title: Immunoassay-based measurement of clinical biomarkers for monitoring changes in nasal cavity.
abstract: BACKGROUND
  Many drugs for treatment of allergies, migraine headaches, inflammation, and other indications are administered into the nasal cavity providing access to the immune and central nervous systems. One of the concerns for using this route of administration is potential damage to the nasal epithelium and mucosal regions. We assembled a panel of clinical biomarkers that can be used to monitor changes in the nasal epithelium, mucosa, and olfactory regions in preparation for clinical trials involving drugs administered via intranasal route. These biomarkers included albumin, elastase, IL-6, IL-8, lactoferrin, myeloperoxidase and nerve growth factor.
  
  
  METHODS
  Immunoassays were developed and used to measure changes in these biomarkers in nasal lavage samples collected twice daily from 30 assumed-healthy volunteers over a 2-day period. Various statistical methods including analysis of variance (ANOVA), paired t-test and Pearson's product-moment correlation were used to evaluate the data.
  
  
  RESULTS
  Although the basal levels of these biomarkers were varied among subjects, the data show that the concentrations of albumin, elastase and IL-8 were significantly higher in samples collected in the morning compared to samples collected later during the day. Pre-washing nasal cavity prior to collecting nasal lavage samples did alter the measurement of elastase and albumin, but did not influence the levels of the other biomarkers.
  
  
  CONCLUSIONS
  These data show that this panel of biomarkers can be used to monitor changes in the nasal cavity including those affected by diurnal fluctuations. These results also provide useful baseline values and sources of variability for each biomarker that could be used to help design clinical trials.
authors.affiliation: Biomarker and Bioanalytical Sciences, Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543, USA. yan.j.zhang@bms.com
authors.forename: Yan J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Sherri
authors.initials: S
authors.lastname: Luroe
authors.forename: Frank
authors.initials: F
authors.lastname: Schieber
authors.forename: Joan
authors.initials: J
authors.lastname: Kelsey
authors.forename: Fizal
authors.initials: F
authors.lastname: Nabbie
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rizzi
authors.forename: Penny
authors.initials: P
authors.lastname: Richards
authors.forename: Russell
authors.initials: R
authors.lastname: Weiner
authors.forename: Paul W
authors.initials: PW
authors.lastname: Rhyne
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000378:metabolism; D015415:Biomarkers / Q000737:chemistry*; D002940:Circadian Rhythm; D002986:Clinical Trials as Topic; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation / Q000379:methods*; D016209:Interleukin-8 / Q000096:biosynthesis; D008875:Middle Aged; D009296:Nasal Cavity / Q000187:drug effects* / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D000418:Albumins; D015415:Biomarkers; D016209:Interleukin-8; D010196:Pancreatic Elastase