Respiratory Physiology & Neurobiology最新文献

{"title":"Deep inspirations prior to oscillometry for detecting lung alterations in a mouse model of asthma: Yea or nay?","authors":"Andrés Rojas-Ruiz,&nbsp;Jules Hugo Fournier,&nbsp;Cyndi Henry,&nbsp;Ynuk Bossé","doi":"10.1016/j.resp.2026.104551","DOIUrl":"10.1016/j.resp.2026.104551","url":null,"abstract":"<div><div>Deep inspirations are avoided prior to oscillometry in humans because they transiently improve respiratory mechanics and thereby mask abnormalities in patients with lung diseases. In mice, oscillometry is measured under anesthesia and deep inspirations are contrastingly recommended since they optimize mechanical ventilation and reduce intersubject variability by recruiting closed airways. However, while modeling asthma, a lung disorder burdened by airway closure, deep inspirations may be counterproductive and mitigate differences between mice with and without experimental asthma. Herein, the effect of deep inspirations on respiratory mechanics was quantified in mice with and without experimental asthma. Male BALB/c and C57BL/6 mice were exposed once-daily to either saline or house-dust mite for 10 consecutive days. The day after the last exposure, respiratory mechanics were measured by oscillometry before and after two deep inspirations. In addition to decrease intersubject variability, deep inspirations improved respiratory mechanics in both mouse strains to a magnitude related to the initial level of impairment. Whether deep inspirations mask the detection of alterations caused by experimental asthma depended on the mouse strain. In fact, this question became irrelevant in BALB/c mice when it was discovered that all oscillometric readouts are unchanged by experimental asthma in this mouse strain. In C57BL/6 mice though, the worsening of respiratory mechanics caused by experimental asthma was largely abolished by deep inspirations. Deep inspirations are thus recommended in BALB/c mice since they reduce intersubject variability. However, their utility in C57BL/6 mice is debatable, since the reduced variability may be outweighed by a decreased effect size.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"342 ","pages":"Article 104551"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193067","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":"Hypoxia-inducible factor mediates tissue-specific mitochondrial responses to acute hypoxia in mice but not in rats","authors":"Maud Demarest,&nbsp;Vincent Joseph","doi":"10.1016/j.resp.2026.104549","DOIUrl":"10.1016/j.resp.2026.104549","url":null,"abstract":"<div><div>Oxygen availability is a key determinant of cellular homeostasis, and the mitochondrial response to hypoxia is essential for maintaining energy balance and limiting oxidative stress. The hypoxia-inducible factor (HIF) orchestrates transcriptional programs that adjust mitochondrial function by reducing respiration and electron transport to limit reactive oxygen species (ROS) production. We previously reported that mice exhibit greater tolerance to hypoxia than rats, showing HIF-1 stabilization associated with decrease metabolic response under acute hypoxia, and a mitochondrial shift from complex I– to complex II–supported respiration in the brain at high altitude. Here, we investigated the role of HIF in regulating mitochondrial oxygen consumption rates (OCR) in the cerebral cortex and liver of mice and rats exposed to acute hypoxia (10 % O₂, 6 h). To determine whether these effects were HIF-dependent, a group of animals were also treated with deferoxamine (a HIF stabilizer) under normoxia or with 2-methoxyestradiol (a HIF inhibitor) under hypoxia. We demonstrated that acute hypoxia significantly decreases OCR in the liver of mice, an effect that was partially reproduced by HIF stabilization and partly prevented by HIF inhibition, indicating a HIF-dependent mitochondrial response. In contrast, OCR remained unchanged in the cerebral cortex of mice and in both tissues of rats, indicating species- and tissue-specific regulation. These findings reveal that HIF activation under acute hypoxia selectively modulates liver mitochondrial function in mice but not in rats, supporting the view that interspecific differences in HIF-mediated metabolic regulation contribute to the superior hypoxic tolerance of mice.