Internet-Based Self-Management Support After High-Altitude Climate Treatment for Severe Asthma: Randomized Controlled Trial.

BACKGROUND: In patients with severe asthma, high-altitude climate treatment has been shown to improve asthma control. However, asthma symptoms and limitations may increase after finishing inpatient rehabilitation programs and returning to sea level. OBJECTIVE: We assessed the effectiveness of a patient-tailored, internet-based, self-management strategy in addition to usual care after finishing high-altitude climate treatment. METHODS: We performed a randomized controlled trial with a 1-year follow-up in patients from a high-altitude asthma center in Davos, Switzerland. At the end of a 12-week multidisciplinary rehabilitation program, 62 adults with asthma were randomized to receive either internet-based self-management support in addition to usual care (n=33) or usual care only after discharge (n=29). The endpoints were changes in asthma-related quality of life according to the Asthma Quality of Life Questionnaire (AQLQ) (a higher score is better) and asthma control according to the Asthma Control Questionnaire (ACQ) (a lower score is better), with a minimally important difference of 0.5 points for both. RESULTS: Asthma-related quality of life and asthma control declined over time in the usual care strategy group, whereas there was a slower decline in the internet-based strategy group. For both endpoints, mixed-model analysis showed a significant positive effect in favor of internet-based self-management during follow-up (mean AQLQ score difference 0.39, 95% CI 0.092-0.69; P=.01 and ACQ score difference -0.50, 95% CI -0.86 to -0.15; P=.006), which was prominent among patients with uncontrolled asthma at discharge (AQLQ score difference 0.59, 95% CI 0.19-0.99; P=.003 and ACQ score difference -0.73, 95% CI -1.18 to -0.28; P=.002). CONCLUSIONS: Internet-based self-management support was associated with a smaller decline in quality of life and asthma control as compared with usual care, especially in patients with lower asthma control, after completion of high-altitude climate treatment. Internet-based self-management support in adults with severe asthma seems feasible and effective to maintain quality of life and asthma control. TRIAL REGISTRATION: The trial is registered in the Netherlands Trial Register (NTR1995).

Perspectives of patients and healthcare professionals on mHealth for asthma self-management.

Mobile healthcare (mHealth) has the potential to revolutionise the self-management of long-term medical conditions such as asthma. A user-centred design is integral if mHealth is to be embraced by patients and healthcare professionals.The aim of this study was to determine the perspectives of individuals with asthma and healthcare professionals on the use of mHealth for asthma self-management.We used a sequential exploratory mixed methods design; focus groups informed the development of questionnaires, which were disseminated to individuals with asthma and healthcare professionals.Focus group participants (18 asthma patients and five healthcare professionals) identified 12 potential uses of mHealth. Questionnaire results showed that individuals with asthma (n=186) most frequently requested an mHealth system to monitor asthma over time (72%) and to collect data to present to healthcare teams (70%). In contrast, healthcare professionals (n=63) most frequently selected a system alerting patients to deteriorating asthma control (86%) and advising them when to seek medical attention (87%). Individuals with asthma were less likely than healthcare professionals (p<0.001) to believe that assessing medication adherence and inhaler technique could improve asthma control.Our data provide strong support for mHealth for asthma self-management, but highlight fundamental differences between the perspectives of patients and healthcare professionals.

Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids.

Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo. During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.In patients using ICS during GL1 and using ICS 0-50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3+ (fold change per year calculated as GL2 minus GL1 2.68, 95% CI 1.87-3.84), CD4+ (1.91, 95% CI 1.33-2.75) and CD8+ cells (1.71, 95% CI 1.15-2.53), and mast cells (1.91, 95% CI 1.36-2.68). The sputum total cell counts increased significantly in GL2 (1.90, 95% CI 1.42-2.54), as did counts of macrophages (2.10, 95% CI 1.55-2.86), neutrophils (1.92, 95% CI 1.39-2.65) and lymphocytes (2.01, 95% CI 1.46-2.78).ICS discontinuation increases airway inflammation in patients with moderate-severe COPD, suggesting that the anti-inflammatory effects of ICS in COPD are not maintained after ICS discontinuation.

Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model.

BACKGROUND: Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management. METHODS: We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+FeNO. Final models were corrected for overoptimism by shrinking the regression coefficients; predictive performance was assessed by the area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test. Models were externally validated in a data set including patients with severe asthma (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes). RESULTS: 80/611 (13.1%) participants experienced ≥1 severe exacerbation. Five predictors (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous hospital admission for asthma and ≥1 severe exacerbation in the previous year) were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer-Lemeshow p value 0.35). Adding spirometry and FeNO subsequently improved discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78 to 0.81), respectively). External validation yielded AUROCs of 0.69 (95% CI 0.63 to 0.75; 0.63 to 0.75 and 0.63 to 0.75) for the three models, respectively; calibration was best for the spirometry ­model. CONCLUSIONS: A simple history-based model extended with spirometry identifies patients who are prone to asthma exacerbations. The additional value of FeNO is modest. These models merit an implementation study in clinical practice to assess their utility. TRIAL REGISTRATION NUMBER: NTR 1756.

Symptom- and fraction of exhaled nitric oxide-driven strategies for asthma control: A cluster-randomized trial in primary care.

BACKGROUND: Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (Feno), allow further tailoring of treatment. OBJECTIVE: We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or Feno-driven controlled asthma (FCa). METHODS: In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score <1.50); (2) aiming at Ca (ACQ score <0.75); and (3) aiming at FCa (ACQ score <0.75 and Feno value <25 ppb). During 12 months' follow-up, treatment was adjusted every 3 months by using an online decision support tool. Outcomes were incremental cost per quality-adjusted life year gained, asthma control (ACQ score), quality of life (Asthma Quality of Life Questionnaire score), asthma medication use, and severe exacerbation rate. RESULTS: Six hundred eleven participants were allocated to the PCa (n = 219), Ca (n = 203), or FCa (n = 189) strategies. The FCa strategy improved asthma control compared with the PCa strategy (P < .02). There were no differences in quality of life (P ≥ .36). Asthma medication use was significantly lower for the PCa and FCa strategies compared with the Ca strategy (medication costs: PCa, $452; Ca, $551; and FCa, $456; P ≤ .04). The FCa strategy had the highest probability of cost-effectiveness at a willingness to pay of $50,000/quality-adjusted life year (86%; PCa, 2%; Ca, 12%). There were no differences in severe exacerbation rate. CONCLUSION: A symptom- plus Feno-driven strategy reduces asthma medication use while sustaining asthma control and quality of life and is the preferred strategy for adult asthmatic patients in primary care.

Early detection of asthma exacerbations by using action points in self-management plans.

Our aim was to validate optimal action points in written action plans for early detection of asthma exacerbations. We analysed daily symptoms and morning peak expiratory flows (PEFs) from two previous studies. Potential action points were based on analysis of symptom scores (standard deviations) percentage of personal best PEF, PEF variability in relation to a run-in period or combinations of these measures. Sensitivity and specificity for predicting exacerbations were obtained for each action point. The numbers needed to treat to prevent one exacerbation and the time interval between reaching action point criteria and the start of the exacerbation were calculated. Based on these parameters, the optimal action points for symptoms, PEF and PEF plus symptoms were determined, and their performance compared with published guidelines' action points. The optimal action points were, for symptoms, statistical variability (standard deviations) and, for PEF, <70% of personal best. The combination of PEF plus symptoms performed best, with improved specificity and earlier detection. The main benefits associated with using these action points was to reduce false positive rates for detecting exacerbations. Early detection of asthma exacerbations can be improved using a composite action point comprising symptoms and PEF measurements over 1 week.

Long-term outcomes of internet-based self-management support in adults with asthma: randomized controlled trial.

