Is Vitamin D deficiency a mechanistic driver of Acute Lung Injury (ALI)?

维生素 D 缺乏是急性肺损伤 (ALI) 的机制驱动因素吗？

• 批准号: MR/J011266/1
• 负责人: Dhruv Parekh
• 金额: $ 20.14万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ011266%2F1
• 关键词: Vitamin; deficiency; mechanistic; driver; Acute

Sunlight is the major natural source of vitamin D and therefore vitamin D deficiency is common in the UK. Vitamin D deficiency can cause many health problems, particulary relating to reduced immunity and increasing susceptibility to infections. Studies have shown that vitamin D has effects on many different aspects of the immune system. Acute Lung Injury (ALI) is a condition that causes respiratory failure in critically ill people. It occurs when the immune system damages the lungs. It can occur as a result of direct injury to the lungs, such as pneumonia, or through indirect damage such septicaemia, trauma or surgery. However, not all patients who have these problems go on to develop ALI.ALI is of considerable public health importance as it has a high mortality rate (40-50%) and leads to a similar number of deaths per year in the UK as breast cancer or AIDS. ALI also has major impact upon patients who survive with 40-50% of those of working age unable to return to work within 12 months.The question we are looking to address is, why do some people develop ALI when others in the same cirumstances do not? Is this linked to their Vitamin D level and it's effect on the immune system?ALI affects 1 in 4 people requiring a surgical operation to remove the gullet (oesphagectomy). We have identified that deficiency of vitamin D may be an important risk factor for developing ALI in this group of people.We will look at the effects of vitamin D on different types of immune cells isolated from samples from blood and lung in patients undergoing oesophagectomy and with ALI. We will also use mouse models that are vitamin D deficient to investigate the effects of vitamin D deficiency and whether its replacment can prevent the onset of acute lung injury. This research will determine the role of vitamin D deficiency as a major contributing factor to the development of ALI and also help define the underlying mechanisms by which it occurs. We will test the effects of treatment with vitamin D as a strategy for preventing lung injury which may lead to the use of vitamin D supplementation in patients with, and at risk of, ALI as a means of preventing and treating the condition.

阳光是维生素D的主要天然来源，因此维生素D缺乏症在英国很常见。维生素D缺乏会导致许多健康问题，特别是与免疫力下降和感染易感性增加有关。研究表明，维生素D对免疫系统的许多不同方面都有影响。急性肺损伤（ALI）是一种导致危重患者呼吸衰竭的疾病。它发生在免疫系统损害肺部时。它可能是由于肺部直接损伤（如肺炎）或间接损伤（如败血症、创伤或手术）而发生的。然而，并非所有患有这些问题的患者都会继续发展为ALI JLI具有相当大的公共卫生重要性，因为它具有高死亡率（40-50%），并且在英国每年导致与乳腺癌或艾滋病相似的死亡人数。急性肺损伤也有重大影响的患者谁生存与40-50%的工作年龄无法返回工作在12个月内。我们正在寻找解决的问题是，为什么有些人发展急性肺损伤时，其他人在相同的情况下没有？这是否与他们的维生素D水平及其对免疫系统的影响有关？每4个人中就有1个人患有ALI，需要进行手术切除食道（食管切除术）。我们已经确定，缺乏维生素D可能是一个重要的危险因素，发展急性肺损伤在这组people.We将看看维生素D对不同类型的免疫细胞分离样本从血液和肺在接受食管切除术和急性肺损伤患者的影响。我们还将使用维生素D缺乏的小鼠模型来研究维生素D缺乏的影响，以及维生素D缺乏是否可以预防急性肺损伤的发生。这项研究将确定维生素D缺乏作为ALI发展的主要因素的作用，并有助于确定其发生的潜在机制。我们将测试维生素D治疗作为预防肺损伤的策略的效果，这可能导致在有ALI风险的患者中使用维生素D补充剂作为预防和治疗该疾病的手段。

项目成果

Simvastatin to modify neutrophil function in older patients with septic pneumonia (SNOOPI): study protocol for a randomised placebo-controlled trial.

• DOI: 10.1186/1745-6215-15-332
• 发表时间: 2014-08-22
• 期刊: Trials
• 影响因子: 2.5
• 作者: Greenwood H;Patel J;Mahida R;Wang Q;Parekh D;Dancer RC;Khiroya H;Sapey E;Thickett DR
• 通讯作者: Thickett DR

Vitamin D and critical illness: what endocrinology can learn from intensive care and vice versa.

• DOI: 10.1530/ec-18-0184
• 发表时间: 2018-12-01
• 期刊: Endocrine connections
• 影响因子: 2.9
• 作者: Amrein K;Papinutti A;Mathew E;Vila G;Parekh D
• 通讯作者: Parekh D

LSC Abstract - Effects of vitamin D supplementation on perioperative markers of inflammation in patients at risk of acute respiratory distress syndrome (ARDS)

LSC 摘要 - 补充维生素 D 对有急性呼吸窘迫综合征 (ARDS) 风险的患者围手术期炎症标志物的影响

• DOI: 10.1183/13993003.congress-2016.pp111
• 发表时间: 2016
• 作者: Dancer R

Assessment of Alveolar Macrophage Dysfunction Using an in vitro Model of Acute Respiratory Distress Syndrome.

• DOI: 10.3389/fmed.2021.737859
• 发表时间: 2021
• 期刊: Frontiers in medicine
• 影响因子: 3.9
• 作者: Mahida RY;Scott A;Parekh D;Lugg ST;Belchamber KBR;Hardy RS;Matthay MA;Naidu B;Thickett DR
• 通讯作者: Thickett DR

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).

• DOI: 10.1136/thoraxjnl-2014-206680
• 发表时间: 2015-07
• 期刊: Thorax
• 影响因子: 10
• 作者: Dancer RC;Parekh D;Lax S;D'Souza V;Zheng S;Bassford CR;Park D;Bartis DG;Mahida R;Turner AM;Sapey E;Wei W;Naidu B;Stewart PM;Fraser WD;Christopher KB;Cooper MS;Gao F;Sansom DM;Martineau AR;Perkins GD;Thickett DR
• 通讯作者: Thickett DR