Pathogenesis of Chronic Sinusitis in Relationship to Tobacco Smoke Exposure

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.

Inclusion Criteria:

All of the subjects will satisfy the recently proposed definition for chronic sinusitis,
i.e. having symptoms for at least 12 weeks with two or more of the following: anterior
and/or posterior mucopurulent drainage, nasal congestion, or facial pain/pressure. Subjects
must also have objective evidence of disease on rhinoscopic examination, consisting of (a)
thick white or colored mucus from at least one sinus area, (b) edema of the middle meatus
or ethmoidal area or (c) the presence of polypoid tissue in the nasal cavity or sinus
areas. Sinus CT scans will not be obtained.

Exclusion Criteria:

Subjects with current or past use of cigarettes. Subjects with a history suggestive of
immune deficiency (i.e. those who have had > one pneumonia in the past 12 months or those
with known immune deficiency) will be excluded. Subjects with a known history of cystic
fibrosis, Kartagener's syndrome, immotile cilia syndrome, hypogammaglobulinemia, and
individuals taking medications that alter clotting and those with bleeding disorders will
also be excluded. Subjects who are pregnant or who have a history of fainting will also be
excluded. Subjects who are pregnant, planning to become pregnant, or breastfeeding.