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104549"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143226","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":"Strain-specific metabolomic and inflammatory profiles in guinea pigs after LPS-induced inflammation: Comparative analysis of Dunkin-Hartley and Trik strains","authors":"Juliana Hanusrichterova ,&nbsp;Eva Baranovicova ,&nbsp;Romana Barosova ,&nbsp;Maros Kolomaznik ,&nbsp;Pavol Mikolka ,&nbsp;Petra Kosutova ,&nbsp;Daniela Mokra ,&nbsp;Juraj Mokry ,&nbsp;Andrea Calkovska","doi":"10.1016/j.resp.2026.104547","DOIUrl":"10.1016/j.resp.2026.104547","url":null,"abstract":"<div><div>Acute inflammation is a complex biological response triggered by various invading agents provoking distinct immune pathways. As inter-strain variability in guinea pigs can influence inflammatory responses, ultimately affecting disease progression, understanding these strain-specific differences can improve the reliability and translational relevance of guinea pig models for studying acute inflammation. In this study, two guinea pig strains, Trik coloured and Dunkin-Hartley albino, were subjected to bacterial endotoxin lipopolysaccharide (LPS) to induce acute systemic inflammation. Specific metabolite alterations in the blood plasma and bronchoalveolar lavage fluid (BALF) were identified using hydrogen-1 nuclear magnetic resonance (¹H NMR) spectroscopy. Distinct differences in the metabolomic profiles in the blood plasma indicated significant inter-strain variability in circulating metabolites during LPS-induced acute inflammation, including those involved in amino acid transamination, ammonia transfer, and immune responses. Metabolomic analysis of BALF from guinea pigs with LPS-induced inflammation revealed decreased levels of specific metabolites. Moreover, changes in blood and BALF white blood cell counts and body weight were evaluated after LPS exposure. In BALF, LPS caused a slight, non-significant increase in total cell count and a significant neutrophil increase in the Dunkin-Hartley strain. In blood, Trik strain showed a significant increase in total count of cells and a significant neutrophil decrease. LPS induced weight loss in both strains, more pronounced in Trik. The study points out strain-specific metabolomic changes in guinea pig LPS model, highlighting the importance of strain selection in inflammation research. While descriptive, these preliminary findings provide a basis for future work to explore inflammatory mechanisms of LPS and improve translation to human disease.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104547"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093925","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":"Description of three dysfunctional breathing patterns in post-COVID dyspnea","authors":"Ivan Guerreiro ,&nbsp;Aurélien Bringard ,&nbsp;Pascal Weber ,&nbsp;Viva Leverington ,&nbsp;Aileen Kharat ,&nbsp;Léon Genecand ,&nbsp;Anna Taboni ,&nbsp;Frédéric Lador","doi":"10.1016/j.resp.2026.104543","DOIUrl":"10.1016/j.resp.2026.104543","url":null,"abstract":"<div><h3>Introduction</h3><div>Dysfunctional breathing (DB) can be defined as a change in breathing pattern associated with respiratory and/or systemic symptoms, after ruling out underlying respiratory or cardiac disease. Recent evidence suggests that DB contributes to dyspnea in post-COVID-19 syndrome (PCS), as demonstrated by ventilation analysis during cardiopulmonary exercise testing (CPET). Nevertheless, the lack of a standardized classification for the different subtypes of DB poses challenges for accurate diagnosis and effective management. We hypothesized that analyzing the evolution of breathing parameters during CPET may help classify DB into three patterns.</div></div><div><h3>Methods</h3><div>We analyzed 79 CPETs performed between July 2020 and May 2022 on patients with persistent respiratory symptoms at least three months after COVID-19 infection. We classified patients into three different categories based on abnormal breathing patterns: hyperventilation (HYPV), erratic breathing (ERBR), and flattening (FLAT).</div></div><div><h3>Results</h3><div>Age, BMI, gender and peak O₂ uptake (V̇O₂) were similar between patterns. Compared to normal pattern (N), we found higher V̇_E – V̇CO₂ slope in HYPV and FLAT, and a lower VT/ V̇_E slope in FLAT and ERBR. The FLAT pattern was also characterized by a higher breathing frequency at peak exercise compared to the other patterns. ERBR and FLAT were associated with higher symptom scores (Nijmegen Questionnaire and Dyspnea-12) compared to N.</div></div><div><h3>Conclusion</h3><div>Analyzing the evolution of ventilatory parameters during incremental exercise enables the classification of dysfunctional breathing into three distinct breathing patterns: hyperventilation, erratic breathing, and flattening.