Paediatric Tracheomalacia.

Intrathoracic tracheomalacia is characterized by increased compliance of the central airway within the thorax. This leads to excessive dynamic collapse during exhalation or periods of increased intrathoracic pressure such as crying. Extrathoracic tracheomalacia involves dynamic collapse of the airway between the glottis and sternal notch that occurs during inhalation rather than exhalation. The tone of the posterior membrane of the trachea increases throughout development and childhood, as does the rigidity of the tracheal cartilage. Abnormalities of airway maturation result in congenital tracheomalacia. Acquired tracheomalacia occurs in the normally developed trachea due to trauma, external compression, or airway inflammation. Although tracheomalacia can be suspected by history, physical examination, and supportive radiographic findings, flexible fiberoptic bronchoscopy remains the "gold standard" for diagnosis. Current treatment strategies involve pharmacotherapy with cholinergic agents, positive pressure ventilation, and surgical repair.

Establishment of smooth muscle and cartilage juxtaposition in the developing mouse upper airways.

In the trachea and bronchi of the mouse, airway smooth muscle (SM) and cartilage are localized to complementary domains surrounding the airway epithelium. Proper juxtaposition of these tissues ensures a balance of elasticity and rigidity that is critical for effective air passage. It is unknown how this tissue complementation is established during development. Here we dissect the developmental relationship between these tissues by genetically disrupting SM formation (through Srf inactivation) or cartilage formation (through Sox9 inactivation) and assessing the impact on the remaining lineage. We found that, in the trachea and main bronchi, loss of SM or cartilage resulted in an increase in cell number of the remaining lineage, namely the cartilage or SM, respectively. However, only in the main bronchi, but not in the trachea, did the loss of SM or cartilage lead to a circumferential expansion of the remaining cartilage or SM domain, respectively. In addition to SM defects, cartilage-deficient tracheas displayed epithelial phenotypes, including decreased basal cell number, precocious club cell differentiation, and increased secretoglobin expression. These findings together delineate the mechanisms through which a cell-autonomous disruption of one structural tissue can have widespread consequences on upper airway function.