|
1
|
Hollinger MK, Grayson EM, Ferreira CM, Sperling AI. Harnessing the Farm Effect: Microbial Products for the Treatment and Prevention of Asthma Throughout Life. Immunol Rev 2025; 330:e70012. [PMID: 40035333 PMCID: PMC11877632 DOI: 10.1111/imr.70012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 02/10/2025] [Indexed: 03/05/2025]
Abstract
It has long been appreciated that farm exposure early in life protects individuals from allergic asthma. Understanding what component(s) of this exposure is responsible for this protection is crucial to understanding allergic asthma pathogenesis and developing strategies to prevent or treat allergic asthma. In this review, we introduce the concept of Farm-Friends, or specific microbes associated with both a farm environment and protection from allergic asthma. We review the mechanism(s) by which these Farm-Friends suppress allergic inflammation, with a focus on the molecule(s) produced by these Farm-Friends. Finally, we discuss the relevance of Farm-Friend administration (oral vs. inhaled) for preventing the development and severity of allergic asthma throughout childhood and adulthood. By developing a fuller understanding of which Farm-Friends modulate host immunity, a greater wealth of prophylactic and therapeutic options becomes available to counter the current allergy epidemic.
Collapse
Affiliation(s)
- Maile K. Hollinger
- Beirne B. Carter Center for Immunology ResearchUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Emily M. Grayson
- Beirne B. Carter Center for Immunology ResearchUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Microbiology, Immunology, and Cancer BiologyUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Caroline M. Ferreira
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
- Institute of Environmental, Chemistry and Pharmaceutics Sciences, Department of Pharmaceutics SciencesFederal University of São PauloSão PauloBrazil
| | - Anne I. Sperling
- Beirne B. Carter Center for Immunology ResearchUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Medicine, Pulmonary and Critical CareUniversity of VirginiaCharlottesvilleVirginiaUSA
- Department of Microbiology, Immunology, and Cancer BiologyUniversity of VirginiaCharlottesvilleVirginiaUSA
| |
Collapse
|
|
2
|
Harvey BJ, McElvaney NG. Sex differences in airway disease: estrogen and airway surface liquid dynamics. Biol Sex Differ 2024; 15:56. [PMID: 39026347 PMCID: PMC11264786 DOI: 10.1186/s13293-024-00633-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 07/03/2024] [Indexed: 07/20/2024] Open
Abstract
Biological sex differences exist for many airway diseases in which females have either worse or better health outcomes. Inflammatory airway diseases such as cystic fibrosis (CF) and asthma display a clear male advantage in post-puberty while a female benefit is observed in asthma during the pre-puberty years. The influence of menstrual cycle stage and pregnancy on the frequency and severity of pulmonary exacerbations in CF and asthma point to a role for sex steroid hormones, particularly estrogen, in underpinning biological sex differences in these diseases. There are many ways by which estrogen may aggravate asthma and CF involving disturbances in airway surface liquid (ASL) dynamics, inappropriate hyper-immune and allergenic responses, as well as exacerbation of pathogen virulence. The deleterious effect of estrogen on pulmonary function in CF and asthma contrasts with the female advantage observed in airway diseases characterised by pulmonary edema such as pneumonia, acute respiratory distress syndrome (ARDS) and COVID-19. Airway surface liquid hypersecretion and alveolar flooding are hallmarks of ARDS and COVID-19, and contribute to the morbidity and mortality of severe forms of these diseases. ASL dynamics encompasses the intrinsic features of the thin lining of fluid covering the airway epithelium which regulate mucociliary clearance (ciliary beat, ASL height, volume, pH, viscosity, mucins, and channel activating proteases) in addition to innate defence mechanisms (pathogen virulence, cytokines, defensins, specialised pro-resolution lipid mediators, and metabolism). Estrogen regulation of ASL dynamics contributing to biological sex differences in CF, asthma and COVID-19 is a major focus of this review.
Collapse
Affiliation(s)
- Brian J Harvey
- Faculty of Medicine and Health Sciences, Royal College of Surgeons in Ireland, 126 St Stephens Green, Dublin 2, Ireland.
- Department of Medicine, RCSI ERC, Beaumont Hospital, Dublin 2, Ireland.
| | - Noel G McElvaney
- Faculty of Medicine and Health Sciences, Royal College of Surgeons in Ireland, 126 St Stephens Green, Dublin 2, Ireland
| |
Collapse
|
|
3
|
Trivedi S, Deering-Rice CE, Aamodt SE, Huecksteadt TP, Myers EJ, Sanders KA, Paine R, Warren KJ. Progesterone amplifies allergic inflammation and airway pathology in association with higher lung ILC2 responses. Am J Physiol Lung Cell Mol Physiol 2024; 327:L65-L78. [PMID: 38651968 PMCID: PMC11380947 DOI: 10.1152/ajplung.00207.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 03/02/2024] [Accepted: 04/22/2024] [Indexed: 04/25/2024] Open
Abstract
Perimenstrual worsening of asthma occurs in up to 40% of women with asthma, leading to increased acute exacerbations requiring clinical care. The role of sex hormones during these times remains unclear. In the current study, we used a translational approach to determine whether progesterone exacerbates allergic inflammation in the traditional chicken egg ovalbumin (OVA) model in BALB/c mice. Simultaneously, we used peripheral blood mononuclear cells (PBMC) from healthy human donors to assess the effects of progesterone on circulating group 2 innate lymphoid cells (ILC2). Briefly, lungs of ovariectomized (OVX) or sham-operated female (F-Sham) controls were implanted with a progesterone (P4, 25 mg) (OVX-P4) or placebo pellet (OVX-Placebo), followed by sensitization and challenge with ovalbumin (OVA). Progesterone increased total inflammatory histologic scores, increased hyper-responsiveness to methacholine (MCh), increased select chemokines in the bronchoalveolar lavage (BAL) and serum, and increased ILC2 and neutrophil numbers, along the airways compared with F-Sham-OVA and OVX-Placebo-OVA animals. Lung ILC2 were sorted from F-Sham-OVA, OVX-Placebo-OVA and OVX-P4-OVA treated animals and stimulated with IL-33. OVX-P4-OVA lung ILC2 were more responsive to interleukin 33 (IL-33) compared with F-Sham-OVA treated, producing more IL-13 and chemokines following IL-33 stimulation. We confirmed the expression of the progesterone receptor (PR) on human ILC2, and showed that P4 + IL-33 stimulation also increased IL-13 and chemokine production from human ILC2. We establish that murine ILC2 are capable of responding to P4 and thereby contribute to allergic inflammation in the lung. We confirmed that human ILC2 are also hyper-responsive to P4 and IL-33 and likely contribute to airway exacerbations following allergen exposures in asthmatic women with increased symptoms around the time of menstruation.NEW & NOTEWORTHY There is a strong association between female biological sex and severe asthma. We investigated the allergic immune response, lung pathology, and airway mechanics in the well-described chicken egg ovalbumin (OVA) model with steady levels of progesterone delivered throughout the treatment period. We found that progesterone enhances the activation of mouse group 2 innate lymphoid cells (ILC2). Human ILC2 are also hyper-responsive to progesterone and interleukin 33 (IL-33), and likely contribute to airway exacerbations following allergen exposures in women with asthma.
