title: Risk factors associated with irreversible airflow limitation in asthma.
abstract: OBJECTIVE
  Irreversible airflow limitation develops in some patients with asthma and is related to poorer prognosis. This paper reviews recent literature on natural course, risk factors, and potential mechanisms of persistent airflow limitation in asthma.
  
  
  RESULTS
  The natural course of persistent airflow limitation in asthma is poorly known, but reduced lung function at disease onset and an increased rate of decline during adult life contribute to its development. Risk factors for progressive irreversible airway obstruction in asthma include adult onset, frequent exacerbations, smoking, occupational exposure, ongoing eosinophilic airway inflammation and airway hyperresponsiveness. Polymorphisms of the ADAM33 gene predict excess decline in lung function, in asthma as well as at population level. It is still not clear how different components of airway remodeling affect lung function in asthma. Airway epithelium and airway smooth muscle seem to be highly important, but the interrelationship between persistent airflow limitation, airway inflammation, remodeling and airway hyperresponsiveness has not been clearly defined.
  
  
  CONCLUSIONS
  Whereas several factors have been implicated as being important in the development of fixed airway obstruction in asthma, we are just beginning to explore the different components of airway remodeling and their relevance, deleterious or beneficial, to clinical outcome.
authors.affiliation: Department of Pulmonology, Medical Center Leeuwarden, Leeuwarden, The Netherlands. a.ten.brinke@znb.nl
authors.forename: Anneke
authors.initials: A
authors.lastname: ten Brinke
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000276:immunology; D000328:Adult; D000367:Age Factors; D000402:Airway Obstruction / Q000209:etiology* / Q000503:physiopathology; D001249:Asthma / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000276:immunology; D018450:Disease Progression; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D045803:Mycoplasma pulmonis / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D012137:Respiratory System / Q000503:physiopathology; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
chemical_list: D014028:Tobacco Smoke Pollution; D051722:ADAM Proteins; C450441:ADAM33 protein, human