Prevention of severe premenstrual asthma attacks by leukotriene receptor antagonist

doi:10.1016/S0091-6749(99)70327-1

Journal of Allergy and Clinical Immunology

Volume 104, Issue 3, September 1999, Pages 585-588

https://doi.org/10.1016/S0091-6749(99)70327-1 Get rights and content

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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Cited by (47)

Executive summary: Japanese guidelines for adult asthma (JGL) 2021
2023, Allergology International
Asthma is characterized by chronic airway inflammation, variable airway narrowing, and sensory nerve irritation, which manifest as wheezing, dyspnea, chest tightness, and cough. Longstanding asthma may result in airway remodeling and become intractable. Despite the increased prevalence of asthma in adults, asthma-associated deaths have decreased in Japan (0.94 per 100,000 people in 2020). The goals of asthma treatment include the control of symptoms and reduction of future risks. A functional partnership between physicians and patients is indispensable for achieving these goals. Long-term management with medications and the elimination of triggers and risk factors are fundamental to asthma treatment. Asthma is managed via four steps of pharmacotherapy (“controllers”), ranging from mild to intensive treatments, depending on disease severity; each step involves daily administration of an inhaled corticosteroid, which varies from low to high dosage. Long-acting β₂ agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs. Allergen immunotherapy is a new option that is employed as a controller treatment. Further, as of 2021, anti-IgE antibody, anti-IL-5 and anti-IL-5 receptor α-chain antibodies, and anti-IL-4 receptor α-chain antibodies are available for the treatment of severe asthma. Bronchial thermoplasty can be performed for asthma treatment, and its long-term efficacy has been reported. Algorithms for their usage have been revised. Comorbidities, such as allergic rhinitis, chronic rhinosinusitis, chronic obstructive pulmonary disease, and aspirin-exacerbated respiratory disease, should also be considered during the treatment of chronic asthma. Depending on the severity of episodes, inhaled short-acting β₂ agonists, systemic corticosteroids, short-acting muscarinic antagonists, oxygen therapy, and other approaches are used as needed (“relievers”) during exacerbation.
Perimenstrual Asthma in Aspirin-Exacerbated Respiratory Disease
2020, Journal of Allergy and Clinical Immunology: In Practice
Aspirin-exacerbated respiratory disease (AERD) is a condition of the upper and lower respiratory tract characterized by reactions to nonsteroidal anti-inflammatory drugs. The Severe Asthma Research Program reported a strong association between perimenstrual asthma (PMA) and aspirin-sensitive asthma.
To evaluate the prevalence and characteristics of PMA among a cohort of patients with AERD.
Women 18 years and older enrolled in the Brigham and Women's AERD registry were surveyed about their reproductive, asthma, and sinus history. Subjects reporting the development of asthma before menopause were included. Continuous and categorical variables were compared between those reporting menstruation as a trigger for asthma symptoms and those who did not. Covariates expected a priori to have a positive effect on the odds of PMA were included in a multivariate logistic regression model to test associations between PMA and clinical factors.
Among females of childbearing potential, 369 of 695 responded to the survey and 322 met inclusion criteria. Twenty-four percent of subjects (n = 74) reported PMA. Earlier age of AERD onset, concurrent worsening of sinus symptoms the week before or during menstruation, increased emergency department visits for asthma, and a change in the severity of respiratory symptoms at menopause were more common in PMA. Earlier age at first nonsteroidal anti-inflammatory drug–induced respiratory reaction and emergency department visits increased the odds of reporting PMA.
PMA and increased sinus symptoms with menstruation are common in females with AERD. Females with AERD should be counseled about upper and lower respiratory symptom deterioration with menstruation.
Specificities of occupational asthma in women and its interactions with hormonal status
2018, Revue de Pneumologie Clinique
L’asthme professionnel (AP) est décrit comme la maladie respiratoire d’origine professionnelle la plus fréquente dans les pays industrialisés. Une prédominance féminine caractérise plusieurs populations de travailleurs asthmatiques. Des différences d’expositions professionnelles selon le genre ainsi que des variations hormonales pourraient influer sur l’AP chez la femme.
Identifier les caractéristiques socioprofessionnelles et médicales de l’AP chez les femmes en comparaison avec les hommes et chercher une éventuelle influence hormonale sur l’AP chez la femme.
Il s’agit d’une étude rétrospective, basée sur les dossiers de patients adressés à la consultation externe du service de médecine de travail et de pathologie professionnelle durant la période s’étalant entre le 1er janvier 2009 et le 30 juin 2016 pour AP avec un contact téléphonique pour le recueil des données manquantes.
Sur un total de 222 cas d’AP, une prédominance féminine a été notée (60,81 %) qui exerçait surtout dans le secteur textile (61,5 %). Cliniquement, les hommes présentaient plus de dyspnée d’effort et de sifflement thoracique, alors que l’association avec la rhinite était significativement plus importante chez les femmes. Le taux de réponse au contact téléphonique a été de 38,5 % des femmes. La majorité des femmes asthmatiques avait des cycles menstruels irréguliers (46,2 %), elles étaient multipares dans 54 %, ménopausées dans 13 % des cas avec un âge moyen de la ménarche de 12 ± 1,65 ans. Une aggravation de l’AP a été notée chez 58 % des femmes pendant leur période péri-menstruelle, chez 75 % pendant la grossesse et chez 14 % des femmes lors de la prise de contraceptifs hormonaux. Chez les femmes asthmatiques, seule la présence d’une hyperréactivité bronchique non spécifique était significativement associée à l’âge de la ménarche (p = 0,007).
Des différences entre les deux genres dans l’AP avec une variabilité des symptômes pendant la vie génitale de la femme ont été identifiées. De plus amples études pour comprendre l’influence des hormones sexuelles sur l’évolution de l’asthme et des stratégies de prise en charge personnalisées pour les femmes doivent être entreprises.
Occupational asthma (OA) is described as the most common respiratory disease in industrialized countries. A female predominance characterizes many populations of asthmatic workers. Differences in occupational exposures by gender as well as hormonal variations could affect OA in women.
To identify the socio-occupational and medical characteristics of OA in women compared to men and to investigate a possible hormonal influence on OA in women.
This is a retrospective study, based on medical records of out patients of the Department of Occupational Medicine during the period between 1st January 2009 and 30 June 2016 for OA completed by a phone call to collect missing data.