Collapse
Affiliation(s)
- Shubhanshi Trivedi
- Division of Infectious Disease, Department of Internal Medicine, University of Utah, Salt Lake City, Utah, United States
- George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States
| | - Cassandra E Deering-Rice
- Department of Pharmacology and Toxicology, University of Utah College of Pharmacy, Salt Lake City, Utah, United States
| | - Samuel E Aamodt
- Division of Pulmonary Medicine, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, United States
| | - Thomas P Huecksteadt
- George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States
| | - Elizabeth J Myers
- Division of Neuroimmunology, Department of Neurology, University of Utah Health, Salt Lake City, Utah, United States
| | - Karl A Sanders
- Division of Pulmonary Medicine, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, United States
- George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States
| | - Robert Paine
- Division of Pulmonary Medicine, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, United States
- George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States
| | - Kristi J Warren
- Division of Pulmonary Medicine, Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah, United States
- George E. Whalen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States
| |
Collapse
|
|
4
|
Zhong Z, Chen M, Dai S, Wang Y, Yao J, Shentu H, Huang J, Yu C, Zhang H, Wang T, Ren W. Association of cesarean section with asthma in children/adolescents: a systematic review and meta-analysis based on cohort studies. BMC Pediatr 2023; 23:571. [PMID: 37974127 PMCID: PMC10652517 DOI: 10.1186/s12887-023-04396-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 10/29/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Whether cesarean section (CS) is a risk factor for asthma in offspring is controversial. The purpose of this study was to investigate the association between CS and asthma in children/adolescents. METHODS Pubmed, Embase, Web of Science, and Cochrane Library electronic databases were searched for cohort studies on the relationship between mode of delivery and asthma in children/adolescents up to February 2023. Birth via CS was considered an exposure factor. Asthma incidence was taken as a result. RESULTS Thirty-five cohort studies (thirteen prospective and twenty-two retrospective cohort studies) were included. The results showed that the incidence of asthma was higher in CS offspring (odds ratio (OR) = 1.18, P < 0.001) than in the vaginal delivery (VD) group. Partial subgroup analyses showed a higher incidence of asthma in female offspring born via CS (OR = 1.26, P < 0.001) compared with the VD group, while there was no difference in males (OR = 1.07, P = 0.325). Asthma incidence was higher in CS offspring than in the VD group in Europe (OR = 1.20, P < 0.001), North America (OR = 1.15, P < 0.001), and Oceania (OR = 1.06, P = 0.008). This trend was not found in the Asian population (OR = 1.17, P = 0.102). The incidence of atopic asthma was higher in offspring born via CS (OR = 1.14, P < 0.001) compared to the VD group. The CS group had a higher incidence of persistent asthma, but the difference did not reach statistical significance (OR = 1.15, P = 0.063). CONCLUSION In this meta-analysis, CS may be a risk factor for asthma in offspring children/adolescents compared with VD. The relationship between CS and asthma was influenced by sex and region.
Collapse
Affiliation(s)
- Ziwei Zhong
- Emergency Medical Center, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China
| | - Meiling Chen
- The Public Health College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Senjie Dai
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yu Wang
- College of Pharmacy, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jie Yao
- The Public Health College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Haojie Shentu
- The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jianing Huang
- The Public Health College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Chiyuan Yu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Hongrui Zhang
- The Medical Technology and Information Engineering College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Tianyue Wang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Wei Ren
- General Family Medicine, Ningbo Yinzhou No. 2 Hospital, 998 North Qianhe Road, Yinzhou District, Ningbo, 315100, Zhejiang, China.
| |
Collapse
|
|
5
|
Alshehre YM, Almutairi SM. Prevalence of falls among adult mothers in Saudi Arabia: a cross-sectional study. BMC Womens Health 2023; 23:587. [PMID: 37946121 PMCID: PMC10636813 DOI: 10.1186/s12905-023-02760-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 11/02/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND The prevalence of falls among mothers (18-49 years old) in Saudi Arabia has been overlooked and understudied. Therefore, the study aimed to identify the 1-year prevalence, rate of falls, and consequent injuries among mothers in Saudi Arabia. METHODS In this cross-sectional study, a self-administered online questionnaire, including sociodemographic data and questions related to the history of falls and consequent injuries during the past 12 months, was disseminated through social media in Saudi Arabia. RESULTS A convenience sample of 986 mothers were voluntarily recruited for this study with a median age of 33 years and an interquartile range of 10 years. The 1-year prevalence of falls among mothers was 14.1 % (n = 139), and 52.5 % (n = 73/139) of the fallers experienced more than one fall. Among mothers who had experienced a fall, 25.4 % (n = 33/139) experienced a fall incident during pregnancy. The reported consequences of falls were pain in 37.4 % (n = 52/139), muscle and ligament injuries in 7.2 % (n = 10/139), and fractures in 2.2 % (n = 3/139) of participants. The study's findings indicate that asthma and high cholesterol level predicts the risk of falls in mothers. CONCLUSIONS According to our convenience sampling, 14.1% of mothers had experienced one or more falls in the past 12 months. The increased prevalence of falls among this age group of women supports the idea that falls are not only an issue for the older adult population, but fall prevention strategies for this age range are also needed.
Collapse
Affiliation(s)
- Yousef M Alshehre
- Department of Physiotherapy, Faculty of Applied Medical Sciences, University of Tabuk, 71491 University of Tabuk, Tabuk, 47713, Saudi Arabia.
| | - Sattam M Almutairi
- Physiotherapy Department, College of Medical Rehabilitation Science, Qassim University, Buraydah, Saudi Arabia
| |
Collapse
|
|
6
|
Gonzalez-Uribe V, Romero-Tapia SJ, Castro-Rodriguez JA. Asthma Phenotypes in the Era of Personalized Medicine. J Clin Med 2023; 12:6207. [PMID: 37834850 PMCID: PMC10573947 DOI: 10.3390/jcm12196207] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/19/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
Asthma is a widespread disease affecting approximately 300-million people globally. This condition leads to significant morbidity, mortality, and economic strain worldwide. Recent clinical and laboratory research advancements have illuminated the immunological factors contributing to asthma. As of now, asthma is understood to be a heterogeneous disease. Personalized medicine involves categorizing asthma by its endotypes, linking observable characteristics to specific immunological mechanisms. Identifying these endotypic mechanisms is paramount in accurately profiling patients and tailoring therapeutic approaches using innovative biological agents targeting distinct immune pathways. This article presents a synopsis of the key immunological mechanisms implicated in the pathogenesis and manifestation of the disease's phenotypic traits and individualized treatments for severe asthma subtypes.
Collapse
Affiliation(s)
- Victor Gonzalez-Uribe
- Alergia e Inmunología Clínica, Hospital Infantil de México Federico Gómez, Ciudad de Mexico 06720, Mexico;
- Facultad Mexicana de Medicina, Universidad La Salle México, Ciudad de Mexico 14000, Mexico
| | - Sergio J. Romero-Tapia
- Health Sciences Academic Division (DACS), Universidad Juárez Autónoma de Tabasco, Villahermosa 86040, Mexico;
| | - Jose A. Castro-Rodriguez
- Department of Pediatric Pulmonology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile
| |
Collapse
|
|
7
|
Taunk ST, Cardet JC, Ledford DK. Clinical implications of asthma endotypes and phenotypes. Allergy Asthma Proc 2022; 43:375-382. [PMID: 36065106 DOI: 10.2500/aap.2022.43.220047] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background: Asthma is a complex disorder with variable clinical expression. Recognizable clinical and laboratory features define phenotypes, and specific biologic pathways define endotypes. Identifying the specific pathway responsible for persistent asthma would enable the clinician to select the optimal inhibitors, which currently are biologic therapies. Objective: To provide an up-to-date review of the current clinical status of endotype and phenotype characterizations of asthma and discuss these categories in relation to the available, or likely available, biologic therapies for asthma. Methods: The medical literature was reviewed based on the search terms: asthma biologics, severe asthma, uncontrolled asthma, corticosteroid-dependent asthma, phenotype, endotype, and type 2. We also used our knowledge of the literature and current research. Results: All of the current biologics, including the recently approved tezepelumab, were most effective with increased type 2 biomarkers, which identify exacerbation-prone asthma. Current biomarkers do not permit consistent identification of specific endotypes to facilitate informed selection of the optimal therapy for an individual patient. Thus, empiricism and the art of care continue to play major roles in treatment selection. Conclusion: Current biologic therapies for asthma and those likely to be U.S. Food and Drug Administration approved within the near future work best in subjects with strong type 2 signatures. Available biomarkers and observable characteristics do not enable clinicians to recognize specific endotypes, but rather subphenotypes or overlapping endotypes. The goal of identifying the optimal patient for a specific therapy remains elusive, but worthy of pursuit. In the interim, the availability of an increasing number of treatment options allows the clinician to help most of his or her patients.
