Respiratory Physiology & Neurobiology最新文献

Obstructive Sleep Apnea Syndrome (OSAS) disrupts millions of lives with its burden of airway obstruction during sleep. Continuous Positive Airway Pressure (CPAP) therapy has been scrutinized for its biomechanical impact on the respiratory tract. This study leverages computational fluid dynamics to investigate CPAP's effects at 9 cm H₂O (882.6 Pa) on the computed-tomography-based nasal-to-14-generation full respiratory tract model compared to ambient conditions, focusing on static pressure, airflow velocity, and shear stress. Our findings reveal that CPAP significantly increases static pressure, enhancing airway patency without adverse changes in airflow velocity or harmful shear stress on lung tissue, challenging prior concerns about its safety. Notably, the larynx experiences the highest shear stress due to its narrow anatomy, yet CPAP therapy overall supports airway walls against collapse. This investigation highlights CPAP's critical role in OSAS treatment, offering reassurance about its safety and efficacy. By clarifying CPAP therapy's physiological impacts, our study contributes vital insights for optimizing OSAS management strategies, affirming CPAP's benefit in maintaining open airways with minimal tissue strain.

Eight pig tracheal strips were stimulated to contract with log increments of methacholine from 10^-8 to 10^-5 M. For each strip, the concentration-response was repeated four times in a randomized order to measure isometric force, isotonic shortening against a load corresponding to either 5 or 10 % of a reference force, and average force, stiffness, elastance and resistance over one cycle while the strip length was oscillating sinusoidally by 5 % at 0.2 Hz. For each readout, the logEC50 was calculated and compared. Isotonic shortening with a 5 % load had the lowest logEC50 (-7.13), yielding a greater sensitivity than any other contractile readout (p<0.05). It was followed by isotonic shortening with a 10 % load (-6.66), elastance (-6.46), stiffness (-6.46), resistance (-6.38), isometric force (-6.32), and average force (-6.30). Some of these differences were significant. For example, the EC50 with the average force was 44 % greater than with the elastance (p=0.001). The methacholine sensitivity is thus affected by the contractile readout being measured.

We investigated whether central or peripheral limitations to oxygen uptake elicit different respiratory sensations and whether dyspnea on exertion (DOE) provokes unpleasantness and negative emotions in patients with heart failure with preserved ejection fraction (HFpEF). 48 patients were categorized based on their cardiac output (Q̇c)/oxygen uptake (V̇O₂) slope and stroke volume (SV) reserve during an incremental cycling test. 15 were classified as centrally limited and 33 were classified as peripherally limited. Ratings of perceived breathlessness (RPB) and unpleasantness (RPU) were assessed (Borg 0–10 scale) during a 20 W cycling test. 15 respiratory sensations statements (1–10 scale) and 5 negative emotions statements (1−10) were subsequently rated. RPB (Central: 3.5±2.0 vs. Peripheral: 3.4±2.0, p=0.86), respiratory sensations, or negative emotions were not different between groups (p>0.05). RPB correlated (p<0.05) with RPU (r=0.925), “anxious” (r=0.610), and “afraid” (r=0.383). While DOE provokes elevated levels of negative emotions, DOE and respiratory sensations seem more related to a common mechanism rather than central and/or peripheral limitations in HFpEF.

The causes and consequences of excess exercise ventilation (EEV) in patients with fibrosing interstitial lung disease (f-ILD) were explored. Twenty-eight adults with f-ILD and 13 controls performed an incremental cardiopulmonary exercise test. EEV was defined as ventilation-carbon dioxide output (⩒E-⩒CO₂) slope ≥36 L/L. Patients showed lower pulmonary function and exercise capacity compared to controls. Lower DL_CO was related to higher ⩒E-⩒CO₂ slope in patients (P<0.05). 13/28 patients (46.4%) showed EEV, reporting higher dyspnea scores (P=0.033). Patients with EEV showed a higher dead space (VD)/tidal volume (VT) ratio while O₂ saturation dropped to a greater extent during exercise compared to those without EEV. Higher breathing frequency and VT/inspiratory capacity ratio were observed during exercise in the former group (P<0.05). An exaggerated ventilatory response to exercise in patients with f-ILD is associated with a blunted decrease in the wasted ventilation in the physiological dead space and greater hypoxemia, prompting higher inspiratory constraints and breathlessness.

