Pulmonary pharmacology & therapeutics最新文献

The importance of biomarkers in the treatable-trait approach to chronic airway diseases. 生物标志物在慢性气道疾病治疗-特征方法中的重要性。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2026-02-02 DOI: 10.1016/j.pupt.2026.102410

Mario Cazzola, Mauro Maniscalco, Maria Gabriella Matera, Paola Rogliani

Chronic airway diseases (CAD), including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and cystic fibrosis, are increasingly recognized as heterogeneous and overlapping syndromes that share treatable biological and clinical characteristics. The Treatable Traits (TT) approach is a precision medicine framework that transcends diagnostic labels. It identifies and targets modifiable pulmonary, extrapulmonary, and behavioral characteristics in each patient. Biomarkers are central to this paradigm, translating latent endotypes into measurable traits that inform diagnosis, treatment selection, and longitudinal monitoring. This review synthesizes contemporary evidence on the role of biomarkers in implementing the TT model across CAD. Peripheral and airway biomarkers, including blood eosinophil count (BEC), fractional exhaled nitric oxide (FeNO), and sputum cell profiles, enable the identification of type 2 inflammatory traits and the prediction of corticosteroid or biologic responsiveness. Imaging and quantitative computed tomography metrics extend trait definition to structural and functional domains. Meanwhile, multi-omic and microbiome signatures reveal the molecular endotypes that underpin disease heterogeneity. Canonical examples include BEC predicting the benefit of inhaled corticosteroids in COPD and FeNO indicating steroid responsiveness in asthma. Additionally, emerging data suggest that rapid trait identification during acute exacerbations may facilitate targeted biologic therapy, extending precision care into acute management contexts. Integrating biomarker-guided assessment with individualized therapy redefines the management of CAD by offering a pathway toward biologically precise, dynamically adaptive care. Continued research should focus on standardizing biomarker thresholds, validating composite panels, and translating omic and imaging discoveries into routine clinical tools to optimize outcomes across the chronic airway disease spectrum.

慢性气道疾病（CAD），包括哮喘、慢性阻塞性肺疾病（COPD）、支气管扩张和囊性纤维化，越来越多地被认为是异质性和重叠综合征，具有可治疗的生物学和临床特征。可治疗特征（TT）方法是一种超越诊断标签的精准医学框架。它确定并针对每个患者可改变的肺、肺外和行为特征。生物标志物是这一范式的核心，将潜在的内源性转化为可测量的特征，为诊断、治疗选择和纵向监测提供信息。这篇综述综合了生物标志物在CAD实施TT模型中的作用的当代证据。外周和气道生物标志物，包括血嗜酸性粒细胞计数（BEC）、呼气一氧化氮分数（FeNO）和痰细胞谱，可以识别2型炎症特征并预测皮质类固醇或生物反应性。成像和定量计算机断层扫描度量将特征定义扩展到结构和功能领域。同时，多组学和微生物组特征揭示了支持疾病异质性的分子内型。典型的例子包括BEC预测COPD患者吸入皮质类固醇的益处和FeNO指示哮喘患者类固醇反应性。此外，新出现的数据表明，在急性加重期间快速识别特征可能有助于靶向生物治疗，将精确护理扩展到急性管理环境中。将生物标志物引导的评估与个体化治疗相结合，通过提供生物学上精确的、动态适应的护理途径，重新定义了CAD的管理。持续的研究应集中于标准化生物标志物阈值，验证复合面板，并将组学和成像发现转化为常规临床工具，以优化整个慢性气道疾病谱系的结果。

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引用次数: 0

Echocardiographic effects of dupilumab in patients with severe type 2 asthma dupilumab对重度2型哮喘患者超声心动图的影响。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2026-01-19 DOI: 10.1016/j.pupt.2026.102409

Corrado Pelaia , Giuseppe Armentaro , Chiara Lupia , Antonio Giacalone , Gianluca Ippolito , Daniela Pastore , Sofia Miceli , Carlo Alberto Pastura , Giandomenico Severini , Carlo Fuoco , Alberto Panza , Filippo Capilupi , Maria Rosangela Scarcelli , Giovanna Lucia Piazzetta , Emanuela Chiarella , Alessandro Vatrella , Girolamo Pelaia , Angela Sciacqua

Background

Severe asthma is characterized by impaired lung function and elevated cardiovascular risk. Type 2 inflammation, primarily mediated by IL-4 and IL-13, contributes to both airway and cardiac remodeling. Dupilumab, an IL-4Rα antagonist, has shown efficacy in improving respiratory outcomes; however, its impact on cardiac function remains insufficiently studied.