Collapse
|
|
8
|
Somayaji R, Chalmers JD. Just breathe: a review of sex and gender in chronic lung disease. Eur Respir Rev 2022; 31:31/163/210111. [PMID: 35022256 DOI: 10.1183/16000617.0111-2021] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 08/20/2021] [Indexed: 01/08/2023] Open
Abstract
Chronic lung diseases are the third leading cause of death worldwide and are increasing in prevalence over time. Although much of our traditional understanding of health and disease is derived from study of the male of the species - be it animal or human - there is increasing evidence that sex and gender contribute to differences in disease risk, prevalence, presentation, severity, treatment approach, response and outcomes. Chronic obstructive pulmonary disease, asthma and bronchiectasis represent the most prevalent and studied chronic lung diseases and have key sex- and gender-based differences which are critical to consider and incorporate into clinical and research approaches. Mechanistic differences present opportunities for therapeutic development whereas behavioural and clinical differences on the part of patients and providers present opportunities for greater education and understanding at multiple levels. In this review, we seek to summarise the sex- and gender-based differences in key chronic lung diseases and outline the clinical and research implications for stakeholders.
Collapse
Affiliation(s)
- Ranjani Somayaji
- Dept of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada .,Dept of Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, Canada.,Dept of Community Health Sciences, University of Calgary, Calgary, Canada
| | - James D Chalmers
- Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
| |
Collapse
|
|
9
|
Mainguy-Seers S, Diaw M, Lavoie JP. Lung Function Variation during the Estrus Cycle of Mares Affected by Severe Asthma. Animals (Basel) 2022; 12:ani12040494. [PMID: 35203202 PMCID: PMC8868231 DOI: 10.3390/ani12040494] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/15/2022] [Accepted: 02/12/2022] [Indexed: 12/04/2022] Open
Abstract
Simple Summary The estrus cycle and sex hormones influence asthma development and severity in humans, but whether the same is occurring in the asthma of horses is unknown. Severe equine asthma (SEA) is characterized by breathing difficulty, even at rest, and although it can be controlled by management and medication, it remains incurable. Stabling and hay feeding are the main contributors to disease exacerbation, but other factors could possibly alter the respiratory compromise. Therefore, the objective of this study was to evaluate the effects of the estrus cycle on airway dysfunction in five mares affected by SEA by assessing the lung function during the follicular and luteal phases of the reproductive cycle. The inspiratory obstruction improved during the luteal phase and the variation in progesterone and the dominant follicle size correlated with lung function parameters, suggesting a role for sex hormones in asthma pathophysiology. This first description of the estrus cycle’s modulation of airway obstruction in horses supports further studies to uncover the effects of sex hormones in asthma in horses and humans. Abstract While the prevalence of asthma is higher in boys than in girls during childhood, this tendency reverses at puberty, suggesting an effect of sex hormones on the disease pathophysiology. Fluctuations of asthma severity concurring with the estrus cycle are reported in women, but this phenomenon has never been investigated in mares to date. The objective of this exploratory study was to determine whether the estrus cycle modulates airway obstruction in severe equine asthma (SEA). Five mares with SEA during exacerbation of the disease were studied. The whole breath, expiratory and inspiratory resistance, and reactance were compared during the follicular and luteal phases of the estrus cycle. The reproductive tract was evaluated by rectal palpation, ultrasound, and serum progesterone levels. The inspiratory resistance and reactance improved during the luteal phase of the estrus cycle, and variation in progesterone levels and the dominant follicle size correlated with several lung function parameters. The fluctuation of airway dysfunction during the estrus cycle is noteworthy as deterioration of the disease could perhaps be expected and prevented by horse owners and veterinarians. Further studies are required to determine if the equine species could be a suitable model to evaluate the effects of sex hormones on asthma.
Collapse
|
|
10
|
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.
Collapse
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
| |
Collapse
|
|
11
|
Gaffin JM, Castro M, Bacharier LB, Fuhlbrigge AL. The Role of Comorbidities in Difficult-to-Control Asthma in Adults and Children. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:397-408. [PMID: 34863928 PMCID: PMC8837696 DOI: 10.1016/j.jaip.2021.11.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/29/2021] [Accepted: 11/22/2021] [Indexed: 02/07/2023]
Abstract
Assessment of asthma comorbidities, conditions that adversely affect the pathobiology of asthma or impair its response to therapies, is a fundamental step in the evaluation and management of patients with difficult-to-treat asthma. Identifying and effectively treating asthma comorbidities, such as obesity, obstructive sleep apnea, and chronic sinusitis with nasal polyps, may improve asthma control and reduce exacerbations. In addition, identifying comorbid T2 inflammatory conditions may help guide optimal selection of biologic therapies. Here, we describe common comorbid conditions found in adult and pediatric difficult-to-control asthma, discuss evidence for the association with asthma morbidity and treatment benefit, and provide information on how and when to assess comorbidities.
Collapse
Affiliation(s)
- Jonathan M. Gaffin
- Division of Pulmonary Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston MA, USA
| | - Mario Castro
- Division of Pulmonary, Critical Care Medicine, University of Kansas School of Medicine, Kansas City, KS, USA
| | - Leonard B. Bacharier
- Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN, USA
| | - Anne L. Fuhlbrigge
- Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA
| |
Collapse
|
|
12
|
Chowdhury NU, Guntur VP, Newcomb DC, Wechsler ME. Sex and gender in asthma. Eur Respir Rev 2021; 30:210067. [PMID: 34789462 PMCID: PMC8783601 DOI: 10.1183/16000617.0067-2021] [Citation(s) in RCA: 211] [Impact Index Per Article: 52.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 06/26/2021] [Indexed: 12/16/2022] Open
Abstract
Asthma is a heterogenous disease, and its prevalence and severity are different in males versus females through various ages. As children, boys have an increased prevalence of asthma. As adults, women have an increased prevalence and severity of asthma. Sex hormones, genetic and epigenetic variations, social and environmental factors, and responses to asthma therapeutics are important factors in the sex differences observed in asthma incidence, prevalence and severity. For women, fluctuations in sex hormone levels during puberty, the menstrual cycle and pregnancy are associated with asthma pathogenesis. Further, sex differences in gene expression and epigenetic modifications and responses to environmental factors, including SARS-CoV-2 infections, are associated with differences in asthma incidence, prevalence and symptoms. We review the role of sex hormones, genetics and epigenetics, and their interactions with the environment in the clinical manifestations and therapeutic response of asthma.