We sought to determine if peripheral hypercapnic chemosensitivity is related to expiratory flow limitation (EFL) during exercise. Twenty participants completed one testing day which consisted of peripheral hypercapnic chemosensitivity testing and a maximal exercise test to exhaustion. The chemosensitivity testing consisting of two breaths of 10% CO₂ (O₂∼21%) repeated 5 times during seated rest and the first 2 exercise intensities during the maximal exercise test. Following chemosensitivity testing, participants continued cycling with the intensity increasing 20 W every 1.5 minutes till exhaustion. Maximal expiratory flow-volume curves were derived from forced expiratory capacity maneuvers performed before and after exercise at varying efforts. Inspiratory capacity maneuvers were performed during each exercise stage to determine EFL. There was no difference between the EFL and non-EFL hypercapnic chemoresponse (mean response during exercise 0.96 ± 0.46 and 0.91 ± 0.33 l min⁻¹ mmHg⁻¹, p=0.783). Peripheral hypercapnic chemosensitivity during mild exercise does not appear to be related to the development of EFL during exercise.

Purpose

Extracellular acidification is a major component of tissue inflammation, including airway inflammation in asthmatics. However, its physiological/pathophysiological significance in bronchial function is not fully understood. Currently, the functional role of extracellular acidification on bronchial contraction was explored.

Methods

Left main bronchi were isolated from male BALB/c mice. Epithelium-removed tissues were exposed to acidic pH under submaximal contraction induced by 10⁻⁵ M acetylcholine in the presence or absence of a COX inhibitor indomethacin (10⁻⁶ M). Effects of AH6809 (10⁻⁶ M, an EP₂ receptor antagonist), BW A868C (10⁻⁷ M, a DP receptor antagonist) and CAY10441 (3×10⁻⁶ M, an IP receptor antagonist) on the acidification-induced change in tension were determined. The release of prostaglandin E₂ (PGE₂) from epithelium-denuded tissues in response to acidic pH was assessed using an ELISA.

Results

In the bronchi stimulated with acetylcholine, change in the extracellular pH from 7.4 to 6.8 caused a transient augmentation of contraction followed by a sustained relaxing response. The latter inhibitory response was abolished by indomethacin and AH6809 but not by BW A868C or CAY10441. Both indomethacin and AH6809 significantly increased potency and efficacy of acetylcholine at pH 6.8. Stimulation with low pH caused an increase in PGE₂ release from epithelium-denuded bronchi. Interestingly, the acidic pH-induced bronchial relaxation was significantly reduced in a murine asthma model that had a bronchial hyperresponsiveness to acetylcholine.

Conclusion

Taken together, extracellular acidification could inhibit the bronchial contraction via autocrine activation of EP₂ receptors. The diminished acidic pH-mediated inhibition of bronchial tone may contribute to excessive bronchoconstriction in inflamed airways such as asthma.

Background

Pulmonary physiology encompasses intricate breathing patterns (BPs), characterized by breathing frequency (Bf), volumes, and flows. The complexities intensify in the presence of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD), especially during exercise. This study seeks to identify pivotal factors driving changes among these variables and establish cutoff values, comparing their efficacy in differentiating BPs to traditional methods, specifically a breathing reserve (BR) of 30% and a Bf of 50 bpm.

Methods

Screening 267 subjects revealed 23 with ILD, 126 with COPD, 33 healthy individuals, and the exclusion of 85 subjects. Lung function tests and ramp-pattern cardiopulmonary exercise testing (CPET) were conducted, identifying crucial BP elements. Changes were compared between groups at peak exercise. The area under the receiver operating characteristic curve (AUC) analysis determined cutoff values.

Results

Inspiratory time (TI) remained constant at peak exercise for all subjects (two-group comparisons, all p=NS). Given known differences in expiratory time (TE) and tidal volume (VT) among ILD, COPD, and healthy states, constant TI could infer patterns for Bf, total breathing cycle time (TTOT=60/Bf), I:E ratio, inspiratory duty cycle (IDC, TI/TTOT), rapid shallow breathing index (Bf/VT), tidal inspiratory and expiratory flows (VT/TI and VT/TE), and minute ventilation (V̇E=Bf×VT) across conditions. These inferences aligned with measurements, with potential type II errors causing inconsistencies. RSBI of 23 bpm/L and VT/TI of 104 L/min may differentiate ILD from control, while V̇E of 54 L/min, BR of 30%, and VT/TE of 108 may differentiate COPD from control. BR of 21%, TE of 0.99 s, and IDC of .45 may differentiate ILD from COPD. The algorithm outperformed traditional methods (AUC 0.84–0.91 versus 0.59–0.90).

