Respiratory Center Research Articles

Tuberculosis in southern Morocco: Retrospective analysis from 2006 to 2012.

Tuberculosis, a global major concern, causes millions of deaths annually despite WHO strategies. A persistent gap in detection and treatment facilitates rapid spread in high-burden countries. Analyze the clinical-epidemiological profile of tuberculosis patients in Laayoune and Tarfaya, Morocco, emphasizing risk factors and evolution of the tuberculosis Methods: Retrospective analysis of 1332 tuberculosis cases at the Respiratory Diseases Diagnosis and Treatment Center in Laayoune (2006-2012). Variables with P < 0.10 in univariate analysis were included in multivariate analysis using multiple logistic regression to define the risk factors for tuberculosis, expressed as odds ratios (OR) with a 95% confidence interval (CI). The analysis revealed a pulmonary predominance (≈61%), with pleural (41.3%) and lymph node (31.5%) tuberculosis prevalent among extrapulmonary cases. Among 515 extrapulmonary tuberculosis cases, intestinal tuberculosis (14 cases) showed the highest mortality rate at 14.29%. The 15 to 64 age groups had a significantly higher risk of contracting pulmonary tuberculosis to children, and the 65 and over age group also had the highest risk of developing pulmonary tuberculosis (aOR=5.83 [2.43, 14.00]). Other risk factors included rural origin, personal history of tuberculosis, and smoking, all significantly associated with pulmonary tuberculosis (aOR=2.40 [1.001, 5.76]; aOR=2.00 [1.11, 3.61]; aOR=2.38 [1.40, 4.06]). Conversely, female gender was a protective factor (aOR=0.53 [0.40, 0.70]). Regarding recovery and loss to follow-up rates, they were higher in those with pulmonary tuberculosis (39.0% vs 2.1%; aOR=33.41 [17, 66.52]; 16.9% vs 10.3%; aOR=1.57 [1.02, 2.41], respectively). Holistic initiatives across various sectors will be essential to eliminate tuberculosis by 2030.

Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked to Morbidity and Mortality a Narrative Review.

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. In this regard, there is the potential for death. Additionally, the rise in fake Xanax tablets containing etizolam and other counterfeit medications has been exacerbated by the difference in regulations regarding these substances in different countries as well as the illegal drug trade. Healthcare providers may also play a role through the over- or underprescribing of certain medications. Thus, in order to combat the rise in counterfeit medications such as fake Xanax, international cooperation, regulation, and enforcement of laws pertaining to the manufacture, prescription, and distribution of these substances are needed.

Respiration and Cough in Pompe Disease: Results from a neuromechanical computational model of the respiratory control system

Late Onset Pompe Disease (LOPD) is an incurable, rare progressive genetic disease. It is characterized by glycogen build-up, due to mutations in the gene encoding the lysosomal enzyme acid alpha glucosidase, throughout muscle and neural regions. This accumulation is associated with cell death and muscle fiber swelling, eventually leading to respiratory insuffciency and airway clearance (i.e. cough) deficiency. Impairments in effective airway clearance result from the inability to clear normal pulmonary volume. Emerging evidence indicates significant respiratory neuron dysfunction, altering pulmonary function in humans and animal models. It has been suggested that respiratory and airway clearance insuffciency observed in LOPD may be attributed to medullary motoneurons potentially associated with the respiratory and cough pattern generators (Fuller et al., 2013; DeRuisseau et al., 2009). However, the precise neural mechanisms that suppress breathing and cough are not fully understood. One possible target for LOPD respiratory insuffciencies may be reduced medullary inspiratory neuron activity within this network, which could result in decreased phrenic motoneuron output. Using a stochastic neural network simulator that consisted of discrete “integrate and fire” populations, we simulated a systematic decrease in three medullary inspiratory neuron populations: inspiratory driver (I-Driver), inspiratory decrementing (I-Dec), or inspiratory augmenting (I-Aug) neurons. We simulated breathing and three cough trials. By targeting these populations, we expected global decreased neural bursts, suppressed inspiratory motor drive, and/or suppressed expiratory motoneuron output. Simulations indicated that when the I-Dec motoneuron population decreased by 25%, it resulted in apnea and abolished cough. Reducing the I-Aug motoneuron population by 20% resulted in longer inspiratory phase durations (TI) and a decreased respiratory rate. During cough, there was a decrease in the duration and amplitudes of the expiratory motoneuronal activity associated with decreased cough receptor and pulmonary stretch receptor afferent feedback. When the I-Driver motoneuron population was reduced by 25%, TI decreased and I amplitude increased during respiration. During cough, lumbar and phrenic motoneuron discharge duration and amplitude decreased. These results are consistent with previously reported in vivo data. Overall, our simulation data support the plausibility of glycogen storage dysfunction impairing medullary neuronal and premotoneuronal excitability within the inspiratory network. Our results also suggest that some neurons may be more sensitive to glycogen storage than others within the brainstem inspiratory network. Supported by NHLBI L30HL165496, NIH T32 HL 134621 and 3OT2OD023854. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Mapping inhibitory and excitatory projections to the preBӧtzinger complex

