75 / 236
DISCUSSION
Physicians, from primary care physicians to otolar-
yngologists, can differentiate the proposed division of
CRS. The subclasses of CRS can be easily determined
from clinical history and readily accessible laboratory or
office testing (Fig. 6). Diagnosis for CF, allergic fungal si-
nusitis, and aspirin triad are well described in the
literature. Patients with allergy and asthma can be diag-
nosed with office or laboratory testing, and CRS can
then be divided as described in Figure 6. The proposed
subclassification of CRS does not require difficult and
expensive laboratory testing such as proteomics or
microarray. The general characteristics of the CRS sub-
classes are described in Figure 7
.
By dividing CRS into
this subclassification, effective targeted management
can be developed for each category of CRS. Also, by
defining the type of CRS that is being evaluated in
either bench or clinical research study, the research data
will hopefully become coherent and produce better
research outcomes.
Nonasthmatic Sinusitis Without Allergy
Typically, NASsA patients have purulence on their
nasal endoscopy and do not have high CT scores (Fig. 8).
The biopsy of the sinus mucosa is not hypercellular and
does not have an abundant amount of eosinophils in the
mucosa. Structural abnormality due to anatomic var-
iants may be a factor in these patients, such as concha
bullosa, infraorbital ethmoid air cell, and deviated sep-
tum, that predisposes them to persistent bacterial sinus
infections.
7
These sinus infections can occur after a viral
exacerbation that leads to persistent cyclical bacterial
infections (Fig. 9).
NASsA is similar to noneosinophilic sinusitis, which
has been previously described.
8
NASsA has an extrinsic
mucosal inflammation that is steered through T helper
cells, CD3
1
CD4
1
. The inflammation in NASsA is
termed extrinsic, because the inflammation is not
derived from the mucosa but rather from an external
source such as an infection that has been distinguished
with elevated levels of IFN-
c
. IFN-
c
is a Th1 cytokine
commonly representing an infectious process. NASsA
patients have elevated levels of IL6 or IL8, similar to
noneosinophilic sinusitis and may benefit from long-
term macrolide therapy.
8
It is possible that innate im-
munity may be involved in NASsA patients, but it was
not evaluated in this study. Hypoxia is also likely to be a
factor in these NASsA patients due to sinus ostium
obstruction.
9
NASsA patients can often improve with a combina-
tion of oral antibiotics and steroids. For those NASsA
patients who do not improve with medical management,
ESS is a good subsequent treatment. However, there are
NASsA patients who have recalcitrant bacterial sinus
infections that persist despite properly opening the
sinuses and being treated with culture-directed antibiot-
ics. The most likely explanation for the obstinate low-
grade bacterial infection causing localized inflammation
is bony bacterial infection or biofilm. Bacterial biofilm in
CRS has been shown to be a Th1-mediated process.
10
Management of bacterial biofilm is difficult, and multi-
modality treatment may be necessary to improve these
patients. Multimodality treatment will likely include
high-dose topical antibiotics with or without topical sur-
factant after mechanical irritation such as ESS or high-
pressure irrigation of the sinuses.
Nonasthmatic Sinusitis With Allergy
If an inflammatory pathway continuum existed
with NASsA on one end and AScA on the other spec-
trum, then NAScA would be between them. NAScA
inflammatory pathway is also likely to be directed by T
helper cells, because CD3
1
CD4
1
was higher in this
group versus the control group. Even though NAScA
had significantly higher levels of IFN-
c
than the control
group, NAScA is likely a combination of an infectious
TABLE VI.
Average Percentage of CD45
1
Cells, CD45
1
CD4
1
Cells, and
CD45
1
CD4
2
Cells With Positive Intracellular Markers.
CRS Subclass
IFN
IL4
IL5
IL13
IL17
Average % of CD45
1
cells with positive intracellular marker
AERD
3.9 1.8
0.2
0.3
0.7
AFS
3.1 1
1.3
1.5
2.4
CF
14.6 0.2
0.8
2
2.7
AScA
12.1 1.3
0.04 0.1
1.3
ASsA
9
3.2
0.2
0.5
2.2
NAScA
14
1.2
0.4
0.3
0.7
NASsA
15.5 0.8
0.1
1.8
1.9
Control
4.4 1.2
0.3
0.4
1.8
Total
9.6 1.2
0.4
0.8
1.6
Average % of CD45
1
CD4
1
cells with positive intracellular marker
AERD
2.6 1.4
0.3
0.4
1.7
AFS
2.3 0.9
2.4
3.2
4
CF
8.6 0.4
0.5
0.3
3.9
AScA
9.7 1.8
0.04 0.2
3.4
ASsA
11.9 3.2
0.2
0.6
2.9
NAScA
22.1 1.3
0.6
0.4
1.9
NASsA
24.4 3
0.2
2.4
2.8
Control
4.1 1.2
0.2
0.6
3.1
Total
11.6 1.7
0.5
0.9
2.9
Average % of CD45
1
CD4
2
cells with positive intracellular marker
AERD
6.5 1.9
0.4
0.6
0.4
AFS
3.6 1.2
0.7
0.6
1.7
CF
17.7 0.04 0.9
2.7
0.9
AScA
10.5 1
0.02 0.1
1.2
ASsA
10
2.5
0.02 0.2
0.6
NAScA
12.9 0.3
0.3
0.3
0.6
NASsA
14.7 0.7
0.07 0.3
1.2
Control
4.8 0.9
0.3
0.4
1.1
Total
9.7 1
0.4
0.6
0.9
AERD
5
aspirin exacerbated respiratory disease also known as aspirin
triad; AFS
5
allergic fungal sinusitis; AScA
5
asthmatic sinusitis with allergy;
ASsA
5
asthmatic sinusitis without allergy; CF
5
cystic fibrosis; CRS
5
chronic
rhinosinusitis; IFN
5
interferon; IL
5
interleukin; NAScA
5
nonasthmatic sinusi-
tis with allergy; NASsA
5
nonasthmatic sinusitis without allergy.
Laryngoscope 123: March 2013
Han:
Subclassification
of Chronic
Sinusitis
53