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MOLECULAR GATED STRATEGY FOR RAPID DETECTION OF KLEBSIELLA PNEUMONIAE AND CARBAPENEM-RESISTANT GENES IN RESPIRATORY AND HOSPITAL-ACQUIRED INFECTIONS [COMUNICACIÓN PREMIADA] 呼吸道感染和医院获得性感染中肺炎克雷伯菌和碳青霉烯耐药基因快速检测的分子门控策略[comunicaciÓn premiada]
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100540
Alba López-Palacios , Andrea Torres-Mesado , María Ángeles Tormo-Mas , Elena Aznar , Ramón Martínez-Máñez

Introduction

Klebsiella pneumoniae is a major pathogen in healthcare-associated infections. This bacterium plays a critical role in severe respiratory infections such as hospital-acquired pneumonia, which can have mortality rates exceeding 50%, especially when multidrug-resistant strains are involved. K. pneumoniae increasing resistance to antibiotics, including carbapenems, makes it one of the most pressing pathogens in clinical environments. Rapid and accurate identification of K. pneumoniae is crucial for effective treatment. As current diagnostic methods based on culture and phenotypic assays can take up to 48 hours, new tools for faster diagnosis are urgently needed.
This work focuses on two main objectives: developing biosensors for the detection and identification of i) K. pneumoniae and ii) resistance genes encoding carbapenemases.

Methods

To achieve this, we have applied molecular gated systems consisting of nanoporous anodic alumina (NAA) films loaded with rhodamine B (RhB), a fluorescent dye and capped with specific recognition motifs. In a first example, after surface functionalization, these supports are capped with a peptide that specifically binds to K. pneumoniae lipopolysaccharide (LPS). This peptide is anchored to the materials surface by a short oligonucleotide acting as the molecular gate that blocks the pores. Upon recognition of the pathogen, the molecular gates open, releasing RhB and producing a fluorescence signal. Additionally, a separate detection system was designed to identify carbapenem-resistance genes. Therefore, the integration of both biosensors into a multiplex system would allow simultaneous identification of K. pneumoniae and its resistance associated with the selected gene.

Results

Both systems demonstrated strong responses, high sensitivity and selectivity in buffered media containing either LPS or the bla-OXA-48-like gene target. Validation in bacterial cultures further confirmed robust performance. Current efforts focus on validating both biosensors in patient-derived samples and developing a multiplexed system capable of simultaneously identifying K. pneumoniae and determining its resistance profile.

Conclusions

These results highlight this technology's potential to detect K. pneumoniae and its resistance providing a powerful clinical tool for guiding appropriate antimicrobial therapy.
肺炎克雷伯菌是卫生保健相关感染的主要病原体。这种细菌在医院获得性肺炎等严重呼吸道感染中起着关键作用,其死亡率可超过50%,特别是涉及耐多药菌株时。肺炎克雷伯菌对包括碳青霉烯类在内的抗生素的耐药性日益增强,使其成为临床环境中最紧迫的病原体之一。快速准确地鉴定肺炎克雷伯菌对有效治疗至关重要。由于目前基于培养和表型分析的诊断方法可能需要长达48小时,因此迫切需要更快诊断的新工具。这项工作主要集中在两个目标上:开发用于检测和鉴定i)肺炎克雷伯菌和ii)编码碳青霉烯酶的抗性基因的生物传感器。为了实现这一目标,我们应用了由纳米多孔阳极氧化铝(NAA)薄膜组成的分子门控系统,NAA薄膜负载罗丹明B (RhB),一种荧光染料,并覆盖特定的识别基元。在第一个例子中,在表面功能化之后,这些支持物被一种特异性结合肺炎克雷伯菌脂多糖(LPS)的肽覆盖。这种肽通过一个短的寡核苷酸固定在材料表面,作为阻断孔隙的分子门。一旦识别病原体,分子门打开,释放RhB并产生荧光信号。此外,设计了一个单独的检测系统来鉴定碳青霉烯抗性基因。因此,将这两种生物传感器整合到一个多重系统中,将允许同时鉴定肺炎克雷伯菌及其与所选基因相关的耐药性。结果两种系统在含有LPS或bla- oxa -48样靶基因的缓冲介质中均表现出强反应、高灵敏度和选择性。在细菌培养中的验证进一步证实了稳健的性能。目前的工作重点是验证患者来源样本中的生物传感器,并开发一种能够同时识别肺炎克雷伯菌并确定其耐药谱的多路系统。结论该技术具有检测肺炎克雷伯菌及其耐药性的潜力,为指导合理的抗菌药物治疗提供了有力的临床工具。
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引用次数: 0
FUNCTIONAL KIR2 AND KATP CHANNELS IN HUMAN PULMONARY VASCULAR SMOOTH MUSCLE AND ENDOTHELIUM MODULATE ARTERIAL TONE 人肺血管平滑肌和内皮细胞中kir2和katp通道的功能调节动脉张力
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100560
Bianca Barreira , Daniel Morales-Cano , Laura Moreno , Beatriz de Olaiz , Rui Adão , Ángel Cogolludo , Francisco Pérez-Vizcaíno , María Sancho

Introduction

The resting membrane potential (VM) of vascular cells is a major determinant of arterial tone, integrating the activity of multiple ionic conductances. In human pulmonary arteries, however, the specific K+ channels that establish VM in smooth muscle and endothelial cells remain poorly characterized.

Methods

Freshly isolated human pulmonary arterial smooth muscle (PASMCs) and endothelial cells (PAECs) were studied using whole-cell patch-clamp electrophysiology, immunofluorescence, and wire myography. Kir2 currents were assessed using Ba2+, whereas KATP activity was evaluated with the synthetic activator pinacidil and the specific blockers glibenclamide and PNU-37883A. Concentration–response effects were examined in intact pulmonary artery rings.

