Respiratory Physiology & Neurobiology最新文献

{"title":"Revisiting Acute Respiratory Distress Syndrome ventilation management: Time for a paradigm shift focusing on tidal volume","authors":"Raffaele Merola ,&nbsp;Maria Vargas ,&nbsp;Denise Battaglini","doi":"10.1016/j.resp.2025.104454","DOIUrl":"10.1016/j.resp.2025.104454","url":null,"abstract":"<div><div>Acute Respiratory Distress Syndrome (ARDS) remains a critical challenge in intensive care medicine, with persistently high mortality despite decades of research and advancements in supportive therapies. Mechanical ventilation, particularly low tidal volume (VT) strategies, has become the cornerstone of ARDS management; however, emerging evidence suggests that a uniform application of these approaches may not be universally beneficial. This viewpoint critically examines the evolution of ARDS ventilation strategies, from high VT methods to protective ventilation protocols centered on reduced VT and plateau pressures. It explores the limitations of current guidelines, highlighting how global parameters such as VT and driving pressure (ΔP) may inadequately capture the complex and heterogeneous pathophysiology of ARDS. Concepts like mechanical power, compliance-based ventilation, and transpulmonary pressure offer promising avenues for more personalized care but remain underutilized in clinical practice. Additionally, this viewpoint underscores the significance of heart-lung interactions and the impact of ventilator settings on cardiovascular function, further complicating one-size-fits-all approaches. Ultimately, this work calls for a reassessment of existing paradigms, advocating for individualized, physiology-driven strategies that move beyond population-based protocols to better address the nuanced needs of ARDS patients.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104454"},"PeriodicalIF":1.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validity and reliability of anharmonic morphological ventilometry for the characterisation of human breathing","authors":"Patrick Hanusse ,&nbsp;Pierantonio Laveneziana ,&nbsp;Marie-Cécile Niérat ,&nbsp;Marion Teulier ,&nbsp;Patrick Berger ,&nbsp;Fabien Beaufils ,&nbsp;Christian Straus ,&nbsp;Thomas Similowski","doi":"10.1016/j.resp.2025.104453","DOIUrl":"10.1016/j.resp.2025.104453","url":null,"abstract":"<div><div>Diagnosing and monitoring respiratory disorders typically rely on pulmonary function testing, which requires full patient cooperation and trained personnel, limiting its applicability. Analysing natural breathing offers a valuable alternative but requires new methodological approaches. This study introduces anharmonic morphological analysis, a novel technique to characterise breathing cycles, and evaluates its reliability and ability to distinguish healthy individuals from patients with chronic obstructive pulmonary disease (COPD). Twenty healthy individuals (17 men; age 28 ± 5 years; body mass index 21 ± 2 kg/m²) and 119 COPD patients (covering all spirometric GOLD stages) were studied during natural breathing using a linear pneumotachograph. Ventilatory flow traces were analysed using anharmonic morphological analysis, enabling the reconstruction of an average ventilatory cycle for each individual (personal respiratory profile, PRP). Comparisons were performed by calculating Euclidean distances between PRPs. Anharmonic morphological analysis enabled precise and reproducible characterisation of ventilatory cycles. PRPs showed high temporal stability. Tessellation based on Euclidean distances distinguished healthy individuals from COPD patients with a sensitivity of 86 % and a specificity of 94 %. Exploratory analyses further suggested the potential of the method to identify COPD patients responsive to bronchodilator administration based on inspiratory capacity changes. Anharmonic morphological analysis offers a reproducible, physiologically meaningful description of natural breathing and shows promise for future development as a spontaneous-breathing-based tool to assist in diagnosing respiratory disorders without requiring patient cooperation.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104453"},"PeriodicalIF":1.