Clinical Study to Improve Diagnosis and Treatment of Sinusitis
Condition: Chronic Sinusitis
MeSH terms: Sinusitis
Study type: Observational

Summary: 
      Chronic rhinosinusitis (CRS) is the most common chronic medical condition that affects
      Americans between 18-44 years of age. While significant advances have been made in the
      understanding of the molecular pathogenesis underlying many subtypes of CRS, this has not
      translated into widespread changes in how physicians manage adult or pediatric CRS. The focus
      of this study is intended to develop testing methods to improve the objectivity and
      specificity of diagnosis and allow for individualized therapy with less invasive, customized
      treatments instead of the traditional, empiric based, and radically exenterative therapies
      commonly employed in clinical practice. Specifically, it is now known that many patients with
      CRS have a greater concentration of non-typeable Haemophilus influenzae (NTHI) in the
      bacterial biofilms located within their sinus cavities compared to healthy patients. The
      specific hypothesis behind the proposed research is that the presence of NTHI biofilms, which
      are known to be highly recalcitrant, are positively correlated with the development of CRS
      and that unique lipooligosaccharides and inflammatory byproducts obtained from nasopharyngeal
      lavage fluids and/or swabs of sinus secretions may be used as a non-invasive biomarker for
      CRS. As a result, patients with symptoms of CRS specifically associated with NTHI biofilms
      could possibly obtain a non-invasive test in the physician's office that would allow the
      clinician to make a more accurate diagnosis and objectively follow each patient's
      responsiveness to customized therapy.
    

Detailed description: 
      Specific Aims:

      Specific Aim 1 will test the hypothesis that a high throughput proteomics-based assay of
      nasopharyngeal lavage fluids and/or swabs of human sinus drainage material will be able to
      identify, with a high degree of sensitivity and specificity, patients with CRS specifically
      due to the presence of NTHI biofilms.

      Specific Aim 2 will test the hypothesis that a priori assay for increased presence of
      phosphorylcholine-rich lipooligosaccharides in nasopharyngeal lavage fluids from chinchillas
      co-infected with adenovirus and biofilm forming NTHI will successfully predict, with a high
      degree of sensitivity and specificity, the development of CRS in this in vivo model.

      Results from this project may: enable the design and conduct of a clinical trial to
      preoperatively identify patients with CRS earlier in their disease course (possibly prior to
      the initiation of long courses of empiric antibiotic therapy); aid in the development of
      non-surgical therapies to eradicate bacterial biofilms with the sinus cavities; result in the
      identification of an objective biomarker to monitor success with therapies; and ultimately
      lead to less morbidity and risk for complications compared to conventional surgical therapy.
      In addition, transforming this paradigm would make progress towards achieving the goals of
      the U.S. Department Health and Human Services Healthy People 2010 objective 14-19, which is
      "reducing the number of courses of antibiotics prescribed for the sole diagnosis of the
      common cold."
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients from age 5 to 90 undergoing endoscopic sinus surgery for treatment of chronic
        rhinosinusitis
      
Biospecimen description: 
      whole blood nasal secretions nasal mucosa nasal polyps
    
Keywords: chronic rhinosinusitis; biofilm; sinus tissue; nasal secretions; proteomics; diagnosis; decreased antibiotics; Develop a test to identify patients with sinusitis subtypes