Louis M. Hall, Graham R. Sharpe, Neil C. Williams, Michael A. Johnson
{"title":"Biological sex differences in the perception of CO2-induced air hunger","authors":"Louis M. Hall, Graham R. Sharpe, Neil C. Williams, Michael A. Johnson","doi":"10.1016/j.resp.2025.104436","DOIUrl":"10.1016/j.resp.2025.104436","url":null,"abstract":"<div><h3>Introduction</h3><div>Biological sex may mediate ‘dyspnoea’ during submaximal exercise, but whether it mediates air hunger (AH), a highly unpleasant form of dyspnoea, remains unclear.</div></div><div><h3>Method</h3><div>Forty healthy adults (twenty females) completed 6-min of quiet breathing (rest) followed by a hyperoxic CO<sub>2</sub> rebreathing task to evoke AH. AH intensity (AH-I) and unpleasantness (AH-U) were measured every 30-s. The Multidimensional Dyspnoea Profile (MDP) was administered after CO<sub>2</sub> rebreathing.</div></div><div><h3>Results</h3><div>Compared to males, AH-I and AH-U thresholds occurred at lower PETCO<sub>2</sub> in females (AH-I: 44.15 ± 2.81 vs 48.90 ± 4.47 mmHg, <em>P</em> < 0.001; AH-U: 43.86 ± 2.57 vs 47.59 ± 2.75 mmHg, <em>P</em> < 0.001) and after a smaller increase in PETCO<sub>2</sub> above resting PETCO<sub>2</sub> (AH-I: 7.04 ± 2.63 vs 10.08 ± 5.28 mmHg, <em>P</em> = 0.027; AH-U: 6.75 ± 2.22 vs 8.77 ± 2.99 mmHg, <em>P</em> = 0.020). AH-I and AH-U were higher in females than males at standardised absolute V̇<sub>E</sub> of 25, 30 and 35 L/min (<em>P</em> < 0.05). AH-U, but not AH-I, remained higher (main effect of sex, <em>P</em> = 0.026) in females than males at standardised relative V̇<sub>E</sub> of 20, 25, and 30 % MVV. More females (<em>n</em> <em>=</em> 9) than males (<em>n=</em> 4) terminated CO<sub>2</sub> rebreathing due to maximal AH perception (<em>P</em> = 0.001). Compared to males, females reported greater intensities of ‘mental effort/concentration’ (7 ± 3 vs 4 ± 3), ‘tight/constricted lungs’ (6 ± 3 vs 2 ± 2), and ‘breathing work/effort’ (6 ± 2 vs 4 ± 3) (all <em>P</em> < 0.05) on the MDP.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that sex differences exist in the perception of AH, which are not entirely accounted for by sex differences in ventilatory capacity.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"335 ","pages":"Article 104436"},"PeriodicalIF":1.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877112","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}
Devin B. Phillips , Christine A. Darko , Matthew D. James , Sandra G. Vincent , Alexandra M. McCartney , Lara K. Sreibers , Nicolle J. Domnik , J. Alberto Neder , Denis E. O’Donnell
{"title":"Neurophysiological mechanisms of exertional dyspnea in advanced pregnancy: A case study","authors":"Devin B. Phillips , Christine A. Darko , Matthew D. James , Sandra G. Vincent , Alexandra M. McCartney , Lara K. Sreibers , Nicolle J. Domnik , J. Alberto Neder , Denis E. O’Donnell","doi":"10.1016/j.resp.2025.104434","DOIUrl":"10.1016/j.resp.2025.104434","url":null,"abstract":"<div><div>The neurophysiological mechanisms of exertional dyspnea in advanced pregnancy remain incompletely understood. This short case report describes the neurophysiological and sensory responses during standardized cardiopulmonary exercise testing (CPET) in one healthy adult female at three timepoints: a) 3 months pre-pregnancy, b) 35 weeks pregnant (third trimester [T3]), and, c) 1 year post-partum. At rest and during exercise, detailed measurements of neurophysiological, gas-exchange and sensory parameters were completed. Compared to both pre-pregnancy and post-partum, ventilatory requirements, electrical activation of the diaphragm (EMGdi, index of inspiratory neural drive) and esophageal pressure swings were higher in T3 throughout exercise. Moreover, at a given work rate, perceived dyspnea was greater in T3 compared with pre-pregnancy and post-partum and increased in close association with heightened EMGdi throughout exercise. At peak exercise in T3, dyspnea/ventilation and EMGdi/ventilation ratios were greater, compared with pre-pregnancy and post-partum. Compared with pre-pregnancy, EMGdi and perceived dyspnea were greater post-partum near the limits of exercise tolerance, secondary to earlier onset of respiratory compensation-mediated increases in ventilation. In the current case, advanced pregnancy was associated with markedly elevated ratings of dyspnea and lower exercise capacity during a standardized clinical CPET. At submaximal intensities, the heightened dyspnea reflected the awareness of pregnancy-induced increases in ventilatory requirements, inspiratory neural drive, and respiratory muscle effort. At the limits of tolerance, heightened dyspnea and inspiratory neural drive reflected a complex combination of increase ventilatory requirements and mechanical constraints on tidal volume expansion. Compared with pre-pregnancy, residual activity-related dyspnea 1-year post-partum appears to reflect physical deconditioning.