Other autoimmune diseases such as ulcerative colitis and Crohn's disease also have an association with bronchiectasis. Additionally, graft-versus-host disease in patients who have undergone stem cell transplantation can lead to bronchiectasis as well. Lung injury Bronchiectasis could be caused by: inhalation of ammonia and other toxic gases, chronic pulmonary aspiration of stomach acid from esophageal reflux, or a hiatal hernia. Congenital Bronchiectasis may result from congenital disorders that affect cilia motility or ion transport. A common genetic cause is cystic fibrosis, which affects chloride ion transport. Another genetic cause is primary ciliary dyskinesia, a rare disorder that leads to immotility of cilia and can lead to situs inversus. When situs inversus is accompanied by chronic sinusitis and bronchiectasis, this is known as Kartagener's syndrome. Other rare genetic causes include Young's syndrome and Williams-Campbell syndrome. Tracheobronchomegaly, or Mournier-Kuhn syndrome is a rare condition characterized by significant tracheobronchial dilation and recurrent lower respiratory tract infections. Individuals with alpha 1-antitrypsin deficiency have been found to be particularly susceptible to bronchiectasis, due to the loss of inhibition to enzyme elastase which cleaves elastin. This decreases the ability of the alveoli to return to normal shape during expiration. Cigarette smoking A causal role for tobacco smoke in bronchiectasis has not been demonstrated. Nonetheless, tobacco smoking can worsen pulmonary function and accelerate the progression of disease that is already present. Pathophysiology The development of bronchiectasis requires two factors: an initial injury to the lung (such as from infection, auto-immune destruction of lung tissue, or other destruction of lung tissue (as seen in gastroesophageal reflux disease or aspiration syndromes)) which leads to impaired mucociliary clearance, obstruction, or a defect in host defense. This triggers a host immune response from neutrophils (elastases), reactive oxygen species, and inflammatory cytokines that results in progressive destruction of normal lung architecture. In particular, the elastic fibers of bronchi are affected. The result is permanent abnormal dilation and destruction of the major bronchi and bronchiole walls. Disordered neutrophil function is believed to play a role in the pathogenesis of bronchiectasis. Neutrophil extracellular traps(NETs), which are extracellular fibers secreted by neutrophils that are used to trap and destroy pathogens, are hyperactive in bronchiectasis. Increased NET activity is associated with more severe bronchiectasis. Neutrophil elastase, which is an extracellular protein secreted by neutrophils to destroy pathogens as well as host tissue, is also hyperactive in many cases of bronchiectasis. An increased neutrophil elastase activity is