AIMS:Transient hypercapnia has been used to examine shear-mediated vasodilation in the internal carotid artery (ICA) in humans. Previously, a 30-second transient hypercapnic protocol using an end-tidal forcing machine has been used. We aimed to investigate if we could simplify this technique by using a Douglas bag instead of an end-tidal forcing machine, thus creating the transient hypercapnic Douglas bag (THCDB) protocol. We hypothesized that by increasing the hypercapnic intensity when using a Douglas bag, a 30-second transient test would elicit shear mediated vasodilation in the internal carotid artery. METHODS:16 participants (7 female) completed the THCDB protocol, breathing 9% CO2. Internal carotid artery diameter (ICAd), velocity, flow, and shear rate were recorded using vascular Duplex ultrasound, with the change in shear rate area under the curve (DSRAUC) between baseline and the time of peak dilation being calculated from these measures; while mean arterial pressure (MAP) was recorded using finger photoplethysmography before, during, and after the THCDB protocol. RESULTS:The THCDB protocol increased shear rate in the ICA (p < 0.0001) and led to significant peak dilation of the ICA (Baseline: 4.9 mm; Peak: 5.2 mm; p < 0.0001). Peak dilation of the ICA occurred 75.9 ± 13.2 s following the onset of CO2 inhalation. The peak %ΔICAd was positively correlated with the change in DSRAUC (R2 = 0.36; p = 0.01). DISCUSSION:The THCDB protocol resulted in shear-mediated vasodilation in the ICA akin to that seen in other transient CO2 tests and therefore represents a novel technique to assess shear-mediated vasodilation of the ICA. While THCDB protocol is reasonably effective at investigating the effects of transient hypercapnia on cerebral hemodynamics, there are several methodological factors that require further experimentation to refine the technique.
Retinopathy of prematurity (ROP) is an eye disease that severely impacts premature infants, especially those born before 31 weeks gestation and those born at very low birth weights (≤1500 g). In this brief review we provide an overview of current challenges in reducing ROP, the methods used to treat ROP and mitigate its impact, the importance of close management of oxygen and respiratory strategies for best outcome in these infants. We highlight gaps that need further research and provide suggestions for future research and changes in treatment strategy to reduce ROP and improve outcomes in preterm infants at risk for severe ROP. Feedback controlled ventilation to maintain peripheral tissue oxygenation (SpO2, measured by pulse-oximetry) between 89% and 92% is a key component of our proposed strategy. This will require a control system that does not only depend on human intervention and, most likely, will require predictive algorithms based on machine learning (ML) methods to provide the most stringent adherence to this goal.
Breath-hold functional MRI (bh-fMRI) is a widely used method for mapping cerebrovascular reactivity (CVR). Normalization of BOLD signal changes to end-tidal CO₂ changes (ΔpetCO₂) is suggested to improve between-subject comparability. The aim was to characterize magnitude and variability of ΔpetCO₂ during short breath-hold maneuvers. Twenty healthy volunteers participated in this study. Ten of these participants performed five breathing paradigms: baseline breathing, and end-expiratory breath-holds of 6, 9, and 12 s, as well as a deep breathing maneuver, each repeated seven times. petCO₂ was recorded continuously via nasal cannula. Within- and between-subject variability were quantified using the coefficient of variation (CV). Differences in ΔpetCO₂ between paradigms were assessed using repeated-measures ANOVA. Ten additional participants underwent the 9 s breath-hold paradigm and spirometry; associations between ΔpetCO₂ and pulmonary volumes, age, and baseline petCO₂ were assessed using Pearson correlation. Within-subject within-paradigm CVs were low (3.4-4.7%), indicating high reproducibility. Between-subject CVs were substantially higher (19.7-35.3%). ΔpetCO₂ differed significantly between the 6 and 9 s paradigms (p = 0.014, pFDR = 0.017) but not between the 9 and 12 s paradigms (p = 0.209, pFDR = 0.209). The deep breathing induced a reproducible petCO₂ decrease. A very strong inverse correlation was observed between ΔpetCO₂ and inspiratory vital capacity (IVC) (r = -0.797 (95%CI: -0.950--0.336), p = 0.006, pFDR = 0.030). Short breath-hold maneuvers induce reproducible, yet variable CO₂ responses within individuals. Pulmonary anatomy is a key determinant of ΔpetCO₂. Inadvertent deep breathing prior to breath-holding may induce petCO₂ decreases of non-negligible magnitude, with potential implications for bh-fMRI interpretation.
