B J Lipworth

Dr Lipworth reports non-financial support (equipment) from GSK; grants, personal fees (consulting, talks and advisory board), other support (attending ATS and ERS) and from AstraZeneca; personal fees (talks and consulting) from Sanofi, personal fees (consulting, talks and advisory board) from Circassia in relation to the submitted work; grants, personal fees (consulting, talks, advisory board), other support (attending ERS) from Teva, personal fees (talks and consulting), grants and other support (attending ERS and BTS) from Chiesi,

Objective: Oral corticosteroids (OCS) are used to treat exacerbations of chronic rhinosinusitis with nasal polyps (CRSwNP). OCS prescribing practices vary as reported from national surveys in Italy, China, Canada, and the United States of America. Methods: Nationwide online survey of ENT doctors practicing in Scotland using Microsoft Forms.Results: 31% response rate. The most common daily dose of OCS course was 25mg and 40mg with the length being 14 and 7 days, respectively. 77% prescribe the same daily dose throughout the course. Rhinologists prescribe longer courses with a smaller daily dose of prednisolone. Only 1 respondent fully agreed that there were clear guidelines regarding the daily dose and the length of OCS course in the treatment of CRSwNP. Conclusion: The heterogeneity of OCS prescribing practice in different countries, including Scotland, reveals the need for clear guidelines with a …

Background Small airway dysfunction (SAD) is common in patients with persistent asthma and is related to poor outcomes. The objective was to compare the relative efficacy of 12 weeks treatment with anti-IL4Rα as dupilumab (Dupi) versus anti-IL5Rα as benralizumab (Benra) on airway oscillometry (AO) defined SAD in type 2 high poorly controlled severe asthma. Methods We performed a post hoc analysis from two prospective phase IV clinical trials: EudraCT 2019-003763-22 with Benra and EudraCT 2021-005593-25 with Dupi, where AO was a secondary end point. Patients were case matched for SAD severity at baseline. 22 patients (11/21 from each study) exhibited SAD defined by resistance heterogeneity between 5Hz and 20Hz (R5-R20)≥ 0.10 kPa/L/s (mean baseline R5-20: Benra 0.22 vs Dupi 0.22 kPa/L/s), while 28 patients (14/21 from each study) exhibited SAD defined by area under reactance curve …

TaggedAPTARAPThe small airways are termed the quiet zone of the lung due to the considerable challenges faced by clinicians when trying to assess and treat disease in this area. Small airway dysfunction (SAD) can be quantified using forced expiratory flow rate between 25% and 75% of forced vital capacity (FEF25%-75%) with spirometry or using heterogeneity in resistance between 5 Hz and 20 Hz (R5-R20) and reactance area (AX) with airway oscillometry (AO). According to the ATLANTIS study, 1 between 35% and 80% of patients with Global Initiative for Asthma− defined moderate-to-severe asthma exhibit spirometry-or AO-defined SAD. Here, the wide range of patients with associated SAD likely reflects the clinical heterogeneity of asthma pathophysiology and differences in pulmonary function modality. Owing to a

Over use of reliever as short acting beta-agonist (SABA) and associated underuse of controller as inhaled corticosteroid (ICS) administered via separate inhalers results in worse asthma outcomes . Such discordance can be obviated by combining both controller and reliever in the same inhaler. So called anti-inflammatory reliever (AIR) therapy comprises the use of a single inhaler containing an ICS such as budesonide (BUD) in conjunction with a reliever as either albuterol (ALB) or formoterol (FORM) ,to be used on demand with variable dosing driven by asthma symptoms in a flexible patient centred regimen. Global guidelines now support the use of BUD-ALB as AIR therapy to reduce exacerbations , either on its own in mild asthma or in conjunction with fixed dose maintenance ICS-long acting beta-agonist (LABA) in moderate to severe asthma . Using BUD-FORM on its own allows patients to seamlessly move in …

Airway hyper-responsiveness (AHR) is a tenet of the persistent asthma phenotype along with reversible airway obstruction and type 2 (T2) inflammation. Indirect acting challenges such as mannitol are more closely related to the underlying T2 inflammatory process as compared with direct challenges. In this review article, we summarise the current literature and explore the future role of mannitol AHR in clinical remission with biologics.

Rationale Asthma is characterized by type 2 (T2) inflammation, small airway dysfunction (SAD), mucus plugging, and remodeling. Airway remodeling is poorly responsive to current therapies, contributing to airflow obstruction. VESTIGE (NCT04400318) is a phase 4 imaging study to demonstrate the effects of dupilumab on airway inflammation through assessment of lung imaging and function, including airway oscillometry (AO). Methods 109 adult patients with uncontrolled T2-high moderate-to-severe asthma were randomized to dupilumab 300 mg (n= 72) or placebo (n= 37) q2 wk for 24 wk. Endpoints reported here include changes from baseline to Wk 24 in air trapping at FRC, the ventilation/perfusion ratio (iV/Q) at TLC, peripheral airway resistance as heterogeneity between 5 and 20 Hz (R5-R20) and peripheral compliance as reactance area (AX) using AO (Thorasys Tremoflo), mucus plugging, and pre …

Conflicts of Interest: Dr Chan reports personal fees (talks) and support attending ERS from AstraZeneca, personal fees (consulting) from Vitalograph, and personal fees (talks) from Thorasys. Dr Duraikannu has no relevant conflicts of interest. Dr Thouseef has no relevant conflicts of interest. Dr Lipworth reports non-financial support (equipment) from GSK; grants, personal fees (consulting, talks and advisory board), other support (attending ATS and ERS) and from AstraZeneca; personal fees (talks and consulting) from Sanofi, personal fees (consulting, talks and advisory board) from Circassia in relation to the submitted work; grants, personal fees (consulting, talks, advisory board), other

BackgroundAllergic rhinitis (AR) and asthma may impact health-related quality-of-life. However, national estimates on the quality-of-life of patients with AR or asthma are lacking.ObjectiveTo provide estimates for utility scores and EQ-5D Visual Analog Scale (VAS) for patients with AR or asthma.MethodsWe conducted a cross-sectional study using direct patient data from the MASK-air® app on European MASK-air® users with self-reported AR or asthma. We used a multiattribute instrument (EQ-5D) to measure quality-of-life (as utility scores and EQ-5D VAS values). Mean scores were calculated per country and disease control level using multilevel regression models with post-stratification, accounting for age and sex biases.ResultsWe assessed data from up to 7905 MASK-air® users reporting a total of up to 82,737 days. For AR, utilities ranged from 0.86-0.99 for good control versus 0.72-0.85 for poor control; EQ-5D …

Type 2 inflammation (T2I) is associated with systemic or local immune dysregulation in multiple conditions including asthma, chronic rhinosinusitis with nasal polyps, chronic urticaria, atopic dermatitis/eczema and eosinophilic esophagitis (EoE). A survey conducted January 23-31, 2023, aimed to understand the patient journey (awareness, knowledge and behaviors) in people aged> 21 years diagnosed with two or more T2Is diseases for at least 1 year. The survey was promoted by GAAPP partner organizations, conducted by interview, and analyzed by Dynata. A parallel survey was conducted for one month and queried healthcare providers (HCPs) who treat 20 or more T2I patients about their perceptions. Of the 641 patient respondents, 15.7% resided in the UK, 15.65% in Italy, 15.6% in the US, 15.6% in France, 15.6% in Germany, and 6.2% in Japan. The patient journey among those with T2I diseases varies by …

Dr Lipworth reports non-financial support (equipment) from GSK; grants, personal fees (consulting, 23 talks and advisory board), other support (attending ATS and ERS) and from AstraZeneca; personal fees 24 (talks and consulting) from Sanofi, personal fees (consulting, talks and advisory board) from Circassia 25 in relation to the submitted work; grants, personal fees (consulting, talks, advisory board), other 26 support (attending ERS) from Teva, personal fees (talks and consulting), grants and other support 27 (attending ERS and BTS) from Chiesi, personal fees (consulting) from Lupin, personal fees (consulting) 28 from Glenmark, personal fees (consulting) from Dr Reddy, personal fees (consulting) from Sandoz; 29 grants, personal fees (consulting, talks, advisory board), other support (attending BTS) from 30 Boehringer Ingelheim, grants and personal fees (advisory board and talks) from Mylan outside of the 31 …

