|
1
|
Bartra J, Turner PJ, Muñoz-Cano RM. Cofactors in food anaphylaxis in adults. Ann Allergy Asthma Immunol 2023; 130:733-740. [PMID: 36958469 DOI: 10.1016/j.anai.2023.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/25/2023]
Abstract
Around 25% to 50% of food-induced allergic reactions in adults cause anaphylaxis, and epidemiologic evidence suggests that food is the most common cause of anaphylaxis. Reaction severity is unpredictable, and patients will often experience reactions of variable severity, even to an identical exposure (both dose and allergen). A common explanation for this phenomenon has been the impact of "cofactors"-factors that might contribute to reaction severity independent of the allergen exposure. Cofactors can influence reaction severity in 2 ways: either by reducing the reaction threshold (ie, the dose needed to trigger any symptoms) so that patients have no symptoms in the absence of the cofactor and only react with the cofactor present, or by increasing reaction severity such that individuals have only mild symptoms in the absence of the cofactor, but a more severe reaction when the cofactor is present. Indeed, the same patient may have reactions with different cofactors or even need more than one cofactor to develop a severe reaction. Cofactors reportedly play a role in approximately 30% of anaphylaxis reactions in adults. Exercise, nonsteroidal, anti-inflammatory drugs, alcohol, and sleep deprivation are the most frequent cofactors reported. Routine evaluation of the possible involvement of cofactors is essential in managing patients with food anaphylaxis: in patients with a suggestive history but a negative oral food challenge, cofactors should be taken into account to provide appropriate advice to reduce the risk of future anaphylaxis.
Collapse
Affiliation(s)
- Joan Bartra
- Department of Allergy, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), RETIC ARADyAL, RICORs REI, Barcelona, Spain
| | - Paul J Turner
- National Heart and Lung Institute, Imperial College London, London, United Kingdom.
| | - Rosa M Muñoz-Cano
- Department of Allergy, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), RETIC ARADyAL, RICORs REI, Barcelona, Spain
| |
Collapse
|
|
2
|
Reddy KD, Oliver BGG. Sexual dimorphism in chronic respiratory diseases. Cell Biosci 2023; 13:47. [PMID: 36882807 PMCID: PMC9993607 DOI: 10.1186/s13578-023-00998-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 02/23/2023] [Indexed: 03/09/2023] Open
Abstract
Sex differences in susceptibility, severity, and progression are prevalent for various diseases in multiple organ systems. This phenomenon is particularly apparent in respiratory diseases. Asthma demonstrates an age-dependent pattern of sexual dimorphism. However, marked differences between males and females exist in other pervasive conditions such as chronic obstructive pulmonary disease (COPD) and lung cancer. The sex hormones estrogen and testosterone are commonly considered the primary factors causing sexual dimorphism in disease. However, how they contribute to differences in disease onset between males and females remains undefined. The sex chromosomes are an under-investigated fundamental form of sexual dimorphism. Recent studies highlight key X and Y-chromosome-linked genes that regulate vital cell processes and can contribute to disease-relevant mechanisms. This review summarises patterns of sex differences in asthma, COPD and lung cancer, highlighting physiological mechanisms causing the observed dimorphism. We also describe the role of the sex hormones and present candidate genes on the sex chromosomes as potential factors contributing to sexual dimorphism in disease.
Collapse
Affiliation(s)
- Karosham Diren Reddy
- Respiratory and Cellular Molecular Biology Group, Woolcock Institute of Medical Research, Glebe, NSW, 2037, Australia.