The purpose of this study was to determine if the ventilatory responses during mechanically sensitive afferent stimulation were augmented in hypertension (HTN). Participants with HTN (n = 11; 52 ± 12 yrs; 27 ± 3 kg/m2) and controls (CTL, n = 11; 56 ± 12 yrs; 27 ± 4 kg/m2) were recruited. Following a resting period, the muscle mechanically sensitive afferents were stimulated with passive leg movement for 30-seconds. Ventilatory variables were measured (breath-by-breath) at rest and during passive leg movement protocols. All data was analyzed with a two-way repeated measures ANOVA. Significance was set at p ≤ 0.05. For ventilation and breathing frequency, there were significant main effects of time (both, p < 0.01), but no significant main effects of group or interaction (all, p > 0.67). There were no significant main effects of time, group, or interaction for tidal volume (all, p > 0.13). These data support that mechanically sensitive afferent stimulation does not elicit an augmented ventilatory response in adults with HTN.
Diaphragm electromyogram (EMGdi) is commonly measured using esophageal multi-paired electrode catheters; however, contamination by cardiac electrical activity can compromise signal quality. This study compared several approaches for reducing electrocardiographic (ECG) artifact and examined whether their performance differed based on sex. We also evaluated their influence on the relationship between EMGdi and force output (PTPdi). Sixteen healthy young adults (7 female, 9 male) performed inspiratory pressure threshold loading (PTL) to task failure while instrumented with a multi-pair esophageal balloon catheter and a simultaneous ECG. EMGdi signals were processed using four approaches: (1) selection of EMG segments between QRS complexes (ECG-R), (2) independent component analysis (ICA), (3) ICA with wavelet transformation (ICA-W), and (4) no artifact removal (RAW). Estimated marginal slopes relating EMGdi to inspiratory PTL did not differ between females and males or among processing methods (all p > 0.05). EMGdi was significantly associated with PTPdi for all processing methods in both sexes. In females, however, these associations were weaker following ICA and ICA-W than with ECG-R (p < 0.05), whereas no differences between methods were observed in males. These findings indicate that all methods effectively reduce ECG artifact during PTL when heart rate remains relatively low. When a simultaneous ECG is unavailable, ICA and ICA-W provide suitable alternatives. However, for studies examining the relationship between EMGdi and diaphragm force output, ECG-guided QRS exclusion is the preferred processing approach.
Hypoxia-inducible factor (HIF) is a key regulator of cellular adaptation to reduced oxygen availability. Chronic intermittent hypoxia (CIH), characterized by recurrent cycles of hypoxia and reoxygenation, promotes oxidative stress and activates hypoxia-sensitive signaling pathways involved in ventilatory control. Luteolin-7-O-glucoside (luteolin), a flavonoid with antioxidant and anti-inflammatory properties, has been proposed as a potential modulator of HIF activity. This study evaluated the effects of a 7-day luteolin treatment on the ventilatory pattern and brainstem HIF expression in mice exposed to CIH, a model that mimics a hallmark feature of obstructive sleep apnea. Ventilation was assessed by whole-body plethysmography under baseline normoxic conditions and during an acute hypoxic challenge. Functional assessments revealed that luteolin administration significantly altered the baseline respiratory pattern, increasing the occurrence of apneas during baseline normoxic breathing in both the normoxic and CIH groups. Under baseline conditions, luteolin-treated CIH animals also exhibited a reduced respiratory frequency and an increased tidal volume, without significant changes in minute ventilation. Despite these alterations in baseline breathing, Luteolin treatment did not alter the acute hypoxic ventilatory response (HVR) in either experimental group. To investigate the molecular mechanisms underlying these ventilatory effects, brainstem analysis was performed. Luteolin treatment (10 μg/kg) reduced Hif1a and Epas1 mRNA expression in the brainstem and decreased the number of neurons exhibiting HIF-1α nuclear immunofluorescence within the nucleus of the solitary tract (NTS). Additionally, luteolin reduced Nox4 expression in the brainstem while elevating nitrite levels, suggesting a direct modulation of redox-related pathways. Together, these findings indicate that luteolin alters the baseline respiratory pattern by increasing apnea occurrence in both normoxia and CIH groups under baseline normoxic conditions, an effect potentially linked to the downregulation of brainstem HIF expression and the modulation of local redox state, while the acute ventilatory response to hypoxia remains preserved.
