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Incidence and pathways of gender differences in adult asthma

English title Incidence and pathways of gender differences in adult asthma
Applicant Zemp Stutz Elisabeth
Number 137180
Funding scheme ProDoc
Research institution Schweizerisches Tropen- und Public Health-Institut
Institution of higher education University of Basel - BS
Main discipline Respiratory Diseases
Start/End 01.04.2012 - 31.03.2015
Approved amount 151'565.00
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All Disciplines (2)

Discipline
Respiratory Diseases
Public Health and Health Services

Keywords (4)

asthma; gender ; adults; pathways

Lay Summary (German)

Lead
Lay summary

Asthma bronchiale, eine oft bereits in der Kindheit beginnende, chronisch-entzündliche Erkrankung der Atemwege, zählt mit einer Prävalenz von 5-10% zu den häufigsten chronischen Erkrankungen im Kindes- und Erwachsenenalter. Geschlechtsunterschiede in der Asthma-Häufigkeit sind zwar belegt, aber wenig verstanden.

Hintergrund:

Der Lebenszeitverlauf der Asthma-Inzidenz weist ein auffälliges geschlechtstypisches Muster auf: In der Kindheit ist die Inzidenz von Asthma bei Knaben bis zu zweimal grösser als bei Mädchen, in der Pubertät kehrt sich das Geschlechterverhältnis um und im Erwachsenenalter erkranken mehr Frauen an Asthma als Männer. Die Wissenslage zum Verlauf im höheren Alter ist spärlich und die Abgrenzung zwischen Asthma und chronisch-obstruktiver Lungenerkrankung wird schwieriger. Zur Erklärung dieses Lebenszeitverlaufs von Asthma wurden vorwiegend reproduktive und hormonelle Faktoren herangezogen. Es gibt jedoch eine Reihe weiterer, nichthormoneller Mechanismen, die dazu beitragen können: genetische, immunologische, systemisch-entzündliche Prozesse, Übergewicht, Stoffwechselfaktoren, durch unterschiedliche Zeit-Aktivitätsmuster bedingte Schadstoffexpositionen, Unterschiede bei der Symptom-Präsentation, beim Hilfesucheverhalten oder in der Gesundheitsversorgung (gender biases bei Diagnose und Therapie). Zu wissen, welche dieser „Gender-Pfade“ tatsächlich eine Rolle spielen, ist im Hinblick auf mögliche Konsequenzen von Relevanz: geschlechtsbezogene Empfehlungen können für so unterschiedliche Bereiche wie Test-Settings, Verhaltensempfehlungen oder Sensibilisierung von Ärzten und Ärztinnen zur Vermeidung von Gender biases notwendig sein. In SAPALDIA, einer seit 20 Jahren laufenden Schweizer Kohortenstudie, die eine Studienpopulation mit einem breiten Altersspektrum umfasst,  können solche Erklärungsmechanismen gezielt untersucht werden.

Ziel:

Das Projekt hat zum Ziel, erstens die Asthma-Inzidenz bei erwachsenen Frauen und Männern bis  ins hohe Alter zu bestimmen. Zweitens soll für drei möglich „Gender-Pfade“, die in der SAPALDIA-Studie untersucht werden können, analysiert werden, ob sie beobachtete Geschlechtsunterschiede in der Asthma-Inzidenz erklären können: a) reproduktive und hormonelle Faktoren, b) systemisch-entzündliche Faktoren, c) diagnostische biases.

Bedeutung:

Das Projekt kann einen Beitrag zu offenen Fragen bezüglich Asthma-Inzidenz im höheren Erwachsenenalter sowie zur Erklärung von Geschlechtsunterschieden leisten. Angesichts der Häufigkeit und Krankheitslast von Asthma wie auch angesichts der durch die Epidemie von Übergewicht, Diabetes und des metabolischen Syndroms erwarteten Zunahme von Asthma ist ein besseres Verständnis der Faktoren, die zur Entstehung von Asthma beitragen, von Relevanz.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
Sex, Gender and Respiratory Health.
Zemp E. Hansen S. Schneider C. Dratva J. (2014), Sex, Gender and Respiratory Health., in Viegi G. Lundbäck B. Annesi-Maesano L. (ed.), European Respiratory Society, , Sheffield, 2014, 125-138.
Gender differences in adult onset of asthma: Results from the Swiss SAPALDIA Cohort Study
3. Hansen S Probst-Hensch N Keidel D Dratva J Bettschart R Pons M Burdet L Bridevaux PO Schi, Gender differences in adult onset of asthma: Results from the Swiss SAPALDIA Cohort Study, in European Respiratory Journal .

