Adjustment, Adjustment, Emotional, Anxiety, Coping Behavior, Depression, Emotional Disorder, Emotional Distress, Emotional Dysfunction, Emotions, Psychological, Psychological Adjustment, Psychological Disorder, Psychological Distress, Psychological Stress, Psychosocial Problem, Psychosocial Stressor, Severe Eosinophilic Asthma
Conditions
Brief summary
This is a real-life pragmatic non-randomised study to explore the impact of mepolizumab on the emotional and affective outcomes of patients with severe eosinophilic asthma and their partners. It will be conducted in two quantitative stages (Phases 1 and 2) with an additional third qualitative component (Phase 3).
Detailed description
This longitudinal observational study will investigate the relationship between patients' asthma control and emotional states and quality of life in patients and their partners where patients have severe eosinophilic asthma. The study will consist of three phases. Phase 1 In order to extend our pilot study findings and help inform the second stage, investigators will gather Geneva Emotional Wheel (GEW) data from 30 patients currently treated and benefitting from mepolizumab (Nucala®). This data will be compared to the GEW data investigators have already gathered from patients with severe asthma not receiving treatment with mepolizumab (Nucala®). This will provide timely data to support a publication on the GEW findings in severe asthma and allow the description of the impact of mepolizumab (Nucala®). In addition, it will help provide power calculations for a prospective study. Parallel assessment of quality of life (SGRQ and SAQ) and anxiety and depression (HADS) will be made to evaluate the relationship between GEW, SGRQ, SAQ and HADS scores. Phase 2 In the second stage, investigators will conduct a prospective study of 45 patients newly prescribed mepolizumab (Nucala®) and their partners measuring participants' emotional composition before and 6 and 12 months after starting treatment. The choice of 60 has been based on likely power requirements but was adjusted to 45 based in Phase 1 results. Investigators will also compare the outcomes from the GEW with other standard outcome measures (HADS, ACQ, SGRQ, SAQ, BIPQ), to establish relationship between changes in these measures and changes in GEW scores, to evaluate the utility of the GEW. This will help determine if the GEW reflects changes in asthma control or whether it is reflecting improvements that the current established instruments do not recognise and allow us to quantify the magnitude of that effect. As these patients will receive mepolizumab as part of their clinical care for a year, whilst assessment of clinical efficacy is being established, investigators will gather data on oral steroid dependent exacerbations (severe exacerbations) during this year and relate to their historic exacerbation history in the year before. Evaluation will be made as to whether the 6-month improvement in GEW scores predicts impact of mepolizumab on exacerbation reduction over the first year of administration. In addition, improvements in the GEW will be explored in relationship to systemic inflammatory impact, with measures of blood eosinophils and serum inflammatory biomarkers (Olink inflammatory panel) at baseline, 6 months and 1 year. Phase 3 Finally, in addition, investigators will conduct qualitative research in the form of semi-structured interviews with a sub-set of couples (20 couples or less if no new information emerges from the interviews) to gain a more detailed insight and identify common key aspects in their subjective experiences, quality of life and emotional processes before starting treatment and after being on treatment with mepolizumab for 6 months.