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"335 ","pages":"Article 104434"},"PeriodicalIF":1.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867713","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}
Stephen M. Johnson, Jacob P. Rastas, Pujal S. Desai, Tracy L. Baker, Jyoti J. Watters
{"title":"Roflumilast, a phosphodiesterase-4 (PDE4) inhibitor, induces respiratory frequency plasticity that is resistant to inflammation in neonatal rat in vitro preparations","authors":"Stephen M. Johnson, Jacob P. Rastas, Pujal S. Desai, Tracy L. Baker, Jyoti J. Watters","doi":"10.1016/j.resp.2025.104435","DOIUrl":"10.1016/j.resp.2025.104435","url":null,"abstract":"<div><div>Premature and newborn infants often have prolonged apneas and are susceptible to bacterial infections that further disrupt breathing. Phoshodiesterase-4 (PDE4) inhibitor drugs increase inspiratory motor activity and appear to induce a long-lasting increase in inspiratory frequency (“frequency plasticity”). To test whether a PDE4 inhibitor drug induces frequency plasticity, neonatal rat brainstem-spinal cords were isolated and exposed to bath-applied roflumilast (10 min, 0.02–1.0 µM). Roflumilast acutely increased burst frequency and induced frequency plasticity in a concentration-dependent manner. Blockade of protein kinase A (PKA) or exchange protein activated by cAMP (EPAC) signaling pathways abolished the induction, but not the maintenance, of roflumilast-induced frequency plasticity. Brainstem-spinal cords isolated from neonatal rats injected with lipopolysaccharide (LPS, 0.1 mg/kg, 3 h prior) expressed frequency plasticity following bath-applied roflumilast at 0.05–0.5 µM, but not at lower concentrations. This shows that roflumilast-induced frequency plasticity is largely resistant to LPS-induced inflammation. Thus, roflumilast increases inspiratory burst frequency acutely and induces frequency plasticity even during ongoing inflammation, which could have important clinical implications.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"335 ","pages":"Article 104435"},"PeriodicalIF":1.9,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829381","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}
Matthew D. James , Devin B. Phillips , Nicolle J. Domnik , J.Alberto Neder
{"title":"Pathophysiological mechanisms of exertional dyspnea in people with cardiopulmonary disease: Recent advances","authors":"Matthew D. James , Devin B. Phillips , Nicolle J. Domnik , J.Alberto Neder","doi":"10.1016/j.resp.2025.104423","DOIUrl":"10.1016/j.resp.2025.104423","url":null,"abstract":"<div><div>Physical activity is a leading trigger of dyspnea in chronic cardiopulmonary diseases. Recently, there has been a renewed interest in uncovering the mechanisms underlying this distressing symptom. We start by articulating a conceptual framework linking cardiorespiratory abnormalities with the central perception of undesirable respiratory sensations during exercise. We specifically emphasize that exertional dyspnea ultimately reflects an imbalance between (high) demand and (low) capacity. As such, the symptom arises in the presence of a heightened inspiratory neural drive – the will to breathe – secondary to a) increased ventilatory output relative to the instantaneous ventilatory capacity (<em>excessive</em> breathing) and/or b) its impeded translation into the act of breathing due to constraints on tidal volume expansion (<em>constrained</em> breathing). In patients with chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and interstitial lung disease (ILD), <em>constrained</em> breathing assumes a more dominant role as the disease progresses. <em>Excessive</em> breathing due to heightened wasted ventilation in the physiological dead space is particularly important in