In the recent report of the Organisation for Economic Coordination and Development (OECD) on Best Practices for Integrating Care to Prevent and Manage Chronic Diseases, an app on rhinitis and asthma (MASK-air®) has been listed. The OECD is a reliable source of evidence-based policy analysis and economic data largely used by governments. It has published several BPs on Public Health. On the 10th of May 2023, the OECD published 13 BPs for Integrating Care to Prevent and Manage Chronic Diseases in the European Union. The report did not cover all models of integrated care, rather, it “focuse(d) on those that are of key strategic interest to policy makers.” New MASK-air® studies (not published in the report) include equity, usability of the app in old age adults, economic impact, quality-of-life and allergen immunotherapy. MASK-air® is freely available on iOS and Android in 30 countries and has been …

MethodsChildren with moderate-to-severe type 2 asthma (baseline blood eosinophil count≥ 150 cells/μL or FeNO≥ 20 ppb) received add-on dupilumab 100/200 mg q2w (by bodyweight), or placebo for 52 weeks. They were stratified according to low, medium, or high tertile subgroups based on the change from baseline in pre-bronchodilator percent predicted forced expiratory volume in 1 second [ppFEV 1] at Week 52 in pooled dupilumab and placebo treatment arms. Using a logistic regression model adjusted for baseline characteristics, we compared the proportion of children with well-controlled asthma (Interviewer-Administered 5-item Asthma Control Questionnaire [ACQ-5-IA] score≤ 0.75) at Week 52 between tertile subgroups.ResultsMean (SD) change from baseline in pre-bronchodilator ppFEV 1 was− 6.87 (8.92), 7.52 (3.25), and 26.89 (16.04) percentage points in the low (n= 102), medium (n= 109), and …

Introduction: Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma. We performed a post hoc indirect case matched analysis from two prospective phase IV trials involving benralizumab 30mg every four weeks (Benra) EudraCT 2019-003763-22 or dupilumab 300mg every 2 weeks (Dupi) EudraCT 2021-005593-25 in Type 2 (T2) high severe uncontrolled asthma. In both studies the primary end point was the shift from baseline in mannitol sensitivity as PD10 threshold expressed as the geo mean fold change after 12 weeks of either biologic. The geometric mean fold change in mannitol reactivity as response dose ratio (RDR) was also calculated. Methods: 12 out of 21 patients from each study (n= 24 total) were case matched according to baseline mannitol PD10: Benra vs Dupi geo mean PD10 (mg) 147 vs 144, difference 1.0 (95% CI 0.6, 1.7). Corresponding median T2 values were Eosinophils (cells …

Current guidelines advocate using regular treatment with intranasal corticosteroid/antihistamine (CS/AH) combination sprays as step-up therapy for adolescent and adult patients with moderate to severe persistent allergic rhinitis (AR) where there is suboptimal control with intranasal CS alone. 1 The therapeutic rationale here is that the CS component is effective at suppressing symptoms attributable to type 2 (T2) inflammation mediated by eosinophils, whereas the AH provides additional activity on T2 symptoms mediated by IgE and mast cells. The evidence from clinical studies shows superior clinical efficacy based on symptom scores when comparing twice-daily CS/AH combination versus twice-daily CS alone, demonstrating additivity of response for the 2 moieties. 2, 3 Moreover, CS/AH exhibits a faster onset compared with CS alone due to the effect of AH moiety. 4 The more rapid onset of symptom relief with CS …

BackgroundThe 22-item sino-nasal outcome test (SNOT-22) is a frequently used patient-recorded outcome measure in patients with chronic rhinosinusitis with nasal polyps (CRSwNPs). Objective findings of nasal polyps and paranasal sinus inflammation are frequently graded using nasal polyp score (NPS) and Lund-Mackay Score (LMS), respectively.ObjectiveTo evaluate a novel, abbreviated, rhinology-focused, five-domain SNOT-5 questionnaire because we had anecdotally noticed a relative disconnect between SNOT-22 and endoscopy and imaging scores.MethodsWe performed a retrospective, cross-sectional, single-center review of patients with CRSwNPs who had filled out a SNOT-22, along with post hoc–derived SNOT-5 scores, which were then assessed in relation to NPS and LMS.ResultsA total of 129 patients were included in the analysis. SNOT-5 but not SNOT-22 scores significantly correlated vs …

Dr Chan reports personal fees (talks) and support attending ERS from AstraZeneca, personal fees (consulting) from Vitalograph, and personal fees (talks) from Thorasys. Dr Lipworth reports non-financial support (equipment) from GSK; grants, personal fees (consulting, talks and advisory board), other support (attending ATS and ERS) from AstraZeneca; personal fees (talks and consulting) from Sanofi, personal fees (consulting, talks and advisory board) from Circassia; grants, personal fees (consulting, talks, advisory board), other support (attending ERS) from Teva; personal fees (talks and consulting), grants and other support (attending ERS and BTS) from Chiesi; personal fees (consulting) from Lupin, personal fees (consulting) from Glenmark; personal fees (consulting) from Dr Reddy; personal fees (consulting) from Sandoz; grants, personal fees (consulting, talks, advisory board), other support (attending BTS …

C95. NEW CLINICAL TRIAL RESULTS IN CHRONIC LUNG DISEASE: The Bisoprolol in COPD Study (BICS): A UK Randomized Controlled Trial o Page 1 Am J Respir Crit Care Med 2024;209:A6612 Internet address: www.atsjournals.org Online Abstracts Issue C95 NEW CLINICAL TRIAL RESULTS IN CHRONIC LUNG DISEASE / Mini Symposium / Tuesday, May 21/02:15 PM-04:15 PM / San Diego Convention Center, Ballroom 20A (Upper Level) The Bisoprolol in COPD Study (BICS): A UK Randomized Controlled Trial of Bisoprolol in People With COPD at Risk of Exacerbation BJ Lipworth1, G. Devereux2, S. Cotton3, M. Nath4, The Bisoprolol in COPD Study (BICS) Trial Group; 1Scottish Centre for Respiratory Research, University of Dundee, Dundee, United Kingdom, 2Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, 3Centre for Healthcare Randomised Trials, University of …

To the Editor: We read with interest the post hoc analysis of the SYNAPSE randomized controlled trial in regard to the effects of eosinophil suppression with mepolizumab on clinical outcomes including corticosteroid usage in patients with severe chronic rhinosinusitis and nasal polyps (CRSwNP). 1 In particular, we were intrigued with these data because our own real-life experience in the NHS rhinology service is that patients treated with mepolizumab or benralizumab for severe eosinophilic unified airways disease exhibited clinically meaningful improvements in asthma control but not in CRSwNP, with the latter based on endoscopic nasal polyp and symptom scores. 2 Indeed, we initially told patients who had severe eosinophilic unified airways disease, in good faith, that they would likely experience marked improvements in both upper and lower airway outcomes with mepolizumab, but this proved not to be the …

Arsenic (As) accumulation in rice grain and subsequent transmission into the food chain is a major global concern. Numerous attempts to minimize As accumulation in rice have been researched till date. The current investigation evaluates the relative susceptibility of different growth stages of rice plant to As stress in terms of As accumulation in grain at maturity using sixty treatment combinations. Our findings suggest that supplementing with selenium (Se) resulted in minimizing As content significantly (at P < 0.001 level) in grain, irrespective of growth stages where As stress was introduced. The findings registered the following order of susceptibility to As stress: flowering > grain filling > maximum tillering. Our findings also showed that Se primed rice plants restricts majority of As accumulation in the root itself and minimizes As translocation to the above ground part. The results of this study shows that cultivation of Se …

