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 integrated disease management for primary care chronic obstructive pulmonary disease patients: results of cluster randomised trial.

__Objective__ To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with usual care. __Design__ 24 month, multicentre, pragmatic cluster randomised controlled trial __Setting__ 40 general practices in the western part of the Netherlands __Participants__ Patients with COPD according to GOLD (Global Initiative for COPD) criteria. Exclusion criteria were terminal illness, cognitive impairment, alcohol or drug misuse, and inability to fill in Dutch questionnaires. Practices were included if they were willing to create a multidisciplinary COPD team. __Intervention__ General practitioners, practice nurses, and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice, including early recognition of exacerbations and self management, smoking cessation, physiotherapeutic reactivation, optimal diagnosis, and drug adherence. Additionally, the course served as a network platform and collaborating healthcare providers designed an individual practice plan to integrate integrated disease management into daily practice. The control group continued usual care (based on

Inhaled corticosteroid dose-response in asthma:Should we measure inflammation?

Background: Inhaled corticosteroid (ICS) titration in asthma is primarily based on symptoms and pulmonary function. ICSs may not be increased on this basis despite residual airway inflammation.ObjectiveTo compare the dose-response relationships of ICSs on measures of pulmonary function, symptoms, and inflammation in patients with persistent asthma.Methods: We performed a pooled post hoc analysis of 121 patients with mild to moderate asthma from 4 randomized clinical trials that incorporated an ICS dose ramp. Dose ramps were 0 to 200, 0 to 800, and 200 to 800 μg/d (beclomethasone equivalents). Outcome measures included spirometry, fractional exhaled nitric oxide, airway hyperresponsiveness (AHR), symptoms, serum eosinophilic cationic protein, and blood eosinophils.Results: We found a plateau beyond a small improvement at 0 to 200 μg for forced expiratory volume in 1 second: 3.3% (95% confidence interval [CI], 2.0%–4.7%) at 0 to 200 μg vs 0.3% (95% CI, −0.8% to 1.4%) 200 to 800 μg (P = .001). A similar plateau was seen for symptom improvement beyond 0 to 200 μg. Inflammatory and AHR outcomes revealed further room for improvement beyond low-dose ICSs. There was dose-related suppression (P < .001) for fractional exhaled nitric oxide: 40.4 ppb (95% CI, 34.7–46.9 ppb) for ICS free, 26.8 ppb (95% CI, 23.4–30.2 ppb) for 200 μg, and 20.8 ppb (95% CI, 18.8–23.1 ppb) for 800 μg. Eosinophilic cationic protein concentration was significantly reduced with both higher dose ramps. Eosinophil counts also improved across all 3 dose ramps, with dose separation of 370/μL (95% CI, 280–450/μL) for ICS free vs 250/μL (95% CI, 200–300/μL) 800 μg (P = .03). AHR improved with all 3 dose ramps, with greater improvement at lower doses for indirect vs direct challenges.Conclusion: ICS dose response may extend beyond low dose for inflammation and AHR but not symptoms or spirometry. Further study is required to identify whether this correlates with suboptimal longitudinal asthma control

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease

Relationship of circulating hyaluronic Acid levels to disease control in asthma and asthmatic pregnancy.

Uncontrolled asthma is a risk factor for pregnancy-related complications. Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in various diseases, promotes eosinophil survival and plays a role in asthmatic airway inflammation as well as in physiological processes necessary to maintain normal pregnancy; however the level of circulating HA in asthma and asthmatic pregnancy is unknown. We investigated HA levels in asthmatic patients (N = 52; asthmatic pregnant (AP) N = 16; asthmatic non-pregnant (ANP) N = 36) and tested their relationship to asthma control. Serum HA level was lower in AP than in ANP patients (27 [24.7-31.55] vs. 37.4 [30.1-66.55] ng/mL, p = 0.006); the difference attenuated to a trend after its adjustment for patients' age (p = 0.056). HA levels and airway resistance were positively (r = 0.467, p = 0.004), HA levels and Asthma Control Test (ACT) total score inversely (r = -0.437, p = 0.01) associated in ANP patients; these relationships remained significant even after their adjustments for age. The potential value of HA in the determination of asthma control was analyzed using ROC analysis which revealed that HA values discriminate patients with ACT total score >/=20 (controlled patients) and <20 (uncontrolled patients) with a 0.826 efficacy (AUC, 95% CI: 0.69-0.97, p = 0.001) when 37.4 ng/mL is used as cut-off value in ANP group, and with 0.78 efficacy (AUC, 95% CI: 0.65-0.92, p = 0.0009) in the whole asthmatic cohort. In conclusion circulating HA might be a marker of asthma control, as it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease of HA level in pregnancy may be the consequence of pregnancy induced immune tolerance

The case for impulse oscillometry in the management of asthma in children and adults

