UNASSIGNED: The individualized PREdiction of DIsease Control using digital sensor Technology (iPREDICT) program was developed for asthma management using digital technology. Devices were integrated into daily lives of patients to establish a predictive model of asthma control by measuring changes from baseline health status with minimal device burden.
UNASSIGNED: To establish baseline disease characteristics of the study participants, detect changes from baseline associated with asthma events, and evaluate algorithms capable of identifying triggers and predicting asthma control changes from baseline data. Patient experience and compliance with the devices were also explored.
UNASSIGNED: This was a multicenter, observational, 24-week, proof-of-concept study conducted in the United States.
UNASSIGNED: Patients (⩾12 years) with severe, uncontrolled asthma engaged with a spirometer, vital sign monitor, sleep monitor, connected inhaler devices, and two mobile applications with embedded patient-reported outcome (PRO) questionnaires. Prospective data were linked to data from electronic health records and transmitted to a secure platform to develop predictive algorithms. The primary endpoint was an asthma event: symptom worsening logged by patients (PRO); peak expiratory flow (PEF) < 65% or forced expiratory volume in 1 s < 80%; increased short-acting β2-agonist (SABA) use (>8 puffs/24 h or >4 puffs/day/48 h). For each endpoint, predictive models were constructed at population, subgroup, and individual levels.
UNASSIGNED: Overall, 108 patients were selected: 66 (61.1%) completed and 42 (38.9%) were excluded for failure to respond/missing data. Predictive accuracy depended on endpoint selection. Population-level models achieved low accuracy in predicting endpoints such as PEF < 65%. Subgroups related to specific allergies, asthma triggers, asthma types, and exacerbation treatments demonstrated high accuracy, with the most accurate, predictive endpoint being >4 SABA puffs/day/48 h. Individual models, constructed for patients with high endpoint overlap, exhibited significant predictive accuracy, especially for PEF < 65% and >4 SABA puffs/day/48 h.
UNASSIGNED: This multidimensional dataset enabled population-, subgroup-, and individual-level analyses, providing proof-of-concept evidence for development of predictive models of fluctuating asthma control.

BACKGROUND: Severe asthma (SA) presents a considerable healthcare challenge despite optimal standard treatment. Dupilumab, which is effective in type 2 (T2) SA patients, demonstrates variable responses, categorizing patients as non-responders, partial responders, or those achieving clinical remission. However, real-world response rates remain underexplored. Additionally, understanding the characteristics of patients achieving clinical remission is crucial for predicting favourable responses to dupilumab.
OBJECTIVE: To investigate responder types and identify predictors of clinical remission and non-response induced by dupilumab in a real-world cohort of SA patients.
METHODS: We analyzed retrospective data from SA patients undergoing dupilumab treatment in a study conducted at Franciscus Gasthuis & Vlietland hospital. Data were collected at baseline and at a 12 to 24-months follow-up (T = 12). Response rates were evaluated at T = 12. Predictors of non-response and clinical remission were investigated using multivariate logistic regression analysis with a stepwise forward variable selection approach.
RESULTS: Among the 175 patients screened, 136 met the inclusion criteria. At T = 12, 31.6 % achieved clinical remission, 47.1 % were partial responders and 21.3 % were non-responders. Predictors associated with clinical remission included high baseline blood eosinophil counts (BEC) and male sex. Conversely, younger age at baseline, low baseline total immunoglobin E (IgE) and low baseline fractional exhaled nitric oxide (FeNO) levels were identified as predictors of non-response.
CONCLUSIONS: Dupilumab results in clinical disease remission in one-third of the treated patients. Clinical remission is predicted by high BEC and male sex, whereas low total IgE, low FeNO and younger age indicate a lower likelihood of response.

