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Karakioulaki M, Berkemeier CM, Grize L, Heijnen I, Polyzos SA, Goulas A, Tamm M, Stolz D. The impact of sensitization patterns on COPD severity and exacerbations: Insights from a case-control and longitudinal study. Eur J Intern Med 2025:S0953-6205(25)00134-7. [PMID: 40222853 DOI: 10.1016/j.ejim.2025.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/30/2025] [Accepted: 04/03/2025] [Indexed: 04/15/2025]
Abstract
BACKGROUND Total Immunoglobulin E (tIgE) and allergen-specific IgE (sIgE) have been linked to asthma in numerous studies, with emerging evidence suggesting IgE sensitization influences chronic obstructive pulmonary disease (COPD) onset and severity. This study explores whether (a) serum tIgE and sIgE profiles differ among COPD, asthma, and controls (case-control substudy) and (b) tIgE and 300 individual sIgE levels correlate with disease severity and outcomes in 343 COPD patients (longitudinal substudy). METHODS The case-control substudy measured tIgE and sIgE in 122 participants (76 COPD, 19 asthma, 27 controls). The longitudinal substudy analyzed tIgE and 300 sIgE in 343 COPD patients, examining links to disease severity and outcomes. Atopy was defined as tIgE>20 kUA/L, while skin-sensitization was determined by skin prick test positivity. RESULTS No significant tIgE differences were observed among asthma, COPD, and controls, however asthma and COPD patients showed distinct sIgE patterns for various allergens. Atopic men reported fewer urgent visits for acute exacerbations of COPD (ECOPD) than non-atopic men (79.07 % vs.91.33 %, p = 0.007), while skin-sensitized women experienced more severe ECOPD than non-skin-sensitized women (46.43 % vs. 24.36 %, p = 0.028). Exacerbation etiology was not associated with atopic or skin-sensitization profiles. Fungal sensitization correlated with older age (p = 0.032), worse 6-minute walking test outcomes (p = 0.007), and reduced diffusion capacity (DLCO/VA %, p = 0.006). CONCLUSION While atopic profiles are similar across groups, asthma features higher aeroallergen sIgE. Skin-sensitization and atopy may influence lung function and symptom severity in COPD but are differently associated with ECOPD between sexes and are not linked to the etiology of ECOPD.
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Affiliation(s)
- Meropi Karakioulaki
- Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland; Clinic of Dermatology and Venereology, Medical Center-University of Freiburg, Germany; Faculty of Medicine, University of Freiburg, Germany
| | | | - Leticia Grize
- Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland; Faculty of Medicine, University of Freiburg, Germany; Clinic of Respiratory Medicine, Medical Center-Univeristy of Freiburg, Germany
| | - Ingmar Heijnen
- Medical Immunology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Antonis Goulas
- First Laboratory of Pharmacology, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; Clinical Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece
| | - Michael Tamm
- Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland
| | - Daiana Stolz
- Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland; Faculty of Medicine, University of Freiburg, Germany; Clinic of Respiratory Medicine, Medical Center-Univeristy of Freiburg, Germany.
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Brown AC, Carroll OR, Mayall JR, Zounemat-Kermani N, Vinzenz SLE, Gomez HM, Mills EF, Kim RY, Donovan C, Baines KJ, Williams EJ, Berthon BS, Wynne K, Scott HA, Pinkerton JW, Guo Y, Hansbro PM, Foster PS, Wark PAB, Dahlen SE, Adcock IM, Wood LG, Horvat JC. Female sex hormones and the oral contraceptive pill modulate asthma severity through GLUT-1. Mucosal Immunol 2025:S1933-0219(25)00024-8. [PMID: 40021011 DOI: 10.1016/j.mucimm.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 02/20/2025] [Accepted: 02/20/2025] [Indexed: 03/03/2025]
Abstract
Females are disproportionately affected by asthma. An increased understanding of how female sex hormones influence key pathophysiological processes that underpin asthma may identify new, more effective asthma therapies, particularly for females with severe, poorly controlled asthma. We assessed the effects of oral ethinylestradiol/levonorgestrel (representing OCP use) and depot-medroxyprogesterone acetate (DMPA) and estradiol injections on key features of experimental asthma, and determined their effects on glucose transporter-1 (GLUT-1). The effects of OCP use on clinical asthma outcomes, and the relationships between estrogen receptors and type 2 (T2), non-T2, and GLUT-1 responses, in clinical asthma were also determined. OCP and DMPA reduce T2 responses, disease features, and lung expression of GLUT-1, whereas estradiol increases lung expression of GLUT-1, and results in severe, corticosteroid-insensitive, neutrophil-enriched disease, in experimental asthma. OCP use is associated with reduced T2 cytokine and GLUT-1 responses in clinical asthma. GLUT-1 expression is increased in sputum of severe asthmatics, and positively correlates with estrogen receptor expression and both T2 and non-T2 inflammatory responses. Significantly, OCP or GLUT-1 inhibition protects against obesity-associated or estradiol-induced, severe, experimental asthma, respectively. Together, these data show how female sex hormones and the OCP likely modulate asthma severity by modifying GLUT-1 responses in the airways.