BACKGROUND: Long-term asthma management falls short of the goals set by international guidelines. The Internet is proposed as an attractive medium to support guided self-management in asthma. Recently, in a multicenter, pragmatic randomized controlled parallel trial with a follow-up period of 1 year, patients were allocated Internet-based self-management (IBSM) support (Internet group [IG]) or usual care (UC) alone. IBSM support was automatically terminated after 12 months of follow-up. In this study, IBSM support has been demonstrated to improve asthma-related quality of life, asthma control, lung function, and the number of symptom-free days as compared to UC. IBSM support was based on known key components for effective self-management and included weekly asthma control monitoring and treatment advice, online and group education, and communication (both online and offline) with a respiratory nurse. OBJECTIVE: The objective of the study was to assess the long-term effects of providing patients 1 year of IBSM support as compared to UC alone. METHODS: Two hundred adults with physician-diagnosed asthma (3 or more months of inhaled corticosteroids prescribed in the past year) from 37 general practices and 1 academic outpatient department who previously participated were invited by letter for additional follow-up at 1.5 years after finishing the study. The Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ) were completed by 107 participants (60 UC participants and 47 IG participants). A minimal clinical important difference in both questionnaires is 0.5 on a 7-point scale. RESULTS: At 30 months after baseline, a sustained and significant difference in terms of asthma-related quality of life of 0.29 (95% CI 0.01-0.57) and asthma control of -0.33 (95% CI -0.61 to -0.05) was found in favor of the IBSM group. No such differences were found for inhaled corticosteroid dosage or for lung function, measured as forced expiratory volume in 1 second. CONCLUSIONS: Improvements in asthma-related quality of life and asthma control were sustained in patients who received IBSM support for 1 year, even up to 1.5 years after terminating support. Future research should be focused on implementation of IBSM on a wider scale within routine asthma care. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 79864465; http://www.controlled-trials.com/ISRCTN79864465 (Archived by WebCite at http://www.webcitation.org/6J4VHhPk4).

Comparison between an online self-administered and an interviewer-administered version of the Asthma Control Questionnaire: a cross-sectional validation study.

BACKGROUND: Online self-management programmes for asthma have recently become available. International guidelines suggest that the Asthma Control Questionnaire (ACQ) can be used in these programmes. In order to assess the current level of control and guide therapy, the same cut-off values are being used as in conventional asthma management. However, results might differ between different types of administration of the ACQ. AIMS: To assess the agreement between an online self-administered version of the ACQ and an interviewer-administered version at a routine visit. METHODS: Cross-sectional data from primary care asthma patients in the Asthma Control Cost Utility Randomized Trial Evaluation (ACCURATE) trial aged 18-50 years and prescribed inhaled steroids were analysed. We selected patients who self-administered an ACQ online and subsequently had an ACQ completed by a nurse practitioner within 7 days at a trial-related control visit. ACQ scores were calculated and agreement assessed by paired t-tests, Pearson's correlation coefficient and a Bland-Altman plot. RESULTS: A total of 351 patients were eligible (68% female, mean age 40 years). The time interval between the two versions was 3.2 days. There was a significant difference of 0.14 (95% CI 0.09 to 0.20; p<0.001) between the results of the online self-administered ACQ (mean 1.04±0.04) and the interviewer-administered ACQ results (0.90±0.04). The Pearson correlation coefficient was 0.79. The limits of agreement (-0.86, 1.14) exceeded the predefined minimal clinically important difference between results (±0.5). The Bland-Altman plot therefore showed insufficient agreement. CONCLUSIONS: Assessment of asthma control by the ACQ is influenced by the type of administration. Our results suggest that better control of asthma is perceived when interacting with a caregiver than by online self-assessment.

Clinical and inflammatory determinants of bronchial hyperresponsiveness in COPD.

