Background:SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of... Show moreBackground:SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data.Methods:This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity.Results:We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curacao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies.Conclusions:Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections. Show less
Bendien, S.A.; Kroes, J.A.; Hal, L.H.G. van; Braunstahl, G.J.; Broeders, M.E.A.C.; Oud, K.T.M.; ... ; Brinke, A. ten 2023
BACKGROUND: Bronchiectasis is a common comorbidity in patients with asthma and is associated with increased disease severity. In patients with severe eosinophilic asthma, biologics targeting IL-5... Show moreBACKGROUND: Bronchiectasis is a common comorbidity in patients with asthma and is associated with increased disease severity. In patients with severe eosinophilic asthma, biologics targeting IL-5/5Ra have beneficial effects on oral corticosteroid (OCS) use and exacerbation frequency. However, how coexisting bronchiectasis affects the response to such treatments is unknown.OBJECTIVE: To evaluate the real-world effectiveness of anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma and comorbid bronchiectasis on exacerbation frequency and daily maintenance and cumulative OCS dose.METHODS: This real-world study evaluated data from 97 adults with severe eosinophilic asthma and computed tomographyeconfirmed bronchiectasis from the Dutch Severe Asthma Registry, who initiated anti-IL5/5Ra biologics (mepolizumab, reslizumab, and benralizumab) and had follow-up data for 12 months or greater. The analysis was performed for the total population and subgroups with or without maintenance OCS use.RESULTS: Anti-IL-5/5Ra therapy significantly reduced exacerbation frequency in patients with maintenance OCS use as well as in those without it. In the year before biologic initiation, 74.5% of all patients had two or more exacerbations, which decreased to 22.1% in the follow-up year (P < .001). The proportion of patients on maintenance OCS decreased from 47% to 30% (P < .001), and in the OCS-dependent patients (n [ 45) maintenance OCS dose decreased from median (interquartile range) of 10.0 mg/d (5-15 mg/d) to 2.5 mg/d (0-5 mg/d) after 1 year (P < .001).CONCLUSIONS: This real-world study shows that anti-IL-5/ 5Ra therapy reduces exacerbation frequency and daily maintenance as well as the cumulative OCS dose in patients with severe eosinophilic asthma and comorbid bronchiectasis. Although it is an exclusion criterion in phase 3 trials, comorbid bronchiectasis should not preclude anti-IL-5/5Ra therapy in patients with severe eosinophilic asthma. (c) 2023 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2023;11:2724-31) Show less
Have, L. ten; Visser, E.; Meulmeester, F.L.; Bendien, S.A.; Braunstahl, G.J.; Broeders, M.E.A.C.; ... ; Brinke, A. ten 2023
Background: Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics... Show moreBackground: Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown.Objectives: To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change.Methods: Real-world data on weight and cumulative OCS dose from adults included in the Dutch Registry of Adult Patients with Severe asthma for Optimal DIsease management before and at least 2 years after starting anti-IL-5/5Ra were analyzed using linear mixed models and linear regression analyses.Results: For the included 389 patients (55% female; mean body mass index, 28 +/- 5 kg/m(2); 58% maintenance OCS), mean weight decreased -0.27 kg/y (95% CI, -0.51 to -0.03; P = .03), with more weight loss in patients with maintenance OCS use than in those without maintenance OCS use (-0.87 kg/y [95% CI, -1.21 to -0.52; P < .001] vs +0.54 kg/y [0.26 to 0.82; P < .001]). Greater weight loss at 2 years was associated with higher cumulative OCS dose in the 2 years before anti-IL-5/5Ra initiation (beta = -0.24 kg/g; 95% CI, -0.38 to -0.10; P < .001) and, independently, greater reduction in cumulative OCS dose during follow-up (beta = 0.27 kg/g; 95% CI, 0.11 to 0.43; P < .001).Conclusions: Anti-IL-5/5Ra therapy is associated with long-term weight reduction, especially in patients with higher OCS exposure before treatment and those able to reduce OCS use during treatment. However, the effect is small and does not apply to all patients, and so additional interventions seem necessary if weight change is desired. Show less
Background The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria... Show moreBackground The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs.Materials and methods We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs ( four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies.Results Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: >= 10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score <= 1.5 and low-dose inhaled corticosteroids.Conclusion A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma. Show less
Valk, J.P.M. van der; Hekking, P.P.; Rauh, S.P.; Patberg, K.W.; Veen, I.A. van; Huisstede, A. van; ... ; RAPSODI Team 2023