We review clinical observations and experimental data to examine the pathophysiological mechanisms by which apnea of prematurity and intermittent hypoxemia destabilizes respiratory control and might lead to neurodevelopmental disorders. Clinically, both apnea and hypoxemia are characterized by marked heterogeneity in definitions, monitoring approaches, and temporal patterns, complicating comparisons across studies. Clinical evidence suggests that cumulative hypoxemic burden, rather than apnea duration alone, is a key determinant of respiratory and neurodevelopmental morbidity in preterm neonates. Repeated hypoxemia-reoxygenation cycles enhance peripheral chemoreceptor sensitivity, narrow the CO₂ reserve, and promote respiratory instability during a critical developmental window. Animal models of intermittent hypoxia demonstrate that this sensitization is mediated by reactive oxygen species (ROS) signaling and a metabolic response involving neuronal adenosine release, activation of xanthine oxidase and NADPH oxidase ultimately converging to inhibition of mitochondrial complex I and metabolic depression during the hypoxic phase. This response is clinically evidenced by a reduction of EEG amplitude occurring during apnea. Recent data suggest that subtle changes in biochemical equilibrium within the Krebs cycle favor succinate accumulation during the hypoxic phase, which is then rapidly oxidized during reoxygenation, leading to enhanced ROS production, as demonstrated in models of ischemia-reperfusion injury and neonatal severe hypoxia. We finally provide preliminary data showing that the succinate dehydrogenase inhibitor dimethyl malonate reduces oxidative phosphorylation in brain sample of mice pups, therefore establishing an experimental framework to address the hypothesis that succinate accumulation contributes to ROS synthesis in a rodent model of apnea of prematurity.
Arterial oxygen saturation is traditionally interpreted using threshold-based paradigms in which physiological significance is primarily attributed to overt hypoxemia. However, evidence from sleep physiology and integrative respiratory research suggests that oxygenation dynamics, including the cumulative burden of transient oxygen desaturation, may provide complementary physiological information beyond average oxygen saturation alone. Whether similar concepts are relevant during wakefulness remains largely unexplored. Among the factors that could influence oxygenation dynamics, breathing route has received surprisingly little attention. Although nasal breathing has recognized advantages for airflow conditioning, nitric oxide delivery, and upper airway mechanics, direct evidence demonstrating that oral breathing alters oxygenation stability during wakefulness is currently lacking. Existing studies instead provide indirect observations and identify important knowledge gaps rather than establishing causal relationships. Here, we propose a conceptual framework in which breathing route is proposed as an experimental model for investigating oxygenation stability during wakefulness. We discuss physiological mechanisms that could plausibly link breathing route to ventilatory efficiency, ventilation-perfusion matching, chemoreflex activation, autonomic regulation, and mitochondrial redox signaling, while emphasizing that these mechanisms remain hypothetical and require direct experimental validation. Rather than arguing that oral breathing causes clinically relevant oxygen desaturation, this Perspective identifies an unresolved question in respiratory physiology and outlines experimentally testable hypotheses to determine whether oxygenation stability represents a previously overlooked physiological variable during wakefulness.
