Nasal Mucus Cytokines Are Correlated with Spirometry Measures in CRS Patients with Comorbid Asthma.

CRS patients with asthma show differential nasal mucus cytokine signatures based on endotype. IL-7 concentration is positively associated with higher %FEV1 and %FVC in CRS patients with asthma.

Endogenous Glucagon-Like Peptide-1 Receptor and Glucose-Dependent Insulinotropic Polypeptide Receptor Signaling Inhibits Aeroallergen-Induced Innate Airway Inflammation.

Background: Anti-inflammatory effects of incretin signaling through the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR) in mice have been reported. Therefore, we hypothesized that signaling through the endogenous GLP-1R and the GIPR individually decreases allergic airway inflammation and that the combination of GLP-1R and GIPR signaling together additively inhibits allergen-induced lung and airway inflammation.

Methods: WT (C57BL/6J), GLP-1R knockout (KO), GIPR KO, and GLP-1R/GIPR double KO (DKO) mice were challenged intranasally with Alternaria alternata extract (Alt-Ext) or vehicle to evaluate the impact of signaling through these receptors on the innate allergen-induced inflammatory response that is primarily driven by group 2 innate lymphoid cells (ILC2).

Androgen signaling restricts glutaminolysis to drive sex-specific Th17 metabolism in allergic airway inflammation.

Female individuals have an increased prevalence of many Th17 cell-mediated diseases, including asthma. Androgen signaling decreases Th17 cell-mediated airway inflammation, and Th17 cells rely on glutaminolysis. However, it remains unclear whether androgen receptor (AR) signaling modifies glutamine metabolism to suppress Th17 cell-mediated airway inflammation.

Subset-specific mitochondrial stress and DNA damage shape T cell responses to fever and inflammation.

Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory T cell suppressive capacity. However, heat-exposed T helper 1 (T1) cells selectively developed mitochondrial stress and DNA damage that activated Trp53 and stimulator of interferon genes pathways.

How early life respiratory viral infections impact airway epithelial development and may lead to asthma.

Childhood asthma is a common chronic disease of the airways that results from host and environment interactions. Most risk factor studies of asthma point to the first year of life as a susceptibility window of mucosal exposure that directly impacts the airway epithelium and airway epithelial cell development. The development of the airway epithelium, which forms a competent barrier resulting from coordinated interactions of different specialized cell subsets, occurs during a critical time frame in normal postnatal development in the first year of life.

Healthcare social network research and the ECHO model™: Exploring a community of practice to support cultural brokers and transfer cultural knowledge.

Background: Project ECHO networks at Children's Health Queensland Hospital and Health Service (CHQHHS) are communities of practice designed to mitigate services and systems fragmentation by building collaborative partnerships addressing priority child and youth health needs. Aboriginal and Torres Strait Islander people experience the negative impacts of fragmentation in addition to historical challenges of absent or culturally inappropriate health services. Access to culturally safe and responsive services can be improved by engaging Aboriginal and Torres Strait Islander Health Workers and similar roles in an online community of practice, supporting the integration of cultural and clinical knowledge and self-determination of Aboriginal and Torres Strait Islander consumers in decisions affecting their health.

The association of infant urinary adrenal steroids with the risk of childhood asthma development.

Background: Adrenal steroids play important roles in early-life development. However, our understanding of the effects of perinatal adrenal steroids on the development of childhood asthma is incomplete.

Objective: To evaluate the associations between early-life adrenal steroid levels and childhood asthma.

Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO), we developed a model of repetitive exposure to SO in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular (PV) disease. Although abnormalities in small airways were not sufficient to alter lung mechanics, PV remodeling resulted in the development of pulmonary hypertension and reduced exercise tolerance in SO-exposed mice.

The Therapeutic Monoclonal Antibody Bamlanivimab Does Not Enhance SARS-CoV-2 Infection by FcR-Mediated Mechanisms.

As part of the non-clinical safety package characterizing bamlanivimab (SARS-CoV-2 neutralizing monoclonal antibody), the risk profile for antibody-dependent enhancement of infection (ADE) was evaluated in vitro and in an African green monkey (AGM) model of COVID-19. In vitro ADE assays in primary human macrophage, Raji, or THP-1 cells were used to evaluate enhancement of viral infection. Bamlanivimab binding to C1q, FcR, and cell-based effector activity was also assessed.

Building and maintaining interprofessional collaborative practice in eyecare: Learnings from the Queensland Paediatric Optometry Alignment Program.

Purpose: The Queensland Children's Hospital Paediatric Optometry Alignment Program commenced with a pilot phase to assess its feasibility, effectiveness and acceptability. This study identified the barriers that hinder effective interprofessional collaboration and the facilitators that contribute to its success, and assessed changes in optometrists' satisfaction since the pilot phase of the collaborative care programme.

