Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register.

BACKGROUND: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. OBJECTIVE: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. METHODS: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. RESULTS: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. CONCLUSION: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry.

BACKGROUND: Investigation for the presence of asthma comorbidities is recommended by the Global Initiative for Asthma because their presence can complicate asthma management. OBJECTIVE: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes. METHODS: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. A total of 30 comorbidities were identified and categorized a priori as any of the following: (1) potentially type 2-related comorbidities, (2) potentially oral corticosteroid (OCS)-related comorbidities, or (3) comorbidities mimicking or aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex (ie male or female). RESULTS: Of the 11,821 patients, 69%, 67%, and 55% had at least 1 potentially type 2-related, potentially OCS-related, or mimicking or aggravating comorbidities, respectively; 57% had 3 or more comorbidities, and 33% had comorbidities in all 3 categories. Patients with allergic rhinitis, nasal polyposis, and chronic rhinosinusitis experienced 1.12 (P = .003), 1.16 (P < .001), and 1.29 times (P < .001) more exacerbations per year, respectively, than those without. Patients with nasal polyposis and chronic rhinosinusitis were 40% and 46% more likely (P < .001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with a greater likelihood of LTOCS use (odds ratios [ORs]: 1.23-2.77) and, except for dyslipidemia, with a greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking or aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81), and all (except chronic obstructive pulmonary disease) with increased likelihood of LTOCS use (ORs: 1.37-1.57). A greater number of comorbidities was associated with worse outcomes. CONCLUSION: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes. CLINICAL TRIAL REGISTRATION: The International Severe Asthma Registry database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization Studies (European Network Centres for Pharmacoepidemiology and Pharmacovigilance [ENCEPP]/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EMA 2014; EUPAS44024) and with all applicable local and international laws and regulations, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=48848). Governance was provided by ADEPT (registration number: ADEPT1121).

Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy.

Background: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics. Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson's chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons. Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147). Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

Distributed practice. The more the merrier? A randomised bronchoscopy simulation study.

INTRODUCTION: The distribution of practice affects the acquisition of skills. Distributed practice has shown to be more effective for skills acquisition than massed training. However, it remains unknown as to which is the most effective distributed practice schedule for learning bronchoscopy skills through simulation training. This study compares two distributed practice schedules: One-day distributed practice and weekly distributed practice. METHOD: Twenty physicians in training were randomly assigned to one-day distributed or weekly distributed bronchoscopy simulation practice. Performance was assessed with a pre-test, a post-test after each practice session, and a 4-week retention test using previously validated simulator measures. Data were analysed with repeated measures ANOVA. RESULTS: No interaction was found between group and test (F(4,72) <1.68, p>0.16), except for the measure 'percent-segments-entered', and no main effect of group was found for any of the measures (F(1,72)< 0.87, p>0.36), which indicates that there was no difference between the learning curves of the one-day distributed practice schedule and the weekly distributed practice schedule. DISCUSSION: We found no difference in effectiveness of bronchoscopy skills acquisition between the one-day distributed practice and the weekly distributed practice. This finding suggests that the choice of bronchoscopy training practice may be guided by what best suits the clinical practice.

Dyad practice is efficient practice: a randomised bronchoscopy simulation study.

CONTEXT: Medical simulation training requires effective and efficient training strategies. Dyad practice may be a training strategy worth pursuing because it has been proven effective and efficient in motor skills learning. In dyad practice two participants collaborate in learning a task they will eventually perform individually. In order to explore the effects of dyad practice in a medical simulation setting, this study examined the effectiveness and efficiency of dyad practice compared with individual practice in the learning of bronchoscopy through simulation-based training. METHODS: A total of 36 students of medicine were randomly assigned to either individual practice or dyad practice. The training setting included video-based instruction, 10 bronchoscopy simulator cases and instructor feedback. Participants in the dyad practice group alternated between physical and observational practice and hence physically undertook only half of the training cases undertaken by participants who practised individually. Pre-, post- and delayed (3 weeks) retention tests were used to assess skills according to previously validated simulator measures. Data were analysed using repeated-measures analysis of variance (anova) on each dependent measure. RESULTS: A significant main effect of test was found for all measures (F2,67  > 23.32, p < 0.001), indicating improvement in performance from pre-tests to post-tests and retention tests. No interaction was found between test and group (F2,67  < 0.26, p > 0.49), indicating parallel learning curves. Most importantly, no main effect of group was found for any of the measures, indicating no difference between learning curves (F1,34  = 2.08, p < 0.16). CONCLUSIONS: Individual practice and dyad practice did not differ in their effectiveness for the acquisition of bronchoscopy skills through supervised simulation training. However, dyad practice proved more efficient than individual practice because two participants practising in dyads learned as much as one participant practising individually but required the same instructor resources and training time as the single learner.

Effects of modelling examples in complex procedural skills training: a randomised study.

CONTEXT: Learning complex procedural skills, such as bronchoscopy, through simulation training, imposes a high cognitive load on novices. Example-based learning has been shown to be an effective way to reduce cognitive load and enhance learning outcomes. Prior research has shown that modelling examples, in which a human model demonstrates the skill to a learner, were effective for learning basic surgical skills. However, principles derived from simple skills training do not necessarily generalise to more complex skills. Therefore, the present study examined the effectiveness of integrating modelling examples into simulation training for a more complex procedural skill - bronchoscopy. Moreover, this study extended previous simulation studies by using a physical demonstration rather than video-based modelling examples. METHODS: Forty-eight medical students were randomised into a modelling group and a control group. They all practised on eight bronchoscopy simulation cases individually, followed by standardised feedback from an instructor. Additionally, the modelling group watched three modelling examples of the simulated bronchoscopy, performed by the instructor. These modelling examples were interspersed between cases. Assessments were carried out at pre-, post- and 3-week retention tests with simulator-measured performance metrics. The primary outcome measure was the percentage of segments entered/minute. Other measures were wall collisions, red-out, the percentage of segments entered and the time to completion. Group differences were examined using repeated measures analysis of variance (anova). RESULTS: A clear learning curve was observed for both groups, but as hypothesised, the modelling group outperformed the control group on all parameters except the percentage of segments entered on the post-test and retained this superiority at the retention test. For the primary outcome measure, the percentage of segments entered/minute, the modelling group achieved a 46% higher score at the post-test and a 43% higher score at the retention test. CONCLUSIONS: The present study shows, that integrating modelling examples into the curriculum of bronchoscopy simulation training optimises the role of the instructor and enhances novices' learning outcomes, presumably by optimising cognitive load during training.