Interventions
OTHERno study intervention. Patients receive standard clinical care
no intervention. observational study
Sponsors
University Hospital Southampton NHS Foundation Trust
Portsmouth Hospitals NHS Trust
University of Derby
Glasgow Gartnavel General Hospital
Hull University Teaching Hospitals NHS Trust
Aberdeen Royal Infirmary
Mid Yorkshire Teaching NHS Trust
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase 1: * Age 18 or over * Having a diagnosis of severe eosinophilic asthma * Currently on mepolizumab (Nucala®) treatment * At least basic command of English * Giving written informed consent Phase 2 Patient eligibility Inclusion criteria * Age 18 or over * Having a diagnosis of severe eosinophilic asthma * Scheduled to start mepolizumab (Nucala®) treatment * At least basic command of English (for sub-study: conversational level of English that does not require a translator) * Giving written informed consent * Co-habiting with an intimate partner who is willing to participate in the study
Exclusion criteria
* Participated in Phase 1 * Currently on mepolizumab (Nucala®) treatment * Major psychiatric disorder currently under treatment * History of any major psychiatric disorder in the last 5 years, excluding depressive and anxiety disorders that can be included if treatment or change of treatment (including change in dose of medication) has not started within the last 6 months * Any diagnosed severe comorbid chronic condition that, in the opinion of the patient's asthma physician, might impact on the patient's or partner's affective state (e.g. cancer, diabetes, heart failure, chronic liver disease, chronic kidney disease, autoimmune or neuro-degenerative disease). * Partners only: diagnosis of severe eosinophilic asthma * Death of spouse, main informal carer or first-degree family member within the last 3 months * Current oral corticosteroid maintenance treatment Partner eligibility Inclusion criteria * Age 18 or over * At least basic command of English (for sub-study: conversational level of English that does not require a translator) * Giving written informed consent * Partners: Co-habiting with an intimate partner who has severe eosinophilic asthma and is willing to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Emotional Composition (Using the Geneva Emotions Wheel) | Change to one year after start of treatment | A 20-item self-report questionnaire identifying 20 discrete emotions with positive or negative valence. Emotions with positive valence are Interest, Amusement, Pride, Joy, Pleasure, Acceptance, Love, Admiration, relief, Compassion. Emotions with negative valence are: Sadness, Guilt, Regret, Shame, Disappointment, Hopelessness, Fear, Contempt, Hate and Anger. The intensity of each emotion can be marked on a 6-point Likert-type scale with circles indicating intensities. For the statistical analysis, these were computed between 0 ( smallest circles ) to 5 ( largest circles) . Lower scores indicate lower intensity of emotions, higher scores indicate higher intensity of emotions. Changes in the individual emotion scores were the outcomes of interest and are given below. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Affective State (Using the Hospital Anxiety and Depression Scale) | Change from baseline to 1 year after start of treatment | Clinical diagnostic self-report questionnaire to assess psychological distress. Consists of anxiety and depression sub-scales. It consists of seven questions for anxiety and seven questions for depression that are in mixed order in the questionnaire. Each question has four possible answers scored from 0-3. There are separate sub-scale scores for anxiety and depression each with cut-off scores 0-7: normal, 8-10: borderline abnormal and 11-21: abnormal. Lower scores mean better outcomes. The HADS is a self-report tool and takes 2-5minutes to complete. |
| Change in Self-reported Asthma Symptom Control (Using the Asthma Control Questionnaire) | Change from baseline to 1 year after start of treatment | 6-item clinical questionnaire to establish self-assessed asthma control (questions 1-6) and lung function measured by healthcare professional (item 7). 6 of the questions are patients self-report about their asthma during the previous week regarding symptoms and bronchodilator use. Responses are given on a 7-point scale (0=no impairment, 6= maximum impairment). The ACQ score is the mean of all the questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled). In general, patients with a score below 1.0 have adequately controlled asthma and above 1.0 their asthma is not controlled. Patients with a score between 0.75 and 1.25 have borderline of adequate control. The smallest clinically important change is 0.5. |
