MyAirCoach: The use of home-monitoring and mHealth systems to predict deterioration in asthma control and the occurrence of asthma exacerbations; Study protocol of an observational study

© Published by the BMJ Publishing Group Limited. Introduction Asthma is a variable lung condition whereby patients experience periods of controlled and uncontrolled asthma symptoms. Patients who experience prolonged periods of uncontrolled asthma have a higher incidence of exacerbations and increased morbidity and mortality rates. The ability to determine and to predict levels of asthma control and the occurrence of exacerbations is crucial in asthma management. Therefore, we aimed to determine to what extent physiological, behavioural and environmental data, obtained by mobile healthcare (mHealth) and home-monitoring sensors, as well as patient characteristics, can be used to predict episodes of uncontrolled asthma and the onset of asthma exacerbations. Methods and analysis In an 1-year observational study, patients will be provided with mHealth and home-monitoring systems to record daily measurements for the first-month (phase I) and weekly measurements during a follow-up period of 11 months (phase II). Our study population consists of 150 patients, aged ≥18 years, with a clinician's diagnosis of asthma, currently on controller medication, with uncontrolled asthma and/or minimally one exacerbation in the past 12 months. They will be enrolled over three participating centres, including Leiden, London and Manchester. Our main outcomes are the association between physiological, behavioural and environmental data and (1) the loss of asthma control and (2) the occurrence of asthma exacerbations. Ethics This study was approved by the Medical Ethics Committee of the Leiden University Medical Center in the Netherlands and by the NHS ethics service in the UK. Trial registration number NCT02774772

Effectiveness of myAirCoach: A mHealth Self-Management System in Asthma

Background: Self-management programs have beneficial effects on asthma control, but their implementation in clinical practice is poor. Mobile health (mHealth) could play an important role in enhancing self-management. Objective: To assess the clinical effectiveness and technology acceptance of myAirCoach-supported self-management on top of usual care in patients with asthma using inhalation medication. Methods: Patients were recruited in 2 separate studies. The myAirCoach system consisted of an inhaler adapter, an indoor air-quality monitor, a physical activity tracker, a portable spirometer, a fraction exhaled nitric oxide device, and an app. The primary outcome was asthma control; secondary outcomes were exacerbations, quality of life, and technology acceptance. In study 1, 30 participants were randomized to either usual care or myAirCoach support for 3 to 6 months; in study 2, 12 participants were provided with the myAirCoach system in a 3-month before-after study. Results: In study 1, asthma control improved in the intervention group compared with controls (Asthma Control Questionnaire difference, 0.70; P = .006). A total of 6 exacerbations occurred in the intervention group compared with 12 in the control group (hazard ratio, 0.31; P = .06). Asthma-related quality of life improved (mini Asthma-related Quality of Life Questionnaire difference, 0.53; P = .04), but forced expiratory volume in 1 second was unchanged. In study 2, asthma control improved by 0.86 compared with baseline (P = .007) and quality of life by 0.16 (P = .64). Participants reported positive attitudes toward the system. Discussion: Using the myAirCoach support system improves asthma control and quality of life, with a reduction in severe asthma exacerbations. Well-validated mHealth technologies should therefore be further studied

Predicting the clinical effect of a short acting bronchodilator in individual patients using artificial neural networks

Artificial neural networks were used in this study to model the relationships between in vitro data, subject characteristics and in vivo outcomes from N = 18 mild–moderate asthmatics receiving monodisperse salbutamol sulphate aerosols of 1.5, 3 and 6 μm mass median aerodynamic diameter in a cumulative dosing schedule of 10, 20, 40 and 100 μg. Input variables to the model were aerodynamic particle size (APS), body surface area (BSA), age, pre-treatment forced expiratory volume in one-second (FEV1), forced vital capacity, cumulative emitted drug dose and bronchodilator reversibility to a standard salbutamol sulphate 200 μg dose MDI (REV(%)). These factors were used by the model to predict the bronchodilator response at 10 (T10) and 20 (T20) min after receiving each of the 4 doses for each of the 3 different particle sizes. Predictability was assessed using data from selected patients in this study, which were set aside and not used in model generation. Models reliably predicted ΔFEV1(%) in individual subjects with non-linear determinants (R2) of ≥0.8. The average error between predicted and observed ΔFEV1(%) for individual subjects was <4% across the cumulative dosing regimen. Increases in APS and drug dose gave improved ΔFEV1(%). Models also showed trends towards improved responses in younger patients and those having greater REV(%), whilst BSA was also shown to influence clinical effect. These data show that APS can be used to discriminate predictably between aerosols giving different bronchodilator responses across a cumulative dosing schedule, whilst patient characteristics can be used to reliably estimate clinical response in individual subjects

Patients’ characteristic.

