Type 1 Immune Responses Related to Viral Infection Influence Corticosteroid Response in Asthma.

Rationale: Corticosteroid-responsive type 2 (T2) inflammation underlies the T2-high asthma endotype. However, we hypothesized that type 1 (T1) inflammation, possibly related to viral infection, may also influence corticosteroid response.

Objectives: To determine the frequency and within-patient variability of T1-high, T2-high, and T1/T2-high asthma endotypes and whether virally influenced T1-high disease influences corticosteroid response in asthma.

In office sampling of eosinophil peroxidase to diagnose eosinophilic chronic rhinosinusitis.

Background: Practical biomarkers for endotypic characterization of chronic rhinosinusitis (CRS) remain elusive, hindering clinical utility. Eosinophil peroxidase (EPX) is an enzyme released by activated eosinophils. The objective of this study was to evaluate a clinic EPX assay as a marker of eosinophilic CRS.

Peroxidase-mediated mucin cross-linking drives pathologic mucus gel formation in IL-13-stimulated airway epithelial cells.

Mucus plugs occlude airways to obstruct airflow in asthma. Studies in patients and in mouse models show that mucus plugs occur in the context of type 2 inflammation, and studies in human airway epithelial cells (HAECs) show that IL-13-activated cells generate pathologic mucus independently of immune cells. To determine how HAECs autonomously generate pathologic mucus, we used a magnetic microwire rheometer to characterize the viscoelastic properties of mucus secreted under varying conditions.

A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus.

A novel DNase assay reveals low DNase activity in severe asthma.

Secreted deoxyribonucleases (DNases), such as DNase-I and DNase-IL3, degrade extracellular DNA, and endogenous DNases have roles in resolving airway inflammation and guarding against autoimmune responses to nucleotides. Subsets of patients with asthma have high airway DNA levels, but information about DNase activity in health and in asthma is lacking. To characterize DNase activity in health and in asthma, we developed a novel kinetic assay using a Taqman probe sequence that is quickly cleaved by DNase-I to produce a large product signal.

Changes in systemic cancer therapy in Australia during the Delta and Omicron waves of the COVID-19 pandemic (2021-2022): a controlled interrupted time series analysis.

Objectives: Australian lockdowns in response to the initial coronavirus disease 2019 (COVID-19) outbreak in 2020 were associated with small and transient changes in the use of systemic cancer therapy. We aimed to investigate the impacts of the longer and more restrictive lockdowns in the Australian states of New South Wales (NSW) and Victoria during both the Delta subvariant lockdowns in mid-2021 and the Omicron subvariant outbreak in late 2021/early 2022.

Study Type: Population-based, controlled interrupted time series analysis.

Rechallenges without desensitization following platinum-based chemotherapy reactions.

Background: There is increasing interest in non-desensitization protocols as a potential way to reintroduce chemotherapy following hypersensitivity reactions (HSR).

Objective: To provide insight into the potential utility of non-desensitization reintroduction, particularly at institutions where allergy consultation may not be available.

Methods: For 70 patients with platinum HSR who underwent rechallenge with standard (≤2 hours), extended (1-bag, 1-step, 4-6 hours), or titrated (4-to-5-bag and -step, 6-7.

Prescribing practices of inhaled corticosteroids for premature infants in the neonatal intensive care unit.

Objective: Despite limited safety and efficacy data, inhaled corticosteroids (ICS) are prescribed to premature infants in the neonatal intensive care unit (NICU). We examined contemporary use and risk factors for ICS use in the NICU.

Study Design: Infants <33 weeks gestational age and <1500 gm birth weight discharged from Pediatrix Medical Group NICUs between 2010 and 2020 were included.

A Novel Air Trapping Segment Score Identifies Opposing Effects of Obesity and Eosinophilia on Air Trapping in Asthma.

Density thresholds in computed tomography (CT) lung scans quantify air trapping (AT) at the whole-lung level but are not informative for AT in specific bronchopulmonary segments. To apply a segment-based measure of AT in asthma to investigate the clinical determinants of AT in asthma. In each of 19 bronchopulmonary segments in CT lung scans from 199 patients with asthma, AT was categorized as present if lung attenuation was less than -856 Hounsfield units at expiration in ⩾15% of the lung area.