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmented activity of suprahyoid muscles during hypothermia in sevoflurane-anesthetized mice","authors":"Mayumi Hashida,&nbsp;Takashi Nishino,&nbsp;Saki Taiji,&nbsp;Hisayo Jin,&nbsp;Shiroh Isono","doi":"10.1016/j.resp.2025.104452","DOIUrl":"10.1016/j.resp.2025.104452","url":null,"abstract":"<div><div>Halogenated volatile anesthetics not only cause profound respiratory depression but also exert a facilitatory influence on the upper airway dilator (UAD) muscles in small rodents. A high concentration of sevoflurane inhalation induces gasping respiration characterized by augmented breaths with mandibular movements, to which elevated activity of suprahyoid muscles (SHMs) contributes significantly. Although similar gasping-like breathing has been observed during hypothermia in sevoflurane-anesthetized spontaneously breathing mice, the effect of sevoflurane during hypothermia on SHMs’ activity remains elusive. We investigated the synergistic effects of sevoflurane, pentobarbital, and hypothermia on ventilation and SHMs’ activity in spontaneously breathing mice. The twenty-one tracheally intubated mice were divided into three groups, i.e., the sevoflurane (N = 7), the pentobarbital (N = 7), and the pentobarbital-sevoflurane (N = 7) groups. Progressive hypothermia was produced by cooling mice in each group from 37 to 36℃ to 25–24℃ while measuring body temperature, breathing patterns, and the SHMs’ activity through subcutaneous electromyography (EMG_SH). The pentobarbital group showed minimal change in tidal volume (V_T) and respiratory-related SHMs’ activity during cooling. In contrast, in the sevoflurane and pentobarbital-sevoflurane groups, the EMG_SH, which behaves like the UAD muscle, was augmented with increased V_T during hypothermia. Notably, the pentobarbital-sevoflurane group showed significantly larger EMG_SH values at body temperatures of 34–33 and 31–30℃, indicating a more pronounced effect. Our study confirms the significant role of sevoflurane in inducing increased V_T and augmented SHMs’ activity during hypothermia. Furthermore, adding pentobarbital to sevoflurane anesthesia during hypothermia led to a further increase in augmented EMG_SH, highlighting the synergistic effects of these factors.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104452"},"PeriodicalIF":1.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrysin-loaded PLGA nanoparticle attenuates ferroptosis in lipopolysaccharide-induced indirect acute lung injury by upregulating Nrf2-dependent antioxidant responses","authors":"Islam Ahmed Abdelmawgood ,&nbsp;Ayman Saber Mohamed ,&nbsp;Noha A. Mahana ,&nbsp;Abdel Hady A. Abdel Wahab ,&nbsp;Abeer Mahmoud Badr ,&nbsp;Asmaa Elsayed Abdelkader","doi":"10.1016/j.resp.2025.104451","DOIUrl":"10.1016/j.resp.2025.104451","url":null,"abstract":"<div><div>Chrysin (CHR) is the principal active compound in honey, propolis and plants. Its pharmacological effects include anti-inflammatory, antiallergic, and antioxidant capabilities. However, its poor solubility and bioavailability constitute a limitation. In this study, Poly-lactic-co-glycolic acid (PLGA) was used as a nanocarrier to enhance the stability, bioavailability, and effectiveness of CHR to protect mice from indirect acute lung injury (ALI) caused by lipopolysaccharide (LPS). CHR-loaded PLGA nanoparticle (CHR-NP) was prepared and characterized using techniques such as FTIR, zeta potential analysis, DLS, in vitro drug release assessment, encapsulation efficiency measurement, and TEM. Prior to the intraperitoneal injection of LPS (10 mg/kg), C57BL/6 mice were orally administered CHR (50 mg/kg), PLGA (50 mg/kg), CHR-NP (50 mg/kg), and dexamethasone (Dexa) (5 mg/kg) for a duration of six days. Following 24 h of LPS or normal saline (control) injection, the mice were anesthetized. CHR-NP increased catalase, glutathione, and glutathione peroxidase while decreasing malondialdehyde, myeloperoxidase, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-12, and interferon (IFN)-γ. Moreover, treatment with CHR-NP augmented the gene and protein expression of the Keap1/Nrf2/ARE signaling pathway utilizing quantitative real-time PCR (RT-PCR), western blotting, and immunohistochemistry. Additionally, CHR-NP reduced histological alterations, pulmonary edema, damage, and iron deposition. Our findings indicate that CHR-NP significantly mitigated indirect ALI, possibly through the suppression of inflammation, oxidative stress, and ferroptosis via the activation of the Keap1/Nrf2/ARE signaling pathways.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104451"},"PeriodicalIF":1.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Ethanol abolishes ventilatory long-term facilitation and blunts the ventilatory response to hypoxia in female rats” [Respir. Physiol. Neurobiol. 332 (2024) 104373]","authors":"Aaron L. Silverstein,&nbsp;Warren J. Alilain","doi":"10.1016/j.resp.2025.104450","DOIUrl":"10.1016/j.resp.2025.104450","url":null,"abstract":"","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104450"},"PeriodicalIF":1.