Collapse
Affiliation(s)
- Nowrin U Chowdhury
- Dept of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA
- The NJH Cohen Family Asthma Institute, Denver, CO, USA
- Equal contribution to first authorship
| | - Vamsi P Guntur
- Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO, USA
- The NJH Cohen Family Asthma Institute, Denver, CO, USA
- Equal contribution to first authorship
| | - Dawn C Newcomb
- Dept of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN, USA
- Dept of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael E Wechsler
- Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO, USA
- The NJH Cohen Family Asthma Institute, Denver, CO, USA
| |
Collapse
|
|
13
|
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
|
|
14
|
Abstract
PURPOSE OF REVIEW The incidence of allergic diseases such as asthma, rhinitis and atopic dermatitis has risen at an alarming rate over the last century. Thus, there is a clear need to understand the critical factors that drive such pathologic immune responses. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that has emerged as an important regulator of multiple cell types involved in the inflammatory response to allergens; from airway epithelial cells to T Helper (TH) cells. RECENT FINDINGS Initial studies suggested that agonists of PPAR-γ could be employed to temper allergic inflammation, suppressing pro-inflammatory gene expression programs in epithelial cells. Several lines of work now suggest that PPAR-γ plays an essential in promoting 'type 2' immune responses that are typically associated with allergic disease. PPAR-γ has been found to promote the functions of TH2 cells, type 2 innate lymphoid cells, M2 macrophages and dendritic cells, regulating lipid metabolism and directly inducing effector gene expression. Moreover, preclinical models of allergy in gene-targeted mice have increasingly implicated PPAR-γ in driving allergic inflammation. Herein, we highlight the contrasting roles of PPAR-γ in allergic inflammation and hypothesize that the availability of environmental ligands for PPAR-γ may be at the heart of the rise in allergic diseases worldwide.
Collapse
Affiliation(s)
- Julian M Stark
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Jonathan M Coquet
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
| | - Christopher A Tibbitt
- Centre for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| |
Collapse
|
|
15
|
Chiarella SE, Cardet JC, Prakash YS. Sex, Cells, and Asthma. Mayo Clin Proc 2021; 96:1955-1969. [PMID: 34218868 PMCID: PMC8262071 DOI: 10.1016/j.mayocp.2020.12.007] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/19/2020] [Accepted: 12/17/2020] [Indexed: 12/15/2022]
Abstract
There are marked sex differences in asthma prevalence and severity. Sex hormones play a central role in these sex biases and directly interact with multiple key cells involved in the pathogenesis of asthma. Here we review the known effects of estrogen, progesterone, and testosterone on airway epithelial cells, airway smooth muscle cells, the mononuclear phagocyte system, innate lymphoid cells, eosinophils, mast cells, T cells, and B cells, all in the context of asthma. Furthermore, we explore unresolved clinical questions, such as the role of sex hormones in the link between asthma and obesity.
Collapse
Affiliation(s)
- Sergio E Chiarella
- Division of Allergic Diseases, Department of Medicine, Mayo Clinic, Rochester, MN
| | - Juan Carlos Cardet
- Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa
| | - Y S Prakash
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN.
| |
Collapse
|
|
16
|
Sex and Gender Differences in Lung Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1304:227-258. [PMID: 34019273 DOI: 10.1007/978-3-030-68748-9_14] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Sex differences in the anatomy and physiology of the respiratory system have been widely reported. These intrinsic sex differences have also been shown to modulate the pathophysiology, incidence, morbidity, and mortality of several lung diseases across the life span. In this chapter, we describe the epidemiology of sex differences in respiratory diseases including neonatal lung disease (respiratory distress syndrome, bronchopulmonary dysplasia) and pediatric and adult disease (including asthma, cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, lymphangioleiomyomatosis, obstructive sleep apnea, pulmonary arterial hypertension, and respiratory viral infections such as respiratory syncytial virus, influenza, and SARS-CoV-2). We also discuss the current state of research on the mechanisms underlying the observed sex differences in lung disease susceptibility and severity and the importance of considering both sex and gender variables in research studies' design and analysis.
Collapse
|
|
17
|
Rodriguez Bauza DE, Silveyra P. Asthma, atopy, and exercise: Sex differences in exercise-induced bronchoconstriction. Exp Biol Med (Maywood) 2021; 246:1400-1409. [PMID: 33794694 DOI: 10.1177/15353702211003858] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Asthma is a chronic inflammatory lung disease affecting approximately 7.7% of the US population. Sex differences in the prevalence, incidence, and severity of asthma have been widely described throughout the lifespan, showing higher rates in boys than girls before puberty, but a reversed pattern in adults. Asthma is often associated with atopy, i.e. the tendency to develop allergic diseases, and can be worsened by environmental stimuli and/or exercise. While not exclusive to patients with asthma, exercise-induced bronchoconstriction (EIB) is a common complication of athletes and individuals who exercise regularly. Currently, there is limited research on sex differences in EIB and its relationship with atopy and asthma in men and women. In this minireview, we summarize the available literature on this topic. Overall, the collective knowledge supports the notion that physiological changes triggered during exercise affect males and females differently, suggesting an interaction among sex, exercise, sex hormones, and atopic status in the course of EIB pathophysiology. Understanding these differences is important to provide personalized management plans to men and women who exercise regularly and suffer from underlying asthma and/or atopy.
Collapse
Affiliation(s)
| | - Patricia Silveyra
- Biobehavioral Laboratory, The University of North Carolina at Chapel Hill, School of Nursing, Chapel Hill, NC 27599, USA.,Department of Environmental and Occupational Health, Indiana University School of Public Health, Bloomington, IN 47405, USA
| |
Collapse
|
|
18
|
Tiwari D, Gupta P. Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment. Front Immunol 2021; 11:594433. [PMID: 33574813 PMCID: PMC7870687 DOI: 10.3389/fimmu.2020.594433] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 12/09/2020] [Indexed: 02/06/2023] Open
Abstract
The escalation in living standards and adoption of 'Western lifestyle' has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific reports bespeak an association between allergic diseases and metabolic dysfunction; hinting toward the critical requirement of organized lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet inflences to overall developmental and physiological processes. As a consequence of such promising attributes, nuclear receptors have historically been at the cutting edge of pharmacy world. This review discusses the recent findings that feature the cardinal importance of nuclear receptors and how they can be instrumental in modulating current asthma pharmacology. Further, it highlights a possible future employment of therapy involving dietary supplements and synthetic ligands that would engage NRs and aid in eliminating both asthma and linked comorbidities. Therefore, uncovering new and evolving roles through analysis of genomic changes would represent a feasible approach in both prevention and alleviation of asthma.
Collapse
Affiliation(s)
| | - Pawan Gupta
- Department of Molecular Biology, Council of Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh, India
| |
Collapse
|
|
19
|
Estradiol and Women's Health: Considering the Role of Estradiol as a Marker in Behavioral Medicine. Int J Behav Med 2020; 27:294-304. [PMID: 32006161 DOI: 10.1007/s12529-019-09820-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The sex hormone estradiol, as measured through saliva, represents a non-invasive and cost-effective approach to understanding the influence of hormonal factors on physical and psychological well-being among women. Estradiol levels dramatically change at hormonal transitions, such as puberty, menopause, and postpartum. It is at these transitions where women are at increased risk for psychological and somatic distress. Salivary estradiol also has implications for decision-making and has been broadly associated with engagement in health-compromising behaviors which can influence women's ability to cope with and manage chronic health conditions. This review summarizes the evidence for salivary estradiol as a marker of physical and psychological health, and discusses practical information regarding saliva collection and assay. The overall intent is to expand and clarify knowledge of the relation between changes in salivary estradiol and women's health as well as to provide a means of integrating salivary estradiol into future behavioral medicine research.
Collapse
|
|
20
|
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.