- School of Life Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia.
| | - Brian Gregory George Oliver
- Respiratory and Cellular Molecular Biology Group, Woolcock Institute of Medical Research, Glebe, NSW, 2037, Australia
- School of Life Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia
| |
Collapse
|
|
3
|
LoMauro A, Aliverti A. Sex and gender in respiratory physiology. Eur Respir Rev 2021; 30:30/162/210038. [PMID: 34750114 DOI: 10.1183/16000617.0038-2021] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 06/08/2021] [Indexed: 11/05/2022] Open
Abstract
Sex is a biological concept determined at conception. Gender is a social concept. Medicine recognises sex as a biological variable and recommends including sex as a factor in clinical practice norms and as a topic of bench and clinical research. Sex plays a role in respiratory physiology according to two pathways: hormones and anatomy, with females characterised by smaller dimensions at every level of the respiratory system. Sex hormones also play specific roles in lung inflammatory processes, breathing control and in response to diseases. The literature is extremely controversial because many factors need to be considered to avoid erroneous comparisons. The main difficulty lies in creating homogeneous groups of subjects according to age, body weight, lung/airway size, fluctuations in circulating hormone levels, and exercise protocol. Because almost all of the knowledge available in physiology is based on research in males, medicine for women is therefore less evidence-based than that being applied to men. Finally, the number of transsexual people is increasing and they represent new challenges for clinicians, due to the anatomical and physiological changes that they undergo.
Collapse
Affiliation(s)
- Antonella LoMauro
- Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy
| | - Andrea Aliverti
- Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy
| |
Collapse
|
|
4
|
Raherison C, Hamzaoui A, Nocent-Ejnaini C, Essari LA, Ouksel H, Zysman M, Prudhomme A. [Woman's asthma throughout life: Towards a personalized management?]. Rev Mal Respir 2020; 37:144-160. [PMID: 32057504 DOI: 10.1016/j.rmr.2019.07.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 07/18/2019] [Indexed: 11/30/2022]
Abstract
In a woman's life, asthma can affect her in a variety of ways, with the onset of premenstrual asthma currently under-diagnosed. It is estimated that about 20% of women with asthma have premenstrual asthma, which is more common in patients with severe asthma. Women with asthma are at high risk of exacerbations and of severe asthma. Asthma is the most common chronic disease during pregnancy with potential maternal and foetal complications. Asthma medications are safe for the foetus and it is essential to continue pre-existing treatment and adapt it to the progress of asthma during the pregnancy. Sex steroids modulate the structure and function of bronchial and immune cells. Understanding their role in asthma pathogenesis is complicated by the ambivalent effects of bronchodilating and pro-inflammatory oestrogens as well as the diversity of response to their association with progesterone. Menopausal asthma is a clinical entity and is part of one of the phenotypes of severe non-allergic and low steroid-sensitive asthma. Targeted assessment of the domestic and professional environment allows optimization of asthma management.
Collapse
Affiliation(s)
- C Raherison
- Service des maladies respiratoires, pôle cardiothoracique, INSERM U1219, université de Bordeaux, CHU Bordeaux, 146, rue Léo-Saignat, 33604 Bordeaux, France.
| | - A Hamzaoui
- Pavillon B, unité de recherche UR12 SP15, hôpital Abderrahmen Mami, faculté de médecine, université de Tunis El Manar, Ariana, Tunisie
| | | | - L-A Essari
- Département de pneumologie, CHRU de Nancy, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France
| | - H Ouksel
- Département de pneumologie, CHU d'Angers, Angers, France
| | - M Zysman
- UMR_S955, université Paris-Est Créteil (UPEC), 94000 Créteil, France; Inserm, U955, Team 4, 94000 Créteil, France
| | - A Prudhomme
- Service de pneumologie, CHG Tarbes, Tarbes, France
| | | |
Collapse
|
|
5
|
Acute Severe Asthma in Adolescent and Adult Patients: Current Perspectives on Assessment and Management. J Clin Med 2019; 8:jcm8091283. [PMID: 31443563 PMCID: PMC6780340 DOI: 10.3390/jcm8091283] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/09/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023] Open
Abstract
Asthma is a chronic airway inflammatory disease that is associated with variable expiratory flow, variable respiratory symptoms, and exacerbations which sometimes require hospitalization or may be fatal. It is not only patients with severe and poorly controlled asthma that are at risk for an acute severe exacerbation, but this has also been observed in patients with otherwise mild or moderate asthma. This review discusses current aspects on the pathogenesis and pathophysiology of acute severe asthma exacerbations and provides the current perspectives on the management of acute severe asthma attacks in the emergency department and the intensive care unit.
