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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

9

0

2

4

6

8

10

12

14

16

PL LTRA

Sym

ptom

sco

res

PMA(+)PMA(-)

p=0.002

Symptom scores of groups

10

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

11

0

1

2

3

4

5

6

7

PF

T le

vels

PMA(-) PMA(+) PMA(-) PMA(+)

PLLTRA

PFTs Levels

FEV1 PEF

p>0.05

12

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

13

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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