Respiratory physiology & neurobiology
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The transcription factor PHOX2B is essential for the development of the autonomic nervous system. In humans, polyalanine expansion mutations in PHOX2B cause Congenital Central Hypoventilation Syndrome (CCHS), a rare life-threatening disorder characterized by hypoventilation during sleep and impaired chemosensitivity. CCHS is combined with comparatively less severe impairments of autonomic functions including thermoregulation, cardiac rhythm, and digestive motility. ⋯ However, these impairments resolved rapidly, whereas the CCHS phenotype is irreversible. Heterozygous Phox2b(27Ala/+) pups exhibited a lack of responsiveness to hypercapnia and unstable breathing; they died within the first few postnatal hours. The generation of mouse models of CCHS provides tools for evaluating treatments aimed at alleviating both the respiratory symptoms and all other autonomic symptoms of CCHS.
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Acute lung injury (ALI) is a common, frequently hospital-acquired condition with a high morbidity and mortality. The stress associated with invasive mechanical ventilation represents a potentially harmful exposure, and attempts to minimize deforming stress through low tidal ventilation have proven efficacious. Lung cells are both sensors and transducers of deforming stress, and are frequently wounded in the setting of mechanical ventilation. ⋯ These downstream effects of mechanotransduction have been referred to collectively as "Biotrauma". Our review will focus on cellular stress failure, that is cell wounding, and the mechanisms mediating subsequent plasma membrane repair, we hold that a better mechanistic understanding of cell plasticity, deformation associated remodeling and repair will reveal candidate approaches for lung protective interventions in mechanically ventilated patients. We will detail one such intervention, lung conditioning with hypertonic solutions as an example of ongoing research in this arena.
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Respir Physiol Neurobiol · Aug 2008
Effects of cystic fibrosis lung disease on gas mixing indices derived from alveolar slope analysis.
S(cond) and S(acin) are derived from analysis of concentration-normalized phase III slopes (Sn(III)) of a multiple breath inert gas washout. Studies in healthy and COPD subjects suggest these reflect ventilation heterogeneity in conducting and acinar airway zones respectively, but similar studies in cystic fibrosis (CF) are lacking. S(cond), S(acin) and lung clearance index (LCI, a measure of overall gas mixing efficiency) were measured in 22 adults and 18 children with CF and 17 adult and 29 child controls. ⋯ S(cond) was elevated in almost all CF patients, including children with mild disease and normal LCI. However, S(cond) did not correlate with other measurements and appeared to reach a maximum; further increase in ventilation heterogeneity being restricted to S(acin). The nature and/or severity of CF lung disease may invalidate assumptions underlying the ability to separate phase III slope analysis of ventilation heterogeneity into proximal and peripheral components, and LCI may be a better indicator of gas mixing in this population.
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Respir Physiol Neurobiol · Aug 2008
ReviewImplication of receptor for advanced glycation end product (RAGE) in pulmonary health and pathophysiology.
Receptor for advanced glycation end products (RAGE) is a membrane bound receptor and member of the immunoglobulin super family and is normally present in a highly abundant basal level expression in lung. This high expression of RAGE in lung alveolar epithelial type I (ATI) cells is presumably involved in the proliferation and differentiation of pulmonary epithelial cells. ⋯ Recently, a soluble form of RAGE (sRAGE) produced by recombinant gene technology was shown to exhibit a therapeutic potential in experimental animal models. Detailed study of RAGE in the pulmonary tissues will facilitate the understanding of the importance of RAGE signaling in the pulmonary health and pathophysiology.
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Respir Physiol Neurobiol · Jul 2008
Pressure loss caused by pediatric endotracheal tubes during high-frequency-oscillation-ventilation.
In a physical model of a pediatric respiratory system we measured the pressure drop across ETTs of 3 and 4mm inner diameter (ID) when we varied frequency, mean airway pressure and pressure amplitude of high-frequency-oscillation-ventilation (HFOV). Depending on ventilator settings the relative loss of mean pressure amplitude caused by the ETT ranged from 3.3% to 24.7% for ETT 4mm ID, respectively, from 23.8% to 51.8% for 3mm ID. In addition to the well-described flow dependency, ventilation frequency affected ETT resistance. ⋯ We conclude that the pressure drop across the ETT during HFOV is dependent on ETT size, pressure amplitude and ventilation frequency. Calculation of this pressure drop with conventional methods is inaccurate. The high-frequency-resistance of the ETT might protect the lungs from excessive pressure amplitudes during HFOV.