Objective

To assess the 12-month effects of dupilumab on echocardiographic parameters and evaluate its potential association with clinical remission in patients with severe type 2 asthma.

Methods

This single-centre observational study enrolled 24 patients with severe type 2 asthma receiving dupilumab. Echocardiographic assessments and lung function tests were conducted at baseline and after 12 months. Clinical remission was defined by meeting all of the following: zero exacerbations, zero OCS use, ACT score ≥20, and pre-bronchodilator FEV₁ ≥ 80 % predicted.

Results

Twelve-month dupilumab therapy led to significant improvements in both cardiac and respiratory parameters. LV-GLS improved from −17.00 % to −19.00 % and RV-GLS from −17.33 % to −19.11 % (both p < 0.0001). TAPSE and TAPSE/S-PAP ratio also increased significantly (p < 0.0001). Lung function showed notable gains in FEV₁ and FEF25-75, alongside reductions in residual volume and airway resistance. Clinical remission was achieved by 45.83 % of patients. Baseline LV-GLS emerged as a strong predictor of remission (AUC = 0.832), unlike RV-GLS (AUC = 0.545).

Conclusions

Dupilumab markedly improved cardiac and pulmonary function and may promote clinical remission. Baseline LV-GLS may serve as a predictive marker, supporting cardiovascular assessment in asthma management.

背景：重度哮喘以肺功能受损和心血管风险升高为特征。2型炎症主要由IL-4和IL-13介导，有助于气道和心脏重塑。IL-4Rα拮抗剂Dupilumab已显示出改善呼吸预后的功效；然而，其对心功能的影响仍未得到充分研究。目的：评估dupilumab对重度2型哮喘患者12个月超声心动图参数的影响，并评估其与临床缓解的潜在关联。方法：这项单中心观察性研究纳入了24例接受dupilumab治疗的严重2型哮喘患者。在基线和12个月后进行超声心动图评估和肺功能检查。临床缓解是通过满足以下所有条件来定义的：零恶化，零OCS使用，ACT评分≥20，支气管扩张剂前FEV1≥80%。结果：12个月的dupilumab治疗导致心脏和呼吸参数的显着改善。LV-GLS从-17.00%提高到-19.00%，RV-GLS从-17.33%提高到-19.11% （p < 0.0001）。TAPSE和TAPSE/S-PAP比值也显著升高（p < 0.0001）。肺功能显示FEV1和FEF25-75显著增加，同时残余体积和气道阻力减少。45.83%的患者达到临床缓解。与RV-GLS （AUC = 0.545）不同，基线LV-GLS是缓解的有力预测因子（AUC = 0.832）。结论：Dupilumab可显著改善心肺功能，并可能促进临床缓解。基线LV-GLS可作为预测指标，支持哮喘管理中的心血管评估。

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引用次数: 0

Targeting ELK-1 transcription factor and mechanosensitive MDM4 receptor using an HCN channel blocker alleviates lung fibrosis 使用HCN通道阻滞剂靶向ELK-1转录因子和机械敏感性MDM4受体减轻肺纤维化。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2026-01-19 DOI: 10.1016/j.pupt.2026.102408

