title: Mucus and MUC in asthma.
abstract: OBJECTIVE
  Asthma is characterized by chronic airway inflammation and a mucus hypersecretory phenotype comprising excess mucus secretion, goblet cell hyperplasia and submucosal gland hypertrophy. This augmented mucus secretion has been relatively undervalued in asthma compared with airway inflammation. However, mucus plugging contributes to airflow limitation and airway hyperresponsiveness, and to morbidity and mortality in asthma. We review recent contributions to this field and therapeutic avenues to control mucus hypersecretion.
  
  
  RESULTS
  A distinct mucus hypersecretory phenotype may present in asthma. Overexpression of MUC5AC, MUC5B and MUC2 have been described in asthma secretions, but identification of defined biochemical abnormalities and polymorphisms of mucin genes linked to asthma remains elusive. Activation of epidermal growth factor receptor (EGFR) activation appears central in transducing many different stimuli, including oxidative stress, proteases and cytokines. In contrast, nitrosative stress has barely been investigated. The existence of crosstalk between EGFR and other receptor systems may provide new clues regarding the activity of acetylcholine, adenosine and other agonists of G-protein-coupled receptors and other receptor families on mucin secretion. Modern techniques for noninvasive detection of mucus pathology will advance clinical research in this field.
  
  
  CONCLUSIONS
  Airway mucus hypersecretion as a part of airway remodelling represents a problem in asthma, and studies of pathophysiology and therapeutic approaches are therefore warranted. Identification of targets such as the EGFR cascade, which are crucial in excessive and abnormal mucus secretion, may lead to the rational design of new antihypersecretory drugs that may enhance future asthma treatment.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Valencia, and Research Foundation of University General Hospital Consortium, Valencia, Spain. esteban.morcillo@uv.es
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Morcillo
authors.forename: Julio
authors.initials: J
authors.lastname: Cortijo
mesh_terms: D001249:Asthma / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D002908:Chronic Disease; D006801:Humans; D009077:Mucins / Q000235:genetics* / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D010641:Phenotype; D020545:Respiratory Mucosa / Q000378:metabolism*
chemical_list: D009077:Mucins