Bronchial hyperresponsiveness (BHR) is regarded as a hallmark of asthma, yet it is also present in a considerable number of chronic obstructive pulmonary disease (COPD) patients. Epidemiological studies have shown that BHR provides complementary information to forced expiratory volume in 1 s (FEV(1)) for development and progression of COPD. We hypothesised that the severity of BHR and its longitudinal changes associate with both clinical and airway inflammation measures in COPD. Our hypothesis was tested in 114 COPD patients (median age 62.9 years, smoking exposure 45.9 pack-yrs) participating in the GLUCOLD (Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease) study, which previously showed an improvement in BHR with fluticasone and fluticasone/salmeterol. At baseline, and 6 and 30 months after treatment, we investigated lung function, including body plethysmography, provocative concentration of methacholine causing a 20% fall in FEV(1), sputum induction, and bronchial biopsies. By performing both cross-sectional and longitudinal analyses, we show that BHR in COPD is predominantly associated with residual volume/total lung capacity (a measure of air trapping) and airway inflammation reflected by the number of neutrophils, macrophages and lymphocytes in sputum and bronchial biopsies. Our findings indicate that BHR is an independent trait in COPD and provides important information on phenotype heterogeneity and disease activity.

Smoking status and anti-inflammatory macrophages in bronchoalveolar lavage and induced sputum in COPD.

BACKGROUND: Macrophages have been implicated in the pathogenesis of COPD. M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties. We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD. Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD. METHODS: 114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months). BAL was collected from 71 patients. CD163+ macrophages were quantified in BAL and sputum cytospins. Pro- and anti-inflammatory mediators were measured in BAL and sputum supernatants. RESULTS: Ex-smokers with COPD had a higher percentage, but lower number of CD163+ macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 × 10(4)/ml, p = 0.001 respectively). The percentage CD163+ M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001). BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+ BAL macrophages (Rs = 0.38, p = 0.003). No significant differences were found between smokers and ex-smokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum. CONCLUSIONS: Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters.

Asthma control cost-utility randomized trial evaluation (ACCURATE): the goals of asthma treatment.

BACKGROUND: Despite the availability of effective therapies, asthma remains a source of significant morbidity and use of health care resources. The central research question of the ACCURATE trial is whether maximal doses of (combination) therapy should be used for long periods in an attempt to achieve complete control of all features of asthma. An additional question is whether patients and society value the potential incremental benefit, if any, sufficiently to concur with such a treatment approach. We assessed patient preferences and cost-effectiveness of three treatment strategies aimed at achieving different levels of clinical control:1. sufficiently controlled asthma2. strictly controlled asthma3. strictly controlled asthma based on exhaled nitric oxide as an additional disease marker DESIGN: 720 Patients with mild to moderate persistent asthma from general practices with a practice nurse, age 18-50 yr, daily treatment with inhaled corticosteroids (more then 3 months usage of inhaled corticosteroids in the previous year), will be identified via patient registries of general practices in the Leiden, Nijmegen, and Amsterdam areas in The Netherlands. The design is a 12-month cluster-randomised parallel trial with 40 general practices in each of the three arms. The patients will visit the general practice at baseline, 3, 6, 9, and 12 months. At each planned and unplanned visit to the general practice treatment will be adjusted with support of an internet-based asthma monitoring system supervised by a central coordinating specialist nurse. Patient preferences and utilities will be assessed by questionnaire and interview. Data on asthma control, treatment step, adherence to treatment, utilities and costs will be obtained every 3 months and at each unplanned visit. Differences in societal costs (medication, other (health) care and productivity) will be compared to differences in the number of limited activity days and in quality adjusted life years (Dutch EQ5D, SF6D, e-TTO, VAS). This is the first study to assess patient preferences and cost-effectiveness of asthma treatment strategies driven by different target levels of asthma control. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1756.

