Prevention of severe premenstrual asthma attacks by leukotriene receptor antagonist,☆☆

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Abstract

Background: The etiology and treatment of premenstrual exacerbations of asthma (PMA) remain uncertain. Objective: We investigated the role of cellular mediators released from inflammatory cells in the airflow limitation during PMA. Methods: Serum levels of leukotriene (LT) B4 , LTC4 , platelet- activating factor, histamine, IL-1β, IL-4, IL-5, IL-6, and GM-CSF were measured at different time points, first just before or during menstruation when the peak expiratory flow rate (PEFR) began to decrease precipitously and second during the menstrual midcycle week (days 10-16) when the PEFR returned to baseline values in patients with PMA and in age-matched asthma patients without PMA at the same intervals. Results: Serum levels of LTC4 were significantly higher during exacerbations of asthma than after recovery (69.0 ± 16.0 pg/mL vs 24.0 ± 9.5 pg/mL, P < .05), whereas those of IL-1β, IL-4, IL-5, IL-6, GM-CSF, histamine, LTB4 , and platelet-activating factor did not differ between 2 periods in 5 patients with PMA. In contrast, in 5 asthmatic patients without PMA serum levels of cellular mediators did not differ between corresponding periods. Oral administration of pranlukast, an LT receptor antagonist (225 mg twice daily), significantly reduced decreases in PEFR from the baseline values (110 ± 21 L/min with pranlukast vs 233 ± 20 L/min without pranlukast, P < .01) in association with an improvement of asthma symptom scores (6.5 ± 1.1 with pranlukast vs 9.8 ± 0.7 without pranlukast, P <0.05) in 5 patients with PMA. Conclusion: LTs are partly involved in the pathogenesis of PMA, and LT receptor antagonists may be useful for preventing airflow obstruction in patients with PMA. (J Allergy Clin Immunol 1999;104:585-8.)

Section snippets

Subjects

Forty-five consecutive women aged 16 to 43 years attending an outpatient clinic for asthma were asked about the variation of their asthma during the menstrual cycle. The questionnaire included questions about the timing of any exacerbation in relation to menstruation, the frequency with which this occurred, the term of incidence, the frequency of admission, and the use of antiasthma drugs. Patients were also asked to record their peak expiratory flow rates (PEFRs) twice daily with use of a

RESULTS

In 5 patients with PMA, serum levels of LTC4 were significantly higher during PMA compared with those in the midcycle week (69.0 ± 16.0 pg/mL vs 24.0 ± 9.5 pg/mL, P < .05). In contrast, histamine (0.1 ± 0.1 ng/mL vs 0.1 ± 0.1 ng/mL, P > .50), IL-1β (0.3 ± 0.1 pg/mL vs 0.4 ± 0.4 pg/mL, P > .50), IL-4 (not detectable), IL-5 (not detectable), IL-6 (0.8 ± 0.4 pg/mL vs 0.4 ± 0.2 pg/mL, P > .20), GM-CSF (not detectable), LTB4 (151 ± 44 pg/mL vs 263 ± 166 pg/mL, P > .10) or PAF (not detectable) did

DISCUSSION

The current study shows that serum levels of LTC4 were increased during PMA and that PMA was attenuated by the LT receptor antagonist pranlukast. Although the origin of cysteinyl LTs in the sera is uncertain, there are several candidates, including T lymphocytes, basophils, and mast cells, that orchestrate airway inflammation in asthma.

Several studies have shown the influence of female sex steroids on inflammatory cells such as mast cells and basophils. Vliagoftis et al12 reported that estrogen

Acknowledgements

We thank Mr G. Crittenden for correcting the English.

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    Reprint requests: Hidetada Sasaki, MD, Department of Geriatric Medicine, Tohoku University School of Medicine, Aoba-ku Seiryo-machi 1-1, Sendai 980, Japan.

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