Collapse
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
| |
Collapse
|
|
21
|
Shah R, Newcomb DC. Sex Bias in Asthma Prevalence and Pathogenesis. Front Immunol 2018; 9:2997. [PMID: 30619350 PMCID: PMC6305471 DOI: 10.3389/fimmu.2018.02997] [Citation(s) in RCA: 134] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 12/04/2018] [Indexed: 12/24/2022] Open
Abstract
Sex-related differences in asthma prevalence are well established and change through the reproductive phases of life. As children, boys have increased prevalence of asthma compared to girls. However, as adults, women have increased prevalence of asthma compared to men. Many factors, including genetics, environment, immunological responses, and sex hormones, affect the sex disparity associated with the development and control of asthma and other allergic diseases. Fluctuations of hormones during puberty, menstruation, pregnancy, and menopause, alter asthma symptoms and severity. In this article, we review clinical and epidemiological studies that examined the sex disparity in asthma and other allergic diseases as well as the role of sex hormones on asthma pathogenesis.
Collapse
Affiliation(s)
- Ruchi Shah
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Dawn C Newcomb
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.,Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, United States
| |
Collapse
|
|
22
|
Fuentes N, Silveyra P. Endocrine regulation of lung disease and inflammation. Exp Biol Med (Maywood) 2018; 243:1313-1322. [PMID: 30509139 DOI: 10.1177/1535370218816653] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
IMPACT STATEMENT Sex-differences in the incidence and severity of inflammatory lung diseases have been recognized for years. Women of reproductive age are more likely to suffer from chronic lung disease, with higher mortality rates than men. Physiological changes in hormone levels such as those occurring during the menstrual cycle, pregnancy, and menopause have been associated with lung function changes and asthma symptoms. Despite this, the roles of sex hormones in the mechanisms associated with lung diseases have not been fully elucidated. This review summarizes basic and clinical studies of sex hormones as potential modulators of lung function and inflammation. The information obtained from sex-specific research on lung physiology and pathology will potentially help in the development of sex-specific therapeutics for inflammatory lung disease that may account for the hormonal status of the patient.
Collapse
Affiliation(s)
- Nathalie Fuentes
- 1 Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Patricia Silveyra
- 1 Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.,2 Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA
| |
Collapse
|
|
23
|
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
|
|
24
|
Young Muslim Women Living with Asthma in Denmark: A Link between Religion and Self-Efficacy. PHARMACY 2018; 6:pharmacy6030073. [PMID: 30041428 PMCID: PMC6165087 DOI: 10.3390/pharmacy6030073] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 07/18/2018] [Accepted: 07/19/2018] [Indexed: 11/17/2022] Open
Abstract
Asthma is a chronic respiratory disease that can be controlled with appropriate medicinal treatment. Adherence to pharmacological treatment is therefore critical. Self-efficacy plays a key role in adherence to medicine in chronic diseases, including asthma. Additionally, ethnic minorities have poor adherence to medicines. However, the impact of religion on self-efficacy and adherence is understudied. Therefore, the aim of this study was to explore the role of self-efficacy in adherence to asthma medicine treatment and the influence of religion on self-efficacy among young, Muslim minority women. A focus group and individual interviews with 10 Muslim minority women (14–24 years of age) living in Denmark were conducted. Data analysis was deductive using Bandura’s theory of self-efficacy and modes of agency. Overall, religion was shown to affect self-efficacy. The women reported changes in self-perceived self-efficacy during the holy month of Ramadan. In addition, praying was used as an alternative to medicine for controlling asthma symptoms. However, the women did not perceive religion and treating asthma with medicine as mutually exclusive, but rather as coexisting for the shared goal of controlling asthma symptoms. It is important for healthcare professionals (HCPs) to be aware of the link between self-efficacy, religion and adherence to asthma medicine treatment. This awareness can aid HCPs in giving advice regarding adherence to asthma treatment, and when monitoring treatment to improve the quality of asthma care for young Muslim minority women.
Collapse
|
|
25
|
Huang YC, Yuan ZF, Yang CH, Shen YJ, Lin JY, Lai CJ. Estrogen Modulates the Sensitivity of Lung Vagal C Fibers in Female Rats Exposed to Intermittent Hypoxia. Front Physiol 2018; 9:847. [PMID: 30026705 PMCID: PMC6041459 DOI: 10.3389/fphys.2018.00847] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Accepted: 06/14/2018] [Indexed: 01/03/2023] Open
Abstract
Obstructive sleep apnea is mainly characterized by intermittent hypoxia (IH), which is associated with hyperreactive airway diseases and lung inflammation. Sensitization of lung vagal C fibers (LVCFs) induced by inflammatory mediators may play a central role in the pathogenesis of airway hypersensitivity. In females, estrogen interferes with inflammatory signaling pathways that may modulate airway hyperreactivity. In this study, we investigated the effects of IH on the reflex and afferent responses of LVCFs to chemical stimulants and lung inflammation in adult female rats, as well as the role of estrogen in these responses. Intact and ovariectomized (OVX) female rats were exposed to room air (RA) or IH for 14 consecutive days. On day 15, IH enhanced apneic responses to right atrial injection of chemical stimulants of LVCFs (e.g., capsaicin, phenylbiguanide, and α,β-methylene-ATP) in intact anesthetized females. Rats subjected to OVX prior to IH exposure exhibited an augmented apneic response to the same dose of stimulants compared with rats subjected to other treatments. Apneic responses to the stimulants were completely abrogated by bilateral vagotomy or perivagal capsaicin treatment, which blocked the neural conduction of LVCFs. Electrophysiological experiments revealed that in IH-exposed rats, OVX potentiated the excitability of LVCFs to stimulants. Moreover, LVCF hypersensitivity in rats subjected to OVX prior to IH exposure was accompanied by enhanced lung inflammation, which was reflected by elevated inflammatory cell infiltration in bronchoalveolar lavage fluid, lung lipid peroxidation, and protein expression of inflammatory cytokines. Supplementation with 17β-estradiol (E2) at a low concentration (30 μg/ml) but not at high concentrations (50 and 150 μg/ml) prevented the augmenting effects of OVX on LVCF sensitivity and lung inflammation caused by IH. These results suggest that ovarian hormones prevent the enhancement of LVCF sensitivity and lung inflammation by IH in female rats, which are related to the effect of low-dose estrogen.
Collapse
Affiliation(s)
- Ya-Chen Huang
- Department of Chest Section, Buddhist Tzu Chi General Hospital, Hualien City, Taiwan.,Master Program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien City, Taiwan
| | - Zung Fan Yuan
- Master Program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien City, Taiwan.,Department of Physiology, Tzu Chi University, Hualien City, Taiwan
| | - Chang-Huan Yang
- Institute of Physiology, National Yang-Ming University, Taipei, Taiwan
| | - Yan-Jhih Shen
- Ph.D. Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Jyun-Yi Lin
- Department of Chest Section, Buddhist Tzu Chi General Hospital, Hualien City, Taiwan.,Master Program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien City, Taiwan
| | - Ching Jung Lai
- Master Program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien City, Taiwan.,Department of Physiology, Tzu Chi University, Hualien City, Taiwan
| |
Collapse
|
|
26
|
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.