Collapse
|
|
6
|
Sessa M, Mascolo A, D'Agostino B, Casciotta A, D'Agostino V, Michele FD, Polverino M, Spaziano G, Andersen MP, Kragholm K, Rossi F, Torp-Pedersen C, Capuano A. Relationship Between Gender and the Effectiveness of Montelukast: An Italian/Danish Register-Based Retrospective Cohort Study. Front Pharmacol 2018; 9:844. [PMID: 30116192 PMCID: PMC6083053 DOI: 10.3389/fphar.2018.00844] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Accepted: 07/13/2018] [Indexed: 11/13/2022] Open
Abstract
Rationale: Gender-related differences in asthma prevalence, pathophysiology and clinical features induced by sex steroids have been investigated, however, how gender influences response to asthma treatments in routine clinical practice have not yet been elucidated fully. This aspect is crucial for montelukast considering the jeopardization of asthmatic patients that benefit from this treatment and the existence of evidence of gender differences in leukotriene levels. Therefore, to fulfill this medical need, we investigated the role of gender on a set of montelukast' effectiveness surrogates in adults and pediatric patients with asthma. Methods: The study settings were Napoli 2 Local Health Unit (southern Italy) and the entire Danish territory. The study population was composed of adult and pediatric patients with asthma. Cumulative incidence curves, unadjusted and adjusted Cox regression were used as statistical models to compare aforementioned outcomes between genders. Results: Adult Italian male users of montelukast had a statistically lower persistence in montelukast treatment compared to female users. In the adjusted analyses, they had a higher hazard of montelukast' withdrawal (Hazard Ratio [HR] 1.07; 95% Confidence Interval [CI] 1.01-1.14), add-on/switch to a long-term treatment for asthma following montelukast withdrawal (HR 1.72; 95%CI 1.39-2.12), and rescue therapy with short-acting β2 agonist (HR 1.24; 95%CI 1.04-1.47). In the adult Danish cohort, we also found that male users had higher a hazard of rescue therapy with oral corticosteroids (HR 1.10; 95%CI 1.04-1.16). In the pediatric cohorts, no statistically significant differences were observed between genders for aforementioned outcomes. Conclusions: In adults, male gender was associated with increased hazards of montelukast discontinuation, add-on/switch to a long-term treatment for asthma following montelukast withdrawal, and rescue therapy with oral corticosteroids or short-acting β2 agonist when compared to the female gender. As expected, these associations were reversed or absent in pediatric patients.
Collapse
Affiliation(s)
- Maurizio Sessa
- Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.,Department of Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Annamaria Mascolo
- Department of Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Bruno D'Agostino
- Department of Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Antonio Casciotta
- Local Health Unit Napoli Second, Department of Pharmaceutical, Naples, Italy
| | - Vincenzo D'Agostino
- Local Health Unit Napoli Second, Department of Pharmaceutical, Naples, Italy
| | | | - Mario Polverino
- Department of Pneumology and Endoscopic Unit, Ospedale Scarlato, Scafati, Italy
| | - Giuseppe Spaziano
- Department of Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | | | - Kristian Kragholm
- Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark.,Department of Cardiology, North Denmark Regional Hospital, Hjørring, Denmark.,Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Francesco Rossi
- Department of Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Christian Torp-Pedersen
- Unit of Epidemiology and Biostatistics, Aalborg University Hospital, Aalborg, Denmark.,Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Annalisa Capuano
- Department of Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| |
Collapse
|
|
7
|
Muñoz-Cano R, Pascal M, Araujo G, Goikoetxea MJ, Valero AL, Picado C, Bartra J. Mechanisms, Cofactors, and Augmenting Factors Involved in Anaphylaxis. Front Immunol 2017; 8:1193. [PMID: 29018449 PMCID: PMC5623009 DOI: 10.3389/fimmu.2017.01193] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 09/08/2017] [Indexed: 01/12/2023] Open
Abstract
Anaphylaxis is an acute and life-threatening systemic reaction. Many triggers have been described, including food, drug, and hymenoptera allergens, which are the most frequently involved. The mechanisms described in anaphylactic reactions are complex and implicate a diversity of pathways. Some of these mechanisms may be key to the development of the anaphylactic reaction, while others may only modify its severity. Although specific IgE, mast cells, and basophils are considered the principal players in anaphylaxis, alternative mechanisms have been proposed in non-IgE anaphylactic reactions. Neutrophils, macrophages, as well as basophils, have been involved, as have IgG-dependent, complement and contact system activation. A range of cationic substances can induce antibody-independent mast cells activation through MRGPRX2 receptor. Cofactors and augmenting factors may explain why, in some patients, food allergen exposure can cause anaphylaxis, while in other clinical scenario it can be tolerated or elicits a mild reaction. With the influence of these factors, food allergic reactions may be induced at lower doses of allergen and/or become more severe. Exercise, alcohol, estrogens, and some drugs such as Non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, β-blockers, and lipid-lowering drugs are the main factors described, though their mechanisms and signaling pathways are poorly understood.