Sahar A Helmy, Nesma A. Abd Elrazik

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease associated with poor prognosis and high mortality rate. It is a chronic irreversible lung disorder, mainly characterized by matrix stiffening. This study aims to investigate the therapeutic potential of targeting ELK-1 transcription factor and mechanosensitive MDM4 receptor using Ivabradine (IVA), an HCN channel blocker, in bleomycin (BLM)-induced pulmonary fibrosis (PF) rat model. Total, differential cell counts and LDH activity were assessed in bronchoalveolar lavage fluid. Pulmonary levels of MDA, GSH, IL-1β, α-SMA, COL1A1, ELK-1, MDM4, p-53, caspase-3, cleaved caspase-3, and CX3CL-1 were measured. Our study demonstrated that IVA induced a marked decrease in MDA and increase in GSH levels. Also, rats treated with IVA revealed a significant reduction in inflammation scores, LDH, IL-1β, α-SMA and COL1A1 levels. IVA-treated group showed a marked downregulation of MDM4 and ELK-1 along with significant upregulation of p-53, caspase-3, cleaved caspase-3, and CX3CL-1 levels when compared to BLM-induced PF group. In conclusion, these findings highlight the therapeutic potential of IVA in the treatment of pulmonary fibrosis. The antifibrotic effects of IVA in the bleomycin-induced rat model may be attributed to restoring redox balance, alleviation of aberrant inflammatory response, sensitizing lung myofibroblasts to apoptosis and promoting their clearance by macrophages.

特发性肺纤维化是一种进行性间质性肺疾病，预后差，死亡率高。它是一种慢性不可逆的肺部疾病，主要特征为基质硬化。本研究旨在探讨HCN通道阻滞剂伊伐布雷定（Ivabradine， IVA）靶向ELK-1转录因子和机械敏感MDM4受体在博来霉素（BLM）诱导的肺纤维化（PF）大鼠模型中的治疗潜力。测定支气管肺泡灌洗液中总细胞计数、差异细胞计数及LDH活性。测定肺组织中MDA、GSH、IL-1β、α-SMA、COL1A1、ELK-1、MDM4、p-53、caspase-3、cleaved caspase-3、CX3CL-1的水平。我们的研究表明，IVA诱导MDA显著降低，GSH水平显著升高。此外，IVA治疗的大鼠炎症评分、LDH、IL-1β、α-SMA和COL1A1水平均显著降低。与blm诱导的PF组相比，iva处理组MDM4和ELK-1水平明显下调，p-53、caspase-3、cleaved caspase-3和CX3CL-1水平显著上调。总之，这些发现突出了IVA治疗肺纤维化的治疗潜力。在博莱霉素诱导的大鼠模型中，IVA的抗纤维化作用可能是由于恢复氧化还原平衡，减轻异常炎症反应，使肺肌成纤维细胞对凋亡敏感，并促进巨噬细胞对其清除。

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引用次数: 0

Effectiveness of Mepolizumab and Dupilumab in patients with asthma-COPD overlap (ACO) compared to severe uncontrolled asthma (SUA): A retrospective observational cohort study Mepolizumab和Dupilumab在哮喘- copd重叠（ACO）患者中与严重未控制哮喘患者相比的有效性：一项回顾性观察队列研究

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2026-01-08 DOI: 10.1016/j.pupt.2025.102407

Belén Muñoz-Sánchez, Antonio León-Lloreda, David Carlos Echavarría, María Polonio-González, Juan Francisco Medina-Gallardo, Marta Ferrer-Galván, Auxiliadora Romero-Falcón, Javier Díez-Sierra, Francisco Javier Álvarez-Gutiérrez

Background

The coexistence of asthma and chronic obstructive pulmonary disease (COPD), known as asthma-COPD overlap (ACO), presents unique diagnostic and therapeutic challenges. Although biological therapies such as Mepolizumab and Dupilumab have transformed the management of severe eosinophilic asthma, their role in ACO remains poorly defined due to the exclusion of this phenotype from most clinical trials.

Methods

This retrospective observational study aimed to evaluate the real-world effectiveness of Mepolizumab and Dupilumab in patients with ACO compared to those with severe uncontrolled asthma (SUA). We included 212 patients treated in a specialized asthma unit between 2017 and 2024, all with at least 12 months of follow-up. Treatment response was assessed using clinical tools (EXACTO scale and SEPAR-REMAS criteria).

