Jurnal Polip Nasal

7/26/2019 Jurnal Polip Nasal

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Annals of Otology, Rhinology Laryngology

I21(9):6I5-6I9.

2012 Annals Publishing Company. All rights reserved.

Analysis of the Roles of Smoking and Allergy in Nasal Polyposis

Orhan Grgl, MD ; Siileyman zdemir, M D; Emre Polat Canbolat, MD;

agda Sayar, MD ; Mustafa Kemal Olgun, M D; YiicelAkba, MD

Objectives Recent studies on the etiopathogenesis of nasal polyps have shown that smok ing and nonallergenic inhalants

such as occupational dust exposure cause chronic inflammation of the nasal mucosa. These factors may be associated

with nasal polyps. The aim of this study was to use laboratory tests to investigate the effects of smoking and allergens on

the development of nasal polyps.

Methods The study included 60 consecutive patients with a diagnosis of nasal polyposis who were treated w ith function-

al endoscopie sinus surgery at our clinic and 25 smoker and 25 nonsmoker participants who constituted a control group.

Results In the patient and control groups, the mean absorbance value for cotinine in smokers was found to be statistically

significantly lower than that in nonsm okers. There was a significant difference between the groups with respect to blood

cotinine positivity. No significant difference was found between the groups in terms of allergy p arameters. In the regres-

sion mo del, smoking was found to be the only significant risk factor for the development of nasal poly ps, independent of

smoking duration, absorbance value, or cotinine positivity.

Conclusions Smoking restriction and avoiding exposure to cigarette smoke by patients with nasal polyps may be an

important strategy in the prevention and recurrence of nasal polyposis. No direct relationship was determined between

allergy and nasal polyposis.

Key Words allergy, immunoglobulin E, nasal polyp, serum cotinine, smoking, tobacco.

INTRODUCTION

Nasal polyposis is a chronic inflammatory con-

dition of the upper respiratory tract, the cause of

which is not well known. Genetic factors, anatomic

disorders, allergic inflammation, chronic local in-

fections, nasal mastocytosis, and environmental fac-

tors may play a role in the etiopathogenesis of na-

sal polyps. Nasal polyps are more frequently en-

countered in men, and this condition is thought to be

due to the fact that men are exposed m ore frequently

than women to occupational chemicals and cigarette

smoke.23 Previous studies have demonstrated that

smoking and nonallergenic inhalants such as occu-

pational dusts can lead to the development of nasal

polyps.4 Houser and Keen^ reported that in addition

to its contribution to the development of nasal pol-

yps,

smoking increased the rate of recurrence and

worsened the prognosis of nasal polyps. Eurther-

more, occupational dusts such as chrome, solvent

dusts, and flour, as well as hyphae and chemicals,

have been observed to affect occupational rhinitis.

These substances are thought to cause a decrease in

nasal immune resistance that leads to chronic nasal

inflammation and nasal polyps.^

It is not yet completely clear whether there is an

increased risk for the development of nasal polyps

in allergic individuals. Elevated levels of immuno-

globulin E (IgE) and positive skin tests to inhalant

allergens have been determined in the majority of

patients with nasal polyps.^ The main conditions

suggestive of allergy in patients with nasal po lyps in-

clude symptoms resembling allergic rhinitis, a high

rate of asthma, a marked eosinophilia in the polyp

tissue, and high IgE levels. In the studies, specific

IgE-mediated allergy has been demonstrated to have

an important role. Thus, allergy tests should be per-

formed in patients with sensitivity to environmental

allergens and in those with positive family histories

of allergy .5

In order to assess active and passive smoking,

many substances have been used, of which cotinine

is the most widely used. Cotinine, found in tobacco,

is an active metabolite of nicotine and can be mea-

sured in serum, urine, and saliva. Previous studies

have dem onstrated that cotinine is a reliable parame-

ter for the assessment of active and passive sm oking

and their effects because of its high serum levels, as

well as its high specificity and sensitivity. ^ The aim

From the Department of Otorhinolaryngology, Adana Num une Education and R esearch Hospital (Grgl, Canbolat , Sayar, Olgun), the

Depa rtmento f O torhinolaryngology, Cukurova University School of Medicine (zdem ir), and the Department of Otorhinolaryngology,

Adana Galeria E NT H ospital (Akba), Adana, Turkey.

