airway vagal

The occurrence of major asthma symptoms is largely attributed to airway vagal hypertonia, of which the central mechanisms remain unclear. This study tests the hypotheses that endothelin-1-mediated brainstem glial activation produces asthmatic airway vagal hypertonia via enhanced action of adenosine 5'-triphosphate on neuronal purinergic P2X4 receptors. A rat model of asthma was prepared using ovalbumin. Airway vagal tone was evaluated by the recurrent laryngeal discharge and plethysmographic measurement of pulmonary function...

Methylglyoxal (MG), a reactive metabolic byproduct of glycolysis, is a causative of painful diabetic neuropathy. Patients with diabetes are associated with more frequent severe asthma exacerbation. Stimulation of capsaicin-sensitive lung vagal (CSLV) afferents may contribute to the pathogenesis of hyperreactive airway diseases such as asthma. However, the possibility of the stimulatory effect of MG on CSLV afferents and the underlying mechanisms remain unknown. Our results showed that intravenous injection of MG (25 mg/kg, MG25) in anesthetized, spontaneously breathing rats elicited pulmonary chemoreflexes characterized by apnea, bradycardia, and hypotension...

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2 . Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch...

In rats and guinea pigs, sensory innervation of the airways is derived largely from the vagus nerve, with the extrapulmonary airways innervated by Wnt1+ jugular neurons and the intrapulmonary airways and lungs by Phox2b+ nodose neurons; however, our knowledge of airway innervation in mice is limited. We used genetically targeted expression of enhanced yellow fluorescent protein-channelrhodopsin-2 (EYFP-ChR2) in Wnt1+ or Phox2b+ tissues to characterize jugular and nodose-mediated physiological responses and airway innervation in mice...

INTRODUCTION: Targeting the parasympathetic nervous system innervating the airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation in the lung. METHODS: A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study...

BACKGROUND: More than 50% of patients with atrial fibrillation (AF) suffer from sleep disordered breathing (SDB). Obstructive respiratory events contribute to a transient vagally-mediated atrial arrhythmogenic substrate, which is resistant to most available antiarrhythmic drugs. OBJECTIVE: To study the effect of pharmacological inhibition of the G-protein-gated acetylcholine-regulated potassium current (IK,ACh ) with and without acute autonomic nervous system activation by nicotine in a pig model for obstructive respiratory events...

SARS-CoV-2, the virus responsible for COVID-19, triggers symptoms such as sneezing, aches and pain. 1 These symptoms are mediated by a subset of sensory neurons, known as nociceptors, that detect noxious stimuli, densely innervate the airway epithelium, and interact with airway resident epithelial and immune cells. 2-6 However, the mechanisms by which viral infection activates these neurons to trigger pain and airway reflexes are unknown. Here, we show that the coronavirus papain-like protease (PLpro) directly activates airway-innervating trigeminal and vagal nociceptors in mice and human iPSC-derived nociceptors...

BACKGROUND: Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory nerve responsivity to tussive stimuli which would be accompanied by alterations in stimulus-induced brainstem activation, measurable with functional magnetic resonance imaging (fMRI). METHODS: We investigated brainstem responses during inhalation of capsaicin and adenosine triphosphate (ATP) in 29 participants with chronic cough and 29 age- and sex-matched controls...

The nucleus ambiguus (nAmb) provides parasympathetic control of cardiorespiratory functions as well as motor control of the upper airways and striated esophagus. A subset of nAmb neurons innervates the heart through the vagus nerve to control cardiac function at rest and during key autonomic reflexes such as the mammalian diving reflex. These cardiovagal nAmb neurons may be molecularly and anatomically distinct, but how they differ from other nAmb neurons in the adult brain remains unclear. We therefore classified adult mouse nAmb neurons based on their genome-wide expression profiles, innervation of cardiac ganglia, and ability to control HR...

Cytokines employ downstream Janus kinases (JAKs) to promote chronic inflammatory diseases. JAK1-dependent type 2 cytokines drive allergic inflammation, and patients with JAK1 gain-of-function (GoF) variants develop atopic dermatitis (AD) and asthma. To explore tissue-specific functions, we inserted a human JAK1 GoF variant (JAK1GoF ) into mice and observed the development of spontaneous AD-like skin disease but unexpected resistance to lung inflammation when JAK1GoF expression was restricted to the stroma. We identified a previously unrecognized role for JAK1 in vagal sensory neurons in suppressing airway inflammation...

