Role
of smoking
Zafirlukast
onexpired
skin prick
test monoxide
Passive
and
carbon
concentrations in healthy and asthmatic children
C. Cuhadaroglu* , M . Erelel* , E. Kiyan* , T. Ece* * , and F. Erkan* * *
Ece*Physician.
, F. Gürkan*
, K. Haspolat*
, O.
Derman*
, and G.*Kırbas
, * * in Chest Department. Department
*A.
Chest
* * Assistant
Professor
in Chest
Department.
* * Professor
of Chest, Istanbul Faculty of M edicine, University of Istanbul, Istanbul, Turkey.
Dicle University Hospital, Departments of * Pediatrics and * * Pulmonology Diyarbakır, Turkey.
SUM M ARY
Background: some anti-allergic and anti-asthmatic
drugs should be discontinued before skin prick test.
But there is no know ledge about zafirlukast effects
on skin prick test. We investigate the effects of zafirlukast on cutaneous response to histamine and specific allergens.
M aterial and methods: 9 patients suffering from
allergic mild asthma or allergic rhinitis and 8 healthy
individuals w ere recruited to the study. All of them
took 20 mg zafirlukast tw ice daily for at least 5 days.
Skin prick test was performed before and after treatment by histamine and specific allergens. There was
no significant difference between pre- and post- treatment skin prick tests in spite of zafirlukast treatment.
Conclusion: zafirlukast does not affect skin reactions against hist amine and specific allergens.
Diagnostic skin prick test can be performed under
zafirlukast treatment.
Key w ords: Zafirlukast. Skin prick test. Anti-leukotrien. Cutaneous reaction. Allergy test.
Allergol et Immunopathol 2001; 29: 66-68.
INTRODUCTION
It has been show n in many reports that antihistamines, steroids, sedatives, H 2 ant agonists,
beta-2-agonists and theophylline reduce cutaneous
reaction against specific allegens (1-3). Consumption
of these drugs should be discontinued before skin
prick test. But it is not clear that w hether anti-leukotriens has to be discontinued or not, before diagnosAllergol et Immunopathol 2001; 29(2): 66-68
tic skin prick test. The purpose of the present study
w as to investigate the effects of zafirlukast on cutaneous response to histamine and specific allergens.
M ATERIAL AND M ETHODS
Subjects
Nine patients suffering from allergic mild asthma
or allergic rhinitis and eight healthy individuals w ere
recruited to the study. Patients selected from out patient’s clinic w ho w ere treated w ith oral zafirlukast
20 mg tw ice daily and short acting beta-2-agonists
w hen necessary. Skin prick test has been performed
routinely for all patients. Healthy individuals were recruited from a volunteers group of our faculty staff and
students w ho do not have any clinically significant
medical illness. A medical history, physical examination, chest X ray, electrocardiography, panel for liver
and renal functions, complete blood analysis, serology’s for hepatitis B and C w ere used to confirm volunteers’ overall good health. We excluded individuals
w ho used anti histamines, theophylline, oral beta-2agonists and steroids last three w eeks (astemizole,
last six weeks), w ho have any prior acute illness in last
tw o-month, chronically health problems other then
allergic disease and w ho did not accept second prick
test.
Healthy individuals underw ent first skin prick test
and than took 20 mg zafirlukast tw ice daily for 5 days.
Each individual underw ent second skin prick test after at least 5 days zafirlukast treatment.
Healthy individuals signed an informed consent for
participation. Patients underw ent second prick test
by a mutual confirmation. All test items and healthy
individuals drug obt ained from commercial source
(table I).
C. Cuhadaroglu, M. Erelel, E. Kiyan, T. Ece, F. Erkan.— ROLE OF ZAFIRLUKAST ON SKIN PRICK TEST
67
Table I
Cases and controls characteristics and results
Histamine
Wheal (mm)
age
1*
Case 1
20
10
Case 2
22
12
Case 3
36
12
Case 4
29
7
Case 5
35
10
Case 6
42
7
Case 7
60
8
Case 8
19
7
Case 9
25
7
Control 1
25
10
Control 2
22
8
Control 3
23
12
Control 4
27
16
Control 5
30
12
Control 6
27
12
Control 7
28
14
Control 8
26
10
M ean ± SD* * 29.1 ± 9.9 10.1 ± 2.6
Specific allergens
Flare (mm)
2*
10
12
14
7
10
8
8
8
8
10
10
10
15
12
12
12
10.3 ± 2.3
1*
Wheal (mm)
2*
32
32
32
30
60
62
32
30
24
24
34
34
32
32
34
38
26
24
32
28
27
27
34
34
48
44
33
34
60
58
55
56
26
28
36.5 ± 11.6 36.1 ± 11.8
Flare (mm)
1*
2*
1*
2*
Positive
allergens
12
10
14
10
8
14
20
13
10
13
8
14
12
10
12
16
12
10
36
32
64
36
16
37
62
32
29
36
32
64
40
16
36
32
24
30
M ites
M ites
M ites
Grass mix
M ites
M ites
M ites
M ites
Grass mix
12.3 ± 3.5
11.8 ± 2.3
38.4 ± 15
34.4 ± 13.1
* 1: before treatment; 2: after treatment; * * standard deviation.