Results

Ba2+-sensitive, strongly inwardly rectifying currents were identified in both PASMCs and PAECs, consistent with Kir2.1/2.2 expression. In intact arteries, BaCl2 induced concentration-dependent contractions and attenuated acetylcholine-evoked, endothelium-dependent relaxation, indicating a tonic vasodilatory influence of Kir2 channels. Pinacidil activated glibenclamide or PNU-sensitive KATP currents and produced vasodilation in isolated arteries, effects that were bunted by glibenclamide or PNU-37883A pretreatment. Robust Kir6.1 and SUR2 immunoreactivity further supported the presence of functional KATP channels.

Conclusions

This study provides the first electrophysiological evidence for native Kir2 and KATP channels in human pulmonary vascular cells and demonstrates their contribution to arterial tone, highlighting these channels as potential therapeutic targets in pulmonary vascular disease.
血管细胞的静息膜电位(VM)是动脉张力的主要决定因素,它综合了多个离子电导的活性。然而,在人肺动脉中,在平滑肌和内皮细胞中建立VM的特定K+通道的特征仍然很差。方法采用全细胞膜片钳电生理、免疫荧光和钢丝肌图对新鲜分离的人肺动脉平滑肌(PASMCs)和内皮细胞(PAECs)进行研究。使用Ba2+评估Kir2电流,而使用合成激活剂pinacidil和特异性阻滞剂格列本脲和PNU-37883A评估KATP活性。在完整的肺动脉环中检测浓度-反应效应。结果PASMCs和PAECs中均检测到ba2 +敏感、向内强整流电流,与Kir2.1/2.2表达一致。在完整动脉中,BaCl2诱导浓度依赖性收缩和乙酰胆碱诱发的内皮依赖性松弛减弱,表明Kir2通道具有强直性血管舒张作用。Pinacidil激活格列本脲或pnu敏感的KATP电流,并在离体动脉中产生血管舒张,这种效应被格列本脲或PNU-37883A预处理所抑制。强大的Kir6.1和SUR2免疫反应性进一步支持功能性KATP通道的存在。结论本研究首次提供了人体肺血管细胞中天然Kir2和KATP通道的电生理证据,并证明了它们对动脉张力的贡献,强调了这些通道是肺血管疾病的潜在治疗靶点。
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引用次数: 0
THE SPECIFIC ROLE OF MAPK13 ISOFORM IN AIRWAY BARRIER DYSFUNCTION AND MUCIN REGULATION mapk13异构体在气道屏障功能障碍和粘蛋白调节中的特殊作用
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100561
Rubén Fernández-Santamaría , Cristina Rosales-Ariza , Lucia Cremades-Jimeno , Jorge Parrón , Eva Batanero , Blanca Cárdaba

Introduction

Asthma is a complex chronic disease that affects the airways. Despite significant advances in recent years, there is still a lack of information, mainly related to the specific molecular mechanisms involved. We have previously demonstrated the implication of four specific proteins: TLR4, STAT1, AKT1 and MAPK13 in asthma. In this study, we aim to study the specific role of the MAPK13 isoform in the underlying mechanisms of asthma.

Methods

The human epithelial cell line CALU-3 was cultured at an air-liquid interface. MAPK13 was specifically silenced using siRNA (siRNA+MAPK13) or without it (siRNA-MAPK13). MAPK13 expression was assessed by RT-qPCR, western blot (WB) and immunofluorescence (IF). siRNA+MAPK13 and siRNA-MAPK13 were stimulated on day 3 with different inflammatory stimuli (IL-5, IL-9, IL-13, LPS and TNFα). Epithelial integrity was measured by transepithelial electrical resistance (TEER) on day 0, 3 and 6, and occludin expression by IF on day 6. Mucus production was measured by RT-qPCR and ELISA.

Results

siRNA+MAPK13 cells showed significantly lower MAPK13 expression compared to siRNA-MAPK13 cells by RT-qPCR, IF and WB. MAPK13 expression increased after stimulation with IL-13 and LPS, mainly in siRNA-MAPK13. MAPK13 silencing has a significant impact on epithelial barrier integrity, with lower TEER results compared to non-silenced cells. This is also consistent with reduced occludin expression. Stimulation with IL-13 significantly reduced TEER values in both cells, while IL-5, IL-9 and TNFα did not affect epithelial barrier integrity, with only LPS capable of increasing TEER values. Mucin production appears to increase when MAPK13 is silenced, but the different stimuli increased its production in siRNA-MAPK13, remaining at low levels when MAPK13 was silenced.

Conclusions

The specific isoform MAPK13 appears to be significantly involved in airway barrier integrity and mucus production, mainly
哮喘是一种影响呼吸道的复杂慢性疾病。尽管近年来取得了重大进展,但仍然缺乏信息,主要涉及具体的分子机制。我们之前已经证明了四种特定蛋白:TLR4、STAT1、AKT1和MAPK13在哮喘中的意义。在这项研究中,我们的目的是研究MAPK13亚型在哮喘的潜在机制中的具体作用。方法采用气液界面培养人上皮细胞系CALU-3。MAPK13通过siRNA (siRNA+MAPK13)或不使用siRNA (siRNA-MAPK13)特异性沉默。采用RT-qPCR、western blot (WB)和免疫荧光(IF)检测MAPK13的表达。在第3天,siRNA+MAPK13和siRNA-MAPK13分别受到不同炎症刺激(IL-5、IL-9、IL-13、LPS和TNFα)的刺激。在第0、3和6天通过上皮电阻值(TEER)检测上皮完整性,在第6天通过IF检测occludin表达。采用RT-qPCR和酶联免疫吸附法检测粘液分泌量。结果通过RT-qPCR、IF和WB检测,sirna +MAPK13细胞的MAPK13表达明显低于siRNA-MAPK13细胞。IL-13和LPS刺激后,MAPK13的表达增加,主要表现在siRNA-MAPK13上。MAPK13沉默对上皮屏障完整性有显著影响,与非沉默细胞相比,TEER结果更低。这也与occludin表达减少一致。IL-13刺激显著降低了两种细胞的TEER值,而IL-5、IL-9和tnf - α不影响上皮屏障的完整性,只有LPS能够增加TEER值。当MAPK13被沉默时,粘蛋白的产生似乎增加,但不同的刺激增加了siRNA-MAPK13的产生,当MAPK13被沉默时,粘蛋白的产生保持在低水平。结论特异性异构体MAPK13似乎主要参与气道屏障完整性和粘液产生
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引用次数: 0
FUNCTIONALISED NANOPARTICLES LOADED WITH DRUGS: A NEW TOOL AGAINST PNEUMOCOCCAL GROWTH AND BIOFILM FORMATION 装载药物的功能化纳米颗粒:对抗肺炎球菌生长和生物膜形成的新工具
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100565
Mirella Llamosí , Pilar Membrillo , Julio Sempere , Mirian Domenech , Jose Yuste , María Rosa Aguilar , Luis García

