None listed
Conditions
Brief summary
Purpose of Study In Australia, asthma affects >10% of adults and costs $28 billion per year. The highest burden occurs in obese, older women, with non-Type 2 (T2), non-eosinophilic severe asthma, which is resistant to corticosteroids. Severe, steroid-resistant disease is the biggest unmet need in asthma therapy, as patients have greatly reduced quality of life, with poor asthma control, frequent exacerbations and side effects from high-dose steroids. Severe asthma also disproportionately contributes to the economic burden of the disease, accounting for >50% of asthma costs. There are no effective therapies for non-T2 obesity-associated asthma, as the underlying mechanisms are largely unknown. We have pilot data showing that the oral contraceptive pill (OCP) may be more effective than corticosteroids in controlling asthma in women, via effects on inflammation and metabolism (immunometabolism). We will extend upon these findings by examining the relationships between sex hormones, immunometabolism and asthma control in a well-defined clinical population of women with and without obesity. Hypothesis Female sex hormones play a major role in asthma control and asthma severity in women with comorbid asthma and obesity. Aims Aim 1 – Observational cross-sectional study: To characterise the association between female sex hormone levels, inflammatory and metabolic markers, and asthma control in women with and without obesity. Aim 2 – Observational longitudinal study: To examine the effect of hormonal fluctuations on asthma control in pre-menopausal women with and without obesity.
Interventions
Study Groups:
Group 1: Pre-menopause not using the oral contraceptive pill (OCP), non-obese
Group 2: Pre-menopause not using the OCP, obese
Group 3: Pre-menopause using the OCP, non-obese
Group 4: Pre-menopause using the OCP, obese
Group 5: Post-menopause, non-obese
Group 6: Post-menopause, obese
Assessment Schedule:
Groups 1 and 2 will attend THREE study visits as follows:
Each visit will be completed at the same time of day for each participant and the timing will be based on the results of
Study Groups: Group 1: Pre-menopause not using the oral contraceptive pill (OCP), non-obese Group 2: Pre-menopause not using the OCP, obese Group 3: Pre-menopause using the OCP, non-obese Group 4: Pre-menopause using the OCP, obese Group 5: Post-menopause, non-obese Group 6: Post-menopause, obese Assessment Schedule: Groups 1 and 2 will attend THREE study visits as follows: Each visit will be completed at the same time of day for each participant and the timing will be based on the results of ovulation test strips used from day 10 of the menstrual cycle. Day 1 is defined as the first day of menstruation. - Visit E: Estrogen surge (approximately Day 10-14 of menstrual cycle). - Visit P: Progesterone surge (approximately Day 19-23 of the menstrual cycle; 5-9 days after ovulation). - Visit L: Low estrogen/progesterone: Visit L will be completed between 12-16 days post-ovulation (up to and including Day 2 of the following menstrual cycle). Groups 3 and 4 will attend ONE study visit between Day 21-28 of their menstrual cycle (during WEEK THREE of their active pill). Day 1 is defined as the first day of taking the placebo pill. Women who are taking the OCP continuously (without the placebo pills) can complete their visit at any point. Group 5 and 6 will attend ONE study visit. Screening Visit: The screening visit is anticipated to take 1.5 hours. Participants will be screened for study eligibility. This visit will include medical history, medication usage, height, weight, lung function, asthma control and blood pressure. It will also include a mannitol challenge and/or measurement of bronchodilator response (post-bronchodilator FEV1 15 minutes following administration of 400µg salbutamol), if required to confirm variable airflow obstruction (VAO). Pre-menopausal participants not using the OCP will be provided with a peak flow meter to take home and a link to complete an online patient diary. This diary will begin on day 1 of the menstrual cycle (first day of menstruation). Participants will also be provided with 10 Ovulation Test Strips. Study Visit: The study visit is anticipated to take 2 hours. Participants will be instructed to withhold their asthma medications for 6-24 hours and antihistamine medications for 3 days. Participants will have their weight checked, a venous blood sample collected, and spirometry will be performed. Sputum induction will be performed using mannitol. Body composition and bone density will be measured by dual-energy x-ray absorptiometry (DXA). Asthma, menstrual, dietary and physical activity questionnaires will be completed. Additional Study Visits (Groups 1 and 2 only; Visit E and P): The additional study visits are anticipated to take 2 hours each. At these visits, participants will perform all procedures as outlined above, except for DXA which will not be performed (i.e. for groups 1 and 2, DXA will only be performed at Visit L).
Sponsors
The University of Newcastle
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Physician diagnosed asthma 2. Female >=18 years of age 3. Confirmed variable airflow obstruction at screening visit or documented within the past 10 years: • Bronchodilator response >200mL OR >12% (post-bronchodilator FEV1 following administration of 400µg salbutamol, pMDI with spacer; after 10 minutes, or following administration of nebulised Ventolin) • Airway hyperresponsiveness (in response to any standard challenge agent) • Peak flow variability >12% when monitored over at least one week • FEV1 variability >12% (between two FEV1 values measured within two months of each other) If not observed at screening visit or documented in file, then provide peak flow meter for two weeks monitoring, if required. 4. Using a combined monophasic oral contraceptive pill (Groups 3 and 4 only). 5. Stable disease with no respiratory infection, asthma exacerbation, corticosteroid burst (>10mg/day) or use of antibiotics to treat an asthma exacerbation, or change in asthma therapy in the four weeks preceding visit 1. 6. Able to provide written informed consent
Exclusion criteria
1. Asthma is not the primary respiratory diagnosis 2. Treatment with oral corticosteroids in the preceding four weeks (unless a low dose is being taken on a long-term basis: >=10mg for >3 months) 3. Current smoker, or smoked in the last six months 4. Perimenopausal (menstrual cycle less frequent or irregular with symptoms of estrogen insufficiency) 5. Pregnancy or breastfeeding 6. Endocrine disorder resulting in amenorrhoea (e.g. thyroid disease, hyper-prolactinoma or known pituitary disorder) 7. Irregular menstrual cycle (variability >15 days between shortest and longest cycle over 12 months or cycle length outside the range of 26-34 days) 8. Hormonal contraceptive use (other than the combined monophasic oral contraceptive pill for Groups 3 and 4) 9. Current lung cancer or other blood, lymphatic or solid organ malignancy 10. NSAID burst within 48 hours of study visit 11. Participant has a clinically important medical illness (including serious psychological disorders) likely to interfere with management or participation in the study
Outcome results
None listed