Collaboration

Group / person Country
Types of collaboration
The European Community Respiratory Health Survey (P.Burney London) Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SAPALDIA Plenary Meeting at SNF Talk given at a conference Gender Differences in Adult-Onset Asthma: Results from the SAPALDIA Cohort 28.11.2014 Bern, Switzerland Probst-Hensch Nicole; Zemp Stutz Elisabeth; Hansen Sofie;
Diss:Kurs event at Basel University Open Day Talk given at a conference Gender Differences in Adult-Onset Asthma: Results from a Swiss Cohort Study 07.10.2014 Basel, Switzerland Hansen Sofie;
European Respiratory Society Annual Congress Poster New-Onset of Asthma: Gender Differences in the SAPALDIA Cohort 08.09.2014 München, Germany Hansen Sofie;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Swiss TPH student seminar Talk 27.04.2015 Basel, Switzerland Hansen Sofie; Zemp Stutz Elisabeth;
Antelope Mentorship Conference ‘JUMP’ Talk 21.11.2014 Basel, Switzerland Hansen Sofie;


Awards

Title Year
European Respiratory Society (ERS) Young Scientist Sponsorship 2014

Associated projects

Number Title Start Funding scheme
177506 SAPALDIA 5 - Cohort on Healthy Aging 01.04.2018 Cohort Studies Large
134276 Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) 01.04.2011 Cohort Studies Large
148470 SAPALDIA Cohort on Healthy Aging 01.04.2014 Cohort Studies Large

Abstract

Asthma, a chronic condition with important consequences in terms of disease burden and health care resources needed, has a complex underlying pathology which is still not fully understood. The incidence of adult asthma is approximately 4/1000 person-years, being higher in women than in men, and seems not to decrease with age, although in the middle-aged and elderly, there is misclassification with COPD. Recent estimates from the SAPALDIA2 study are at 1.39 incident cases per 1000 person-years in non-smokers.An interesting pattern of gender differences across the life span has been documented with higher prevalence rates in boys compared to girls, a reversing of the gender ratio in puberty, and a female preponderance in early adulthood. The picture is less clear for later adulthood, and, in women, for the menopausal transition. The explanation of this gender-differential life course of lung development and asthma is yet insufficient und under-researched. The differences have been related primarily to reproductive status and reproductive hormones. However, further potential mechanisms are likely to contribute to the observed lifetime pattern: asthma seems not to be a condition affecting exclusively the airways but rather be a systemic condition through its relationship with systemic inflammation, obesity, and metabolic factors. Further mechanisms seem to be influential, such as genetic pathways, or immunologic mechanisms. Also, exposure to environmental and occupational exposures may differ in men and women, possibly related to differential time-activity patterns, indoor or outdoor, or to different susceptibility related to airway caliber. Interaction between gender and behavioral factors, help seeking and also management of asthma furthermore are likely to affect disease rates, as it has been evidenced for a gender bias in diagnosis of asthma.The planned PhD project makes use of the ongoing SAPALDIA cohort study, covering now 20 years of longitudinal observation with a broad age range (from 18-60 years 1991 to 38-80 years in 2011) and aims to assess the incidence of asthma in later adulthood and to investigate three gender-related pathways which have a hypothesized impact on asthma incidence and can be tested in the SAPALDIA cohort. The specific project aims of this project are1.To determine the incidence of asthma in men and women across adulthood in the SAPALDIA cohort, for the period of observation from 1991 to 2010/11 2.To investigate the impact of three possibly gender-related pathways on asthma incidence:a. to assess the association between reproductive and hormonal factors and incidence of asthma in women (pathway 1)b.to assess the association between systemic inflammation, obesity and the metabolic syndrome and incidence of asthma in men and women (pathway 2) c.to explore interactions between effects of reproductive factors analysed in a) and effects of the factors analysed in b) for asthma incidenced.to analyse whether there is diagnostic bias for asthma in the SAPALDIA cohort population (pathway 3)The outcome of main interest is new onset of self-reported asthma. The definition of self-report of doctor diagnosed asthma is based on a positive answer to the two following questions: “Have you ever had asthma?” and “Was this confirmed by a doctor?” To define new onset of asthma, those who reported asthma at baseline in 1991 or asthma onset prior to baseline will be excluded. Furthermore, based on post-dilatation spirometry conducted in SAPALDIA3, providing an objective measure for fixed versus reversible obstruction, subjects with COPD (showing fixed obstruction) will be excluded. Sex- and age-specific incidence rates of asthma will be calculated, if possible stratifying also for smoking and atopy, and adjusting for relevant further confounders.The impact of reproductive pathologies (pathway 1) will be investigated in women participating in SAPALDIA2 and 3 who provided reproductive information, have blood measurements and have undergone post-dilatation spirometry in SAPALDIA3. Logistic regression techniques and Cox analyses will be applied. Exposures for pathway 1 consist in reproductive pathologies and exogenous hormonal intake assessed by a Women’s Health Questionnaire in SAPALDIA2 (for n=3’153) and in a more detailed version in SAPALDIA3 in 2011 (estimated n=2’300 postmenopausal and approx. 800 pre-menopausal women). The analyses regarding pathway 2 will be conducted in men and women participating in SAPALDIA 3 (estimated n=6’000) who gave blood and underwent post-dilatation spirometry. Exposures consist in systemic inflammation (hs-CRP), obesity (measured by BMI and anthropometric measures including body shapes across life course) and metabolic factors (blood sugar, HbA1c, self-reported diabetes, tryglicerides and cholesterol). Diagnostic bias (pathway 3) will be analysed in the SAPALDIA2 population, by calculating the likelihood of asthma diagnosis given asthma-like symptoms and bronchial hyper-reactivity in SAPALDIA2. The project, embedded in ongoing research activities of the SAPALDIA cohort and linked to the European Respiratory Health Survey, will contribute to open questions regarding asthma incidence in later adulthood and regarding gender-related differences. Given the importance of asthma in terms of disease burden as well as the epidemics of obesity, diabetes, and the metabolic syndrome, a better understanding of gender-specific risks and potential prevention strategies is warranted. Consequences, recommendations or response to disease and treatment may vary considerably according to these diverse phenomena underlying sex/gender differences.
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