Results

Among Mepolizumab-treated patients (ACO n = 10; SUA n = 132), those with ACO had significantly lower baseline FEV₁ and lower rates of good/complete response (14.2 % vs. 60 %, p < 0.03) and clinical remission (0 % vs. 20.9 %). In the Dupilumab group (ACO n = 10; SUA n = 60), ACO patients showed lower baseline ACT scores and FEV₁, with reduced response rates (25 % vs. 55 %) and no clinical remission, although differences were not statistically significant. Despite limited power due to small ACO sample sizes, the magnitude of these differences suggests a clinically relevant reduction in biologic effectiveness in ACO.

Conclusion

These findings emphasize the urgent need for dedicated studies in ACO, a population with a high disease burden and limited treatment guidance. Individualized therapeutic approaches should be prioritized until robust clinical trial data becomes available.

背景：哮喘和慢性阻塞性肺疾病（COPD）的共存，被称为哮喘-COPD重叠（ACO），提出了独特的诊断和治疗挑战。尽管Mepolizumab和Dupilumab等生物疗法已经改变了严重嗜酸性粒细胞哮喘的治疗，但由于大多数临床试验排除了这种表型，它们在ACO中的作用仍然不明确。方法：这项回顾性观察性研究旨在评估Mepolizumab和Dupilumab在ACO患者与严重未控制哮喘（SUA）患者中的实际疗效。我们纳入了2017年至2024年间在专门哮喘病房接受治疗的212例患者，所有患者均进行了至少12个月的随访。使用临床工具（EXACTO量表和spe - remas标准）评估治疗效果。结果：在mepolizumab治疗的患者（ACO n = 10; SUA n = 132）中，ACO患者的基线FEV1显著降低，良好/完全缓解率（14.2% vs. 60%, p < 0.03）和临床缓解率（0% vs. 20.9%）较低。在Dupilumab组（ACO n = 10; SUA n = 60）， ACO患者表现出较低的基线ACT评分和FEV1，反应率降低（25% vs 55%），无临床缓解，尽管差异无统计学意义。尽管由于ACO样本量小，研究结果有限，但这些差异的大小表明ACO的生物学有效性在临床上有一定的降低。结论：这些发现强调了迫切需要对ACO进行专门研究，这是一个疾病负担高且治疗指导有限的人群。在获得可靠的临床试验数据之前，应优先考虑个体化治疗方法。

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引用次数: 0

Setting expectations with oral selexipag: an expert consensus-based approach on best practices to initiate, dose, titrate, and manage side effects (SEs) in patients with pulmonary arterial hypertension (PAH) 设定口服selexipag的期望：基于专家共识的最佳实践方法，以启动，剂量，滴定和管理肺动脉高压（PAH）患者的副作用（SEs）。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2026-01-08 DOI: 10.1016/j.pupt.2025.102406

Sheryl E. Wu , Jeremy A. Mazurek , Jennalyn D. Mayeux , Naomi G. Habib , Gurinderpal S. Doad , Christina K. Benninger , Michelle C. Cho , Paul M. Strachan , Richard M. Perry , Daisy Bridge , Medi A. Stone , Charlotte W. Oswald , Luis Val-Maranes , J. Wesley McConnell

Background

Oral selexipag, a prostacyclin receptor agonist, has been shown to delay pulmonary arterial hypertension (PAH) progression and reduce the risk of hospitalization for PAH. To ensure optimal patient outcomes with selexipag, careful treatment titration and expected side effect (SE) management are required. This study aimed to obtain expert consensus on the appropriate management of patients with PAH treated with selexipag.

Methods

United States (US) healthcare professionals (N = 17, 11 physicians; 5 nurse practitioners; 1 registered nurse) participated in this modified-Delphi panel comprising two online surveys and a consensus meeting. Consensus was defined as ≥80% panelists agreeing using a 9-point Likert scale.

Results

Panelists prescribed selexipag according to FDA label recommendations to patients with PAH. Panelists acknowledged considerations prompting adjustment in titration speed, agreeing that individual maximum dose is based on SE tolerability.

It was agreed that the duration of SEs is variable and patient-specific, however, SEs often become manageable over time. Panelists identified methods for managing SEs, agreeing this should be proactive. Panelists highlighted the importance of communicating with patients to set expectations, to enhance engagement and adherence.

