Cycloserine

As previously announced, low dose D-cycloserine has been associated with augmentation of the antidepressant and antisuicidal response achieved by Transcranial Magnetic Stimulation (TMS).NRx has amended its Investigational New Drug filing for NRX-101 (D-cycloserine/lurasidone) to include its use in association with TMS for the treatment of depression, including suicidal depression. This protocol will be available to patients both through a clinical trial and under NRx’s Expanded Access protocols.NRx currently has more than 25,000 manufactured investigational doses available WILMINGTON, Del., Dec. 03, 2025 (GLOBE NEWSWIRE) -- NRx Pharmaceuticals, Inc. (Nasdaq: NRXP), a clinical-stage biopharmaceutical company, today announced that it has amended its Investigational New Drug filing for NRX-101 (D-cycloserine/lurasidone) to include the use of NRX-101 in association with Transcranial Magnetic Stimulation (TMS) for the treatment of depression, including suicidal depression. In the third quarter, the Company identified a promising new indication for NRX-101 that potentially offers rapid path to commercialization for this Breakthrough Therapy-designated drug. Recent evidence suggests that NRX-101 may confer a significant added advantage to the clinical results of Transcranial Magnetic Stimulation. Cole and colleagues reported that patients randomized to D-cycloserine (DCS) vs. Placebo concurrent with TMS using a standard protocol experienced a greater than two-fold benefit in terms of reduction in symptoms of depression. Clinical response of 75% and remission of 40% was seen in the DCS-treated group.1 A substantial body of nonclinical literature has been published in subsequent years demonstrating that DCS at low doses exerts a neuroplasticity effect and causes dendritic sprouting in areas of the brain associated with depression. On November 4, 2025, Real World Data were presented in conjunction with use of a modern Theta Burst FDA-cleared TMS device and a one day TMS protocol, combined with a single administration of oral DCS. The authors reported 87% clinical response and 72% remission manifesting at 6 weeks after a single day of treatment on the Hamilton