<p>Values are expressed median (interquartile range) except for gender, Atopy, smoking status.</p>*<p>FEV₁: Forced expiratory volume in one second.</p>†<p>FVC: Forced vital capacity.</p>‡<p>PEF: Peak expiratory flow.</p>**<p>p<0.01 compare to HV.</p>||<p>p<0.0001 compare to HV.</p>§<p>p<0.001 compare to NSA.</p>††<p>p<0.0001 compare to HV. and NSA.</p

Corticosteroid sensitivity and GR nuclear translocation in asthma. A.

<p>Dex (10⁻¹¹–10⁻⁶ M) was incubated 1 hour followed by 24 hours stimulation with TNFα. ELISA was used to measure IL-8 levels in 8 healthy volunteers (HV), 14 non-severe asthmatics (NSA), and 14 severe asthmatics (SA). IC₅₀dex (50% inhibitory concentration) was measured and plotted in graph <b>B. B.</b> IC₅₀dex measured from <b>A.</b> was plotted for 8 HV, 14 NSA and 14 SA. <b>C.</b> Example of nuclear translocation as assessed by immunocytochemistry of PBMCs treated with Dex (1 µM) for 4 hrs. PBMCs were cytospined into slides and air dried. GR was detected using an anti-GR antibody with a secondary cy3-conjugated antibody (red). The nucleus was counter-stained using a cy5 To-Pro-3 (blue). A fixed area was drawn and used to measure the intensities of the red and blue channels in the nucleus. Ten cells per experiment were counted and the ratio cy3/cy5 used as the representation of nuclear GR which was normalized for Dex treatment. The fold induction of the signal ratio of 4 hours incubation with Dex over non-treatment was calculated as the index of GR nuclear translocation (GNI: GR nuclear translocation index). Four patients’ pictures from confocal microscopy are shown. (−); non-treatment, (Dex); Dex (1 µM) for 4 hrs. (i) Healthy volunteer with GNI = 4.2. (ii) Non-severe asthmatic with GNI = 2.4. (iii) Severe asthmatic with GNI = 1.2. (iv) Severe asthmatic with GNI = 1.2. <b>D.</b> Correlation between GNI and IC₅₀dex in all asthmatics (n = 24). <b>E.</b> Correlation between GNI and lung function as measured by FEV₁ (%pred) in asthma (n = 32). Data was plotted as median ± SEM. <i>p</i><0.05 is significant.</p

Effect of SB203580 on steroid sensitivity and GR nuclear translocation in U937. A.

<p>U937 cells were initially incubated with IL-2/IL-4 for 48 hours. Cells were pre-treated with SB203580 (5 µM) for 30 min followed by Dex (10⁻¹¹−10⁻⁶ M) for 1 hour and TNFα stimulation (10 ng/ml) overnight. TNFα-induced IL-8 release was evaluated by ELISA and IC₅₀dex values for Dex on IL-8 production were calculated. Values represent means of three experiments ± SEM. # <i>p</i><0.05 (vs. non-treatment control; NT), and* <i>p</i><0.01 (vs. treatment with IL-2/IL-4 only). <b>B.</b> U937 cells were incubated with IL-2/IL-4 for 48 hours. Cells were then stimulated with SB203580 (5 µM) for 30 min followed by Dex 10⁻⁶ M for 4 hours. Nuclear protein was extracted and GR was detected using SDS-PAGE/Western Blotting. TBP was detected as loading control. Ratio of GR nuclear translocation was calculated dividing GR absorbance by TBP.*** <i>p</i><0.001 (IL-2/IL-4+ dex vs. treatment with IL-2/IL-4 only), # <i>p</i><0.05 (IL-2/IL-4+ dex + SB vs. treatment with IL-2/IL-4+ dex), n = 3. <b>C.</b> U937s were stimulated with IL-2/4 for 48 hours and then stimulated with SB203580 (5 µM) for 30 minutes prior whole-cell extraction and SDS-PAGE/Western-Blotting. Phosphorylation of Serine 226 was determined with anti-S226 GR antibody normalized to GR expression. The band density was calculated by densitometry. ## <i>p</i><0.01 (vs. non-treatment control),* <i>p</i><0.05 (vs. treatment with IL-2/IL-4 only), n = 4.</p