| Change in Functioning and Quality of Life (Using the St Georges Respiratory Questionnaire) | Change from baseline to 1 year after start of treatment | Clinical questionnaire to assess disease impact on quality of life. The questionnaire has two parts. Part 1 (Questions 1 to 8) covers the patients' recollection of their symptoms over the preceding period (range 1 month to 1 year). Part 2 (Questions 9 to 16) is related to the patients' current state. The answers to the questions can be grouped in to 3 subscales. The Symptom score is reflective of physical wellbeing over the last year .The Activity score covers functioning related to patients' current daily physical activity. The Impacts score relates to the psychosocial functioning. Subscale total scores can be between 0 (no impairment ) to 100 ( maximum impairment). Scoring is weighted and higher scores indicate worse outcomes. Clinically, the total score is used as a meaningful outcome measure. |
| Change in Asthma-related Quality of Life (Using the Severe Asthma Questionnaire) | Change from baseline to 1 year after start of treatment | Severe Asthma Questionnaire (SAQ) assesses the impact of severe asthma and the effects of treatment on patient's self-reported health-related quality of life. The questionnaire produces two scores: a total domain score and a global quality of life score.1. The total domain score is the aggregation of 16 different Quality of Life (QoL) domains ( individual scores are between 1 and 7) where higher scores indicate higher adverse impact on the responder's life. The total score for this domain is obtained by the sum of scores divided by the number of questions answered and can be between 1 and 7. 2. SAQ-global score where participants scire their quality of life on a 100-point scale. Higher scores mean better quality of life. The scale takes between 3 to 6 minutes to complete, but completion time reduces on subsequent occasions. |
| Change in Illness Perception (Using the Brief Illness Perception Questionnaire) | Change from baseline to 1 year after start of treatment | Questionnaire assessing the beliefs individuals have about the cause, controllability and impact on them of the illness. Comprises 9 questions. 8 questions use a Likert scale response. Question 9 can be answered by free text about the perceived cause of illness. Total scores can be between 0 and 80 with higher scores indicating worse outcomes. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited from severe asthma specialist centres in 5 locations in the United Kingdom.
Pre-assignment details
This study had three phases. Participants in Phase 1 were 30 individuals who have already received mepolizumab treatment and were a different cohort from the participants in Phase 2. Participants in Phase 2 consisted of 45 individuals who were mepolizumab treatment naive at the time of enrolment and their romantic partners (n=45). Participants in Phase 3 were sub-set of participants from Phase 2.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous Partners of Phase 2 patients | 57.8 years STANDARD_DEVIATION 13.9 |
| Age, Continuous Phase 1 patients with severe eosinophilic asthma | 57 years STANDARD_DEVIATION 12.26 |
| Age, Continuous Phase 2 partients with severe eosinophilic asthma | 57.8 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Partners of Phase 2 patients Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Partners of Phase 2 patients Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Partners of Phase 2 patients Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Phase 1 patients with severe eosinophilic asthma Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Phase 1 patients with severe eosinophilic asthma Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Phase 1 patients with severe eosinophilic asthma Unknown or Not Reported | 0 Participants |
| Ethnicity (NIH/OMB) Phase 2 patients with severe eosinophilic asthma Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Phase 2 patients with severe eosinophilic asthma Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Phase 2 patients with severe eosinophilic asthma Unknown or Not Reported | 0 Participants |
| Height Partners of patients with severe eosinophilic asthma in Phase 2 | 1.72 meters STANDARD_DEVIATION 0.11 |
| Height Phase 1 patients with severe eosinophilic asthma | 1.70 meters STANDARD_DEVIATION 0.1 |
| Height Phase 2 patients with severe eosinophilic asthma | 1.68 meters STANDARD_DEVIATION 0.1 |
| Lenght of relationship Partners of Phase 2 patients | 27.6 years STANDARD_DEVIATION 16.9 |
| Lenght of relationship Phase 1 patients with severe eosinophilic asthma | 29.18 years STANDARD_DEVIATION 17.65 |
| Lenght of relationship Phase 2 patients with severe eosinophilic asthma | 27.6 years STANDARD_DEVIATION 16.8 |
| marital status Partners of Phase 2 patients co-habiting | 0 Participants |