Correspondence: Orhan Grgl, MD, Huzurevleri mah Turkmenhasi Bui Akgl 5 si t Ahlok 8/15 Cukurova, Adana, Turkey, 01500.

6 1 5


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616

Grgl et al, Smoking Allergy in Polyposis

of the present study was to investigate the effects of

smoking and allergens on the development of nasal

polyps and to use laboratory findings to determine

the effects of these factors in the prevention of nasal

polyp development and recurrence.

PATIENTS AND METHODS

Patients.

Sixty consecutive patients who had

a diagnosis of nasal polyposis and had been treat-

ed with functional endoscopie sinus surgery at the

Adana Numune Education and Research Hospital

Department of Otorhinolaryngology were included

in the present study. The control group comprised

25 smokers and 25 nonsmokers. Smoking exposure

was measured in pack-years, ie, number of cigarette

packs smoked per day times the number of years

of smoking. After obtaining approval for the study

from the Local Ethics Committee of our hospital,

we obtained informed consent from all patients. Pa-

tients and control subjects w ith a previous diagnosis

of genetic and/or metabolic diseases such as cystic

fibrosis, Churg-Strauss syndrome, aspirin hypersen-

sitivity, or bronchial asthma and those with a medi-

cal history of extensive exposure to passive smok-

ing were excluded from the study.

Blood samples of the patients and volunteers who

consented to participate in the study were obtained

before treatment and centrifuged. The obtained

serums were stored in a deep freezer at -20 C to

-25C and were analyzed within 2 weeks. The se-

rum cotinine levels by biochemical analysis, the se-

rum total IgE levels, and the allergen-specific IgE

levels included in the Turkish Mix 20 protocol were

measured.

In the measurements, the cutoff value for the se-

rum cotinine level was determined as 25 ng/mL; a

serum cotinine level of 25 ng/mL or greater and an

absorbance value of 0.777 or less were considered

positive. For the determination of serum total IgE

levels and gra des, a serum total IgE level oflessthan

100 IU/mL w as accepted as negative and a serum to-

tal IgE level of 100 IU/m L or more w as accepted as

positive. For the determination of the allergen-spe-

cific IgE levels and grades; a value of less than 26

IU/mL was accepted as negative and a value of 26

IU/mL or m ore was accepted as positive.

Methods. Serum cotinine levels were measured

with the Triturus micro-enzyme-linked immunoas-

say device (Grifols Technologies, Barcelona, Spain)

by the photometric method. This technique, an en-

zyme-competitive method used for screening coti-

nine in human serum, measures the amount of co-

tinine in serum qualitatively. Microtitration strips

coated with anti-cotinine antibodies bind to free co-

tinine in the sam ples at the end of the incubation pe -

riod, and then the absorbance of the bound cotinine

is measured spectrophotometrically at 450 nm. Se-

rum total IgE and allergen-specific IgE levels were

measured with the Elecsys 2010 device (Roche, Hi-

tachi-High Technologies Corporation, Tokyo, Ja-

pan) by the electrochemiluminescence immunoas-

say method, which is a quantitative method of mea-

surement in which human IgE-specific monoclonal

antibodies are used.

Statistical Analysis.

Analysis of the data was

performed with the Statistical Package for the So-

cial Sciences for Windows (SPSS 12.0) program.

The differences between the groups were analyzed

with the x^ test for categorical variables and with

the ICruskal-Wallis test for numerical variables. A p

value of less than 0.005 was considered statistical-

ly significant. Analysis of subgroups was performed

by the Mann-Whitney U test for numerical vari-

ables. The alpha level of significance was adjusted

with the Bonferroni correction. Logistic regression

analysis was performed to determine the risk factors

affecting the development of nasal polyps.

RESULTS

The mean age of the patients (42 men and 18

wom en) with nasal polyps was 40.1 9.8 yea rs. The

mean age of the participants in the control group (33

men and 17 women) was 42.7 10.8 years. There

was no significant difference between the groups in

terms of age or gender distribution (p = 0.198 and p

= 0.654, respec tively). The majority of patients with

nasal polyps (70 ) were smokers. Thirty percent of

the patients had never sm oked. A mean SD of 22.1

1 3.6 pack-years w ere smoked by the patient smok-

ers,

whereas a mean SD of 20.7 14.2 pack-years

were smoked by participants in the smoker control

group. No significant difference was found with re-

spect to smoking status between the smoker patients

and smoker control subjects.