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104543"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948845","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":"Tongue blade neuromuscular junction defects in old F344 rats","authors":"John F. Kemp ,&nbsp;Gary C. Sieck ,&nbsp;Matthew J. Fogarty","doi":"10.1016/j.resp.2026.104545","DOIUrl":"10.1016/j.resp.2026.104545","url":null,"abstract":"<div><div>Tongue-muscle associated behaviours (swallow, speech) are impaired in the elderly. In the Fischer 344 (F344) rat model of aging, hypoglossal motor neurons (MNs) and intrinsic tongue muscle weakness and atrophy are evident. Here we evaluated young (6-months) and old (24-months-old) F344 rat longitudinal muscles for neuromuscular junction (NMJ) innervation. In 140 µm free floating sections, presynaptic components were labelled with synaptophysin and neurofilament. Postsynaptic acetylcholine receptors were labelled with α-Bungarotoxin. NMJs were imaged using confocal microscopy with presynaptic invasion of the postsynaptic endplate quantified. We found marked denervation of female and male tongue NMJs in old age. Our findings are consistent with the significant role that tongue dysfunction has in aged tongue muscle dysfunction and hypoglossal MN death.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104545"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019580","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":"Effects of postural instability on diaphragm and sternocleidomastoid recruitment during a loaded-inspiratory task in healthy adults","authors":"Fang Liu ,&nbsp;Mak Yi On ,&nbsp;Cheung Kwan Tang ,&nbsp;Lai In Tung ,&nbsp;Cheung Chun Hin ,&nbsp;Alice Y.M. Jones ,&nbsp;William W.N. Tsang","doi":"10.1016/j.resp.2025.104541","DOIUrl":"10.1016/j.resp.2025.104541","url":null,"abstract":"<div><h3>Background</h3><div>Inspiratory muscle training (IMT) is commonly used to improve inspiratory muscle strength. However, the relationship between postural stability and recruitment of inspiratory muscles during IMT remains unclear.</div></div><div><h3>Objective</h3><div>To investigate the effect of concurrent seated postural instability and loaded inspiratory breathing on diaphragmatic and sternocleidomastoid (SCM) muscle recruitment activities in healthy adults.</div></div><div><h3>Methods</h3><div>Healthy young adults performed 10 breaths with inspiratory load at 50 % Maximal Inspiratory Pressure (MIP) under four seating conditions in random order: (A) sitting on a stable surface; (B) on a balance pad with both feet on ground; (C) on a balance pad with each foot on separate balance pads; and (D) on a balance pad with both feet on a single balance pad. Right SCM and right hemidiaphragm muscle activity were recorded simultaneously using surface electromyography (sEMG) and ultrasonography, respectively. Self-perceived exertion was recorded after each task.</div></div><div><h3>Results</h3><div>Forty-eight healthy young adults participated in this study. Diaphragmatic contraction, as reflected by the diaphragm thickening fraction (DTf), and SCM muscle activity both increased progressively with greater seated postural instability (from position A to D). Significant incremental increases in recruitment of diaphragm and SCM were observed across all positions, and the largest and statistically significant changes were found between position A and position D, with DTf increased by 40 % (P &lt; 0.001, 95 % CI: 31–49 %) and SCM activity by 17 % (P &lt; 0.001, 95 % CI: 14–20 %). No significant differences in self-perceived exertion levels were observed among the seated conditions.</div></div><div><h3>Conclusion</h3><div>Postural instability during loaded inspiration significantly enhanced diaphragmatic contraction and moderately increased SCM activity in healthy adults. Incorporating postural challenges in IMT protocols may further enhance diaphragmatic training and warrants further study.