For instance, another gene with an entirely different function, Tafazzin, is unrelated to EHE but confusingly, also referred to as TAZ. In any case, the EHE translocation results in an abnormal ‘fusion gene’ that expresses an abnormal mRNA resulting in synthesis of a fusion protein variant of TAZ that is always turned on. This form of TAZ always resides in the nucleus and therefore is constitutively active. It binds and turns on a very important member of the TEAD family of transcription factors and this causes cells to proliferate. It is this production of the TAZ-TEAD transcriptome that causes the affected endothelial cells to grow into tumors. In normal cells, TAZ is considered a major negative transducer of the Hippo pathway, a signaling system that regulates organ size by causing cells to stop growing when they touch each other (contact inhibition). Many upstream inputs regulate the Hippo signal which normally functions to turn off or de-activate TAZ by keeping it in the cytoplasm and out of the nucleus. In EHE cells, the abnormal fusion TAZ is ‘immune’ to this input and just stays in the nucleus, and continuing to stimulate cell growth. Note that about 10% of EHE patients harbor a different translocation. This one similarly results in the constitutive activation of YAP, an orthologue of TAZ (i.e., a gene that has sequence and function that are very similar to TAZ). This also results in persistent, unregulated growth of the affected cells and therefore causes EHE-type tumors.
Classifications
There are three types of tracheomalacia:
Type 1—congenital, sometimes associated with tracheoesophageal fistula or esophageal atresia
Type 2—extrinsic compression sometimes due to vascular rings
Type 3—acquired due to chronic infection or prolonged intubation or inflammatory conditions like relapsing polychondritis

Treatment
According to the 2012 Cochrane review, there is no evidence supporting medical therapy over surgical therapy for significant tracheomalacia, or vice versa. Current recommendations for mild to moderate non-life-threatening tracheomalacia focuses on symptom management. Regular use of hypertonic saline nebulizers
Low dose inhaled steroids may help decrease airway inflammation and swelling
Inhaled Ipratropium may help decrease secretions and stiffen smaller airways
Antibiotics during active respiratory infection may decrease severity and length of symptoms
Continuous Airway Positive Pressure (CPAP) provides additional intraluminal pressureLife is usually saved if the airway is opened via a hole in the throat. If a person survives, they may have symptoms, but usually will get better after the airway is reopened. If the symptoms are severe enough, treatment may be needed. These range from medical management over mechanical ventilation (both continuous positive airway pressure (CPAP), or bi-level positive airway pressure (BiPAP) to tracheal stenting and surgery. Surgical techniques include aortopexy, tracheopexy, tracheobronchoplasty, and tracheostomy. The role of the nebulised recombinant human deoxyribonuclease (rhDNase) remains inconclusive. See also
Tracheal collapse for the condition in dogs

References


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