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of the anterior insular cortex and interoception on dyspnea in chronic obstructive pulmonary disease","authors":"Anna L. Hudson ,&nbsp;Molly-Eve Day ,&nbsp;Marie T. Williams ,&nbsp;Olivia K. Harrison","doi":"10.1016/j.resp.2025.104441","DOIUrl":"10.1016/j.resp.2025.104441","url":null,"abstract":"<div><div>Dyspnea (the perception of breathing discomfort) can be an immensely debilitating symptom for people with chronic obstructive pulmonary disease (COPD) and is not fully reflective of physiological measures of disease severity. We propose that the anterior insular cortex (AIC) and its key role in interoception (the perception of signals from within the body) are important mediators of dyspnea symptomology. Interoception encompasses respiratory motor drive, corollary discharge, sensory afferents, central neural integration, error signal generation, gating, decision processing and behavioral adaptation. Neuroimaging evidence supports this notion as decreased AIC activity in people with COPD is associated with heightened dyspnea, and respiratory interoceptive attention tasks have been shown to increase activation in this area of the brain. Therefore, activity in the AIC within the interoceptive processing pathway may explain some of the variability in symptom burden in people living with COPD. We explore these theories in the context of the current knowledge on the physiology and neuroscience of dyspnea, drawing on the implementation of interoceptive measures in other respiratory and mental health conditions. Given the evidence that the AIC has a key role in interoception and is a likely mediator within dyspnea symptomology, advances in our understanding of the role of interoceptive processing on symptom burden in people living with COPD, as well as appropriate methods to measure and treat it, should be research priorities.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104441"},"PeriodicalIF":1.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic pathways for earlier diagnosis and treatment towards better outcomes for adults living with chronic breathlessness","authors":"Gillian E. Doe ,&nbsp;Max Olsson ,&nbsp;Rachael A. Evans","doi":"10.1016/j.resp.2025.104439","DOIUrl":"10.1016/j.resp.2025.104439","url":null,"abstract":"<div><div>Chronic breathlessness is a common and distressing symptom, negatively impacting physical function and quality of life. Many individuals presenting with chronic breathlessness wait years for an explanatory diagnosis, leading to delays in accessing effective treatments and worse individual outcomes including premature mortality. In addition, delays to diagnosis are associated with increased healthcare utilisation and therefore potentially avoidable burden on healthcare systems. Diagnosing the underlying causes of chronic breathlessness is complex and can be challenging for clinicians. The current clinical diagnostic approach, related guidelines, and healthcare service structure are typically aligned with a disease-based focus. For this article, we are using a working definition of ‘Chronic Breathlessness’ to infer breathlessness that has persisted for at least eight weeks. In this narrative review, using the latest available evidence, we aimed to describe a symptom-based approach to diagnosis for adults presenting with chronic breathlessness alongside describing the potential for this approach to improve both clinical outcomes and efficiency for healthcare systems. Therefore, our objectives were to: 1) summarise what is currently known about the time to diagnosis for adults presenting with breathlessness, 2) describe the impact and possible explanations for the current delays to diagnosis, 3) describe potential solutions towards an effective symptom-based diagnosis, 4) review the potential for Artificial Intelligence (AI) to support several areas along the diagnostic pathway for breathlessness, 5) describe how a symptom-based approach to diagnosis can be directly utilised to enable a ‘matched’ personalised holistic approach to treatment.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104439"},"PeriodicalIF":1.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of non-NMDA glutamate receptors in respiratory control and hyperoxia-induced plasticity in neonatal rats","authors":"Matthew D. Danielson,&nbsp;Brielle J. Antonelli,&nbsp;Megan R. Gonzalez,&nbsp;Ryan W. Bavis","doi":"10.1016/j.resp.2025.104440","DOIUrl":"10.1016/j.resp.2025.104440","url":null,"abstract":"<div><div>Newborn rats have a biphasic hypoxic ventilatory response (HVR) that typically matures during the second postnatal week, but rats reared in moderate hyperoxia (30–60 % O₂) already exhibit a sustained increase in ventilation during the late-phase of the HVR by 3 days of age (P3). Enhanced glutamatergic neurotransmission through NMDA receptors contributes to both normal maturation of the HVR and hyperoxia-induced developmental plasticity, but the role of non-NMDA glutamate receptors is unclear. To investigate the involvement of non-NMDA glutamate receptors in respiratory control and hyperoxia-induced plasticity, newborn Sprague Dawley rats were exposed to 21 % O₂ (Control) or 60 % O₂ (Hyperoxia) until their HVR was measured by head-body plethysmography at P3–4. Systemic administration of the AMPA/kainate receptor antagonist NBQX (12.5 mg kg⁻¹, i.p.) caused