Severe asthma with fungal sensitization (SAFS) is an allergic immune-mediated disorder existing on the spectrum between nonsensitized asthma and allergic bronchopulmonary aspergillosis (ABPA). 1 Fungal sensitization is associated with life-threatening acute asthma attacks requiring intensive care admissions and asthmarelated deaths, and it has a higher prevalence in patients with severe asthma. 2 Prospectively, it has been found that immunoglobulin (Ig) E sensitization to Aspergillus fumigatus is associated with worse lung function as forced expiratory volume in 1 second (FEV1), greater total IgE levels, and a higher prevalence of A fumigatus in sputum culture compared with nonsensitized patients with asthma. 3 In the present study, we hypothesize that patients with SAFS because of A fumigatus have worse small airway dysfunction (SAD) measured by spirometry forced expiratory flow between 25% and 75 …

IntroductionEosinophil depletion with benralizumab reduces exacerbations and improves disease control and FEV1 in patients with severe eosinophilic asthma. However, few studies have investigated the effect of biologics on small airways dysfunction (SAD) even though the latter correlates better with poor asthma control and type 2 inflammation.Methods21 GINA-defined severe asthma patients who were treated with benralizumab and who had baseline oscillometry-defined SAD were included in this study. Here, SAD was diagnosed only if patients satisfied both R5–R20≥0.10 kPa/L/s and AX≥1.0 kPa/L. The mean duration of follow-up between pre-benralizumab versus post-benralizumab clinical measurements was 8 months.ResultsMean values for FEV1% and FVC% but not FEF25%–75% significantly increased following benralizumab, along with significant reductions in Asthma Control Questionnaire (ACQ …

Eosinophilic upper gastrointestinal diseases, including eosinophilic oesophagitis and eosinophilic gastritis, are characterised by tissue eosinophilia from endoscopic biopsies. The role of key type 2 (T2) cytokines, such as interleukin (IL)-4, IL-5, and IL-13, in such conditions has received increasing attention as promising therapeutic targets using biologics. In a phase 2 trial of the IL-5 receptor-α blocker benralizumab in patients with eosinophilic gastritis, Kara L Kliewer and colleagues1 found depletion of tissue eosinophils but no impact on patient-reported outcomes. Similar discordant preliminary results were reported with benralizumab in the phase 3 MESSINA trial in patients with eosinophilic oesophagitis (NCT04543409). This disconnect between significant tissue eosinophil depletion and the absence of symptom responses in turn begs the pertinent question as to the central role of eosinophils in relation to T2 …

BackgroundThe effort-independent tidal breathing test used by oscillometry presents a viable alternative for following up patients whose condition is stable while they are receiving biologic therapy.ObjectiveWe aimed to determine intrasession and intersession repeatability values for airwave oscillometry (AOS) and spirometry in patients who were already taking benralizumab.MethodsIn all, 21 patients with severe eosinophilic asthma attended the Scottish Centre for Respiratory Research as part of a clinical trial (EudraCT identification number 2019-003763-22). Paired AOS and spirometry values were obtained at 3 separate visits (baseline and days 28 and 56) with no change in asthma therapy.ResultsIntrasession agreement between repeated measurements for AOS and spirometry was excellent (intraclass correlation coefficient ≥ 0.90) at all 3 visits. Intersession agreement was also excellent (intraclass …

BackgroundMucus plugging is recognized as a contributory factor to airway obstruction and symptoms in persistent asthma.ObjectiveWe aimed to determine phenotypic associations of mucus plugging in patients with moderate to severe asthma in a real-life clinic setting.MethodsMucus plugs (MPs) were identified by a thoracic radiologist upon high-resolution computed tomography imaging. A MP score was subsequently calculated and analyzed along with type 2 biomarkers, spirometry, severe exacerbations, and asthma control for 126 patients with moderate to severe asthma before biologic therapy.ResultsAsthma patients with MP had significantly worse FEV1%, forced expiratory flow at 25% to 75% of FVC percent, and FEV1/FVC as well as higher levels of peripheral blood eosinophils, FeNO, total IgE, and Aspergillus fumigatus IgE titers, and had previously experienced more frequent severe exacerbations. FEV …

Introduction Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK‐air®, these data have only been analyzed cross‐sectionally, without considering the changes of symptoms over time. We analyzed data from MASK‐air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods We analyzed MASK‐air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k‐means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results We analyzed …

CORRESPONDENCE AND REPLIES 1575 exacerbation rates (AAER) in both T2-high and-low patient phenotypes characterized by cutoffs according to blood eosinophils (Eos) of 300 cells/mL or fractional exhaled nitric oxide (FeNO) of 25 parts per billion (ppb). It was evident that the respective 95% confidence intervals for AAER did not overlap, in turn indicating that the relative efficacy was significantly superior in T2-high patients amounting to a 25% difference for Eos> _300 cells/mL versus< 300 cells/mL and a 32% difference for FeNO> _25 ppb versus< 25 ppb. This is perhaps unsurprising given that tezepelumab attenuates downstream expression of T2 cytokines including IL4, IL5, and IL13. Because tezepelumab only partially suppresses Eos compared with depletion by benralizumab, we would therefore be interested in a pragmatic head-to-head comparison in SUA to look at super-responders, especially for …

Precision medicine in asthma refers to the collection of a wide array of data including clinical, biomarker, radiological, lifestyle, and genetic information to optimize patient outcomes. It involves the identification of treatable traits that can be targeted to produce better results compared with conventional care. Our aim was to investigate the impact of a particular phenotype, dual bronchial wall thickening (BWT) and mucus plugging (MP), detected on high-resolution computed tomography (HRCT) imaging, on spirometry, type 2 (T2) biomarkers, and exacerbation frequency in patients with poorly controlled asthma. We chose this combination phenotype because there have been recent studies looking at the effect of biologics on both BWT and MP individually, but not together. The hypothesis was that the dual MP-BWT phenotype confers worse clinical outcomes than either phenotype alone.Data on 62 patients, diagnosed …

Dr Lipworth reports non-financial support (equipment) from GSK; grants, personal fees (consulting, talks and advisory board), other support (attending ATS and ERS) and from AstraZeneca, grants, personal fees (consulting, talks, advisory board), other support (attending ERS) from Teva, personal fees (consulting) from Sanofi, personal fees (consulting, talks and advisory board) from Circassia, personal fees from Thorasys (consulting, talks) in relation to the submitted work; personal fees (consulting) from Lupin, personal fees (consulting) from Glenmark, personal fees (consulting) from Dr Reddy, personal fees (consulting) from Sandoz; grants, personal fees (consulting, talks, advisory board), other support (attending BTS) from Boehringer Ingelheim, grants and personal fees (advisory board and talks) from Mylan outside of the submitted work; and the son of BJL is presently an employee of AstraZeneca.

TaggedAPTARAPHistorically, chronic rhinosinusitis (CRS) has been categorized as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps. 1 The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 guidelines suggest classifying CRS on the basis of type 2 (T2) biomarkers. 2 Type 2 inflammation is responsible for driving the disease in 80% to 90% of patients with CRSwNP. 1 In clinical practice, peripheral blood eosinophils (PBE) and total IgE may help assess, but cannot fully confirm, whether CRS is driven by T2 inflammation. Peripheral blood eosinophils and IgE reflect T2 cytokines interleukin (IL)-5, and IL-4 and IL-13, respectively. We aimed to assess how PBE and total IgE are associated with symptoms and quality of life using the 22-item sinonasal outcome test (SNOT-22) and objective findings of CRSwNP on the basis of Lund-Mackay score (LMS) on computed tomography imaging …

Introduction Chronic rhinosinusitis with nasal polyps (CRSwNP) and severe eosinophilic asthma (SEA) are common comorbidities characterised by type 2 inflammation associated with increased expression of interleukin 5. Methods Eight patients with SEA and severe CRSwNP attended the Scottish Centre for Respiratory Research as part of a clinical trial (EudraCT number 2019-003763-22). Following an initial 4-week run-in period (baseline) when patients took their usual inhaled and intranasal corticosteroid treatment for SEA and CRSwNP, they all received subcutaneous benralizumab 30 mg q4w for 12 weeks. Results Following 12 weeks of benralizumab, no significant differences were detected in nasal global symptom visual analogue score (VAS), hyposmia VAS, total nasal symptom score, or peak nasal inspiratory flow. In contrast, Asthma Control Questionnaire significantly improved along with near-complete depletion of peripheral blood eosinophils by 99%, while eosinophil-derived neurotoxin fell by 72%. Conclusions Greater improvements in patient-reported outcomes related to asthma were observed than with CRSwNP in response to benralizumab.

