Asthma Severity in Women: The Influence of Training and Menopause

Not Applicable

Terminated

• Conditions: Late-Onset Asthma
• Interventions: Behavioral: Aerobic exercise

• Registration Number: NCT03747211
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

Introduction: Late-onset asthma in women is characterized by poor disease control and reduced quality of life despite intensive treatment with inhaled steroid and beta2-agonist. The condition is further worsened at menopause due to the loss of estrogen leading to increased asthma exacerbation frequency, increased airway inflammation and decreased lung function. Exercise training may increase disease control of asthma patients, but to what extent the same effect is seen in postmenopausal women with late-onset asthma is unknown. These asthma patients represent a phenotype that is characterized by low eosinophilic airway inflammation, severe symptoms, moderate obesity and poor response to conventional medicine. Thus, our hypothesis is that regular physical exercise is especially associated with an improvement in asthma control in this phenotype. The aim of this project is to test this hypothesis and to assess whether an improvement is associated with reduced local and systemic inflammation, change in heart function, lung function and/or body composition.

Study design: 40 postmenopausal women with late-onset asthma are recruited via the outpatient clinic at the Respiratory Department at Bispebjerg Hospital and through advertisement. The participants are randomized 1:1 into two groups. One group performs supervised exercise training (spinning) three times per week for 12 weeks while the other group is a control group. Before and after the intervention asthma control, local and systemic inflammation, heart function and body composition is measured.

Results: Analysis will be performed to detect changes within and between the groups before and after intervention. Primary outcome is change in ACQ (Asthma Control Questionnaire). Local and systemic inflammation is measured by changes in bronchial challenge to methacholine, sputum cell count and blood tests. Furthermore, secondary outcomes include change in heart function measured by stress-echocardiography and change in body composition measured by Dual-energy X-ray absorptiometry (DEXA).

Conclusion: There are to date no prospective studies that can support recommendations containing asthma rehabilitation with supervised regular physical activity for postmenopausal women. Thus, this study will provide novel understanding of the importance of physical activity in a chronic disease such as asthma.

Detailed Description

Overall study design

The study is a single-blinded randomized controlled intervention study. Forty postmenopausal women with late-onset asthma (\>16 years at debut) are recruited from the asthma outpatient-clinic at Bispebjerg Hospital or other hospital/practitioner in the region and/or by advertisement. The participants are block-randomized into two groups of 20, where one group is control and the other undergoes a period of regular exercise training. The investigators will be blinded and will not know whether the subjects have trained or not.

Detailed study design

Participants allocated to the exercise training group undergo a training intervention consisting of 45 minutes of intermittent high intensity aerobic spinning training three times per week for 12 weeks. Participants allocated to the control group will continue usual care without training. No changes to current treatment will be made by the investigators on any of the groups.

The training will consist of short periods of high intensity intervals where subjects reach above 80% of maximal oxygen consumption. Spinning sessions will be fully supervised by trained instructors with a bachelor of sports and science or bachelor of medicine and conducted in the Department of Nutrition, Exercise and Sports, University of Copenhagen. Subjects will wear heart rate monitors to ensure adherence to the training protocol. Within two weeks, before and after the intervention, participants from both groups undergo 3 days of testing.

To ensure equal compliance with asthma medication both groups will receive daily electronic reminders. Once a week, all participants will be asked about their compliance to their medication.

Study Timeline

• Study First Submitted: 2018-11-09
• Study First Submitted QC: 2018-11-19
• Study First Posted: 2018-11-20
• Study Start: 2019-02-12
• Primary Completion: 2021-05-01
• Study Completion: 2021-05-01
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-17
• Last Update Posted: 2021-06-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 12

Inclusion Criteria

• Late onset asthma (Debut ≥ 16 years of age)
• ACQ ≥ 1.25
• Daily treatment for asthma (GINA 2 and above)
• Age 45 - 75
• Postmenopausal defined as no menstruation for 6 months, Serum Follicle stimulating hormone >20 International Units per Liter and P-Estradiol nmol/L <0.09
• BMI 25 - 35
• Positive bronchial challenge to methacholine, mannitol or positive reversibility to beta2-agonist now or historically
• Untrained (no participation in vigorous exercise for more than 1 hour per week during the last 2 months)
• Capable of exercising on a bike