The Role of Education, Monitoring, and Symptom Perception in Internet-Based Self-management Among Adolescents With Asthma: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Internet-based self-management programs improve asthma control and the asthma-related quality of life in adults and adolescents. The components of self-management programs include education and the web-based self-monitoring of symptoms; the latter requires adequate perception in order to timely adjust lifestyle or medication or to contact a care provider. OBJECTIVE: We aimed to test the hypothesis that adherence to education and web-based monitoring and adequate symptom perception are important determinants for the improvement of asthma control in self-management programs. METHODS: We conducted a subgroup analysis of the intervention group of a randomized controlled trial, which included adolescents who participated in the internet-based self-management arm. We assessed the impacts that attendance in education sessions, the frequency of web-based monitoring, and the level of perception had on changes in asthma control (Asthma Control Questionnaire [ACQ]) and asthma-related quality of life (Pediatric Asthma Quality of Life Questionnaire) from baseline to 12 months after intervention. RESULTS: Adolescents who attended education sessions had significant and clinically relevant improvements in asthma control (ACQ score difference: -0.6; P=.03) and exhibited a nonsignificant trend of improvement in asthma-related quality of life (Pediatric Asthma Quality of Life Questionnaire score difference: -0.45; P=.15) when compared to those who did not adhere to education. Frequent monitoring alone did not improve asthma control (P=.07) and quality of life (P=.44) significantly, but its combination with education did result in improved ACQ scores (difference: -0.88; P=.02). There were no significant differences in outcomes between normoperceivers and hypoperceivers. CONCLUSIONS: Education, especially in combination with frequent web-based monitoring, is an important determinant for the 1-year outcomes of asthma control in internet-based self-management programs for adolescents with partly controlled and uncontrolled asthma; however, we could not establish the effect of symptom perception. This study provides important knowledge on the effects of asthma education and monitoring in daily life.

Effect of fluticasone with and without salmeterol on pulmonary outcomes in chronic obstructive pulmonary disease: a randomized trial.

BACKGROUND: Inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847) SETTING: 2 university medical centers in The Netherlands. PATIENTS: 114 steroid-naive current or former smokers with moderate to severe COPD. MEASUREMENTS: Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months. INTERVENTION: Random assignment by minimization method to receive fluticasone propionate, 500 microg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 microg twice daily, and salmeterol, 50 microg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29). RESULTS: 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3(+) cells (-55% [95% CI, -74% to -22%]; P = 0.004), CD4(+) cells (-78% [CI, -88% to 60%]; P < 0.001), CD8(+) cells (-57% [CI, -77% to -18%]; P = 0.010), and mast cells (-38% [CI, -60% to -2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV(1) decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3(+) cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV(1) level. LIMITATIONS: The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months. CONCLUSION: ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. .

Validation of online Asthma Control Questionnaire and Asthma Quality of Life Questionnaire.

OBJECTIVE: Several newly developed eHealth applications use online questionnaires to monitor asthma control. The Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) are two such commonly used questionnaires. These questionnaires are validated for use on paper. This study aims to validate them by assessing the agreement between online and paper versions of the ACQ and AQLQ. METHODS: Patients (aged 18 years and older) from the Self-Management in Asthma Supported by Hospitals, ICT, Nurses and General Practitioners (SMASHING)-trial and Davos@home study were included in this study. Patients completed both the paper and online Dutch versions of the ACQ and AQLQ in a random order within a 2-week interval. Agreement between the different versions was assessed with paired t-tests, intraclass correlation coefficients and Bland-Altman plots. RESULTS: In total 44 patients were eligible for analysis. The mean difference between the paper and online versions of the ACQ was 0.04 (p=0.40) and for the AQLQ it was 0.08 (p=0.06). The intraclass correlation coefficient scores were 0.94 for the ACQ and 0.95 for the AQLQ. CONCLUSION: The online versions of the ACQ and AQLQ show high levels of agreement with the paper versions and can therefore be safely used in eHealth applications to respectively monitor asthma control and quality of life.

Personalised exhaled nitric oxygen fraction (F ENO)-driven asthma management in primary care: a F ENO subgroup analysis of the ACCURATE trial.

BACKGROUND: The aim of this study was to identify patients who benefit most from exhaled nitric oxide fraction (F ENO)-driven asthma management in primary care, based on prespecified subgroups with different levels of F ENO. METHODS: We used data from 179 adults with asthma from a 12-month primary care randomised controlled trial with 3-monthly assessments of F ENO, asthma control, medication usage, costs of medication, severe asthma exacerbations and quality of life. In the original study, patients were randomised to either a symptom-driven treatment strategy (controlled asthma (Ca) strategy) or a F ENO+symptom-driven strategy (FCa). In both groups, patients were categorised by their baseline level of F ENO as low (<25 ppb), intermediate (25-50 ppb) and high (>50 ppb). At 12 months, we compared, for each prespecified F ENO subgroup, asthma control, asthma-related quality of life, medication usage, and costs of medication between the Ca and FCa strategy. RESULTS: We found a difference between the Ca and FCa strategy for the mean dosage of beclomethasone strategy of 223 µg (95% CI 6-439), p=0.04) and for the total costs of asthma medication a mean reduction of US$159 (95% CI US$33-285), p=0.03) in patients with a low baseline F ENO level. No differences were found for asthma control, severe asthma exacerbations and asthma-related quality of life in patients with a low baseline F ENO level. Furthermore, in patients with intermediate or high level of F ENO, no differences were found. CONCLUSIONS: In primary care, F ENO-driven asthma management is effective in patients with a low F ENO level, for whom it is possible to down-titrate medication, while preserving asthma control and quality of life.

