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Research

Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

Neutrophil elastase is a significant risk factor for structural lung disease in cystic fibrosis, and Pseudomonas aeruginosa airway infection is linked with neutrophilic inflammation and substantial respiratory morbidity. We aimed to evaluate how neutrophil elastase (NE) activity changes after P. aeruginosa eradication and influences early disease outcomes. We assessed participants in the AREST CF cohort between 2000 and 2018 who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid and who underwent eradication treatment and a post eradication BAL. Factors associated with persistent P. aeruginosa infection, persistent neutrophilic inflammation following eradication and worse structural lung disease one year post-eradication were evaluated.

Research

Primary Nasal Epithelial Cells as a Surrogate Cell Culture Model for Type-II Alveolar Cells to Study ABCA-3 Deficiency

ATP Binding Cassette Subfamily A Member 3 (ABCA-3) is a lipid transporter protein highly expressed in type-II alveolar (AT-II) cells. Mutations in ABCA3 can result in severe respiratory disease in infants and children. To study ABCA-3 deficiency in vitro, primary AT-II cells would be the cell culture of choice although sample accessibility is limited. Our aim was to investigate the suitability of primary nasal epithelial cells, as a surrogate culture model for AT-II cells, to study ABCA-3 deficiency.

Research

Dysregulated Notch Signaling in the Airway Epithelium of Children with Wheeze

The airway epithelium of children with wheeze is characterized by defective repair that contributes to disease pathobiology. Dysregulation of developmental processes controlled by Notch has been identified in chronic asthma. However, its role in airway epithelial cells of young children with wheeze, particularly during repair, is yet to be determined.

Research

A near-complete genome of the uncultured Staphylococcus aureus phage COMBAT-CF_PAR1 isolated from the lungs of an infant with cystic fibrosis

In cystic fibrosis, bacteria–bacteriophage interaction in the lower airways is poorly understood. We present the near-complete genome of the uncultured Siphovirus-like bacteriophage, Staphylococcus aureus phage COMBAT-CF_PAR1, isolated from the lower airways. The genome spans 41,510 bp with 33.45% guanine–cytosine content and contains 65 open reading frames.

Research

A Small Device May Deliver King-Sized Solutions for Patients With an Exacerbation of Cystic Fibrosis

The aim is to examine whether using a portable spring-infusor device to deliver antibiotics compared with a standard infusion pump (SIP) translated to (i) improve health outcomes, (ii) reduce the length of stay (LoS), and (iii) reduce cost for treatment of exacerbations of cystic fibrosis.

Research

Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial

Repurposed drugs with host-directed antiviral and immunomodulatory properties have shown promise in the treatment of COVID-19, but few trials have studied combinations of these agents. The aim of this trial was to assess the effectiveness of affordable, widely available, repurposed drugs used in combination for treatment of COVID-19, which may be particularly relevant to low-resource countries. 

Research

Net benefit of smaller human populations to environmental integrity and individual health and wellbeing

The global human population is still growing such that our collective enterprise is driving environmental catastrophe. Despite a decline in average population growth rate, we are still experiencing the highest annual increase of global human population size in the history of our species-averaging an additional 84 million people per year since 1990.

Research

Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes

Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRβ) repertoire dynamics contribute to the therapeutic response. 

Research

Determinants of lung function development from birth to age 5 years: an interrupted time series analysis of a South African birth cohort

Early life is a key period that determines long-term health. Lung development in childhood predicts lung function attained in adulthood and morbidity and mortality across the life course. We aimed to assess the effect of early-life lower respiratory tract infection (LRTI) and associated risk factors on lung development from birth to school age in a South African birth cohort.

Research

How climate change degrades child health: A systematic review and meta-analysis

Children are more vulnerable than adults to climate-related health threats, but reviews examining how climate change affects human health have been mainly descriptive and lack an assessment of the magnitude of health effects children face. This is the first systematic review and meta-analysis that identifies which climate-health relationships pose the greatest threats to children.