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104541"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878728","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":"Invasive cardiopulmonary exercise testing: Physiologic assessment of unexplained dyspnea and exercise intolerance","authors":"Emily A. Harris,&nbsp;Aaron B. Waxman","doi":"10.1016/j.resp.2026.104550","DOIUrl":"10.1016/j.resp.2026.104550","url":null,"abstract":"<div><div>Unexplained dyspnea and exertional intolerance are common, burdensome clinical problems that may persist despite routine resting cardiopulmonary testing. Invasive cardiopulmonary exercise testing (iCPET) integrates breath-by-breath gas exchange with invasive hemodynamic and blood gas assessment during incremental exercise, enabling evaluation of physiologic abnormalities that may be unapparent at rest. This review summarizes practical considerations for iCPET performance (including upright cycle ergometry, catheter-based pressure measurements, direct Fick cardiac output, and symptom assessment using separate visual analog Modified Borg ratings for dyspnea and leg fatigue at peak exercise), and presents a structured approach to interpretation using pressure–flow relationships and age-related reference ranges. Emphasis is placed on how characteristic iCPET patterns inform mechanistic contributors to exertional dyspnea by identifying upstream physiologic triggers—such as abnormal rises in pulmonary arterial wedge pressure (exercise-HFpEF), abnormal pulmonary vascular pressure–flow responses (exercise-PAH), impaired preload augmentation associated with autonomic dysfunction, and impaired peripheral oxygen extraction consistent with mitochondrial myopathy. The review also highlights evolving applications in post-pulmonary embolism syndromes and acknowledges that exercise hemodynamic thresholds and protocols vary across centers, underscoring the need for broader standardization.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104550"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119572","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":"Ventilatory limitation to exercise in patients with HFpEF and obesity: No room to breathe","authors":"Tony G. Babb ,&nbsp;Bryce N. Balmain ,&nbsp;Andrew R. Tomlinson ,&nbsp;Linda S. Hynan ,&nbsp;Benjamin D. Levine ,&nbsp;James P. MacNamara ,&nbsp;Satyam Sarma","doi":"10.1016/j.resp.2026.104546","DOIUrl":"10.1016/j.resp.2026.104546","url":null,"abstract":"<div><h3>Background</h3><div>Lowering pulmonary capillary wedge pressure (PCWP) by sublingual nitroglycerin (NTG) fails to increase exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). These findings beg the question as to the origin of exercise limitation. Our objective was to determine whether exercise tolerance could be ventilatory limited in older patients with HFpEF and obesity.</div></div><div><h3>Methods</h3><div>Patients with HFpEF and obesity (n = 42) underwent pulmonary artery and radial artery catheterizations. Cardiorespiratory responses, breathing mechanics, and arterial blood gases were measured at rest, 20 W, and at peak exercise before and after NTG.</div></div><div><h3>Results</h3><div>At rest, there was a drop in cardiac output and PaO₂ (p &lt; 0.01) with subsequent increases in HR, a-<span><math><mover><mrow><mi>v</mi></mrow><mo>¯</mo></mover></math></span>O₂ difference, and A-aO₂ difference (p &lt; 0.001) after NTG. At 20 W, there were increases in HR, a-<span><math><mover><mrow><mi>v</mi></mrow><mo>¯</mo></mover></math></span>O₂ difference, V̇_E/V̇CO₂, lactate, PaO₂, and A-aO₂ difference (p &lt; 0.05). At peak exercise, there was an increase in V̇_E/V̇CO₂ and pH (p &lt; 0.01), and a decrease in PaCO₂ (p &lt; 0.001). However, before and after treatment, there was a qualitative decline in V̇_E/V̇CO₂ from 20 W to peak exercise suggesting these patients could not increase V̇_E further. There were no differences in breathing mechanics at rest, 20 W, or peak exercise after NTG.</div></div><div><h3>Conclusions</h3><div>We conclude that mechanical ventilatory constraints coupled with increased ventilatory inefficiency impose a ventilatory limitation to exercise in patients with HFpEF and obesity.</div></div><div><h3>Clinical Trial Information</h3><div>Clinical Trials number: NCT04068844</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104546"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078495","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":"Effect of superior laryngeal nerve stimulation on swallowing and respiratory coordination in dexmedetomidine-administered adult rats","authors":"Hinata Kubota,&nbsp;Ryoji Ide,&nbsp;Nana Sato Hashizume,&nbsp;Eishi Nakamura,&nbsp;Chikako Saiki","doi":"10.1016/j.resp.2026.104542","DOIUrl":"10.1016/j.resp.2026.104542","url":null,"abstract":"<div><div>It is not clear whether swallowing, which is induced by electrical stimulation of the superior laryngeal nerve (SLN), dominantly suppresses respiration. We examined how