Respiratory Physiology & Neurobiology最新文献

Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model – the mdx mouse – is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function.

Shape and size of the nasopharyngeal airway is controlled by muscles innervated facial, glossopharyngeal, vagal, and hypoglossal cranial nerves. Contrary to brainstem networks that drive facial, vagal and hypoglossal nerve activities (FNA, VNA, HNA) the discharge patterns and origins of glossopharyngeal nerve activity (GPNA) remain poorly investigated. Here, an in situ perfused brainstem preparation (n=19) was used for recordings of GPNA in relation to phrenic (PNA), FNA, VNA and HNA. Brainstem transections were performed (n=10/19) to explore the role of pontomedullary synaptic interactions in generating GPNA. GPNA generally mirrors FNA and HNA discharge patterns and displays pre-inspiratory activity relative to the PNA, followed by robust inspiratory discharge in coincidence with PNA. Postinspiratory (early expiratory) discharge was, contrary to VNA, generally absent in FNA, GPNA or HNA. As described previously FNA and HNA discharge was virtually eliminated after pontomedullary transection while an apneustic inspiratory motor discharge was maintained in PNA, VNA and GPNA. After brainstem transection GPNA displayed an increased tonic activity starting during mid-expiration and thus developed prolonged pre-inspiratory activity compared to control. In conclusion respiratory GPNA reflects FNA and HNA which implies similar function in controlling upper airway patency during breathing. That GPNA preserved its pre-inspiratory/inspiratory discharge pattern in relation PNA after pontomedullary transection suggest that GPNA premotor circuits may have a different anatomical distribution compared HNA and FNA and thus may therefore hold a unique role in preserving airway patency.

Objectives

We investigated the effect of inspiratory muscle training (IMT) on inspiratory muscle strength, functional capacity and respiratory muscle kinematics during exercise in healthy older adults.

Methods

24 adults were randomised into an IMT or SHAM-IMT group. Both groups performed 30 breaths, twice daily, for 8 weeks, at intensities of ∼50 % maximal inspiratory pressure (PImax; IMT) or <15 % PImax (SHAM-IMT). Measurements of PImax, breathing discomfort during a bout of IMT, six-minute walk distance, physical activity levels, and balance were assessed pre- and post-intervention. Respiratory muscle kinematics were assessed via optoelectronic plethysmography (OEP) during constant work rate cycling.

Results

PImax was significantly improved (by 20.0±11.9 cmH₂O; p=0.001) in the IMT group only. Breathing discomfort ratings during IMT significantly decreased (from 3.5±0.9–1.7±0.8). Daily sedentary time was decreased (by 28.0±39.8 min; p=0.042), and reactive balance significantly improved (by 1.2±0.8; p<0.001) in the IMT group only. OEP measures showed a significantly greater contribution of the pulmonary and abdominal rib cage compartments to total tidal volume expansion post-IMT.

Conclusions

IMT significantly improves inspiratory muscle strength and breathing discomfort in this population. IMT induces greater rib cage expansion and diaphragm descent during exercise, thereby suggesting a less restrictive effect on thoracic expansion and increased diaphragmatic power generation.

The objective of this study is to explore the transport, size growth, and deposition of Salbutamol Sulphate (SS) using Computational Fluid Dynamics (CFD). A CT-based realistic model of human airways from the oral cavity to the 5th generation of the lung was utilized as the computational domain. Four Test Cases (TC) with varying temperature and relative humidity (RH) under two inspiratory waveforms were considered to completely evaluate the impact of inhalation conditions on particle growth. Salbutamol Sulphate (SS) is a β2-adrenergic agonist and has been extensively used for asthma treatment. A monodispersed distribution of SS particles with an initial diameter of 167 nm was considered at the mouth inlet based on pharmaceutical data. Results indicated that inhalation of saturated/supersaturated air (RH>100%) leads to significant hygroscopic growth of SS particles with a factor of 10. In addition, the deposition efficiency of SS particles under the Quick and Deep (QD) inhalation profile was enhanced as the flow temperature and humidity increased. However, the implementation of Slow and Deep (SD) inspiratory waveform revealed that the same particle size growth is achieved in the respiratory system with lower deposition efficiency in the mouth-throat (less than 3%) and tracheobronchial airway (less than 2.18%). For the escaped particles form the right lung, in the SD waveform under TC 3, the maximum particle size distribution was for 600 nm particles with 25% probability. In the left lung, 30% of the particles were increased up to 950 nm in size. For the QD waveform in TC 3 and TC4, the most frequent particles were 800 nm with 36% probability. This holds practical significance in the context of deep lung delivery for asthmatic patients with enhanced deposition efficiency and large particle size. The findings of the present study can contribute to the development of targeted drug delivery strategies for the treatment of pulmonary diseases using hygroscopic dry powder formulations.

