Vitamin D and asthma: another dimension.
Vitamin D and asthma: another dimension.
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维生素 D 和哮喘：另一个层面。
DOI：
10.1164/rccm.201109-1737ed
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发表时间：
2011
影响因子：
24.7
通讯作者：
Sutherland,ERand
中科院分区：
文献类型：
--
作者：
Gerber,AnthonyN;Sutherland,ERand
在本期杂志中，Gupta和同事（pp. 1342-1349）增加了报道维生素D状态（如血清25（OH）D浓度所反映的）与哮喘严重程度和控制措施之间的关联的不断扩大的文献主体（1）。在一个特征明确的中度或重度（难治性）哮喘儿童临床队列中，他们研究了血清25（OH）D与肺功能、哮喘控制、急性发作和用药史之间的关系。根据先前的报道，研究人员发现25（OH）D与哮喘严重程度、急性发作和吸入糖皮质激素需求之间呈负相关，而25（OH）D与肺功能和哮喘控制之间呈正相关。这些发现验证了直接从严重哮喘患者获得的数据，其他报告中维生素D状态与儿童哮喘严重程度相关（2-4）。然而，作者将他们的发现更进一步，还为我们提供了有关维生素D和气道病理学方面的数据。根据既定方案，在对一部分重度哮喘儿童进行临床评价期间进行纤维支气管镜检查。使用这些患者的支气管内活检标本，研究人员能够量化维生素D状态下组织炎症和气道重塑的测量。虽然25（OH）D和组织嗜酸性粒细胞，中性粒细胞，肥大细胞之间没有关系，有一个显着的负相关性25（OH）D和气道平滑肌（ASM）的体积分数，独立于肌细胞增殖的差异。这种与较低维生素D水平相关的ASM体积增加与气道重塑的其他病理结果无关。虽然作者指出了他们的数据集的局限性，并且在这种规模和设计的研究中，在解开环境，种族/民族，特应性和同时治疗等变量的混淆作用方面存在固有的挑战，但这些观察结果为维生素D-哮喘相关性的临床研究开辟了另一个维度。大部分儿科哮喘的现有文献都集中在维生素D作为免疫功能的潜在调节剂，例如通过降低急性发作风险（5），或作为糖皮质激素敏感性的调节剂（4）。但也有报告称，血清25（OH）D降低与气流、支气管扩张剂反应性和气道高反应性指标相关，本手稿的研究结果表明，这些观察结果部分由ASM结构和/或功能的变化介导。在一些报道的临床研究中，维生素D相关的肺功能改变发生在特应性或气道炎症标志物（例如总IgE、皮肤点刺试验反应性或循环嗜酸性粒细胞）不同时增加的情况下（3）。因此，尽管目前关于气道重塑的概念表明，ASM细胞生长、增殖或迁移的增加发生在持续的组织炎症的背景下，并与其他变化如上皮下纤维化、基底膜增厚和血管生成同步（6），但该领域的临床文献表明，本文报道的ASM体积与炎症脱钩可能并非完全出乎意料。事实上，作者推测，他们的数据提供了体外实验的体内验证，表明维生素D对气道平滑肌增殖具有直接的抑制作用，而不依赖于对气道炎症的任何影响（7...
In this issue of the Journal, Gupta and colleagues (pp. 1342–1349) add to the ever-enlarging body of literature reporting associations between vitamin D status (as reflected by serum 25 (OH) D concentrations) and measures of asthma severity and control (1). In a well-characterized clinical cohort of children with either moderate or severe (treatment-resistant) asthma, they investigated associations between serum 25 (OH) D and lung function, asthma control, exacerbations, and medication history. As might be expected in light of prior reports, the investigators found an inverse relationship between 25 (OH) D and asthma severity, exacerbations, and inhaled glucocorticoid requirement, and a positive relationship between 25 (OH) D and both lung function and asthma control. These findings validate, using data obtained directly from patients with severe asthma, other reports in which vitamin D status is associated with asthma severity in children (2–4). The authors take their findings a step further, however, by also providing us with data regarding vitamin D and aspects of airway pathology. Per established protocol, fiberoptic bronchoscopy was performed during the clinical evaluation of a subset of the children with severe asthma. Using endobronchial biopsy specimens from these patients, the investigators were able to quantify measures of tissue inflammation and airway remodeling in the context of vitamin D status. While there was not a relationship between 25 (OH) D and tissue eosinophils, neutrophils, or mast cells, there was a significant and inverse correlation between 25 (OH) D and the volume fraction of airway smooth muscle (ASM), independent of differences in myocyte proliferation. This increase in ASM volume associated with lower vitamin D levels was observed independent of other pathological findings of airway remodeling. While the authors point out the limitations of their dataset, and while there are challenges inherent in disentangling the confounding roles of variables such as environment, race/ethnicity, atopy, and concurrent treatment in a study of this size and design, these observations open another dimension in clinical investigation of the vitamin D–asthma association. Much of the existing literature in pediatric asthma has focused on vitamin D either as a potential modulator of immune function, for example by reducing exacerbation risk (5), or as a modifier of sensitivity to glucocorticoids (4). But there have also been reports that reduced serum 25 (OH) D is unfavorably associated with measures of airflow, bronchodilator responsiveness, and airway hyperresponsiveness, and the findings in this manuscript suggest that these observations are mediated in part by changes in ASM structure and/or function. In some of the reported clinical studies, vitamin D–associated alterations in lung function occur in the absence of concurrent increases in markers of atopy or airway inflammation, for example, total IgE, skin prick test reactivity, or circulating eosinophils (3). Thus, although current concepts regarding airway remodeling would suggest that increases in ASM cell growth, proliferation, or migration occur in the setting of ongoing tissue inflammation and in step with other changes such as subepithelial fibrosis, basement membrane thickening, and angiogenesis (6), the clinical literature in this area would suggest that the decoupling of ASM volume from inflammation reported herein may not be entirely unexpected. Indeed, the authors speculate that their data provide in vivo validation of in vitro experiments indicating that vitamin D has direct inhibitory effects on airway smooth muscle proliferation, independent of any effects on airway inflammation (7 …
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