1

ASSESSMENT OF ASSESSMENT OF BRONCHOPROVOCATION TEST BRONCHOPROVOCATION TEST POSITIVITY AND RESPONSE TO POSITIVITY AND RESPONSE TO MONTELUKAST THERAPHY IN MONTELUKAST THERAPHY IN

CHRONIC URTICARIA PATIENTSCHRONIC URTICARIA PATIENTS

Yavuz Havlucu*,Yavuz Havlucu*, Deniz Yurtman Havlucu**, Deniz Yurtman Havlucu**, Serap Öztürkcan**, Arzu Yorgancıoğlu*Serap Öztürkcan**, Arzu Yorgancıoğlu*

Celal Bayar University Medical Faculty Department Of Celal Bayar University Medical Faculty Department Of *Chest Disease and **Dermatology *Chest Disease and **Dermatology

2

CLASSIFICATIONCLASSIFICATION

Acute urticariaAcute urticaria

Chronic urticariaChronic urticaria

3

PATHOGENESISPATHOGENESIS

Mast cellMast cell → → HistamineHistamine →→ LeukotrieneLeukotriene → → Prostaglandin D2Prostaglandin D2 → → IL-2, IL-3, IL-4, IL-5, IL-6, IL-8IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 → → BradykininBradykinin → → TNF-TNF- → …… → ……..

Champion RH. Br J Dermatol 1988;119:427-436.

5

PATHOGENESISPATHOGENESIS

After antigen stimulationAfter antigen stimulation

within first hour (due to mast cellwithin first hour (due to mast cell

degranulation)degranulation)

after 11-12 hours (from basophils)after 11-12 hours (from basophils)

Histamine reaches peak levelHistamine reaches peak level

Sabroe RA. Arch Dermatol 1997;133:1003-1008.

6

PATHOGENESISPATHOGENESIS

Presence of mast cell in skin without Presence of mast cell in skin without

urticarial lesion was shownurticarial lesion was shown

Sabroe RA. Arch Dermatol 1997;133:1003-1008.

7

PATHOGENESISPATHOGENESIS

Exacerbations Exacerbations

ChronicityChronicity

Presence of late-phase responsePresence of late-phase response

Presence of inflammation in the skin Presence of inflammation in the skin

without lesion without lesion

CHRONIC-SYSTEMIC INFLAMMATIONCHRONIC-SYSTEMIC INFLAMMATION

8

PURPOSEPURPOSE

To determine the frequency of bronchial To determine the frequency of bronchial

hypereactivity in patients with chronic urticariahypereactivity in patients with chronic urticaria

To determine the effect of leukotriene receptor To determine the effect of leukotriene receptor

antagonists on inflammation seen in patients antagonists on inflammation seen in patients

with chronic urticaria by bronchial provocation with chronic urticaria by bronchial provocation

test indirectlytest indirectly

9

MATERIALS AND METHODSMATERIALS AND METHODS

Inclusion Criteria;Inclusion Criteria;

Duration of chronic urticaria more thanDuration of chronic urticaria more than

one yearone year

No urticarial exacerbation within twoNo urticarial exacerbation within two

months months

10

MATERIALS AND METHODSMATERIALS AND METHODS

Exclusion Criteria;Exclusion Criteria;

Presence of respiratory symptoms and Presence of respiratory symptoms and

asthmaasthma

Abnormal pulmonary function testAbnormal pulmonary function test

Usage of anihistamines andUsage of anihistamines and

corticosteroid within one month corticosteroid within one month

11

MATERIALS AND METHODSMATERIALS AND METHODS

Exclusion Criteria;Exclusion Criteria;

Presence of any condition that causing Presence of any condition that causing

methacholine challenge test positivitymethacholine challenge test positivity

Any contrindication to application ofAny contrindication to application of

methacholine challenge test methacholine challenge test

12

MATERIALS AND METHODSMATERIALS AND METHODS

156 patients156 patients Pulmonary function test Pulmonary function test → methacholine→ methacholine

challenge testchallenge test Methacholine challenge test (+)Methacholine challenge test (+)

→ → Montelukast 10 mg/dayMontelukast 10 mg/day After 8 weeks methacholine challenge test After 8 weeks methacholine challenge test

was repeated was repeated

13

RESULTSRESULTS

48 (30,8%) 48 (30,8%) men, 108 (69,2%) womenmen, 108 (69,2%) women

Mean age 42,54 Mean age 42,54 13,19 years (18-70) 13,19 years (18-70)

Duration of disease 6,05 Duration of disease 6,05 4,33 years (1- 4,33 years (1-

25)25)

41 (26,3%) methacholine challenge test (+) 41 (26,3%) methacholine challenge test (+)

14

RESULTSRESULTS

MPT (+)MPT (+)

(n:41)(n:41)

MPT (-)MPT (-)

(n:115)(n:115)

pp

AGEAGE 38,32 38,32 12,78 12,78 44,04 44,04 13,0613,06

<0,05<0,05

GENDERGENDER

(M/W)(M/W)

16/2516/25 32/8332/83 =0,30=0,30

DURATION DURATION OF DISEASEOF DISEASE

6,29 6,29 5,18 5,18 5,97 5,97 4,01 4,01 =0,69=0,69

IgEIgE 217,56 217,56 170,56170,56

89,57 89,57 80,5080,50

<0,05<0,05

15

RESULTSRESULTS

Methacholine challenge test (+); mean Methacholine challenge test (+); mean

provocative dose 2,64 provocative dose 2,64 3,36 mg/ml 3,36 mg/ml

(at the beginning)(at the beginning)

End of the study End of the study → → 4,57 4,57 4,87 mg/ml 4,87 mg/ml

16

RESULTSRESULTS

End of the studyEnd of the study

Provocative dose increased in 30 patientsProvocative dose increased in 30 patients

(73,2%) (73,2%)

It was same in 11 patients (26,8%)It was same in 11 patients (26,8%)

17

Asero found that presence of bronchial Asero found that presence of bronchial

hyperreactivity was 85% and claimed that hyperreactivity was 85% and claimed that

it was due to the systemic inflammation it was due to the systemic inflammation

Asero R, Madonini E. J Investig Allergol Clin Immunol 2006

18

Response to the treatment was better in Response to the treatment was better in

patients under leukotriene receptor patients under leukotriene receptor

antagonist + conventional treatment than antagonist + conventional treatment than

patients under only conventional treatmentpatients under only conventional treatment

Sanada s. Arch Dermatol Res. 2005 Sep;297(3):134-8.Nettis E. Clin Exp Allergy. 2004 Sep;34(9):1401-7.Sekerel BE. Pediatr Alergy Immunol. 2003;14:212-215.Erbagci Z. Allergy Clin Immunol. 2002 Sep;110(3):484-8. Pacor ML. Clin Exp Allergy. 2001 Oct;31(10):1607-14.

19

RESULTRESULT

Methacholine challenge test can Methacholine challenge test can

be positive in patients with chronic be positive in patients with chronic

urticariaurticaria

20

RESULTRESULT

Provocative dose can be increased Provocative dose can be increased

with the medication against with the medication against

leukotrienes in patients with leukotrienes in patients with

chronic urticariachronic urticaria

21

RESULTRESULT

These may be result of mediators These may be result of mediators

that causing atopythat causing atopy