Zinc intervention in prevention of pneumonia in elderly

肺炎（PNA）是老年人死亡的主要原因，也是老年人的主要公共卫生问题， 养老院（Nursing Home）因此，迫切需要有效的策略来预防老年人的PNA。 可能导致老年人PNA发病率较高的一个重要诱发因素是年龄- T细胞功能下降。重要的是，锌缺乏和 年龄引起的T细胞变化。我们已经表明，29%的NH居民血清锌水平低， 与PNA的高发病率和持续时间以及抗生素的使用相关。虽然我们的初步数据 强烈提示低血清锌是老年人PNA独立危险因素，对照临床试验 是迫切需要的，以确定锌补充剂在PNA预防在这一人群中的疗效。的 一项更大规模的临床试验将继续进行本R34中提出的研究，其目的是确定 补充锌对NH老年人PNA结果的影响，并了解其机制基础。我们的中央 假设改善低血清锌的NH老年人的锌状况将减少发病率和持续时间 的PNA，和抗生素的使用频率，锌的影响主要是通过介导的， 改善T细胞功能和/或先天免疫。我们进行拟议临床试验的理由是 确定锌补充剂作为一种廉价、易于实施的干预措施的价值， 有助于预防老年人的PNA。 在我们以前的研究中，NH老年人血清锌水平低，谁补充了30毫克/天的锌， 必需微量营养素的半RDA显示，平均而言，显着改善血清锌水平。但只有 58%的受试者血清锌充足。因此，我们假设，无论是更高的剂量或更长的 补充锌的持续时间需要达到足够的血清锌水平在所有锌缺乏的老年人。我们 进行拟议的试点研究的基本原理是确定锌的最有效但安全的剂量 在NH居民中的补充剂将用于上述更大的临床试验。 拟议的为期两年的试点研究的具体目标是确定补充锌的最佳剂量， 达到足够的锌状态，并改善缺锌老年人的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， 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细胞介导的和先天性免疫，以及不良事件。这项提案的结果是科学的， 必要的，但足够的，使我们能够作出明确的决定，通知我们的计划的最终设计， 临床试验，旨在建立锌补充剂作为一种廉价，易于实施的 干预，这将有助于预防PNA，限制PNA的持续时间，从而减少 老年人需要抗菌治疗。

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.