Breathing relies on rhythmic activity generated by the preBӧtzinger complex (preBӧtC), a small brainstem region. Because breathing is influenced by many different physiological, behavioral, and emotional contexts, the preBӧtC is not only highly connected with nearby respiratory related regions in the hindbrain, but also has widespread connections with other mid-and forebrain regions not generally implicated in the regulation of breathing. The specific functions for many of these preBӧtC inputs remain unclear. Although afferent pathways indiscriminately target excitatory and inhibitory neurons in the preBӧtC, we hypothesized that inputs to the preBӧtC would map to distinct brain regions based on the inhibitory or excitatory phenotype of the projecting neurons. To test this, mice that express tdTomato only when both Cre and FlpO recombinases are present (Ai65) were bred with mice that express Cre in inhibitory neurons ( VgatCre). Adult offspring ( VgatCre; Ai65) received a unilateral preBӧtC injection of a retrograde AAV that expresses FlpO recombinase (AAVrg-Flpo), thereby specifically activating tdTomato expression in any inhibitory neurons that project directly to the preBӧtC. Whole-brain imaging revealed many labeled neurons along the ipsilateral ventral respiratory column (VRC), far rostral and caudal of the injection site, extending along the intermediate reticular zone (IRt) from the VII nucleus through the caudal end of the ventral respiratory group (VRG). Interestingly, this well-defined and continuous column of labeled neurons was confined to the ventral IRt at its caudal end but moved dorsally at its rostral end. Only a small number of neurons were labeled along the contralateral VRC. Sparse labeling was present in the medial parabrachial, Kolliker-Fuse, and reticular regions of the pons. Many projecting neurons were observed across subregions of the amygdala, which were almost exclusively ipsilateral. The hypothalamus contained diffuse projecting neurons along its rostral-caudal extent that were also mostly ipsilateral. However, denser labeling was present in a distinctly curved cluster of the lateral hypothalamus, which was observed on both the ipsilateral and contralateral side. Consistent with the preBӧtC having distinct inhibitory and excitatory input pathways, we did not observe significant labelling in other regions with known projections to the preBotC identified previously using non-cell-type specific tracing strategies. These included cortex, lateral parabrachial, NTS, and RVM. This will be tested further by replicating this experiment with targeting of glutamatergic ( Vglut2) neurons. Defining these cell-type-specific inputs to the preBӧtC will provide an essential foundation for future functional studies to determine how these circuits may regulate breathing. R01 HL1660317 (Baertsch) R00 HL145004 (Baertsch). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

