ARE LEUKOTRIENE RECEPTOR ANTAGONISTS EFFECTIVE IN PREMENSTRUAL ASTHMA?
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ARE LEUKOTRIENE RECEPTOR ANTAGONISTS
EFFECTIVE IN PREMENSTRUAL ASTHMA?
GÜLDEN PAŞAOĞLU *, DİLŞAD MUNGAN**, ÖZNUR ABADOĞLU***, ZEYNEP MISIRLIGİL**
** Hospital of Acibadem, Istanbul
** Ankara University, Medical School, Allergic Diseases Department, Ankara,
*** Cumhuriyet University, Medical School, Allergic Diseases Department, Sivas, Turkey
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Recently, several studies suggest that some female asthmatic patients have an increase in asthma symptoms during the premenstrual period. This occasion has been named as premenstrual asthma (PMA).
The vast majority of women with perimenstrual worsening of asthma are treated like all asthmatic patients.
However, forty percent of asthmatic patients have perimenstrual exacerbations of asthma uncontrolled by steroid therapy.
INTRODUCTION
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Stepwise therapy in chronic asthma
To relieve symptom: as needed rapid-acting inhaled β2-agonistTo relieve symptom: as needed rapid-acting inhaled β2-agonist
Controller: Inhaled steroid
or Theophylline Chromone LTRA
Controller: Inh. steroid +
long-acting inh. β2-agonist or
İnh. steroid + Theophylline,or
Inh. steroid + oral 2 agonist
Inh. steroid + LTRA
High-dose inh. Steroid
Controller: Inhaled steroid Long-acting
inhaled β2-agonist
plus(if needed)
Once control of asthma is achieved,
Step down
Mild Intermitan
Mild Intermitan Mild persistentMild persistent Moderate
persistentModerate persistent
Severe persistentSevere
persistentStep downStep down
Controller:none
-Theophylline (sustained-release)
-LTRA -Long-acting oral β2- agonist -Oral steroid -Anti-IgE
GINA, 2005
LTRA
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Nowadays the efficacy of Leukotriene Receptor Antagonists (LTRAs) on treatment of asthma is known well.
Only a two studies have shown that premenstrual exacerbation of asthma is better controlled by the addition of a leukotriene modifiying agents to regimen containing inhaled steroids.
INTRODUCTION
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The aim of this study was to investigate the effects of leukotriene receptor antagonists on premenstrual exacerbation of asthma.
PURPOSE
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Asthmatic woman
n=29
1. menstrualcycles (run-in)
2. menstrualcycles
3. menstrualcycles
IS+PL IS+Montelukast
STUDY DESIGN
Symptom scores
Morning and evening PEFR
PFTs, Es,Pg,FSH,LH
PFTs, Es,Pg,FSH,LH
PFTs, Es,Pg,FSH,LH
IS
PMA(+)
(n=14)
PMA(-)
(n=15)
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RESULTS
Mild persistent asthmatic woman
n=25
Mild persistent asthmatic woman
n=25
Mean age: 36.6±6.1(25-47)
PMA (+)(n=12)
PMA (+)(n=12)
PMA (-)(n=13)
PMA (-)(n=13)
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-2,00
0,00
2,00
4,00
6,00
8,00
10,00
12,00
14,00
16,00
18,00
1 2 3 4 5 6 7 8 9 10 11 12 13
Patients
PE
F v
aria
bil
ity
PMA(-) LTRA
PMA(-) PL
PMA(+)LTRA
PMA(+)PL
PEF variabilities of groups
p=0.005p=0.005
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0
2
4
6
8
10
12
14
16
PL LTRA
Sym
ptom
sco
res
PMA(+)PMA(-)
p=0.002
Symptom scores of groups
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FEV1
(%)
PEF
(%)Estrogen Progesteron LH FSH
PL LTRA PL LTRA PL LTRA PL LTRA PL LTRA PL LTRA
PMA(-)
n=13
2.65
(108)
2.66
(102)
5.64
(87.7)6.35
(100.8)72.0 93.7 9.2 7.2 4.9 4.8 3.1 3.9
PMA(+)
n=13
2.93
(102)
2.77
(95.8)
6.18
(90.3)
6.57
(98.3)89.3 93.8 7.3 5.0 3.5 4.4 20.8 22.3
PFTs and hormone levels
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0
1
2
3
4
5
6
7
PF
T le
vels
PMA(-) PMA(+) PMA(-) PMA(+)
PLLTRA
PFTs Levels
FEV1 PEF
p>0.05
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0
10
20
30
40
50
60
70
80
90
100
Est
roge
n pg
/mL
PMA(-) PMA(+)
Estrogen levels
PL
LTRA
Hormone levels
p>0.05 p>0.05
0
5
10
15
20
25
30
35
40
Pro
gest
eron
e n
g/m
L
PMA(-) PMA(+)
Progesterone levels
PL
LTRA
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0
0,5
1
1,5
2
2,5
3
3,5
4
4,5
5
LH
m
lU/m
L
PMA(-) PMA(+)
LH levels
PL
LTRA
Hormone levels
p>0.05
0
5
10
15
20
25
FS
Hm
IU/m
L
PMA(-) PMA(+)
FSH levels
PL
LTRAp=0.05
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DISCUSSION
Prevention of severe premenstrual asthma attack by leukotriene receptor antagonist
Nakasato et al. JACI 1999;104:585-8.
5 patients with PMA and 5 controls: During 3 menstrual cycles
Morning PEFR Symptom scoresHistamineCytokines (IL-1, IL-4,IL-5, IL-6 VE GM-CSF)
LTC4, LTB4 ve PAF
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Prevention of severe premenstrual asthma attack by leukotriene receptor antagonist
0
50
100
150
200
250
PE
FR
L
/ml
PMA (+)
PEFR of patients with PMA after Pranlukast
(-)
Pranlukast
Nakasato et al. JACI 1999;104:585-8.
0
2
4
6
8
10
Sym
pto
m s
core
s
PMA(+)
Symptom scores of patients with PMA after Pranlukast
(-)
Pranlukast
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The level of LTC4 significantly increased during menstruation (69.016.0 pg/mL vs 24.0 9.5 pg/mL, p<0.05).
Prevention of severe premenstrual asthma attack by leukotriene receptor antagonist
ØØ
Nakasato et al. JACI 1999;104:585-8.
Histamin
IL-1,
IL-6
LTB4
PAF
Histamin
IL-1,
IL-6
LTB4
PAF
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Based on the data in hand it could be stated that LTRAs have ensured the control of symptoms and improved PEFR variability in patients with PMA by supressing inflamation.
We are of the view that LTRAs would be a
right choice in therapy for patients with PMA.
CONCLUSION
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