Respiratory pressure regulation contributes to trunk stabilisation and force transmission during physically demanding tasks. Traditional martial arts are associated with enhanced respiratory pressure regulation and trunk muscle activation, but the respiratory-motor strategies underlying these adaptations are time-intensive to learn and poorly understood. This study examined whether a martial arts-derived respiratory-motor training approach integrating augmented feedback (Neuropotency Training) could acutely modify respiratory pressure generation and abdominal muscle activation during force production and postural control tasks. Healthy adults without martial arts experience were randomly assigned to a Neuropotency (n = 10) or control (n = 10) group. Gastric, oesophageal, and transdiaphragmatic pressures were measured using an oesophageal catheter alongside surface electromyography of abdominal and respiratory musculature. The Neuropotency group received vibro-tactile and visual force feedback. Groups were compared using independent t-tests and effect sizes (Cohen's d). Compared with controls, the Neuropotency group demonstrated greater absolute and normalised transdiaphragmatic pressure generation across most tasks (P < 0.05, d ≥ 1.0) and greater abdominal muscle activation during several tasks (P < 0.05, d = 0.64-1.4), without differences in external force output. These findings provide the first experimental evidence that respiratory pressure regulation during functional tasks can be rapidly modified through targeted respiratory-motor training. The accompanying changes in abdominal muscle activation indicate acute adaptations in respiratory-motor coordination that are not captured by external performance measures alone. These findings suggest that respiratory pressure regulation may represent a modifiable target for interventions seeking to optimise physical capability in physically demanding occupational and tactical settings. They highlight the importance of internal physiological measures when evaluating respiratory-motor training adaptations.
The relevance of ventilatory efficiency to aerobic performance in endurance athletes remains incompletely understood, particularly when potential sex-related differences are considered. This study investigated whether ventilatory efficiency is associated with cardiorespiratory fitness and whether sex moderates this association in amateur triathletes. In this cross-sectional study, 59 amateur triathletes (37 male and 22 female) performed a maximal cardiopulmonary exercise test on a cycle ergometer. Ventilatory efficiency was assessed using the nadir of the minute ventilation to carbon dioxide production ratio (V̇E/V̇CO2), defined as the lowest continuous 20-second average achieved during test. Cardiorespiratory fitness was assessed by maximal oxygen uptake (V̇O2max). Multiple linear regression was used to examine the association between V̇E/V̇CO2-Nadir and V̇O2max, including an interaction term for sex, followed by sex-stratified analyses. In the overall sample, V̇E/V̇CO2-Nadir was significantly associated with lower V̇O2max (β = -1.70, p = 0.002). A significant interaction between V̇E/V̇CO2-Nadir and sex was also observed (β = 2.19, p = 0.005), whereas the main effect of sex was not significant (β = 0.373, p = 0.877). In female athletes, higher V̇E/V̇CO₂ nadir was associated with lower V̇O₂max (β = -1.64, p = 0.048, R² = 0.223), whereas no significant association was observed in male athletes (β = 0.49, p = 0.343, R² = 0.026). Overall, these findings suggest that the association between ventilatory efficiency and cardiorespiratory fitness may differ according to sex. While V̇E/V̇CO₂ nadir was associated with V̇O₂max in female athletes, this relationship was not observed in males, indicating a potential sex-dependent interaction that warrants confirmation in larger studies.