Depression Rating Scale with similar findings on other standard test measures.2 Nonclinical evidence suggests that D-cycloserine acts to augment neuroplasticity in association with TMS. Should the findings of these two clinical studies be replicated in registration trials conducted to current regulatory standards, the Company anticipates D-cycloserine or similar medicines will become standard of care therapy in association with TMS. The response rate from TMS with cycloserine (>80%) in these two studies compares favorably to the 30% success rate now reported in association with SSRI antidepressants, without the well known side effects of SSRI medications. In addition to containing D-cycloserine, NRX-101 contains a low dose of lurasidone, a medicine already approved for treatment of depression and known to have anti-hallucinatory properties. D-cycloserine by itself is well known to have a low, but measurable potential for inducing low-grade hallucinations, resulting in a labeled contraindication against the use of Seromycin® (D-cycloserine) in patients with depression. This contraindication originally led the founders of NRx to develop and patent the NRX-101 drug combination, which has now obtained composition of matter patent protection in all major jurisdictions. NRx believes that the clinical benefit demonstrated in these two published trials can be demonstrated in a well-controlled trials of approximately 120 participants. The Company is in partnership discussion with manufacturers of currently-marketed TMS devices to configure a joint clinical trial that will lead to drug registration and augmentation of FDA labeling of currently-approved TMS devices. Because TMS is already an approved and reimbursed therapy for patients with depression, the Company anticipates that such trials can be accomplished at modest expense. Given current trends, the Company expects that more than 1 million Americans per year may be treated with TMS by the year 2030, creating a substantial new potential market for NRX-101 not previously anticipated. As required by law for Breakthrough Therapy drugs such as NRX-101, the Company has published an Expanded Access policy for this