the swallowing coordinates with respiration in adult rats under continuous infusion of dexmedetomidine, which possesses α₂-adrenoceptor/imidazoline I₁ receptor (α₂AR/I₁R) mediated sedative-analgesic profile with minimal direct GABAergic potentiation, thereby reducing interference with swallowing circuitry. Prior to the experiment, adult rats (203–322 g, n = 12) under isoflurane anesthesia had their tail vein cannulated for dexmedetomidine administration and tail artery cannulated for analysis of arterial pressure, pulse rate, blood gases (PaO₂, PaCO₂, pH), blood glucose, hematocrit and hemoglobin. After recovery, the animals received continuous infusion of dexmedetomidine intravenously. An incision was made in the neck for SLN electrical stimulation and for recording mylohyoid electromyograms to detect swallowing. Another incision was made in the upper abdomen for recording diaphragm electromyograms to detect inspiratory movements. The spontaneously breathing animals showed no response to tactile or noxious stimulations under continuous infusion of dexmedetomidine. During SLN stimulation at different frequencies (20, 50, or 100 Hz for 10 s), the number of swallows increased in a frequency-dependent manner. Increased swallowing primarily occurred with suppressed respiration (Phase I) and thereafter occurred just after inspiration (Phase II), during which the respiratory frequency recovered to the level before stimulation. The results suggest that, in adult rats receiving dexmedetomidine, SLN stimulation not only triggers swallowing and apnea, but also allows respiration to be resumed and control the occurrence of the swallowing in coordination with respiration.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104542"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918367","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":"Quantitative morphometric analysis of asthmatic mouse lungs using micro-CT: A preclinical imaging study","authors":"Hoang Bao Lam Nguyen ,&nbsp;Juwan Kim ,&nbsp;Ngan-Khanh Chau ,&nbsp;Gyuri Kim ,&nbsp;Hyunseop Kim ,&nbsp;Kum Ju Chae ,&nbsp;Sujeong Kim ,&nbsp;Kyungrim Yi ,&nbsp;Sori Kim ,&nbsp;Ji-Seung Yoo ,&nbsp;Sanghun Choi","doi":"10.1016/j.resp.2026.104548","DOIUrl":"10.1016/j.resp.2026.104548","url":null,"abstract":"<div><div>Asthma is a heterogeneous disease comprising eosinophilic (EOS) and neutrophilic (NEU) phenotypes with distinct airway and parenchymal alterations. Using murine models, this study explored phenotype-specific structural and densitometric changes that are difficult to capture in human cohorts. Sixteen female C57BL/6NCrlOri mice were assigned to negative control (n = 5), EOS (n = 6), or NEU (n = 5) asthma groups. High-resolution micro-computed tomography (micro-CT) was used to quantify airway and parenchymal alterations. Morphometric parameters included bifurcation angle (<span><math><mi>θ</mi></math></span>), circularity (Cr), hydraulic diameter (D_h), wall thickness (WT), and luminal volume (LV). Voxel-wise parenchymal analysis, based on CT Hounsfield unit (HU) thresholds, classified regions as emphysema-like lung, ground-glass opacity (GGO), semi-consolidation, consolidation, and fibrosis. Compared with controls, asthmatic groups showed distinct but partially overlapping structural patterns. EOS demonstrated predominant alterations in distal airways and main bronchi, with increased Cr and D_h, accompanied by higher GGO and semi-consolidation. NEU caused widespread proximal airway dilation, reflected by greater LV, but showed minimal parenchymal changes. Tracheal Cr, D_h, and LV, correlated positively with GGO and semi-consolidation, suggesting a potential association between airway enlargement and parenchymal alterations. Besides, bronchoalveolar lavage (BAL) flow cytometry confirmed distinct inflammatory endotypes, with eosinophil enrichment in EOS mice and increased neutrophils and monocytes in NEU mice. Consistently, lung histopathology showed greater peribronchial inflammation and collagen-associated airway remodeling in NEU mice, whereas EOS mice exhibited moderate inflammatory infiltration with localized matrix deposition. Overall, quantitative micro-CT differentiates EOS and NEU asthma phenotypes by capturing airway and parenchymal features, supporting non-invasive preclinical phenotyping and phenotype-targeted therapy development.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104548"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093898","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}