the initial stages of COPD, while alveolar hyperventilation has a major contributory role in hypoxemic patients with ILD. Hyperventilation is also a leading driver of dyspnea in heart failure (HF) with reduced ejection fraction (EF), while high physiological dead space is the main underlying mechanism in HF with preserved EF. Similarly, wasted ventilation in poorly perfused lung tissue dominates the scene in pulmonary vascular disease. New artificial intelligence-based approaches to expose the contribution of <em>excessive</em> and <em>constrained</em> breathing may enhance the yield of cardiopulmonary exercise testing in investigating exertional dyspnea in these patients.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104423"},"PeriodicalIF":1.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739229","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":"Swallowing and ventilation patterns in stable COPD patients: An observational study","authors":"Virgil Rolland , Armand Bonne , Rimeh Ayari , Grégoire Prum , Eric Verin","doi":"10.1016/j.resp.2025.104419","DOIUrl":"10.1016/j.resp.2025.104419","url":null,"abstract":"<div><div>Our study aimed to investigate swallowing coordination by analyzing ventilatory patterns during of solids and liquids food intakes. Twenty-one patients with severe to very severe stable COPD (GOLD III and IV) underwent ventilation and swallowing recordings while performing standardized swallowing tasks. The results revealed that the expiratory-expiratory (EE) swallowing pattern was predominant, accounting for 80 % of swallows, with no significant differences between solid and liquid swallows. Non-EE patterns occurred in an average of 20.68 % of swallows per patient. Our results demonstrated an increased inspiratory time (IT) during liquid swallows compared to rest (1.05 ± 0.28 s vs 1.29 ± 0.22 s; <em>p</em> < 0.0125), as well as prolonged expiratory time (ET: 2.09 ± 0.78 s vs 3.42 ± 1.16 s; <em>p</em> < 0.001) and total respiratory cycle time (TT: 3.14 ± 1.03 s vs 4.70 ± 1.21 s; <em>p</em> < 0.01) during both solid and liquid swallows compared to rest. These changes resulted in a decreased IT/TT ratio during swallowing. Our findings confirm that the EE swallowing pattern remains predominant in stable COPD patients, consistent with observations in healthy individuals. Additionally, the study highlights significant alterations in ventilatory patterns during swallowing. These results contribute to a better understanding of the interplay between swallowing and ventilation in COPD and its potential implications for airways protection.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104419"},"PeriodicalIF":1.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kohei Sato , Tatsuki Kamoda , Rintaro Sakamoto , Keisho Katayama , Toru Neki , Masaki Katayose , Erika Iwamoto
{"title":"Effects of inspiratory muscle metaboreflex on cerebral circulation at rest and during light-intensity exercise in healthy males","authors":"Kohei Sato , Tatsuki Kamoda , Rintaro Sakamoto , Keisho Katayama , Toru Neki , Masaki Katayose , Erika Iwamoto","doi":"10.1016/j.resp.2025.104422","DOIUrl":"10.1016/j.resp.2025.104422","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aimed to clarify the effects of inspiratory muscle metaboreflex on cerebral circulation at rest and during exercise.</div></div><div><h3>Methods</h3><div>Twelve young males randomly completed two trials (rest and exercise [leg cycling at 40 % peak oxygen uptake] trials) on separate days. In each trial, the internal carotid artery (ICA), an index of cerebral circulation, was measured using Doppler ultrasound 2 min after inspiratory loading breathing (IL condition) or non-loading breathing (control condition). During ICA assessments, participants engaged in 3 min of spontaneous breathing (SB), followed by 3 min of isocapnic hyperventilation (IHV).</div></div><div><h3>Results</h3><div>ICA conductance was lower in the IL condition than in the control condition in both rest and exercise trials. Inspiratory muscle metaboreflex did not reduce ICA blood flow during SB but decreased it during IHV in both trials.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that inspiratory muscle metaboreflex could decrease cerebrovascular conductance from rest to light-intensity exercise and attenuates cerebral blood flow with increased respiratory muscle work.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104422"},"PeriodicalIF":1.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739228","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}