medication. Treating physicians who believe that their patients might benefit from NRX-101 in association with TMS may contact the Company for further information. About NRx Pharmaceuticals, Inc.NRx Pharmaceuticals, Inc. (www.nrxpharma.com), is a clinical-stage biopharmaceutical company developing therapeutics based on its NMDA platform for the treatment of central nervous system disorders, specifically suicidal depression, chronic pain, and PTSD. The Company is developing NRX-100 (preservative-free intravenous ketamine) and NRX-101, (oral D-cycloserine/lurasidone). NRX-100 has been awarded Fast Track Designation for the treatment of Suicidal ideation in Depression, including Bipolar Depression. NRX-101 has been awarded Breakthrough Therapy Designation for the treatment of suicidal bipolar depression. NRx has recently re-filed an Abbreviated New Drug Application (ANDA), and initiated a New Drug Application filing for NRX-100 with an application for the Commissioner’s National Priority Voucher Program for the treatment of suicidal ideation in patients with depression, including bipolar depression. Notice Regarding Forward-Looking StatementsThe information contained herein includes forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as "may," "will," "should," "would," "expect," "plan," "believe," "intend," "look forward," and other similar expressions among others. These statements relate to future events or to the Company's future financial performance, and involve known and unknown risks, uncertainties and other factors that may cause the Company's actual results to be materially different from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. The Company has reported regulatory milestones as they have been achieved but has not predicted the outcome of any future regulatory determination. You should not place undue reliance on forward-looking statements since they involve known and unknown risks, uncertainties and other factors which are, in some cases, beyond the Company's control and which could, and likely will, materially affect actual results, levels of activity, performance or achievements. Any forward-looking statement reflects the Company's current views with respect to future events and is subject to these and other risks, including uncertainties and assumptions relating to the Company's operations, results of operations, growth strategy, and, among other things, liquidity. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's most recent Annual Report on Form 10-K and other filings with the Securities and Exchange Commission. Investors and security holders are urged to read these documents free of charge on the SEC's website at http://www.sec.gov. Except as may be required by applicable law, the Company assumes no obligation to publicly update or revise these forward-looking statements for any reason, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, whether as a result of new information, future events or otherwise. For further information: Matthew Duffy Brian KorbChief Business Officer, NRx Managing Partner, astr partners(646) 335-5923 (917) 653-5122mduffy@nrxpharma.com brian.korb@astrpartners.com 1 Cole J, et.al. Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022;79(12):1153–1161. doi:10.1001/jamapsychiatry.2022.32552 Vaughn, Donald & Marino, Brooke & Engelbertson, Alex & Dojnov, Aleksandra & Weiss, Nick & Vila-Rodriguez, Fidel & Nanos, Georgine & Downar, Jonathan. (2024). Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using Optimized, Neuroplastogen-Enhanced techniques in Depression (ONE-D). 10.21203/rs.3.rs-5679327/v1.

慢性阻塞性肺疾病(COPD)是一种以气道持续性炎症和气流受限为特征的常见疾病。近年来,肠肺轴在COPD急性加重期(AECOPD)中的免疫调控作用引起了广泛关注。肠道微生物群的失调、黏膜屏障功能的破坏及系统性炎症反应等因素,可能通过复杂的免疫机制加剧肺部炎症并加速疾病的进展。该文综述了肠肺轴在AECOPD中的免疫调控机制,旨在为AECOPD的预防和治疗提供新的思路和策略。 慢性阻塞性肺疾病(COPD)是一种常见的异质性肺部疾病,其特征是持续性、不可逆的气流受限,通常伴随慢性呼吸系统症状,如呼吸困难、咳嗽和咳痰。目前,COPD已成为全球第3大致死病因,其发病率在全球范围内呈上升趋势,根据世界卫生组织预测,在未来10年内,COPD将成为首要致死病因。2019年,全球约有4.55亿COPD病例,导致了390万例患者死亡。COPD是一个严重的公共卫生问题,并对经济造成了不利影响,2010年,全球COPD的经济负担为2.1万亿美元,预计到2030年将增至4.8万亿美元。在我国,这一现状尤为突出。据2018年《中国成人肺部健康研究》显示,我国40岁以上人群中COPD的患病率已达13.7%,远高于2007年报道的8.2%。这一数据表明,全国约有1亿人受到COPD的影响,其已成为我国最常见的慢性呼吸系统疾病之一。 COPD急性加重期(AECOPD)是一个常见且严重的临床事件。AECOPD指的是COPD患者在短时间内(通常为14 d内)出现呼吸困难、咳嗽或咳痰等症状显著加重,并可能伴有呼吸急促或心动过速。这种急性加重通常由呼吸道感染、空气污染或其他损伤气道的因素引发。AECOPD不仅是COPD患者的主要死亡原因之一,也是疾病管理中的重要挑战。研究表明,COPD患者每年平均发生0.5～3.5次急性加重,而每次急性加重都会进一步恶化患者的肺功能。