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Affiliation(s)
- Alexandra C Brown
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Olivia R Carroll
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Jemma R Mayall
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | | | - Samantha L E Vinzenz
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Henry M Gomez
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Ed F Mills
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Richard Y Kim
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia; Woolcock Institute of Medical Research, Sydney, New South Wales, Australia
| | - Chantal Donovan
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia; Woolcock Institute of Medical Research, Sydney, New South Wales, Australia
| | - Katherine J Baines
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Evan J Williams
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Bronwyn S Berthon
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Katie Wynne
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Hayley A Scott
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - James W Pinkerton
- Respiratory Pharmacology & Toxicology Group, National Heart & Lung Institute, Imperial College London, London, United Kingdom
| | - Yike Guo
- Hong Kong University of Science and Technology, Hong Kong
| | - Philip M Hansbro
- Centre for Inflammation, Centenary Institute, and Faculty of Science, University of Technology Sydney, Sydney, New South Wales, Australia
| | - Paul S Foster
- Woolcock Institute of Medical Research and Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Peter A B Wark
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia; School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Sven-Erik Dahlen
- Clinical Lung and Allergy Research Unit, Department of Medicine Huddinge, Karolinska Institutet, and, Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, and Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Ian M Adcock
- The Airway Disease Section, National Heart & Lung Institute, Imperial College London, London, United Kingdom
| | - Lisa G Wood
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
| | - Jay C Horvat
- The University of Newcastle and Immune Health Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
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Calcaterra V, Nappi RE, Farolfi A, Tiranini L, Rossi V, Regalbuto C, Zuccotti G. Perimenstrual Asthma in Adolescents: A Shared Condition in Pediatric and Gynecological Endocrinology. CHILDREN 2022; 9:children9020233. [PMID: 35204953 PMCID: PMC8870409 DOI: 10.3390/children9020233] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/04/2022] [Accepted: 02/07/2022] [Indexed: 12/12/2022]
Abstract
Asthma is a frequent medical condition in adolescence. The worsening of the most common symptoms perimenstrually is defined as perimenstrual asthma (PMA). The cause of PMA remains unclear, but a role for hormonal milieu is plausible. Data on PMA in adolescents are limited, and its management is not fully established. We aimed to discuss the PMA phenomenon in young females from pathophysiology to preventive strategies, focusing on the relationship with the hormonal pattern. The fluctuation of estrogens at ovulation and before menstruation and the progesterone secretion during the luteal phase and its subsequent withdrawal seem to be the culprits, because the deterioration of asthma is cyclical during the luteal phase and/or during the first days of the menstrual cycle. Conventional asthma therapies are not always effective for PMA. Preventive strategies may include innovative hormonal contraception. Even a possible beneficial effect of other hormonal treatments, including estrogens, progestogens, and androgens, as well as leukotriene receptor antagonists and explorative approach using microbial-directed therapy, is considered. The underlying mechanisms, through which sex-hormone fluctuations influence asthma symptoms, represent a challenge in the clinical management of such a distressing condition. Further studies focused on young females are mandatory to promote adolescent health.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
- Correspondence:
| | - Rossella Elena Nappi
- Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (R.E.N.); (L.T.)
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
| | - Andrea Farolfi
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
| | - Lara Tiranini
- Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (R.E.N.); (L.T.)
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy
| | - Virginia Rossi
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
| | - Corrado Regalbuto
- Pediatric Unit, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy;
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, “Vittore Buzzi” Children’s Hospital, 20154 Milano, Italy; (A.F.); (V.R.); (G.Z.)
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milano, 20157 Milano, Italy
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Role of Sex Hormones at Different Physiobiological Conditions and Therapeutic Potential in MBD2 Mediated Severe Asthma. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:7097797. [PMID: 35096261 PMCID: PMC8799366 DOI: 10.1155/2021/7097797] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 11/29/2021] [Indexed: 12/16/2022]
Abstract
Sex hormone has become a “hot topic” to evaluate the hormonal therapeutic potential in severe asthma. Th17 cell is one of the main influencing factors involved in the pathogenesis of severe asthma, hence also called as kernel of severe asthma, and Th17 subtype of non-T2 asthma is less responsive (resistance) to inhaled corticosteroid (ICS), so severe in nature. Methyl-CpG binding domain protein 2 (MBD2) is overexpressed and regulates the Th17 differentiation, showing the possibility of therapeutic target in treating Th17 mediated severe asthma. Sex hormone fluctuates at the different physiobiological conditions of the human body and affects the asthma pathobiology showing its role in asthma prevalence, severity, remission, and therapy. This review briefly overviews the sex hormones, their influence in asthma at the different physiobiological conditions of human body, and MBD2 severe asthma connection with the possible therapeutic potential of sex steroids in MBD2 mediated Th17 predominant severe asthma. Male sex hormone tends to show a beneficial effect and possibly downregulates the expression of Th17 cells via regulating MBD2 through a mechanism distinct from corticosteroid treatment and guides us towards discovery of new therapeutic agent, reduces the asthma-related complications, and promotes long-term survival by lowering the risk of therapy-resistant issues of old age severe asthma.
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Reyes-García J, Montaño LM, Carbajal-García A, Wang YX. Sex Hormones and Lung Inflammation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1304:259-321. [PMID: 34019274 DOI: 10.1007/978-3-030-68748-9_15] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Inflammation is a characteristic marker in numerous lung disorders. Several immune cells, such as macrophages, dendritic cells, eosinophils, as well as T and B lymphocytes, synthetize and release cytokines involved in the inflammatory process. Gender differences in the incidence and severity of inflammatory lung ailments including asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), lung cancer (LC), and infectious related illnesses have been reported. Moreover, the effects of sex hormones on both androgens and estrogens, such as testosterone (TES) and 17β-estradiol (E2), driving characteristic inflammatory patterns in those lung inflammatory diseases have been investigated. In general, androgens seem to display anti-inflammatory actions, whereas estrogens produce pro-inflammatory effects. For instance, androgens regulate negatively inflammation in asthma by targeting type 2 innate lymphoid cells (ILC2s) and T-helper (Th)-2 cells to attenuate interleukin (IL)-17A-mediated responses and leukotriene (LT) biosynthesis pathway. Estrogens may promote neutrophilic inflammation in subjects with asthma and COPD. Moreover, the activation of estrogen receptors might induce tumorigenesis. In this chapter, we summarize the most recent advances in the functional roles and associated signaling pathways of inflammatory cellular responses in asthma, COPD, PF, LC, and newly occurring COVID-19 disease. We also meticulously deliberate the influence of sex steroids on the development and progress of these common and severe lung diseases.
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Affiliation(s)
- Jorge Reyes-García
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico City, Mexico.,Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA
| | - Luis M Montaño
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico City, Mexico
| | - Abril Carbajal-García
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico City, Mexico
| | - Yong-Xiao Wang
- Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA.
