title: Refractory asthma: importance of bronchoscopy to identify phenotypes and direct therapy.
abstract: BACKGROUND
  The pathophysiology of refractory asthma is not well understood; thus, treatment modalities are not targeted to specific phenotypes but rather to a broad-based treatment approach. The objective of this study was to develop refractory asthma phenotypes based on bronchoscopic evaluation and to develop from this information specific, directed, personalized therapy.
  
  
  METHODS
  Fifty-eight patients with difficult-to-treat (refractory) asthma were characterized by the use of fiber-optic bronchoscopy with visual scoring systems of the upper and lower airways as well as with BAL, endobronchial biopsy, and brush. Response to changes in therapy was evaluated by changes in the Asthma Control Test and pulmonary function.
  
  
  RESULTS
  Five mutually exclusive phenotypes were formulated based on bronchoscopic evaluation: gastroesophageal reflux, subacute bacterial infection, tissue eosinophilia, combination, and nonspecific. Specific directed therapy yielded a significant improvement in the Asthma Control Test and pulmonary function for the entire group as well as for each defined subgroup except for the nonspecific group. Of interest, visual scoring of the supraglottic abnormalities identified 34 of 35 patients with gastroesophageal reflux and may give a better insight into asthmatic problems associated with chronic proximal reflux than standard testing.
  
  
  CONCLUSIONS
  Bronchoscopic evaluation of the upper and lower airways can provide important information toward characterizing refractory asthma so as to better individualize therapeutic options and improve asthma control and lung function in patients with difficult-to-treat asthma.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health and the University of Colorado Denver, Denver, CO.
authors.forename: James T
authors.initials: JT
authors.lastname: Good
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health and the University of Colorado Denver, Denver, CO.
authors.forename: Christena A
authors.initials: CA
authors.lastname: Kolakowski
authors.affiliation: Division of Pathology, Department of Medicine, National Jewish Health and the University of Colorado Denver, Denver, CO.
authors.forename: Steve D
authors.initials: SD
authors.lastname: Groshong
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Medicine, National Jewish Health and the University of Colorado Denver, Denver, CO.
authors.forename: James R
authors.initials: JR
authors.lastname: Murphy
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, National Jewish Health and the University of Colorado Denver, Denver, CO. Electronic address: martinr@njhealth.org.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D001424:Bacterial Infections / Q000150:complications / Q000175:diagnosis; D001999:Bronchoscopy / Q000379:methods*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D057285:Precision Medicine; D011657:Pulmonary Eosinophilia / Q000150:complications / Q000175:diagnosis; D012129:Respiratory Function Tests