Collapse
Affiliation(s)
- Rosa Muñoz-Cano
- Unitat d'Allergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Mariona Pascal
- Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Servei d'Immunologia, Centre de Diagnòstic Biomèdic (CDB), Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
| | - Giovanna Araujo
- Unitat d'Allergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - M J Goikoetxea
- Allergy and Immunology Department, Universidad de Navarra, Navarra, Spain
| | - Antonio L Valero
- Unitat d'Allergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Cesar Picado
- Unitat d'Allergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Joan Bartra
- Unitat d'Allergia, Servei de Pneumologia, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| |
Collapse
|
|
8
|
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
| |
Collapse
|
|
9
|
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.
Collapse
Affiliation(s)
- Alessandra Graziottin
- Center of Gynecology and Medical Sexology, San Raffaele Resnati Hospital, Milan, Italy
- Via Enrico Panzacchi 6, 20123 Milan, Italy
| | | |
Collapse
|
|
10
|
Raherison C, Bourdin A, Bonniaud P, Deslée G, Garcia G, Leroyer C, Taillé C, De Blic J, Dubus JC, Tillié-Leblond I, Chanez P. Updated guidelines (2015) for management and monitoring of adult and adolescent asthmatic patients (from 12 years and older) of the Société de Pneumologie de Langue Française (SPLF) (Full length text). Rev Mal Respir 2016; 33:279-325. [PMID: 27147308 DOI: 10.1016/j.rmr.2016.03.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- C Raherison
- Inserm U1219, ISPED, service des maladies respiratoires, pôle cardio-thoracique, CHU de Bordeaux, université de Bordeaux, 33000 Bordeaux, France.
| | - A Bourdin
- Inserm U1046, département de pneumologie et addictologie, hôpital Arnaud-de-Villeneuve, CHU de Montpellier, université Montpellier 1, 34000 Montpellier, France
| | - P Bonniaud
- Inserm U866, service de pneumologie et soins intensifs respiratoires, CHU de Bourgogne, université de Bourgogne, 21079 Dijon, France
| | - G Deslée
- Service de pneumologie, CHU Maison-Blanche, université de Reims - Champagne-Ardennes, 51000 Reims, France
| | - G Garcia
- Inserm, UMRS 999, service de pneumologie, département hospitalo-universitaire (DHU) thorax innovation, hôpital de Bicêtre, Centre national de référence de l'hypertension pulmonaire sévère, faculté de médecine, université Paris-Sud, AP-HP, 94270 Le Kremlin-Bicêtre, France
| | - C Leroyer
- Département de médecine interne et de pneumologie, CHU de la Cavale-Blanche, université de Bretagne Occidentale, 29000 Brest, France
| | - C Taillé
- Service de pneumologie, département hospitalo-universitaire FIRE, centre de compétence des maladies pulmonaires rares, hôpital Bichat, université Paris-Diderot, AP-HP, 75018 Paris, France
| | - J De Blic
- Service de pneumologie et allergologie pédiatriques, hôpital Necker-Enfants-Malades, 75743 Paris, France
| | - J-C Dubus
- Unité de pneumologie et médecine infantile, hôpital Nord, 13000 Marseille, France
| | - I Tillié-Leblond
- Service de pneumo-allergologie, CHRU de Lille, 59000 Lille, France
| | - P Chanez
- UMR 7333 Inserm U 1067, service de pneumologie, hôpital Nord, université Aix Marseille, AP-HM, 13000 Marseille, France
| |
Collapse
|
|
11
|
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.