SARS-CoV-2 Decreases Neuronal Activity in Brainstem Respiratory Centers in C57BI6/J Mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, targets the respiratory system, leading to symptoms such as cough, fever, and diffculty breathing. As the mechanisms behind SARS-CoV-2 infections continues to be studied, understanding of how this virus targets specific tissues becomes more apparent. Angiotensin-converting enzyme-2 (ACE2), the target of SARS-CoV infections and a functional receptor for SARS-CoV-2 invasions, is highly expressed in many tissues throughout the body, including the lungs, kidneys, and brain. Notably, our group previously reported that neurons are the main cells within the brain expressing ACE2. Accordingly, we hypothesized that neuronal infection of brainstem respiratory centers by SARS-CoV-2 could contribute to respiratory symptoms associated with COVID-19, specifically respiratory failure. C57BI6/J mice were mock infected or received SARS-CoV-2 (7.5x103 or 1.5x104) intranasally in a BSL-3 facility (University of Texas in Galveston) and were euthanized by CO2 hypoxia after 5 days post infection. The heads were harvested and immersed in formalin for 3 days before being transferred to LSU Health-NO for processing. Brains were carefully dissected out and preserved in optimal cutting temperature (OCT) before sectioning on a cryostat. Sections (30 μm) containing the retrotrapezoid nucleus (RTN) were selected as its neurons are part of the pontomedullary regions that generate the respiratory rhythm and pattern. Immunohistochemistry for c-Fos, a marker of neuronal activity, was used to assess neuronal activity in the RTN. Sections were incubated overnight with a primary monoclonal antibody (rabbit anti c-Fos, 1:1000) followed with a secondary goat antirabbit fluorescent IgG (GFP, 1:200, 1h) antibody. Sections were then mounted to slides in the dark to preserve the fluorescence and observed under the microscope. Images of neurons present in the RTN were captured and neurons were then hand counted and averaged. Neuronal activity in the RTN was decreased with the dose of SARS-CoV-2 used to infect cells in the brain. The greater the dose of SARS-CoV-2, the lower the number of c-Fos-positive neurons was detected in the RTN. Mock brains had the greatest number of neurons and brains infected with 1.5x104 SARS-CoV-2 had the lowest number of neurons in the RTN. This was demonstrated by counting neurons at 3 different intervals and taking the average. We conclude that SARS-CoV-2 targets neurons in respiratory centers, possibly contributing to impaired respiratory function in infected patients. NIH/NHLBI HL163814. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Functional Impact of nTS Glutamate Stress on Respiration in an Alzheimer’s Disease Model

Alzheimer’s disease (AD) is closely associated with obstructive sleep apnea (OSA). Such hypoxic insults trigger glutamate release of chemoafferents into the nucleus tractus solitarii (nTS), an important upstream center of the chemoreflex. Potential alterations of glutamate handling in the nTS may lead to the respiratory dysfunction seen in AD patients. Using the streptozotocin (STZ)-induced rat model — an effective proxy for human AD — we studied the functional consequences of nTS glutamate stress on respiration. STZ-AD was induced in 6-week-old male Sprague Dawley rats via intracerebroventricular injections of 2 - 2.25 mg/kg STZ. After two weeks, EMG recordings of diaphragm activity served as surrogate for respiratory responses to glutamate microinjections (20 nL of 40 mM) into the caudal nTS. In a subset of rats, chemoafferent terminals were labeled with the fluorescent tracer DiI to permit patch clamp recordings of identified 2nd order nTS neurons participating in the chemoreflex loop. Evoked glutamatergic excitatory postsynaptic currents (TS-EPSCs) were generated via tractus solitarii stimulation at frequencies (10 - 40 Hz) typical for afferent discharge during hypoxia. Acute glutamate injections into the caudal nTS increased respiratory frequency by 15 - 20 breaths per minute. The response magnitude was similar between CTL and STZ-AD animals. Excitatory stress with repeated glutamate injections (5 min. apart) evoked a reliable respiratory response in CTL that slowly declined to ~65% from its maximum over the course of 10 injections. In contrast, the decline of respiratory response in STZ-AD was more pronounced and occurred significantly earlier than in CTL, indicating altered glutamate handling in the caudal nTS of STZ-AD rats. Next, we used patch clamp electrophysiology to analyze increased glutamate release of chemoafferents onto 2nd order nTS neurons. High frequency stimulation of chemoafferents induced a successive depression of TS-EPSC amplitude in nTS neurons. TS-EPSC depression was significantly stronger in STZ-AD and may be due to altered glutamate handling at the synapse. Western Blot analysis of STZ-AD brainstem tissue including the nTS revealed a significant increase in glial fibrillary acidic protein (GFAP) expression and a decrease of excitatory amino acid transporters (EAATs) expression, suggesting astrocyte involvement in compromised nTS glutamate handling in STZ-AD. In summary, the STZ-AD model showed reduced respiratory responses to glutamate stress in the caudal nTS. The altered stress response may come from enhanced depression of TS-EPSC amplitude at nTS neurons in the chemoreflex. Altered astrocytic glutamate removal from the synaptic cleft may contribute to TS-EPSC depression. Together, altered glutamate handling in a respiratory brainstem center may contribute to OSA in AD patients. NIH R15AG065927 (TDO &amp; DO), KCOM Biomedical Graduate Program (RKT &amp;TDO), ATSU Research Support (SKRC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Changes in Tryptophan Hydroxylase 2 and 5HT1A Receptor Density May Contribute to Developmental Variation in Response to Serotonin in the in vitro Bullfrog Brainstem