Background Ventilation distribution varies with body position because of gravitational loading, thoracic morphology, and respiratory muscle activity. Electrical impedance tomography (EIT) enables real-time assessment of regional ventilation; however, quantitative characterization of posture-related ventilation redistribution and its associated factors in healthy subjects remains limited. Objective To characterize posture-dependent changes in regional ventilation distribution using EIT in healthy subjects and to explore anthropometric and diaphragmatic factors associated with gravity-related ventilation redistribution. Methods 10 healthy male volunteers underwent EIT measurements during quiet breathing in the supine, right lateral decubitus, prone, left lateral decubitus, and sitting positions. Regional ventilation was quantified using predefined regions of interest. Posture-related redistribution was evaluated using Δ ventilation distribution, defined as within-subject changes in regional ventilation proportion relative to supine, to detect subtle redistribution. Associations between Δ ventilation distribution and body mass index (BMI), cardiothoracic ratio (CTR), diaphragm thickness change ratio, and diaphragmatic excursion (DE) were also analyzed. Results Lateral decubitus positioning induced marked gravity-dependent redistribution toward dependent lung regions, with greater asymmetry in the right lateral position. Although overall dorsoventral ventilation patterns appeared similar among supine, prone, and sitting positions, Δ ventilation distribution analysis detected subtle but significant regional redistribution during prone and sitting. Redistribution during lateral positioning was associated with CTR and BMI, whereas redistribution during sitting was associated with DE. Conclusions Posture-related ventilation redistribution may reflect interactions between gravitational loading, thoracic morphology, and diaphragmatic motion. These exploratory findings provide a sensitive physiological framework for quantifying regional redistribution and may improve understanding of position-dependent respiratory mechanics.
Background High-frequency mechanical vibration facilitates respiratory muscle activity via muscle spindle afferents. Although synchronised multi-site chest wall vibration enhances ventilation, the associated intercostal electromyographic (EMG) responses and their contribution to ventilatory changes remain unclear. This study investigated the effects of multi-site chest wall vibration on intercostal muscle activation and ventilation in healthy adults. Methods Twenty healthy adults underwent phase-synchronised chest wall vibration delivered to four or eight intercostal sites during inspiration and expiration. Surface EMG of inspiratory and expiratory intercostal muscles, tidal volume (VT), respiratory rate, and thoracoabdominal motion were recorded. EMG amplitudes were normalised to maximal voluntary contraction (%MVC), and ventilatory variables were compared across conditions. Results Multi-site chest wall vibration significantly increased intercostal EMG activity during inspiration and expiration. Eight-site stimulation elicited greater EMG responses than four-site stimulation in both directly stimulated and adjacent intercostal muscles (4th inspiratory intercostal: 17.65 vs. 11.59%MVC; 3rd: 15.35 vs. 10.54%MVC; p < 0.01). These changes were accompanied by increases in VT (0.86 vs. 0.65 L, p < 0.01), minute ventilation (9.63 vs. 7.33 L/min, p < 0.05), and rib cage displacement (183.6 vs. 157.7%, p < 0.05), without changes in respiratory rate or abdominal motion. Changes in intercostal EMG were positively correlated with VT (inspiratory: r = 0.524; expiratory: r = 0.439; p < 0.01). Conclusion Synchronised multi-site chest wall vibration enhances intercostal muscle activation and ventilation, likely via spatial summation of proprioceptive input, increasing respiratory motor output. This approach may represent a promising non-invasive strategy to augment ventilation.
Early-life exposure to fine particulate matter (PM₂.₅) is increasingly implicated in the developmental origins of chronic respiratory diseases; however, the underlying molecular mechanisms remain poorly defined. This study employed Weighted Gene Co-expression Network Analysis (WGCNA) to investigate transcriptomic alterations associated with intrauterine and early neonatal PM₂.₅ exposure in the developing murine lung. Microarray data (GSE104656) spanning embryonic (E14.5, E18.5) and postnatal (P40) stages were processed using robust normalization and variance filtering to construct a scale-free co-expression network. Principal component analysis revealed that developmental maturation was the primary driver of global transcriptional variation, with no distinct separation attributable to PM₂.₅ exposure. WGCNA identified biologically relevant gene modules involved in immune and metabolic processes as well as cell cycle regulation, that exhibited strong correlations with developmental progression. Functional enrichment analysis confirmed significant involvement in immune activation, leukocyte adhesion, DNA replication, and chromosomal organisation. Although differential expression analysis under stringent thresholds did not detect significant PM₂.₅-responsive genes, integrative network analysis identified eleven exposure-associated genes embedded within key modules. These genes, including Vnn1, Gprc6a, Mfap1a, Rgs16, and Fpr1, represent highly connected hub nodes implicated in oxidative stress regulation, extracellular matrix remodelling, metabolic signalling, and immune modulation. It was concluded that early-life PM₂.₅ exposure did not globally disrupt lung transcriptomic architecture but selectively perturbs critical hub genes within developmental networks. This targeted sub-network vulnerability provided a mechanistic basis for the developmental programming of COPD susceptibility, linking early environmental insults to long-term respiratory dysfunction.