Exclusion Criteria

• Unable to speak and understand Danish or English.
• Current or former smokers (>6 months cessation) with >20 years of daily smoking with 20 cigarettes per day.
• Other respiratory disease of clinical significance
• Cardiovascular: Unstable ischemic heart disease, myocardial infarction within the last 12 months, symptomatic heart failure (EF <40%), symptomatic heart arrhythmia (documented with ECG), uncontrolled hypertension (>155/100)
• Any disorder that is not stable and in the opinion of the investigator could affect the safety of the subject throughout the study
• Subjects, who by investigators determination, will not be able to adhere to study protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aerobic exercise intervention	Aerobic exercise	Aerobic exercise by high intensity interval training, 3 times per week for 12 weeks

Primary Outcome Measures

Name	Time	Method
Asthma control - Asthma Control Questionnaire (ACQ)	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in Asthma Control Questionnaire (ACQ) 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use)

Secondary Outcome Measures

Name	Time	Method
Heart function - Stroke volume	-21 to 0 days before intervention and 0 to 14 days post intervention	Stroke volume
Heart rhytm	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in: - Heart rhythm
Heart Rate Variability	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in: - Heart rate variability
Heart function - Tricuspid annular plane systolic excursion	-21 to 0 days before intervention and 0 to 14 days post intervention	Measured by stress-echocardiography; - Tricuspid annular plane systolic excursion
Local airway inflammation - Fraction of exhaled nitric oxide	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Fraction of exhaled nitric oxide
Compliance - Foster score	-21 to 0 days before intervention and 0 to 14 days post intervention	Change in; - Foster score Answers describe last weeks medicine use. Answers range form 0/7 - 7/7 with low values being worse.
Heart function - Cardiac output	-21 to 0 days before intervention and 0 to 14 days post intervention	Cardiac output
Systemic inflammation - Tumor Necrosis Factor alpha	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Tumor Necrosis Factor alpha
Systemic inflammation - high sensitivity c reactive protein	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - high sensitivity c reactive protein
Other asthma related questionnaires - Nijmegen questionnaire	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Nijmegen questionnaire Values range from 0-64 and values below 20 are considered normal.
Heart function - Strain	-21 to 0 days before intervention and 0 to 14 days post intervention	Measured by stress-echocardiography; - Strain
Systemic inflammation - Leukocytes + differential cell count count	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Leukocytes + differential cell count count
Systemic inflammation - Interleukin 6	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Interleukin 6
Systemic inflammation	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Other interleukins
Body Composition	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Weight
Other asthma related questionnaires - Mini Asthma Quality of Life Questionnaire (miniAQLQ)	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Mini Asthma Quality of Life Questionnaire (miniAQLQ) 7-point Likert scale (7 = not impaired at all - 1 = severely impaired).
Heart function - Right ventricular function	-21 to 0 days before intervention and 0 to 14 days post intervention	Measured by stress-echocardiography; - Right ventricular function
Heart function - Lung covered cor	-21 to 0 days before intervention and 0 to 14 days post intervention	Measured by stress-echocardiography; - Lung covered cor
Systemic inflammation - Interleukin 8	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Interleukin 8
Microbiome	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in the microbiota in sputum, oral cavity and nasal cavity before and after the training intervention
Heart Rate	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in: - electrocardiography
Heart function - Ejection fraction	-21 to 0 days before intervention and 0 to 14 days post intervention	Measured by stress-echocardiography; - Ejection fraction
Heart function - Pulmonary pressure	-21 to 0 days before intervention and 0 to 14 days post intervention	Measured by stress-echocardiography; - Pulmonary pressure
Heart function - Blood pressure	-21 to 0 days before intervention and 0 to 14 days post intervention	Blood pressure
Heart function - Total peripheral resistance	-21 to 0 days before intervention and 0 to 14 days post intervention	Total peripheral resistance
Systemic inflammation - Total immunoglobulin E, Specific immunoglobulin E	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; * Total immunoglobulin E; * Specific immunoglobulin E
Local airway inflammation - Sputum cell count	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Sputum cell count
Local airway inflammation - Hyperreactivity to inhaled methacholine	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Hyperreactivity to inhaled methacholine
Other asthma related questionnaires - Hospital Anxiety and Depression Scale (HADS) 2 items with 7 questions regarding anxiety and depression. (0 = no sign of depression/anxiety, 21 = maximal signs of anxiety/depression)	-21 to 0 days before intervention and 0 to 14 days post intervention	Changes in; - Hospital Anxiety and Depression Scale (HADS)

Trial Locations

Locations (1)

Respiratory research unit, Bispebjerg University Hospital; 🇩🇰 Copenhagen, Denmark