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.

Development and Validation of Personalized Prediction to Estimate Future Risk of Severe Exacerbations and Uncontrolled Asthma in Patients with Asthma, Using Clinical Parameters and Early Treatment Response.

BACKGROUND: Current level of asthma control can be easily assessed by validated instruments, but it is currently difficult to assess individuals' level of future risk. OBJECTIVE: Develop, and validate, a risk prediction score for level of future risk, including patient characteristics and information on early treatment response. METHODS: We used data of 304 adult patients with asthma from a 12-month primary care randomized controlled trial with 3-monthly assessments. With logistic regression we modeled the association between the level of future risk and patient characteristics including early treatment response. Future risk was defined as Asthma Control Questionnaire (ACQ) score of 1.5 or more at 12 months or the experience of at least 1 exacerbation during the final 6 months. We developed a risk prediction score on the basis of regression coefficients. RESULTS: Performance of the risk prediction score improved, taking into account data on early treatment response (area under receiver-operating curve [AUROC] = 0.84) compared with a model containing only baseline characteristics (AUROC = 0.78). The score includes 6 easy-to-obtain predictors: sex, ACQ score and exacerbations in the previous year at baseline and at first follow-up, and smoking status and exacerbations in the previous 3 months (indicating early treatment response). External validation yielded an AUROC of 0.77. The risk prediction score classified patients into 3 risk groups: low (absolute risk, 11.7%), intermediate (47.0%), and high (72.7%). CONCLUSIONS: We developed and externally validated a risk prediction score, quantifying both level of current asthma control and the guideline-defined future risk. Patients' individual risk can now be estimated in an easy way, as proposed but not specified, by asthma management guidelines.

Exacerbations in Adults with Asthma: A Systematic Review and External Validation of Prediction Models.

BACKGROUND: Several prediction models assessing future risk of exacerbations in adult patients with asthma have been published. Applicability of these models is uncertain because their predictive performance has often not been assessed beyond the population in which they were derived. OBJECTIVE: This study aimed to identify and critically appraise prediction models for asthma exacerbations and validate them in 2 clinically distinct populations. METHODS: PubMed and EMBASE were searched to April 2017 for reports describing adult asthma populations in which multivariable models were constructed to predict exacerbations during any time frame. After critical appraisal, the models' predictive performances were assessed in a primary and a secondary care population for author-defined exacerbations and for American Thoracic Society/European Respiratory Society-defined severe exacerbations. RESULTS: We found 12 reports from which 24 prediction models were evaluated. Three predictors (previous health care utilization, symptoms, and spirometry values) were retained in most models. Assessment was hampered by suboptimal methodology and reporting, and by differences in exacerbation outcomes. Discrimination (area under the receiver-operating characteristic curve [c-statistic]) of models for author-defined exacerbations was better in the primary care population (mean, 0.71) than in the secondary care population (mean, 0.60) and similar (0.65 and 0.62, respectively) for American Thoracic Society/European Respiratory Society-defined severe exacerbations. Model calibration was generally poor, but consistent between the 2 populations. CONCLUSIONS: The preservation of 3 predictors in models derived from variable populations and the fairly consistent predictive properties of most models in 2 distinct validation populations suggest the feasibility of a generalizable model predicting severe exacerbations. Nevertheless, improvement of the models is warranted because predictive performances are below the desired level.

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.