INTRODUCTION:Intermittent hypoxemia (IH) frequently occurs in preterm infants and is increasingly linked to adverse outcomes. We previously demonstrated a relationship between IH and S100B, a brain injury biomarker. Here, we assess these relationships with glial fibrillary acidic protein (GFAP), a protein released following astrocyte injury. METHODS:Infants ≤ 32 weeks' gestation were prospectively enrolled. Oxygen saturation was continuously monitored. IH metrics were quantified using validated algorithms using multiple SpO₂ thresholds. Urine was collected at multiple time points, and GFAP concentrations were measured using an ultrasensitive immunoassay. Infants with severe intraventricular hemorrhage were excluded. Associations between IH metrics and urinary GFAP were examined using weighted Spearman correlation analyses (ρ). RESULTS:Twenty-nine infants contributed 71 urine samples with a median of 2.4 samples per infant [IQR 1.0-4.0] collected at a median postnatal age of 36.0 days [IQR 24.0-45.3]. Higher GFAP concentrations were associated with greater IH burden, including greater percent time in hypoxemia (ρ=0.45-0.47), increased IH frequency (ρ=0.42-0.44), longer IH duration (ρ=0.47-0.48), and lower nadir (ρ= -0.42 to -0.44), all p < 0.001. When stratified by gestational age, extremely preterm infants (<28 weeks gestational age) demonstrated strong relationships between GFAP and IH events of both short (<1 min) and longer (≥1 min) duration, whereas very preterm infants (28-31 weeks gestational age) showed significant associations primarily with longer IH events. CONCLUSIONS:Urinary GFAP levels increase with greater IH exposure in preterm infants. Together with our prior findings for S100B, these results suggest that GFAP represents another astroglial biomarker associated with IH-related brain injury and may provide both mechanistic insight and a noninvasive tool for detecting early brain injury in this vulnerable population.
Few studies have described physiological and cardiac rhythm responses to maximal voluntary breath-holding in elite freedivers. This case study presents minute ventilation, PETO2, PETCO2, involuntary breathing movements (IBMs; surface electromyography), SpO2, muscle and cerebral oxygenation (near-infrared spectroscopy), and cardiac rhythm changes (electrocardiogram) before, during, and after a maximal dry static voluntary breath-hold in a world champion freediver. Glossopharyngeal insufflation prior to the breath-hold increased forced vital capacity from 6.92 L (138% predicted) to 9.04 L (180% predicted). Compared to resting end-tidal gas pressures, the breathe-up in preparation of the breath-hold increased PETO2 (108 mmHg to 135 mmHg) and decreased PETCO2 (36 mmHg to 21 mmHg). The breath-hold was 06'07" in duration, of which 02'20" was spent in the easy-going phase and 03'47" in the struggle phase - the latter encompassing a total of 48 IBMs. Throughout the breath-hold, PETO2 decreased to 38 mmHg and PETCO2 increased to 65 mmHg. SpO2 decreased from 97% to 73%. Muscle oxygenation decreased from 50% to 22%, whereas cerebral oxygenation remained relatively stable until the final ∼20 s of the breath-hold (∼68% to ∼62%). Heart rate variability-based markers of autonomic cardiac activity decreased during the easy-going phase, increased during the struggle phase, and normalized after. Asymptomatic bradycardia with competition between sinus bradycardia and junctional rhythm and (supra)ventricular extrasystoles manifested throughout the struggle phase and resolved after breath-hold cessation. This report of a world champion freediver shows that a long voluntary breath-hold induced transient asymptomatic cardiac arrhythmias, likely linked to the physiological stress of extreme voluntary breath-holding.