Panelists agreed that treatment initiation, titration, and SE management should be individualized to suit each patient, with decision-making primarily based on patient characteristics and treatment preference.

Discussion

This panel provided expert opinions on the clinical use of and best practices for treatment titration and management of expected SEs for oral selexipag. Insights are valuable for developing standardized clinical guidelines and best practices, as well as ensuring personalized treatment to improve patient care.

背景：口服selexipag是一种前列环素受体激动剂，已被证明可以延缓肺动脉高压（PAH）的进展并降低PAH住院的风险。为了确保患者使用selexipag的最佳结果，需要仔细的治疗滴定和预期的副作用（SE）管理。本研究旨在就selexipag治疗PAH患者的适当管理获得专家共识。方法：美国医疗保健专业人员（N=17, 11名内科医生，5名执业护士，1名注册护士）参与了这个修改的德尔菲小组，包括两次在线调查和一次共识会议。共识被定义为≥80%的小组成员同意使用9分李克特量表。结果：小组成员根据FDA标签对PAH患者的推荐处方selexipag。小组成员承认需要考虑调整滴定速度，同意个人最大剂量是基于硒耐受性。人们一致认为，SEs的持续时间是可变的，因人而异，然而，随着时间的推移，SEs通常变得可控。小组成员确定了管理企业的方法，并同意这应该是积极主动的。小组成员强调了与患者沟通的重要性，以设定期望，提高参与度和依从性。小组成员一致认为，治疗开始、滴定和SE管理应个体化，以适应每位患者，决策主要基于患者特征和治疗偏好。讨论：该小组就口服selexipag的临床使用和治疗滴定的最佳实践以及预期SEs的管理提供了专家意见。这些见解对于制定标准化的临床指南和最佳实践，以及确保个性化治疗以改善患者护理非常有价值。

{"title":"Setting expectations with oral selexipag: an expert consensus-based approach on best practices to initiate, dose, titrate, and manage side effects (SEs) in patients with pulmonary arterial hypertension (PAH)","authors":"Sheryl E. Wu , Jeremy A. Mazurek , Jennalyn D. Mayeux , Naomi G. Habib , Gurinderpal S. Doad , Christina K. Benninger , Michelle C. Cho , Paul M. Strachan , Richard M. Perry , Daisy Bridge , Medi A. Stone , Charlotte W. Oswald , Luis Val-Maranes , J. Wesley McConnell","doi":"10.1016/j.pupt.2025.102406","DOIUrl":"10.1016/j.pupt.2025.102406","url":null,"abstract":"<div><h3>Background</h3><div>Oral selexipag, a prostacyclin receptor agonist, has been shown to delay pulmonary arterial hypertension (PAH) progression and reduce the risk of hospitalization for PAH. To ensure optimal patient outcomes with selexipag, careful treatment titration and expected side effect (SE) management are required. This study aimed to obtain expert consensus on the appropriate management of patients with PAH treated with selexipag.</div></div><div><h3>Methods</h3><div>United States (US) healthcare professionals (N = 17, 11 physicians; 5 nurse practitioners; 1 registered nurse) participated in this modified-Delphi panel comprising two online surveys and a consensus meeting. Consensus was defined as ≥80% panelists agreeing using a 9-point Likert scale.</div></div><div><h3>Results</h3><div>Panelists prescribed selexipag according to FDA label recommendations to patients with PAH. Panelists acknowledged considerations prompting adjustment in titration speed, agreeing that individual maximum dose is based on SE tolerability.</div><div>It was agreed that the duration of SEs is variable and patient-specific, however, SEs often become manageable over time. Panelists identified methods for managing SEs, agreeing this should be proactive. Panelists highlighted the importance of communicating with patients to set expectations, to enhance engagement and adherence.</div><div>Panelists agreed that treatment initiation, titration, and SE management should be individualized to suit each patient, with decision-making primarily based on patient characteristics and treatment preference.</div></div><div><h3>Discussion</h3><div>This panel provided expert opinions on the clinical use of and best practices for treatment titration and management of expected SEs for oral selexipag. Insights are valuable for developing standardized clinical guidelines and best practices, as well as ensuring personalized treatment to improve patient care.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"92 ","pages":"Article 102406"},"PeriodicalIF":2.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Artificial intelligence in the development of Rentosertib: A novel TNIK inhibitor for idiopathic pulmonary fibrosis – A letter to editor 人工智能在Rentosertib开发中的应用：一种治疗特发性肺纤维化的新型TNIK抑制剂-致编辑的一封信