此外,AECOPD的高发病率也导致了巨大的经济负担,特别是在住院治疗费用方面,AECOPD的治疗费用占据了COPD总体医疗支出的主要部分,并呈逐年上升的趋势。这些数据突显了加强AECOPD的预防和管理对于减少COPD相关死亡率和疾病负担的重要性。 COPD的异质性和复杂性使得AECOPD的诊断和管理充满挑战。目前缺乏AECOPD的特定生物标志物,但精确的诊断对于预防和减少急性加重的发生至关重要。近年来,随着对肠肺轴研究的深入,人们逐渐认识到肠道与肺部之间的相互作用对AECOPD的免疫调控机制具有重要影响。肠道微生物群的失调、黏膜屏障功能的破坏及系统性炎症反应等因素,可能通过复杂的免疫机制加剧肺部炎症并加速疾病的进展。本文综述了肠肺轴在AECOPD中的免疫调控机制,并重点探讨肠道免疫细胞的迁移、黏膜免疫屏障的破坏、肠道微环境的改变及迷走神经的炎症反射机制对COPD进展的影响。通过深入理解这些机制,有望为AECOPD的预防和治疗提供新的思路和策略。一、肠肺轴中的微生物及免疫学基础 越来越多的证据表明,肠道微生物失调是COPD病理生理学机制的重要组成部分。肠道和肺部在解剖上是不同的,但肺泡上皮、黏膜上皮均由原肠内胚层分化而成,肺与肠道所具备的黏膜结构,是黏膜免疫系统保护机体的主要组成部分,并且都存在着丰富的细菌群落。肠道和肺部中平衡的微生物群落对于调节免疫功能和维护宿主的整体健康至关重要,肠道微生物与肺部微生物之间的交互作用被称为“肠肺轴”。 肠道微生物群是人体中最丰富的微生物群,主要分布于口腔、食道、胃、小肠和结肠等部位。研究表明,在盲肠和近端结肠区域,微生物生物量最大,而小肠的微生物群尽管较少,但仍然发挥重要作用。不同区域的微生物组成各异,口腔和食道中以厚壁菌门、拟杆菌门、变形菌门、放线菌门和梭杆菌门为主;胃和十二指肠由于高酸性环境,仅有少量微生物存活,如链球菌科和肠杆菌科;小肠主要由变形菌门和乳酸菌门占据,而在末端回肠和结肠中,拟杆菌门、厚壁菌门、疣微菌门等占主导地位。在AECOPD患者中,肠道微生物群的失调与疾病进展密切相关。研究发现,AECOPD患者拟杆菌门和变形菌门丰度增加,而厚壁菌门和放线菌门丰度减少,并与肺功能下降及炎症标志物升高呈显著相关,且AECOPD患者肠道微生物群多样性和丰富度下降,但此现象未在健康个体和稳定期COPD患者中观察到。特定的微生物群可能通过影响炎症反应,参与COPD的恶化进程。 以往认为肺部是无菌的,直到在健康肺组织中检测到细菌DNA。与肠道相比,呼吸道是一个低生物量的环境,微生物密度从上呼吸道到下呼吸道逐渐减少。常见的细菌门包括厚壁菌门和拟杆菌门,普遍的属有普雷沃氏菌、链球菌和韦荣球菌。肺部微生物群可能通过微吸入从上呼吸道迁移,并受到宿主防御机制的影响,因此健康呼吸道微生物群更多是间歇性吸入的结果。在AECOPD中,呼吸道微生物组的一个共同特征是α-多样性降低及变形菌门的主导。在使用16S rRNA和宏基因组测序的研究中,AECOPD患者α-多样性显著低于稳定期COPD患者,并且α-多样性的下降与急性加重的频率及较高的死亡率相关。此外,微生物群组成的偏离与肺功能参数第1秒用力呼气容积和用力肺活量的下降有关。然而,呼吸道微生物组的重塑并非发生在所有AECOPD患者中,而是仅限于一部分患者,表明AECOPD的诱因存在多样性。变形菌门,尤其是卡他莫拉菌和流感嗜血杆菌的增加,与共生菌如韦荣球菌的减少密切相关。流感嗜血杆菌的存在通常伴随着其他共生菌的减少,而莫拉菌则独立引发加重。此外,韦荣球菌的减少与AECOPD患者的高死亡率密切相关。有研究表明,AECOPD患者呼吸道微生物组存在显著异质性,表明不同的病原体可能引发不同患者的急性加重。总体而言,变形菌门的优势及共生菌的减少与AECOPD的频率、严重程度及预后密切相关。 二、肠肺轴在COPD急性加重中的免疫调控机制 2.1 肠道免疫细胞迁移对COPD进展的双重作用 在AECOPD中,肠道免疫细胞通过肠肺轴迁移至肺部,对疾病的进展产生复杂影响。先天淋巴细胞(ILCs)作为黏膜免疫中的关键调节细胞,其在肺部的积累往往与疾病的加剧相关。ILC1通过分泌γ干扰素等促炎因子,增强了Th1型免疫反应,从而加剧气道炎症和肺部损伤。相似地,ILC3细胞通过分泌白细胞介素(IL)-22,进一步增强了呼吸道感染的易感性,尤其是当这些细胞从肠道迁移至肺部时,IL-22与ILC3的流入与呼吸道感染的加剧密切相关。有研究表明,ILC2在COPD小鼠模型中的活化可通过IL-25的诱导从肠道迁移至肺部,导致局部炎症加剧。在循环系统互连的小鼠试验中,IL-25的腹膜注射不仅激活了ILC2细胞,还促使这些细胞从1只小鼠的肠道迁移到2只小鼠的肺部,显著加剧了肺部炎症反应。这些研究结果揭示了ILCs在COPD中扮演着放大炎症反应的重要角色。 相比ILCs的促炎作用,单核细胞和树突状细胞(DCs)在肺部的迁移则展现出不同的调节机制,可能对疾病进展起到保护作用。短链脂肪酸等肠道微生物代谢产物通过诱导单核细胞的生成和成熟,促进这些细胞向肺部迁移。在肺部,单核细胞分化为DCs,能够通过诱导调节性T细胞(Treg),减少炎症反应,进而调控COPD中过度活跃的Th2反应。