The neural control of breathing exhibits sex differences. There is now a large effort to account for biological sex in mammalian research, but the degree to which ectothermic vertebrates exhibit sex differences in the central control of breathing is not well-established. Therefore, we compared respiratory-related neural activity in brainstem-spinal cord preparations from female and male bullfrogs to determine if important aspects of the central control of breathing vary with sex. We found that the breathing pattern was similar across males and females, but baseline frequency of the respiratory network was faster in females. The magnitude of the central response to hypercapnia was similar across sexes, but the time to reach maximum burst rate occurred more slowly in females. These results suggest that sex differences may account for variation in traits associated with the control of breathing and that future work should carefully account for sex of the animal in analysis.

This study aimed to evaluate the presence of dynamic hyperinflation (DH) during the Glittre-ADL test (TGlittre) coupled to the dynamic ventilation measurements in people with central obesity (pwCO) and to correlate it with lung mechanics at rest. Sixty-four pwCO underwent TGlittre and the following resting lung function tests: spirometry and impulse oscillometry system (IOS). On TGlittre, 22 participants presented DH at the end of the test (DH group), while 42 did not present DH (NDH group). Body mass index (BMI), waist circumference (WC), and hip circumference (HC) were higher in the DH group than in the NDH group. IOS abnormalities were more common in the DH group compared to the NDH group. TGlittre time significantly correlated with BMI, WC, waist-to-hip ratio (WHR), and neck circumference (NC). Delta inspiratory capacity correlated significantly with WC, HC, NC, and resonance frequency measured by IOS. Thus, pwCO perform worse on TGlittre, and DH is frequent in those with higher anthropometric indices and worse lung mechanics.

The aim of this study was to characterize the breathing patterns of individuals with obesity during routine activities such as sitting and standing, and to identify potential contributors to alterations in these patterns. Measurements performed in 20 male subjects with obesity (BMI, 31.8±1.5 kg/m²) and 20 controls (BMI, 23.5±1.4 kg/m²) included anthropometric parameters, breathing-patterns in sitting and standing positions, spirometry, maximal respiratory pressures, and diaphragm B-mode ultrasonography. Individuals with obesity exhibited lower tidal volume and increased respiratory rate to maintain a similar minute-ventilation (p<0.05). Subjects with obesity demonstrated impaired spirometry and respiratory muscle strength, with inspiratory functions being notably compromised (p<0.05). Individuals with obesity had a greater diaphragm thickness at end inspiration but lower thickening-fraction at end quiet and forced breathings and reduced diaphragmatic displacement and excursion during maximal breaths (p<0.05). BMI was negatively associated with all respiratory function markers (p<0.05). Individuals with obesity exhibit a higher respiratory rate but lower tidal volume, likely to accommodate decreased compliance and excess thoracic and abdominal fat, further hindering inspiratory function. Moreover, increased adiposity is associated with a thicker but weaker diaphragm, primarily due to the diaphragm's mechanical disadvantage rather than its intrinsic inability to generate force.

Obstructive sleep apnea (OSA) patients who use continuous positive airway pressure (CPAP) often complain of nasal dryness and nasal obstruction as side effects of CPAP. The physiological mechanisms by which CPAP may cause nasal dryness and nasal obstruction remain poorly understood. It has been hypothesized that CPAP interferes with the nasal cycle, abolishing the resting phase of the cycle and leading to nasal dryness. We performed rhinomanometry measurements in 31 OSA patients sitting, laid supine, and supine after 10 min of CPAP at 10 cmH₂O. A posture change from sitting to supine led to more symmetric airflow partitioning between the left and right nostrils in the supine position. CPAP did not have a significant impact on nasal resistance, unilateral airflows, or airflow partitioning. Our results suggest that airflow partitioning becomes more symmetric immediately after changing to a supine position, while CPAP had no effect on nasal airflow, thus preserving the nearly symmetric airflow partitioning achieved after the posture change.

For measurements of exercise intensity, an individual's oxygen uptake (V̇O₂) is measured with an exhaled gas analyzer that involves a mask, but exercise coaching would benefit if an individual's V̇O₂ could be estimated with more easily obtained predictors. We investigated the predictability of V̇O₂ by electromyography (EMG) of the neck inspiratory muscles. We analyzed the EMG results of the sternocleidomastoid (EMGst) and scalene (EMGsc) muscles of 14 healthy adults who performed a treadmill exercise load test. Their V̇O₂, inspiratory flow rate, and heart rate were simultaneously recorded during the exercise. The exercise load test was performed twice at a ≥2-day interval. The first visit was an incremental exercise test, and the second was a repeated two-load exercise test at levels below and above the participant's ventilatory threshold (VT) as determined in the first test. We observed that the integrated EMG values for each exercise load showed partially significant positive correlations with the EMGst and EMGsc. However, the cervical inspiratory muscle EMGs did not show as high a correlation as the minute ventilation. These results indicate that (i) EMG of the cervical inspiratory muscles could be used to estimate V̇O₂, but (ii) these EMG parameters alone should be considered insufficient for estimating V̇O₂.

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.