2016 Section 5 Green Book

rhinitis and asthma. Interestingly AERD or aspirin triad

patients commonly do not have a history of pediatric

allergy or asthma. In fact, AERD patients have less atopy

than aspirin-tolerant asthmatics or AScA (unified airway)

patients.

Asthma in ASsA usually develops during the

adult years. This is similar to AERD and unlike AScA.

The natural progression of AERD patients demonstrates

that rhinitis develops first. Asthma appears an average of

2 years after initial symptoms of rhinitis.

Nasal polypo-

sis then ensues, followed finally by aspirin sensitivity. In

other words, AERD patients can develop asthma and

nasal polyposis while still being aspirin tolerant for a few

years prior to eventually becoming aspirin intolerant.

This is consistent with our study, because ASsA is

younger than the AERD (Table II). The ASsA patient can

represent a precursor of AERD prior to aspirin intoler-

ance. In fact, a few patients under the author’s care with

adult onset asthma and severe nasal polyposis who were

initially aspirin tolerant, eventually became aspirin intol-

erant during the course of their management. However,

to confirm that ASsA might be a precursor to AERD, ele-

vated levels of cysteinyl leukotrienes or urine LTE4

should be measured and confirmed. For now, these ASsA

patients are counseled to avoid the use of NSAIDS.

It was interesting to note that CD4 cells were

higher in ASsA than the control group. This finding

implies that T helper cells may play a role for these

patients. In fact, IL4 was higher in ASsA than CF.

Another CRS subclass that had higher IL4 than CF but

did not reach significance was AERD, which lends cre-

dence that ASsA may be a precursor to AERD.

Aspirin Triad or Aspirin Exacerbated

Respiratory Disease

Aspirin triad or AERD patients have the worst

sinus symptoms among CRS patients.

In our study

they had the highest statistically significant CSS score.

Aspirin triad patients have a history of adult onset

asthma and usually do not have a history of pediatric

asthma. Aspirin triad or AERD patients also have less

atopy than aspirin-tolerant asthmatics.

Even when

AERD patients do have a positive allergy test, the reac-

tion to the allergy test is often mild and does not

correlate to the severity of their nasal polyposis or

asthma. In other words, the total serum IgE in AERD

patients is lower than AScA (unified airway) CRS.

On nasal endscopy, AERD patients had an abun-

dant amount of polyps and the highest NE score (Table

III). The nasal polyps biopsy demonstrates an extensive

amount of eosinophils, mast cells, and hypercellularity.

Even though AERD and AScA have similar phenotype,

and both have intrinsic inflammation, they are different

in terms of their immunologic inflammatory pathway.

Aspirin-exacerbated respiratory disease inflamma-

tion has been classically described by elevated levels of

cysteinyl leukotrienes and not described as an adaptive

immunity process.

However, in our study, the CD4

cells were elevated in AERD compared to the control

group. If there is an adaptive immunity involved with

AERD, it likely involves IL4, because IL4-producing cells

were elevated in AERD. An interesting discovery was

that the elevated IL4-producing cells in AERD were

CD45

CD4

cells. That means that IL4 is not being

produced by Th2 cells, but rather by another CD45

cell. The most likely CD45

CD4

cell producing the

IL4 is the mast cell, which was elevated in AERD and

ASsA patients. The interplay between IL4 and cysteinyl

leukotrienes is that IL4 stimulates expression of LTC

synthase and upregulates cysLT1 receptor expression.

Also, IL4 can prolong eosinophil survival and is a cofac-

tor for mast cell growth.

Similar to AScA, the amount of inflammation in

AERD is so high that it is difficult to manage with medi-

cal treatment alone. In a study evaluating urine LTE4

in AERD patients, urine LTE4 was measured before and

after ESS.

Urine LTE4 dropped from 227 pg/mg preop-

eratively to 72 pg/mg postoperatively (

.05). Because

urine LTE4 is a metabolite of cysteinyl leukotriene, this

study demonstrated that debulking the nasal polyp dur-

ing ESS decreases the primary inflammatory mediator

in AERD patients.

Detailed management of aspirin triad has been

described.

To summarize, initial medical management

of oral steroid and oral zileuton should be considered.

Zileuton is an inhibitor of 5-lipoxygenase and thus inhib-

its the production of cysteinyl leukotrienes. However, a

baseline liver function test should be performed prior to

the use of zileuton, because there is a 4% chance of liver

toxicity. If the medical management does not control the

patient’s symptoms, ESS should be performed to debulk

the inflammatory polyp to decrease the inflammatory

load in the nasal polyps and to allow for topical medica-

tions into the sinuses. Postoperatively, zileuton should

be continued with careful monitoring of the liver

enzymes, specifically alanine aminotransferase. Topical

steroid spray, irrigation, or drops should be considered

in conjunction with the zileuton. Aspirin desensitization

is another possibility, especially if pharmacotherapy is

not effective. The exact mechanism for aspirin

Fig. 11. Axial computed tomography of the frontal sinus demon-

strating an expansile heterogenous mass in the right frontal sinus

extending into the right frontal lobe. The inflammatory process

has extended from the right frontal sinus to involve the left frontal

sinus.

Han: Subclassification of Chronic Sinusitis

Laryngoscope

123: March

2013