| marital status Partners of Phase 2 patients divorced | 0 Participants |
| marital status Partners of Phase 2 patients married/civil partnership | 37 Participants |
| marital status Partners of Phase 2 patients single | 0 Participants |
| marital status Partners of Phase 2 patients widowed | 0 Participants |
| marital status Phase 1 patients with severe eosinophilic asthma co-habiting | 2 Participants |
| marital status Phase 1 patients with severe eosinophilic asthma divorced | 0 Participants |
| marital status Phase 1 patients with severe eosinophilic asthma married/civil partnership | 0 Participants |
| marital status Phase 1 patients with severe eosinophilic asthma single | 0 Participants |
| marital status Phase 1 patients with severe eosinophilic asthma widowed | 1 Participants |
| marital status Phase 2 patients with severe eosinophilic asthma co-habiting | 0 Participants |
| marital status Phase 2 patients with severe eosinophilic asthma divorced | 0 Participants |
| marital status Phase 2 patients with severe eosinophilic asthma married/civil partnership | 37 Participants |
| marital status Phase 2 patients with severe eosinophilic asthma single | 0 Participants |
| marital status Phase 2 patients with severe eosinophilic asthma widowed | 0 Participants |
| Same sex partner Partners of patients with severe eosinophilic asthma Phase 2 No same sex partner | 41 Participants |
| Same sex partner Partners of patients with severe eosinophilic asthma Phase 2 Yes same sex partner | 3 Participants |
| Same sex partner Patients with severe eosinophilic asthma Phase 1 No same sex partner | 25 Participants |
| Same sex partner Patients with severe eosinophilic asthma Phase 1 Yes same sex partner | 0 Participants |
| Same sex partner Patients with severe eosinophilic asthma Phase 2 No same sex partner | 41 Participants |
| Same sex partner Patients with severe eosinophilic asthma Phase 2 Yes same sex partner | 4 Participants |
| Sex: Female, Male Partners of Phase 2 patients Female | 0 Participants |
| Sex: Female, Male Partners of Phase 2 patients Male | 0 Participants |
| Sex: Female, Male Phase 1 Patients with severe eosinophilic asthma Female | 17 Participants |
| Sex: Female, Male Phase 1 Patients with severe eosinophilic asthma Male | 13 Participants |
| Sex: Female, Male Phase 2 patients with severe eosinophilic asthma Female | 24 Participants |
| Sex: Female, Male Phase 2 patients with severe eosinophilic asthma Male | 21 Participants |
| Weight Partners of patients with severe eosinophilic asthma in Phase 2 | 83 kilograms STANDARD_DEVIATION 18.5 |
| Weight Phase 1 patients with severe eosinophilic asthma | 83.51 kilograms STANDARD_DEVIATION 17.8 |
| Weight Phase 2 patients with severe eosinophilic asthma | 88.8 kilograms STANDARD_DEVIATION 16.5 |
| working status Partners of Phase 2 patients not working due to asthma related reasons | 0 Participants |
| working status Partners of Phase 2 patients not working due to other reasons | 0 Participants |
| working status Partners of Phase 2 patients working full time | 23 Participants |
| working status Partners of Phase 2 patients working part time due to other reasons than asthma | 0 Participants |
| working status Partners of Phase 2 patients working part-time for asthma related reason | 0 Participants |
| working status Phase 1 patients with severe eosinophic asthma not working due to asthma related reasons | 0 Participants |
| working status Phase 1 patients with severe eosinophic asthma not working due to other reasons | 13 Participants |
| working status Phase 1 patients with severe eosinophic asthma working full time | 0 Participants |
| working status Phase 1 patients with severe eosinophic asthma working part time due to other reasons than asthma | 0 Participants |
| working status Phase 1 patients with severe eosinophic asthma working part-time for asthma related reason | 0 Participants |
| working status Phase 2 patients with severe eosinophilic asthma not working due to asthma related reasons | 0 Participants |
| working status Phase 2 patients with severe eosinophilic asthma not working due to other reasons | 0 Participants |
| working status Phase 2 patients with severe eosinophilic asthma working full time | 23 Participants |
| working status Phase 2 patients with severe eosinophilic asthma working part time due to other reasons than asthma | 3 Participants |
| working status Phase 2 patients with severe eosinophilic asthma working part-time for asthma related reason | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 45 | 0 / 45 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 30 | 6 / 45 | 2 / 45 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 30 | 3 / 45 | 1 / 45 | 0 / 12 | 0 / 12 |
Outcome results
None listed