Introduction

Streptococcus pneumoniae is one of the deadliest bacterial pathogens with high clinical significance in invasive pneumococcal disease (IPD). Vaccines have reduced the burden of disease caused by S. pneumoniae, but the increase in antibiotic-resistant strains and serotypes not covered by vaccines is concerning. Therefore, the development of new therapies to prevent and treat this disease is crucial.

Methods

The efficacy of nanoparticles developed by the Rocasolano Institute of Physical Chemistry (CSIC) was evaluated. These nanoparticles were functionalised with vitamin E and loaded with three hydrophobic drugs—a macrolide, an antihistamine, and a glucocorticoid—and combinations thereof, both in biofilm and in planktonic culture of S. pneumoniae. Three strains of pneumococcus were used for this purpose: a reference strain of serotype 19F, an isogenic mutant of serotype 19A, and a multidrug-resistant clinical strain also of this serotype.

Results

It was observed that, in the reference strain, both empty nanoparticles and combinations with drugs inhibited growth at concentrations of 1.25% or 2.5%. Even when using nanoparticles with combinations of macrolide and the other two drugs, a decrease to 0.7% and 1.25% was observed. In the case of the isogenic mutant, this effect was also observed in viability but at higher concentrations, and with the multidrug-resistant strain, a decrease in growth was observed with the nanoparticle loaded with the antihistamine and the nanoparticle loaded with the combination of this together with the macrolide. In the inhibition of the biofilm of the reference strain, it was observed that the three loaded nanoparticles inhibit the biofilm at concentrations higher than the minimum inhibitory concentration, and in the case of the combinations, the macrolide nanoparticle with the glucocorticoid and the triple combination of the three drugs in the nanoparticle show an effect. However, in the treatment of biofilm, greater disintegration is observed when empty nanoparticles are used rather than loaded ones, which differs from what occurs in inhibition.

Conclusions

Nanoparticles loaded with different types of drugs and combinations thereof show a notable effect in inhibiting the growth of pneumococcus and even in inhibiting the biofilm of this pathogen. The nanoparticle loaded with the antihistamine has the greatest growth-inhibiting effect, and in the case of biofilm inhibition, the three loaded nanoparticles, as well as the combination of macrolide with glucocorticoid and the triple combination, show the greatest effect. These strategies may be presented as alternatives for the prevention and treatment of this disease.
肺炎链球菌是侵袭性肺炎球菌病(IPD)中最致命的细菌病原体之一,具有重要的临床意义。疫苗减轻了肺炎链球菌引起的疾病负担,但疫苗未涵盖的抗生素耐药菌株和血清型的增加令人担忧。因此,开发新的疗法来预防和治疗这种疾病是至关重要的。方法对罗卡索拉诺物理化学研究所(CSIC)研制的纳米颗粒进行药效评价。在生物膜和肺炎链球菌浮游培养中,这些纳米颗粒被维生素E功能化,并装载了三种疏水药物——大环内酯、抗组胺药和糖皮质激素及其组合。为此目的使用了三株肺炎球菌:血清型19F的参考菌株,血清型19A的等基因突变株,以及该血清型的多药耐药临床菌株。结果在对照菌株中,在1.25%和2.5%的浓度下,空纳米颗粒和药物联合对细菌生长均有抑制作用。即使使用纳米颗粒与大环内酯和其他两种药物的组合,也下降到0.7%和1.25%。在等基因突变体的情况下,这种影响在生存能力中也被观察到,但在更高的浓度下,对于多重耐药菌株,纳米颗粒装载抗组胺剂和纳米颗粒与大环内酯的组合,可以观察到生长的减少。在对参考菌株生物膜的抑制中,观察到三种负载的纳米颗粒对生物膜的抑制浓度均高于最低抑制浓度,并且在联合的情况下,大环内酯类纳米颗粒与糖皮质激素以及纳米颗粒中三种药物的三联用药均有效果。然而,在生物膜的处理中,当使用空纳米颗粒而不是负载纳米颗粒时,观察到更大的分解,这与抑制中发生的情况不同。结论纳米颗粒负载不同类型的药物及其组合对抑制肺炎球菌生长甚至抑制该病原体的生物膜均有显著作用。负载抗组胺的纳米颗粒具有最大的生长抑制作用,在生物膜抑制情况下,负载三种纳米颗粒以及大环内酯与糖皮质激素的联合和三联用药效果最大。这些策略可以作为预防和治疗这种疾病的备选方案。