IntroductionSevere asthma is associated with a serious disease burden, partially caused by limitations in activity and work impairment.Aims and objectivesThis study aims to relate treatment with... Show moreIntroductionSevere asthma is associated with a serious disease burden, partially caused by limitations in activity and work impairment.Aims and objectivesThis study aims to relate treatment with biologics targeting IL-5/5Ra to work productivity and activity in the long term in a real-world context.Material and methodsThis is a registry-based multi-center cohort study evaluating data from adults with severe eosinophilic asthma included in the Dutch Register of Adult Patients with Severe Asthma for Optimal DIsease management (RAPSODI). Patients that started with anti-IL-5/5Ra biologics and completed the work productivity and activity improvement questionnaire, were included. Study and patient characteristics were compared between the employed and unemployed patients. Work productivity and activity impairment are related to accompanying improvements in clinical outcomes.ResultsAt baseline, 91 of 137 patients (66%) were employed which remained stable throughout the follow-up period. Patients in the working age category were younger and had significantly better asthma control (p = 0.02). Mean overall work impairment due to health decreased significantly from 25.5% (SD2.6) to 17.6% (SD 2.8) during 12 months anti-IL-5/5Ra biologics treatment (P = 0.010). There was a significant association between ACQ6 and overall work improvement after targeted therapy (beta = 8.7, CI 2.1-15.4, P = 0.01). The improvement of asthma control of 0.5 points on the asthma Control Questionnaire was associated with an overall work impairment of -9%.ConclusionsWork productivity and activity in severe eosinophilic asthma improved after starting anti-IL-5/5Ra biologics. Clinically relevant improvement in asthma control was associated with an overall work impairment score of -9% in this study. Show less
Kroes, J.A.; Jong, K. de; Hashimoto, S.; Zielhuis, S.W.; Roon, E.N. van; Sont, J.K.; ... ; RAPSODI Team 2023
Background Benralizumab is highly effective in many, but not all, patients with severe asthma. Baseline characteristics alone are insufficient to predict an individual's probability of long-term... Show moreBackground Benralizumab is highly effective in many, but not all, patients with severe asthma. Baseline characteristics alone are insufficient to predict an individual's probability of long-term benralizumab response. The objectives of the present study were to: 1) study whether parameters at 3 months, in addition to baseline characteristics, contribute to the prediction of benralizumab response at 1 year; and 2) develop an easy-to-use prediction tool to assess an individual's probability of long-term response. Methods We assessed the effect of benralizumab treatment in 192 patients from the Dutch severe asthma registry (RAPSODI). To investigate predictors of long-term benralizumab response (.50% reduction in maintenance oral corticosteroid (OCS) dose or annual exacerbation frequency) we used logistic regression, including baseline characteristics and 3-month Asthma Control Questionnaire (ACQ-6) score and maintenance OCS dose. Results Benralizumab treatment significantly improved several clinical outcomes, and 144 (75%) patients were classified as long-term responders. Response prediction improved significantly when 3-month outcomes were added to a predictive model with baseline characteristics only (area under the receiveroperating characteristic (AUROC) 0.85 versus 0.72, p=0.001). Based on this model, a prediction tool using sex, prior biologic use, baseline blood eosinophils, forced expiratory volume in 1 s, and at 3 months OCS dose and ACQ-6 was developed which classified patients into three categories with increasing probability of long-term response (95% CI): 25% (3-65%), 67% (57-77%) and 97% (91-99%), respectively. Conclusion In addition to baseline characteristics, treatment outcomes at 3 months contribute to the prediction of benralizumab response at 1 year in patients with severe eosinophilic asthma. Prediction tools as proposed in this study may help physicians optimise the use of costly biologics. Show less
Kroes, J.A.; Alfonso-Cristancho, R.; Bansal, A.T.; Berret, E.; Bieksiene, K.; Bourdin, A.; ... ; Brinke, A. ten 2023
Background An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level... Show moreBackground An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg center dot day(-1), 95% CI -5.24-2.62 mg center dot day(-1)) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner. Show less
BackgroundPrevious studies have proposed different formulas of estimating glomerular filtration rate (eGFR) among clinical patients. The comprehensive comparison of eGFR formulas is not well... Show moreBackgroundPrevious studies have proposed different formulas of estimating glomerular filtration rate (eGFR) among clinical patients. The comprehensive comparison of eGFR formulas is not well established in a Japanese population. We compared eGFR values and chronic kidney disease (CKD) classification of nine different eGFR in a Japanese general population sample.MethodsWe analyzed 469 Japanese community-dwelling adults (184 men) without any self-reported kidney disease. GFR estimated using the 4- and 6-parameter Modification of Diet in Renal Disease (MDRD) formulas (MDRD4 and MDRD6); the CKD-EPI formulas based on creatinine with (CKD-EPI-2009) and without race coefficient (CKD-EPI-2021), on cystatin C (CKD-EPI-Cys), on