Bullfrog, Lithobates catesbeiana, is a vertebrate animal model that can be used to study toxicology and developmental physiology. Our research is focused on better understanding vulnerability to brainstem respiratory centers in the pathology of sudden infant death syndrome (SIDS). We propose that a link between nicotine exposure during development leads to changes in the serotonergic signaling cascades of respiratory coordinating neurons. Caudal raphe neurons send serotonergic fibers that arborize and terminate directly on or near respiratory neurons in the brainstem. In bullfrogs, serotonin elicits a developmentally dependent effect on respiratory motor output. Late metamorphic tadpoles demonstrate an increase in lung burst activity with exposure to low concentrations of serotonin (≤ 0.5μM 5-hydroxytryptamine; 5-HT) mediated in part by 5-HT1a receptor (5HT1aR) activation. This developmental change in activity may be due to changes in the number of serotonergic fibers and/or 5-HT1a receptor density. Using the NIH Basic Local Alignment Search Tool (BLAST) we compared human and bullfrog 5HT1aR and tryptophan hydroxylase 2 (TH2) protein sequences and found a 34 and 65 percent identity match respectively. Quantitative western blot analysis of both proteins indicates developmental shifts in the serotonergic network during metamorphosis. These results were supported by immunohistochemical staining of 5HT1aR and TH2 in caudal raphe containing brainstem sections from pre-metamorphic tadpoles and post-metamorphic frogs. Impairments in the maturation of this serotonergic network may underlie the toxidrome associated with developmental nicotine exposure and further support the increased risk of SIDS following that exposure. This research was supported by the University of Wisconsin- La Crosse (UWL) through support from the UWL College of Science and Health, two UWL Undergraduate Research Creative Grants and a UWL FY23/24 Faculty Research Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The occurrence mechanism, assessment, and non-pharmacological treatment of dyspnea.

Dyspnea is a subjective sensation often described as a feeling of respiratory effort, tightness, or air hunger. The underlying mechanisms of this symptom are multifaceted and involve factors such as respiratory centers, cardiovascular system, airways, neuromuscular components, and metabolic factors, although not fully elucidated. The classical theory of imbalance between inspiratory neural drive (IND) and the simultaneous dynamic responses of the respiratory system posits that the disruption of a normal and harmonious relationship fundamentally shapes the expression of respiratory discomfort. Assessment and comprehensive treatment of dyspnea are crucial for patient rehabilitation, including subjective self-reporting and objective clinical measurements. Non-pharmacological interventions, such as pulmonary rehabilitation, fan therapy, exercise, chest wall vibration, virtual reality technology, traditional Chinese medicine (acupuncture and acupressure), and yoga, have shown promise in alleviating dyspnea symptoms. Additionally, oxygen therapy, has demonstrated short-term benefits for patients with pre-hospital respiratory distress and hypoxemia. This review provides a comprehensive overview of dyspnea, emphasizing the importance of a multifaceted approach for its assessment and management, with a focus on non-pharmacological interventions that contribute to enhanced patient outcomes and quality of life.

Novel utilization and quantification of Xsight diaphragm tracking for respiratory motion compensation in Cyberknife Synchrony treatment of liver tumors.