{"title":"FUNCTIONALISED NANOPARTICLES LOADED WITH DRUGS: A NEW TOOL AGAINST PNEUMOCOCCAL GROWTH AND BIOFILM FORMATION","authors":"Mirella Llamosí ,&nbsp;Pilar Membrillo ,&nbsp;Julio Sempere ,&nbsp;Mirian Domenech ,&nbsp;Jose Yuste ,&nbsp;María Rosa Aguilar ,&nbsp;Luis García","doi":"10.1016/j.opresp.2026.100565","DOIUrl":"10.1016/j.opresp.2026.100565","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Streptococcus pneumoniae</em> is one of the deadliest bacterial pathogens with high clinical significance in invasive pneumococcal disease (IPD). Vaccines have reduced the burden of disease caused by S. pneumoniae, but the increase in antibiotic-resistant strains and serotypes not covered by vaccines is concerning. Therefore, the development of new therapies to prevent and treat this disease is crucial.</div></div><div><h3>Methods</h3><div>The efficacy of nanoparticles developed by the Rocasolano Institute of Physical Chemistry (CSIC) was evaluated. These nanoparticles were functionalised with vitamin E and loaded with three hydrophobic drugs—a macrolide, an antihistamine, and a glucocorticoid—and combinations thereof, both in biofilm and in planktonic culture of <em>S. pneumoniae</em>. Three strains of pneumococcus were used for this purpose: a reference strain of serotype 19F, an isogenic mutant of serotype 19A, and a multidrug-resistant clinical strain also of this serotype.</div></div><div><h3>Results</h3><div>It was observed that, in the reference strain, both empty nanoparticles and combinations with drugs inhibited growth at concentrations of 1.25% or 2.5%. Even when using nanoparticles with combinations of macrolide and the other two drugs, a decrease to 0.7% and 1.25% was observed. In the case of the isogenic mutant, this effect was also observed in viability but at higher concentrations, and with the multidrug-resistant strain, a decrease in growth was observed with the nanoparticle loaded with the antihistamine and the nanoparticle loaded with the combination of this together with the macrolide. In the inhibition of the biofilm of the reference strain, it was observed that the three loaded nanoparticles inhibit the biofilm at concentrations higher than the minimum inhibitory concentration, and in the case of the combinations, the macrolide nanoparticle with the glucocorticoid and the triple combination of the three drugs in the nanoparticle show an effect. However, in the treatment of biofilm, greater disintegration is observed when empty nanoparticles are used rather than loaded ones, which differs from what occurs in inhibition.</div></div><div><h3>Conclusions</h3><div>Nanoparticles loaded with different types of drugs and combinations thereof show a notable effect in inhibiting the growth of pneumococcus and even in inhibiting the biofilm of this pathogen. The nanoparticle loaded with the antihistamine has the greatest growth-inhibiting effect, and in the case of biofilm inhibition, the three loaded nanoparticles, as well as the combination of macrolide with glucocorticoid and the triple combination, show the greatest effect. These strategies may be presented as alternatives for the prevention and treatment of this disease.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100565"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ASSESSMENT OF ILLUMINA AND OXFORD NANOPORE SEQUENCING APPROACHES FOR 16S RRNA-BASED CHARACTERIZATION OF RESPIRATORY MICROBIAL COMMUNITIES 基于16s rrna的呼吸道微生物群落表征的illumina和Oxford纳米孔测序方法的评估
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100566
Guillem Macip , Alba Soler-Comas , Andrea Palomeque , Ana Motos , Blanca Llonch , Joan Canseco-Ribas , Leticia Bueno-Freire , Davide Calabretta , Kasra Kiarostami , Roberto Cabrera , Miquel Ferrer , Antoni Torres , Laia Fernandez-Barat