Over 222 cases of OA, a female predominance was noted (60.81%), which was predominantly in the textile sector (61.5%). Clinically, men had more exercise dyspnea and wheezing, whereas the association with rhinitis was significantly greater in women. The majority of women with asthma had irregular menstrual cycles (46.2%), they were multiparous in 54%, menopaused in 13% of cases with a mean age of menarche of 12 ± 1.65 years. A worsening of OA was noted in 58% of women during their perimenstrual period, 75% during pregnancy and 14% of women when taking hormonal contraceptives. In asthmatic women, only the presence of non-specific bronchial hyperreactivity was significantly associated with menarche age (P = 0.007).
Differences between men and women in OA with variability of symptoms during female genital life have been identified. Further studies to personalized care strategies for women need to be undertaken.
Asthma and gender: The female lung
2017, Pharmacological Research
Asthma is a common chronic disease that affects over 300 million people worldwide, resulting in a considerable socio-economic burden.
Literature data suggest that asthma has a higher incidence in females, particularly at certain stages of pubertal development. Moreover, women seem to experience more asthma symptoms than men and to use more rescue medications, resulting in a reduced quality of life.
Although several mechanisms have been proposed to explain these differences, there are not yet final data available in the literature on the role of gender in the pathogenesis of asthma and different behavior in females.
Some study suggested a more prevalent hyper-responsiveness in women than in men. Nevertheless, in the literature definitive data on a possible different response to drugs used for asthma between males and females are not described.
Understanding the mechanisms that underlie these gender differences in clinical history of asthma patients could give inspiration to new areas of research to obtain a more specific diagnostic and therapeutic approach gender-oriented.
Premenstrual asthma and leukotriene variations in the menstrual cycle
2012, Allergologia et Immunopathologia
Citation Excerpt :
Our analysis did not include patients with such a high degree of premenstrual deterioration, only between 20% and 40%, so a strict comparison between the two studies cannot be made. Regarding the latter, we would highlight the following: although PMA with the severity of those described by Nakasato et al.15 might be most attractive to a specific treatment of PMA, the majority of them referred worsening asthma premenstrual, as we found in our study, do not reach this level of deterioration of baseline. Another aspect to consider and which might explain the different results of our study with the study of Nakasato et al.15 is the possibility that these asthmatics with symptomatic deterioration and worsening clear perimenstrual of peak flow values above 40% may have some pathogenic factors and/or behaviour therapy (or LTC4) different than the rest.
Several authors have reported an increase in leukotriene C4 in the premenstrual phase in women with severe premenstrual asthma, indicating that antileukotrienes could be used in treatment.
To analyse the role of leukotrienes in premenstrual asthma.
A questionnaire on respiratory symptoms and peak flow during one complete menstrual cycle was given to women of fertile age to define them as asthmatics who suffered from premenstrual asthma or not. Premenstrual asthma (PMA) was defined as a clinical or functional deterioration (≥20%) in the premenstrual phase compared with the preovulatory phase. Blood samples to measure leukotriene C4 were taken during the preovulatory and premenstrual phases.
Blood samples were taken in 62 asthmatic women, 34 of whom (54.3%) presented PMA criteria, all with a premenstrual deterioration of between 20 and 40%. There was no difference in leukotriene C4 levels between the preovulatory and premenstrual phases in the women who suffered from PMA (1.50 ng/mL vs. 1.31 ng/mL; p = 0.32) and those who did not (1.40 ng/mL vs. 1.29 ng/mL; p = 0.62). Neither were there any differences in leukotriene levels between women with or without PMA. The results were similar for each category of asthma severity.
Our data show that leukotriene C4 does not appear to be involved in the pathogenesis of premenstrual asthma, or support the use of anti-leukotrienes in the specific treatment of premenstrual asthma, at least in women with a moderate premenstrual deterioration. No differences appeared in any of the categories of asthma severity.
Clinical characteristics of women with menstrual-linked asthma
2012, Respiratory Medicine
Citation Excerpt :
Fluctuations in the level of estrogen and progesterone are believed to affect airway inflammation, bronchial responsiveness, and expiratory airflow. Specifically, it has been identified that inflammatory modulators important in the pathophysiology of asthma including neutrophils, eosinophils, Th2-cytokines, and leukotrienes, vary over the course of the menstrual cycle.10–12 In addition, there is in vitro evidence of increased B2-receptor responsiveness after exposure to progesterone, and clinical evidence of increased peak-expiratory flow (PEF) variability, bronchial responsiveness, symptoms, and B2-agonist utilization in the late luteal and early follicular phase of the menstrual cycle, when progesterone levels are lowest.3,4,7,12–16
Menstrual-linked asthma (MLA) is described in pre-menopausal women who experience a deterioration of asthma control peri-menstrually. The clinical characteristics of MLA remain incompletely defined. Our objective was to define the characteristics of MLA in a large female asthma cohort.
Cross-sectional population survey. A comprehensive health questionnaire that included questions about MLA was administered to 1260 consecutive female asthma patients aged 12–55 years. Univariate and multivariate analyses were completed.
The survey response rate was 43% (540/1260). The prevalence of self-reported MLA was 11% (60/540). Univariate: women with MLA compared to women without MLA had more urgent/emergent asthma-related healthcare visits/year, 6.18 (SD = ±6.67) vs. 4.71 (SD = ±5.91) (p = 0.033), more emergency room visits, 1.50 (SD = ±3.57) vs. 0.88 (SD = ±2.27) (p = 0.035), higher asthma-related absenteeism, 33/60 (57%) vs. 170/471 (37%) (p = 0.003), and used almost twice the number of B₂-agonist rescue doses/day, 1.13 (SD = ±1.70) vs. 0.68 (SD = ±1.32) (p = 0.015). Multivariate: statistical significance was retained for absenteeism (p = 0.016) and B₂-agonist use (p = 0.007) but lost for urgent healthcare visits (p = 0.150) and emergency room visits (p = 0.068).
Self-reported MLA is common. Women with MLA in our population had a greater frequency of urgent healthcare visits, a higher rate of absenteeism, and used significantly more B₂-agonist rescue than women without MLA. The association of increased health services use was not confirmed on multivariate analysis indicating that baseline characteristics associated with MLA in our population affected this outcome. MLA should be considered by healthcare providers when developing an asthma management plan.

