Zinc intervention in prevention of pneumonia in elderly

肺炎(PNA)是老年人死亡的主要原因，也是一个主要的公共卫生问题，特别是对 养老院(NH)居民。因此，迫切需要有效的策略来预防老年人的PNA。 老年人PNA发病率较高的一个重要易感因素是年龄- 相关的T细胞功能下降。重要的是，缺锌和缺锌之间有显著的相似性。 增龄性T细胞的变化。我们已经表明，29%的NH居民的血清锌水平较低，这 与较高的PNA发生率和持续时间以及抗生素的使用有关。虽然我们的初步数据 一项对照临床试验强烈提示低血清锌是老年人PNA的独立危险因素 在这一人群中，迫切需要确定补充锌在预防PNA方面的效果。这个 将进行本R34中建议的研究的更大规模临床试验的目标是确定 补锌对老年NH患者PNA结局的影响及其机制探讨。我们的中央 假设改善血清锌水平低的NH老年患者的锌状况将减少发病率和病程。 PNA和抗生素的使用频率，锌的作用主要是通过 改善T细胞功能和/或天然免疫力。我们进行拟议的临床试验的理由是 为了确定补锌的价值，作为一种廉价、易于实施的干预措施，它将 帮助老年人预防PNA。 在我们先前的研究中，血清锌水平低的老年NH患者，每天补充30 mg锌和 1.平均而言，必需微量营养素的RDA显著改善了血清锌水平。然而，只有 58%的受试者达到血清锌充足水平。因此我们假设，无论是更高的剂量还是更长的剂量 在所有缺锌的老年人中，补充锌的持续时间是达到足够的血清锌水平所必需的。我们的 进行拟议的初步研究的基本原理是确定锌的最有效但安全的剂量 NH居民中的补充剂将用于上述更大规模的临床试验。 这项拟议的为期两年的初步研究的具体目标是确定补充锌的最佳剂量 达到足够的锌营养状态，改善缺锌老年人的T细胞功能。我们将实现这一目标 通过进行随机、安慰剂对照、双盲临床试验来测试 补充30或60 mg/d锌12个月对血清和免疫细胞锌水平的影响 T细胞介导的先天免疫和不良反应。这项提议的发现是科学的 这是必要的，但也是足够的，使我们能够做出确定的决定，从而为我们计划的 临床试验，旨在确定补锌的价值，作为一种廉价、易于实施的 有助于预防PNA的干预措施，限制PNA的持续时间，从而减少 老年人抗菌治疗的必要性。

Pneumonia (PNA) is a leading cause of death and a major public health problem in the elderly, particularly for nursing home (NH) residents. Thus, there is an urgent need for effective strategies to prevent PNA in elderly. An important predisposing factor that may account for the higher incidence of PNA in older adults is the age- associated decline in T cell function. Importantly, there are remarkable similarities between Zn deficiency and age-induced changes in T cells. We have shown that 29% of NH residents have low serum Zn levels, which was associated with higher incidence and duration of PNA, and antibiotic use. Although our preliminary data strongly suggest that low serum Zn is an independent risk factor for PNA in the elderly, a controlled clinical trial is critically needed to determine the efficacy of Zn supplementation in PNA prevention in this population. The objective of the larger clinical trial that will pursue the studies proposed in this R34 is to determine the effects of Zn supplementation on PNA outcomes in NH elderly and to understand their mechanistic basis. Our central hypothesis is that improving Zn status in NH elderly with low serum Zn will reduce the incidence and duration of PNA, and the frequency of antibiotic use, and that the effect of Zn is mediated mainly through the improvement of T cell function and/or innate immunity. Our rationale for conducting the proposed clinical trial is to determine the value of Zn supplementation as an inexpensive, easily implemented intervention that would aid in the prevention of PNA in the elderly. In our previous study NH elderly with low serum Zn levels, who were supplemented with 30 mg/d of Zn and ½ RDA of essential micronutrients showed, on average, significantly improved serum Zn levels. However, only 58% of participant became serum Zn adequate. We therefore hypothesize that either a higher dose or a longer duration of supplementation is required to achieve adequate serum Zn levels in all Zn deficient elderly. Our rationale for conducting the proposed pilot study is to determine the most effective yet safe dose for Zn supplementation in NH residents to be used in the larger clinical trial described above. The Specific Aim of the proposed two-year, pilot study is to establish the optimal dose of supplemental Zn to achieve adequate Zn status, and improved T cell function in Zn deficient elderly. We will accomplish this goal by conducting a randomized, placebo-controlled, double-blind clinical trial to test the efficacy of supplementation with 30 or 60 mg/d of Zn for 12 months on serum and immune cell Zn levels, key measures of T cell mediated and innate immunity, and adverse events. The findings of this proposal are scientifically essential, yet sufficient, to allow us to make definitive decisions that inform the final design of our planned clinical trial, which aims to establish the value of Zn supplementation as an inexpensive, easily implemented intervention that would aid in the prevention of PNA, limit the duration of PNA, and consequently reduce the need for antimicrobial therapy in the elderly.