Background

The respiratory microbiome is central to health and disease, requiring accurate sequencing for characterization. We compared Illumina NextSeq and Oxford Nanopore Technologies (ONT) for 16S rRNA profiling. Illumina produces short, highly accurate reads (∼300 bp) suited for genus-level classification but limited at species resolution. ONT generates full-length reads (∼1,500 bp), enabling higher resolution but with historically lower accuracy.

Methods

We sequenced 34 respiratory samples from ventilator-associated pneumonia (VAP) patients (n=20) and a swine model (n=14) using Illumina (V3–V4) and ONT (whole gene). Data were processed with nf-core/ampliseq or epi2me-labs/wf-16s using the Silva 138.1 database. Diversity metrics and taxonomic profiles were compared.

Results

Alpha diversity showed greater species richness with Illumina, while evenness was comparable. Beta diversity differences were significant in pigs but not humans, suggesting stronger platform effects in complex microbiomes. Illumina detected a broader taxonomic range, while ONT resolved dominant species. ANCOM-BC2 revealed platform-specific biases: ONT overrepresented Enterococcus and Klebsiella but underrepresented Prevotella and Bacteroides.

Conclusions

Illumina is suited for broad surveys, while ONT excels in species-level resolution and real-time use. Hybrid approaches may best leverage both technologies in clinical and preclinical studies.
呼吸微生物组是健康和疾病的核心,需要准确的测序来表征。我们比较了Illumina NextSeq和Oxford Nanopore Technologies (ONT)的16S rRNA分析。Illumina产生短的、高度精确的读数(~ 300 bp),适合于属水平的分类,但在物种分辨率上受到限制。ONT生成全长读取(~ 1,500 bp),实现更高的分辨率,但历史上的精度较低。方法应用Illumina (V3-V4)和ONT(全基因)对呼吸机相关性肺炎(VAP)患者(n=20)和猪模型(n=14)的34份呼吸道样本进行测序。数据采用nf-core/ampliseq或epi2me-labs/wf-16s处理,使用Silva 138.1数据库。比较了多样性指标和分类学特征。结果salpha多样性与Illumina的物种丰富度较高,均匀度与Illumina相当。猪的β多样性差异显著,但人类没有,这表明在复杂的微生物组中有更强的平台效应。Illumina检测到的分类范围更广,而ONT检测到的是优势种。ANCOM-BC2显示平台特异性偏差:ONT过度代表肠球菌和克雷伯氏菌,但未充分代表普雷沃氏菌和拟杆菌。结论illumina适用于广泛的调查,而ONT在物种水平分辨率和实时使用方面具有优势。混合方法可以在临床和临床前研究中最好地利用这两种技术。
{"title":"ASSESSMENT OF ILLUMINA AND OXFORD NANOPORE SEQUENCING APPROACHES FOR 16S RRNA-BASED CHARACTERIZATION OF RESPIRATORY MICROBIAL COMMUNITIES","authors":"Guillem Macip ,&nbsp;Alba Soler-Comas ,&nbsp;Andrea Palomeque ,&nbsp;Ana Motos ,&nbsp;Blanca Llonch ,&nbsp;Joan Canseco-Ribas ,&nbsp;Leticia Bueno-Freire ,&nbsp;Davide Calabretta ,&nbsp;Kasra Kiarostami ,&nbsp;Roberto Cabrera ,&nbsp;Miquel Ferrer ,&nbsp;Antoni Torres ,&nbsp;Laia Fernandez-Barat","doi":"10.1016/j.opresp.2026.100566","DOIUrl":"10.1016/j.opresp.2026.100566","url":null,"abstract":"<div><h3>Background</h3><div>The respiratory microbiome is central to health and disease, requiring accurate sequencing for characterization. We compared Illumina NextSeq and Oxford Nanopore Technologies (ONT) for 16S rRNA profiling. Illumina produces short, highly accurate reads (∼300 bp) suited for genus-level classification but limited at species resolution. ONT generates full-length reads (∼1,500 bp), enabling higher resolution but with historically lower accuracy.</div></div><div><h3>Methods</h3><div>We sequenced 34 respiratory samples from ventilator-associated pneumonia (VAP) patients (n=20) and a swine model (n=14) using Illumina (V3–V4) and ONT (whole gene). Data were processed with nf-core/ampliseq or epi2me-labs/wf-16s using the Silva 138.1 database. Diversity metrics and taxonomic profiles were compared.</div></div><div><h3>Results</h3><div>Alpha diversity showed greater species richness with Illumina, while evenness was comparable. Beta diversity differences were significant in pigs but not humans, suggesting stronger platform effects in complex microbiomes. Illumina detected a broader taxonomic range, while ONT resolved dominant species. ANCOM-BC2 revealed platform-specific biases: ONT overrepresented Enterococcus and Klebsiella but underrepresented Prevotella and Bacteroides.</div></div><div><h3>Conclusions</h3><div>Illumina is suited for broad surveys, while ONT excels in species-level resolution and real-time use. Hybrid approaches may best leverage both technologies in clinical and preclinical studies.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100566"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DIFFERENTIAL CELLULAR IMMUNE RESPONSE IN BAL AFTER INHALATION OF PIGEON SERUM AND ASPERGILLUS EXTRACT IN ACUTE AND CHRONIC MURINE MODELS OF HYPERSENSITIVITY PNEUMONITIS 急性和慢性超敏性肺炎小鼠模型吸入鸽子血清和曲霉提取物后bal的差异细胞免疫反应
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100570
Massa-Gómez Marc , Soler-Segovia David , Espejo David , Pilia María-Florencia , Ojanguren Iñigo , Muñoz-Montull Lidia , Muñoz Xavier , Cruz María Jesús

Introduction

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of, mainly, avian and fungal antigens. However, the immunological mechanisms involved are not yet well understood. The objective of the study was to compare the cellular immune response after exposure to pigeon serum and Aspergillus sp. extract in acute and chronic murine models of hypersensitivity pneumonitis (HP).

Methods

The animal models were conducted using C57BL/6J strain mice. The HP groups were sensitized with two injections (48 hours apart) of 100 µL of pigeon serum (200 µg/ml) for the avian-origin HP group (HPA) and Aspergillus extract (200 µg/ml) for the fungal-origin HP group (HPF). The control group was sensitized with saline serum. Antigen exposure was performed via intranasal instillations of 40 µL on three consecutive days per week for three weeks in acute model and sixteen weeks in chronic model. Leukocyte patterns were evaluated in bronchoalveolar lavage (BAL).

Results

Both acute HP groups showed a higher number of total cells (p=0.0015 and p=0.0059), neutrophils (p=0.0002 and p<0.0001), eosinophils (p<0.0001 and p=0.0351), and lymphocytes (p=0.0070 and p<0.0001) in the BAL compared to control group. The acute HPA group exhibited a greater presence of eosinophils (p=0.0047) compared to the HPF group, while the acute HPF group had a higher number of neutrophils (p=0.0002) and lymphocytes (p=0.0463) compared to the acute HPA group. Both chronic HP groups had a higher number of total cells (p=0.0088 and p<0.0001), neutrophils (p=0.0037 and p<0.0001), eosinophils (p<0.0001 and p=0.0096) and lymphocytes (p=0.0016 and p<0.0001) in BAL compared to control group. In addition, chronic FHP showed more total cells (p=0.0001) than chronic AHP, more macrophages (p=0.0002 and p=0.0011) than control and chronic AHP and more neutrophils (p=0.0476) and lymphocytes (p=0.0083) than chronic AHP.

