CCHS should be suspected in individuals presenting with unexplained hypoventilation and/or seizures after anesthetics or sedatives. This is the first report of LO-CCHS in a kindred with the PHOX2B 20/24 genotype. The incomplete penetrance observed in this family suggests a gene-environment interaction.

To study the roles of substance P (SP) and endogenous peptidases in regulating mucus secretion from ferret trachea, we measured the SP-induced release of 35SO4-labeled macromolecules after incubating segments of trachea in Ussing chambers in the presence and absence of selected inhibitors of proteolytic enzymes. Our strategy was based on the idea that if endogenous peptidases degrade SP, then inhibitors of these enzymes should potentiate SP-induced secretion. We found that tracheas of ferrets contained SP-like immunoreactivity, and that SP stimulated the release of bound 35SO4 with rapid onset and offset. Eighty-five percent of the total macromolecular radioactivity released was contained in fractions of molecular weights greater than 10(6). The response to SP was concentration-dependent and reproducible. Thiorphan potentiated the secretory response to SP in a concentration-dependent fashion and phosphoramidon potentiated SP-induced secretion, whereas other inhibitors of proteinases and peptidases were without effects. These results suggest that substance P may regulate mucus secretion in ferrets, and that enkephalinase (dipeptidyl carboxypeptidase II, EC 3.4.24.11) in the airway degrades SP in a physiologically significant fashion, and thereby regulates peptide-induced secretion.

Our aim was to determine whether flow from the submucosal glands of the trachea is reflexly regulated by sensory stimuli from the stomach in the cat, and, if such a gastropulmonary reflex exists, what sensory and motor pathways are important. We found that mechanical stimulation of the gastric mucosa increased submucosal gland secretions from 7.9 +/- 0.7 to 17.4 +/- 1.7 nl/min (mean +/- SE, P less than 0.001). This effect was prevented reversibly by cooling both abdominal vagus nerves to -3 degrees C before stimulation and was restored by rewarming the nerves. The effect was prevented irreversibly by cutting both abdominal vagus nerves and was then mimicked by electrically stimulating the central cut end of one of the nerves. This increase in secretions caused by electrical stimulation of the nerve was prevented by administration of atropine sulfate before stimulation. We conclude that stimuli from the stomach reflexly affect the rate of submucosal gland secretion. The sensory limb of this reflex lies in the abdominal vagus nerves, and the motor pathways are mediated by cholinergic muscarinic receptors.

BACKGROUND: During the first wave of the COVID-19 pandemic, shortages of ventilators and ICU beds overwhelmed health-care systems. Whether early tracheostomy reduces the duration of mechanical ventilation and ICU stay is controversial.RESEARCH QUESTION: Can failure-free day outcomes focused on ICU resources help to decide the optimal timing of tracheostomy in overburdened health-care systems during viral epidemics? STUDY DESIGN AND METHODS: This retrospective cohort study included consecutive patients with COVID-19 pneumonia who had undergone tracheostomy in 15 Spanish ICUs during the surge, when ICU occupancy modified clinician criteria to perform tracheostomy in Patients with COVID-19. We compared ventilator-free days at 28 and 60 days and ICU-and hospital bed-free days at 28 and 60 days in propensity score-matched cohorts who underwent tracheostomy at different timings (# 7 days, 8-10 days, and 11-14 days after intubation).RESULTS: Of 1,939 patients admitted with COVID-19 pneumonia, 682 (35.2%) underwent tracheostomy, 382 (56%) within 14 days. Earlier tracheostomy was associated with more ventilator-free days at 28 days (# 7 days vs > 7 days [116 patients included in the analysis]: median, 9 days [interquartile range (IQR), 0-15 days] vs 3 days [IQR,[0][1][2][3][4][5][6][7]; difference between groups, 4.5 days; 95% CI, 2.3-6.7 days; 8-10 days vs > 10 days [222 patients analyzed]: 6 days [IQR, 0-10 days] vs 0 days [IQR, 0-6 days]; difference, 3.1 days; 95% CI, 1.7-4.5 days; 11-14 days vs > 14 days [318 patients analyzed]: 4 days [IQR, 0-9 days] vs 0 days [IQR, 0-2 days]; difference, 3 days; 95% CI, 2.1-3.9 days). Except hospital bed-free days at 28 days, all other end points were better with early tracheostomy.INTERPRETATION: Optimal timing of tracheostomy may improve patient outcomes and may alleviate ICU capacity strain during the COVID-19 pandemic without increasing mortality. Tracheostomy within the first work on a ventilator in particular may improve ICU availability.

The idea that the fluid component of cat tracheal submucosal gland secretions is produced by Na-linked secretion of Cl was tested. Gland secretion was stimulated with phenylephrine; gland fluid flow, net salt movement, and output of 35SO4-labeled macromolecules were measured. With CI, I, NO3, or Br as the major anion, phenylephrine caused equal increases in gland flow and output of 35S-labeled macromolecules while increasing net transepithelial 22Na movement from 0 to about 10 mu eq X cm-2 X h-1. With the impermeant gluconate as a major anion, phenylephrine caused the same increase in output of 35S label, a smaller increase in gland flow, and had no effect on net 22Na movement. Short circuiting in the presence of Cl, or high concentrations of the loop diuretics, furosemide or bumetanide, did not alter the actions of phenylephrine. Ouabain or replacement of Na by choline or Li abolished all secretory effects of phenylephrine. We conclude that active Cl secretion is not responsible for the transepithelial flows of salt and water induced by phenylephrine. Instead, these flows may be secondary to the release of osmotically active components of the secretory granules.