The Xsight lung tracking system (XLTS) utilizes an advanced image processing algorithm to precisely identify the position of a tumor and determine its location in orthogonal x-ray images, instead of finding fiducials, thereby minimizing the risk of fiducial insertion-related side effects. To assess and gauge the effectiveness of CyberKnife Synchrony in treating liver tumors located in close proximity to or within the diaphragm, we employed the Xsight diaphragm tracking system (XDTS), which was based on the XLTS. We looked back at the treatment logs of 11 patients (8/11 [XDTS], 3/11 [Fiducial-based Target Tracking System-FTTS]) who had liver tumors in close proximity to or within the diaphragm. And the results are compared with the patients who undergo the treatment of FTTS. The breathing data information was calculated as a rolling average to reduce the effect of irregular breathing. We tested the tracking accuracy with a dynamic phantom (18023-A) on the basis of patient-specific respiratory curve. The average values for the XDTS and FTTS correlation errors were 1.38±0.65 versus 1.50±0.26mm (superior-inferior), 1.28±0.48 versus 0.40±0.09mm (left-right), and 0.96±0.32 versus 0.47±0.10mm(anterior-posterior), respectively. The prediction errors for two methods of 0.65±0.16 versus 5.48±3.33mm in the S-I direction, 0.34±0.10 versus 1.41±0.76mm in the A-P direction, and 0.22±0.072 versus 1.22±0.48mm in the L-R direction. The coverage rate of FTTS slightly less than that of XDTS, such as 96.53±8.19% (FTTS) versus 98.03±1.54 (XDTS). The prediction error, the motion amplitude, and the variation of the respiratory center phase were strongly related to each other. Especially, the higher the amplitude and the variation, the higher the prediction error. The diaphragm has the potential to serve as an alternative to gold fiducial markers for detecting liver tumors in close proximity or within it. We also found that we needed to reduce the motion amplitude and train the respiration of the patients during liver radiotherapy, as well as control and evaluate their breathing.

Improving inpatient results endorsement in a tertiary cardiac, respiratory and cancer centre

Improving inpatient results endorsement in a tertiary cardiac, respiratory and cancer centre

Use of CPAP Ventilation in Non-ICU Wards May Influence Outcomes in Patients with Severe Respiratory COVID-19.

Background and Objectives: The COVID-19 disease has significantly burdened the healthcare system, including all units of severe patient treatment. Non-intensive care units were established to rationalize the capacity within the Intensive Care Unit (ICU) and to create a unit where patients with Acute Respiratory Distress Syndrome (ARDS) could be treated with non-invasive Continuous Positive Air Pressure (CPAP) outside the ICU. This unicentric retrospective study aimed to assess the efficacy of NIV Treatment in Patients of the fourth pandemic wave and how its application affects the frequency and mortality of ICU-treated patients at University Hospital Rijeka compared to earlier waves of the COVID-19 pandemic. Furthermore, the study showcases the effect of the Patient/Nurse ratio (P/N ratio) on overall mortality in the ICU. Materials and Methods: The study was conducted on two groups of patients with respiratory insufficiency in the second and third pandemic waves, treated in the COVID Respiratory Centre (CRC) (153 patients). We also reviewed a cohort of patients from the fourth pandemic wave who were initially hospitalized in a COVID-6 non-intensive unit from 1 October 2021 to 1 November 2022 (102 patients), and some of them escalated to CRC. Results: The introduction of the CPAP non-invasive ventilation method as a means of hypoxic respiratory failure treatment in non-intensive care units has decreased the strain, overall number of admissions, and CRC patient mortality. The overall fourth wave mortality was 29.4%, compared to the 58.2% overall mortality of the second and third waves. Conclusions: As a result, this has decreased CRC patient admissions and, by itself, overall mortality.