Skin prick test
Stallergens’ alyostal prick test solutions were used
for skin prick test. A drop of histamine hydrochlorur
(10 mg/ml) and drops of mould mix, mites, grass mix,
eastern trees pollen, dander’s pelts w ere placed on
the front arm and a sterile stallerpoint needle used to
break the superficial skin through the each drops of
solution. After 20 minutes and 60 minutes skin w heal and flare diameter were measured by a ruler.
Statistics
Student t test was performed to compare variables.
RESULTS
Patients and controls characteristics and study results were show n in table I. In both group, cutaneous
w heal and flare responds to histamine did not change significantly w ith zafirlukast (respectively, p = 0.3,
p = 0.2). In allergic patients, cutaneous w heal and flare responds to allergens did not also change w ith za-
firlukast (respectively, p = 0.2, p = 0.1). In only one
case cutaneous reaction to specific allergen was distinctly diminished w ith zafirlukast.
DISCUSSION
In this study w e have show n that zafirlukast does
not affected w heal and flare reaction of skin against
to histamine and specific aeroallergens.
In atopic individuals, specific allergen exposure to
skin, nasal mucosa, conjunctiva and bronchus result
in an immediate IgE mediated mast cell degranulation w ith release of performed mediators such as histamine as w ell as new ly formed mediators such as
cysteinyl leukotriens (4).
These mediators cause w heal and flare reaction in
the skin. Histamine is the main mediator of allergic reaction. The role of arachidionic acid metabolites is not
clear in allergic skin reaction. How ever, inhibitors of
these metabolites used to determine their role in
allergic reactions, in several studies. Atkins et al demonstrated that antagonist of cyclooxygenase metabolites does not inhibit w heal and flare reaction of
skin (5). They concluded that cyclooxygenase meAllergol et Immunopathol 2001; 29(2): 67- 66-68
68
C. Cuhadaroglu, M. Erelel, E. Kiyan, T. Ece, F. Erkan.— ROLE OF ZAFIRLUKAST ON SKIN PRICK TEST
tabolites are not important in the development of skin
inflammatory response in human. Leng and M iura reported that leukotriens are not important role in the
allergic reaction of rat skin (6, 7). But Chan et al demonstrated that cysteinyl leukotriens result in w heal
and flare raction in human skin, w hen they are injected intradermally (8). Annila et al recently showed that
bee venom induces histamine and leukotriene C4 release in sensitised beekeeper skin (11).
Zafirlukast is a cysteinyl leukotriene 1 receptor antagonist and this type of receptor is found mainly in
human bronchus. Zafirlukast in an anti-inflammatory
drug, w hich is show n to reduce airway inflammation
after allergen challenge and reduce peripheral eosinophil count. Bernstein and Dahlen reported that zafirlukast inhibit skin w heal and flare reaction against
injected cysteinyl leukotriens (10, 11). Dahlen also demonstrated that zafirlukast does not inhibit skin reaction against histamine. We have show n the similar
reaction against histamine during zafirlukast treatment.
In early inflammatory response to allergens, cysteinyl leukotriens and hist amine are released.
Anti-hist amines inhibit early skin reaction against
allergen (1, 2). But in the study zafirlukast is show n
no effect early inflammatory response to allergen in
the human skin. Anti-histamines, beta-2-agonists and
theophylline reduce early inflammatory response
and they should be stopped before diagnostic skin
prick test. But zafirlukast does not affect skin reactions against histamine and specific allergens.
We concluded that diagnostic skin prick test can
be performed under zafirlukast treatment.
RESUM EN
Fundamento: algunos fármacos antialérgicos y antiasmáticos deben interrumpirse antes de las pruebas cutáneas (prick test). Investigamos los efectos de
zafirlukast sobre la respuesta cutánea a la histamina
y a alergenos específicos.
M aterial y métodos: se recogieron en el estudio 9
pacientes que experimentaban asma alérgica leve o
rinitis alérgica y 8 individios sanos. Todos los pacientes recibieron 20 mg de zafirlukast 2 veces al día durante como mínimo 5 días. Antes y después del
tratamiento, se llevó a cabo una prueba cutánea mediante histamina y alergenos específicos. No se detectaron diferencias significativas en las pruebas cutáneas pretratamiento y postratamiento, a pesar del
tratamiento con zafirlukast.
Conclusión: el zafirlukast no afecta a las reacciones cutáneas frente a histamina y a alergenos espeAllergol et Immunopathol 2001; 29(2): 66-68
cíficos. Durante el tratamiento con zafirlukast pueden
llevarse a cabo pruebas cutáneas.
Palabras clave: Zafirlukast. Pruebas cutáneas.
Antileucotrienos. Reacción cutánea.
Correspondence:
Caglar Cuhadaroglu.
Istanbul Tip Facultesi
Gogus Hastaliklari ABD
34390 Capa, Istanbul, Turkey
Tel: + 90 212 5334364
Fax: + 90 212 6352708
e-mail: cuhad@turk.net or cuhad@yahoo.com
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Esen Kiyan