Respiratory viral infection can lead to activation of sensory afferent nerves as indicated by the consequential sore throat, sneezing, coughing, and reflex secretions. In addition to causing troubling symptoms, sensory nerve activation likely accelerates viral spreading. The mechanism how viruses activate sensory nerve terminals during infection is unknown. In this study, we investigate whether coronavirus spike protein activates sensory nerves terminating in the airways. We used isolated vagally-innervated mouse trachea-lung preparation for two-photon microscopy and extracellular electrophysiological recordings...

OBJECTIVE: Semaphorin3E (Sema3E) mediates reorganization of the actin cytoskeleton, and plays an important role in ensuring the specificity of synapse formation and angiogenesis. However, the role of Sema3E in allergic asthma (AS) and eosinophilic bronchitis (EB) is still elusive. This study aimed to investigate the relationship between Sema3E in vagal ganglion and lung tissue, airway reactivity, and eosinophilic inflammation. METHODS: The frequency of coughs and airway reactivity as well as the airway inflammation were observed in ovalbumin- (OVA-) induced AS and EB mouse models...

A cough is one of several defensive responses that protect and clear the airways of inhaled, aspirated or locally produced chemicals and matter. The neural components needed to initiate a cough begin to develop in utero, and at birth the airways and lungs already have a rich supply of sensory and motor-neural innervation. However, a cough is not always the primary defensive response to airway challenge in very young infants, but instead develops in the first postnatal months and matures further into puberty...

BACKGROUND: To provide new ideas for the clinical and mechanism research of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD), this study systematically reviews clinical research and the progress of basic research of acupuncture in the treatment of COPD. METHODS: PubMed and Web of Science databases were searched using acupuncture and COPD as keywords in the last 10 years, and the included literature was determined according to exclusion criteria...

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel that is activated by electrophilic irritants, oxidative stress, cold temperature and GPCR signaling. TRPA1 expression has been primarily identified in subsets of nociceptive sensory afferents and is considered a target for future analgesics. Nevertheless, TRPA1 has been implicated in other cell types including keratinocytes, epithelium, enterochromaffin cells, endothelium, astrocytes and CNS neurons. Here, we developed a knock-in mouse which expresses the recombinase FlpO in TRPA1-expressing cells...

INTRODUCTION: The Valsalva maneuver and its modifications have been utilized across several conditions in medicine; however, there have been difficulties in its application. Thus, at the University of Texas Health Science Center in San Antonio, we designed and patented an affordable and accessible device that mimics Valsalva called " Forced Inspiratory Suction and Swallow Tool (FISST). AREAS COVERED: In this review, we discuss the premise for the design of FISST, based on applications of the law of conservation energy, the continuity equation, and Bernoulli's principle...

BACKGROUND: Non-intubated thoracic surgery has not achieved widespread acceptance despite its potential to improve postoperative outcomes. To ensure airway safety, our institute has developed a technique combining spontaneous ventilation with double-lumen tube intubation (SVI). This study aimed to verify the feasibility and limitations of this SVI technique. METHODS: For the SVI method, anesthesia induction involves fentanyl and propofol target-controlled infusion, with mivacurium administration...

INTRODUCTION: There is growing interest in how breathing pace, pattern, and training (e.g., device-guided or -resisted breathing) affect cardiovascular health. It is unknown whether the route of breathing (nasal versus oral) affects prognostic cardiovascular variables. Because nasal breathing can improve other physiological variables (e.g., airway dilation), we hypothesized that nasal compared with oral breathing would acutely lower blood pressure (BP) and improve heart rate variability (HRV) metrics...

OBJECTIVE: The anti-tussive effect of gabapentin and its underlying neuromodulatory mechanism were investigated via a modified guinea pig model of gastroesophageal reflux-related cough (GERC). METHODS: Intra-esophageal perfusion with hydrochloric acid (HCl) was performed every other day 12 times to establish the GERC model. High-dose gabapentin (48 mg/kg), low-dose gabapentin (8 mg/kg), or saline was orally administered for 2 weeks after modeling. Cough sensitivity, airway inflammation, lung and esophagus histology, levels of substance P (SP), and neurokinin-1 (NK1 )-receptors were monitored...

BACKGROUND: Suctioning of the posterior pharynx immediately after birth during neonatal resuscitation can produce a vagal response resulting in bradycardia or apnea. The feasibility of delaying any airway suctioning and avoiding deep suctioning has not been studied. OBJECTIVES: To test the hypothesis that newborn resuscitation is feasible with the following two guidelines: 1) avoiding any suctioning until the infant establishes spontaneous respiration, and 2) avoiding the use of deep suction with catheters...