BACKGROUND:Thoracic expansion (TE) is associated with respiratory muscle strength and pulmonary function. However, in patients with stroke who present unilateral motor impairment, the relationship between asymmetry in TE measured bilaterally, physical function, and percent vital capacity (%VC) remains unclear. OBJECTIVE:This study aimed to investigate differences in TE between the sound and hemiplegic sides in patients with stroke, and to examine the associations between TE asymmetry, physical function, and %VC. METHODS:Forty male patients with post-stroke hemiplegia were enrolled. TE was measured bilaterally using a unilateral measurement method developed previously. Differences between the sound and hemiplegic sides were analyzed. TE difference and an asymmetry index were calculated, and their correlations with physical function and %VC were examined. Participants were classified into symmetric and asymmetric groups and physical function and %VC were compared between the two groups. RESULTS:TE on the hemiplegic side was significantly lower than that on the sound side. The asymmetry index showed moderate correlations of TE with physical function, demonstrating broader associations than simple side-to-side differences. The results of the between group comparisons showed that classification based on the asymmetry index more clearly reflected the decline in physical function and %VC. Adjusted %VC was 12.9% higher in the symmetric group, but the difference was not significant. CONCLUSIONS:In stroke patients, TE on the hemiplegic side is significantly reduced. When quantified using the asymmetry index, it may serve as a practical and clinically relevant assessment parameter of functional decline.
Spirometry is central to measuring pulmonary function and diagnosing respiratory disease. From spirometry, a flow-volume curve is generated and evaluating the shape of this curve may provide additional insight into pulmonary dysfunction compared to spirometry alone. We sought to determine if the shape of the flow-volume curve could detect signs of abnormal lung emptying in asymptomatic ex-smokers compared to never-smokers. A retrospective analysis of the shape of the flow-volume curves generated from routine spirometry from 61 ex-smokers (46% female) with normal spirometry and no diagnosis of respiratory disease and 42 never-smokers (58% female) was performed. The shape of the flow-volume curve was quantified via the slope ratio method. A slope ratio of 1 would indicate a linear decrease in flow with decreasing lung volume, whereas a slope ratio > 1 indicates a scooped pattern to the flow-volume curve, as seen in obstructive lung disease. Both ex-smokers and never-smokers had normal pulmonary function (Forced Expiratory Volume in 1 s (FEV1): 97 ± 20 vs. 97 ± 18%predicted; forced vital capacity (FVC): 99 ± 21 vs. 98 ± 18%predicted; and FEV1/FVC ratio: 97 ± 05 vs. 99 ± 6%predicted, all p > 0.05). The average slope ratio was higher in ex-smokers compared to never-smokers (1.90 ± 0.93 vs. 1.50 ± 0.78, p < 0.001). These findings suggest that slope ratio analyses may supplement pulmonary function testing to identify subclinical patterns of abnormal lung emptying dynamics in ostensibly healthy ex-smokers. This pattern is distinct from normal healthy ageing and support the inclusion of slope ratio as a tool to supplement evaluation of pulmonary function.
INTRODUCTION:Emphysema and airway disease are major pathological features in smokers, including those with chronic obstructive pulmonary disease (COPD); however, how these two distinct pathologies interact to impair exercise capacity remains poorly understood. This study aimed to comprehensively compare physical performance, body composition, and physical activity across four computed tomography (CT)-based phenotypes: emphysema-dominant (ED), airway disease-dominant (AD), both-dominant (Mixed), and neither-dominant (Mild). METHODS:This cross-sectional analysis used baseline data from a single-center prospective cohort of smokers enriched for COPD. Alongside spirometry and 6-minute walk distance (6MWD), chest CT was performed to quantify the low attenuation volume percentage (LAV%) and airway wall area (Pi10), which enabled classification into Mild, AD, ED, and Mixed phenotypes. RESULTS:A total of 181 smokers (77.9% with COPD) were categorized into Mild, AD, ED, and Mixed groups (n = 62/33/55/31, respectively). The Mixed group exhibited a significantly shorter 6MWD compared with the Mild group. Furthermore, the ED and Mixed phenotypes showed greater dyspnea and oxygen desaturation during exercise. In multivariable analysis, both LAV% and Pi10 were independently associated with 6MWD after adjusting for relevant clinical covariates and muscle strength. A significant interaction between LAV% and Pi10 was observed, demonstrating their synergistic detrimental effect on 6MWD. CONCLUSION:Emphysema and airway disease independently and synergistically contribute to impaired exercise tolerance in smokers. CT-based phenotyping, particularly identification of the Mixed phenotype, may be useful to stratify functional risk and guide targeted interventions for preserving physical function in this population.
