哮喘联盟

   摘要
   背景：支气管扩张剂的扩张支气管作用在很大一部分慢性阻塞性肺疾病 (COPD) 患者中已被认识到。然而，也有不一致的报道称β₂受体激动剂可以导致支气管收缩。β₂受体激动剂所致的无症状支气管收缩可能比有症状的更常见，但目前尚未见系统的研究报道。我们评估了这种反常作用在伴或不伴COPD的吸烟者和既往吸烟者中的发生率，以及其放射学相关性和临床意义。
   方法：根据支气管扩张剂是否产生反常收缩作用，把来自一个大型多中心研究COPDGene的非西班牙裔白人和黑人患者(45 - 80岁)分为两组。这种反常作用定义为在服用短效β₂受体激动剂(180μg沙丁胺醇)以后FEV₁或FVC下降至少12%且绝对值下降至少200毫升，或两者兼有。
   结果：招募2008年1月-2011年6月10364名参加COPDGene研究中的9986(96%)患者，平均年龄59.6± 9.0岁。9986名患者中的453 (5%) 发现对支气管扩张剂有反常反应，COPD患者的发生率(198/4439, 4%)和吸烟但不伴有气流阻塞者(255/5547, 5%的)相似。非裔美国人的这种反常作用(227/3282，7%)是白种人的两倍(226/3282, 3%) (p < 0.0001)。多元分析发现，非裔美国人的种族起源(调整后的优势比1.89，95%可信区间1.50-2.39；p < 0.0001)，更少的肺气肿(0.96, 0.92-0.99; p=0.023)，和增加的节段气道壁区域百分比(1.04,1.01-1.08; p = 0.023)分别与支气管扩张剂的反常作用独立相关。这种反常作用还与更严重的呼吸困难(MMRC的校正β为0.12 [95%可信区间0.00为0.24];p = 0.05)，较短的6分钟步行距离(-45.8 [-78.5-13.2]; p = 0.006)，高体重指数、气流阻塞、呼吸困难、运动耐量(BODE)指数(0.31 [0.19 – 0.43], p < 0•0001)，和更严重的发作频率(增加了1.35个系数[1.00-1.81]; p = 0.048)独立相关。
   结论：β₂受体激动剂的反常作用与呼吸系统疾病发病率相关，并在非裔美国人更常见。这些发现可能对β2受体激动剂在一些患者中的应用产生影响。
 

（南方医科大学南方医院 梁俊杰 赵海金）
Bhatt SP, Wells JM, Kim V, et al.Lancet Respir Med. 2014 Nov;2(11):911-8.
 

Radiological correlates and clinical implications of the paradoxical lung function response to β₂ agonists: an observational study.

Bhatt SP, Wells JM, Kim V, et al.Lancet Respir Med. 2014 Nov;2(11):911-8.

Abstract
BACKGROUND:Bronchodilator response has been noted in a significant proportion of patients with chronic obstructive pulmonary disease (COPD). However, there are also reports of a paradoxical response to β₂ agonists resulting in bronchoconstriction. Asymptomatic bronchoconstriction is likely to be far more common than is symptomatic bronchoconstriction with β₂ agonists, but no systematic studies have been done. We assessed the prevalence of paradoxical response in current and former smokers with and without COPD, and its radiological correlates and clinical implications.
METHODS:Non-Hispanic white and African-American patients (aged 45-80 years) from a large multicentre study COPDGene were classified into two groups on the basis of a paradoxical response, defined as at least a 12% and 200 mL reduction in forced expiratory volume in 1 sec (FEV₁) or forced vital capacity (FVC), or both, after administration of a shortacting β₂ agonist (180 μg salbutamol).
FINDINGS:Patients were recruited from January, 2008, to June, 2011. 9986 (96%) of 10,364 patients enrolled in the COPDGene study were included in the analysis population (mean age 59•6 years [SD 9•0]). Paradoxical response was noted in 453 (5%) of 9986 patients and the frequency was similar in patients with COPD (198 [4%] of 4439) and smokers without airflow obstruction (255 [5%] of 5547). Compared with white patients, a paradoxical response was twice as common in African-American patients (227 [7%] of 3282 vs 226 [3%] of 6704; p<0•0001). In the multivariate analyses, African-American ethnic origin (adjusted odds ratio 1•89, 95% CI 1•50-2•39; p<0•0001), less emphysema (0•96, 0•92-0•99; p=0•023), and increased wall-area percentage of the segmental airways (1•04, 1•01-1•08; p=0•023) were independently associated with a paradoxical response. A paradoxical response was independently associated with worse dyspnoea (adjusted β for Modified Medical Research Council Dyspnoea Scale 0•12 [95% CI 0•00 to 0•24]; p=0•05), lower 6 min walk distance (-45•8 [-78•5 to -13•2]; p=0•006), higher Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index (0•31 [0•19 to 0•43]; p<0•0001), and a greater frequency of severe exacerbations (increased by a factor of 1•35, 1•00-1•81; p=0•048).
INTERPRETATION:Paradoxical response to β₂ agonists is associated with respiratory morbidity and is more common in African-Americans. These findings might have implications for the use of β2agonists in some patients.