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-12-30 DOI: 10.1016/j.pupt.2025.102405

Devipriya R. Namboothiri , Aswathy Sivanandan , Gladyston Netto , Midhun Mathew

引用次数: 0

Advances in novel therapeutics for idiopathic pulmonary fibrosis 特发性肺纤维化新疗法研究进展。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-10-20 DOI: 10.1016/j.pupt.2025.102396

Menghao Li , Bokun Chen , Xinhui Zhang, Tingting Zhuo, Xiuju Liu

IPF is a chronic, progressive interstitial lung disease characterized by irreversible lung scarring, leading to exertional dyspnea and a gradual decline in pulmonary function. Its pathogenesis involves multiple mechanisms, including chronic inflammation, aberrant cytokine signaling, and alveolar epithelial injury. Currently, IPF remains incurable, and treatment primarily aims to slow disease progression and improve survival. This paper systematically reviews recent clinical trials of novel IPF drug therapies that have demonstrated promising efficacy, aiming to inform future drug development.

IPF是一种慢性进行性间质性肺疾病，其特征是不可逆的肺瘢痕形成，导致用力呼吸困难和肺功能逐渐下降。其发病机制涉及多种机制，包括慢性炎症、细胞因子信号异常和肺泡上皮损伤。目前，IPF仍然无法治愈，治疗的主要目的是减缓疾病进展和提高生存率。本文系统回顾了近年来新型IPF药物治疗的临床试验，这些试验已经证明了有希望的疗效，旨在为未来的药物开发提供信息。

引用次数: 0

Drug-drug interactions in vanzacaftor–tezacaftor–deutivacaftor versus elexacaftor–tezacaftor-ivacaftor vanzacator - tezacator - detivacator与elexaftor - tezacator - ivacaftor的药物相互作用。

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-10-18 DOI: 10.1016/j.pupt.2025.102395

Esen Deniz Akman Ar, Nadir Yalcin

引用次数: 0

Targeting the immunometabolism interface: A novel strategy for IPF therapy 靶向免疫代谢界面：IPF治疗的新策略

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-09-10 DOI: 10.1016/j.pupt.2025.102394

Ganggang Li , Yuzhi Huo , Xiaochuan Pan , Nan Jia , Xuanyu Wu , Xinhui Wu , Fei Wang , Quanyu Du

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by aberrant tissue remodeling and excessive deposition of extracellular matrix components. Emerging evidence underscores the critical role of the immunometabolism in the pathogenesis of IPF, highlighting how dysregulated metabolic pathways modulate immune responses and contribute to fibrotic progression. Key molecular regulators such as PPARG (peroxisome proliferator activated receptor gamma) and SPP1 (secreted phosphoprotein 1), along with signaling pathways including mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and hypoxia-inducible factor 1-alpha (HIF-1α), orchestrate immune cell polarization, fibroblast activation, and extracellular matrix production. These insights reveal promising therapeutic targets at the intersection of metabolism and immunity. This review synthesizes current findings on immunometabolism interactions in IPF, emphasizing the potential of metabolic reprogramming and immune modulation as novel treatment strategies. Despite substantial advances, significant challenges persist in elucidating the precise mechanisms underlying these interactions and translating preclinical insights into effective clinical interventions. Future research should prioritize the identification of actionable metabolic biomarkers, refinement of molecular targets, and development of personalized therapeutic approaches. Addressing these gaps may pave the way for innovative therapies capable of halting or even reversing fibrosis, ultimately improving outcomes for patients with IPF.