Retrospective Study of Bronchoscopic Intervention Therapy for Bronchopleural Fistula Induced by Pulmonary Surgery

As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P<0.05). By telephone follow-up or readmission during 1 month to 38 months after treament, median survival time was 21 months. 33 patients (51.6%) showed complete response, 7 patients (10.9%) showed complete clinical response, 18 patients (28.1%) showed partial response, and 6 patients (9.4%) showed no response. As a whole, the total effective rate of bronchoscopic intervention for BPF was 90.6%. BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating. Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

Pathophysiology of Respiratory Failure in Neuromuscular Diseases

Based on a recent review by Krohn et al, the respiratory center and its regulatory mechanisms are described. Although the respiratory control centers in the medulla and pons ensure rhythmic respiration, maintaining and regulating respiration involves a complex network of peripheral chemoreceptors, vagal nerves, and central chemoreceptors. This review discusses the pathophysiology of respiratory disorders in neuromuscular diseases and evaluation and treatment methods based on the anatomy of the respiratory network.

Effect of chronic prenatal exposure to the food additive titanium dioxide E171 on respiratory activity in newborn mice.

Nanoparticles (NPs) possess unique properties that make their use valuable in all industries. Titanium dioxide (TiO2) NPs are extensively used as a white pigment in food (labeled under the European number E171) and personal care products, which creates a significant potential for chronic consumer exposure. Concerns about the potential toxic effects of TiO2 NPs have arisen, particularly in vulnerable populations, including pregnant women and infants. Recently, human materno-fetal transfer of E171 was demonstrated, and simultaneously, we reported that chronic prenatal exposure to reference P25 TiO2 NPs was found to alter the developing respiratory neural networks. In this study, using whole body plethysmography from postnatal day (P) 0 to P7, we assessed the respiratory function of newborn mice born to mothers fed with E171 during pregnancy. We also evaluated the potential alterations to respiratory centers by using brainstem-spinal cord electrophysiological recordings from P0 to P6. Our study reveals that E171-prenatally exposed animals displayed an abnormally elevated breathing rate from P3 onwards. From P5 to P6, the respiratory-related burst frequency generated by the isolated brainstem-spinal cord preparations was significantly higher in E171-exposed animals than in non-exposed animals. These findings demonstrate prenatal toxicity of E171 to the developing respiratory function and may contribute to policy-making regarding the use of TiO2 NPs.

Carotid Body Function in Tyrosine Hydroxylase Conditional Olfr78 Knockout Mice.

The Olfr78 gene encodes a G-protein-coupled olfactory receptor that is expressed in several ectopic sites. Olfr78 is one of the most abundant mRNA species in carotid body (CB) glomus cells. These cells are the prototypical oxygen (O2) sensitive arterial chemoreceptors, which, in response to lowered O2 tension (hypoxia), activate the respiratory centers to induce hyperventilation. It has been proposed that Olfr78 is a lactate receptor and that glomus cell activation by the increase in blood lactate mediates the hypoxic ventilatory response (HVR). However, this proposal has been challenged by several groups showing that Olfr78 is not a physiologically relevant lactate receptor and that the O2-based regulation of breathing is not affected in constitutive Olfr78 knockout mice. In another study, constitutive Olfr78 knockout mice were reported to have altered systemic and CB responses to mild hypoxia. To further characterize the functional role of Olfr78 in CB glomus cells, we here generated a conditional Olfr78 knockout mouse strain and then restricted the knockout to glomus cells and other catecholaminergic cells by crossing with a tyrosine hydroxylase-specific Cre driver strain (TH-Olfr78 KO mice). We find that TH-Olfr78 KO mice have a normal HVR. Interestingly, glomus cells of TH-Olfr78 KO mice exhibit molecular and electrophysiological alterations as well as a reduced dopamine content in secretory vesicles and neurosecretory activity. These functional characteristics resemble those of CB neuroblasts in wild-type mice. We suggest that, although Olfr78 is not essential for CB O2 sensing, activation of Olfr78-dependent pathways is required for maturation of glomus cells.

Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.

Monitoring of physiologic features and treatment aspects of children on home invasive mechanical ventilation.

