Publications by authors named "Ian Pavord"

Background And Objectives: Treatable trait-based personalised medicine improves outcomes in severe asthma clinics. We assessed the feasibility of a randomised controlled trial (RCT) of protocolised treatable trait-guided asthma management in patients not under a severe asthma clinic.

Methods: Ten week single-group cohort study.

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Introduction/aim: Lung inhomogeneity measures obtained using computed cardiopulmonography (CCP) are sensitive to small-airways disease. Here, we assessed changes in lung inhomogeneity in patients with type-2 high asthma treated with biological therapy and explored the relationship between inhomogeneity measures and conventional asthma disease markers.

Methods: This was an observational study of 91 severe type-2 high asthma patients recruited from a tertiary asthma clinic, of whom 67 subsequently started anti-IL5 or anti-IL5R biologics.

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The Epithelial Science Expert Group convened on 18-19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated.

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Macrolides reduce exacerbations when added to inhaled therapy in severe asthma. However, there is little published evidence for effectiveness in patients treated with biologics. We conducted a retrospective audit of all patients who started azithromycin while on biologics in our centre.

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Asthma is a common multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes and endotypes and the availability of targeted biologic treatment options, the disease remains uncontrolled in a substantial proportion of patients with risk of exacerbations, requiring systemic corticosteroids, and with progressive disease. Current international guidelines advocate a personalized management approach to patients with uncontrolled severe asthma.

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Background: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, which has shown increased expression in patients with chronic obstructive pulmonary disease (COPD) compared with healthy individuals. We aimed to assess the efficacy and safety of tezepelumab in patients with moderate to very severe COPD despite receiving triple inhaled therapy.

Methods: COURSE was a double-blind, randomised, placebo-controlled, phase 2a trial across 90 sites in ten countries in Asia, Europe, and North America.

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The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report states that the diagnosis of COPD should be considered in individuals with chronic respiratory symptoms and/or exposure to risk factors. Forced spirometry demonstrating airflow obstruction after bronchodilation is required to confirm the diagnosis using a threshold of forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) ratio <0.7.

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Background: Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are important events and are associated with critical illness. Eosinophilic inflammation is a treatable trait commonly found during acute exacerbations of asthma and COPD. We hypothesised that for patients with eosinophilic exacerbations, a single injection of benralizumab, a humanised monoclonal antibody against interleukin-5 receptor-α, alone or in combination with prednisolone, will improve clinical outcomes compared with prednisolone, the standard of care.

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Objectives: Long-term safety monitoring of mepolizumab is necessary to support real-world use for the treatment of severe asthma. This Long-Term Access Program assessed the safety and benefit:risk of mepolizumab in pediatric, adolescent, and adult patients with severe asthma.

Materials And Methods: This was a multicenter, Phase IIIb safety, open-label extension study of multiple prior studies assessing mepolizumab in addition to standard of care (Aug 2015 - Aug 2022).

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Background: Remission is proposed as a multicomponent outcome for patients with severe asthma.

Objective: This post hoc analysis of QUEST (NCT02414854) and TRAVERSE (NCT02134028) evaluated whether dupilumab treatment leads to clinical asthma remission (≥12 months with no severe exacerbations, zero oral corticosteroid use, stabilized or improved lung function, patient-reported asthma control <1.5) and assessed its durability in patients with uncontrolled, moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb at parent-study baseline) who are not receiving maintenance oral corticosteroids.

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Biologics in Asthma: Role of Biomarkers.

Immunol Allergy Clin North Am

November 2024

Our modern understanding of asthma mainly concerns identification of inflammatory endotype to guide management. The distinction mostly concerns identification of type-2 inflammation, for which different biomarkers have been well characterized. Blood eosinophils corroborate activity in the interleukin (IL)-5 axis while fraction of exhaled nitric oxide is indicative of the IL-4/IL-13 axis, giving us an indication of activity in these distinct but complementary pathways.

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Article Synopsis
  • The studies NAVIGATOR and DESTINATION evaluated the effectiveness of tezepelumab in treating severe, uncontrolled asthma.
  • Results showed that a higher percentage of patients receiving tezepelumab experienced a complete clinical response and on-treatment clinical remission compared to those on placebo.
  • Conclusion suggests that tezepelumab significantly improves patient outcomes, leading to better lung function and fewer asthma exacerbations over time.
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Background: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.

Methods: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care.

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In this installment of the How I Do It series on severe asthma, we tackle the clinical conundrum of choosing the right biologic for the right patient with severe asthma. With six biologics now approved for use in this area comprising four different targeting strategies (anti-Ig E: omalizumab; anti-IL-5 and anti-IL-5-receptor: mepolizumab, reslizumab, and benralizumab; anti-IL-4-receptor: dupilumab; anti-thymic stromal lymphopoietin: tezepelumab), this question is increasingly complex. Recognizing that no head-to-head trial has compared biologics, we based our review on the expected effects of inhibiting different aspects of type 2 airway inflammation, supported whenever possible by clinical trial and real-world data.

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Article Synopsis
  • The study aimed to characterize the airway microbiome in severe asthma at the species level and examine how specific bacteria relate to mucosal immune responses, particularly in a subgroup of asthma known for low type-2 inflammation.
  • Researchers analyzed sputum and nasal samples from two cohorts of adults with severe asthma using advanced sequencing techniques and integrated data with clinical and protein assessments.
  • Findings indicated that a significant portion of severe asthma cases were dominated by specific pathogens like H. influenzae and M. catarrhalis, with distinct relationships observed between these bacteria and inflammatory responses in the airways.
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Article Synopsis
  • Mepolizumab is an anti-IL-5 antibody used to treat severe eosinophilic asthma while oral corticosteroids like prednisolone are commonly used for persistent symptoms despite mepolizumab therapy.
  • The MAPLE trial investigated how well prednisolone reduces airway inflammation in patients on mepolizumab, examining sputum and plasma samples for inflammatory proteins.
  • Results showed that prednisolone significantly reduced various proteins associated with type 2 inflammation and inflammation pathways, suggesting its important role in managing exacerbations even when patients are treated with mepolizumab.
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Introduction: The hallmark of most patients with severe asthma is type 2 inflammation, driven by innate and adaptive immune responses leading to either allergic or non-allergic eosinophilic infiltration of airways. The cellular and molecular pathways underlying severe type 2 asthma can be successfully targeted by specific monoclonal antibodies.

Areas Covered: This review article provides a concise overview of the pathophysiology of type 2 asthma, followed by an updated appraisal of the mechanisms of action and therapeutic efficacy of currently available biologic treatments used for management of severe type 2 asthma.

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Introduction: The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR).

Methods: Reduction in reliever medication use (puffs/24 h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12 months were simulated in a cohort of patients with different baseline characteristics (e.

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