Nutr Diabetes:社区获得性肺炎中也存在肥胖悖论吗?

2022-04-03 MedSci原创 MedSci原创

肥胖与多种慢性病和死亡率的风险增加有关,如Stroke:房颤患者结局也存在肥胖悖论吗?,J Clin Med:真实世界研究中卒中住院患者的肥胖悖论。加拿大一项新研究发现,在患肺炎住院的病人中,肥胖病人

肥胖与多种慢性病和死亡率的风险增加有关,Stroke:房颤患者结局也存在肥胖悖论吗?J Clin Med:真实世界研究中卒中住院患者的肥胖悖论。加拿大一项新研究发现,在患肺炎住院的病人中,肥胖病人比体重正常的病人存活率更高,这进一步支持了"肥胖悖论"现象的存在。后续又有不少研究支持这一观点,认为肥胖对社区获得性肺炎 (CAP) 等急性疾病中的有益,称为“肥胖悖论”。事实上,最近一项汇总超过 150 万患者的社区获得性肺炎 (CAP) 患者结局的荟萃分析表明,与正常和体重不足的患者相比,超重或肥胖患者的死亡风险分别较低。

事实上,有几个病理生理学方面也支持肥胖悖论:(i)代谢储备增加,在急性传染病期间对分解代谢状态提供更大的抵抗力; (ii) 肥胖作为慢性低度炎症的一种状态,可能会增强免疫反应,从而增强 T 辅助 1 型细胞活化; (iii) 胸壁肥胖会“束缚”胸腔,这可能会减少肺炎和/或机械通气情况下的跨肺压介导的肺损伤; 和 (iv) 瘦素升高已显示可增加巨噬细胞吞噬作用、中性粒细胞趋化性、自然杀伤细胞细胞毒性以及 B 和 T 细胞功能。

然而,迄今为止,关于肺炎患者临床结果的大多数数据都是基于观察性研究,这些研究并未彻底解释偏倚,例如体重过轻患者中主动吸烟者的比例较高,以及与癌症相关的恶病质,两者都导致 BMI 较低的患者预后较差。

这是一项由研究者发起的、多中心、平行组、随机、双盲、安慰剂对照试验STEP试验的二次分析,该试验涉及急诊科收治的所有 CAP 严重程度的患者。 本研究共纳入 773 名 CAP 住院患者。根据基线 BMI 将患者分为四组(体重不足 <18.5、正常体重 18.5-25、超重 25-30 和肥胖 >30 kg/m2)。

本研究的主要目的是研究 BMI 与临床稳定时间(TTCS;定义为在两次连续测量时生命体征稳定的时间12 小时相隔)。 次要目标包括分析 BMI 与 30 天全因死亡率、重症监护病房 (ICU) 入院率、CAP 并发症(包括复发、急性呼吸窘迫综合征、脓胸、医院感染和可能与 CAP)、住院时间 (LOS) 以及总和静脉抗生素治疗的时间。

结果显示,基线时,中位年龄为 73 岁,大多数 CAP 患者(62%)为男性。 大多数患者体重正常(36.7%)或超重(35.4%)。 与体重正常或体重不足的患者相比,肥胖患者更常患有高血压(69.2%),糖尿病发病率更高(35.5%)。 在体重不足组的患者中,吸烟者(32.6%)和癌症患者(13.0%)的比例最高。 根据 PSI 评分,来自所有四个 BMI 组的患者的肺炎严重程度相当,大约一半的患者处于高危 PSI IV 级和 V 级。

在超重患者 [3.0 天 (IQR 2.6–4.0)] 和正常体重患者 [3.4 天 (IQR 3.0–4.0)] 中观察到临床稳定的最短时间; p > 0.05]。 与体重正常的患者相比,体重过轻 [4.4 天 (IQR 3.0–6.8)] 的 TTCS 显着延长,肥胖患者 [4.4 天 (IQR 3.5–5.0)] 的 TTCS 有延长的趋势(表 2) . 多变量 Cox 回归分析显示,体重不足 BMI 组 [HR 0.63, (95%CI, 0.45–0.89; p = 0.008)] 和肥胖患者 [HR 0.82, (95%CI)] 达到临床稳定性的风险显着降低 , 0.67–1.02; p = 0.07)],但在肥胖患者中没有达到统计学意义。 多变量分数多项式交互作用的分析证实了 BMI 和 TTCS 之间的 U 形关联,在 27 和 29 kg/m2 之间的超重 BMI 时临床稳定的时间最短(图 1)。

