Expert review of respiratory medicine
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Tracheal replacement has been attempted since the beginning of the last century, but always failed because of the difficulties in harvesting and revascularizing its microvascular network and the necessity for heavy immunosuppression. Regenerative medicine is an emerging interdisciplinary field of research and clinical applications focused on the repair, replacement or regeneration of cells, tissues or organs to restore impaired function. ⋯ By doing so, immunosuppression is avoided. In this article, we describe the strategies that could have relevant clinical applications and the translational research approaches used to clinically replace irreversible diseases of the trachea, and discuss how to make this stem cell-based technology available to everyone.
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The clinical syndrome of obstructive sleep apnea (OSAS) in children is a distinct, yet somewhat overlapping disorder with the condition that occurs in adults, such that the clinical manifestations, polysomnographic findings, diagnostic criteria and treatment approaches need to be considered in an age-specific manner. Childhood OSAS has now become widely recognized as a frequent disorder and as a major public health problem. ⋯ Although adenotonsillectomy (T&A) remains the first line of treatment, evidence in recent years suggests that the outcomes of this surgical procedure may not be as favorable as expected, such that post-T&A polysomnographic evaluation may be needed, especially in high-risk patient groups. In addition, incorporation of nonsurgical approaches for milder forms of the disorder and for residual OSAS after T&A is now being investigated.
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Expert Rev Respir Med · Jun 2011
ReviewThe role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and α-1 anti-trypsin deficiency.
The serine proteinase inhibitor α-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. ⋯ However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences.
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Expert Rev Respir Med · Apr 2011
ReviewTargeting soluble guanylate cyclase for the treatment of pulmonary hypertension.
Pulmonary arterial hypertension is a disease characterized by a sustained increase in pulmonary arterial pressure leading to right heart failure. Current treatments focus on endothelial dysfunction and an aberrant regulatory pathway for vascular tone. ⋯ Here, we briefly discuss the pathophysiology of pulmonary hypertension and endothelial dysfunction, along with current treatments. We then present a focused review of recent animal studies and human trials examining the use of activators and stimulators of soluble guanylate cyclase for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.