Introduction Previous studies using 16S rRNA sequencing have identified changes in the airway microbiome associated with inhaled corticosteroid treatment (ICS). Recent data has shown that studying microbial interactions (the interactome) may provide additive clinical insight. This study aimed to evaluate the effect of ICS withdrawal on the airway metagenome in patients with COPD. Methods Stable patients with moderate to severe COPD currently treated with ICS and with a blood eosinophil count< 300cell/ul were enrolled. Patients were randomised to receive either Tiotropium and Olodaterol (ICS withdrawal) or Fluticasone Furoate/Vilanterol (ICS continuation) for 6 months. Sputum samples were taken at baseline and months 1, 2, 3 and 6 and during exacerbation. The primary outcome was sputum bacterial load using 16S qPCR and the secondary outcome was microbiome characterisation by 16S rRNA …

BackgroundSystemic corticosteroids have been widely used for treating patients with severe acute respiratory distress syndrome. Inhaled corticosteroids may have a protective effect for treating acute coronavirus disease 2019 (COVID-19); however, little is known about the potential effect of intranasal corticosteroids (INCS) on COVID-19 outcomes and severity.ObjectiveTo assess the impact of prior long-term INCS exposure on COVID-19 mortality among patients with chronic respiratory disease and in the general population.MethodsA retrospective cohort study was conducted. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between INCS exposure and all-cause and COVID-19 mortality, adjusted by age, sex, deprivation, exacerbations in the last year, and comorbidities.ResultsExposure to INCS did not have a significant association with …

BackgroundChronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH.MethodsWe measured isotime inspiratory capacity (IC) during cycle endurance testing in eleven moderate-severe COPD subjects, alongside other non-invasive cardiopulmonary exercise, bioreactance cardiac output, pulmonary function, biomarkers and daily domiciliary measures. Participants received titrated doses of either bisoprolol (maximim 5 mg) or celiprolol (maximum 400 mg) in randomised crossover fashion, each over 4 weeks.ResultsClinically relevant DH …

Background: The 22-item sinonasal outcome test (SNOT-22) is a commonly used patient-recorded outcome measure in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Objective findings of nasal polyps and paranasal sinus inflammation are commonly graded using nasal polyp score (NPS) and Lund-Mackay score (LMS), respectively.Objective: We had anecdotally noticed a relative disconnect between SNOT-22 versus endoscopy and imaging scores, therefore we evaluated a novel abbreviated rhinology focused five domain SNOT-5 questionnaire.Methods: We performed a retrospective cross-sectional single-centre review of CRSwNP patients who had filled out a SNOT-22, along with post hoc derived SNOT-5 scores, which were then assessed in relation to NPS and LMS.Results: 129 patients were included in the analysis. SNOT-5 but not SNOT-22 scores significantly correlated versus either NPS (p< 0.005) and LMS (p< 0.001), while only SNOT-5 differed significantly when comparing the cohort's lowest and highest tertiles for mean LMS: 11.8 vs 16.8 (95% CI 1.5 to 8.4) p< 0.01, and for mean NPS 12.4 vs 15.6 (95% CI 0.5 to 5.9) p< 0.05.Conclusion: In a retrospective real-life cohort study of CRSwNP there was a relative disconnect between the significant association of SNOT-5 but not SNOT-22 in relation to objective endoscopy and imaging measures. We therefore propose that further prospective intervention studies are indicated in CRSwNP to evaluate the SNOT-5 score including establishing the minimal clinically important difference.

Bronchiectasis is defined as irreversible bronchial dilatation typically associated with characteristic radiologic and clinical features. 1 Its prevalence in asthma varies but is generally accepted to be higher in patients with more severe disease (range 25%-68%), especially in the presence of allergic fungal sensitization. 2 A previous analysis revealed that the asthma bronchiectasis (AB) phenotype is related to higher blood eosinophil counts. 3 However, the same study found no differences in spirometry compared with patients having asthma without bronchiectasis. 3 Another large retrospective study 4 found that patients with AB had lower forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) coupled with a significantly greater history of tuberculosis and nontuberculous mycobacterial lung disease. Nevertheless, there is limited data regarding differences in clinical characteristics in patients …

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined …

Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with mucosal inflammation in asthma. In recent years, the advent of biologics and antialarmins has transformed severe asthma treatment in terms of reducing oral-corticosteroid–requiring exacerbations and improving disease control, asthma quality of life, and spirometry-measured lung function. In contrast, there have been comparatively fewer studies investigating the efficacy of biologics in airway hyperresponsiveness. In this focused review, we summarize the existing evidence base in this area regarding omalizumab, mepolizumab, benralizumab, and tezepelumab.

Dr Lipworth reports non-financial support (equipment) from GSK; grants, personal fees 24 (consulting, talks and advisory board), other support (attending ATS and ERS) and from 25 AstraZeneca; personal fees (talks and consulting) from Sanofi, personal fees (consulting, talks 26 and advisory board) from Circassia in relation to the submitted work; grants, personal fees 27 (consulting, talks, advisory board), other support (attending ERS) from Teva, personal fees 28 (talks and consulting), grants and other support (attending ERS and BTS) from Chiesi, personal 29 fees (consulting) from Lupin, personal fees (consulting) from Glenmark, personal fees 30 (consulting) from Dr Reddy, personal fees (consulting) from Sandoz; grants, personal fees 31 (consulting, talks, advisory board), other support (attending BTS) from Boehringer Ingelheim, 32

TaggedAPTARAPDupilumab is a humanized immunoglobulin G (IgG)− 4 monoclonal antibody that exerts its anti-inflammatory properties by binding to the interleukin (IL)-4Ra receptor to mediate IL-13 and IL-4 activity. 1 It has been reported in phase 3 randomized controlled trials to improve the forced expiratory volume in 1 second (FEV1), severe exacerbation frequency, and symptom control in persistent asthma. 2 There is a paucity of data looking at the impact of dupilumab therapy on small airway dysfunction (SAD) despite the latter being closely associated with type 2 inflammation and asthma control. 3 In this regard, airway oscillometry (AO) is a reliable method of quantifying the degree of SAD. Useful values that can be obtained include the frequency-dependent resistance heterogeneity between 5 Hz and 20 Hz (R5-R20) indicating peripheral airway resistance, and reactance at 5 Hz (X5), and area under the …

BackgroundAirway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma.ObjectiveWe investigated whether eosinophil depletion with benralizumab might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open-label design.MethodsAfter a 4-week run-in period with provision of usual inhaled corticosteroids and/or long-acting β-agonist (baseline), adults with mannitol-responsive uncontrolled severe eosinophilic asthma received 3 doses of open-label benralizumab 30 mg every 4 weeks, followed by 16 weeks’ washout after the last dose. The primary outcome was doubling difference (DD) in provocative dose of mannitol required to decrease FEV1 by 10% (PD10) at the end point after 12 weeks, powered at 90% with 18 patients required to detect 1 DD. Secondary outcomes included measures assessed by the asthma control questionnaire and mini-asthma …