In the patient and control groups, the mean ab-

sorbance value for cotinine in smokers was found

to be significantly lower than that in nonsmokers (p

< 0.001 and p = 0.002, respectively). A statistically

significant difference was determined between the

groups (p = 0.003; Table 1).The rates of blood coti-

nine positivity were higher in the smoking patients

and smoking control subjects than in the nonsmok-

ing patients and nonsmoking control subjects. sig-

nificant difference was found between the patient

and control groups in terms of the rates of blood co-

tinine positivity (p < 0.001). This difference was sta-

tistically significant between the smoking and non-

smoking groups (p < 0.001 for both groups; Table


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Grgl et al, Smoking & Allergy in Polyposis

617

TABLE L ABSORBANCE VALUES FOR COTININE

IN STUDY GROUPS

TABLE 3. REGRESSION MO DEL INCLUDING FACTORS

AFFECTING DEVELO PMENT O F NASAL POLYPS

Absorbance Value

Group

N Mean SD M edian Range

Nonsmoking patients

Smoking patients

Nonsmoking control

subjects

Smoking control

subjects

Total

Analysis of difference

test.

18 1.417 0 .6 84 1.356 0.402-2.640

42 0.716 0. 640 0.555 0.008-2.564

25 1.318 0 .75 7 1.492 0.037-2.346

25 0.606 0. 565 0.465 0.015-2.277

110 0.943 0. 73 4 0.719 0.008-2.640

among 4 groups, p = 0.003, Kruskal-Wallis

2).

It was observed that there was an inverse pro-

portion between the serum cotinine levels and the

absorbance values.

There was no significant difference between the

groups in terms of the mean IgE levels (p = 0.591).

In addition, there was no significant difference be-

tween the groups with respect to serum total IgE

positivity (p = 0.680) . Allergy was present in 25.0%

of the patients with nasal polyps and in 28.0% of the

control group. No significant difference was deter-

mined between the patients with nasal polyps and

the control group in terms of allergy prevalence (p

= 0.722).

Allergy tests revealed that none of the individ-

uals in the study groups had allergies to penicil-

lin, milk, barley, wheat, ribwort plantain, rye, oat,

grass, pine, oak, cockroach, or feather. There were

also no significant differences between the groups

in terms of the rates of allergy to egg, oak, dog, cat,

the mite

Dermatophagoides pteronyssinus,

or the

mite

Dermatophagoides farinae.

In the regression

model including the factors and the positive aller-

gens that were considered to affect development of

nasal polyps (smoking, duration of smoking [pack-

years]), age, gender, cotinine positivity, absorbance

value, dog, cat, the mite

D pteronyssinus,

and the

miteDfarinae), smoking was determined to be the

TABLE 2. RATES OF BLOOD COTININE POSITIVITY

IN STUDY GROUPS

Group

Nonsmoking patients

Smoking patients

Nonsmoking control

subjects

Smoking control subjects

Total

Cotinine-

Positive*

No .

3

30

6

20

59

%

16.7

71.4

24.0

80.0

53.6

Cotinine-

Negativef

No.

15

12

19

5

51

Analysis of data among 4 groups, p 25 ng/mL.

t


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r iilii et al, Smoking Allergy in Polyposis

Previously, a limited number of studies have in-

vestigated the role of smoking in the etiopathogene-

sis of nasal poly ps. In a study by H ouser and Keen,^

a strong relationship was determined between direct

tobacco consumption and the development of nasal

polyps. In that particular study, a significant rela-

tionship between the amount of cigarettes smoked

and the development and recurrence of nasal polyps

was determined in smoking patients with allergy,

and it was found that the increase in the amount of

cigarettes smoked was directly proportional to the

development and recurrence of nasal polyps.^ Fur-

thermore, allergen desensitization occurs in smok-

ing patients in association with cigarette smoking,

and sensitivity to allergens decrea ses in smoking p a-

tients with nasal polyps . 'It has been con sidered that

smoking and environmental inhalants exert their ef-

fects on the development of nasal polyps by causing

chronic inflammation in the nasal mucosa.^'^ The

mechanism of this relationship was demonstrated in

another study to be the immun osuppressive effect of

smoking, and this condition has also been consid-

ered the cause of insensitivity to allergens in smok-

ers. ' ' 'Collins et aF investigated smoking and the in-

cidence of nasal polyps in 900 patients and reported

the rate of smoking in male patients with nasal pol-

yps to be 2.3 times higher than that in female pa-

tients with nasal polyps.