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Ridolo E, Incorvaia C, Martignago I, Caminati M, Canonica GW, Senna G. Sex in Respiratory and Skin Allergies. Clin Rev Allergy Immunol 2019; 56:322-332. [PMID: 29306980 DOI: 10.1007/s12016-017-8661-0] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
A bulk of literature demonstrated that respiratory allergy, and especially asthma, is prevalent in males during childhood, while it becomes more frequent in females from adolescence, i.e., after menarche, to adulthood. The mechanisms underlying the difference between females and males are the effects on the immune response of female hormones and in particular the modulation of inflammatory response by estrogens, as well as the result of the activity of various cells, such as dendritic cells, innate lymphoid cells, Th1, Th2, T regulatory (Treg) and B regulatory (Bregs) cells, and a number of proteins and cytokines, which include interleukin (IL)-4, IL-5, IL-10, and IL-13. As far as sexual dimorphism is concerned, a gender difference in the expression profiles of histamine receptors and of mast cells was demonstrated in experimental studies. A critical phase of hormone production is the menstrual cycle, which often is associated with asthma deterioration, as assessed by worsening of clinical symptoms and increase of bronchial hyperresponsiveness. In asthmatic woman, there is a high risk to develop more severe asthma during menstruation. The higher prevalence of asthma in females is confirmed also in the post-menopause age, but the underlying mechanisms are not yet understood. In pregnancy, asthma may worsen but may also improve or remain unchanged, with no significant difference in frequency of these three outcomes. For allergic rhinitis, the available studies indicate, likewise asthma, a male predominance in prevalence in childhood that shifts to a female predominance in adolescence and adulthood, but further investigation is needed.
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Affiliation(s)
- Erminia Ridolo
- Medicine and Surgery Department, University of Parma, Parma, Italy
| | | | - Irene Martignago
- Medicine and Surgery Department, University of Parma, Parma, Italy
| | - Marco Caminati
- Asthma Center and Allergy Unit, Verona University Hospital, P.le L.A. Scuro 10, 37134, Verona, Italy.
| | - Giorgio Walter Canonica
- Personalized Medicine Asthma & Allergy Clinic, Humanitas University, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Gianenrico Senna
- Asthma Center and Allergy Unit, Verona University Hospital, P.le L.A. Scuro 10, 37134, Verona, Italy
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Impact of allergic diseases on fertility. Postepy Dermatol Alergol 2019; 36:507-512. [PMID: 31839765 PMCID: PMC6906954 DOI: 10.5114/ada.2019.89501] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 05/10/2018] [Indexed: 01/24/2023] Open
Abstract
The incidence of allergic diseases has been increasing in recent decades, and currently, nearly 30% of the European population suffer from some type of allergy. Also, an increasing number of people are suffering from infertility. Both diseases are related to the hormonal and immune systems, which prompts the question as to whether there is a causal relationship between allergic disorders and the reproductive system. The purpose of this review is to evaluate whether there is a link between allergic diseases and infertility, using the available literature.
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Lei Z, Yanhan D, Yi W, Shengdao X, Weining X. Perimenstrual asthma: Report of a case with therapeutic intervention of oral prednisone. J Asthma 2018; 55:1328-1330. [PMID: 29584459 DOI: 10.1080/02770903.2017.1418886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
INTRODUCTION Many asthmatic women of childbearing age experience cyclical aggravation of asthmatic symptoms during the perimenstrual period, or perimenstrual asthma (PMA). PMA is considered to be a difficult-to-treat asthma phenotype; conventional asthma therapies are not always effective against PMA. CASE STUDY We report a case of a 27-year-old female with PMA who had received standard asthma treatment since 2013. RESULT The patient showed a dramatic response to therapeutic intervention of oral prednisone, taken for 7 days prior to menstruation each month, in a dose-dependent manner. CONCLUSION Premenstrual treatment with oral prednisone may be a successful new direction for the treatment of PMA, a troublesome type of asthma.
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Affiliation(s)
- Zhang Lei
- a Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College , Huazhong University of Sciences & Technology , Wuhan , Hubei , China
| | - Deng Yanhan
- a Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College , Huazhong University of Sciences & Technology , Wuhan , Hubei , China
| | - Wang Yi
- a Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College , Huazhong University of Sciences & Technology , Wuhan , Hubei , China
| | - Xiong Shengdao
- a Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College , Huazhong University of Sciences & Technology , Wuhan , Hubei , China
| | - Xiong Weining
- a Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College , Huazhong University of Sciences & Technology , Wuhan , Hubei , China
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Studying allergic inflammation and spirometry over menstrual cycles in well-controlled asthmatic women: Changes in progesterone and estradiol affect neither FENO levels nor lung function. Nitric Oxide 2018; 75:95-100. [PMID: 29486305 DOI: 10.1016/j.niox.2018.02.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 01/17/2018] [Accepted: 02/21/2018] [Indexed: 11/22/2022]
Abstract
It has been reported that female sex hormones influence on allergic inflammation and ventilation parameters in asthma but conclusions drawn by different researchers are divergent. The aim of our study was to assess the impact of progesterone (Pg) and estradiol (E) on the dynamics of allergic inflammation and spirometry test results in regularly menstruating women with stable allergic asthma. 13 women (28 days menstrual cycle), aged 18-45, taking no hormonal contraceptives, with mild and moderate asthma, without reported exacerbations at the near-ovulation and/or menstruation time, were monitored during two consecutive menstrual cycles. They had 4 visits per cycle (the first day of menstruation was assumed to be day 1 of the cycle; visits were carried out on days: 3-4, 10-11, 13-14 and 23-24). At each visit asthma symptoms, asthma control test (ACT) results, asthma treatment, fractioned nitric oxide (FENO) levels, spirometry test results, Pg and E, levels were analyzed. As a result of the study, no essential variability in FENO values and ventilation parameters' values in the course of menstruation cycle were observed. Negative correlation between FENO values and Pg concentrations was demonstrated (r = 0.27), but no correlation between FENO values and E levels was shown. No relationship between the ACT values and ventilation parameters and the levels of the sex hormones under investigation was detected. We conclude that changing levels of estradiol and progesterone (regardless of the negative correlation of progesterone and FENO values) affect neither the dynamics of allergic inflammation nor pulmonary function in women with stable allergic mild/moderate asthma.
