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通过监测痰液细胞计数确定哮喘治疗方案:对病情加重的影响

Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations.

作者信息

Jayaram L, Pizzichini M M, Cook R J, Boulet L-P, Lemière C, Pizzichini E, Cartier A, Hussack P, Goldsmith C H, Laviolette M, Parameswaran K, Hargreave F E

机构信息

Firestone Institute for Respiratory Health, St. Joseph's Healthcare and McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.

出版信息

Eur Respir J. 2006 Mar;27(3):483-94. doi: 10.1183/09031936.06.00137704.

Abstract

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils<or=2%; symptoms and spirometry were used to identify clinical control, exacerbations and other treatments. Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS, thus removing bias. First, the minimum treatment to maintain control was identified in 107 patients (Phase 1) and then this treatment was continued (Phase 2) for the remaining of the 2 yrs. The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation. The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed. The duration and number of exacerbations in Phase 1 were similar in both groups. In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS (62.7%) and 47 (37.3%) in the SS groups. The majority of the 126 exacerbations (101; 80.1%) were mild. The majority of the 102 exacerbations, where sputum examination was performed before any treatment (n=70), were noneosinophilic. In the SS patients, the time to the first exacerbation was longer (by 213 days) especially in those considered to need treatment with a long acting beta2-agonist (by 490 days), the relative risk ratio was lower (by 49%), and the number of exacerbations needing prednisone was reduced (5 versus 15). This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone>250 microg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.

摘要

哮喘治疗的一个重要目标是减少病情加重。本研究作者调查了使用痰液细胞计数来指导治疗是否能实现这一目标。在一项为期2年的多中心、随机、平行组有效性研究中,共有117名成年哮喘患者被纳入两种治疗策略的研究。在一种策略(临床策略:CS)中,治疗基于症状和肺功能测定。在另一种策略(痰液策略:SS)中,痰液细胞计数用于指导皮质类固醇治疗,以使嗜酸性粒细胞≤2%;症状和肺功能测定用于确定临床控制、病情加重情况及其他治疗。在两种策略中,患者对痰液细胞计数均不知情,在CS策略中医生也不知情,从而消除了偏差。首先,在107名患者中确定维持控制的最低治疗方案(第1阶段),然后在接下来的2年中继续采用该治疗方案(第2阶段)。主要结局指标为第2阶段首次病情加重发生的相对风险降低情况以及无病情加重的时间长度。本研究作者还检查了病情加重的类型和严重程度以及所需吸入性类固醇的累积剂量。第1阶段两组的病情加重持续时间和次数相似。在第2阶段,共发生126次病情加重,其中79次发生在CS组(62.7%),47次(37.3%)发生在SS组。126次病情加重中的大多数(101次;80.1%)为轻度。在102次病情加重中,大多数(在任何治疗前进行痰液检查的70例中)为非嗜酸性粒细胞性加重。在SS组患者中,首次病情加重的时间更长(长213天),尤其是那些被认为需要使用长效β2受体激动剂治疗的患者(长490天),相对风险比更低(低49%),需要使用泼尼松治疗的病情加重次数减少(5次对15次)。这种益处主要见于每日需要吸入相当于>250微克氟替卡松剂量类固醇治疗的患者,且归因于嗜酸性粒细胞性病情加重次数减少。试验期间两组皮质类固醇的累积剂量相似。研究发现,监测痰液细胞计数可使中重度哮喘患者受益,可减少嗜酸性粒细胞性病情加重次数,降低嗜酸性粒细胞性和非嗜酸性粒细胞性病情加重的严重程度,且不增加皮质类固醇的总剂量。它对非嗜酸性粒细胞性病情加重的频率没有影响,而非嗜酸性粒细胞性病情加重是最常见的病情加重类型。

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