Rory Chan

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 …

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,

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 …

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 …

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

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.

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 …

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 …

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 …

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 …

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 …

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.

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 …

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 …

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.

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 …

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 …