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McCleary N, Nwaru BI, Nurmatov UB, Critchley H, Sheikh A. Endogenous and exogenous sex steroid hormones in asthma and allergy in females: A systematic review and meta-analysis. J Allergy Clin Immunol 2018; 141:1510-1513.e8. [PMID: 29305316 PMCID: PMC5883329 DOI: 10.1016/j.jaci.2017.11.034] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 11/20/2017] [Accepted: 11/30/2017] [Indexed: 12/01/2022]
Affiliation(s)
- Nicola McCleary
- Asthma UK Centre for Applied Research, Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
| | - Bright I Nwaru
- Asthma UK Centre for Applied Research, Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom; Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Ulugbek B Nurmatov
- Asthma UK Centre for Applied Research, Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom; Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, United Kingdom
| | - Hilary Critchley
- Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Aziz Sheikh
- Asthma UK Centre for Applied Research, Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
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Koper I, Hufnagl K, Ehmann R. Gender aspects and influence of hormones on bronchial asthma - Secondary publication and update. World Allergy Organ J 2017; 10:46. [PMID: 29308113 PMCID: PMC5745695 DOI: 10.1186/s40413-017-0177-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 12/06/2017] [Indexed: 01/13/2023] Open
Abstract
There is good evidence for gender-specific differences in asthma regarding all affected areas, from intra- to extra-cellular mediators to the whole organ structure und functioning of the lung. These result from complex, in parts synergistic, in other parts opposing, effects - especially of female sex hormones, and rather protective effects of male hormones against asthma, which include effects on the cellular immune system. Additionally, there are gender differences of sociocultural origin, regarding presentation, doctor's diagnosis and treatment of asthma symptoms, as well as the undertaken coping strategies concerning the female or male patient's complaints. Taking into account gender-specific differences in asthma would contribute to improved individual diagnosis and therapies.
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Affiliation(s)
- Iris Koper
- Department of Internal Medicine/Pneumology, Sana Kliniken Ostholstein, Clinics Oldenburg, Oldenburg, Germany
| | - Karin Hufnagl
- Comparative Medicine, The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Austria Veterinärplatz 1, 1210 Vienna, Austria
| | - Rainer Ehmann
- Severe Asthma Center, Ambulante Pneumologie mit Allergiezentrum (BAG), Rotebühlplatz 19, 70178 Stuttgart, Germany
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Abstract
PURPOSE OF REVIEW Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis. RECENT FINDINGS Clinical evidence shows that increased asthma symptoms occur in females starting at puberty compared to those in boys. However, after puberty, the role for sex hormones in regulating asthma symptoms during menstruation, pregnancy, and menopause is not as clear. Animal studies have shown that estrogen increases and testosterone decreases Th2-mediated airway inflammation, and that females have increased IL-17A-mediated airway inflammation compared to males. Further, females had increased DC and Mϕ function compared to males. However, the mechanisms driving the types of allergic inflammation are not fully elucidated. Overall, ovarian hormones increased and testosterone decreased airway inflammation in asthma, but the mechanisms remain unclear. Delineating these pathways using animal models as well as women and men with various phenotypes of asthma will help determine if women with asthma should take (or avoid) hormonal contraceptives as well as predict changes in asthma symptoms during life phases, including pregnancy and menopause, when sex hormones are dramatically changing.
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Skoczynski S, Semik-Orzech A, Sozanska E, Szanecki W, Kołodziejczyk K, Radziewicz-Winnicki I, Witek A, Pierzchała W, Barczyk A. Bronchial hyperreactivity in perimenstrual asthma is associated with increased Th-2 response in lower airways. J Thorac Dis 2017; 9:2015-2021. [PMID: 28840001 DOI: 10.21037/jtd.2017.06.121] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Perimenstrual asthma (PMA) is a commonly observed, usually difficult-to-treat asthma phenotype. The mechanisms underlying this phenomenon remain unexplained. The aim of the study was to assess the degree of airway hyperresponsiveness and its relationship to proinflammatory cytokines concentration in lower airways of PMA compared to non-PMA patients. METHODS Premenopausal women with regular menstrual cycles diagnosed as: PMA (n=12), non-PMA asthmatics (n=9), and healthy controls (n=10) were prospectively followed for 10 weeks over two consecutive menstrual cycles. The bronchial responsiveness (BR) test to methacholine was performed in each subject prior to the study. The serum for total immunoglobulin E (IgE) concentrations was taken and sputum was induced in the 26th day of each of the two cycles. Sputum concentration of eotaxin, IL-4 and IL-10 were measured by ELISA. RESULTS Levels of BR to metacholine as well, as total blood IgE concentrations in PMA subjects were significantly higher than in non-PMA asthmatics and healthy controls (P=0.001, P=0.022 respectively) and correlated with each other (P=0.030; r =-0.65). Sputum eotaxin and IL-4 concentrations in luteal phase were increased in PMA patients when compared with non-PMA asthmatics (P=0.016; P=0.041, respectively) and healthy subjects (P<0.001 both cytokines). No differences for the sputum levels of IL-10 among studied groups were seen. CONCLUSIONS BR level in perimenstrual asthma is higher than in non-PMA asthmatics and correlates with increased total IgE serum concentration. The increased level of BR in PMA patients is associated with a shift in the type-1/type-2 cytokine balance toward a type-2 response.
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Affiliation(s)
- Szymon Skoczynski
- Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Aleksandra Semik-Orzech
- Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Ewa Sozanska
- Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Wojciech Szanecki
- Department of Gynaecology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | | | | | - Andrzej Witek
- Department of Gynaecology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Władysław Pierzchała
- Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Adam Barczyk
- Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
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14
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de Benedictis D, Bush A. Asthma in adolescence: Is there any news? Pediatr Pulmonol 2017; 52:129-138. [PMID: 27273858 DOI: 10.1002/ppul.23498] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 05/18/2016] [Accepted: 05/25/2016] [Indexed: 12/22/2022]
Abstract
Asthma is a chronic disease that has a significant impact quality of life, which is particularly important in adolescence. We will discuss aspects of epidemiology, the clinical spectrum, diagnostics, and management of asthma in adolescence. In particular, we will highlight the psychological implications of having asthma during this developmental period. Data published in the past 10 years, since we last reviewed the subject, will be the main focus of this paper. The care of the teenager with asthma should take into account the rapid physical, emotional, cognitive, and social changes that occur during normal adolescence. The diagnostic process may be more difficult since teenagers tend to deny their illness. Thus, both under-diagnosis and under-assessment of asthma severity may lead to under-treatment and potentially avoidable morbidity and even mortality. Conversely, teenagers may be often misdiagnosed as having asthma or their asthma severity may be overestimated leading to inappropriate and sometimes excessive treatment. Educational programs, environmental avoidance measures, proper use of medications along with a skilled approach, and a caring attitude of health providers are all very important for successful management. Pediatr Pulmonol. 2017;52:129-138. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
| | - Andrew Bush
- Department of Pediatrics, Imperial College, London, UK.,Department of Pediatric Respiratory Medicine, National Heart and Lung Institute, London, UK.,Department of Pediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UK
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15
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Abstract
CONTEXT AND OBJECTIVE: The relationship between sex hormones and asthma has been evaluated in several studies. The aim of this review article was to investigate the association between asthma and female sex hormones, under different conditions (premenstrual asthma, use of oral contraceptives, menopause, hormone replacement therapy and pregnancy). DESIGN AND SETTING: Narrative review of the medical literature, Universidade Federal do Tocantins (UFT) and Universidade Federal de São Paulo (Unifesp). METHODS: We searched the CAPES journal portal, a Brazilian platform that provides access to articles in the MEDLINE, PubMed, SciELO, and LILACS databases. The following keywords were used based on Medical Subject Headings: asthma, sex hormones, women and use of oral contraceptives. RESULTS: The associations between sex hormones and asthma remain obscure. In adults, asthma is more common in women than in men. In addition, mortality due to asthma is significantly higher among females. The immune system is influenced by sex hormones: either because progesterone stimulates progesterone-induced blocking factor and Th2 cytokines or because contraceptives derived from progesterone and estrogen stimulate the transcription factor GATA-3. CONCLUSIONS: The associations between asthma and female sex hormones remain obscure. We speculate that estrogen fluctuations are responsible for asthma exacerbations that occur in women. Because of the anti-inflammatory action of estrogen, it decreases TNF-α production, interferon-γ expression and NK cell activity. We suggest that further studies that highlight the underlying physiopathological mechanisms contributing towards these interactions should be conducted.