BackgroundA recent study demonstrated a significant correlation between bronchial biopsy airway remodeling and quantitative computed tomography looking at bronchial wall thickness.ObjectiveTo identify clinical associations with bronchial wall thickness in moderate to severe asthma.MethodsNinety-two respiratory physician–diagnosed Global Initiative for Asthma–defined patients with moderate to severe asthma were included in this retrospective cohort study. Blinded to all clinical data, 2 senior thoracic radiologists independently measured airway lumen and total airway area at 4 different bronchopulmonary segments using high-resolution computed tomography imaging. We calculated adjusted odds ratios with regard to the association of bronchial wall thickness with spirometry, oscillometry, exacerbations, and nasal polyps.ResultsThe pooled analysis for all 4 bronchopulmonary segments showed that an area …

To the Editor: We read with interest the study of Wang et al 1 looking at domiciliary spirometry and FeNO in relation to asthma control in a real-life clinic setting. Despite poor adherence and missing values, they reported that a higher coefficient of variation for FeNO predicted poorer disease control. Domiciliary measurement of FEV1 and FeNO was evaluated prospectively by Anderson et al 2 in a randomized crossover design to assess the dose response to fluticasone propionate (FP) 100 and 500 mg daily. There was significant diurnal variability in FeNO, in which the mean amplitude of diurnal variability between morning and evening readings was 15.6%(P 5. 004) in the washout period and 24.3% with FP 100 mg (P 5. 01) and 28.9% with FP 500 mg (P 5. 01), with morning values being higher. This in turn points to a circadian rhythm for type 2 asthma inflammation that is mediated by IL-13. The speed of onset for …

BackgroundSome chronic rhinosinusitis with nasal polyps patients undergo revision surgery at some point following initial functional endoscopic sinus surgery. This review aimed to identify the predictive factors for recurrence of nasal polyps requiring oral corticosteroids or revision surgery in chronic rhinosinusitis with nasal polyps following functional endoscopic sinus surgery.MethodA retrospective analysis of 221 patients who underwent functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps in a tertiary rhinology centre, between January 2015 and December 2018, was undertaken.ResultsForty-four (21.6 per cent) patients underwent medical polypectomy, 19 (9 per cent) underwent revision surgery and 51 (24.3 per cent) underwent combined polypectomy during the mean follow-up time of 5.3 years. Patients aged less than 55 years of age, with a history of previous functional endoscopic …

BackgroundIn the year 2035, projections have estimated that 5% of the Scottish population will be morbidly obese defined as a body mass index (BMI) greater than or equal to 40 kg/m2. Airway oscillometry is an effort-independent test akin to bronchial sonar which measures resistance and compliance.ObjectiveTo evaluate the impact of obesity on lung mechanics using oscillometry.MethodsClinical data for 188 patients with respiratory physician–diagnosed moderate-to-severe asthma were retrospectively collected and analyzed.ResultsObesity (BMI 30-39.9 kg/m2) and morbid obesity (BMI ≥ 40 kg/m2) were associated with a significantly worse heterogeneity of peripheral resistance between 5 Hz and 20 Hz and peripheral compliance as low-frequency reactance at 5 Hz and area under the reactance curve, as compared with normal weight (BMI 18.5-24.9 kg/m2). Cluster analysis incorporating oscillometry …

To the Editor, The presence of bronchodilator response (BDR) is one of the key hallmarks in diagnosing asthma and is traditionally defined as a> 200 ml and> 12% improvement in spirometry forced expiratory volume in 1 s (FEV1) following short acting beta agonist therapy. Patients who demonstrate BDR typically have higher levels of airway inflammation, poorer asthma control and a greater spirometric response to inhaled corticosteroid (ICS) therapy. 1–3 Airway oscillometry is an effort-independent tidal breathing manoeuvre that also assesses small airway function through measuring differences in resistance between 5 and 20 Hz (R5-R20), reactance at 5 Hz (X5) and area under reactance curve (AX). 4 It has previously been demonstrated that oscillometry BDR is related to asthma control, 5 and that R5-R20 and AX bronchodilator response display greater sensitivity compared to that of FEV1 or FEF25-75 in …

Asthma patients remain susceptible to severe exacerbations even when their condition is seemingly brought under control, 1 potentially suggesting an element of disconnect between exacerbations and asthma control. It has recently been shown that combining oscillometry and spirometry measurements of pulmonary function identifies patients with worse asthma control and more frequent severe exacerbations requiring oral corticosteroids (OCS). 2 Moreover, those with combined elevation of peripheral blood eosinophil (PBE) counts and fractional exhaled nitric oxide (FeNO) subsequently have higher asthma exacerbation rates across all asthma severities but especially in those with more severe disease. 3However, to date, there are no available data looking at combining measurements of airway physiology with type 2 (T2) biomarkers. Here we, therefore, aim to calculate odds ratios (ORs) in association with …

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel …

Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real‐life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK‐air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK‐air® data of European users with self‐reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom‐medication score (CSMS). We applied Bayesian mixed‐effects models, with clustering by patient, country and pollen season. Results We analysed a total of …

Socioeconomic status (SES), which has traditionally been reported with education, income, and occupation, 1 was thought to influence health through ability to pay for services and treatments; establishment of early health habits; and resultant education, job opportunities, and income potential. Extensive research over the past 5 decades has underscored the gradient in health associated with differences in SES, and such a gradient has never been more relevant than today, when marked inequities in health are being observed in a public way through the effects of the COVID-19 pandemic. 2Addressing disparities resulting from differences in SES seems as if it would be especially relevant for asthma, the most prevalent chronic disease in pediatrics. Lower SES has been shown to be related to a higher prevalence of asthma. The current rate of asthma among children living below the poverty threshold is estimated at …

IntroductionForced vital capacity (FVC) is often preserved in severe asthma unless there is evidence of either airway remodelling or air trapping. Area under the reactance curve (AX) can be used to assess small airways dysfunction related lung stiffness and is related to disease control in severe asthma.MethodsWe explore if there may be a potential synergistic interaction between FVC and AX in terms of impaired asthma control as ACQ and exacerbations requiring oral corticosteroids (OCS). We pragmatically defined < 100% and ≥ 1.0 kPa/L/s as impaired FVC or AX, respectively. ResultsPatients with combined impairment of FVC and AX had significantly worse asthma control as higher ACQ, more severe exacerbations requiring OCS and worse spirometry (FEV1 and FEF25–75) than those with impaired FVC but preserved AX.ConclusionThis in turn supports using both spirometry and oscillometry to …

Current Global Initiative for Asthma guidelines advocate the use of long-acting muscarinic antagonists (LAMAs) as add-on therapy to inhaled corticosteroid (ICS) combined with long-acting b-agonist (LABA) at steps 4 and 5 to improve control and reduce exacerbations in persistent adult asthma. Such triple therapy (ICS and LABA and LAMA) can either be open as 2 separate inhalers; ICS combined with LABA and a separate LAMA inhaler, or closed as a single triple inhaler. Muiser et al 1 recently provided an excellent overview on LAMAs in asthma as either open or closed therapies. Here, we will briefly critique the current evidence appertaining to pivotal phase 3 trials involving closed single inhaler triple therapy particularly focusing on exacerbations. Such trials allow for a valid head-to-head comparison of single triple vs dual therapy by the same inhaler platform. There are 3 currently available single triple and …

Background Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., “real‐world data”). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co‐medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. Methods We assessed the MASK‐air® app data (May 2015–December 2020) by users self‐reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co‐medication. Results We analysed 269,837 days from 10,860 users …

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ‐5D (EuroQuol) and WPAI‐AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality‐of‐life data (EQ‐5D visual analogue scale and WPA‐IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0‐2). Users with a score of 3 or 4 had a significant impairment in quality‐of‐life questionnaires.

Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air(R) app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK-air(R) data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales-VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season. Results We analysed a total of 42 …

We were therefore intrigued to read the post hoc analysis of the SYNAPSE trial in severe CRSwNP, in which the clinical response to mepolizumab was not determined by baseline PBE levels for the coprimary end points of endoscopic nasal polyp score (NPS) and nasal obstruction visual analog scale. 3 For example the proportion of patients with at least a 1-point improvement in nasal polyp score for the difference between mepolizumab and placebo was 21.7% for patients with a PBE level less than 300 cells/mL compared with 22.3% for patients with a PBE level of at least 300 cells/mL.For the key secondary end point of rescue surgical polypectomy, a significant reduction was observed with mepolizumab in patients with a baseline PBE level of at least 300 cells/mL but not with a PBE level less than 300 cells/mL, although the CIs for the hazard ratios were widely overlapping. Similar findings were reported in …

Andrew Menzies-Gow and colleagues1 reported the results of the PONENTE trial, which showed that a personalised regimen of tapering oral corticosteroids in the presence of the anti-IL5 receptor α-directed cytolytic monoclonal antibody benralizumab can help to achieve elimination or dose reduction of oral corticosteroids in a large proportion of patients with severe eosinophilic asthma. A 250 µg dose of adrenocorticotropic hormone (ACTH) dynamic stimulation test was used to assess the degree of impaired adrenal reserve. However, the 250 µg dose of ACTH is supraphysiologic and will inevitably result in a relatively higher proportion of tests with apparently normal stimulated cortisol levels compared with a more physiological dose of 0· 5–1 µg. 2 Therefore, the presence of a normal cortisol response after stimulation with 250 µg of ACTH in turn might lull clinicians into a false sense of security in terms of …

Background Co‐medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis‐related search patterns in Google Trends. This study aims to assess AR co‐medication and its regional patterns in Europe, using real‐world data. Methods We analysed 2015–2020 MASK‐air® European data. We compared days under no medication, monotherapy and co‐medication using the visual analogue scale (VAS) levels for overall allergic symptoms (‘VAS Global Symptoms’) and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. Results We analysed …

It was a usual morning when one of the authors (LK), a dermatologist, awoke with many extremely pruritic papules over her anterior and posterior trunk (Figure 1). Beside her was her husband (MW), an allergist/immunologist, who had no similar lesions that day. With the assistance of a pest control service owner (ST) with entomological knowledge and his entomologist colleague (JS), the diagnosis of bird mite dermatitis was made. Gamasoidosis (acariasis, avian-mite dermatitis or bird-mite dermatitis) can be distinguished from other arthropod bites. 1Diagnosis is based on the gross morphology, severe pruritus, and presence of a recently abandoned bird’s nest contiguous with the house. The pruritic papules of bird-mite dermatitis have other classical features that point to the diagnosis. The multiple, very pruritic papules occur over the trunk, proximal extremities, particularly in the folds of the elbows, and under …

Introduction: Impact of anti-IL5rα benralizumab (Benra) on airway hyperresponsiveness (AHR) to mannitol is unknown.Methods: After a 4wk run-in period on usual ICS/LABA (baseline), adults with mannitol responsive uncontrolled severe eosinophilic asthma (SEA) received 3 doses of open label Benra 30mg Q4wk. Primary outcome was doubling dose (DD) change in mannitol PD10 at 12wk, powered at 90% with n=18 pts to detect a 1DD diff. Study was registered as EudraCT 2019-003763-22.Results: Preliminary data are presented for 21pts at 12wk post Benra (Table). Mean age 53yr,FEV1 80%,ICS dose 1895µg,n=12 LAMA,n=13 LTRA. There were no sig changes in any outcomes pre vs post run-in. Improvement in mannitol PD10 was sig by 4wk with a 2.1DD (95%CI 1.0-3.3,p<0.001) diff at wk12, while ACQ/mini-AQLQ changes were sig by 2wk. Eos were depleted by 2wk (449 to 6 cells/µl). No clinically …

To the Editor: The excellent recent article by Jenkins et al 1 reviewed the importance of sex and gender differences in asthma inflammation and disease control outcomes. However, we were surprised that little or no mention was made as to the impact of sex hormones on two key aspects of persistent asthma: airway hyperresponsiveness (AHR) and especially b2-receptor function. This is fundamental because commonly used treatments such as inhaled corticosteroids (ICS) attenuate AHR whereas long acting b-agonists (LABAs) stabilize airway smooth muscle. In this regard, women with asthma have augmented AHR during the premenstrual period. 2 Moreover, asthmatic females exhibit abnormal b2-receptor function evident as a lack of normal upregulation seen in nonasthmatic individuals occurring during the postovulatory phase, 2 whereas in tandem, the postovulatory surge in progesterone paradoxically …

No funding was received for this work. Conflicts of interest: K. Milger reports speaker fees for AstraZeneca, GSK, Novartis, and Sanofi, all outside the submitted work. N. Kneidinger reports personal fees from AstraZeneca and Novartis, all outside the submitted work. C. Mümmler declares that he has no relevant conflicts of interest.

Clinical Implications: Numerous mobile health apps are available to patients with food 16 allergies, which include features such as recipes, education, sharing of food allergy profiles, and 17 identification and translation of ingredients. The apps were overall acceptable when using a 18 validated rating criteria. 19

Dyspnea, tachypnea, and throat tightness following vaccination provoke concern for anaphylaxis, but these symptoms are also characteristic of vocal cord dysfunction/inducible laryngeal obstruction. We report the first case series of vocal cord dysfunction/inducible laryngeal obstruction occurring in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(coronavirus disease 2019 [COVID-19]) vaccination.The Brighton Collaboration anaphylaxis definition includes symptoms of respiratory distress, tachypnea, hoarse voice, stridor, and a sensation of throat closure. 1 These features significantly overlap with manifestations of vocal cord dysfunction/inducible laryngeal obstruction (s)(VCD/ILO), a disorder characterized by intermittent laryngeal obstruction. 2 We have recently proposed cardinal VCD/ILO phenotypes, including incident-associated VCD/ILO, which may be linked to vaccination. 3 This …

Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma — Discovery - the University of Dundee Research Portal Skip to main navigation Skip to search Skip to main content Discovery - the University of Dundee Research Portal Home Discovery - the University of Dundee Research Portal Logo Home Profiles Research units Research Outputs Projects Datasets Theses Activity Press/Media Research Facilities Prizes Search by expertise, name or affiliation Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma Brian J. Lipworth (Lead / Corresponding author), Rory Chan, Kirsten E. Stewart Molecular and Clinical Medicine Research output: Contribution to journal › Letter › peer-review 34 Citations (Scopus) Overview Original language English Pages (from-to) 662-663 Number of pages 2 Journal New England Journal of Medicine Volume 387 Issue number 7 Early online date 15 …

Introduction: The presence of bronchodilator response (BDR) is one of the key hallmarks in diagnosing asthma and is traditionally defined as a ≥200ml and ≥12% improvement in FEV1 following short-acting beta-agonist therapy. Although oscillometry BDR is associated with poor asthma control it is less well characterised.Objective: In this prospective cohort study we aim to elucidate relative BDRs for spirometry and oscillometry and calculate the signal-to-noise ratio as standardised response means (SRM).Methods: 33 severe eosinophilic asthma patients were enrolled between December 2020 and October 2021. Spirometry and oscillometry were performed before and 15 minutes after 400µg salbutamol.Results: Spirometry and oscillometry values were all statistically significant (p<0.001) pre- versus post-bronchodilator. The greatest improvements after bronchodilation were observed for R5-R20 (37.9%) and AX …

Small airways dysfunction defined by spirometry and oscillometry together confers worse outcomes in moderate to severe asthma. This emphasises the importance of combining spirometry and oscillometry to characterise the small airway asthma phenotype. https://bit.ly/3CcaZ3e

The small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree. Recently, this has become particularly relevant as measurements of small airways using airway oscillometry for example, are strong determinants of asthma control and exacerbations in moderate-to-severe asthma. The small airways can be assessed using spirometry as forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25–75) and has been deemed more accurate in detecting small airways dysfunction than forced expiratory volume in 1 s (FEV1). Oscillometry as the heterogeneity in resistance between 5 and 20 Hz (R5–R20), low frequency reactance at 5 Hz (X5) or area under the reactance curve between 5 Hz and the resonant frequency can also be used to assess the small airways. The small airways can also be …

BackgroundChronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.MethodsBICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post …

