About this Research Topic
Elevated levels of CO2 (hypercapnia) are often observed in acute and chronic lung diseases as an indication of alveolar hypoventilation and altered gas exchange. It has been long debated whether hypercapnia is a consequence of these disease states or rather a contributor to pathophysiology. Hypercapnia exerts anti-inflammatory effects mainly due to the associated acidosis, which historically led to the notion that hypercapnia might be tolerated (permissive) or even therapeutic. In contrast, recently, it has become increasingly evident that levels of CO2 are sensed by various non-excitable cells via an as-yet unknown mechanism that leads to highly specific signaling cascades, many of which are detrimental. Importantly, these effects of hypercapnia are not limited to the lung, the site of CO2 elimination.
Elevated CO2 levels impair alveolar epithelial barrier and bronchial airway function and also promote skeletal muscle dysfunction. Moreover, hypercapnia weakens innate immunity, cellular repair and regeneration, however, the molecular mechanisms driving these injurious effects remain incompletely understood. As it is increasingly evident that hypercapnia is an independent risk factor and driver of poor outcome in patients with acute and chronic pulmonary diseases, interfering with the specific CO2-induced cellular events may improve outcome of hypercapnic patients. In particular, better understanding of the mechanisms by which CO2 is sensed and the effects of hypercapnia in human pathophysiology may lead to novel therapeutic modalities in patients with elevated CO2 levels.
Original articles and reviews addressing novel aspects of CO2 sensing and signaling as well as the (patho)physiological effects of hypercapnia at the molecular, cellular and organ level are welcome. We also seek to receive perspectives on the implications of these aspects in human health and disease and potential rescue mechanisms in the setting of acute or chronic hypercapnia. Contributions focusing on the potentially advantageous vs. disadvantageous nature of hypercapnia are also anticipated. Potential themes for the proposed Research Topic include:
• Molecular mechanisms of CO2 sensing and signaling
• Effects of hypercapnia on lungs, skeletal muscles and other organs
• Role of elevated CO2 in host immunity
• Hypercapnia in cellular proliferation and repair
• Potentially advantageous effects of hypercapnia
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.