both (CKD-EPI-CreCys); the Japanese creatinine-based formula (JPN-Cre), cystatin C-based formula (JPN-Cys), and modified CKD-EPI formula (JPN-CKD-EPI). CKD stages were defined by KDIGO guidelines (eGFR < 60 ml/min/1.73 m2).ResultseGFRJPN-Cre (mean = 71.2; SD = 14.3) were much lower than eGFRCKD-EPI-2021 (mean = 94.2; SD = 12.7), while eGFRJPN-Cys (mean = 102.8; SD = 24.2) was comparable to the MDRD and CKD-EPI formulas. The difference between eGFRCKD-EPI-2021 and eGFRJPN-Cre showed a V-shaped distribution across eGFR levels, indicating complex errors between these formulas. We observed very low agreement in CKD classification between eGFRJPN-Cre and the eGFRCKD-EPI-2021 (kappa = 0.13; 95% confidence interval: 0.06, 0.23).ConclusionsJPN-Cre was substantially different from the CKD-EPI formula without race term (CKD-EPI-2021), which means that it is impossible to recalibrate those with a simple coefficient. Although a comparison with measured GFR should be necessary, choice of the estimation method needs caution in clinical decision-making and academic research. Show less
Kroes, J.A.; Zielhuis, S.W.J.; Jong, K. de; Hashimoto, S.; Sont, J.K.; Zielhuis, S.W.; ... ; RAPSODI Team 2022
Background: Anti-interleukin (IL)-5/IL-5 receptor alpha (IL-5Ra) therapy has been shown to reduce maintenance oral corticosteroid (OCS) dose in severe eosinophilic asthma. However, the effect on... Show moreBackground: Anti-interleukin (IL)-5/IL-5 receptor alpha (IL-5Ra) therapy has been shown to reduce maintenance oral corticosteroid (OCS) dose in severe eosinophilic asthma. However, the effect on cumulative OCS exposure is currently unknown. Neither is it known how prior OCS exposure affects response to anti-IL-5/5Ra treatment. We aimed primarily to compare the cumulative OCS exposure over a 2-year period before and after anti-IL-5/5Ra initiation, and secondarily to investigate whether duration and cumulative OCS exposure prior to anti-IL-5/5Ra influence the ability to discontinue OCS within 2 years of anti-IL-5/5Ra therapy. Methods: This real-world nationwide observational registry-based study evaluated all dispensed OCS from 389 adults with severe eosinophilic asthma included in the Dutch Severe Asthma Registry (RAPSODI) 2 years before and 2 years after initiating anti-IL-5/5Ra. The Wilcoxon signed-rank test and multivariable regression analyses were used. Results: Median (interquartile range) cumulative OCS exposure in the 2 years before and after anti-IL-5/ 5Ra initiation decreased from 2.715 (1.150-5.539) to 1.050 (0.300-3.640) g (p<0.001). 52% of patients were able to discontinue OCS within 2 years after anti-IL-5/5Ra therapy, which was independently predicted by lower and shorter prior OCS exposure. Conclusions: This real-world study showed that anti-IL-5/5Ra therapy leads to a significant reduction in cumulative OCS exposure over a 2-year period. Patients with lower and shorter OCS exposure were more likely to completely eliminate OCS. Since cumulative exposure increased progressively prior to anti-IL-5/ 5Ra initiation, our data suggest that early intervention leads to a better long-term prognosis in patients with severe eosinophilic asthma. Show less
BACKGROUND: Reslizumab, a biologic targeting IL-5, has been shown to reduce asthma exacerbations and maintenance oral corticosteroid use in randomized controlled trials and pre-post studies in... Show moreBACKGROUND: Reslizumab, a biologic targeting IL-5, has been shown to reduce asthma exacerbations and maintenance oral corticosteroid use in randomized controlled trials and pre-post studies in patients with severe eosinophilic asthma. However, real-world effectiveness data of reslizumab are scarce, and it is unknown whether reslizumab has added value after switching from another type 2 biologic.OBJECTIVE: To evaluate (1) the real-world effectiveness of reslizumab on severe asthma exacerbations, maintenance oral corticosteroid use, and overall treatment response, both in biologic-naive patients who initiated reslizumab and in those who switched from another type 2 biologic; and (2) physicians' experience with reslizumab treatment.METHODS: This observational real-world study evaluated data from 134 adults with severe eosinophilic asthma included in the Dutch severe asthma registry (RAPSODI), who initiated reslizumab treatment (4-weekly infusions, 0.3 mg/kg) before April 2020 and had follow-up data for 6 months and greater. Clinical asthma experts completed surveys on their experience with reslizumab treatment.RESULTS: Overall, reslizumab reduced the exacerbation rate (odds ratio [95% CI] = 0.10 [0.05-0.21]; P<.001), oral corticosteroid use (OR [95% CI], 0.2 [0.0-0.5]; P<.001), and maintenance dose (median [CI], 5.0 [0.0-10.0] to 0.0 [0.0-5.0]; P<.001), with comparable results in biologic-naive reslizumab initiators and switchers. The overall response to reslizumab was graded good or excellent in 59.2% of patients. The additive effectiveness of reslizumab after switching from another biologic was reflected in physicians' surveys.CONCLUSIONS: Real-world data show that reslizumab reduces severe asthma exacerbations and oral corticosteroid use in patients with severe eosinophilic asthma, both in biologic-naive reslizumab initiators and in those who switched from another type 2 biologic. This additional value of reslizumab was recognized by clinical asthma experts. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. Show less