Conclusions

A different cellular response was observed in the BAL depending on the causative antigen. In avian-induced HP, eosinophils appear to play a more significant role, whereas in fungal-induced HP, neutrophils and lymphocytes were more prevalent. This suggests that during the inflammatory phase of HP, two distinct immune responses could develop depending on the causative agent.
过敏性肺炎(hypersensitivity pneumonitis, HP)是一种肺间质性疾病,主要由吸入禽类和真菌抗原引起。然而,所涉及的免疫学机制尚不清楚。本研究的目的是比较暴露于鸽子血清和曲霉菌提取物对急性和慢性超敏性肺炎(HP)小鼠模型的细胞免疫反应。方法采用C57BL/6J品系小鼠建立动物模型。禽源性HP组(HPA)分别注射100µL鸽子血清(200µg/ml)和真菌源性HP组(HPF)的曲霉提取物(200µg/ml),两次致敏(间隔48小时)。对照组给予生理盐水血清致敏。急性模型连续3周,慢性模型连续16周,每周连续3天鼻内滴注抗原40µL。在支气管肺泡灌洗(BAL)中评估白细胞模式。结果急性HP组与对照组相比,BAL细胞总数(p=0.0015和p=0.0059)、中性粒细胞(p=0.0002和p= 0.0001)、嗜酸性粒细胞(p= 0.0001和p=0.0351)和淋巴细胞(p=0.0070和p= 0.0001)均显著增加。急性HPA组比急性HPA组有更多的嗜酸性粒细胞(p=0.0047),而急性HPF组比急性HPA组有更多的中性粒细胞(p=0.0002)和淋巴细胞(p=0.0463)。慢性HP组与对照组相比,BAL细胞总数(p=0.0088和p= lt;0.0001)、中性粒细胞(p=0.0037和p= lt;0.0001)、嗜酸性粒细胞(p= 0.000001和p=0.0096)和淋巴细胞(p=0.0016和p= lt;0.0001)均较高。此外,慢性FHP的总细胞数(p=0.0001)高于慢性AHP,巨噬细胞数(p=0.0002和p=0.0011)高于对照组和慢性AHP,中性粒细胞(p=0.0476)和淋巴细胞(p=0.0083)高于慢性AHP。结论不同抗原对BAL有不同的细胞应答。在禽类诱导的HP中,嗜酸性粒细胞似乎起着更重要的作用,而在真菌诱导的HP中,中性粒细胞和淋巴细胞更为普遍。这表明,在HP的炎症期,两种不同的免疫反应可能根据病原体而发展。
{"title":"DIFFERENTIAL CELLULAR IMMUNE RESPONSE IN BAL AFTER INHALATION OF PIGEON SERUM AND ASPERGILLUS EXTRACT IN ACUTE AND CHRONIC MURINE MODELS OF HYPERSENSITIVITY PNEUMONITIS","authors":"Massa-Gómez Marc ,&nbsp;Soler-Segovia David ,&nbsp;Espejo David ,&nbsp;Pilia María-Florencia ,&nbsp;Ojanguren Iñigo ,&nbsp;Muñoz-Montull Lidia ,&nbsp;Muñoz Xavier ,&nbsp;Cruz María Jesús","doi":"10.1016/j.opresp.2026.100570","DOIUrl":"10.1016/j.opresp.2026.100570","url":null,"abstract":"<div><h3>Introduction</h3><div>Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by inhalation of, mainly, avian and fungal antigens. However, the immunological mechanisms involved are not yet well understood. The objective of the study was to compare the cellular immune response after exposure to pigeon serum and Aspergillus sp. extract in acute and chronic murine models of hypersensitivity pneumonitis (HP).</div></div><div><h3>Methods</h3><div>The animal models were conducted using C57BL/6J strain mice. The HP groups were sensitized with two injections (48 hours apart) of 100 µL of pigeon serum (200 µg/ml) for the avian-origin HP group (HPA) and Aspergillus extract (200 µg/ml) for the fungal-origin HP group (HPF). The control group was sensitized with saline serum. Antigen exposure was performed via intranasal instillations of 40 µL on three consecutive days per week for three weeks in acute model and sixteen weeks in chronic model. Leukocyte patterns were evaluated in bronchoalveolar lavage (BAL).</div></div><div><h3>Results</h3><div>Both acute HP groups showed a higher number of total cells (p=0.0015 and p=0.0059), neutrophils (p=0.0002 and p&lt;0.0001), eosinophils (p&lt;0.0001 and p=0.0351), and lymphocytes (p=0.0070 and p&lt;0.0001) in the BAL compared to control group. The acute HPA group exhibited a greater presence of eosinophils (p=0.0047) compared to the HPF group, while the acute HPF group had a higher number of neutrophils (p=0.0002) and lymphocytes (p=0.0463) compared to the acute HPA group. Both chronic HP groups had a higher number of total cells (p=0.0088 and p&lt;0.0001), neutrophils (p=0.0037 and p&lt;0.0001), eosinophils (p&lt;0.0001 and p=0.0096) and lymphocytes (p=0.0016 and p&lt;0.0001) in BAL compared to control group. In addition, chronic FHP showed more total cells (p=0.0001) than chronic AHP, more macrophages (p=0.0002 and p=0.0011) than control and chronic AHP and more neutrophils (p=0.0476) and lymphocytes (p=0.0083) than chronic AHP.</div></div><div><h3>Conclusions</h3><div>A different cellular response was observed in the BAL depending on the causative antigen. In avian-induced HP, eosinophils appear to play a more significant role, whereas in fungal-induced HP, neutrophils and lymphocytes were more prevalent. This suggests that during the inflammatory phase of HP, two distinct immune responses could develop depending on the causative agent.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100570"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ROLE OF MIRNAS SHUTTLED BY LPS-PRIMED MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN MODULATING MACROPHAGE ACTIVATION lps引发的间充质干细胞来源的细胞外囊泡穿梭micnas在调节巨噬细胞活化中的作用
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100574
Aina Areny-Balagueró , Navneet Purewal-Chohan , Marta Camprubí-Rimblas , Elena Campaña-Duel , Antoni Berenguer-Llergo , Adrián Ceccato , Antonio Artigas , Daniel Closa

Introduction

Mesenchymal stem cells (MSCs) have regenerative and immunomodulatory properties largely mediated by extracellular vesicles (EVs). Priming MSCs with lipopolysaccharide (LPS) enhances the therapeutic efficacy of their EVs, particularly in acute lung injury. This study investigates the role of differentially expressed miRNAs between EVs from naïve (C-EVs) and LPS-primed MSCs (LPS-EVs) and their immunomodulatory effects.

Methods

miRNA profiling of C-EVs and LPS-EVs was performed using GeneChip miRNA 4.0 Array (n=2). Differentially expressed miRNAs (fold-change ≥ 1.5) were identified, and pathway enrichment was analyzed using GSEA with KEGG, GO, Biocarta, Broad Hallmarks, and PID databases. Selected overexpressed miRNAs were validated by RT-qPCR and tested for immunomodulatory effects in Pseudomonas aeruginosa-infected THP-1 cells, individually and in combination (MIMIX).

Results

Twenty-one miRNAs were differentially expressed between C-EVs and LPS-EVs (16 upregulated, 5 downregulated in LPS-EVs). Enriched pathways included inflammation, epithelial regeneration, and endothelial barrier integrity. RT-qPCR confirmed overexpression of miR-297, let-7b-5p, and miR-93-5p in LPS-EVs, which reduced IL1B, IL6, and IL8 expression in infected THP-1 cells. Notably, only the combined administration of these three miRNAs induced M2 polarization, increasing CD206, CD163, and TGFβ expression.