One of the most reliable methods in the assess-

ment of smoking and exposure to cigarette smoke is

to measure the level of the main metabolite of nico-

tine, namely, cotinine. An ideal biological marker to

be used for the assessment of smoking and expo-

sure to cigarette sm oke should have a long half-life

within the body, and should be precisely d etermined

even in very small amounts. Additionally, it should

be cheap and should be measured in specimens that

are collected easily and through noninvasive tech-

niques.'^ Cotinine can be measured by micro-en-

zyme-linked immunosorbent assay, gas chromatog-

raphy, high-performance liquid chromatography,

or radioimmunoassay. In smokers, the elimination

half-life of cotinine ranges from 10 to 37 hou rs, with

a mean of 20 hours.'^

Whittet et al'^ measured serum cotinine level as

an objective marker in the assessment of smoking

and exposure to cigarette smoke in patients with la-

ryngeal cancer, and cotinine was found to be pres-

ent in 92% of the smoking patients. In a study by

Seccareccia et al'^ in which environmental cigarette

smoke exposure was investigated, serum cotinine

was used as a marker and the cutoff po int for serum

cotinine was determined as 15 ng/mL

to

differentiate

nonsmokers from smokers in an Italian population.

In our study, this value was determined as 25 ng/

mL. These values are consistent with those repor

ed in studies carried out in other countries.'^'''^-'

The serum cotinine levels determined in the group

in our study were comparable to those reported i

previous studies conducted to assess smoking an

exposure to cigarette smoke. In the present stud

a statistically significant difference was determine

between the patient and control groups in terms o

the cotinine levels.

In the literature, the development of allergy an

exposure to cigarette smoke as a cause of this a

lergy is a controversial issue. In a study performe

on mice with asthma that were exposed to cigarett

smoke, exposure to cigarette smoke was demon

strated to decrease the normal lung homeostatic to

erance to innocuous allergens, consequently leadin

to sensitization and respiratory tract diseases. Thi

condition explains why active cigarette smoking i

a risk factor in the pathogenesis of asthm a.'^ In con

trast, in a study by Therriault et al,''' exposure t

cigarette smoke was suggested to play an inhibitor

role in the nasal mucosa for the development of al

lergy by decreasing the sensitivity to allergens in th

sinonasal mucosa. However, despite that fact tha

atopy is not a direct cause of nasal polyposis, it i

known that there is an association between allerg

and recu rrent n asal po lypos is. Asero and Bottazzi^

reported that 44% of patients with nasal polyps an

1 of individuals in a control group were found

have specific IgE againstCan dida albicansand th

70 % of the individuals in the patient group wer

found to have sensitivity to animal hair and hous

dust mites. Although studies have demonstrated th

specific IgE-mediated allergy has a significant rol

it is not yet clear whether there is an increased ris

for the developme nt of nasal polyps in patients w it

allergy.^ The relationship between allergy and na

sal polyps has not yet been completely elucidate

and there are ongoing studies on this subject. In ou

study, despite the low rate of allergy in patients wit

nasal polyps compared to the normal population an

the control groups, no statistical significance wa

determined for its prevalence in patients with nasa

polyps.

In the regression model including the positive a

lergens and the factors that w ere considered to affe

nasal polyp development, smoking was determine

to be the only significant risk factor in the deve

opment of nasal polyps, independent of absorbanc

value, cotinine positivity, and other factors. The se

rum cotinine level w as found to be a highly sensitiv

biological parameter in the assessment of smokin

and exposure to cigarette smoke. These results sug

gest that quitting smoking, not smoking cigarette

and prevention of exposure to cigarette smoke ma


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rg lii et al. Smokin g Allergy in Polyposis

619

play im portant roles in the prevention of nasal polyp

development and recurrence. Euture com prehensive

studies may elucidate this issue and c ontribute to the

literature.

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