Conclusion

The quasi-fixed TI, in conjunction with TE and VT, proves effective in inferring time-related variables of BPs. The findings have the potential to significantly enhance medical education in interpreting cardiopulmonary exercise testing. Moreover, the study introduces a novel algorithm for distinguishing BPs among individuals with ILD, COPD, and those who are healthy.

The determination the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) during spirometry studies, is at the core of the evaluation of the pulmonary function of patients with respiratory diseases. The Global Lung Function Initiative (GLI) offers the most extensive data set of normal lung functions available, which is currently used to determine the average expected/predicted FEV1 and FVC (_predV), and their lower limit of normal (LLN, 5th percentile) at any given height and age for women and men. These prediction equations are currently expressed in a rather complex form: _predV = exp [p+ (a x Ln (height) + (n x Ln (age)) + spline] and LLN = exp(Ln (_predV) + Ln (1 – 1.645 x S x CV)/S); and are currently used to generate interpretations in commercialized spinographic system. However, as shown in this paper, these equations contain physiological and fundamental allometric information on lung volumes that become obvious when rewriting mean predicted values as a “simple” power function of height and LLN as a percentage of the mean predicted values. We therefore propose to present the equations of prediction obtained from the GLI data using simplified expressions in adults (18–95 years old) to reveal some of their physiological and allometric meaning. Indeed, when predicted FEV1 and FVC (_predV) were expressed under the form _predV= αx height^a x b(age), the resulting exponent (a) ranges between 2 and 3, transforming the one dimension of a length (size) into a volume, akin to the third-order power (cubic) function of height historically used to predict lung volumes. Only one function, b (age), is necessary to replace all the factors related to age, including the tables of discrete data of spline functions original equations. Similarly, LLN can be expressed as LLN = c (age) x _predV to become a simple percentage of the predicted values, as a function of age. The equations with their respective new polynomial functions were validated in 52,764 consecutive spirometry tests performed in 2022 in 22,612 men and 30,152 women at the Cleveland Clinic. Using these equations, it become obvious that for both women and men, FEV1/FVC ratio decreases with the size as the exponent of the power function of height is lower for FEV1 than FVC. We conclude that rewriting the GLI predicted equations with simpler formulations restitutes to the GLI data some of their original allometric meaning, without altering the accuracy of their prediction.

Motor behaviors such as breathing required temporal coordination of different muscle groups to insured efficient ventilation and provide oxygen to the body. This action is the result of interactions between neural networks located within the brainstem. Inspiration and expiration depend at least in part on interactions between two separate oscillators: inspiration is driven by a neural network located in the preBötzinger complex (PreBötC) and active expiration is driven by a network in the parafacial respiratory group (pFRG). Neurons of the pFRG are silent at rest and become active when the respiratory drive increased. This study investigated the temporal coordination between the brainstem respiratory network and the lumbar spinal network that generates spontaneous activities that is different of the induced fictive locomotion. The remaining question is how these activities coordinate early during the development. Results of this study show that brainstem networks contribute to the temporal coordination of the lumbar spontaneous activity during inspiration since lumbar motor activity occurs exclusively during the expiratory time. This study also investigated the role of the β-noradrenergic modulation on the respiratory activities. β-noradrenergic receptors activation increased the frequency of the double bursts and increased expiratory activity at the lumbar level. These results suggest interactions between brainstem and spinal networks and reveal a descending drive that may contribute to the coordination of the respiratory and lumbar spontaneous activities.

In this study, we hypothesized that long-term administration of hesperidin can modulate the inflammatory response and oxidative stress in animals submitted to mechanical ventilation (MV). Twenty-five C57BL/6 male mice were divided into 5 groups: control, MV, animals receiving hesperidin in three doses 10, 25 and 50 mg/kg. The animals received the doses of hesperidin for 30 days via orogastric gavage, and at the end of the period the animals were submitted to MV. In animals submitted to MV, increased lymphocyte, neutrophil and monocyte/macrophage cell counts were observed in the blood and airways. Associated to this, MV promoted an increase in inflammatory cytokine levels such as CCL2, IL-12 and TNFα. The daily administration of hesperidin in the three doses prevented the effects caused by MV, which was observed by a lower influx of inflammatory cells into the airways, a reduction in inflammatory markers and less oxidative damage.