Collapse
|
|
12
|
Draijer C, Hylkema MN, Boorsma CE, Klok PA, Robbe P, Timens W, Postma DS, Greene CM, Melgert BN. Sexual maturation protects against development of lung inflammation through estrogen. Am J Physiol Lung Cell Mol Physiol 2015; 310:L166-74. [PMID: 26608529 DOI: 10.1152/ajplung.00119.2015] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 11/20/2015] [Indexed: 02/06/2023] Open
Abstract
Increasing levels of estrogen and progesterone are suggested to play a role in the gender switch in asthma prevalence during puberty. We investigated whether the process of sexual maturation in mice affects the development of lung inflammation in adulthood and the contributing roles of estrogen and progesterone during this process. By inducing ovalbumin-induced lung inflammation in sexually mature and immature (ovariectomized before sexual maturation) adult mice, we showed that sexually immature adult mice developed more eosinophilic lung inflammation. This protective effect of "puberty" appears to be dependent on estrogen, as estrogen supplementation at the time of ovariectomy protected against development of lung inflammation in adulthood whereas progesterone supplementation did not. Investigating the underlying mechanism of estrogen-mediated protection, we found that estrogen-treated mice had higher expression of the anti-inflammatory mediator secretory leukoprotease inhibitor (SLPI) and lower expression of the proasthmatic cytokine IL-33 in parenchymal lung tissue and that their expressions colocalized with type II alveolar epithelial cells (AECII). Treating AECII directly with SLPI significantly inhibited IL-33 production upon stimulation with ATP. Our data suggest that estrogen during puberty has a protective effect on asthma development, which is accompanied by induction of anti-inflammatory SLPI production and inhibition of proinflammatory IL-33 production by AECII.
Collapse
Affiliation(s)
- Christina Draijer
- University of Groningen, Department of Pharmacokinetics, Toxicology, and Targeting, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands;
| | - Machteld N Hylkema
- University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands
| | - Carian E Boorsma
- University of Groningen, Department of Pharmacokinetics, Toxicology, and Targeting, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands
| | - Pieter A Klok
- University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands
| | - Patricia Robbe
- University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands
| | - Wim Timens
- University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands
| | - Dirkje S Postma
- University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands
| | - Catherine M Greene
- Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland; and
| | - Barbro N Melgert
- University of Groningen, Department of Pharmacokinetics, Toxicology, and Targeting, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands
| |
Collapse
|
|
13
|
Williams N, Johnson M, Hunter K, Sharpe G. Reproducibility of the bronchoconstrictive response to eucapnic voluntary hyperpnoea. Respir Med 2015; 109:1262-7. [DOI: 10.1016/j.rmed.2015.08.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 07/20/2015] [Accepted: 08/10/2015] [Indexed: 10/23/2022]
|
|
14
|
Exhaled nitric oxide is associated with cyclic changes in sexual hormones. Pulm Pharmacol Ther 2013; 26:644-8. [DOI: 10.1016/j.pupt.2013.04.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Revised: 04/24/2013] [Accepted: 04/25/2013] [Indexed: 11/19/2022]
|
|
15
|
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.
Collapse
Affiliation(s)
- Ferenc Macsali
- Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
16
|
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.