Objective: To provide a clinical rationale for including impulse oscillometry (IOS) as a part of standard office-based asthma assessment.Data Sources: PubMed and Google search, limited to English language and human disease, with the keywords IOS and asthma.Study Selections: Articles included in this review were based on the expert opinion and previous publications by the authors.Results: In children, IOS was more useful than spirometry in identifying asthma and uncontrolled asthma and predicting loss of control and exacerbations. IOS predicts young children at risk for loss of lung function with age and the potential for early intervention to prevent further sequelae. In adults, peripheral airway impairment detected by IOS or spirometry (ie, forced expiratory flow between 25% and 75%) commonly occurs across severity, and each measure may be complementary in predicting loss of control even with normal forced expiratory volume in 1 second. Extrafine inhaled corticosteroids with or without long-acting β-agonists proved superior to standard particle aerosols in improving IOS-detected peripheral airway obstruction. Our data also suggest that currently available commercial reference values for lung resistance at 5 Hz and lung reactance at 5 Hz are applicable across diverse populations, but further studies are needed.Conclusion: The findings of this review suggest that IOS can add value to traditional clinical and spirometric assessment and thus improve management of asthma in children and adults, as well as have the potential to detect early dysfunction of the peripheral airways, which may result in better outcomes.</p

Non-invasive markers of airway inflammation and remodeling in childhood asthma

To evaluate the relationship between pro-inflammatory and pro-remodeling mediators and severity and control of asthma in children, the levels of IL-8, MMP-9, TIMP-1 in induced sputum supernatants, the number of sputum eosinophils, as well as FeNO, were investigated in 35 asthmatic children, 12 with intermittent (IA) and 23 with moderate asthma (MA), and 9 controls (C). The patients with asthma were followed for 1 yr and sputum was obtained twice during the follow-up. Biomarker levels were correlated with the number of exacerbations. We found that IL-8, MMP-9, TIMP-1 and the numbers of eosinophils in induced sputum, as well as FeNO, were increased in children with IA and MA in comparison to C. The ongoing inflammation was confirmed by increased nuclear p65 NF-kappaB subunit localization in sputum cells. In MA, FeNO measurements, sputum eosinophils and IL-8 levels, positively correlated with the occurrence of disease exacerbations during a 1-yr follow-up. According to FeNO, sputum eosinophils and IL-8 sputum concentrations, and the number of exacerbations, two distinct phenotypes of MA were identified. This study shows that the presence of bronchial inflammation is detectable in the airways of some IA, as well as in the airways of MA, despite the regular ICS treatment. This study also proposes the need to perform large prospective studies to confirm the importance of measuring specific biomarkers in induced sputum, concomitantly to FeNO analyses, to assess sub-clinical airway inflammation and disease control in children with asthma

Fasting parameters for estimation of stimulated beta cell function in islet transplant recipients with or without basal insulin treatment

In order to assess beta cell secretory capacity after islet transplantation, standardized mixed meal stimulation tests are often used. But these tests are cumbersome and the effect of exogenous insulin on the test results is unclear. The aim of our study was to determine to what extent fasting glycemic indices can estimate stimulated beta cell function in islet transplant recipients with and without basal insulin. In total 100 mixed meal stimulation tests, including 31 with concurrent basal insulin treatment, were performed in 36 islet transplant recipients. In a multivariate model, fasting C-peptide and fasting glucose together estimated peak C-peptide withR(2) = .87 and area under the curve (AUC) C-peptide with aR(2) = .93. There was a larger increase of glucose during tests in which exogenous insulin was used (+7.9 vs +5.3 mmol/L,P < .001) and exogenous insulin use was associated with a slightly lower estimated peak C-peptide (relative change: -15%,P = .02). In islet transplant recipients the combination of fasting C-peptide and glucose can be used to accurately estimate stimulated beta cell function after a mixed meal stimulation test, whether exogenous basal insulin is present or not. These data indicate that graft function can be reliably determined during exogenous insulin treatment and that regular islet graft stimulation tests can be minimized.Analysis and support of clinical decision makin

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.

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

Patients' and Health Care Providers' Perceptions on mHealth Use After High-Altitude Climate Therapy for Severe Asthma: Mixed Methods Study

Background: Asthma is a common chronic disease with various clinical presentations. Although most patients are able to reach good asthma control, some patients are not able to reach sufficient asthma control following the regular treatment guidelines and could be referred to high-altitude climate therapy (HACT). HACT includes environmental trigger avoidance in the alpine climate with multidisciplinary clinical treatment. Patients with severe and difficult-to-control asthma, who are unable to reach asthma control at sea level, can follow a 12-week lung rehabilitation program at 1600 m above sea level. Mobile health (mHealth) tools can be used to enhance self-management in these patients when they return home. For an mHealth system to be effective, it must meet the expectations of the end users. Objective: In this Davos@home study, we explored the attitudes toward mHealth aimed at supporting the self-management of patients with severe, difficult-to-control asthma who underwent HACT and asthma health care providers. Methods: In the first stage, interviews with referrers to HACT and focus groups with patients with asthma who participated in or completed HACT were conducted. The data were then analyzed thematically. On the basis of these results, a questionnaire was developed. In the second stage of the study, this questionnaire, combined with the Asthma Control Questionnaire and the Individual Innovativeness Questionnaire, was provided to patients who completed HACT. Results: In total, 11 interviews and 3 focus groups (n=18, age 47.6, SD 12.1 years, Asthma Control Questionnaire score 2.6, SD 1.0) were conducted. A total of 3 themes were identified: potential goals, useful measurements, and perceived barriers and facilitators. The questionnaire developed in stage 2 included items based on these results. The most agreed-upon goal among the 52 patients who completed the questionnaire was to increase their asthma control (45/52, 86% of the patients). Conclusions: Different patients reported that they would benefit the most from different functionalities. Therefore, it is important to tailor functionalities to individual (treatment) goals. When developing an mHealth intervention, it is important to allow personalization to avoid overwhelming the users