Collapse
|
|
27
|
Yung JA, Fuseini H, Newcomb DC. Hormones, sex, and asthma. Ann Allergy Asthma Immunol 2018; 120:488-494. [PMID: 29410216 DOI: 10.1016/j.anai.2018.01.016] [Citation(s) in RCA: 135] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 12/22/2017] [Accepted: 01/12/2018] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To summarize the current literature on the sex disparity in asthma and the role of sex hormone signaling in allergic and neutrophilic airway inflammation. DATA SOURCES PubMed and Centers for Disease Control and Prevention health surveys were searched. STUDY SELECTIONS Clinical and epidemiologic studies in children and adults as well as animal models of asthma were included in this review. RESULTS Compared with males, females have an increase in asthma prevalence starting around puberty, and fluctuations in hormones during menstruation, pregnancy, and menopause are associated with changes in asthma symptoms. Animal studies using genetic deletions of estrogen receptors or androgen receptors have shown that estrogen signaling promotes and androgen signaling attenuates allergen-mediated type 2 airway inflammation. Furthermore, animal studies have found that ovarian hormones are important for interleukin 17A-mediated airway inflammation. CONCLUSION Sex hormones are important in regulating asthma pathogenesis. However, additional studies need to be conducted to further elucidate how sex hormones are initiating and driving the inflammatory response(s) in asthma. Determining these pathways will provide the foundation necessary for the development of treatment strategies and potentially new therapeutics for patients, in particular females, with asthma.
Collapse
Affiliation(s)
- Jeffrey A Yung
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Hubaida Fuseini
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Dawn C Newcomb
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
| |
Collapse
|
|
28
|
Abstract
The menstrual cycle is a physiological phenomenon that is accompanied by several hormonal fluctuations involving oestrogen and progesterone. Oestrogen and progesterone exert several physiological effects. There are many questions pertaining to the influence of the physiology of menstruation on anaesthesia. We attempted to find out whether the phase of the menstrual cycle can alter the physiological functions during anaesthesia, the perioperative management and outcomes. We performed a literature search in Google Scholar, PubMed and Cochrane databases for original and reviewed articles on the phases of the menstrual cycle and their relation to anaesthesia-related physiological parameters to find an answer to these questions. Many studies have shown that women, perimenstrually, may have increased pain perception, exacerbation of systemic diseases, vocal cord/peripheral oedema and post-operative nausea and vomiting (PONV). Some of the other notable findings in most studies were sleep disturbances in the luteal phase (LP), increased occurrence of PONV in the ovulatory phase and a lower requirement of intravenous sedative and anaesthetic drug requirements in the LP. We found contradictory results concerning pain perception and PONV in relation to the follicular and LPs. However, we found that literature regarding the phase of the menstrual cycle and the haemodynamic response to intubation, anaesthesia-induced hypnosis and perioperative blood loss is relatively scarce. Thus, there is a need to conduct good quality research on these topics.
Collapse
Affiliation(s)
- Madhuri S Kurdi
- Department of Anaesthesiology, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India
| | - Ashwini H Ramaswamy
- Department of Anaesthesiology, Karnataka Institute of Medical Sciences, Hubli, Karnataka, India
| |
Collapse
|
|
29
|
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.
Collapse
|
|
30
|
Abstract
Asthma is a common chronic disease that affects over 300 million people worldwide, resulting in a considerable socio-economic burden. Literature data suggest that asthma has a higher incidence in females, particularly at certain stages of pubertal development. Moreover, women seem to experience more asthma symptoms than men and to use more rescue medications, resulting in a reduced quality of life. Although several mechanisms have been proposed to explain these differences, there are not yet final data available in the literature on the role of gender in the pathogenesis of asthma and different behavior in females. Some study suggested a more prevalent hyper-responsiveness in women than in men. Nevertheless, in the literature definitive data on a possible different response to drugs used for asthma between males and females are not described. Understanding the mechanisms that underlie these gender differences in clinical history of asthma patients could give inspiration to new areas of research to obtain a more specific diagnostic and therapeutic approach gender-oriented.
Collapse
|
|
31
|
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
|
|
32
|
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
|
|
33
|
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
|
|
34
|
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
|
|
35
|
Affiliation(s)
- Linda E. Keyes
- Department of Emergency Medicine, University of Colorado, Aurora, Colorado
| |
Collapse
|
|
36
|
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
| | | | | | | | | |
Collapse
|
|
37
|
|
|
38
|
Lisspers K, Ställberg B, Janson C, Johansson G, Svärdsudd K. Sex-differences in quality of life and asthma control in Swedish asthma patients. J Asthma 2013; 50:1090-5. [PMID: 23947390 DOI: 10.3109/02770903.2013.834502] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND To study sex-related differences in quality of life, asthma control and asthma management in different age groups. METHODS A cross-sectional survey and patient record study in primary and secondary care. A total of 1226 patients in primary and 499 in secondary care, ages 18-75 and randomly selected, with a response rate of 71%. Patients were classified into four groups, 18-34, 35-49, 50-64 and 65-75 years. RESULTS Younger women (18-49 years) had a lower total MiniAQLQ score than men in the same age group (5.41 vs. 5.80, p < 0.001), while no significant difference was found between older women and men (50-75 years) (5.08 vs. 5.16, p = 0.42). The sex differences in the younger group remained significant after adjusting for medication, educational level, smoking, body mass index, allergy and depression (p = 0.008). The odds ratios for younger women to have night-awakenings was 1.7 (95%CI 1.07-2.57), for asthma exacerbations 1.9 (95%CI 1.21-2.98) and for not achieving asthma control 1.5 (95%CI 1.00-2.13) when adjusting for smoking, educational level and body mass index. No differences in asthma control were found when comparing older women with men of similar ages. CONCLUSIONS Younger women had lower quality of life and less often asthma control than men in the same age range, while no corresponding sex differences were found between older women and men of similar ages. Female sex hormones could be an important factor affecting these outcomes.
Collapse
Affiliation(s)
- Karin Lisspers
- Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University , Uppsala , Sweden and
| | | | | | | | | |
Collapse
|
|
39
|
Rao CK, Moore CG, Bleecker E, Busse WW, Calhoun W, Castro M, Chung KF, Erzurum SC, Israel E, Curran-Everett D, Wenzel SE. Characteristics of perimenstrual asthma and its relation to asthma severity and control: data from the Severe Asthma Research Program. Chest 2013; 143:984-992. [PMID: 23632943 DOI: 10.1378/chest.12-0973] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control. METHODS Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control. RESULTS Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization. CONCLUSIONS PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype.
Collapse
Affiliation(s)
- Chitra K Rao
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, The University of Pittsburgh Asthma Institute @UPMC and the University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Charity G Moore
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, The University of Pittsburgh Asthma Institute @UPMC and the University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Eugene Bleecker
- Division of Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Department of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC
| | - William W Busse
- Division of Allergy and Clinical Immunology, Department of Medicine, University of Wisconsin-Madison, Madison, WI
| | - William Calhoun
- Division of Allergy, Pulmonary, Immunology, Critical Care, and Sleep, Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX
| | - Mario Castro
- Division of Pulmonary & Critical Care Medicine, Department of Medicine, Washington University in St Louis, St Louis, MO
| | - Kian Fan Chung
- Division of Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Imperial College London, London, England
| | | | - Elliot Israel
- Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Boston, MA
| | - Douglas Curran-Everett
- Division of Biostatistics, Department of Preventive Medicine and Biometrics and Department of Physiology and Biophysics, University of Colorado Denver and National Jewish Health, Denver, CO
| | - Sally E Wenzel
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, The University of Pittsburgh Asthma Institute @UPMC and the University of Pittsburgh School of Medicine, Pittsburgh, PA.
| |
Collapse
|
|
40
|
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
|
|
41
|
Fajt ML, Wenzel SE. Asthma phenotypes in adults and clinical implications. Expert Rev Respir Med 2011; 3:607-25. [PMID: 20477351 DOI: 10.1586/ers.09.57] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
It is becoming increasingly recognized that asthma is a heterogeneous disease, whether based on clinical factors, including the patient's age at diagnosis, symptom spectrum and treatment response, triggering factors, or the level and type of inflammation. Attempts to analyze the importance of these characteristics to the clinical presentation of asthma have led to the appreciation of numerous separate and overlapping asthma phenotypes. However, these approaches are 'biased' and based on the clinician/scientist's own experience. Recently, unbiased approaches have also been attempted using both molecular and statistical tools. Early results from these approaches have supported and expanded on the clinician's concepts. However, until specific biologic markers are identified for any of these proposed phenotypes, the definitive nature of any phenotype will remain speculative.