Collapse
|
|
17
|
Wegienka G, Hasiec E, Boushey H, Johnson CC, Strickler R, Zoratti E, Havstad S. Studying forced expiratory volume at 1 second over menstrual segments in asthmatic and non-asthmatic women: assessing protocol feasibility. BMC Res Notes 2012; 5:261. [PMID: 22642760 PMCID: PMC3392749 DOI: 10.1186/1756-0500-5-261] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Accepted: 05/29/2012] [Indexed: 12/25/2022] Open
Abstract
Background Sex hormones may play an important role in observed gender differences in asthma incidence and severity, as well as in the observed changes in asthma symptoms during times of hormonal fluctuation (i.e.; premenstrual, pregnancy, etc.). This pilot study sought to demonstrate the feasibility of data collection methods to investigate the effects of sex hormones on lung function in women. Findings A cohort of 13 women (6 with and 7 without prior asthma diagnoses) who were having menstrual periods and were not taking hormones collected urine samples daily for measurement of estrogen (estrone E1C) and progesterone (Pregnanediol-glucuronide PDG) metabolites over the course of a menstrual segment (bleeding episode plus the following bleeding-free interval). Hormones were used to estimate menstrual segment phase (follicular versus luteal) based on a published algorithm. Daily bleeding and FEV1 measurements were recorded and percent predicted FEV1 was calculated. Percent predicted FEV1 decreased over the course of the follicular but not the luteal phase. More specifically, among women without a prior asthma diagnosis, the E1C/PDG ratio and E1C and PDG were individually associated with FEV1 in the follicular phase. No associations were found between hormones and percent predicted FEV1 in the luteal phase or among asthmatic women. E1C was associated with FEV1 in the five days before bleeding onset only among non-asthmatic women. Discussion A study of contiguous daily hormones and symptoms over menstrual segments from a large group of women with and without asthma is needed to better determine within-woman cyclicity of the observed patterns.
Collapse
Affiliation(s)
- Ganesa Wegienka
- Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA.
| | | | | | | | | | | | | |
Collapse
|
|
18
|
Pereira-Vega A, Sánchez JL, Maldonado JA, Borrero F, Rico IV, Vázquez R, Alvarez F, Ignacio JM, Romero P, Gil FL. Premenstrual asthma and atopy markers. Ann Allergy Asthma Immunol 2010; 105:218-22. [PMID: 20800788 DOI: 10.1016/j.anai.2010.06.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2010] [Revised: 06/11/2010] [Accepted: 06/29/2010] [Indexed: 12/27/2022]
Abstract
BACKGROUND The frequency of atopy in women with premenstrual asthma (PMA) and its possible effect on the premenstrual exacerbation of asthma are unknown. OBJECTIVE To analyze the relation between atopy markers (total IgE, Phadiatop, and specific IgE) and PMA. METHODS Asthmatic women of reproductive age completed a questionnaire about respiratory symptoms and recorded peak flow during an entire menstrual cycle to be classified as asthmatic patients with or without PMA. Their asthma severity was graded according to the 2005 Global Initiative for Asthma scale. PMA was defined as a clinical or functional exacerbation (>or=20%) in the premenstrual phase compared with the preovulatory phase. Blood tests for several atopy markers were conducted for: total IgE and screening for aeroallergens (Phadiatop) and specific IgE. RESULTS Blood determinations were performed in 59 asthmatic women, of whom 31 (53%) had PMA. Twenty-six patients with PMA (84%) and 12 without PMA (43%) had total IgE values greater than 100 kU/L (P=.001). Twenty-one patients with PMA (68%) and 14 without PMA (50%) tested positive for Phadiatop (P=.17). Those who were positive for Phadiatop were also tested for specific IgE. No relation was found between specific IgE and PMA; values for ryegrass (63%), olive (60%), and Dermatophagoides pteronyssinus (54%) exceeded 0.35 kU/L. CONCLUSIONS PMA seems to be closely linked to total IgE levels but not to specific allergens. The atopy affects the clinical manifestations of PMA in women of reproductive age.
Collapse
Affiliation(s)
- Antonio Pereira-Vega
- Pneumology Section, Hospital Juan Ramón Jiménez de Huelva, Department of Nursing, University of Huelva, Huelva, Spain.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
19
|
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.
Collapse
Affiliation(s)
- Inseon S Choi
- Department of Allergy, Chonnam National University Medical School, Gwangju, Korea
| |
Collapse
|