Publications by authors named "David Peden"

The twenty-first century has seen a fundamental shift in disease epidemiology with anthropogenic environmental change emerging as the likely dominant factor affecting the distribution and severity of current and future human disease. This is especially true of allergic diseases and asthma with their intimate relationship with the natural environment. Climate change-related variables including increased ambient temperature, heat waves, extreme weather events, air pollution, and rainfall distribution, all can affect asthma in children, but each of these variables also affects asthma via alterations in pollen production and release, outdoor allergen exposure or the microbiome.

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Background: Inhalation of biomass smoke is associated with adverse respiratory effects in those with chronic pulmonary conditions. There are few published data regarding the effects of anti-inflammatory interventions on these outcomes.

Objective: Our aim was to assess the effects of postexposure prednisone on woodsmoke (WS)-induced sputum neutrophilia.

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Rationale: Epidemiologic studies on asthmatics and data suggest a protective role of T2 inflammation in SARS-CoV-2 infection.

Objective: Using a large, multisite cohort, we studied clinical outcomes following SARS-CoV-2 infection in multiple asthma endotypes and examined the effects of T2-directed biologics in infected asthmatics.in Methods: The National COVID Cohort Collaborative (N3C) Data Enclave was used to identify and stratify asthmatic patients by endotype to include non-T2 and T2 asthmatics, as well as exposure to T2-directed biologic therapy.

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Article Synopsis
  • The study investigates if inhaling endotoxin (LPS) causes immediate changes in cardiovascular function due to systemic inflammation.
  • Fifteen adult volunteers inhaled a specific amount of LPS, with blood and lung samples taken before and after exposure to assess various cardiovascular measures.
  • Results showed that while LPS inhalation increased levels of certain immune cells, it did not lead to significant changes in blood pressure or heart function in healthy adults, indicating the need for further research on other particulate matter components.
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Respiratory Health Effects of Air Pollutants.

Immunol Allergy Clin North Am

February 2024

Air pollution is a risk factor for asthma and respiratory infection. Avoidance of air pollution is the best approach to mitigating the impacts of pollution. Personal preventive strategies are possible, but policy interventions are the most effective ways to prevent pollution and its effect on asthma and respiratory infection.

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Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation.

Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans.

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The Precision Interventions for Severe and/or Exacerbation-Prone Asthma clinical trials network is actively assessing novel treatments for severe asthma during the coronavirus disease (COVID-19) pandemic and has needed to adapt to various clinical dilemmas posed by the COVID-19 pandemic. Pharmacologic interactions between established asthma therapies and novel drug interventions for COVID-19 infection, including antivirals, biologics, and vaccines, have emerged as a critical and unanticipated issue in the clinical care of asthma. In particular, impaired metabolism of some long-acting beta-2 agonists by the cytochrome P4503A4 enzyme in the setting of antiviral treatment using ritonavir-boosted nirmatrelvir (NVM/r, brand name Paxlovid) may increase risk for adverse cardiovascular events.

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Background: Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses.

Objective: We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis.

Methods: We conducted a double-blind parallel design trial in patients with cat allergy.

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Biomass fuel smoke, secondhand smoke, and oxides of nitrogen are common causes of household air pollution (HAP). Almost 2.4 billion people worldwide use solid fuels for cooking and heating, mostly in low- and middle-income countries.

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Article Synopsis
  • The study evaluated human volunteers' sputum PMN responses after exposure to wood smoke particles at 6 and 24 hours to identify individuals for future inflammation mitigation studies.
  • Results indicated that responders at 6 hours were often the same at 24 hours, but significant inflammatory markers like IL-1beta, IL-6, and IL-8 increased notably at 24 hours.
  • The research concluded that the 24-hour data is more useful for understanding airway inflammation, highlighting the roles of GSTM1 genotype and asthma status in influencing PMN response to wood smoke exposure.
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Article Synopsis
  • - An outbreak of COVID-19, caused by the SARS-CoV-2 virus, began in Wuhan, China and spread globally, with mixed evidence on how asthma impacts the severity of infection, highlighting the need for more research.
  • - Asthma patients should continue their treatments as COVID-19 doesn’t seem to trigger asthma attacks, and interestingly, the type of asthma (like non-allergic forms) may be linked to varying risks of severe COVID-19.
  • - The pandemic caused behavioral shifts, with more people staying indoors due to lockdowns, potentially altering exposure to allergens—some allergies may have improved while others worsened based on living conditions and changes in outdoor allergen levels.
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Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough.

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Background: The Integrated Clinical and Environmental Exposures Service (ICEES) serves as an open-source, disease-agnostic, regulatory-compliant framework and approach for openly exposing and exploring clinical data that have been integrated at the patient level with a variety of environmental exposures data. ICEES is equipped with tools to support basic statistical exploration of the integrated data in a completely open manner.

Objective: This study aims to further develop and apply ICEES as a novel tool for openly exposing and exploring integrated clinical and environmental data.

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Article Synopsis
  • Allergic asthma (AA) is a type of asthma that requires proof of IgE-sensitization to allergens and its role in causing symptoms; bronchial allergen challenge (BAC) may help identify AA cases among atopic asthmatics.
  • Current BAC methods are mainly used in research settings focused on mild asthma, which limits their application for moderate-to-severe cases in clinical practice.
  • The EAACI Task Force suggests a new BAC methodology aimed at improving patient identification for effective treatments like immunotherapy, ultimately enhancing asthma management in real-world scenarios.
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Background: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition.

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Background: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive.

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γ-Tocopherol (γT) is a major form of vitamin E in the US diet and the second most abundant vitamin E in the blood and tissues, while α-tocopherol (αT) is the predominant vitamin E in tissues. During the last >25 years, research has revealed that γT has unique antioxidant and anti-inflammatory activities relevant to disease prevention compared to αT. While both compounds are potent lipophilic antioxidants, γT but not αT can trap reactive nitrogen species by forming 5-nitro-γT, and appears to show superior protection of mitochondrial function.

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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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ICEES (Integrated Clinical and Environmental Exposures Service) provides a disease-agnostic, regulatory-compliant approach for openly exposing and analyzing clinical data that have been integrated at the patient level with environmental exposures data. ICEES is equipped with basic features to support exploratory analysis using statistical approaches, such as bivariate chi-square tests. We recently developed a method for using ICEES to generate multivariate tables for subsequent application of machine learning and statistical models.

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Background: Impaired mucus clearance and airway mucus plugging have been shown to occur in moderate-severe asthma, especially during acute exacerbations. In cystic fibrosis, where airway mucus is dehydrated, it has been shown that inhaled hypertonic saline (HS) produces both acute and sustained enhancement of mucociliary clearance (MCC). The current study was designed to assess the acute and sustained effect of inhaled 7% HS on MCC in adult asthma.

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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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