figure 1

所有 BMI 亚组患者的中位住院时间为 7 天(IQR 体重不足 7-11 天,正常体重 6-7 天,超重 6-7 天,肥胖患者 6-8 天)(表 2 ) 在体重过轻的组中住院时间相对较长。 在多变量 cox 回归分析中,与体重正常的患者相比,体重过轻的 BMI 组出院风险显着降低 [HR 0.55 (95%CI, 0.40-0.76; p < 0.001] (表 2)。住院时间, BMI 与 BMI 范围为 29 至 32 kg/m2 的最短住院时间呈 U 型关联(图 2)。

figure 2

入院后 30 天内死亡的比例最大的是体重不足的 BMI 组(8.7%),是正常体重患者(3.5%)的两倍多。 体重过轻的 BMI 组有较高的 30 天死亡率 [OR 2.19 (95%CI, 0.53–9.00)] 和超重 BMI 组的死亡率降低 [OR 0.58 (95% CI, 0.19–1.82)] ( 表 2)。 然而,多变量 cox 回归分析无法揭示 BMI 亚组之间的显着差异。 同样,BMI 等级之间的 ICU 入院率没有差异(p > 0.05)(表 2)。

与体重正常的患者相比,体重过轻 [5 天 (IQR 3.0–8.0)] 和超重组 [5 天 (IQR 3.0–6.5)] 的患者静脉注射抗生素治疗的持续时间分别延长了约 1 天。 4 天 (IQR 3.0–5.0)]。 多变量调整回归分析显示,体重过轻的 BMI 组平均治疗延长 1.47 天(95%CI,0.01-2.94;p = 0.049)

在体重过轻的 BMI 组中也观察到更长的抗生素治疗总持续时间,中位持续时间为 10 天(IQR 7.5-14),比超重和肥胖患者多一天,需要 9 天(IQR 7-11),以及 体重正常的患者仅需 8 天(IQR 7-11)。 多变量 cox 回归分析显示,与体重正常的患者相比,体重不足的 BMI 组间差异延长了 2.5 天(95%CI,0.88-4.20,p = 0.003)。

在评估本研究结果时需要考虑一些潜在的局限性:首先,我们缺乏关于我们队列中体重和组成的时间动态的数据,因此不能排除体重随时间的变化。其次,我们的研究主要代表老年人,因此我们的结果不能外推到年轻人群。同样,该研究仅包括需要住院的 CAP 患者,因此结果不适用于门诊患者。最后,该研究无法调查对 ARDS 患者死亡率或结局的影响。然而,这项研究有几个优势:一个大型且特征明确的队列,具有不同严重程度的 CAP 代表,用于通常在急诊科和医院接受治疗的患者。评估临床相关结果,包括临床稳定性,这是短期结果的良好标志。重要的是,所有结果都针对主要混杂因素进行了精心控制:吸烟状况、癌症和与营养不良相关的合并症。

总之,我们的研究不能证实“肥胖悖论”,但它强调体重不足可能会加重 CAP 住院患者的病程。 尽管在我们的 MFPI 图中超重的 TTCS 和 LOS 处于最低点,但我们的多变量回归分析并未显示临床结果的优势。 为了揭示超重患者是否有任何益处,未来的研究应该包括更多的临床方面,如腰围、臀腰比或脂肪量,以便比单独的 BMI 更好地反映代谢状态。 此外,该领域的机制研究有必要调查肥胖、免疫代谢和急性全身感染的潜在机制。

原始出处:

Borisov AN, Blum CA, Christ-Crain M, Ebrahimi F. No obesity paradox in patients with community-acquired pneumonia - secondary analysis of a randomized controlled trial.Nutr Diabetes. 2022 Mar 23;12(1):12. doi: 10.1038/s41387-022-00190-7

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    2022-04-04 玉兰儿

    受益

    0

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