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

Abstract

Section snippets

Subjects

RESULTS

DISCUSSION

Acknowledgements

Asthme et menstruation

Presse Med

Asthme et perturbations des secretions hormonales de l’ovaire

Presse Med

An aetiological study of premenstrual asthma

J Psychosom Res

Influence of the menstrual cycle on airway function in asthmatic and normal subjects

Am Rev Respir Dis

Asthma variation with menstruation

Br J Dis Chest

Premenstrual exacerbation of asthma

Thorax

The effect of sodium meclofenamate in premenstrual asthma: a controlled clinical trial

J Allergy Clin Immunol

Severe premenstrual exacerbations of asthma: effect of intramuscular progesterone

Lancet

Serum theophylline and menstrual asthma attack

Lancet

The effect of the menstrual cycle on asthma presentations in the emergency department

Arch Intern Med

Mast cell and eosinophil distribution and activation in human endometrium throughout the menstrual cycle

Biol Reprod

Estradiol augments while tamoxifen inhibits rat mast cell secretion

Int Arch Allergy Immunol

New concepts about the mast cell

N Engl J Med

The role of interleukin-1 in disease

N Engl J Med

Effect of human recombinant interleukin 4 in vitro granulopoiesis of human bone marrow cells

Growth Factors

Regulation of IL-5 in onchocerciasis

J Immunol

Circulating interleukin-6 levels in patients with bronchial asthma

Am J Respir Crit Care Med