Respiratory Physiology & Neurobiology最新文献

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.

This study aimed to evaluate the timing and frequency of spontaneous apneas during breathing and swallowing by using cineradiography on mouse models of early/initial or late/advanced Parkinson’s disease (PD). C57BL/6 J mice received either 6-OHDA or vehicle injections into their right striatum, followed by respiratory movement recordings during spontaneous breathing and swallowing, and a stress challenge, two weeks later. Experimental group animals showed a significantly lower respiratory rate (158.66 ± 32.88 breaths/minute in late PD, 173.16 ± 25.19 in early PD versus 185.27 ± 25.36 in controls; p<0.001) and a significantly higher frequency of apneas (median 1 apnea/minute in both groups versus 0 in controls; p<0.001). Other changes included reduced food intake and the absence of swallow apneas in experimental mice. 6-OHDA-induced nigrostriatal degeneration in mice disrupted respiratory control, swallowing, stress responsiveness, and feeding behaviors, potentially hindering airway protection and elevating the risk of aspiration.

The airway epithelium serves as a critical interface with the external environment, making it vulnerable to various external stimuli. Airway epithelial stress acts as a catalyst for the onset of numerous pulmonary and systemic diseases. Our previous studies have highlighted the impact of acute stress stimuli, especially bacterial lipopolysaccharide (LPS) and hydrogen peroxide (H₂O₂), on the continuous elevation of intracellular chloride concentration ([Cl⁻]_i). However, the precise mechanism behind this [Cl−]_i elevation and the consequential effects of such stress on the injury repair function of airway epithelial cells remain unclear. Our findings indicate that H₂O₂ induces an elevation in [Cl⁻]_i by modulating the expression of CF transmembrane conductance regulator (CFTR) and Ca-activated transmembrane protein 16 A (TMEM16A) in airway epithelial cells (BEAS-2B), whereas LPS achieves this solely through CFTR. Subsequently, the elevated [Cl⁻]_i level facilitated the injury repair process of airway epithelial cells by activating focal adhesion kinase (FAK). In summary, the [Cl⁻]_i−FAK axis appears to play a promoting effect on the injury repair process triggered by stress stimulation. Furthermore, our findings suggest that abnormalities in the [Cl⁻]_i−FAK signaling axis may play a crucial role in the pathogenesis of chronic airway diseases. Therefore, controlling the structure and function of airway epithelial barriers through the modulation of [Cl⁻]_i holds promising prospects for future applications in managing and treating such conditions.

We investigated whether pediatric patients with overweight and obesity are more likely to have dyspnea compared with those who are non-overweight. We collected de-identified data from TriNetX, a global federated multicenter research database, using both the UT Southwestern Medical Center and multinational Research Networks. Our analysis focused on patients aged 8–12 years. We identified overweight and obesity using ICD-10-CM codes E66 and dyspnea using code R06.0. Patients with overweight and obesity had a significantly higher risk of dyspnea compared with those who were non-overweight. This association was observed in both the UT Southwestern Network (risk ratio: 1.81, p < 0.001) and the Research Network (risk ratio: 2.70, p < 0.001). Furthermore, within the UT Southwestern Network, the risk was found to be higher in females compared with males (risk ratio: 2.17 vs. 1.67). These results have significant clinical implications, suggesting that clinicians should consider overweight and obesity as independent risk factors for dyspnea in pediatric patients after excluding other possible contributing factors.

Purpose

This study examined the magnitude of physiological strain imposed by repeated maximal static and dynamic apneas through assessing a panel of stress-related biomarkers.

Methods

Eleven healthy men performed on three separate occasions (≥72-h apart): a series of five repeated maximal (i) static (STA) or (ii) dynamic apneas (DYN) or (iii) a static eupneic protocol (CTL). Venous blood samples were drawn at 30, 90, and 180-min after each protocol to determine ischaemia modified albumin (IMA), neuron-specific enolase (NSE), myoglobin, and high sensitivity cardiac troponin T (hscTnT) concentrations.

Results

IMA was elevated after the apnoeic interventions (STA,+86%;DYN,+332%,p ≤ 0.047) but not CTL (p = 0.385). Myoglobin was higher than baseline (23.6 ± 3.9 ng/mL) 30-min post DYN (+70%,38.8 ± 13.3 ng/mL,p = 0.030). A greater myoglobin release was recorded in DYN compared with STA and CTL (p ≤ 0.035). No changes were observed in NSE (p = 0.207) or hscTnT (p = 0.274).

Conclusions

Five repeated maximal DYN led to a greater muscle injury compared with STA but neither elicited myocardial injury or neuronal-parenchymal damage.

This study investigated the respiratory activity in adult Wistar rats across different behavioral seizure severity induced by pentylenetetrazole (PTZ). Animals underwent surgery for electrodes implantation, allowing simultaneous EEG and diaphragm EMG (DIA_EMG) recordings and the respiratory frequency and DIA_EMG amplitude were measured. Seizures were acutely induced through PTZ injection and classified based on a pre-established score, with absence-like seizures (spike wave discharge (SWD) events on EEG) representing the lowest score. The respiratory activity was grouped into the different seizure severities. During absence-like and myoclonic jerk seizures, the breathing frequency decreased significantly (∼50% decrease) compared to pre- and post-ictal periods. Pronounced changes occurred with more severe seizures (clonic and tonic) with periods of apnea, especially during tonic seizures. Apnea duration was significantly higher in tonic compared to clonic seizures. Notably, during PTZ-induced tonic seizures the apnea events were marked by tonic DIA_EMG contraction (tonic-phase apnea). In the majority of animals (5 out of 7) this was a fatal event in which the seizure-induced respiratory arrest preceded the asystole. In conclusion, we provide an assessment of the respiratory activity in the PTZ-induced acute seizures and showed that breathing dysfunction is more pronounced in seizures with higher severity.