Ethan S. Benevides , Sabhya Rana , David D. Fuller
{"title":"Chemogenetic activation of the diaphragm after spinal cord injury in rats","authors":"Ethan S. Benevides , Sabhya Rana , David D. Fuller","doi":"10.1016/j.resp.2025.104421","DOIUrl":"10.1016/j.resp.2025.104421","url":null,"abstract":"<div><div>We tested the hypothesis that activation of DREADDs in the mid-cervical spinal cord could restore diaphragm activation during spontaneous breathing after cervical spinal cord injury (SCI). Adult Sprague Dawley rats (n = 7) received bilateral mid-cervical ventral horn injections of an AAV construct encoding an excitatory DREADD (AAV9-hSyn-HA-hM3D(Gq)-mCherry; titer: 2.44 × 10<sup>13</sup> vg/mL). Subsequently, diaphragm electromyogram (EMG) activity was recorded during spontaneous breathing under isoflurane anesthesia. The selective DREADD ligand JHU37160 (J60) was administered intravenously at acute (3 days), sub-acute (2 weeks), and chronic (2 months) timepoints following cervical hemilesion at spinal level C2. J60 administration resulted in robust increases in diaphragm EMG output at all timepoints, and near-complete restoration of diaphragm EMG activity from the paralyzed hemi-diaphragm in 50 % of trials. Administration of J60 to DREADD naïve, spinal intact rats (n = 8) did not produce an increase in diaphragm activity. These proof-of-concept results indicate that refinement of this technique may provide a strategy for improving diaphragm activation after cervical SCI.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104421"},"PeriodicalIF":1.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743516","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}
Edward J. Zuperku , Francis A. Hopp , Astrid G. Stucke
{"title":"Pulmonary stretch receptor modulation of synaptic inhibition shapes the discharge pattern of respiratory premotor neurons","authors":"Edward J. Zuperku , Francis A. Hopp , Astrid G. Stucke","doi":"10.1016/j.resp.2025.104420","DOIUrl":"10.1016/j.resp.2025.104420","url":null,"abstract":"<div><div>Many studies focus on the mechanisms of respiratory rhythm generation through neuronal interactions in the preBötzinger and Bötzinger complex area. There is limited insight into how the varied discharge patterns of propriobulbar, rhythm generating neurons are integrated to generate the slowly augmenting and decrementing discharge patterns observed in respiratory premotor neurons. Neuronal discharge patterns were obtained, <em>in vivo</em>, from inspiratory (I) and expiratory (E) premotor neurons in the ventral respiratory group of adult, anesthetized and vagotomized canines. Electrical activation of vagal afferents was used to produce pulmonary stretch receptor (PSR), step-input patterns, throughout or within either the I- or E-phase. PSR inputs decreased the discharge pattern slopes of augmenting and decrementing E-neurons and increased the slopes of augmenting and decrementing I-neurons. PSR inputs that were applied only for part of the phase acutely changed the discharge pattern to the trajectory associated with those PSR throughout-phase inputs, but the pattern returned immediately to the original trajectory after the PSR input terminated. These types of responses can be reproduced with high fidelity by a mathematical model based on reciprocal inhibition between augmenting and decrementing neurons of the same respiratory phase. Best fit is achieved when PSR inputs solely modulate the strength of the synaptic inhibition of decrementing neurons by augmenting neurons at the presynaptic level. Leaky integrator functions are not necessary to generate the gradually augmenting and decrementing patterns. This model offers a novel and different mechanistic way to conceptualize the generation and PSR control of respiratory discharge patterns.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104420"},"PeriodicalIF":1.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731503","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}
Valentina Jelinčić , Pei-Ying S. Chan , Paul W. Davenport , Andreas von Leupoldt
