Pathogenesis of Chronic Sinusitis in Relationship to Tobacco Smoke Exposure
Condition: Chronic Rhinosinusitis
MeSH terms: Sinusitis
Study type: Interventional

Summary: 
      The purpose of the study is to better understand the causes of chronic rhinosinusitis
      (CRS)and to determine if being around secondhand cigarette smoke causes swelling in the
      sinuses. To answer this question, we are inviting healthy volunteers, volunteers with chronic
      sinusitis, and volunteers with chronic sinusitis with nasal polyposis to complete a
      questionnaire and undergo a series of tests. These tests will measure their allergies, their
      exposure to cigarette smoke and the swelling in their sinuses. We are asking you to take part
      because you are in one of these groups. About 166 people will take part in this research
      study. All subjects will be enrolled at Massachusetts General Hospital (MGH). The Flight
      Attendants Medical Research Institute (FAMRI) and the Harvard Clinical and Translational
      Science Center Harvard Catalyst) are paying for this study.
    

Detailed description: 
      Chronic sinusitis is one of the most prevalent chronic illnesses in the United States and a
      significant health concern in terms of public health care expenditure. We wish to learn more
      about pathogenic factors causing or contributing to chronic sinusitis. One of these factors
      is secondhand smoke (SS) exposure. However, several other factors are involved, including
      allergic, environmental, genetic and microbiologic factors and in any given patient, several
      of these factors may be contributing to the disease. One of our goals is to see whether
      specific patterns of inflammatory cells, cytokines or chemokines exist that can differentiate
      these causative factors and to help us to better understand their individual contributions to
      the disease.

      Several inflammatory cells, cytokines and chemokines are present in chronically inflamed
      sinus tissue, and we believe they form the basis for the disease process. At present, we know
      very little about what drives them into the sinus tissues. We believe that the types of
      inflammatory cells, cytokines and chemokines elicited in this disease depend on the inciting
      stimulus.

      Cigarette smoke has well-documented deleterious effects on respiratory mucosa that could
      promote the development of chronic sinusitis. These include reduction in normal mucociliary
      function; increased nasal airway resistance; induction of mucin gene expression and induction
      of chronic inflammation. In the proposed study, we will extend our previous findings to
      investigate the relationships between SS exposure and these inflammatory markers and also
      examine the relationship of these cytokines to the expression of particular mucins.

      Extracts of cigarette smoke have been shown to induce numerous other proinflammatory effects
      on respiratory epithelial cells either in vivo or in vitro. In this study we will analyze the
      gene expression of inflammatory markers in a nasal mucosal biopsy. Our intent is to study
      sinusitis rather than rhinitis. Nonetheless, we will examine nasal rather than sinus mucosa
      largely owing to the difficulties posed by obtaining samples directly from the sinuses.
      Furthermore, recent consensus reports have emphasized the importance of viewing sinusitis as
      a continuum of nasal and sinus mucosal inflammation. These same arguments have been put
      forward in terms of the concept of "one airway, one disease" which has emphasized the
      commonality of mucosal inflammation seen in the upper airway (rhinitis, sinusitis) and the
      lower airway (asthma). The biopsies will come from the middle turbinate. The latter structure
      has the same pseudostratified columnar epithelium and a virtually identical appearance to
      that of maxillary or ethmoid sinus mucosa. We have used biopsies from the middle turbinate in
      several previous studies of chronic sinusitis, primarily as a comparative tissue representing
      "healthy" sinus mucosa.
    

Intervention name(s): Biopsy
Intervention type(s): Other
Intervention description(s): Percutaneous 2-3 mm biopsies of middle turbinate mucosae and nasal polyps will be obtained with 5 mm Thrucut® (Smith & Nephew, Memphis, TN) biopsy forceps. Generally, 2-3 specimens will be obtained from each side as in previous studies. Healthy controls and subjects with CRS without NP will have biopsies from both middle turbinates. Subjects with CRS with NP will have two nasal polyp biopsies and one middle turbinate biopsy.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: CRS