Methods: Qualitative deductive and inductive content analysis was applied to open-ended free-text survey responses collected in 2018 from the optometrists involved in the Program's pilot phase.

Loss of p73 Expression Contributes to Chronic Obstructive Pulmonary Disease.

Multiciliated cell (MCC) loss and/or dysfunction is common in the small airways of patients with chronic obstructive pulmonary disease (COPD), but it is unclear if this contributes to COPD lung pathology. To determine if loss of p73 causes a COPD-like phenotype in mice and explore whether smoking or COPD impact p73 expression. p73 mice were crossed with Shh-Cre mice to generate mice lacking MCCs in the airway epithelium.

Tissue-Specific Dependence of Th1 Cells on the Amino Acid Transporter SLC38A1 in Inflammation.

Amino acid (AA) uptake is essential for T cell metabolism and function, but how tissue sites and inflammation affect CD4 T cell subset requirements for specific AA remains uncertain. Here we tested CD4 T cell AA demands with and multiple CRISPR screens and identify subset- and tissue-specific dependencies on the AA transporter SLC38A1 (SNAT1). While dispensable for T cell persistence and expansion over time and lung inflammation, SLC38A1 was critical for Th1 but not Th17 cell-driven Experimental Autoimmune Encephalomyelitis (EAE) and contributed to Th1 cell-driven inflammatory bowel disease.

Building Career Paths for Ph.D., Basic and Translational Scientists in Clinical Departments in the United States: An Official American Thoracic Society Workshop Report.

To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units.

Repetitive Sulfur Dioxide Exposure in Mice Models Post-Deployment Respiratory Syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than non-deployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the deployers in this cohort reported exposure to sulfur dioxide (SO ), we developed a model of repetitive exposure to SO in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular disease (PVD). Although abnormalities in small airways were not sufficient to alter lung mechanics, PVD was associated with the development of pulmonary hypertension and reduced exercise tolerance in SO exposed mice.

Asthma innovations from the first International Collaborative Asthma Network forum.

Background: Many patients have uncontrolled asthma despite available treatments. Most of the new asthma therapies have focused on type 2 (T2) inflammation, leaving an unmet need for innovative research into mechanisms of asthma beyond T2 and immunity. An international group of investigators developed the International Collaborative Asthma Network (ICAN) with the goal of sharing innovative research on disease mechanisms, developing new technologies and therapies, organising pilot studies and engaging early-stage career investigators from across the world.

Turning Strategy into Action - Using the ECHO Model to Empower the Australian Workforce to Integrate Care.

Introduction: Children's Health Queensland (CHQ) established a telementoring hub in Queensland, using the Project ECHO® model, to pilot and scale a range of virtual communities of practice (CoP) to empower the Australian workforce to integrate care.

Description: The establishment of the first Project ECHO hub in Queensland facilitated the implementation of a variety of child and youth health CoP that strategically aligned to the organisation's approach to integrate care through workforce development. Subsequently, other organisations nationally have also been trained to implement and replicate the ECHO model to effect more integrated care through CoPs in other priority areas.

Cystic Fibrosis Reprograms Airway Epithelial IL-33 Release and Licenses IL-33-Dependent Inflammation.

Type 2 inflammation has been described in people with cystic fibrosis (CF). Whether loss of CFTR (cystic fibrosis transmembrane conductance regulator) function contributes directly to a type 2 inflammatory response has not been fully defined. The potent alarmin IL-33 has emerged as a critical regulator of type 2 inflammation.

Low Gut Microbial Diversity Augments Estrogen-Driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease.

Although profibrotic cytokines, such as IL-17A and TGF-β1, have been implicated in the pathogenesis of interstitial lung disease (ILD), the interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as the phosphorylation of STAT3, have not been defined. Here, through chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells, we show that regions within the STAT3 locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung.

Low Gut Microbial Diversity Augments Estrogen-driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease.

Although profibrotic cytokines such as IL-17A and TGF-β1 have been implicated in interstitial lung disease (ILD) pathogenesis, interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as phosphorylation of STAT3, have not been defined. Here we show by chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells that regions within the locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung.

The paediatric optometry alignment program - a model of interprofessional collaborative eyecare.

Clinical Relevance: Collaboration  between hospital-based ophthalmology and community-based optometry could pave the way to improve access to paediatric eyecare services.

Background: The Paediatric Optometry Alignment Program (POAP) began in 2016 as a proof-of-concept pilot project that aimed to improve access to specialist paediatric ophthalmology services. If found to be effective at improving patient access, and the quality of care acceptable to patients and professionals then the strategic intent was to upscale the programme to  serve as a model for paediatric eye care in the community.