Collapse
Affiliation(s)
- Merritt L Fajt
- Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh Asthma Institute, School of Medicine, UPMC Montefiore, NW 931 Montefiore, 3459 Fifth Avenue, Pittsburgh, PA 15213, USA.
| | | |
Collapse
|
|
42
|
Abstract
PURPOSE OF REVIEW asthma is a common chronic disease with significant clinical impact worldwide. Sex-related disparities in asthma epidemiology and morbidity exist but debate continues regarding the mechanisms for these differences. There is a need to review the recent findings for asthma care providers and to highlight areas in need of additional research. RECENT FINDINGS recent data illustrate striking sex-related differences in asthma epidemiology and disease expression. Studies show an increased incidence of asthma in women. Data demonstrate that asthmatic women have a poorer quality of life and increased utilization of healthcare compared to their male counterparts despite similar medical treatment and baseline pulmonary function. Research continues to explore hypotheses for these differences including the potential influences of the female sex hormones, altered perception of airflow obstruction, increased bronchial hyper-responsiveness, and medication compliance and technique. However, no single explanation has been able to fully explain the disparities. SUMMARY women are more likely to be diagnosed with asthma and suffer greater morbidity than men. The physiologic mechanisms for these differences are not well understood. Understanding sex-related differences in asthma and providing patients with education geared toward these disparities are important in establishing effective, individualized asthma management strategies for all patients.
Collapse
|
|
43
|
Dratva J, Schindler C, Curjuric I, Stolz D, Macsali F, Gomez FR, Zemp E. Perimenstrual increase in bronchial hyperreactivity in premenopausal women: results from the population-based SAPALDIA 2 cohort. J Allergy Clin Immunol 2010; 125:823-9. [PMID: 20227756 DOI: 10.1016/j.jaci.2009.12.938] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2009] [Revised: 12/08/2009] [Accepted: 12/15/2009] [Indexed: 02/08/2023]
Abstract
BACKGROUND Studies on perimenstrual asthma are inconsistent, and different methodologies limit comparisons. OBJECTIVE To investigate cyclic variations in bronchial hyperreactivity (BHR) to methacholine in premenopausal women in a population-based cohort and assess effect modification by oral contraceptives (OCs). METHODS Day of menstruation cycle at the time of methacholine challenge was calculated in 571 menstruating women without hormonal treatment, age 28 to 58 years, on the basis of questionnaire data from the Swiss cohort study on Air Pollution And Lung Disease In Adults (SAPALDIA) cohort 2001/2002. A window of risk was defined 3 days before and after the first day of menstruation. Logistic and linear regression analyses were performed adjusting for main predictors of BHR and stratifying for asthma status. The impact of OCs was studied in the same sample enlarged by 130 women taking OCs. RESULTS The prevalence of BHR was 13% (fall of > or =20% in FEV(1) up to a maximal cumulative dose of 2 mg), and 6% had asthma. A total of 143 women had undergone methacholine challenge within the risk window. We observed a significant increase in BHR within the window of risk (odds ratio [OR], 2.3; 95% CI, 1.27-4.29). A cyclic association pattern was confirmed by trigonometric functions. Effect modification by asthma status and oral contraceptive use was found, with lower OR in subjects without asthma and OR <1 in women using OCs. CONCLUSION The data provide evidence of a systematic variation in BHR during the menstruation cycle, supporting the hypothesis of a hormonal influence. OCs appear to have a protective effect. Cyclicity of BHR could be of clinical importance in view of future medication recommendations and timing of respiratory function tests in women.
Collapse
Affiliation(s)
- Julia Dratva
- Institute of Social and Preventive Medicine at the Swiss Tropical Institute, Basel, Switzerland.
| | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Rodrigo GJ, Plaza V, Bellido-Casado J, Neffen H, Bazús MT, Levy G, Armengol J. The study of severe asthma in Latin America and Spain (1994-2004): characteristics of patients hospitalized with acute severe asthma. J Bras Pneumol 2010; 35:635-44. [PMID: 19669001 DOI: 10.1590/s1806-37132009000700004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2009] [Accepted: 02/26/2009] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE Studies assessing the characteristics and management of patients hospitalized with asthma have been limited to a small number of facilities and have evaluated short time periods. The present study evaluated long-term changes among hospitalized asthma patients at a large number of facilities. METHODS This was a retrospective, hospital-based observational case series, designated the Study of Severe Asthma in Latin America and Spain, which was conducted in Spain and in eight Latin-American countries. We reviewed the hospital records of 3,038 patients (age range, 15-69 years) hospitalized with acute severe asthma at one of nineteen tertiary-care hospitals in 1994, 1999 and 2004. RESULTS Over time, the use of inhaled corticosteroids and long-acting beta2 agonists increased significantly, whereas the use of theophylline as a controller medication decreased. The utilization of pulmonary function tests also increased. There was a significant reduction in the mean hospital stay (8.5 days, 7.4 days and 7.1 days in 1994, 1999 and 2004, respectively, p = 0.0001) and a significant increase in the mean of the lowest arterial pH at hospital admission. In contrast, there was a significant decrease in the proportion of cases in which PEF was determined in the emergency room (48.6% in 1994 vs. 43.5% in 2004, p = 0.0001). We found the quality of asthma management and care to be generally better in Spain than in Latin America. CONCLUSIONS Although there have been certain improvements in the management of asthma between severe exacerbations and during hospitalization, asthma management remains suboptimal in Spain and, especially, in Latin America.
Collapse
Affiliation(s)
- Gustavo Javier Rodrigo
- Department of Emergency Services, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay.
| | | | | | | | | | | | | |
Collapse
|
|
45
|
Mandhane PJ, Hanna SE, Inman MD, Duncan JM, Greene JM, Wang HY, Sears MR. Changes in exhaled nitric oxide related to estrogen and progesterone during the menstrual cycle. Chest 2009; 136:1301-1307. [PMID: 19617403 DOI: 10.1378/chest.09-0604] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Significant changes in asthma and atopy occur throughout the menstrual cycle. We hypothesized that the characteristics of asthma (eg, symptoms, exhaled nitric oxide [eNO] levels as a marker of airway inflammation, pulmonary function, and atopy) vary throughout the menstrual cycle in relation to changes in the levels of estrogen or progesterone and that this variation is attenuated in women using oral contraception (OC). METHODS Seventeen women with asthma were studied over the course of their menstrual cycle through daily measurements of symptoms, eNO, spirometry, 17beta-estradiol, and progesterone levels, and through the performance of alternate-day allergy skin-prick tests (SPTs). RESULTS Of 534 potential daily visits, 526 (98.5%) were completed. Women not using OC (n = 8) had higher mean eNO levels (48.2 parts per billion [ppb]; 95% CI, 43.1 ppb to 53.3 ppb) than women using OC (27.0 ppb; 95% CI, 24.2 ppb to 29.7 ppb; p <or= 0.005). Among women not using OC, a 10 pmol/L increase in 17beta-estradiol levels was associated with a 15.2-ppm decrease in eNO levels (95% CI, -23.4 ppb to -7.0 ppm; p < 0.005). In contrast, an increase in progesterone level of 0.5 nmol/L was significantly associated with a 10.0-ppb increase in eNO (95% CI, 1.2 ppb to 18.7 ppb; p <or= 0.05). Consistent and significant results were found for 17beta-estradiol and progesterone levels and SPT. There were no significant associations between sex hormones and markers of asthma among women using OC. CONCLUSION During natural menstrual cycles, increases in estrogen levels were associated with decreased eNO levels, whereas increases in progesterone levels were associated with increased eNO levels and SPT wheal size. These effects were not observed among women using OC.
