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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
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CLASSIFICATIONCLASSIFICATION
Acute urticariaAcute urticaria
Chronic urticariaChronic urticaria
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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.
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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.
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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.
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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
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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
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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
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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
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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
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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
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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 (+)
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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
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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
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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%)
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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
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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.
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RESULTRESULT
Methacholine challenge test can Methacholine challenge test can
be positive in patients with chronic be positive in patients with chronic
urticariaurticaria
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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
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RESULTRESULT
These may be result of mediators These may be result of mediators
that causing atopythat causing atopy