Conclusions

LPS priming enhances the immunomodulatory potential of MSC-derived EVs, partly through overexpression of miR-297, miR-93-5p, and let-7b-5p, which synergistically promote M2 macrophage polarization.
间充质干细胞(MSCs)具有再生和免疫调节特性,主要由细胞外囊泡(EVs)介导。用脂多糖(LPS)诱导间充质干细胞可以提高其EVs的治疗效果,特别是在急性肺损伤中。本研究探讨了来自naïve的EVs (C-EVs)和lps - MSCs (LPS-EVs)之间差异表达的mirna的作用及其免疫调节作用。方法采用GeneChip miRNA 4.0阵列(n=2)对c - ev和lps - ev进行miRNA分析。鉴定出差异表达的mirna (fold-change≥1.5),并使用GSEA与KEGG、GO、Biocarta、Broad Hallmarks和PID数据库分析途径富集。选择过表达的mirna通过RT-qPCR验证,并测试单独和联合(MIMIX)在铜绿假单胞菌感染的THP-1细胞中的免疫调节作用。结果21个mirna在c - ev和lps - ev之间存在差异表达(lps - ev中表达上调16个,下调5个)。富集通路包括炎症、上皮再生和内皮屏障完整性。RT-qPCR证实了lps - ev中miR-297、let-7b-5p和miR-93-5p的过表达,从而降低了感染THP-1细胞中IL1B、IL6和IL8的表达。值得注意的是,只有联合使用这三种mirna才能诱导M2极化,增加CD206、CD163和TGFβ的表达。结论slps启动增强了msc来源的ev的免疫调节潜能,部分是通过过表达miR-297、miR-93-5p和let-7b-5p,协同促进M2巨噬细胞极化。
{"title":"ROLE OF MIRNAS SHUTTLED BY LPS-PRIMED MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN MODULATING MACROPHAGE ACTIVATION","authors":"Aina Areny-Balagueró ,&nbsp;Navneet Purewal-Chohan ,&nbsp;Marta Camprubí-Rimblas ,&nbsp;Elena Campaña-Duel ,&nbsp;Antoni Berenguer-Llergo ,&nbsp;Adrián Ceccato ,&nbsp;Antonio Artigas ,&nbsp;Daniel Closa","doi":"10.1016/j.opresp.2026.100574","DOIUrl":"10.1016/j.opresp.2026.100574","url":null,"abstract":"<div><h3>Introduction</h3><div>Mesenchymal stem cells (MSCs) have regenerative and immunomodulatory properties largely mediated by extracellular vesicles (EVs). Priming MSCs with lipopolysaccharide (LPS) enhances the therapeutic efficacy of their EVs, particularly in acute lung injury. This study investigates the role of differentially expressed miRNAs between EVs from naïve (C-EVs) and LPS-primed MSCs (LPS-EVs) and their immunomodulatory effects.</div></div><div><h3>Methods</h3><div>miRNA profiling of C-EVs and LPS-EVs was performed using GeneChip miRNA 4.0 Array (n=2). Differentially expressed miRNAs (fold-change ≥ 1.5) were identified, and pathway enrichment was analyzed using GSEA with KEGG, GO, Biocarta, Broad Hallmarks, and PID databases. Selected overexpressed miRNAs were validated by RT-qPCR and tested for immunomodulatory effects in Pseudomonas aeruginosa-infected THP-1 cells, individually and in combination (MIMIX).</div></div><div><h3>Results</h3><div>Twenty-one miRNAs were differentially expressed between C-EVs and LPS-EVs (16 upregulated, 5 downregulated in LPS-EVs). Enriched pathways included inflammation, epithelial regeneration, and endothelial barrier integrity. RT-qPCR confirmed overexpression of miR-297, let-7b-5p, and miR-93-5p in LPS-EVs, which reduced IL1B, IL6, and IL8 expression in infected THP-1 cells. Notably, only the combined administration of these three miRNAs induced M2 polarization, increasing CD206, CD163, and TGFβ expression.</div></div><div><h3>Conclusions</h3><div>LPS priming enhances the immunomodulatory potential of MSC-derived EVs, partly through overexpression of miR-297, miR-93-5p, and let-7b-5p, which synergistically promote M2 macrophage polarization.</div></div>","PeriodicalId":34317,"journal":{"name":"Open Respiratory Archives","volume":"8 ","pages":"Article 100574"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146162088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SERUM BIOMARKERS IN INTERSTITIAL LUNG ABNORMALITIES AND FAMILIAL EARLY INTERSTITIAL LUNG DISEASE 间质性肺异常和家族性早期间质性肺疾病的血清生物标志物
Q4 Medicine Pub Date : 2026-02-01 DOI: 10.1016/j.opresp.2026.100558
Elsie Vera-Santiesteban , Marta Gabasa , Yasmina Gutiérrez-Rodríguez , Jose Palma-Rodríguez , Guadalupe Bermudo , Mireya Fuentes , Maria Molina-Molina , Vanesa Vicens-Zygmunt

Introduction

Interstitial lung abnormalities (ILA) are incidental findings at thorax computed tomography in asymptomatic patients that could progress and could be sporadic (ILA) or with a genetic substrate (EARLY interstitial lung disease (ILD)).

Objectives

The aim of this study was to analyse serum biomarkers and clinical behaviour of subjects with ILA (incidental sporadic mild ILD) with healthy controls (Control-ILA) and subjects with mild ILD with a 1st degree familial ILD (EARLY familial ILD) and without it (familial control-EARLY).

Methods

Serum levels of KL6, GAL3, CCL18, SPD and αKlotho were quantified by ELISA. Demographic, genetic and pulmonary function tests (PFT) including FVC, TLC, DLCO and 6-minute walking test were evaluated. Correlations were performed between serum biomarkers and functional parameters. Parametric and non-parametric statistical tests were used. p<0.05 was considered statistically significant.

Results

ILA patients were older than EARLY ones with a higher proportion of males and less smokers than their controls in both groups. TLC was diminished in ILA compared with their controls (p<0.05). DLCO was decreased in ILA and EARLY compared with their controls (p<0.05). Regarding baseline serum biomarkers, ILA had increased KL6, SPD and α-Klotho compared to their controls, while EARLY had increased KL6 and decreased α-Klotho(p<0.05). A negative correlation between SPD and FVC was observed in EARLY subjects.