Collapse
Affiliation(s)
- Piush J Mandhane
- Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada.
| | - Steven E Hanna
- Department of Clinical Epidemiology and Biostatistics, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada
| | - Mark D Inman
- Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada
| | - Joanne M Duncan
- Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada
| | - Justina M Greene
- Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada
| | - Hong-Yu Wang
- Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada
| | - Malcolm R Sears
- Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada
| |
Collapse
|
|
46
|
|
|
47
|
Murphy VE, Gibson PG. Premenstrual asthma: prevalence, cycle-to-cycle variability and relationship to oral contraceptive use and menstrual symptoms. J Asthma 2008; 45:696-704. [PMID: 18951263 DOI: 10.1080/02770900802207279] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The prevalence of asthma is higher in women than men of reproductive age and almost half of all hospitalisations for asthma in women occur during the perimenstrual phase of the cycle. The mechanisms of premenstrual asthma (PMA) are unknown and a definition of PMA has not been clearly presented in the literature. The objective of this study was to determine the prevalence of PMA using a variety of definitions, to investigate the cycle-to-cycle variation in PMA, the effects of oral contraceptive use and the relationship between PMA and premenstrual symptoms. Premenopausal women with asthma (n = 28) were prospectively followed for at least 12 weeks over 2-4 consecutive menstrual cycles. Asthma symptoms, beta(2)-agonist and inhaled corticosteroid use and morning and evening peak expiratory flow were recorded daily. The following types of PMA definitions were investigated: self-reported PMA, increased symptoms, increased medication use, decreased peak flow or a combination of changes in symptoms, medication and peak flow. Changes of more than 20%, for at least 2 consecutive days of the luteal phase (last 14 days of the cycle prior to menstruation) compared to the early follicular phase average (first 7 days after menstruation) were considered PMA. Using a composite definition where subjects experienced increased symptoms and medication use with or without a change in peak flow, 16 subjects were classified as having PMA (57%), while 12 did not have PMA. Only 4 subjects (25%) had PMA in every cycle examined. Fifty-five percent of subjects who used oral contraceptives had PMA, while 59% of subjects who did not use oral contraceptives had PMA. Women who were defined PMA using the composite definition were more likely than those without PMA to experience a 20% decrease in peak flow during the luteal phase. There was no relationship between asthma symptoms and premenstrual symptoms on day 1 of the menstrual cycle in women with PMA. PMA resulting in increased symptoms and medication use occurred in 57% of subjects studied for 2-4 menstrual cycles. The use of oral contraceptives is not protective and further work is required to elucidate the mechanisms of PMA.
Collapse
Affiliation(s)
- Vanessa E Murphy
- Centre for Asthma and Respiratory Diseases, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia.
| | | |
Collapse
|
|
48
|
Goksör E, Gustafsson PM, Alm B, Amark M, Wennergren G. Reduced airway function in early adulthood among subjects with wheezing disorder before two years of age. Pediatr Pulmonol 2008; 43:396-403. [PMID: 18306325 DOI: 10.1002/ppul.20798] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
AIM To compare airway function in early adulthood in subjects with wheezing in infancy with age-matched controls and to analyze what accounts for a possible difference. METHODS Asthma development has been prospectively studied in 101 children hospitalized due to wheezing before the age of two. The cohort was re-investigated at age 17-20 years and tested with spirometry and for bronchial hyper-responsiveness and allergic sensitization. An age-matched population (n = 294) was used for comparison. RESULTS The cohort had a significantly lower FEV(1)/FVC ratio and MEF(50), both pre- and post-bronchodilation, compared with the controls, P < 0.01. The reduction in airway function was most evident in current asthmatic female subjects, but a reduced pre-bronchodilation FEV(1)/FVC ratio was also seen in symptom-free cohort subjects, P = 0.03. In the multivariate analysis, female gender was the most prominent independent risk factor for reduced airway function in early adulthood, pre-bronchodilation OR 4.0 (1.4-11.3) and post-bronchodilation OR 8.8 (1.8-42.0). In addition, a history of early wheezing, that is, belonging to the cohort, was an independent risk factor for reduced airway function pre-bronchodilation, OR 3.3 (1.3-8.7). Furthermore, there was an association between current bronchial hyper-responsiveness and an increased risk of reduced airway function post-bronchodilation, OR 7.3 (2.0-26.6). CONCLUSION Reduced airway function in early adulthood was found in subjects with wheezing early in life, compared with age-matched controls. The reduction was most prominent in females with current asthma.
Collapse
Affiliation(s)
- Emma Goksör
- Department of Paediatrics, Göteborg University, Queen Silvia Children's Hospital, Göteborg, Sweden.
| | | | | | | | | |
Collapse
|
|
49
|
Abstract
There has been a recent increase in the prevalence of asthma worldwide; however, the 5-10% of patients with severe disease account for a substantial proportion of the health costs. Although most asthma cases can be satisfactorily managed with a combination of anti-inflammatory drugs and bronchodilators, patients who remain symptomatic despite maximum combination treatment represent a heterogeneous group consisting of those who are under-treated or non-adherent with their prescribed medication. After excluding under-treatment and poor compliance, corticosteroid refractory asthma can be identified as a subphenotype characterised by a heightened neutrophilic airway inflammatory response in the presence or absence of eosinophils, with evidence of increased tissue injury and remodelling. Although a wide range of environmental factors such as allergens, smoking, air pollution, infection, hormones, and specific drugs can contribute to this phenotype, other features associated with changes in the airway inflammatory response should be taken into account. Aberrant communication between an injured airway epithelium and underlying mesenchyme contributes to disease chronicity and refractoriness to corticosteroids. The importance of identifying underlying causative factors and the recent introduction of novel therapeutic approaches, including the targeting of immunoglobulin E and tumour necrosis factor alpha with biological agents, emphasise the need for careful phenotyping of patients with severe disease to target improved management of the individual patient's needs.
Collapse
Affiliation(s)
- Stephen T Holgate
- AIR Division, Level D Centre Block, Southampton General Hospital, Southampton, UK.
| | | |
Collapse
|
|
50
|
Abstract
Asthma exacerbations may be triggered by a number of atmospheric and domiciliary environmental factors as well as by those encountered in schools and workplaces. The majority of exacerbations, particularly in children, coincide with respiratory viral infections, most commonly rhinovirus. As most respiratory viruses and many aeroallergens appear in seasonal patterns, asthma exacerbations, particularly those requiring emergency treatment, show analogous seasonal cycles which differ in form in children and adults. While similar in form between the sexes, they differ in amplitude, with boys having higher risks of exacerbation in childhood and women in adult life. Simultaneous exposure of asthmatics with respiratory viral infections to allergens or air pollutants may significantly increase the risks of exacerbation. Access to and compliance with inhaled corticosteroid treatment is an important predictor of the likelihood of asthma exacerbations occurring, including those that occur during respiratory viral infections. Epidemiologically, the degree of asthma control achieved by asthmatics is an important predictor of the likelihood of disease exacerbation including respiratory failure, death, and health service consumption.
Collapse
Affiliation(s)
- N W Johnston
- Firestone Institute for Respiratory Health, St Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
| | | |
Collapse
|