中性粒细胞性哮喘（痰液中性粒细胞> 61%）、混合型粒细胞性哮喘（嗜酸性粒细胞和中性粒细胞均增加）和寡粒细胞性哮喘（嗜酸性粒细胞和中性粒细胞水平均正常）。
在非嗜酸细胞性哮喘患者中，中性粒细胞性哮喘与低水平eNO（中位数(IQR)：12 ppb (8-27 ppb)）相关，而寡粒细胞性哮喘患者eNO水平（48 ppb (29-65 ppb)）与混合型粒细胞性哮喘患者相当（47 ppb (33-112 ppb)。纯粹的嗜酸细胞性哮喘与较高水平（77 ppb (37-122 ppb)）eNO相关。而且，中性粒细胞性哮喘患者对甘露醇的气道高反应性程度较低（PD(15): (中位数 (IQR) 512 mg (291-610 mg))），而寡粒细胞性哮喘患者表现为中度气道高反应性（238 mg (77-467 mg)），后者与混合粒细胞性哮喘患者相当（186 mg (35-355 mg)）。纯粹嗜酸细胞性哮喘患者对甘露醇的气道高反应性程度最高（107 mg (68-245 mg)）。
总之，对嗜酸细胞性哮喘和非嗜酸细胞性哮喘的进一步分型显示，炎症亚型在对甘露醇的气道高反应性和呼出NO水平上有显著差别。
（林江涛 审校）
Porsbjerg C, et al. J Asthma. 2009 Aug;46(6):606-612.
Inflammatory subtypes in asthma are related to airway hyperresponsiveness to mannitol and exhaled NO.
Porsbjerg C, Lund TK, Pedersen L, Backer V.
Asthma may be defined as eosinophilic or non-eosinophilic based on the presence of eosinophils in sputum. Recently a further classification into four inflammatory subtypes has been suggested. The aim of the present study was to describe the association between these inflammatory subtypes and markers of airway inflammation and hyperresponsiveness. In 62 adult non-smoking asthmatics, (18-65 yr) not taking inhaled steroids, sputum induction, bronchial challenge with mannitol and measurement of exhaled NO (eNO) were performed. Based on the eosinophil and neutrophil proportions in sputum, subjects were categorised into four inflammatory subtypes: Eosinophilic asthma: i.e., sputum eosinophils > 1.0%. Neutrophilic asthma: i.e., sputum neutrophils > 61%. Mixed granulocytic asthma: both increased eosinophils and neutrophils. Paucigranulocytic asthma: i.e., normal levels of both eosinophils and neutrophils. Among subjects with non-eosinophilic asthma, neutrophilic asthma was associated with low levels of eNO (Median (IQR): 12 ppb (8-27 ppb), whereas subjects with non-eosinophilic asthma of the paucigranulocytic subtype had levels of eNO (48 ppb (29-65 ppb)) that were comparable to subjects with eosinophilic asthma of the mixed granulocytic type (47 ppb (33-112 ppb). Purely eosinophilic asthma was associated with higher levels of eNO (77 ppb (37-122 ppb)). Furthermore, a low degree of airway hyperresponsiveness to mannitol was observed in neutrophilic asthma (PD(15): (Median (IQR) 512 mg (291-610 mg))), whereas it was moderate in paucigranulocytic asthma (238 mg (77-467 mg)) and comparable to eosinophilic asthma of the mixed granulocytic subtype (186 mg (35-355 mg)). The highest degree of AHR to mannitol was observed in purely eosinophilic asthma (107 mg (68-245 mg)). In conclusion, further subclassification of eosinophilic and non-eosinophilic asthma showed significant differences in airway hyperresponsiveness to mannitol and exhaled NO levels among the four inflammatory subtypes.
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脉冲振荡法检测哮喘患儿对甘露醇的气道反应性
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甘露醇和运动激发试验在哮喘患儿中的应用