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Affiliation(s)
| | - Ivaldo Silva
- MD, PhD. Adjunct Professor, Gynecology, Universidade Federal do São Paulo (SP), Brazil.
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16
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Sánchez-Ramos JL, Pereira-Vega AR, Alvarado-Gómez F, Maldonado-Pérez JA, Svanes C, Gómez-Real F. Risk factors for premenstrual asthma: a systematic review and meta-analysis. Expert Rev Respir Med 2016; 11:57-72. [DOI: 10.1080/17476348.2017.1270762] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
| | | | - Francisco Alvarado-Gómez
- Library, Juan Ramón Jiménez Hospital, Huelva, Spain
- Andalusian Health Service e-Library, Seville, Spain
| | | | - Cecilie Svanes
- Centre for International Health, University of Bergen, Bergen, Norway
- Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway
| | - Francisco Gómez-Real
- Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
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17
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Tse SM, Rifas-Shiman SL, Coull BA, Litonjua AA, Oken E, Gold DR. Sex-specific risk factors for childhood wheeze and longitudinal phenotypes of wheeze. J Allergy Clin Immunol 2016; 138:1561-1568.e6. [PMID: 27246527 PMCID: PMC5083247 DOI: 10.1016/j.jaci.2016.04.005] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2015] [Revised: 04/05/2016] [Accepted: 04/13/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Although sexual dimorphism in wheeze and asthma prevalence are well documented, sex-specific risk factors for wheeze and longitudinal wheeze phenotypes have not been well elucidated. OBJECTIVE By using a large prebirth cohort, this study aimed to identify sex-specific risk factors for wheeze from birth through midchildhood and identify distinct longitudinal wheeze phenotypes and the sex-specific risk factors associated with these phenotypes. METHODS Mothers reported child wheeze symptoms over the past year approximately yearly on 9 occasions starting at age 1 year. We identified sex-specific predictors of wheeze, wheeze phenotypes, and sex-specific predictors of these phenotypes by using generalized estimating equations, latent class mixed models, and multinomial logistic analysis, respectively. RESULTS A total of 1623 children had information on wheeze at 1 or more time points. Paternal asthma was a stronger predictor of ever wheezing in boys (odds ratio [OR], 2.15; 95% CI, 1.74-2.66) than in girls (OR, 1.53; 95% CI, 1.19-1.96; P for sex by paternal asthma interaction = .03), whereas being black or Hispanic, birth weight for gestational age z score, and breast-feeding duration had stronger associations among girls. We identified 3 longitudinal wheeze phenotypes: never/infrequent wheeze (74.1%), early transient wheeze (12.7%), and persistent wheeze (13.1%). Compared with never/infrequent wheeze, maternal asthma, infant bronchiolitis, and atopic dermatitis were associated with persistent wheeze in both sexes, but paternal asthma was associated with persistent wheeze in boys only (OR, 4.27; 95% CI, 2.33-7.83; P for sex by paternal asthma interaction = .02), whereas being black or Hispanic was a predictor for girls only. CONCLUSION We identified sex-specific predictors of wheeze and longitudinal wheeze patterns, which might have important prognostic value and allow for a more personalized approach to wheeze and asthma treatment.
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Affiliation(s)
- Sze Man Tse
- Division of Respiratory Medicine, Department of Pediatrics, Sainte-Justine University Hospital Center and University of Montreal, Montreal, Quebec, Canada.
| | - Sheryl L Rifas-Shiman
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass
| | - Brent A Coull
- Department of Biostatistics, Harvard School of Public Health, Boston, Mass
| | - Augusto A Litonjua
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
| | - Emily Oken
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass
| | - Diane R Gold
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass
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18
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Asthma as a disruption in iron homeostasis. Biometals 2016; 29:751-79. [PMID: 27595579 DOI: 10.1007/s10534-016-9948-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 07/07/2016] [Indexed: 12/28/2022]
Abstract
Over several decades, asthma has evolved from being recognized as a single disease to include a diverse group of phenotypes with dissimilar natural histories, pathophysiologies, responses to treatment, and distinctive molecular pathways. With the application of Occam's razor to asthma, it is proposed that there is one cause underlying the numerous phenotypes of this disease and that the responsible molecular pathway is a deficiency of iron in the lung tissues. This deficiency can be either absolute (e.g. asthma in the neonate and during both pregnancy and menstruation) or functional (e.g. asthma associated with infections, smoking, and obesity). Comparable associations between asthma co-morbidity (e.g. eczema, urticaria, restless leg syndrome, and pulmonary hypertension) with iron deficiency support such a shared mechanistic pathway. Therapies directed at asthma demonstrate a capacity to impact iron homeostasis, further strengthening the relationship. Finally, pathophysiologic events producing asthma, including inflammation, increases in Th2 cells, and muscle contraction, can correlate with iron availability. Recognition of a potential association between asthma and an absolute and/or functional iron deficiency suggests specific therapeutic interventions including inhaled iron.