rats from both treatment groups to adopt a slower, deeper breathing pattern with a modest reduction in baseline minute ventilation and convection requirement. NBQX also attenuated the HVR measured during the first minute of hypoxia in both treatment groups, but it did not alter the overall shape of the HVR; Hyperoxia rats exhibited a sustained increase in ventilation throughout the entire 15-min exposure to 11 % O₂ regardless of whether they received saline or NBQX injections, while Control rats had a strongly biphasic HVR. Therefore, glutamatergic neurotransmission via non-NMDA glutamate receptors plays an important role in the respiratory control of neonatal rats but not in the respiratory plasticity expressed after chronic postnatal hyperoxia.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104440"},"PeriodicalIF":1.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GAA replacement improves respiratory muscle, neural, and alveolar pathology in the pompe mouse","authors":"Angela L. Roger ,&nbsp;Lea El Haddad ,&nbsp;Meredith L. Huston ,&nbsp;Sean Kehoe ,&nbsp;Davina Le ,&nbsp;Mainur Khan ,&nbsp;Evelyn Scarrow ,&nbsp;Trevor Gonzalez ,&nbsp;Abigail Benkert ,&nbsp;Aravind Asokan ,&nbsp;Mai K. ElMallah","doi":"10.1016/j.resp.2025.104433","DOIUrl":"10.1016/j.resp.2025.104433","url":null,"abstract":"<div><div>Pompe disease is a devastating neuromuscular disorder caused by mutations in the gene <em>GAA</em>. These mutations result in a deficiency of the enzyme acid α-glucosidase (GAA), leading to lysosomal glycogen accumulation in cardiac, skeletal, and smooth muscle, motor neurons, and alveolar epithelial cells. Respiratory failure due to neuromuscular weakness, recurrent aspiration pneumonia, and tracheo-bronchomalacia are the leading causes of morbidity and mortality in PD patients. Enzyme replacement therapy (ERT) is currently the only FDA approved treatment for Pompe disease, however, gene therapy with naturally occurring and engineered adeno-associated viral vectors are also widely studied as an alternative treatment. In the present study we directly compared the benefits of existing and novel treatment modalities - ERT, AAV9-<em>GAA</em>, and AAVcc47-<em>GAA</em>, with an emphasis on correction of pathologies related to respiratory function. We find that GAA replacement in early adult mice improves respiration through 9 months of age. This improvement is attributed to glycogen clearance in the tongue, diaphragm, and lungs, which subsequently improved diaphragm neuromuscular junctions and reduced lysosomes within the alveolar epithelia.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"335 ","pages":"Article 104433"},"PeriodicalIF":1.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cockroach allergen exposure alters redox homeostasis and mediates airway inflammation","authors":"Swati Sharma ,&nbsp;Ekta Nagar ,&nbsp;Naveen Arora","doi":"10.1016/j.resp.2025.104438","DOIUrl":"10.1016/j.resp.2025.104438","url":null,"abstract":"<div><div>Allergic diseases are orchestrated by complex interplay of allergens with components of immune system as well as structural cells. As airway epithelium lies at the interface of environment and host immune responses, therefore we sought to study role of cockroach allergen exposure in context of oxidative stress in epithelia and its functional role in allergic pathophysiology. In vitro studies on Beas2B cells indicated elevation of intracellular ROS levels upon cockroach allergen (CE) exposure and transcriptional regulation of epithelial activation markers (CXCL-8 and IL-1 α) and endogenous antioxidant SOD-2. To corroborate ROS induction in vivo, mice model of cockroach hypersensitivity was generated and cytosolic and mitochondrial superoxide levels in lung of mice were estimated along with markers of allergic inflammation (cellular infiltration and epithelial activation cytokines (IL-33, TSLP and IL-25), proinflammatory (Th2 cytokines) and antioxidant pathways. Antioxidant supplementation with NAC, GSH and mitochondria specific ROS scavenger Mito-Tempo significantly reduced allergic inflammation. To discern the role of antioxidant pathways, we examined Nrf2 and SOD2 levels in mice lungs. Our results indicate that cockroach allergen exposure offsets the redox balance in lung with reduced glutathione peroxidase and catalase levels, however antioxidant treatment was able to restore redox equilibrium in lung by upregulating the expression of major regulator of antioxidant signalling, Nrf2 and enzymatic antioxidant SOD2. Our studies indicate crucial role of cockroach allergen induced ROS in allergic pathophysiology and targeting allergen induced oxidative stress may be utilised as an adjunct therapy for allergic diseases.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"335 ","pages":"Article 104438"},"PeriodicalIF":1.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}