Prevalence of Australians exposed to potentially cardiotoxic cancer medicines: a population-based cohort study.

Background: Cardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia.

Impact of an Inpatient Allergy Guideline on β-Lactam and Alternative Antibiotic Use.

Background: A guideline identifying when inpatients with penicillin or cephalosporin antibiotic allergy labels (PCAAL) can receive β-lactam antibiotics increased β-lactam receipt at a large northeastern US health care system.

Objective: To report outcomes of implementing a similar guideline and electronic order set (OS) at an independent academic health care system.

Methods: Penicillin/cephalosporin receipt (percentage of inpatients receiving full doses) and alternative antibiotic use (days of therapy per 1000 patient-days [DOT/1000PD]) were compared over 3 periods before (February 1, 2017, to January 31, 2018) and after guideline implementation (February 1, 2018, to January 31, 2019), and after OS implementation (February 1, 2019, to January 31, 2020) among inpatients with PCAAL admitted on medical services with access to guideline/OS and education (Medical-PCAAL, n = 8721), surgical services with access to guideline/OS without education (Surgical-PCAAL, n = 5069), and obstetrics/gynecology services without interventions (Ob/Gyn-PCAAL, n = 798) and inpatients without PCAAL admitted on the same services (Medical-No-PCAAL, n = 50,840; Surgical-No-PCAAL, n = 29,845; Ob/Gyn-No-PCAAL, n = 6109).

International consensus statement on allergy and rhinology: Allergic rhinitis - 2023.

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated.

Harnessing Real-World Evidence to Advance Cancer Research.

Randomized controlled trials (RCTs) form a cornerstone of oncology research by generating evidence about the efficacy of therapies in selected patient populations. However, their implementation is often resource- and cost-intensive, and their generalisability to patients treated in routine practice may be limited. Real-world evidence leverages data collected about patients receiving clinical care in routine practice outside of clinical trial settings and provides opportunities to identify and address gaps in clinical trial evidence.

Exploring antiviral and anti-inflammatory effects of thiol drugs in COVID-19.

The redox status of the cysteine-rich SARS-CoV-2 spike glycoprotein (SARS-2-S) is important for the binding of SARS-2-S to angiotensin-converting enzyme 2 (ACE2), suggesting that drugs with a functional thiol group ("thiol drugs") may cleave cystines to disrupt SARS-CoV-2 cell entry. In addition, neutrophil-induced oxidative stress is a mechanism of COVID-19 lung injury, and the antioxidant and anti-inflammatory properties of thiol drugs, especially cysteamine, may limit this injury. To first explore the antiviral effects of thiol drugs in COVID-19, we used an ACE-2 binding assay and cell entry assays utilizing reporter pseudoviruses and authentic SARS-CoV-2 viruses.

Allergy to Local Anesthetics is a Rarity: Review of Diagnostics and Strategies for Clinical Management.

Local anesthetics (LA) are commonly used in procedures and in topical agents for pain management. With the increasing use of LA drugs, the management of LA reactions is more frequently encountered in the office and in operating rooms. True allergic reactions involving IgE-mediated reactions and anaphylaxis are rare; they have only been identified in case reports and account for less than 1% of adverse LA reactions.

Coronavirus disease 2019 vaccine administration in patients with reported reactions to polyethylene glycol- and polysorbate-containing therapeutics.

Background: Polyethylene glycol (PEG) and polysorbate reactions were initially implicated as a likely risk factor for reacting to coronavirus disease 2019 (COVID-19) vaccines and remain a source of vaccine hesitancy despite increasing evidence that they do not pose an increased risk for COVID-19 vaccine reactions.

Objective: To investigate COVID-19 vaccine safety outcomes in patients with reported reactions to PEG- and polysorbate-containing medications and vaccines.

Methods: COVID-19 vaccine safety was reviewed in patients with PEG or polysorbate reactions documented in their electronic medical records at a tertiary academic medical center (cohort 1) and patients referred to Allergy and Immunology with reported PEG or polysorbate reactions (cohort 2).