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19
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Graziottin A, Serafini A. Perimenstrual asthma: from pathophysiology to treatment strategies. Multidiscip Respir Med 2016; 11:30. [PMID: 27482380 PMCID: PMC4967997 DOI: 10.1186/s40248-016-0065-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 05/05/2016] [Indexed: 12/19/2022] Open
Abstract
The prevalence of asthma is about 9,7 % in women and 5,5 % in men. Asthma can deteriorate during the perimenstrual period, a phenomenon known as perimenstrual asthma (PMA), which represents a unique, highly symptomatic asthma phenotype. It is distinguished from traditional allergic asthma by aspirin sensitivity, less atopy, and lower lung capacity. PMA incidence is reported to vary between 19 and 40 % of asthmatic women. The presence of PMA has been related to increases in asthma-related emergency department visits, hospitalizations and emergency treatment including intubations. It is hypothesized that hormonal status may influence asthma in women, focusing on the role of sex hormones, and specifically on the impact of estrogens' fluctuations at ovulation and before periods. This paper will focus on the pathophysiology of hormone triggered cycle related inflammatory/allergic events and their relation with asthma. We reviewed the scientific literature on Pubmed database for studies on PMA. Key word were PMA, mastcells, estrogens, inflammation, oral contraception, hormonal replacement therapy (HRT), and hormone free interval (HFI). Special attention will be devoted to the possibility of reducing the perimenstrual worsening of asthma and associated symptoms by reducing estrogens fluctuations, with appropriate hormonal contraception and reduced HFI. This novel therapeutical approach will be finally discussed.
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Affiliation(s)
- Alessandra Graziottin
- Center of Gynecology and Medical Sexology, San Raffaele Resnati Hospital, Milan, Italy
- Via Enrico Panzacchi 6, 20123 Milan, Italy
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20
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Sathish V, Prakash Y. Sex Differences in Pulmonary Anatomy and Physiology. SEX DIFFERENCES IN PHYSIOLOGY 2016:89-103. [DOI: 10.1016/b978-0-12-802388-4.00006-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
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21
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Pereira-Vega A, Sánchez-Ramos JL. Questions relating to premenstrual asthma. World J Respirol 2015; 5:180-187. [DOI: 10.5320/wjr.v5.i3.180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 08/05/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
The study of asthma in fertile women needs to consider its potentially recurrent exacerbation in a specific phase of the menstrual cycle. Premenstrual asthma (PMA) refers to the deterioration of asthma in some women of fertile age during the premenstrual phase. Prevalence varies considerably according to studies (11%-47.44%) mainly because there is no standardized definition of the illness. There is a possible link between PMA and premenstrual syndrome, which is a set of physical and psychic manifestations that occur in some fertile women during the same premenstrual phase. This relation has been widely studied but there are still several unknowns. PMA etiopathogeny is not known. It involves possible causes such as hormonal variations in the premenstrual phase, the coexistence of atopy, variations during the cycle in substances related to inflammation, like LTC4 leukotrienes, catecholamines, E2 and F2α prostaglandins and certain cytokines. Also considered are psychological factors related to this phase of the menstrual cycle, a high susceptibility to infection or increased bronchial hyperreactivity prior to menstruation. Yet no factor fully explains its etiology, consequently no specific treatment exists. Researchers have investigated hormones, anti-leukotrienes, prostaglandin synthesis inhibitors, diuretics, phytoestrogens and alternative therapies, but none has been shown to be effective.
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22
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Tse SM, Coull BA, Sordillo JE, Datta S, Gold DR. Gender- and age-specific risk factors for wheeze from birth through adolescence. Pediatr Pulmonol 2015; 50:955-62. [PMID: 25348842 PMCID: PMC4800823 DOI: 10.1002/ppul.23113] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 07/29/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVE Cross-sectional gender differences in wheeze are well documented, but few studies have examined the gender-specific risk factors for wheeze longitudinally. This study aims to identify gender- and age-specific risk factors for wheeze from birth through adolescence. METHODS The incidence of wheeze was ascertained every 6 months through age 14 years in a birth cohort consisting of 499 children with a parental history of atopy. Gender- and age-specific risk factors were identified through generalized estimating equations. RESULTS A total of 454 (91.0%) and 351 (70.3%) children were followed past age 7 and 13 years, respectively. Maternal asthma was a risk factor for wheeze in girls (OR = 2.05, 95% CI 1.44-2.91, P < 0.0001) and boys (OR = 1.79, 1.29-2.48, P = 0.0004) and had a similar effect on wheeze throughout the ages. Paternal asthma (OR = 1.83, 1.38-2.57, P = 0.0005) and infant bronchiolitis (OR = 2.15, 1.47-3.14, P < 0.0001) were risk factors for boys only, with similar effects throughout the ages. CONCLUSION Using a prospective cohort, we identified gender- and age-specific risk factors for wheeze. The identification of gender-specific early life risk factors may allow for timely interventions and a more personalized approach to the treatment of asthma.
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Affiliation(s)
- Sze Man Tse
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, Quebec, Canada
| | - Brent A Coull
- Department of Biostatistics, Harvard School of Public Health, Boston, Massachusett
| | - Joanne E Sordillo
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Soma Datta
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Diane R Gold
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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23
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Graziottin A. The shorter, the better: A review of the evidence for a shorter contraceptive hormone-free interval. EUR J CONTRACEP REPR 2015; 21:93-105. [PMID: 26291185 DOI: 10.3109/13625187.2015.1077380] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVES The menstrual cycle is characterised by cyclical fluctuations in oestrogens, progesterone and androgens. Changes in hormone levels in the premenstrual phase with the decline in progesterone trigger a physiological reaction which culminates in menstruation. This process is accompanied in many women by various symptoms such as pelvic pain, headache, mood disorders and gastrointestinal discomfort. The aim of this article was to summarise the latest findings on the physiology and pathophysiology of menstruation and review the impact of shortening the hormone-free interval (HFI) on the health and wellbeing of women. RESULTS Menstruation can be viewed as an inflammatory event in which local and systemic effects produce symptoms in genital and extragenital regions of the body. The mast cells are the main mediator of this reaction. In women using hormonal contraceptives, menstrual bleeding is not biologically necessary and it may be advantageous to maintain more stable levels of oestrogens, progesterone and androgens throughout the cycle. New combined oral contraceptives (COCs) have been formulated with a progressively shorter HFI (24/4 and 26/2) than traditional 21/7 pills, with the rationale of reducing hormone withdrawal- associated symptoms. Several studies have shown the beneficial effects of these regimens, which reduce the inflammatory exposure of the female organism and thus have the capacity to increase the quality of life of women. A combination of estradiol valerate (E2V) and dienogest (DNG) is administered on the shortest 26/2 regimen. This regimen has a broad evidence base from randomised controlled trials that have examined the impact of E2V/DNG on symptoms and quality of life. CONCLUSIONS Shortening the HFI reduces the occurrence of bleeding-related inflammatory processes and subsequent physical and mental symptoms. The shortest interval with evidence of reproductive and sexual health benefits is provided by a 26/2 regimen.