UNASSIGNED: Specific biomarkers, such as eosinophilia in peripheral blood or fractional exhaled nitric oxide (FeNO), can guide us in the choice of biologic therapy, allowing a more personalized approach. Although there are multiple evidences in the literature about the role of FeNO as a predictor of response to different biologic treatments, there are no data on the relationship between FeNO changes and clinical response to the four biologic drugs currently in use.
UNASSIGNED: To evaluate and to compare the expression of multiple-flows FeNO parameters in a cohort of patients with severe asthma (SA) before and during the treatment with biologics to evaluate the performance of these biomarkers in predicting the achievement of clinical remission.
UNASSIGNED: We prospectively enrolled 50 patients with severe asthma eligible for biologic therapy. Patients underwent clinical and functional monitoring at baseline (T0) and after 1, 6, and 12 months of treatment (T1, T6, T12), including multiple flows FeNO assessment.
UNASSIGNED: A statistically significant reduction of FeNO50 values and J\'awNO was observed only in benralizumab and dupilumab subgroups. Among biomarkers, the reduction of FeNO 50 values at T1 was associated with a higher probability of achieving clinical remission at T12 (p = 0.003), which was also confirmed by ROC curve analysis (AUC 0.758, p = 0.002; sensitivity 60% and specificity 74% for a reduction of 16 ppb).
UNASSIGNED: These data confirm the potential of this biomarker in predicting clinical response to biologic treatment in patients with severe asthma in order to guide clinical decisions and evaluate a shift to other biologic therapy.

BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic procedure for patients with severe uncontrolled asthma, but randomized controlled studies of its efficacy in severe asthma with frequent exacerbations are lacking. The current aim was to assess BT efficacy in this patient population.
METHODS: Thirty patients with asthma (GINA 5) who had experienced at least four severe exacerbations in the preceding year were randomized to BT (n = 15) or control groups (n = 15). All patients had four follow-up visits over the following 15 months, corresponding to 3, 6, 9, and 12 months after the last procedure for the BT group. The primary outcome was number of exacerbations at 15 months after inclusion (i.e. 12 months after bronchial thermoplasty).
RESULTS: All but three patients had received an asthma biologic without receiving benefit. In the year preceding enrollment, patients in the BT group had an average of five exacerbations, compared with six among controls. For patients in the BT group, oral steroid intake was 9.3 mg/d, compared with 11.0 mg/d among controls. The BT group had 1.58 fewer severe exacerbations (mean, 6.09) compared with controls (mean, 8.28) in the 12-month period after the therapy (p = 0.047). Oral steroid intake during follow-up after BT was significantly lower in the BT group (ratio vs controls: 0.61; p = 0.0002). Quality-of-life measures between inclusion and the last visit were significantly improved in the BT group, but not among controls. Few mild to moderate adverse events were reported, and all were controlled within days.
CONCLUSIONS: In patients with severe asthma and frequent severe exacerbations, BT significantly decreased the rate of severe exacerbations and oral steroid intake and led to improved quality of life during the 15 months after inclusion. BT appears to offer a therapeutic option for severe asthma with frequent exacerbations.

BACKGROUND: Switching biologics is now common practice in severe eosinophilic asthma. After insufficient response to anti-IL-5 or 5 receptor (anti-IL-5/5R), the optimal switch between an anti-IL-4R mAb (interclass) or another anti-IL-5/5R drug (intraclass) remains unknown.
OBJECTIVE: We sought to compare the effectiveness of these 2 strategies in asthma control in patients with severe eosinophilic asthma and insufficient response to an anti-IL-5/5R mAb.
METHODS: We emulated a target randomized trial using observational data from the Recherche sur les AsthMes SEvèreS (RAMSES) cohort. Eligible patients were switched to an anti-IL-4R mAb or another anti-IL-5/5R drug after insufficient response to an anti-IL-5/5R mAb. The primary outcome was the change in Asthma Control Test score at 6 months.
RESULTS: Among the 2046 patients in the cohort, 151 were included in the study: 103 switched to an anti-IL-4R mAb and 48 to another anti-IL-5/5R. At 6 months, the difference in Asthma Control Test score improvement was not statistically significant (mean difference groups, 0.82 [-0.47 to 2.10], P = .213). The interclass group exhibited greater cumulative reduction in oral corticosteroid dose (Pinter-intra, -1.05 g [-1.76 to -0.34], P = .041). The interclass group had a better effect, although not significantly, on reducing exacerbations (Δinter-intra, -0.37 [-0.77 to 0.02], P = .124) and increasing lung function (FEV1) (126.8 mL [-12.7 to 266.4], P = .124).
CONCLUSIONS: After anti-IL-5/5R mAb insufficient response, switching to dupilumab demonstrated similar improvement in Asthma Control Test scores compared with intraclass switching. However, it appeared more effective in reducing oral corticosteroid use. Larger studies are warranted to confirm these results.

BACKGROUND: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR.
METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52 weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study.
RESULTS: Tezepelumab reduced the AAER over 52 weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline.
CONCLUSIONS: These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers\' treatment decisions.
BACKGROUND: NAVIGATOR (NCT03347279).

