Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital central hypoventilation syndrome (CCHS) patients exhibit respiratory deficits to ventilatory challenges, diminished breathing drive during sleep, and reduction of respiratory-related heart rate variation, but at least partially preserved peripheral chemoreception. We hypothesized that integration of afferent activity with respiratory motor output is deficient in CCHS, rather than chemoreceptor failure, and that examination of trends in heart and breathing rates and variabilities following ventilatory challenges may clarify the deficient mechanisms. Twelve children with CCHS and 12 age- and gender-matched control cases were subjected to hyperoxic hypercapnic, poikylocapnic hypoxic, and hyperoxic challenges while supine. Heart and respiratory rates and variabilities during 60-s baseline and 120-s challenge periods were assessed. Hypoxia and hypercapnia enhanced breathing rate in control subjects; in CCHS cases, the rise differed during hypercapnia and did not occur to hypoxia. Hyperoxia showed initial transient patterns in breathing rate that differed between groups. A heart rate increase to hypoxia and late decline to hyperoxia were muted in CCHS patients. In hypercapnia, heart rate followed similar rising patterns in both groups. Overall CCHS heart rate variability was lower in baseline and challenge periods, principally due to diminished respiratory-related variation, especially during hypercapnia. No heart rate variability group differences emerged in hypoxia, and only a late increase for CCHS cases developed in hyperoxia. The findings indicate retention of aspects of chemoreceptor sensitivity in CCHS cases. The heart rate alterations to ventilatory challenges suggest specific compensatory responses of a slower nature remain intact in CCHS, whereas other rapidly changing components are deficient.
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PMID:Temporal trends of cardiac and respiratory responses to ventilatory challenges in congenital central hypoventilation syndrome. 1502 46

Congenital central hypoventilation syndrome is a rare disorder caused by a mutation in the PHOX2B gene resulting in hypoventilation that is worse during sleep. Human physiologic studies show that patients with CCHS have absent or decreased rebreathing ventilatory responses to hypercapnia and hypoxemia during sleep as well as during wakefulness. Some ventilatory responses to hypoxia and hyperoxia can be demonstrated using a step change in inspired oxygen. However, these suggest that both central and peripheral chemoreceptor functions are generally defective in all states in children with CCHS. The defect in CCHS may lie in central nervous system pathways regulating ventilation, whose development and function are controlled by PHOX2B. Moreover, the retrotrapezoid nucleus (RTN) may be the major defect in CCHS, where central and peripheral inputs converge. Human physiological studies predicted that the defect in CCHS lies in central integration of the central and peripheral chemoreceptor signals. New evidence suggests the RTN may be the respiratory controller where chemoreceptor inputs are integrated. In this review we present the clinical presentation of CCHS, revisit results of human physiologic studies, and discuss the findings in light of new knowledge about the role of PHOX2B and RTN in CCHS.
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PMID:Peripheral chemoreceptors in congenital central hypoventilation syndrome. 2309 21

Congenital central hypoventilation syndrome (CCHS) is a neurodevelopmental disorder characterized by life-threatening hypoventilation, possibly resulting from disruption of central chemosensory integration. However, animal models suggest the possibility of residual chemosensory function in the human disease. Cardioventilatory function in a large cohort with CCHS and verified paired-like homeobox 2B (PHOX2B) mutations was assessed to determine the extent and genotype dependence of any residual chemosensory function in these patients. As part of inpatient clinical care and evaluation, 64 distinct studies from 32 infants, children, and young adults with the disorder were evaluated for physiological response to three different inspired steady-state gas exposures of 3 min each: hyperoxia [100% oxygen (O2)]; hyperoxic hypercapnia [95% O2 and 5% carbon dioxide (CO2)]; and hypoxic hypercapnia [14% O2 and 7% CO2 balanced with nitrogen (N2)]. These were followed by a hypoxia challenge consisting of five or seven breaths of N2 (100% N2). In addition, a control group of 15 young adults was exposed to all but the hypoxic challenge. Comprehensive monitoring was used to derive breath-to-breath and beat-to-beat measures of ventilatory, cardiovascular, and cerebrovascular function. On average, patients showed a residual awake ventilatory response to chemosensory challenge, independent of the specific patient PHOX2B genotype. Graded dysfunction in cardiovascular regulation was found to associate with genotype, suggesting differential effects on different autonomic subsystems. In addition, differences between cases and controls in the cerebrovascular response to chemosensory challenge may indicate alterations in cerebral autoregulation. Thus residual cardiorespiratory responses suggest partial preservation of central nervous system networks that could provide a fulcrum for potential pharmacological interventions.
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PMID:Residual chemosensitivity to ventilatory challenges in genotyped congenital central hypoventilation syndrome. 2438 Nov 23