FHIR PIT: a geospatial and spatiotemporal data integration pipeline to support subject-level clinical research.

Background: Environmental exposures such as airborne pollutant exposures and socio-economic indicators are increasingly recognized as important to consider when conducting clinical research using electronic health record (EHR) data or other sources of clinical data such as survey data. While numerous public sources of geospatial and spatiotemporal data are available to support such research, the data are challenging to work with due to inconsistencies in file formats and spatiotemporal resolutions, computational challenges with large file sizes, and a lack of tools for patient- or subject-level data integration.

Results: We developed FHIR PIT (HL7® Fast Healthcare Interoperability Resources Patient data Integration Tool) as an open-source, modular, data-integration software pipeline that consumes EHR data in FHIR® format and integrates the data at the level of the patient or subject with environmental exposures data of varying spatiotemporal resolutions and file formats.

Effects of Food Processing on Allergenicity.

Purpose Of Review: There is an increasing awareness among clinicians that industrial and household food processing methods can increase or decrease the allergenicity of foods. Modification to allergen properties through processing can enable dietary liberations. Reduced allergenicity may also allow for lower risk immunotherapy approaches.

Predictors of Potentially Inappropriate Stimulant Prescribing Among Adults.

Purpose: Increases in adult stimulant prescribing pose a potential risk due to the higher prevalence of contraindicated conditions among this population. We sought to identify patient, provider, and visit characteristics predictive of potentially inappropriate adult stimulant prescriptions.

Methods: We conducted a repeated cross-sectional study using the National Ambulatory Medical Care Survey, a nationally representative weighted sample of 5 453 702 723 ambulatory care visits from 2012 to 2019.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

Chronic rhinosinusitis with nasal polyps: Key considerations in the multidisciplinary team approach.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a recurrent inflammatory disease associated with several comorbidities and a significant disease burden for patients. Treatments include corticosteroids and sinonasal surgery, but these can be associated with the risk of adverse events and nasal polyp recurrence. Biologic treatments such as mepolizumab can be used as an add-on treatment and are effective at reducing surgery and corticosteroid use.

TGF-β Receptor-dependent Tissue Factor Release and Proteomic Profiling of Extracellular Vesicles from Mechanically Compressed Human Bronchial Epithelial Cells.

In asthma, tissue factor (TF) levels are elevated in the lung. In our previous studies using mechanically compressed human bronchial epithelial (HBE) cells, which are a well-defined in vitro model of bronchoconstriction during asthma exacerbations, we detected TF within extracellular vesicles (EVs) released from compressed HBE cells. Here, to better characterize the potential role of this mechanism in asthma, we tested the extent to which the transcriptional regulation of epithelial cell-derived TF varied between donors with and without asthma.

Low-Dose Oral Ginger Improves Daily Symptom Scores in Asthma.

A significant number of individuals with asthma have poorly controlled daily symptoms and utilize dietary supplements such as ginger in a quest for improved symptom control; however, its effectiveness at improving the control of symptoms is unproven. We questioned whether low-dose oral ginger would improve subjective and objective measurements of asthma control in mild-to-moderate asthmatics. We performed a randomized, placebo-controlled, double-blinded study of a low dose (1 g twice daily) of a dietary supplement of ginger in 32 mild-to-moderate uncontrolled asthmatics over a 2-month trial period while maintaining daily conventional asthma therapies.

Food Allergy Prevalence in Two Population-Based UK Cohorts Born 12 Years Apart.

Background: Adverse food reactions include food allergy (FA; immune-mediated) and food intolerances (non-immune-mediated). FA are classified into IgE- and non-IgE-mediated FA. There is limited information available about changes in FA prevalence over time.

Covariate-adaptive biased coin randomization for master protocols with multiple interventions and biomarker-stratified allocation.

In a multi-arm trial with predefined subgroups for each intervention to target, it is often desirable to enrich assignment to an intervention by enrolling more biomarker-positive participants to the intervention. We describe how to implement a biased coin design to achieve desired allocation ratios among interventions and between the number of biomarker-positive and biomarker-negative participants assigned to each intervention. We illustrate the proposed method with the randomization algorithm implemented in the Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) trial.

Profiling endogenous airway proteases and antiproteases and modeling proteolytic activation of Influenza HA using in vitro and ex vivo human airway surface liquid samples.

Imbalance of airway proteases and antiproteases has been implicated in diseases such as COPD and environmental exposures including cigarette smoke and ozone. To initiate infection, endogenous proteases are commandeered by respiratory viruses upon encountering the airway epithelium. The airway proteolytic environment likely contains redundant antiproteases and proteases with diverse catalytic mechanisms, however a proteomic profile of these enzymes and inhibitors in airway samples has not been reported.

An overview of climate changes and its effects on health - from mechanisms to One Health.

Human activities, primarily the burning of fossil fuels, widespread deforestation, soil erosion or machine-intensive farming methods, manufacturing, food processing, mining, and construction iron, cement, steel, and chemicals industry, have been the main drivers of the observed increase in Earth's average surface temperature and climate change. Rising global temperatures, extreme weather events, ecosystems disruption, agricultural impacts, water scarcity, problems in access to good quality water, food and housing, and profound environmental disruptions such as biodiversity loss and extreme pollution are expected to steeply increase the prevalence and severity of acute and chronic diseases. Its long-term effects cannot be adequately predicted or mitigated without a comprehensive understanding of the adaptive ecosystems.

Semi-parametric sensitivity analysis for trials with irregular and informative assessment times.