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Affiliation(s)
- Alessandra Graziottin
- a Center of Gynecology and Medical Sexology , H. San Raffaele Resnati, Milan , Italy
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24
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Sex steroid signaling: implications for lung diseases. Pharmacol Ther 2015; 150:94-108. [PMID: 25595323 DOI: 10.1016/j.pharmthera.2015.01.007] [Citation(s) in RCA: 129] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 01/09/2015] [Indexed: 12/12/2022]
Abstract
There is increasing recognition that sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are still not well-understood. Accordingly, it becomes important to ask the following questions: 1) Which sex steroids are involved? 2) How do they affect different components of the lung under normal circumstances? 3) How does sex steroid signaling change in or contribute to lung disease, and in this regard, are sex steroids detrimental or beneficial? As our understanding of sex steroid signaling in the lung improves, it is important to consider whether such information can be used to develop new therapeutic strategies to target lung diseases, perhaps in both sexes or in a sex-specific manner. In this review, we focus on the basics of sex steroid signaling, and the current state of knowledge regarding how they influence structure and function of specific lung components across the life span and in the context of some important lung diseases. We then summarize the potential for sex steroids as useful biomarkers and therapeutic targets in these lung diseases as a basis for future translational research in the area of gender and individualized medicine.
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Lieberoth S, Gade EJ, Brok J, Backer V, Thomsen SF. Age at menarche and risk of asthma: systematic review and meta-analysis. J Asthma 2014; 51:559-65. [PMID: 24628525 DOI: 10.3109/02770903.2014.903966] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Several studies have suggested a relationship between the age at menarche and risk of asthma development. OBJECTIVE To conduct a systematic review and meta-analysis of the relationship between the age at menarche and the risk of asthma. METHODS This systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A pre specified literature search strategy was used to identify studies of potential relevance and independent reviews were carried out by two authors. Raw data was pooled using the software package RevMan to calculate summary odds ratios. The risk of publication bias was assessed graphically by using a funnel plot and the robustness of the overall estimate obtained was assessed by using sensitivity analyses. RESULTS The searches identified 61 potentially relevant articles of which seven articles, with a total of 22,859 subjects, matched the inclusion criteria for the meta-analysis. Pooling of the seven studies showed that girls with early menarche (<12 years) had an increased risk of asthma relative to girls with late menarche; random effects odds ratio = 1.37 (1.15-1.64), (p = 0.0005). Substantial heterogeneity was revealed (I(2) = 55%). Sensitivity analysis showed that the risk estimate was not markedly changed when excluding any of the studies. The funnel plot did not indicate publication bias. CONCLUSIONS Early menarche appears to be associated with increased risk of asthma. Hormonal, immunological, genetic and environmental factors may act in a developmental context to explain this relationship. Future studies are warranted to further determine the mechanisms responsible for this observation.
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Affiliation(s)
- Sofie Lieberoth
- Department of Respiratory Medicine, Bispebjerg Hospital , Copenhagen , Denmark
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26
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Macsali F, Svanes C, Bjørge L, Omenaas ER, Gómez Real F. Respiratory health in women: from menarche to menopause. Expert Rev Respir Med 2014; 6:187-200; quiz 201-2. [PMID: 22455491 DOI: 10.1586/ers.12.15] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Ferenc Macsali
- Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
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27
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Abstract
PURPOSE OF REVIEW Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Of these, estrogen has been the subject of much study. This review highlights recent research exploring the effects of estrogen in allergic disease. RECENT FINDINGS Estrogen receptors are found on numerous immunoregulatory cells and estrogen's actions skew immune responses toward allergy. It may act directly to create deleterious effects in asthma, or indirectly via modulation of various pathways including secretory leukoprotease inhibitor, transient receptor potential vanilloid type 1 ion channel and nitric oxide production to exert effects on lung mechanics and inflammation. Not only do endogenous estrogens appear to play a role, but environmental estrogens have also been implicated. Environmental estrogens (xenoestrogens) including bisphenol A and phthalates enhance allergic sensitization in animal models and may enhance development of atopic disorders like asthma in humans. SUMMARY Estrogen's role in allergic disease remains complex. As allergic diseases continue to increase in prevalence and affect women disproportionately, gaining a fuller understanding of its effects in these disorders will be essential. Of particular importance may be effects of xenoestrogens on allergic disease.
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Affiliation(s)
- Rana S Bonds
- Division of Allergy/Immunology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555, USA.
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28
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Macsali F, Svanes C, Sothern RB, Benediktsdottir B, Bjørge L, Dratva J, Franklin KA, Holm M, Janson C, Johannessen A, Lindberg E, Omenaas ER, Schlünssen V, Zemp E, Real FG. Menstrual cycle and respiratory symptoms in a general Nordic-Baltic population. Am J Respir Crit Care Med 2012. [PMID: 23204251 DOI: 10.1164/rccm.201206-1112oc] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
RATIONALE There is little knowledge of variations in respiratory symptoms during the menstrual cycle in a general population, and potential modifying factors are not investigated. OBJECTIVES To investigate menstrual cycle variation in respiratory symptoms in a large general population, using chronobiology methodology, and stratifying by body mass index (BMI), smoking, and asthma status. METHODS A total of 3,926 women with regular cycles less than or equal to 28 days and not taking exogenous sex hormones answered a postal questionnaire regarding the first day of their last menstruation and respiratory symptoms in the last 3 days. Moving 4-day means were computed to smooth uneven records of daily sampling; best-fitting 28-day composite cosine curves were applied to each time series to describe rhythmicity. MEASUREMENTS AND MAIN RESULTS Significant rhythmic variations over the menstrual cycle were found in each symptom for all subjects and subgroups. Wheezing was higher on cycle Days 10-22, with a midcycle dip near the time of putative ovulation (approximately Days 14-16) in most subgroups. Shortness of breath was higher on days 7-21, with a dip just before midcycle in many subgroups. Cough was higher just after putative ovulation for subjects with asthma, BMI greater than or equal to 23 kg/m(2), and smokers, or just before ovulation and menses onset for low symptomatic subgroups. CONCLUSIONS Respiratory symptoms varied significantly during the menstrual cycle and were most frequent from the midluteal to midfollicular stages, often with a dip near the time of ovulation. The patterns varied by BMI, smoking, and asthma status. These relations link respiratory symptoms with hormonal changes through the menstrual cycle and imply a potential for individualized chronotherapy for respiratory diseases.
