Publications by authors named "Paul Pfeffer"

Article Synopsis
  • The study explores the implementation of a digital health intervention (DHI) designed for supporting self-management among long COVID patients, involving a patient app and a clinician dashboard.
  • Using qualitative analysis and Normalisation Process Theory, researchers found that the DHI was adaptable to various healthcare settings, enhancing collaboration among healthcare professionals while acknowledging the necessity for in-person care.
  • The findings suggest that DHIs can potentially transform traditional healthcare engagement patterns, emphasizing the importance of organizational context and individual experiences in successful implementation.
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Objectives: To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.

Design: A population-based longitudinal cohort study using real-time user data.

Setting: 35 specialised long COVID clinics in the UK.

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Introduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies.

Methods: This was a historical cohort study of patients with severe asthma (aged ≥18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4.

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Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge.

Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium).

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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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Background: Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood.

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Background: Severe asthma pathology encompasses a wide range of pulmonary and extrapulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health-related quality-of-life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities.

Objective: We sought to examine the impact of pulmonary and extrapulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centers.

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Background: Type 2 low-severe asthma phenotype is often a result of corticosteroid-overtreated type 2 disease owing to persistent symptoms, often unrelated to asthma and unlikely to respond to high-dose corticosteroid treatment.

Objective: This study aimed to characterize patients with severe asthma with low eosinophil counts (<300 cells/μL) and describe their disease burden and treatment across health care settings in the United Kingdom.

Methods: A retrospective cohort study of patients with severe asthma using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients according to the latest blood eosinophil count (BEC).

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Article Synopsis
  • The PHOSP-COVID study examined long-term outcomes in COVID-19 hospitalised patients with pre-existing airway diseases compared to those without.* -
  • Out of 615 participants with airway diseases, many reported lower recovery rates, higher anxiety and depression levels, and greater mobility issues one year post-discharge.* -
  • Overall, individuals with pre-existing airway conditions experienced worse health-related quality of life and more persistent symptoms like breathlessness and fatigue after recovering from COVID-19.*
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Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.

Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13).

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Objective: Asthma is a major global disease affecting adults and children, which can lead to hospitalization and death due to breathing difficulties. Although targeted monoclonal antibody therapies have revolutionized treatment of severe asthma, some patients still fail to respond. Here we critically evaluate the literature on biologic therapy failure in asthma patients with particular reference to anti-drug antibody production, and subsequent loss of response, as the potential primary cause of drug failure in asthma patients.

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Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.

Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.

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Article Synopsis
  • The study investigates how pre-biologic biomarker levels, specifically immunoglobulin E (IgE), blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO), influence asthma treatment outcomes when patients start biologic therapy.
  • Conducted across 23 countries with over 3750 patients, the research focused on changes in exacerbation rates, symptom control, and lung function about a year after starting treatment.
  • Results showed that higher levels of BEC and FeNO were linked to significant improvements in lung function for specific biologic therapies, while IgE was not a strong predictor of treatment effectiveness.
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Article Synopsis
  • There is currently no agreed-upon definition for asthma remission in real life, and the factors that help patients achieve it after starting biologics are not well understood.
  • A study analyzed data from 23 countries to see how many adults with severe asthma reached multidomain-defined remission after beginning biologic treatment, using specific criteria for remission.
  • Results showed that less than a quarter of participants achieved full remission, with higher chances for those with fewer exacerbations, lower corticosteroid use, and better control and lung function before treatment, suggesting that early intervention is crucial for better outcomes.
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Background: Exacerbation frequency strongly influences treatment choices in patients with severe asthma.

Research Question: What is the extent of the variability of exacerbation rate across countries and its implications in disease management?

Study Design And Methods: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit.

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Background: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma.

Objective: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma.

Methods: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.

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Article Synopsis
  • After puberty, females are more prone to developing severe asthma than males, influenced by various complex factors.
  • A study analyzed data from two databases, showing that while women with severe asthma tended to report more symptoms and higher obesity rates, they also demonstrated better lung function (FEV%) and lower levels of certain asthma-related biomarkers compared to men.
  • The findings suggest significant gender differences in asthma presentation and treatment, highlighting the need for tailored approaches to management in females.
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Background: Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms.

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Ethnic disparities exist within asthma; however, country of birth is rarely investigated. We described demographic and clinical characteristics by ethnicity and country of birth within the UK Biobank. Lung function and asthma hospitalisations were similar for white, black and North-East Asian participants, however, South-East (SE) Asians more commonly had an FEV below the lower limits of normal (LLN; 53.

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Background: The Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown.

Methods: Data was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951).

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Article Synopsis
  • Previous studies on how comorbidities affect the effectiveness of biologic agents in asthma were limited in size and duration, lacking comparisons between different biologic classes.
  • This cohort study analyzed data from the International Severe Asthma Registry across 21 countries to assess changes in asthma outcomes after starting biologic therapy in patients with type 2-related comorbidities.
  • Results showed that patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs) experienced significantly better outcomes, including fewer exacerbations and improved asthma control, while allergic rhinitis and atopic dermatitis did not influence therapy effectiveness.
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Asthma continues to be a major cause of illness with a significant mortality, despite its increasing range of treatments. Adoption of a treatable traits approach in specialist centres has led to improvements in control of asthma and reduced exacerbations in patients with severe asthma. However, most patients with this illness, particularly those with mild-to-moderate asthma, are cared for in primary care according to guidelines that emphasise the use of pharmacotherapeutic ladders uniformly implemented across all patients.

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Article Synopsis
  • The study aimed to evaluate the prevalence and impact of comorbidities in adults with severe asthma, as their presence can complicate asthma management practices.* -
  • Data was analyzed from the International Severe Asthma Registry, identifying 30 comorbidities linked to asthma, with findings indicating a significant percentage of patients experience multiple comorbidities that affect their asthma outcomes.* -
  • Results showed that patients with specific comorbidities like allergic rhinitis and nasal polyposis had higher rates of asthma exacerbations and were more likely to require long-term oral corticosteroids, highlighting the need for effective management strategies.*
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