Biologics, including omalizumab, mepolizumab, benralizumab, and dupilumab, targeting downstream IgE, cytokines IL-5, and IL-4/13, respectively, have shown promising effects in terms of reduction in annualized asthma exacerbation rates (AER), oral corticosteroid-sparing effects, improvements in forced expiratory volume in 1 second, and improved Asthma Control Questionnaire scores. However, despite these welcome advances, approximately 30% of patients with severe asthma receiving biologics tailored to their specific downstream type 2 biomarkers, including total IgE, peripheral blood eosinophils, and fractional exhaled nitric oxide, do not experience meaningful improvements in their AER. Instead of blocking downstream cytokines, targeting upstream epithelial alarmins, including IL-33, thymic stromal lymphopoietin, and IL-25, has been proposed to tackle the immunologic heterogeneity of asthma. This …

Introduction: Mucus plugging (MP) is recognised as a contributory factor to airway obstruction and symptoms in persistent asthma. We aimed to determine clinical predictors and phenotypic associations of mucus plugging in moderate-to-severe asthma in a real-life clinic setting.Methods: MPs were identified by a thoracic radiologist on HRCT. A MP score (MPS) was subsequently calculated and analysed along with type 2 (T2) biomarkers, spirometry, severe exacerbations and asthma control for 126 moderate to severe asthma patients.Results: Asthma patients with MP had significantly worse FEV1%, FEF25-75% and FEV1/FVC; higher levels of peripheral blood eosinophils, fractional exhaled nitric oxide, total IgE and A. fumigatus IgE titres associated with more frequent severe exacerbations. Adjusted odds ratios (95%CI) for prediction of MP were as follows: FEV1/FVC 3.01(1.14,7.97); ≥2 exacerbations/yr 5.00(1.55 …

Respiratory oscillometry is an effort-independent pulmonary function test that can assess respiratory impedance over a range of frequencies, comprising resistance (R) and reactance (X) moieties. Governed by Poiseuille’s law, airway resistance is largely determined by airway caliber and length, whereas reactance comprises elastance and inertance components and can be used as a measurement for lung stiffness at various frequencies. Low-frequency sound waves penetrate further down the airways and hence reflect changes in the whole lung. Therefore, total airway resistance can be assessed by measuring at 5 Hz (R5), whereas airway compliance can be assessed as reactance at 5 Hz (X5). 1 Recently it has been shown that adults with a positive bronchodilator response assessed by R5 or X5 have a higher prevalence of asthma and wheezing. 2 Furthermore, X5 has greater sensitivity in identifying poor …

Several tools can assess the control of allergic rhinitis (AR), including symptom scores, control scores (eg, Control of Allergic Rhinitis and Asthma Test–CARAT (1); Allergic Rhinitis Control Test-ARCT (2)), patients’ self-administered visual analogue scales (VASs), and patients’ reported outcomes for quality-of-life and work.Mobile apps can incorporate these tools, allowing a multidimensional assessment of AR patients. As an example, MASK-air®(Mobile Airways Sentinel NetworK) is a validated app for rhinitis and asthma, certified as a Good Practice of DG Santé (3). MASK-air® VASs were shown to be reliable and valid instruments (4), and to be associated with air pollutant levels and pollen exposure (5). MASK-air® uses VASs to daily register users’ AR symptoms and their impact on work. In addition, users can answer optional questionnaires, such as CARAT, EQ-5D-5L and the Work Productivity and Activity Impairment: Allergic Specific (WPAI: AS)(6).

Persistent asthma is characterized by the presence of reversible airflow obstruction, airway hyperresponsiveness, and symptoms and exacerbations in association with airway inflammation. Measurement of type 2 (T2) biomarkers in patients with poorly controlled asthma is important in defining the particular inflammatory phenotype. In real-life clinical practice, this involves measuring fractional exhaled nitric oxide (FENO), peripheral blood eosinophils (PBEs), and IgE. These biomarkers are commonly used to infer activity of T2 proinflammatory cytokines, namely, IL-4, IL-5, and IL-13, with PBE being predominantly driven by IL-5, and IgE and FENO by IL-4 and IL-13. 1 Such patients with T2-high asthma usually respond well to corticosteroids and T2 biologics. In contrast, patients with T2-low asthma may have increased expression of IL-17 in association with more neutrophilic inflammation, which tends to be …

In this study, we therefore evaluate whether using airflow obstruction (defined by forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC]< 0.7) as a starting point in a real-life National Health Service (NHS) asthma clinic setting is associated with oscillometry-defined small airways dysfunction (SAD) and type 2 inflammation, focusing on more severe asthma. Notably, the presence of SAD using oscillometry is associated with poorer control in mildto-moderate asthma. 2This retrospective cohort study included 193 patients who were defined by the respiratory physician Global Initiative for Asthma as having moderate-to-severe asthma and who attended the NHS Tayside asthma clinic between January 2016 and July 2022. Fractional exhaled nitric oxide was measured using NIOX VERO (Circassia, Oxford, United Kingdom) according to the manufacturer’s instructions and American Thoracic Society and …

The Article by Evelijn S Lourijsen and colleagues1 suggests a significant but clinically irrelevant effect of combining endoscopic sinus surgery (ESS) with medical therapy in chronic rhinosinusitis with nasal polyposis (CRSwNP) for the primary outcome of sinonasal outcome test 22. Notably, patients with asthma and CRSwNP have higher type-2 biomarkers as peripheral blood eosinophils and fractional exhaled-breath nitric oxide than patients with asthma alone. 2 Such elevated type-2 biomarkers are associated with a better response to corticosteroid therapy. Therefore, we would be especially interested to know whether the authors have additional phenotypic information at baseline to show whether ESS might better facilitate the response to corticosteroid therapy in patients with such high biomarkers. With regards to what might currently be considered optimal medical therapy, the advent of type-2 biologics such as …

Repeatability of impulse oscillometry in severe asthma is unknown. This study reports on medium term repeatability for IOS and proposes values for within subject biological variability in patients with poorly controlled severe asthma. https://bit.ly/3a5o52W

Introduction Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma and can be assessed using indirect challenge with mannitol. However, the effect of the anti-IL5rα monoclonal antibody benralizumab (Benra) on AHR is currently unknown. Methods After an initial 4 wk run-in period on usual ICS/LABA (baseline), adults with uncontrolled (ACQ≥ 1.5) severe eosinophilic asthma (SEA) received 3 doses of open label Benra 30mg Q4wk in addition to usual therapy. The primary endpoint was the doubling dose (DD) change in mannitol sensitivity as PD10 FEV1 after 12 wk compared to baseline, powered at 90% with n= 18 patients to detect a 1 DD difference. Key secondary outcomes included mannitol reactivity as response dose ratio (RDR), spirometry, oscillometry, ACQ-6, mini-AQLQ, peripheral blood eosinophils (PBE) and FeNO. This study was registered with EudraCT as 2019-003763-22. Results …

2. METHODSA bibliographic survey identified common symptoms induced by VOC Delta and Omicron. Then, a Delphi questionnaire regarding key symptoms associated with SARS‐CoV‐2 infection was developed based on the items from ARIA‐EAACI‐GA2LEN consensus 2 and from literature. Symptoms included common cold (upper airway), chemosensory, bronchial, and pulmonary as well as systemic illness symptoms (Table 1).

