Department of Medicine, Washington University School of Medicine, St. Louis, MO.
Portex Respiratory Unit, University College London, Institute of Child Health, London, England.
Chest. 2011 Mar;139(3):563-568. doi: 10.1378/chest.10-1243. Epub 2010 Aug 19.
The high prevalence of airway hyperresponsiveness (AHR) among children with sickle cell anemia (SCA) remains unexplained.
To determine the relationship between AHR, features of asthma, and clinical characteristics of SCA, we conducted a multicenter, prospective cohort study of children with SCA. Dose response slope (DRS) was calculated to describe methacholine responsiveness, because 30% of participants did not achieve a 20% decrease in FEV1 after inhalation of the highest methacholine concentration, 25 mg/mL. Multiple linear regression analysis was done to identify independent predictors of DRS.
Methacholine challenge was performed in 99 children with SCA aged 5.6 to 19.9 years (median, 12.8 years). Fifty-four (55%) children had a provocative concentration of methacholine producing a 20% decrease in FEV1<4 mg/mL. In a multivariate analysis, independent associations were found between increased methacholine responsiveness and age (P<.001), IgE (P=.009), and lactate dehydrogenase (LDH) levels (P=.005). There was no association between methacholine responsiveness and a parent report of a doctor diagnosis of asthma (P=.986). Other characteristics of asthma were not associated with methacholine responsiveness, including positive skin tests to aeroallergens, exhaled nitric oxide, peripheral blood eosinophil count, and pulmonary function measures indicating airflow obstruction.
In children with SCA, AHR to methacholine is prevalent. Younger age, serum IgE concentration, and LDH level, a marker of hemolysis, are associated with AHR. With the exception of serum IgE, no signs or symptoms of an allergic diathesis are associated with AHR. Although the relationship between methacholine responsiveness and LDH suggests that factors related to SCA may contribute to AHR, these results will need to be validated in future studies.
镰状细胞贫血（SCA）患儿气道高反应性（AHR）的高发率仍未得到解释。
为了确定 AHR、哮喘特征与 SCA 临床特征之间的关系，我们对 SCA 患儿进行了一项多中心前瞻性队列研究。计算了气道反应性斜率（DRS）来描述乙酰甲胆碱的反应性，因为 30%的参与者在吸入最高乙酰甲胆碱浓度 25mg/ml 后没有达到 FEV1 下降 20%。采用多元线性回归分析确定 DRS 的独立预测因子。
对 99 名年龄在 5.6 至 19.9 岁（中位数 12.8 岁）的 SCA 患儿进行了乙酰甲胆碱激发试验。54 名（55%）患儿的乙酰甲胆碱激发浓度使 FEV1 下降 20%<4mg/ml。在多变量分析中，发现乙酰甲胆碱反应性增加与年龄（P<0.001）、IgE（P=0.009）和乳酸脱氢酶（LDH）水平（P=0.005）独立相关。乙酰甲胆碱反应性与父母报告的医生诊断哮喘之间无关联（P=0.986）。哮喘的其他特征与乙酰甲胆碱反应性无关，包括对气传过敏原、呼气一氧化氮、外周血嗜酸性粒细胞计数和表明气流阻塞的肺功能测量的阳性皮肤试验。
在 SCA 患儿中，乙酰甲胆碱诱导的 AHR 很常见。年龄较小、血清 IgE 浓度和 LDH 水平（溶血的标志物）与 AHR 相关。除了血清 IgE 外，过敏素质的任何体征或症状都与 AHR 无关。尽管乙酰甲胆碱反应性与 LDH 之间的关系表明与 SCA 相关的因素可能导致 AHR，但这些结果需要在未来的研究中得到验证。
