Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Respiratory and Critical Care Medicine, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.
Front Immunol. 2023 Jan 30;14:1107031. doi: 10.3389/fimmu.2023.1107031. eCollection 2023.
Asthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown.
We clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish "T2-high" asthma or OVA combined with ozone exposure (OVA + ozone) to induce "T2-low" asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed.
Serum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (R) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma.
The potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.
哮喘主要分为两类：2 型（T2-高）和非 2 型（T2-低）。已经确定了哮喘严重程度与维生素 D 缺乏之间的关系，但它对每种哮喘表型的影响尚不清楚。
我们临床检查了维生素 D 对 T2-高（n = 60）或 T2-低哮喘（n = 36）患者与对照组（n = 40）的影响。测量血清 25（OH）D 水平、炎症细胞因子和肺功能。然后使用小鼠模型进一步分析维生素 D 对这两种哮喘表型的影响。在哺乳期，将 BALB/c 小鼠用维生素 D 缺乏（LVD）、充足（NVD）或补充（HVD）饮食喂养，断奶后后代也遵循相同的饮食。用卵清蛋白（OVA）致敏/激发后代建立“T2-高”哮喘，或用 OVA 联合臭氧暴露（OVA+臭氧）诱导“T2-低”哮喘。分析肺功能、血清、支气管肺泡灌洗液（BALF）和肺组织。
与对照组相比，哮喘患者的血清 25（OH）D 水平降低。维生素 D 缺乏（Lo）的患者在两种哮喘表型中均有不同程度的促炎细胞因子 IL-5、IL-6 和 IL-17A 升高，抗炎细胞因子 IL-10 表达降低，用力呼气量第一秒百分比（FEV%pred）降低。维生素 D 状态与 T2-低哮喘的 FEV%pred 相关性更强，而 25（OH）D 水平仅与 T2-低组的最大中期呼气流量百分比（MMEF%pred）呈正相关。与对照组相比，两种哮喘模型均出现炎症、高反应性和气道阻力（R）增加，而维生素 D 缺乏进一步增加了气道炎症和气道阻塞。这些发现尤其在 T2-低哮喘中更为明显。
应单独研究维生素 D 和两种哮喘表型的潜在功能和机制，并且需要进一步分析涉及 T2-低哮喘的维生素 D 相关的潜在信号通路。
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