Conclusions

KL6 and αKlotho in both groups and SPD in ILA are the most altered biomarkers in our cohort. This different profile could impact on ILD progression.
肺间质性异常(ILA)是在无症状患者的胸部计算机断层扫描中偶然发现的,可能是进展,可能是散发的(ILA)或具有遗传底物(早期间质性肺疾病(ILD))。目的:本研究的目的是分析ILA(偶发性轻度ILD)与健康对照(Control-ILA)、轻度ILD合并1度家族性ILD(早期家族性ILD)和无家族性ILD(早期家族性ILD)受试者的血清生物标志物和临床行为。方法采用ELISA法测定血清中KL6、GAL3、CCL18、SPD、α - klotho的水平。对FVC、TLC、DLCO、6分钟步行测试等人口统计学、遗传学和肺功能测试(PFT)进行评估。在血清生物标志物和功能参数之间进行相关性分析。采用参数和非参数统计检验。P<;0.05认为有统计学意义。结果sila患者比EARLY患者年龄大,男性比例高,吸烟人数少于对照组。与对照组相比,ILA组的TLC减少(p < 0.05)。与对照组相比,ILA和EARLY组DLCO降低(p < 0.05)。在基线血清生物标志物方面,与对照组相比,ILA升高了KL6、SPD和α-Klotho,而EARLY升高了KL6,降低了α-Klotho(p < 0.05)。SPD和FVC在早期被试中呈负相关。结论两组患者的skl6和αKlotho以及ILA患者的SPD是本组患者中变化最大的生物标志物。这种不同的特征可能会影响ILD的进展。
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引用次数: 0
Immune Checkpoint Inhibitors and Interstitial Lung Disease: A Comprehensive Review of Pathogenesis, Diagnosis, and Management 免疫检查点抑制剂和间质性肺疾病:发病机制、诊断和治疗的综合综述
Q4 Medicine Pub Date : 2026-01-15 DOI: 10.1016/j.opresp.2026.100578
María Florencia Pilia , Enriqueta Felip , David Espejo , Nuria Pardo , Marta Andreu Casas , David Clofent , Ana Villar , Iñigo Ojanguren
Immune checkpoint inhibitors associated interstitial lung diseases (ICI-ILD) affect approximately 2–5% of patients receiving immunotherapy and represent one of the most serious and potentially life-threatening immune-related adverse events. The pathogenesis remains incompletely elucidated; however, current understanding suggests a multifactorial etiology involving immune dysregulation, genetic susceptibility, and pre-existing pulmonary vulnerability. ICI-ILD can occur at any time during immunotherapy, with a median onset typically occurring two to three months after the initiation of treatment. Nevertheless, cases have been reported as early as a few days and as late as one year after starting therapy. Clinical manifestations can vary considerably, ranging from asymptomatic radiographic abnormalities to severe respiratory distress. The findings of computed tomography are highly variable, and may include ground-glass opacities, consolidation, reticulation, centrilobular nodules, septal thickening, honeycombing, and traction bronchiectasis. Flexible bronchoscopy is an invasive procedure used to assess airway patency, identify endobronchial lesions, aspirate secretions, and perform bronchoalveolar lavage and transbronchial biopsy. Performing bronchoalveolar lavage is recommended to rule out infection, particularly in immunosuppressed patients, as well as to identify signs of alveolar hemorrhage. Management of ICI-ILD primarily involves systemic corticosteroids, with dosage and duration determined by the severity of the disease. Steroid-refractory immune checkpoint inhibitor pneumonitis is defined as the absence of clinical improvement after 48–72 h of high-dose corticosteroid therapy. In such cases, immunosuppressive agents such as infliximab, mycophenolate mofetil, cyclophosphamide, tocilizumab, intravenous immunoglobulin, or plasmapheresis are recommended. Rechallenge with immune checkpoint inhibitors must be individualized, considering the high risk of recurrence, particularly following severe pneumonitis.
免疫检查点抑制剂相关间质性肺疾病(ICI-ILD)影响约2-5%接受免疫治疗的患者,是最严重和可能危及生命的免疫相关不良事件之一。发病机制尚未完全阐明;然而,目前的理解表明,其病因是多因素的,包括免疫失调、遗传易感性和先前存在的肺部易感性。ICI-ILD可在免疫治疗期间的任何时间发生,中位发病通常发生在治疗开始后2 - 3个月。然而,早在开始治疗后几天,晚在治疗后一年就有病例报告。临床表现差异很大,从无症状的影像学异常到严重的呼吸窘迫。计算机断层扫描的表现变化很大,可能包括毛玻璃影、实变、网状、小叶中心结节、间隔增厚、蜂窝状和牵引性支气管扩张。柔性支气管镜检查是一种侵入性检查,用于评估气道通畅,识别支气管内病变,吸痰分泌物,进行支气管肺泡灌洗和经支气管活检。建议进行支气管肺泡灌洗,以排除感染,特别是免疫抑制患者,以及识别肺泡出血的迹象。ICI-ILD的治疗主要涉及全身皮质类固醇,剂量和持续时间取决于疾病的严重程度。类固醇难治性免疫检查点抑制剂肺炎被定义为在高剂量皮质类固醇治疗48-72小时后没有临床改善。在这种情况下,推荐使用免疫抑制剂,如英夫利昔单抗、霉酚酸酯、环磷酰胺、托珠单抗、静脉注射免疫球蛋白或血浆置换。考虑到复发的高风险,特别是在严重肺炎之后,免疫检查点抑制剂的再挑战必须个体化。
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引用次数: 0
Nintedanib in a Dialysis Patient with Idiopathic Pulmonary Fibrosis: A One-Year Follow-Up Without Major Adverse Events 尼达尼布治疗特发性肺纤维化透析患者:1年随访无重大不良事件
Q4 Medicine Pub Date : 2026-01-15 DOI: 10.1016/j.opresp.2026.100579
Cristina Matesanz-López, María Asunción Nieto-Barbero
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引用次数: 0
期刊
Open Respiratory Archives
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