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desensitization has not been clearly defined, but one pos-
sible explanation is that aspirin inhibits IL4
transcription in peripheral T cells.
21
In a study examin-
ing IL4 after aspirin desensitization in AERD patients,
IL4 levels were significantly decreased after 6 months of
daily aspirin maintenance.
22
Allergic Fungal Sinusitis
AFS is well defined in the literature.
23
It has been
described as a IgE-mediated Th2 process, much like
AScA or unified airway CRS. Even though AFS has an
intrinsic inflammatory process like AScA, AFS does not
share the same attributes as AScA. In a broad sense, the
difference between AFS and AScA is that the AFS is a
localized disease process, whereas AScA is more of a sys-
temic issue. Allergic fungal sinusitis patients rarely have
asthma as a confounding variable, but for AScA, asthma
is part of it identity. Also, AFS has a specific allergic reac-
tion to a fungus, whereas in AScA it has a more
undifferentiated response to any sensitized inhalant aller-
gens. Allergic fungal sinusitis is mostly a unilateral
disease, whereas AScA commonly involves bilateral
sinuses. In severe cases, allergic fungal sinusitis can
have bilateral involvement (Fig. 11). Both AFS and AScA
can have eosinophilic mucin deposited in the sinuses.
However, AFS has fungus within the mucin detected
with Grocott’s silver stain, and AScA does not stain for
fungus. Although the presence of purulence between AFS
and AScA was not statistically different in our study, pu-
rulence is commonly seen in AFS and less so in AScA.
Interestingly, CD4 was not elevated in AFS as it was
demonstrated in AScA. Even though CD4 was not higher
than the control group for AFS, AFS is likely a Th2-medi-
ated inflammatory process, because AFS had a
significantly higher amount of Th2 cytokines expression
such as IL5. Even though AScA and AFS are both medi-
ated by an IgE inflammatory pathway, AScA and AFS do
not have the same immunologic pathway. Interleukin 4
and IL13 are more likely to play a role in AScA, whereas
AFS likely has IL4, IL5, and IL13 involved. In a study by
Upadhyaya et al., Th2 cells were divided into two subpo-
pulations.
24
One group of Th2 cells expressed IL4 and
IL13 but not IL5, whereas another group of Th2 cells
expressed IL4, IL5, and IL13. IL4 and IL13 can be coex-
pressed without IL5, because their genes are adjacent,
and the IL5 gene is in the opposite orientation. Also, the
expression of IL5 demonstrates a more differentiated Th2
inflammatory pathway.
25
The fact that IL5 is strongly
expressed in AFS and not in AScA appears to be consist-
ent, that AFS may be a more differentiated eosinophilic
disease than AScA.
Another interesting finding for AFS was that AFS
had elevated CD19 and plasma cells in comparison to
the control group. Having elevated CD19 and plasma
cells in AFS is coherent, because B cells (CD19) develop
into plasma cells. A possible explanation that both CD19
and plasma cells were high for AFS is that immunoglob-
ulin may play a large role in this disease process.
Fortunately, the inflammatory drive in AFS is not
as severe as AERD or AScA, so complete evacuation of
the eosinophilic fungal mucin with post-operative topical
steroid irrigation reduces the recurrence rate of AFS to
a minimum. One factor to consider in AFS is the coexis-
tence of fungal and bacterial biofilms that can persist
after the inflammatory process to fungus in AFS is
removed.
26
Cystic Fibrosis
CF patients are probably the most difficult CRS
patients to manage. On nasal endoscopy, thick tenacious
mucus and purulence is characteristic of the CF sinus-
nasal cavities. CT scores are high and often demonstrate
underdeveloped sinuses. On histopathology, CF tissue
samples demonstrate subepithelial cell distribution that
is consistent with an infectious pattern. Cystic fibrosis
had the highest ratio of PMN, which also points to an in-
fectious process. Even though CF is most likely an
infectious process like NASsA, CF tissue samples were
different than NASsA. Cystic fibrosis tissues were hyper-
cellular with a high number of mast cells, which was
also seen among eosinophilic-based CRS such as AERD,
AFS, AScA, and ASsA.
Cystic fibrosis CRS had the highest quantity of
mast cells, and it was statistically higher than all of the
other CRS subclasses. Mast cells were higher in CRS
subclasses with intrinsic mucosal inflammatory CRS
subclasses such as asthmatic sinusitis and aspirin triad.
This is an expected result, because the mast cell is sec-
ond only to eosinophil as a potent inflammatory cell. CF
tissue was expected to have low mast cells and low cellu-
larity, because it was thought to be predominantly an
infectious sinusitis. Cystic fibrosis did have low eosino-
phil counts as expected but then had the highest mast
cell count.
Even though CF has traits that are consistent with
an infectious process, CF CRS is not mediated by Th1
cells like NASsA. CF did not have statistical difference
in CD4 cells or IFN-
c
to control like NASsA. The most
likely explanation to solidify the data for CF is that CF
has an infectious inflammatory process that is associated
with mast cells.
Cystic fibrosis involves an infectious or external
inflammation that is associated with mast cell, LTB4,
and IL6. In a study examining LTB4 and IL6 in breath
condensate, LTB4 and IL6 were measured between CF
and a control group.
27
Cystic fibrosis had elevated LTB4
and IL6 compared to the control group (
P
<
.01). Also,
when the CF patients were given antibiotics for their
infections, there was a significant drop in the LTB4 and
IL6 (
P
<
.01). Another interesting finding in the study
was that an active
Pseudomonas aeruginosa
infection
increased LTB4 and IL6 production in comparison to
other bacterial infections in CF patients.
The most likely source for the LTB4 in CF patients
is the mast cells that were very high in CF. Leukotriene
B4 is a strong PMN chemoattractant and therefore
accounts for the high PMN count in CF patients.
28
The
high PMN count in CF sinus tissue is also likely respon-
sible for the destruction of the epithelium and goblet
cells as seen in our study. Another interesting finding
Laryngoscope 123: March 2013
Han:
Subclassification
of Chronic
Sinusitis
57