Asthma is characterized by airway constriction, excess mucus, and inflammation. We use mouse ex vivo lung slices to show that the inflammation and mucus secretion results from the excessive crowding due to mechanical bronchoconstriction, which causes so much cell extrusion that it destroys the airway epithelial barrier. Surprisingly, reversing bronchoconstriction with albuterol ((ALB), the current therapy) did not block this destruction but actually made it worse. However, inhibiting stretch-activated channels (GD) prevented extrusion, inflammation, and mucus secretion. Our findings propose a new etiology for asthma where the mechanical crowding from bronchoconstriction causes so much extrusion that it compromises the barrier, triggering subsequent inflammation.