Respiratory Physiology & Neurobiology最新文献

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.

Breathing is the only vital function that can be volitionally controlled. However, a detailed understanding how volitional (cortical) motor commands can transform vital breathing activity into adaptive breathing patterns that accommodate orofacial behaviors such as swallowing, vocalization or sniffing remains to be developed. Recent neuroanatomical tract tracing studies have identified patterns and origins of descending forebrain projections that target brain nuclei involved in laryngeal adductor function which is critically involved in orofacial behavior. These nuclei include the midbrain periaqueductal gray and nuclei of the respiratory rhythm and pattern generating network in the brainstem, specifically including the pontine Kölliker-Fuse nucleus and the pre-Bötzinger complex in the medulla oblongata. This review discusses the functional implications of the forebrain-brainstem anatomical connectivity that could underlie the volitional control and coordination of orofacial behaviors with breathing.

Acute Lung Injury (ALI) manifests as an acute exacerbation of pulmonary inflammation with high mortality. The potential application of Danshensu methyl ester (DME, synthesized in our lab) in ameliorating ALI has not been elucidated. Our results demonstrated that DME led to a remarkable reduction in lung injury. DME promoted a marked increase in antioxidant enzymes, like superoxide dismutase (SOD), and glutathione (GSH), accompanied by a substantial decrease in reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA). Moreover, DME decreased the production of IL-1β, TNF-α and IL-6, in vitro and in vivo. TLR4 and MyD88 expression is reduced in the DME-treated cells or tissues, which further leading to a decrease of p-p65 and p-IκBα. Meanwhile, DME effectively facilitated an elevation in cytoplasmic p65 expression. In summary, DME could ameliorate ALI by its antioxidant functionality and anti-inflammation effects through TLR4/NF-κB, which implied that DME may be a viable medicine for lung injury.

Introduction

Air-trapping affects clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and may be detected by reactance at 5 Hz (X5) on respiratory oscillometry because X5 sensitively reflects the elasticity of the chest wall, airway and lung. However, the longitudinal association between X5 and air-trapping remains to be explored. This study aimed to test whether longitudinal changes in X5 could be associated with air-trapping progression, exacerbations, and mortality in patients with COPD.

Methods

In this prospective COPD observational study, the follow-up period consisted of the first 4 years to obtain longitudinal changes in X5 and residual volume (RV) and number of exacerbations and the remaining years (year 4 to 10) to test mortality. Patients were divided into large, middle, and small X5 decline groups based on the tertiles of longitudinal change in X5, and mortality after 4 years was compared between the groups.

Results

Patients with COPD (n = 114) were enrolled. The large X5 decline group (n = 38) showed a greater longitudinal change in RV and more exacerbations compared with the small X5 decline group (n = 39) in multivariable models adjusted for age, sex, body mass index, and smoking history. Long-term mortality after the 4-year follow-up was higher in the large X5 decline group than in the small X5 decline group (hazard ratio [95 % confidence interval] = 8.37[1.01, 69.0]) in the multivariable Cox proportional hazard model.

Conclusion

Longitudinal changes in respiratory reactance could be associated with progressive air-trapping, exacerbation frequency, and increased mortality in patients with COPD.