{"title":"Neural gating of respiratory sensations as a potential mechanism of dyspnea perception: State-of-the-art and future directions","authors":"Valentina Jelinčić , Pei-Ying S. Chan , Paul W. Davenport , Andreas von Leupoldt","doi":"10.1016/j.resp.2025.104418","DOIUrl":"10.1016/j.resp.2025.104418","url":null,"abstract":"<div><h3>Context</h3><div>Dyspnea – the subjective experience of breathing discomfort – is a prevalent and debilitating symptom in various chronic conditions, featuring a complex interplay of sensory, cognitive, and emotional factors contributing to its perception. In recent years, growing evidence emerged for the importance of neural processing in shaping symptom experiences such as dyspnea.</div></div><div><h3>Objective</h3><div>This frontiers review focuses on the neural gating of respiratory sensations (NGRS), as a potential neural mechanism underlying dyspnea perception. NGRS is measured by the repetition suppression of respiratory-related evoked potentials (RREP) elicited by paired inspiratory occlusions. NGRS may reflect the brain’s capacity to filter redundant respiratory input, and reduced NGRS may constitute a biomarker for aversive dyspnea experience.</div></div><div><h3>Review</h3><div>We summarize the current state-of-the-art on the relationships between NGRS and dyspnea, noting the inconsistent findings in healthy individuals along with promising evidence from clinical populations, such as chronic obstructive pulmonary disease (COPD). The inconsistent findings may be attributed to methodological limitations, including the significant variability in experimental designs and analytical choices hampering NGRS reliability, and the influence of top-down attention and expectations. In the final part of the review, we suggest future directions for the investigation of the NGRS-dyspnea relationship, including mechanistic research using advanced EEG analysis, mobile neuroimaging, and brain stimulation techniques to delineate the contributions of top-down and bottom-up mechanisms to NGRS.</div></div><div><h3>Conclusions</h3><div>By addressing the current knowledge gaps, this review forms a part of the concentrated effort to promote brain-based interventions for alleviating the distressing experience of chronic dyspnea.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104418"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731501","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}
Tomas Buday , Mariana Brozmanova , Janka Jakusova , Zuzana Biringerova , Lukas Martvon , Jana Plevkova
{"title":"Complex respiratory effects of nebulised citric acid and capsaicin as tussive agents: A comparative study in conventional and specific pathogen-free guinea pigs","authors":"Tomas Buday , Mariana Brozmanova , Janka Jakusova , Zuzana Biringerova , Lukas Martvon , Jana Plevkova","doi":"10.1016/j.resp.2025.104417","DOIUrl":"10.1016/j.resp.2025.104417","url":null,"abstract":"<div><h3>Background</h3><div>Citric acid and capsaicin are commonly used in cough research due to their reproducible effects on animal models and humans. However, these extend beyond cough provocation.</div></div><div><h3>Objective</h3><div>To characterize and describe the respiratory responses to citric acid and capsaicin exposure using whole-body plethysmography in conventional (CON) and specific pathogen-free (SPF) guinea pigs.</div></div><div><h3>Methods</h3><div>Male and female guinea pigs were exposed to aerosols of saline, citric acid (0.4 M), and capsaicin (25 µM). Cough and respiratory parameters (inspiratory and expiratory time, respiratory rate, tidal volume, enhanced pause and mid-expiratory flow) were recorded.</div></div><div><h3>Results</h3><div>Both tussive agents induced upper and lower airway responses besides cough, with significant differences in respiratory parameters between CON and SPF animals. Citric acid elicited a stronger upper airway response compared to capsaicin.</div></div><div><h3>Conclusion</h3><div>Citric acid and capsaicin trigger complex respiratory responses (bronchoconstriction, braking, breathing pattern changes). These findings highlight the need to consider broader respiratory responses in translational cough research.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"334 ","pages":"Article 104417"},"PeriodicalIF":1.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704507","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}