在荚膜嗜血杆菌感染的小鼠模型中,肿瘤坏死因子抑制剂能够诱导肠道中的CD103+CD11b+树突状细胞迁移至肺部,显著增加Treg细胞的数量,减少IL-17等促炎因子的分泌,从而降低肺部的炎症反应和组织损伤。这些结果表明,DCs在肠肺轴中的迁移对于减轻COPD患者的肺部炎症具有重要的调节作用。 2.2 黏膜免疫障碍在AECOPD中的作用 肠道与气道黏膜在结构与功能上存在显著相似性,均由内胚层发育而来,并形成了共同的黏膜免疫系统。肠道黏膜的微绒毛和气道黏膜的纤毛上皮不仅在物理屏障功能上相似,还通过相似的免疫反应调节全身免疫平衡。呼吸道和胃肠道均含有共同的黏膜相关淋巴组织,这些组织有助于抵御外界病原体的入侵,并通过“共同黏膜免疫”系统维持局部和全身的免疫协调。例如,肠道微生物群能够通过诱导B细胞产生免疫球蛋白A,这种抗体可通过血液和淋巴系统传递至气道黏膜,增强肺部的免疫防御功能,减少呼吸道感染的风险。 在AECOPD中,黏膜屏障功能障碍被认为是加重疾病进展的关键因素。吸烟不仅是COPD的重要致病因素之一,还会显著破坏气道和肠道的黏膜屏障功能,增加其通透性。长期暴露于烟草烟雾会导致气道上皮损伤、氧化应激反应增强,并减少紧密连接蛋白的表达。这种屏障功能的破坏不仅仅限于气道,肠道的屏障功能也同样会受到损伤,可导致肠道微生物群失调和促炎因子的过度释放。氧化应激的增加不仅导致气道上皮细胞受损,还通过减少肠道血流量引起肠道缺氧,从而加重肠道屏障功能障碍,增加肠道内毒素[如脂多糖(LPS)]的血液渗透,进而加剧全身炎症反应。 2.3 肠道微环境的改变对AECOPD的影响 肠道微环境的改变通过多种细胞因子和炎症介质调控肺部免疫反应,对COPD患者的病情加重有着重要的影响。肠道微生物群的失衡会导致促炎细胞因子[如IL-6、肿瘤坏死因子α(TNF-α)、IL-17]水平的上升,这些细胞因子通过全身循环系统到达肺部,加剧气道炎症。有研究显示,IL-6是一种重要的促炎性细胞因子,其在AECOPD患者中显著升高,并与气道中性粒细胞的浸润相关联,进一步导致气道重构和肺功能的恶化。IL-17在肠道Th17细胞的活化下显著增加,并通过肠道屏障进入血液,最终作用于肺部。Th17细胞的上调导致了气道炎症的加剧,尤其是中性粒细胞的过度活化。此外,肠道失调导致的LPS水平升高,也被证明是COPD患者全身性炎症的重要驱动因素,LPS通过肠道屏障进入循环系统,激活肺部巨噬细胞和其他免疫细胞,释放更多的促炎性细胞因子,进一步恶化肺部炎症。 NLRP3炎性小体在肠肺轴中的作用是通过识别多种免疫信号和促炎性因子,协调肠道和肺部的免疫反应。在COPD患者中,NLRP3炎性小体不仅在肺部免疫反应中发挥核心作用,还通过与肠道微生物群的相互作用调控全身性炎症反应。NLRP3炎性小体由NOD样受体蛋白3(NLRP3)组成,通常被多种病原体相关分子模式或损伤相关分子模式激活。在COPD患者中,吸烟及环境污染物等刺激物会导致活性氧(ROS)的生成,ROS可直接激活NLRP3炎性小体,并促使其释放促炎细胞因子(如IL-1β、IL-18),加剧气道炎症反应。肠道微环境的改变,例如细菌内毒素的释放,也能够通过系统循环进入肺部,其通过与Toll样受体和其他模式识别受体的相互作用,激活肠道巨噬细胞和树突状细胞,从而进一步推动NLRP3炎性小体的活化。在AECOPD患者中,NLRP3、半胱氨酸蛋白酶-1、IL-1β、IL-18等基因的mRNA水平在支气管组织和外周血单核细胞中显著升高,表明NLRP3炎性小体的激活与急性加重的气道炎症密切相关。 2.4 肠肺轴与神经免疫调控机制 迷走神经通过其炎症反射机制在调节免疫稳态中发挥关键作用。炎症反射是由迷走神经感知和调控的一个复杂过程,主要通过迷走神经的传入纤维感知外周炎症信号,并将信号传递至延髓的孤束核。在孤束核中,这些信号被整合后,通过迷走神经的传出纤维启动抗炎效应。此过程的核心机制是胆碱能抗炎途径,迷走神经末梢释放的乙酰胆碱能够与巨噬细胞上的α7烟碱型乙酰胆碱受体结合,抑制促炎细胞因子(如TNF-α、IL-6)的过度释放,同时维持抗炎细胞因子的平衡。在AECOPD患者中,炎症反射的有效性直接影响疾病的进程。在急性加重期间,全身性炎症标志物的升高,如C反应蛋白和IL,可能通过迷走神经的传入通路被检测到。迷走神经通过调节系统性炎症反应,限制过度免疫激活,从而减少肺部的炎症损伤。此外,迷走神经还能够通过调控肠道微生物群的组成,影响其代谢产物(如短链脂肪酸)的产生,这些代谢产物可进一步通过血液循环和神经通路作用于肺部,调控局部的免疫细胞活性。这一机制的失调可能导致AECOPD患者的炎症反应失控。迷走神经活性的降低会削弱其抗炎功能,从而使促炎细胞因子的释放失去抑制,导致肺部和全身炎症的加剧。三、基于肠肺轴免疫调控机制的AECOPD治疗策略 目前,针对AECOPD的免疫调控治疗主要集中在控制炎症反应。传统的治疗方法包括使用皮质类固醇、磷酸二酯酶-4抑制剂和靶向细胞因子(如IL-1、IL-18)的单克隆抗体。然而,许多抗炎治疗未能在AECOPD患者中显著改善肺功能,这可能是因为这些治疗未能全面考虑肠肺轴的相互作用。因此,目前的免疫调控策略需要进一步优化,以更有效地调节肠肺轴中的免疫反应。 