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Affiliation(s)
- Ferenc Macsali
- Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway.
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29
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Premenstrual asthma and leukotriene variations in the menstrual cycle. Allergol Immunopathol (Madr) 2012; 40:368-73. [PMID: 22115570 DOI: 10.1016/j.aller.2011.09.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2011] [Accepted: 09/06/2011] [Indexed: 12/24/2022]
Abstract
BACKGROUND 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. OBJECTIVE To analyse the role of leukotrienes in premenstrual asthma. METHODS 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. RESULTS 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 (1.50ng/mL vs. 1.31ng/mL; p=0.32) and those who did not (1.40ng/mL vs. 1.29ng/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. CONCLUSIONS 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.
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Galobardes B, Patel S, Henderson J, Jeffreys M, Smith GD. The association between irregular menstruations and acne with asthma and atopy phenotypes. Am J Epidemiol 2012; 176:733-7. [PMID: 23028012 PMCID: PMC3472614 DOI: 10.1093/aje/kws161] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Earlier menarche and irregular periods, among other markers of sex-hormone levels, have been associated with a higher risk of asthma and allergic diseases. This has suggested an etiologic role of sex hormones in the development of these conditions. The authors investigated the association of age at menarche, irregular periods, duration of menstruation, and acne with reported medical history of asthma and/or atopy (hay fever and/or eczema/urticaria) in a historical cohort of students born before the rise in asthma prevalence in the United Kingdom and attending university in 1948–1968. Finding consistent associations in a cohort that has experienced different life-course exposures and has different confounding structure can help to identify causal associations. In the Glasgow Alumni Cohort, irregular periods were associated with atopic asthma (multinomial odds ratio (MOR) = 2.79, 95% confidence interval (CI): 1.33, 5.83) and atopy alone (MOR = 1.40, 95% CI: 1.06, 1.84) but not with nonatopic asthma (MOR = 1.02, 95% CI: 0.45, 2.30), compared with students reporting no asthma and no atopy. The authors found no association with acne, a marker of high testosterone levels, that they hypothesized could point to polycystic ovary syndrome underpinning these associations. In summary, the authors found evidence for a potentially etiologic role of irregular menstruations with some specific asthma phenotypes, namely, atopic asthma and atopy, but not with nonatopic asthma.
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Affiliation(s)
- Bruna Galobardes
- School of Social and Community Medicine, University of Bristol, Bristol, UK.
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Bastarache JA, Diamond JM, Kawut SM, Lederer DJ, Ware LB, Christie JD. Postoperative estradiol levels associate with development of primary graft dysfunction in lung transplantation patients. ACTA ACUST UNITED AC 2012; 9:154-65. [PMID: 22361838 DOI: 10.1016/j.genm.2012.01.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2011] [Revised: 01/04/2012] [Accepted: 01/18/2012] [Indexed: 01/11/2023]
Abstract
BACKGROUND Primary graft dysfunction (PGD) frequently complicates lung transplantation in the immediate postoperative period. Both female gender and estradiol modulate the body's response to injury and can influence the rate of alveolar fluid clearance. OBJECTIVE We hypothesized that female gender and higher estradiol levels would be associated with a lower risk of PGD after lung transplantation. METHODS We measured plasma estradiol levels preoperatively, 6 hours postoperatively, and 24 hours postoperatively in a cohort of 111 lung transplant recipients at 2 institutions. RESULTS Mean age was 57 years (12.5) and 52% were female. Median postoperative estradiol level was 63.9 pg/mL (interquartile range, 28.8-154.3 pg/mL) in male and 65.1 pg/mL (interquartile range, 28.4-217.2 pg/mL) in female patients. Contrary to our hypothesis, higher estradiol levels at 24 hours were associated with an increased risk of PGD at 72 hours in male patients (P = 0.001). This association was preserved when accounting for other factors known to be associated with PGD. However, there was no relationship between gender and risk of PGD or between estradiol levels and PGD in females. CONCLUSION These findings suggest that there might be different biologic effects of estrogens in males and females, and highlight the importance of considering gender differences in future studies of PGD.
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Affiliation(s)
- Julie A Bastarache
- Division of Allergy, Pulmonary and Critical Care, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA.
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Choi IS. Gender-specific asthma treatment. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2010; 3:74-80. [PMID: 21461245 PMCID: PMC3062799 DOI: 10.4168/aair.2011.3.2.74] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/28/2010] [Accepted: 09/24/2010] [Indexed: 01/16/2023]
Abstract
Because genetic characteristics vary among subjects, the therapeutic effects of a certain drug differ among patients with the same disease. For this reason, special interest has focused on tailored treatments. Although it is well known that sex is genetically determined, little attention has been paid to sex differences in the clinical features and treatment of asthma. Females are more likely to suffer allergic asthma, to have difficulty controlling asthma symptoms, and to show adverse effects to drugs. As asthma symptoms show cyclic changes depending on female hormone levels in many women of child-bearing age, the use of contraceptives may specifically help to treat female patients with asthma such as those with perimenstrual asthma and severe asthma. Generally, testosterone seems to suppress asthma, and dehydroepiandrosterone (DHEA), a less virilizing androgen, may be effective for treating asthma. Evidence exists for a therapeutic and steroid-sparing effect of DHEA. However, further studies on the optimal dose and route of DHEA for each sex are needed. Monitoring of the serum DHEA-S level is necessary for patients with asthma on inhaled steroid treatment, and at minimum, replacement therapy for patients with a low level of DHEA may be helpful for treating their asthma.
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Affiliation(s)
- Inseon S Choi
- Department of Allergy, Chonnam National University Medical School, Gwangju, Korea
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