2016 Section 5 Green Book

from our study was that CF had high CD19 and plasma

cells. This is consistent with the literature, which states

that CF patients have elevated levels of IgG, IgM, and

IgA, especially during an infection.

So it is very likely

that immunoglobulin also contributes to combating the

bacterial sinus infection commonly encountered in CF

patients.

The treatment for CRS in CF patients will likely

involve multimodal treatments. One treatment would be

to loosen the tenacious mucus with inhaled dornase

alfa

or hypertonic sinus irrigation. Topical nasal ste-

roid spray can be used to decrease the local

inflammation of the sinuses. Also, because LTB4 is

increased in CF patients, especially with an active pseu-

domonas infection, zileuton could be used to block the

production of LTB4 and minimize PMN recruitment that

causes local epithelial destruction. By minimizing PMN

recruitment and release of elastase, immunoglobulin can

be spared to prevent bacterial infection along mucosal

surfaces.

It is theoretical that zileuton has the possibil-

ity of improving the upper respiratory tract as well as

the lower respiratory tract. However, the liver needs to

be carefully monitored for liver toxicity when using of

zileuton. As a last resort and after medical treatment

has failed, if sinus surgery is needed, making large an-

trostomies and opening up all the sinuses should be

considered. By creating large opening into the sinuses,

this will allow for topical medication to get into the

sinuses and to prevent future sinus surgery.

Limitations

There are some limitations of the proposed subclas-

sification of CRS. First, this classification of CRS may

not address all the different forms of CRS, such as CRS

due to vasculitis or sarcoidosis. Another limitation is

that although the presence or absence of allergy and

asthma was documented, the severity was not. For

allergy, total serum IgE could be used as a measure to

determine the severity of the allergy. However, this was

difficult to do in this study because some of the patients

received a radioallergosorbent test, whereas others

received skin prick testing. One other limitation is that

the innate immunity was not investigated in the CRS

study group. It is likely that innate immunity may play

a role for some of the CRS subclasses, especially for non-

asthmatic sinusitis. Finally, the number of patients in

each CRS subclasses was not large. With a higher num-

ber of specimens in each CRS subclass, statistical

significance may be found that was not demonstrated in

this study. However, this study nonetheless is an impres-

sive undertaking. This is the first study to

comprehensively compile the phenotype characteristics

among CRS patients and also include the difference of

biomarker with intracellular staining of cytokines

among CRS patients.

CONCLUSION

Nasal mucosal swelling and polyps are the end

product of sinus inflammation. By characterizing the

phenotype and pathway of nasal polyp inflammation for

various types of CRS, well-characterized and distinct

groups of CRS have been defined. By defining the differ-

ent discrete category for CRS, a targeted treatment plan

for each CRS subclass has been discussed in the article.

Also, by defining specific CRS entities, hopefully these

CRS subclassifications can be use in future bench and

clinical research studies.

Acknowledgement

First of all, I would like to thank God who made all

things possible. I appreciate Larry Borish, MD and

Thomas Platts-Mill, MD for helping me better understand

allergy. I am grateful to Marc Silverberg, MD for his ex-

pertise in the histologic examination and Elena Galkina,

PhD in the flow cytometry. I extend my graditude to

Christopher Benson, Rachel Moebus, and Matthew

Butcher for their insightful perspective and assistance.

Finally for her inspiration and constant support, I owe my

thesis to my wonderful wife Caroline Han, MD.

BIBLIOGRAPHY

1. Chester AC, Antisdel JL, Sindwani R. Symptom specific outcomes of endo-

scopic sinus surgery: a systemic review.

Otolaryngol Head Neck Surg

2009;140:633–639.

2. Ebbens, FA, Georgala C, Luiten S, et al. The effect of topical amphotericin

B on inflammatory markers in patients with chronic rhinosinusitis: a

multicenter randomized controlled study.

Laryngoscope

2009;119:401–

408.

3. Wallwork B, Coman W, MacKay-Sim A, et al. A double-blind randomized

placebo controlled trial of macrolide in the treatment of chronic rhinosi-

nusitis.

Laryngoscope

2006;116:189–193.

4. Haruna, S, Shimada C, Ozawa M, et al. A study of poor responders for

long term low dose macrolide for chronic sinusitis.

Rhinology

2009;47:66–71.

5. Demarcantonio MA, Han JK. Systemic therapies in managing sinonasal

inflammation.

Otolaryngol Clin North Am

2010;43:551–563.

6. Krouse JH, Brown RW, Fineman SJ, et al. Asthma and the unified airway.

Otolaryngol Head Neck Surg

2007;136(5 suppl):S75–S106.

7. Caughey RJ, Jameson MJ, Gross CW, et al. Anatomic risk factors for sinus

disease: fact or fiction?

Am J Rhinol

2005;19:334–339.

8. Payne SC, Han JK, Huyett P, et al. Microarray analysis of distinct gene

transcription profiles in noneosinophilic chronic sinusitis with nasal pol-

yps.

Am J Rhinol

2008;22:568–581.

9. Early SB, Hise K, Han JK, et al. Hypoxia stimulates inflammatory and

fibrotic responses from nasal polyp derived fibroblasts.

Laryngoscope

2007;117:511–515.

10. Hekiert AM, Kofonow JM, Doghramji, et al. Biofilms correlate with Th1

inflammation in the sinonasal tissue of patients with chronic rhinosinu-

sitis.

Otolaryng Head Neck Surg

2009;141:448–453.

11. Braunstahl GJ, Overbeek SE, Kleinjan A, et al. Nasal allergen provocation

induces adhesion molecule expression and tissue eosinophilia in upper

and lower airways.

J Allergy Clin Immunol

107:469–476.

12. Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the

IL4/IL13/STAT 6 pathway for treatment of asthma.

Eur Respir Rev

2000;19:46–54.

13. Bachert C, Zhang N, Holtappels G, et al. Presence of IL5 protein and

IgE antibodies to staphylococcal enterotoxins in nasal polyps is

associated with comorbid asthma.

J Allergy Clin Immunol

2010;126:962–968.

14. Steinke JW, Payne SC, Tessier ME, et al. Pilot study of budesonide inhal-

ant suspension irrigations for chronic eosinophilic sinusitis.

J Allergy

Clin Immunol

2009;124:1352–1354.

15. Tanaka A, Obashi Y, Kakinoki Y, et al. Immunotherapy suppresses both

Th1 and Th2 responses by allergen stimulation, but suppression of the

Th2 response is more important mechanism related to the clinical effi-

cacy of immunotherapy for perennial allergic rhinitis.

Scand J Immunol

1998;48:201–211.

16. Nelson HS. Advances in upper airway diseases and allergen immunother-

apy.

J Allergy Clin Immunol

2007;119:872–880.

17. Kim BS, Park SM, Uhm TG, et al. Effect of single nucleotide

polymorphisms within IL4 promoter on aspirin intolerance in asth-

matics and IL4 promoter activity.

Pharmacogenet Genomics

2010;20:748–758.

18. Higashi N, Taniguchi M, Mita H, et al. Clinical features of asthmatic

patients with increase urinary LTE4 excretion; Involvement of chronic

hyperplastic rhinosinusitis with nasal polyposis.

J Allergy Clin Immunol

2004;113:277–283.

Laryngoscope 123: March 2013

Han: Subclassification of Chronic Sinusitis