Infants born prematurely often develop apnea of prematurity (AOP), characterized by periodic apneas with intermittent hypoxia (IH) and commonly treated with supplemental oxygen. On the other hand, infants born at high altitude experience sustained hypoxia from birth. Thus, during critical developmental period, many infants experience abnormal oxygen environments, including hypoxia or hyperoxia. Emerging evidence indicates that disrupted neonatal oxygen homeostasis can produce long-lasting effects on cardiorespiratory function. Preterm infants also exhibit systemic inflammation, and elevated inflammatory cytokines, which may influence respiratory control. This review summarizes clinical and experimental studies examining how neonatal extreme O2 environment and inflammation affect respiratory control, with an emphasis on underlying mechanisms. Clinical and experimental findings show that IH associated with AOP enhances the hypoxic ventilatory response (HVR) and promotes breathing instability, largely through carotid body chemoreflex sensitization. These changes can persist in adulthood and may increase susceptibility to early-onset cardiorespiratory disease, potentially through epigenetic disruption of redox homeostasis. By contrast, neonatal sustained hypoxia transiently impairs carotid body oxygen sensing and ventilatory responses but typically resolves with maturation. Neonatal hyperoxia, however, causes persistent structural and functional impairment of carotid body function. Whether shared epigenetic mechanisms underlie IH and hyperoxia-induced effects, and how altered carotid body signaling reshapes central respiratory networks, remain important questions for future research.
BACKGROUND:Parkinson's Disease (PD) is a progressive neurological disorder associated with respiratory dysfunction, including inspiratory muscle weakness that contributes to morbidity and mortality. Despite this, the contributory role of the diaphragm remains unclear. This study assessed diaphragm thickness and contractility during tidal breathing in early-stage PD compared with matched controls using ultrasound imaging. METHODS:Twelve participants with early-stage PD (mean age 66.75 +/-8.07 years, mean disease duration 5.33 +/-5.6 years, Hoehn and Yahr stage 2), and twelve matched controls were assessed. Ultrasound measures included diaphragm thickness at end expiration (Tdiexp), end inspiration (Tdiinsp), and contractile thickness (Tdiinsp-Tdiexp). Contractility was evaluated using thickening ratio (DTr), thickening fraction (DTf), and contraction speed (mm/sec). Dyspnoea and respiratory disability were assessed using self-report and the Modified Medical Research Council (mMRC) scale. Correlations between diaphragm measures, motor severity using the MDS-UPDRS, and disease duration were explored. RESULTS:Dyspnoea prevalence and mMRC scores were significantly higher in PD participants. Despite this, no significant between-group differences were observed for Tdiexp (PD: 3.2 +/-0.77 mm; versus matched-controls: 3.01 +/-0.57 mm) or Tdiinsp (PD: 4.27 +/-0.95 mm versus 4.14 +/-1.06 mm) with small effect sizes. DTr and DTf were comparable between groups. Contractile thickness was lower (mean difference 0.03 mm), and contraction speed slower (mean difference 0.03 mm/sec), in PD with small effect sizes noted. No notable relationships between measures and PD disease duration were observed. CONCLUSIONS:Diaphragm thickness and contractility appear maintained in early-stage PD despite increased dyspnoea. Further investigation in larger longitudinal studies across all PD stages and subtypes is required.
