title: Relative resistance to oral theophylline treatment in patients with hyposmia manifested by decreased secretion of nasal mucus cyclic nucleotides.
abstract: BACKGROUND
  Oral treatment with the phosphodiesterase inhibitor theophylline in an open-label fixed-design clinical trial in 312 patients with hyposmia improved smell function in >50%. Before treatment, all patients had lower than normal levels of nasal mucus cAMP and cGMP. The purpose of this study was to study relationships among changes in smell function, theophylline levels and nasal mucus cAMP and cGMP among patients whose smell function improved (responders) and those who did not improve (nonresponders) on oral theophylline treatment.
  
  
  METHODS
  After all data analysis from the clinical trial was completed, data from each of the 31 of the 312 patients in whom nasal mucus cAMP and cGMP and theophylline levels were available before and after theophylline treatment at several drug doses were evaluated. At initiation and at termination of each treatment, dose smell function, nasal mucus cAMP and cGMP and plasma theophylline were analyzed.
  
  
  RESULTS
  On the same theophylline dose, although serum theophylline increased among both responders and nonresponders, serum levels were consistently higher among responders. Nasal mucus cAMP and cGMP were also higher among responders than nonresponders. At higher theophylline doses, cGMP reached normal levels among responders, whereas it did not change significantly among nonresponders.
  
  
  CONCLUSIONS
  Some patients with hyposmia with initially low nasal mucus cAMP and cGMP levels may be relatively resistant to oral theophylline treatment. This result may offer a mechanism of response lack among some patients whose smell function did not improve after oral theophylline treatment although other factors may influence their response lack.
authors.affiliation: Taste and Smell Clinic, Center for Molecular Nutrition and Sensory Disorders, Washington, DC 20016, USA. doc@tasteandsmell.com
authors.forename: Robert I
authors.initials: RI
authors.lastname: Henkin
authors.forename: Irina
authors.initials: I
authors.lastname: Velicu
authors.forename: Loren
authors.initials: L
authors.lastname: Schmidt
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000242:Cyclic AMP / Q000737:chemistry / Q000378:metabolism*; D006152:Cyclic GMP / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009093:Mucus / Q000737:chemistry / Q000378:metabolism*; D000857:Olfaction Disorders / Q000188:drug therapy*; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000627:therapeutic use*; D013806:Theophylline / Q000097:blood / Q000627:therapeutic use*; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D010726:Phosphodiesterase Inhibitors; D013806:Theophylline; D000242:Cyclic AMP; D006152:Cyclic GMP