Respiratory physiology & neurobiology
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Respir Physiol Neurobiol · Jul 2005
ReviewGenetic determinants of upper airway structures that predispose to obstructive sleep apnea.
Genetic factors are thought to play an important role in human development. Recent data indicate that obstructive sleep apnea may have a genetic basis. Sleep apnea is a very common disorder with significant cardiovascular and neurophysiologic morbidity. ⋯ The reduction in airway size is secondary to increased adipose tissue (enlargement of the parapharyngeal fat pads), alterations in craniofacial structure (reduction in mandibular size) and enlargement of the surrounding soft tissue structures (tongue, lateral pharyngeal walls). Genetic factors are one of the factors that have been proposed to mediate the size of each of these anatomic risk factors for sleep apnea. Recent evidence is accumulating about the genetic loci for these structural risk factors that predispose to the development of obstructive sleep apnea.
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Respir Physiol Neurobiol · Aug 2004
ReviewImplications of hypoxic hypometabolism during mammalian ontogenesis.
During hypoxia, many newborn mammals, including the human infant, decrease metabolic rate, therefore adopting a strategy common to many living creatures of all classes, but usually not adopted by adult humans and other large mammals. In acute hypoxic conditions, hypometabolism largely consists in actively dropping mechanisms of thermoregulation. One implication is a decrease in body temperature. ⋯ Upon termination of hypoxia, the newborn's metabolic rate recovers and growth resumes at higher rate. Even if body weight may be completely regained, alterations in the respiratory mechanical properties and in aspects of ventilatory control can persist into adulthood, a phenomenon not seen when the hypoxia was experienced at later stages of development. Some of the long-term respiratory effects of neonatal hypoxia are reminiscent of those observed in adult animals and humans native and living in high altitude regions.
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Respir Physiol Neurobiol · Sep 2003
ReviewMechanisms of inflammation-mediated airway smooth muscle plasticity and airways remodeling in asthma.
Recent evidence points to progressive structural change in the airway wall, driven by chronic local inflammation, as a fundamental component for development of irreversible airway hyperresponsiveness. Acute and chronic inflammation is orchestrated by cytokines from recruited inflammatory cells, airway myofibroblasts and myocytes. Airway myocytes exhibit functional plasticity in their capacity for contraction, proliferation, and synthesis of matrix protein and cytokines. ⋯ Functional plasticity of airway smooth muscle (ASM) is regulated by an array of environmental cues, including cytokines, which mediate their effects through receptors and a number of intracellular signaling pathways. Despite numerous studies of the cellular effects of cytokines on cultured airway myocytes, few have identified how intracellular signaling pathways modulate or induce these cellular responses. This review summarizes current understanding of these concepts and presents a model for the effects of inflammatory mediators on functional plasticity of ASM in asthma.
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Respir Physiol Neurobiol · Jul 2003
ReviewSleepiness and residual sleepiness in adults with obstructive sleep apnea.
Sleepiness is a common, but not necessary symptom of the obstructive sleep apnea syndrome (OSA) and is a frequent chief complaint of patients with OSA who seek medical attention. While sleepiness may seem simple in nature, the underlying mechanisms producing daytime sleepiness in OSA are complex and poorly characterized. Moreover, the meaningful assessment of pathological sleepiness is frequently far from straightforward. ⋯ An unknown percentage of treated OSA patients, however, remain sleepy during waking hours. The assessment and treatment of residual sleepiness in treated OSA can range from simple to difficult, depending on the nature and causes of the continued sleepiness. Recently, however, data from clinical trials have been generated which provide direction in the evaluation and management of the OSA patient suffering residual daytime sleepiness.
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Respir Physiol Neurobiol · May 2003
ReviewGenetic aspects of breathing: on interactions between hypercapnia and hypoxia.
Indeed, specific genes in humans and mice regulate breathing pattern at baseline and breathing control during chemical stimulation. The current review addresses the question of coupling plausible candidate genes to physiological variation in control of breathing. That is, can genes discovered in mice be candidates assigned to similar physiological mechanisms as genetic control of breathing in humans? As an illustration, this review examines the interaction of hypoxia in affecting the hypercapnic ventilatory sensitivity (HCVS) curve in humans and mice. ⋯ As a mechanism associated with the chemical control of breathing in humans, the absence of CO(2) potentiation in mice suggests that specific genes interact to establish variation in complex breathing traits among mouse strains and between species. If future studies support the current evidence, the absence of CO(2) potentiation in mice compared with humans suggest a clearly defined species difference, which may depend on alternative hypoxic interactions such as hypometabolic and central neuronal depressive mechanisms in mice. Because the complexity of breathing mechanisms varies with modest adjustments in the environment, gene-targeting strategies that achieve 'one-gene, one-phenotype' results must be complimented with alternative strategies that consider integrating complex respiratory mechanisms with gene-to-gene interactions.