Artificial intelligence (AI) applications and digital technologies (DTs) are increasingly present in the daily lives of citizens, in cities and in industries. These developments generate large... Show moreArtificial intelligence (AI) applications and digital technologies (DTs) are increasingly present in the daily lives of citizens, in cities and in industries. These developments generate large amounts of data and enhance analytical capabilities that could benefit the industrial ecology (IE) community and sustainability research in general. With this communication, we would like to address some of the opportunities, challenges, and next steps that could be undertaken by the industrial ecology community in this realm. This article is an adapted summary of the discussion held by experts in industrial ecology, AI, and sustainability during the 2021 Industrial Ecology Day conference session titled “The Future of Artificial Intelligence in the Context of Industrial Ecology.” In brief, building on previous studies and communications, we advise the industrial ecology community to: (1) create internal committees and working groups to monitor and coordinate AI applications within and outside the community; (2) promote and ensure transdisciplinary efforts; (3) determine optimal infrastructure and governance of AI for IE to minimize undesired effects; and (4) act on effective representation and on reduction of digital divides. Show less
Background: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch... Show moreBackground: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch children.Patients and Methods: We conducted a national survey asking Dutch pediatricians to share their experiences on long-COVID in children. We furthermore describe a case series of six children with long-COVID to explore the clinical features in greater detail.Results: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2-18 years, suspected of long-COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post-COVID complaints.Conclusion: Our study shows that long-COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management. Show less
Nakazawa, Y.; Hara, Y.; Oka, Y.; Komine, O.; Heuvel, D. van den; Guo, C.W.; ... ; Ogi, T. 2020
Transcription-coupled nucleotide excision repair (TC-NER) is initiated by the stalling of elongating RNA polymerase H (RNAPIIo) at DNA lesions. The ubiquitination of RNAPIIo in response to DNA... Show moreTranscription-coupled nucleotide excision repair (TC-NER) is initiated by the stalling of elongating RNA polymerase H (RNAPIIo) at DNA lesions. The ubiquitination of RNAPIIo in response to DNA damage is an evolutionarily conserved event, but its function in mammals is unknown. Here, we identified a single DNA damage-induced ubiquitination site in RNAPII at RPB1-K1268, which regulates transcription recovery and DNA damage resistance. Mechanistically, RPB1-K1268 ubiquitination stimulates the association of the core-TFIIH complex with stalled RNAPIIo through a transfer mechanism that also involves UVSSA-K414 ubiquitination. We developed a strand-specific ChIP-seq method, which revealed RPB1-K1268 ubiquitination is important for repair and the resolution of transcriptional bottlenecks at DNA lesions. Finally, RPB1-K1268R knockin mice displayed a short life-span, premature aging, and neurodegeneration. Our results reveal RNAPII ubiquitination provides a two-tier protection mechanism by activating TC-NER and, in parallel, the processing of DNA damage-stalled RNAPIIo, which together prevent prolonged transcription arrest and protect against neurodegeneration. Show less
Background In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects. However, the optimal... Show moreBackground In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects. However, the optimal strategy for tapering oral corticosteroids is unknown. Objective To investigate whether an internet-based management tool including home monitoring of symptoms, lung function and fraction of exhaled nitric oxide (FENO) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life. Methods In a 6-month pragmatic randomised prospective multicentre study, 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies: according to conventional treatment (n=43) or guided by a novel internet-based monitoring system (internet strategy) (n=52). Primary outcomes were cumulative sparing of prednisone, asthma control and asthma-related quality of life. Secondary outcomes were forced expiratory volume in 1 s (FEV1), exacerbations, hospitalisations and patient's satisfaction with the tapering strategy. Results Median cumulative sparing of prednisone was 205 (25-75th percentile -221 to 777) mg in the internet strategy group compared with 0 (-497 to 282) mg in the conventional treatment group (p=0.02). Changes in prednisone dose (mixed effect regression model) from baseline were -4.79 mg/day and +1.59 mg/day, respectively (p<0.001). Asthma control, asthma-related quality of life, FEV1, exacerbations, hospitalisations and satisfaction with the strategy were not different between groups. Conclusions An internet-based management tool including home monitoring of symptoms, lung function and FENO in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life. Show less