OBJECTIVE: To assess clinical and demographic characteristics of severe asthma (SA) patients and their management in Russian Federation.
METHODS: This publication provides data for Russian part of population of the international observational study. In Phase I, retrospective analysis of medical records of patients with SA was performed with assessment of clinical and demographic data, medical history, comorbidities, treatment approaches and healthcare utilization. Phase II was a cross-sectional collection of patient-reported outcomes: level of asthma control assessed by ACT (Asthma Control Test) and health-related quality of life (HRQoL) measured using the EQ-5D-5L questionnaire. Phase I patients were enrolled into Phase II if they signed a written consent form.
RESULTS: A total of 315 patients were included in Phase I of the study, 106 (33.6%) of them entered Phase II. Majority of study participants were either obese (n=103; 39.8%) or overweight (n=94; 36.3%). The most common comorbidities were cardiovascular diseases (n=217; 71.4%), followed by chronic respiratory diseases (n=198; 68.8%). There were 268 (85.1%) patients who had at least one exacerbation during last 12 months. Data for blood eosinophil count were available in 176 patients; 81.3% of them (n=143) had only one test in the last 12 months. The mean (SD) last available blood eosinophil count was 161.2 (181.2) cells/mm3. Serum Immunoglobulin E (IgE) value was known for 88 patients, and the mean (SD) last measured IgE value was 254.3 (249.7) ng/mL. Only 4.7% of Phase II participants had ACT scores indicative of controlled asthma (>20). As much as 74.5% had scores ≤15 suggesting uncontrolled disease. Most patients also had impaired HRQoL.
CONCLUSIONS: Most SA patients had poor disease control with frequent exacerbations and high number of comorbidities. Blood eosinophils and IgE level measurements were not evaluated routinely which might be a barrier for appropriate phenotyping and treatment selection.
Цель. Оценить клинико-демографические характеристики и особенности ведения пациентов с тяжелой бронхиальной астмой (ТБА) в России. Материалы и методы. В публикации представлены данные российской популяции международного наблюдательного исследования. В Фазу I включены 315 пациентов, 106 (33,6%) из них вошли в Фазу II. Фаза I включала ретроспективный анализ медицинских документов взрослых больных ТБА с оценкой демографических данных, особенностей анамнеза, сопутствующих заболеваний, подходов к терапии и использования ресурсов здравоохранения. Фаза II представляла собой одномоментное исследование, проводимое для оценки контроля заболевания при помощи Теста по контролю над астмой (Asthma Control Test – ACT) и качества жизни, связанного со здоровьем (HRQoL), по Европейскому опроснику оценки качества жизни (EQ-5D-5L). Участников Фазы I включали в Фазу II после подписания информированного согласия. Результаты. Большинство участников имели ожирение (n=103; 39,8%) или избыточную массу тела (n=94; 36,3%). Самыми частыми сопутствующими заболеваниями оказались сердечно-сосудистые (n=217; 71,4%) и хронические заболевания органов дыхания (n=198; 68,8%). У 268 (85,1%) пациентов в предыдущие 12 мес отмечалось по меньшей мере одно обострение. Данные о количестве эозинофилов крови доступны у 176 пациентов; у 81,3% из них анализ выполнен однократно в течение 12 мес. Среднее значение последнего зарегистрированного количества эозинофилов крови (SD) составило 161,2 (181,2) клеток на 1 мкл. Уровень общего иммуноглобулина E (IgE) оказался известен у 88 пациентов. Средняя величина последнего значения общего IgE (SD) составила 254,3 (249,7) нг/мл. Лишь у 4,7% участников Фазы II показатели АСТ соответствовали контролируемой БА (сумма баллов >20). У 74,5% сумма баллов ACT составила ≤15, что предполагало отсутствие контроля. Пациенты также демонстрировали сниженные показатели качества жизни, ассоциированного со здоровьем. Заключение. У большинства больных ТБА отмечены неудовлетворительный контроль заболевания с частыми обострениями, а также значительное число сопутствующих заболеваний. Количество эозинофилов и уровень IgE редко оцениваются в рутинной практике, что может препятствовать подбору фенотип-ориентированной терапии.