Background Although there are many asymptomatic patients, one of the problems of COVID‐19 is early recognition of the disease. COVID‐19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID‐19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA‐EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID‐19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID‐19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two‐way ANOVA revealed significant differences in the symptom intensity between the three …

Introduction Bronchodilator response (BDR) is conventionally defined as a 200ml or 12% improvement in FEV1. In mild to moderate asthma, forced oscillation technique (FOT) BDR is closely related to asthma control.1 FOT BDR in patients with severe eosinophilic asthma (SEA) is however unknown.Aim To determine relative BDR for spirometry and airway oscillometry (AOS,Thorasys Tremoflo) in SEA.Methods Preliminary baseline data from a prospective study (EudraCT No. 2019-003763-22) are presented on SEA patients in response to 400µg salbutamol.Results Mean values were age 52, FEV174%, FEF25-7541%, R5 184%, ACQ 2.9, Eosinophils 576 cells/µl, FeNO 54ppb and BDP equivalent ICS dose 1809µg.Mean absolute changes were: FEV10.202 L (p<0.001); FEF25-750.308 L/s (p<0.001); resistance at 5Hz R5 0.12 kPa/L/s (p=0.001); peripheral airway resistance between 5 and 20Hz R5-R20 0.08 kPa/L …

BackgroundNasal polyps (NPs) are a common comorbidity of asthma. Differences in disease endotype and phenotype may have treatment implications for these concomitant conditions, including biologic therapies.ObjectiveTo determine putative differences in type 2 biomarkers, lung function, and asthma control in patients with asthma with NPs (AwNPs) and those with asthma alone (A).MethodsA total of 140 consecutive patients with moderate to severe asthma with or without endoscopic NPs taking a daily inhaled corticosteroid dose of greater than or equal to 800 µg and at least 1 second-line controller were identified from our National Health Service specialist respiratory and rhinology clinics. Data were collected before starting on biologics, including peripheral blood eosinophils (PBEs), fractional exhaled nitric oxide (FeNO), allergy status, spirometry, impulse oscillometry, Asthma Control Questionnaire, oral …

which in vulnerable individuals showed inhaled budesonide to confer a non-significant–25%(95% CI–45 to 3) relative reduction in the composite coprimary endpoint of hospital admission or death, with the number needed to treat being 50.

Forced expiratory flow between 25% and 75% of forced vital capacity should be incorporated to assess improvement in small airways dysfunction (SAD) for patients with severe asthma receiving biologics. Impulse oscillometry (IOS) can be useful as an adjunct, particularly in those with baseline IOS-defined SAD.In Scotland, the current licensed biologic therapies for severe refractory asthma include omalizumab, mepolizumab, and benralizumab. These agents have been shown to significantly reduce asthma exacerbations and oral corticosteroid (OCS) use. 1 Although the improvements observed in patient-reported outcomes and lung function measured by forced expiratory volume in 1 second (FEV1) were statistically significant, neither achieved the minimal clinically important difference (MCID). 1 Small airways dysfunction (SAD) can be measured using spirometry expressed as the forced expiratory flow between …

We appreciate the interest shown by J.F.M. van Boven and co-workers in our study. PACT [1] was first and foremost designed as a pragmatic randomised controlled trial (RCT) reflecting current UK primary care practice. While addition of controller treatment for those in the personalised care group with poor control was guided by the study algorithm, the decisions with respect to monotherapy versus combination therapy, inhaler type and use of a spacer was down to the discretion of the participant's primary care team.

Background: The fractional exhaled nitric oxide (FENO) test is a point-of-care test that is used in the assessment of asthma. Objective: To provide evidence-based clinical guidance on whether FENO testing is indicated to optimize asthma treatment in patients with asthma in whom treatment is being considered. Methods: An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FENO. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop …

Introduction Impulse oscillometry (IOS) has advantages over spirometry especially where accurate forced volumetric measurements may be difficult. The coefficient of variation (CV) is commonly used as a measure of precision and repeatability and can also be utilised to assess variability between different devices that perform similar tasks irrespective of units of measurement. Biological variability (BV), a measurement of natural fluctuation, is calculated as the within subject one sided 97.5% CI. Its value can be used as a surrogate for the minimal change that must be exceeded for a clinically significant treatment effect to occur.Aim To assess the medium term within subject CVs and BVs for IOS (Jaeger Masterscreen) and spirometry.Methods Data on 42 poorly controlled severe asthma patients attending clinic who underwent no change in treatment between two timepoints (T1 and T2) were retrospectively evaluated …

IntroductionThe A allele of rs1042713 (Arg16 amino acid) in the β2-adrenoreceptor is associated with poor response to long-acting β2-agonist (LABA) in young people with asthma. Our aim was to assess whether the prescribing of second-line controller with LABA or a leukotriene receptor antagonist according to Arg16Gly genotype would result in improvements in Pediatric Asthma-Related Quality of Life Questionnaire (PAQLQ).MethodsWe performed a pragmatic randomised controlled trial (RCT) via a primary care clinical research network covering England and Scotland. We enrolled participants aged 12–18 years with asthma taking inhaled corticosteroids. 241 participants (mean±sd age 14.7±1.91 years) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following a 4-week run-in participants were followed for 12 months. The primary outcome …

Persistent ill health after acute COVID-19—referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition—has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and …

Abstract Key Points: The use of adenosine monophosphate challenge and basal cortisol as short‐term surrogate end points of airway‐systemic effects of inhaled corticosteroids in asthma is not suitable to properly determine the clinically relevant long‐term therapeutic index.

Coronavirus disease 2019 (COVID-19) is a multisystem condition associated with cytokine-mediated hyperinflammation and coagulopathy due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The nose is usually the first portal of viral entry to the respiratory tract, followed by rapid nasociliary clearance of secretions to the oropharynx and aspiration into the lungs. Early involvement of the nose explains why patients with COVID-19 often experience an alteration in the sense of smell as a presenting symptom. Indeed, the nasopharynx is the most common site for SARS-CoV-2 swab testing. In more severe cases, often in susceptible older individuals with relevant comorbidities, SARS-CoV-2 infection may result in pneumonitis with hypoxia followed by adult respiratory distress syndrome, requirement for mechanical ventilation, and ultimately death. The cascade of pro-inflammatory cytokine …

BackgroundAngiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs, requiring switching to an angiotensin-II receptor blocker (ARB). Angiotensin converting enzyme inhibitor intolerance may be mediated by bradykinin, potentially affecting airway hyperresponsiveness.ObjectiveTo assess the risk for switching to ARBs in asthma.MethodsWe conducted a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink. The risk for switching to ARBs in people with asthma or chronic obstructive pulmonary disease and the general population was compared. Adjusted hazard ratios (HRs) were calculated using Cox regression, stratified by British Thoracic Society (BTS) treatment step and ACEI type.ResultsOf 642,336 new users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR = 1 …

Local and systemic effects of inhaled and intranasal corticosteroid in ambulatory COVID-19 — Discovery - the University of Dundee Research Portal Skip to main navigation Skip to search Skip to main content Discovery - the University of Dundee Research Portal Home Discovery - the University of Dundee Research Portal Logo Home Profiles Research units Research Outputs Projects Datasets Theses Activity Press/Media Research Facilities Prizes Search by expertise, name or affiliation Local and systemic effects of inhaled and intranasal corticosteroid in ambulatory COVID-19 Brian Lipworth (Lead / Corresponding author), Rory Chan, Kirsten Stewart, Rashad Misorovs Molecular and Clinical Medicine Research output: Contribution to journal › Comment/debate › peer-review Overview Original language English Journal BMJ Volume 375 Publication status Published - 11 Nov 2021 Other files and links Final …

BackgroundClinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition.ObjectiveTo survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR.MethodsThe Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members.ResultsConsensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more …

BackgroundStudies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use.MethodsWe analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16 …

Patients with severe chronic rhinosinusitis with nasal polyps represent an unmet clinical need in terms of recurrent disease despite current medical and surgical therapy. Targeting type 2 inflammatory cytokines (IL4/5/13) appears to be a promising therapeutic approach for such patients akin to what has already been seen in severe asthma. An indirect comparison from phase 3 placebo-controlled trials has shown relative improvements in the coprimary end point of nasal polyp score (NPS) ranging from a 15% reduction (−0.8 units) with mepolizumab, 18% with omalizumab (−1.14 units), and 35% (−2.06 units) with dupilumab. This trend was mirrored by relative improvements in health status with the 22-item Sinonasal Outcome Test score showing a 21% reduction (−13.7 units) with mepolizumab, 27% (−16.1 units) with omalizumab, and 43% (−21.1 units) with dupilumab, all exceeding the minimal clinically important …