3.1 饮食调节在肠肺轴免疫调控中的作用 饮食调节可以通过促进肠道微生物群健康及其代谢功能改善肠肺轴功能,从而在AECOPD中发挥治疗作用。益生元和膳食纤维是重要的调节因素,可通过促进短链脂肪酸的生成,增强调节性T细胞的活性,减少促炎因子的释放,维持全身免疫稳态。此外,膳食中富含ω-3多不饱和脂肪酸的食物,如鱼油,能够通过其抗炎特性保护肠道屏障功能,同时缓解气道炎症,改善AECOPD患者的肺功能。多酚类化合物,如茶多酚和蓝莓中的花青素,则通过抗氧化和促进有益菌增殖的作用,进一步优化肠道微环境,减轻全身及肺部的炎症反应。这些饮食干预措施在增强肠道与肺部免疫调控中的协同作用,为AECOPD的治疗提供了新的可能性。 3.2 中药干预在AECOPD中的治疗潜力 中药以其多靶点和整体调节的特点,在AECOPD的肠肺轴调控中展现出巨大潜力,尤其是通过改善肠道微生物群和免疫功能实现治疗效果。中药多糖(如石斛多糖和茯苓多糖)可作为益生元,改善肠道微生物群的组成,增加短链脂肪酸的生成,从而减轻全身炎症反应。黄甘方等中药复方则通过增强肠道屏障功能、抑制促炎因子生成,显著改善肠道微环境并减轻肺部炎症。此外,富含黄酮类和多酚类成分的中药提取物(如槲皮素和丹参)通过抗氧化机制减少氧化应激对肠道和肺部的损害,从而抑制肠肺轴相关炎症。结合这些多样化的中药干预手段,不仅可以改善AECOPD患者的全身免疫状态,还为个性化治疗提供了更多选择。 3.3 NLRP3炎性小体靶向治疗在AECOPD中的挑战与前景 NLRP3炎性小体的靶向治疗也是一个潜在方向,尤其是通过开发能够调节炎性小体活化的药物,可能有助于降低AECOPD患者的炎症反应。但是,目前靶向NLRP3或其下游效应子的治疗效果有限。例如,抗IL-1β单克隆抗体canakinumab在中度至重度COPD患者中的临床试验未显示显著改善肺功能的效果。同样,其他靶向NLRP3炎性小体的疗法(如IL-18抑制剂和P2X7受体拮抗剂)也未显示出显著的临床获益。这些研究结果表明,尽管NLRP3炎性小体在AECOPD的发病机制中起重要作用,但其调控的复杂性及潜在的治疗靶点仍需进一步研究。四、小结与展望 肠肺轴在COPD急性加重中的免疫调控作用已被广泛认可,其通过肠道微生物群、免疫细胞迁移及炎症介质的双向调节,直接影响疾病的进展。肠道微环境的改变能够加剧全身性炎症,并通过细胞因子和炎症介质进一步加重肺部的免疫反应。在AECOPD的病理生理过程中,免疫细胞通过肠肺轴迁移至肺部,直接加剧了气道炎症和气道重塑。此外,NLRP3炎性小体的激活在COPD的急性加重中起到了核心作用,其通过促炎细胞因子的释放,导致局部和全身的炎症反应增强。迷走神经通过感知炎症信号并调节免疫系统,抑制过度的炎症反应,从而在保持免疫稳态中起到至关重要的作用。调节肠肺轴的免疫反应不仅对疾病的进展具有决定性作用,还为临床管理COPD急性加重提供了新的干预途径。 理解肠肺轴的免疫机制为开发新型治疗方法提供了重要基础。现有的AECOPD治疗方法,虽然能够在一定程度上控制症状并减轻炎症,但并未充分关注肠肺轴在免疫调控中的核心作用。因此,未来的治疗策略应更加重视通过调节肠道微生物群或靶向肠肺轴的免疫机制来减少全身性和局部的炎症反应。未来的研究方向应聚焦于大规模临床试验,探索调节肠肺轴的免疫治疗在AECOPD中的实际效果。同时,应进一步研究肠道微生物群在AECOPD病程中的具体作用机制,以便开发更具靶向性的治疗方法,这将对改善患者的生活质量和预防急性加重具有重要临床意义。     贾晓周，毕业于河北医科大学，中西医结合、临床医学双学历，后于辽宁中医药大学附属医院进修，曾就职于辽宁航空航天附属医院，曾受聘于北京至道中医研究院任副院长，重庆慢性呼吸系统病防治中心会诊专家、国家生活方式医学领域专家顾问，传统武式太极拳精英传承人，世界医疗健康管理协会会员，长年从事创新性医药领域及临床诊疗技术应用学术研究工作。    目前主要从事呼吸领域相关疾病临床诊疗进展、儿童生长发育及慢性骨病中西医联合诊疗领域科研工作，国内外先进特色诊疗技术挖掘及整理。曾参加中国咳嗽诊疗指南万里行巡讲，作为“气道炎症专场”特邀专家，2018年发起“中国基层咳嗽诊疗指南万里行”活动，2020年发起“中国基层儿童咳喘病全国巡讲”活动，2021年发起“中国基层慢病规范化诊治”全国巡讲活动，2023年新冠病毒感染及其并发症的临床规范化诊治方案更新，推进基层《新冠感染咳嗽专科门诊》、《呼吸慢病专科门诊》等专科门诊机构的建立，2025年进行关于儿童生长发育及慢性骨病中西医临床最新诊疗模式进展探究，深入研究“疏木六君子汤”“清肺汤等”在呼吸及相关肿瘤领域的应用进展，进一步提升最新生物制剂相关特效雾化治疗方案相关难治性、难愈性呼吸系统疾病治疗，推进基层“气道炎症计”呼出气一氧化氮精准化气道炎症水平测定及指导相关呼吸系统疾病中西医结合治疗方案。立足于目前临床最新医学进展领域：阶梯式治疗方案、呼吸免疫治疗方案、上下气道同治治疗方案、精准化诊治治疗方案、常见病快速评估等及针对中西医结合临床一线指南推荐用药等做全面总结研究，以帮助更多的同仁完成科学、精准、规范的诊治，开展更多医疗领域学术交流会议，推进常见多发病的预防、科学的健康管理新理念。