BACKGROUND: Severe asthma is characterized by frequent exacerbations, altered lung function, and impaired quality of life. Tailored patient education allows for the improvement of both asthma management and quality of life. Our study aimed to assess the needs of severe asthma patient in therapeutic education, according to previous therapeutic patient education background and asthma phenotype.
METHODS: Consecutive patients monitored for severe asthma in a tertiary referral center were considered for inclusion and answered a questionnaire detailing their patient education needs and the topics they would like to discuss. Asthma history, clinical and biological data, and lung function results were recorded.
RESULTS: Fifty-three patients were included and 47 (88.7%) expressed at least one need. The most frequently selected topics were \"life with asthma\" (83%), \"treatment use\" (68%), and \"exacerbation management\" (60%), independent of previous participation in a patient education program dedicated to asthma. Patients of older age at inclusion, uncontrolled asthma, and T2-high phenotypes were associated with different profiles of patient education needs.
CONCLUSIONS: Our study identified frequent and various patient educational needs among severe asthmatics, highlighting the importance of an in-depth assessment of severe asthmatics expectations and the crucial need for the development of dedicated educational tools.

UNASSIGNED: Uncontrolled asthma (UCA) is different from severe asthma and can be identified in children across all ranges of prescribed treatment.
UNASSIGNED: Our aim was to characterize uncontrolled childhood asthma in pediatric specialist care.
UNASSIGNED: We performed a nationwide cross-sectional study of 5497 children (aged 6-17 years) with asthma who were treated by pediatricians at outpatient clinics during 2019 and registered in the Swedish National Airway Register. UCA was defined as an Asthma Control Test score of 19 or lower and/or 2 or more exacerbations in the past year and/or an FEV1 value less than 80% predicted. Treatment was categorized from step 1 to step 5 according to the Global Initiative for Asthma.
UNASSIGNED: UCA was identified in 1690 children (31%), of whom 64% had an Asthma Control Test score of 19 or lower, 20% had recurrent exacerbations, and 31% had an FEV1 value less than 80% predicted. UCA was associated with female sex (odds ratio [OR] = 1.29 [95% CI = 1.15-1.45]), older age (OR = 1.02 [95% CI = 1.00-1.04]), obesity (OR = 1.43 [95% CI = 1.12-1.83]), and more treatment using steps 1 and 2 as a reference (step 3, OR = 1.28 [95% CI = 1.12-1.46]); steps 4-5, OR = 1.32 [95% CI = 1.10-1.57]). UCA in children prescribed treatment steps 1 and 2 (group UCA1-2) occurred in 28% of all children at this treatment step (n = 887). Children in group UCA1-2 had exacerbations more frequently than did those children with UCA who were prescribed steps 4 and 5 treatment (24% vs 15% [P = .001]).
UNASSIGNED: UCA was common and associated with female sex, increasing age, obesity, and higher Global Initiative for Asthma treatment step. Surprisingly, UCA was also common in children prescribed less than the maximum treatment, and those children could be considered undertreated patients.

BACKGROUND: Targeting the parasympathetic nervous system innervating the airway with pharmacologic products has been proved to improve the clinical outcomes of severe asthma. Bronchial cryo-denervation (BCD) is a novel non-pharmacologic treatment for severe asthma using an endobronchial cryo-balloon administered via bronchoscopy to denervate parasympathetic pulmonary nerves. Preclinical studies have demonstrated that BCD significantly disrupted vagal innervation in the lung.
METHODS: A total of 15 patients with severe asthma were enrolled in this prospective, single-center pilot study. Patients underwent bifurcated BCD treatment at a 30-day interval after baseline assessment. Follow-up through 12 months included assessment of adverse events, technical feasibility, and changes in pulmonary function; asthma control questionnaire-7 (ACQ-7); and asthma control test (ACT).
RESULTS: BCD was performed on all 15 severe asthma patients, with technical feasibility of 96.7%. There were no device-related and 2 procedure-related serious adverse events through 12 months, which resolved without sequelae. The most frequent nonserious procedure-related adverse event was increased cough in 60% (9 of 15) patients. Pulmonary function remained unchanged, and significant improvements from baseline ACQ-7 (mean, -1.19, p = 0.0032) and ACT (mean, 3.18, p = 0.0011) scores were observed since the first month\'s follow-up after a single lung airway treatment, with similar trends till the end of the 12-month follow-up.
CONCLUSIONS: This study provides the first clinical evidence of the safety, feasibility, and initial efficacy of BCD in patients with severe asthma.