特发性肺纤维化（IPF）是一种慢性进行性间质性肺疾病，其特征是异常组织重塑和细胞外基质成分过度沉积。新出现的证据强调了免疫代谢在IPF发病机制中的关键作用，强调了失调的代谢途径如何调节免疫反应并促进纤维化进展。关键的分子调节因子，如PPARG（过氧化物酶体增殖体激活受体γ）和SPP1（分泌磷酸化蛋白1），以及包括哺乳动物雷帕霉素靶点（mTOR）、amp激活蛋白激酶（AMPK）和缺氧诱导因子1- α (HIF-1α)在内的信号通路，协调免疫细胞极化、成纤维细胞激活和细胞外基质的产生。这些见解揭示了代谢和免疫交叉的有希望的治疗靶点。本文综述了IPF中免疫代谢相互作用的最新研究结果，强调了代谢重编程和免疫调节作为新的治疗策略的潜力。尽管取得了重大进展，但在阐明这些相互作用的确切机制以及将临床前见解转化为有效的临床干预措施方面，仍然存在重大挑战。未来的研究应优先确定可操作的代谢生物标志物，改进分子靶点，并开发个性化的治疗方法。解决这些空白可能为能够阻止甚至逆转纤维化的创新疗法铺平道路，最终改善IPF患者的预后。

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引用次数: 0

Exploring the role of β2- and β3-adrenergic receptors in cystic fibrosis 探讨β2-和β3肾上腺素能受体在囊性纤维化中的作用

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Pulmonary pharmacology & therapeutics

Pub Date : 2025-08-18 DOI: 10.1016/j.pupt.2025.102385

Alessandro Cannavo , Marika Comegna , Alice Castaldo , Caterina Vinciguerra , Anna Lauritano , Giulia Renata Franco , Giovanna Casoria , Graziamaria Corbi , Giuseppe Rengo , Giuseppe Castaldo

Cystic fibrosis (CF) is an autosomal recessive disorder that affects multiple organs, with clinical manifestations, disease progression, and response to therapy varying among individuals. This effect is mainly caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel.

In recent decades, other genes and their allelic variants, beyond CFTR mutations, have been proposed as genetic modifiers of CF phenotype. For instance, different polymorphic β2-adrenergic receptor (β2AR) polymorphic variants have been reported in CF individuals and appear to influence correct receptor function. β2AR belongs to the βAR family, which includes three subtypes: β1AR, β2AR, and β3AR. These receptors are crucial G protein-coupled receptors (GPCRs) expressed in various cell types and serve as key modulators of cAMP production, making their function particularly relevant in CF pathophysiology. β2AR is abundantly expressed in airway epithelial and smooth muscle cells, and studies revealed that it plays a crucial role in modulating CFTR activity and smooth muscle contractility through cAMP signaling. For these reasons, β2-agonists are widely used in clinical healthcare to treat patients with obstructive airway disorders, including CF.

Emerging evidence has also supported a role for β3AR, which is expressed in the canine and human bronchial epithelium and have been reported to enhance ciliary motility and regulate CFTR function, making it a potential therapeutic target in CF.

囊性纤维化（CF）是一种常染色体隐性遗传病，可影响多个器官，其临床表现、疾病进展和对治疗的反应因人而异。这种影响主要是由编码CF跨膜电导调节器（CFTR）的基因突变引起的，CFTR是camp调节的氯离子通道。近几十年来，除了CFTR突变外，其他基因及其等位变异也被认为是CF表型的遗传修饰因子。例如，在CF个体中已经报道了不同的多态β2-肾上腺素能受体（β2AR）多态变异，并且似乎影响了正确的受体功能。β2AR属于βAR家族，包括β1AR、β2AR和β3AR三个亚型。这些受体是关键的G蛋白偶联受体（gpcr），在各种细胞类型中表达，并作为cAMP产生的关键调节剂，使其功能与CF病理生理特别相关。β2AR在气道上皮细胞和平滑肌细胞中大量表达，研究发现它通过cAMP信号通路在调节CFTR活性和平滑肌收缩力中起着至关重要的作用。由于这些原因，β2激动剂被广泛应用于临床医疗保健，用于治疗包括CF在内的阻塞性气道疾病。新的证据也支持β3AR的作用，β3AR在犬和人的支气管上皮中表达，据报道可增强纤毛运动性并调节CFTR功能，使其成为CF的潜在治疗靶点。

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引用次数: 0