Pediatric home invasive mechanical ventilation patients are a small but resource-intensive cohort, requiring close monitoring and multidisciplinary care. Patients are often dependent on their ventilator for life support, with any significant complications such as equipment failure, tracheostomy blockage, or accidental decannulation becoming potentially life-threatening if not identified quickly. This review discusses the indications and variations in practice worldwide, in terms of models of care, including home care provision, choice of equipment, and monitoring. With advances in technology, optimal monitoring strategies for home, continue to be debated: In-built ventilator alarms are often inadequately sensitive for pediatric patients, necessitating additional external monitoring devices to minimize risk. Pulse oximetry has been the preferred monitoring modality at home, though in some special circumstances such as congenital central hypoventilation syndrome, home carbon dioxide monitoring may be important to consider. Children should be under regular follow-up at specialist respiratory centers where clinical evaluation, nocturnal oximetry, and capnography monitoring and/or poly(somno)graphy and analysis of ventilator download data can be performed regularly to monitor progress. Recent exciting advances in technology, particularly in telemonitoring, which have potential to hugely benefit this complex group of patients are also discussed.

A qualitative study on factors that influence the degree of comfort experienced by patients undergoing respiratory endoscopy in combination with intravenous injections of remimazolam besylate and fentanyl

Purpose: To investigate the level of discomfort in patients undergoing respiratory endoscopy in order to provide experimental evidence for the formulation of a comfort assessment scale for this procedure, and for guiding future research and intervention measures.&#x0D; Methods: Using the phenomenological research method of qualitative research, semi-structured interviews were conducted with 18 patients who underwent respiratory endoscopy in the Respiratory Intervention Center of the Fourth Affiliated Hospital of Zhejiang University School of Medicine. The interview data were analyzed, and the theme was extracted using the Colaizzi 7-step analysis method. During the surgery, remimazolam besylate (intravenous injection, 5 - 7.5 mg) was used in combination with fentanyl (intravenous injection, 1 - 2 µg/kg) for flexible bronchoscopy examination.&#x0D; Results: From the interview data, 3 themes and 9 sub-themes that affect the comfort of patients undergoing respiratory endoscopic surgery were identified. These comprised individual factors (fear and worry about the outcome), family factors (family financial difficulties and lack of care from family), and medical care factors (attitude of medical caregivers, insufficient health education, unreasonable operation arrangements, inconvenient care, and surgical complications). &#x0D; Conclusion: Patients undergoing respiratory endoscopy experience a higher degree of comfort when remimazolam besylate is used in combination with fentanyl. Medical staff should correctly identify the sources of discomfort in patients undergoing respiratory endoscopy under general anesthesia, and provide targeted interventions to improve the comfort experienced. Moreover, the quality of service provided by medical staff should be improved.

Axonal projection of the medullary expiratory neurons in the feline thoracic spinal cord

Expiratory neurons in the caudal ventral respiratory group extend descending axons to the lumbar and sacral spinal cord, and they possess axon collaterals, the distribution of which has been well-documented. Likewise, these expiratory neurons extend axons to the thoracic spinal cord and innervate thoracic expiratory motoneurons. These axons also give rise to collaterals, and their distribution may influence the strength of synaptic connectivity between the axons and the thoracic expiratory motoneurons. We investigated the distribution of axon collaterals in the thoracic spinal cord using a microstimulation technique. This study was performed on cats; one cat was used to make an anatomical atlas and six were used in the experiment. Extracellular spikes of expiratory neurons were recorded in artificially ventilated cats. The thoracic spinal gray matter was microstimulated from dorsal to ventral sites at 100-μm intervals using a glass-insulated tungsten microelectrode with a current of 150–250 μA. The stimulation tracks were made at 1 mm intervals along the spinal cord in segments Th9 to Th13, and the effective stimulating sites of antidromic activation in axon collaterals were systematically mapped. The effective stimulating sites in the contralateral thoracic spinal cord with expiratory neurons in the caudal ventral respiratory group (cVRG) occupied 14.4% of the total length of the thoracic spinal cord examined. The mean percentage of effective stimulating tracks per unit was 18.6 ± 4.4%. The distribution of axon collaterals of expiratory neurons in the feline thoracic spinal cord indeed resembled that reported in the upper lumbar spinal cord. We propose that a single medullary expiratory neuron exerts excitatory effects across multiple segments of the thoracic spinal cord via its collaterals.

Severely obese 14-year-old boy with central sleep apnea several years after head trauma

Severely obese 14-year-old boy with central sleep apnea several years after head trauma