Many trials are designed to collect outcomes at or around pre-specified times after randomization. If there is variability in the times when participants are actually assessed, this can pose a challenge to learning the effect of treatment, since not all participants have outcome assessments at the times of interest. Furthermore, observed outcome values may not be representative of all participants' outcomes at a given time.

Evidence of sex differences in ozone-induced oxysterol and cytokine levels in differentiated human nasal epithelial cells.

Acute exposure to ozone (O) causes upper and lower airway inflammation. We and others have previously demonstrated that O oxidizes lipids, particularly cholesterol, into electrophilic oxysterols, such as secosterol B (SecoB), which can adduct proteins, thus altering cellular signaling pathways. To investigate how O-derived oxysterols influence cytokine and chemokine release, nasal epithelial cells (HNECs) from healthy donors (N = 18 donors) were exposed to 0.

Keeping up with Recent Developments in Immunodeficiency.

Inborn Errors of Immunity are a rapidly expanding group of monogenetic disorders affecting the immune system. Advancements in genetic testing and functional validation studies have accelerated the pace of IEI gene discovery and mechanism of disease, particularly in the past five years. To keep up with this rapid expansion, the International Union of Immunological Societies (IUIS) Expert Committee has periodically, since 1999, released updated IEI classifications with corresponding genotypic and phenotypic catalogues with its most recent update in 2022.

E-cigarette, or Vaping, Product Use Associated Lung Injury: Epidemiology, Challenges, and Implications With COVID-19.

Background: E-cigarette, or vaping products produce an aerosol by heating nicotine, or cannabis including tetrahydrocannabinol (THC) and cannabidiol (CBD), mixed with other chemicals that help make the aerosol. They are increasingly popular among teenagers and young adults, with a 2023 survey reporting that 2.13 million middle and high school students in the United States used e-cigarettes within the last 30 days.

Human Monocyte-Derived Macrophages Demonstrate Distinct Responses to Ambient Particulate Matter in a Polarization State- and Particle Seasonality-Specific Manner.

Macrophages are professional phagocytic immune cells that, following activation, polarize on a spectrum between the proinflammatory M1 and the proresolution M2 states. Macrophages have further been demonstrated to retain plasticity, allowing for the reprogramming of their polarization states following exposure to new stimuli. Particulate matter (PM) has been repeatedly shown to modify macrophage function and polarization while also inducing worsening respiratory infection morbidity and mortality.

Treatment of food allergy: Immunotherapy, omalizumab, or both.

Food allergy is a common disease which has substantial impacts on the quality of life of patients and their families, and all reactions have the potential for causing life-threatening anaphylaxis. Food allergic individuals currently have 2 FDA approved therapeutic options available to them aside from life-long allergen avoidance: oral immunotherapy (OIT), and omalizumab. OIT for food allergy has been extensively studied in clinical trials and currently provides the greatest level of protection, however it also has a high burden of treatment.

Multicohort Analysis of Bronchial Epithelial Cell Expression in Healthy Subjects and Patients with Asthma Reveals Four Clinically Distinct Clusters.

Asthma is a heterogeneous disease with variable presentation and characteristics. There is a critical need to identify underlying molecular endotypes of asthma. We performed the largest transcriptomic analysis of 808 bronchial epithelial cell (BEC) samples across 11 independent cohorts, including 3 cohorts from the Severe Asthma Research Program (SARP).

Caregiver worry about COVID-19 as a predictor of social mitigation behaviours and SARS-CoV-2 infection in a 12-city U.S. surveillance study of households with children.

Objective: Understanding compliance with COVID-19 mitigation recommendations is critical for informing efforts to contain future infectious disease outbreaks. This study tested the hypothesis that higher levels of worry about COVID-19 illness among household caregivers would predict lower (a) levels of overall and discretionary social exposure activities and (b) rates of household SARS-CoV-2 infections.

Methods: Data were drawn from a surveillance study of households with children ( = 1913) recruited from 12 U.

Intranasal Dexmedetomidine Administration Precipitates Respiratory Failure in Child With Croup and Asthma.

Intranasal dexmedetomidine administration in clinically recommended doses has a small but important risk of causing catastrophic respiratory failure in the setting of preexisting severe respiratory workloads.

Simulated burn pit smoke condensates cause sustained impact on human airway epithelial cells.

Inhalation of smoke from burn pits during military deployment is associated with several adverse pulmonary outcomes. We exposed human airway epithelial cells to smoke condensates from burn pit waste materials. Single and repeated exposure of condensates triggered unique and common responses in terms of gene expression, that sustained through the recovery phase.

Systematic review on maternal dietary patterns during pregnancy and offspring allergy.

Allergic diseases including food allergy, atopic dermatitis, asthma, and allergic rhinitis are increasing. Nutritional intake may play a role in this increase. Systematic reviews indicate that intake of specific nutrients and foods does not prevent allergic diseases.

The environmental neuroactive chemicals list of prioritized substances for human biomonitoring and neurotoxicity testing: A database and high-throughput toxicokinetics approach.

There is a diversity of chemicals to which humans are potentially exposed. Few of these chemicals have linked human biomonitoring data, and most have very limited neurotoxicity testing. Of particular concern are environmental exposures impacting children, who constitute a population of heightened susceptibility due to rapid neural growth and plasticity, yet lack biomonitoring data compared to other age/population subgroups.

A case of spontaneous pneumomediastinum in a triathlete.

Spontaneous pneumomediastinum is an infrequent condition typically secondary to smoking, illicit drug use, or asthma. The condition often follows barotrauma or bronchial hyperactivity, causing alveolar destruction and air trapping within the mediastinum. Rarely, it may present following strenuous exercise, particularly in tall, thin males, resembling the presentation of pneumothorax.