Publications by authors named "Mark C Liu"

Background: Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-IgE biologics.

Objective: This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A study.

Methods: The clinically significant asthma exacerbation (CSE) rate was assessed 1 year prior to (pre-treatment) and following (follow-up) mepolizumab treatment, stratified by baseline total IgE levels (tIgE; <60, 60-<190, 190-<550, and ≥550 kU/L), atopic status (yes/no/unknown), prior omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count (BEC) threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells/µL).

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Background: Severe asthma is complex; comorbidities may influence disease outcomes.

Objective: To assess mepolizumab effectiveness in patients with severe asthma and comorbidities.

Methods: REALITI-A was a 2-year international, prospective study enrolling adults with asthma newly prescribed mepolizumab (100 mg subcutaneously) at physician's discretion.

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Asthma worsening and symptom control are clinically important health outcomes in patients with severe eosinophilic asthma. This analysis of COMET evaluated whether stopping continuing long-term mepolizumab therapy impacted these outcomes. Patients with severe eosinophilic asthma with ≥3 years continuous mepolizumab treatment ( COLUMBA (NCT01691859) or COSMEX (NCT02135692) open-label studies) were eligible to enter COMET (NCT02555371), a randomised, double-blind, placebo-controlled study.

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Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden.

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Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects.

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Background: The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.

Methods: COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study.

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Background: Severe asthma is associated with a broad range of phenotypes and clinical characteristics. This analysis assessed whether select baseline patient characteristics could prognosticate mepolizumab efficacy in severe eosinophilic asthma.

Methods: This was a post hoc meta-analysis of data from the Phase III MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862) studies.

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Introduction: Cathelicidin is a vitamin D-regulated, antimicrobial peptide involved in the innate immune response of the airways. Reduced plasma cathelicidin concentrations are independently associated with worse pulmonary outcomes in current and former smokers. This study aimed to determine whether oral vitamin D supplementation in vitamin D-deficient current smokers increases plasma and bronchoalveolar lavage (BAL) cathelicidin levels.

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Background: The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. The objective of this analysis was to assess the proportion of patients achieving pre-defined improvements in up to four efficacy outcomes and the relationship between patient baseline characteristics and treatment response.

Methods: This was a post hoc analysis of OSMO study data (GSK ID:204471; ClinicalTrials.

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Severe asthma accounts for almost half the cost associated with asthma. Severe asthma is driven by heterogeneous molecular mechanisms. Conventional clinical trial design often lacks the power and efficiency to target subgroups with specific pathobiological mechanisms.

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Allergic asthma affects more women than men. It is mediated partially by IL-4/IL-13-driven polarization of monocyte-derived macrophages in the lung. We tested whether sex differences in asthma are due to differential IL-4 responsiveness and/or chemokine receptor expression in monocytes and monocyte-derived macrophages from healthy and allergic asthmatic men and women.

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The Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) study is an adaptive platform trial designed to investigate novel interventions to severe asthma. The study is conducted under a master protocol and utilizes a crossover design with each participant receiving up to five interventions and at least one placebo. Treatment assignments are based on the patients' biomarker profiles and precision health methods are incorporated into the interim and final analyses.

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Background: Little is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma overlap and atopy is needed to better target therapies.

Research Question: What is the overlap between atopy and asthma status among individuals with COPD, and how are categories defined by the presence of atopy and asthma status associated with clinical and radiologic phenotypes and outcomes in the Genetic Epidemiology of COPD Study (COPDGene) and Subpopulation and Intermediate Outcome Measures in COPD Study (SPIROMICS)?

Study Design And Methods: Four hundred three individuals with COPD from SPIROMICS and 696 individuals from COPDGene with data about specific IgEs to 10 common allergens and mixes (simultaneous assessment of combination of allergens in similar category) were included.

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Background: Patients with severe asthma can present with overlapping eosinophilic and allergic phenotypes, which makes it challenging when deciding which biologic therapy is most appropriate to reduce exacerbations and help achieve asthma control.

Objective: This post hoc meta-analysis evaluated the efficacy of the licensed dose of mepolizumab (100 mg administered subcutaneously [SC]) versus placebo in patients with severe eosinophilic asthma (SEA), according to omalizumab eligibility and associated allergic characteristics.

Methods: Data from two Phase 3 studies (MENSA [MEA115588/NCT01691521]; MUSCA [200862/NCT02281318]) were analyzed.

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Background: Mepolizumab and omalizumab are treatments for distinct but overlapping severe asthma phenotypes.

Objective: To assess if patients eligible for both biologics but not optimally controlled with omalizumab experience improved asthma control when switched directly to mepolizumab.

Methods: OSMO was a multicenter, open-label, single-arm, 32-week trial in patients with ≥2 asthma exacerbations in the year prior to enrollment, despite receiving high-dose inhaled corticosteroids and other controller(s), plus omalizumab (≥4 months).

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Background: We have previously shown that oncostatin M (OSM) levels are increased in nasal polyps (NPs) of patients with chronic rhinosinusitis (CRS), as well as in bronchoalveolar lavage fluid, after segmental allergen challenge in allergic asthmatic patients. We also showed in vitro that physiologic levels of OSM impair barrier function in differentiated airway epithelium.

Objective: We sought to determine which hematopoietic or resident cell type or types were the source of the OSM expressed in patients with mucosal airways disease.

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Background: Epithelial barrier dysfunction is thought to play a role in many mucosal diseases, including asthma, chronic rhinosinusitis (CRS), and eosinophilic esophagitis.

Objective: The objective of this study was to investigate the role of oncostatin M (OSM) in epithelial barrier dysfunction in human mucosal disease.

Methods: OSM expression was measured in tissue extracts, nasal secretions, and bronchoalveolar lavage fluid.

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Background: Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids.

Methods: In this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks.

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Background: The D-prostanoid receptor and the chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) are implicated in asthma pathogenesis. AMG 853 is a potent, selective, orally bioavailable, small-molecule dual antagonist of human D-prostanoid and CRTH2.

Objective: We sought to determine the efficacy and safety of AMG 853 compared with placebo in patients with inadequately controlled asthma.

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Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder of unknown cause with no effective treatment. Cough affects up to 80% of patients with IPF, is frequently disabling, and lacks effective therapy.

Objective: To determine the efficacy of thalidomide in suppressing cough in patients with IPF.

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Background: Outcomes of pulmonary physiology have a central place in asthma clinical research.

Objective: At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to provide recommendations on the use of pulmonary function measures as asthma outcomes that should be assessed in a standardized fashion in future asthma clinical trials and studies to allow for cross-study comparisons.

Methods: Our subcommittee conducted a comprehensive search of PubMed to identify studies that focused on the validation of various airway response tests used in asthma clinical research.

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Background: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as alphagamma(2), which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to T(H) cells.

Objectives: To use omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic cells and to assess whether this results in altered DC-dependent T-cell responsiveness to allergen ex vivo.

Methods: Subjects with cat allergy were enrolled in a 3.

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Background: Omalizumab treatment suppresses FcepsilonRI expression faster on blood basophils than skin mast cells.

Objective: We used omalizumab to elucidate the relative contributions of basophil versus mast cell FcepsilonRI activation in a nasal allergen challenge (NAC) model.

Methods: Eighteen subjects with cat allergy were enrolled in a 3.

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