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An infant nasal microbial gene atlas uncovers intervention-driven microbiome shifts and salt-resistant pathogen expansion

Functional studies of how early-life interventions shape the airway microbiome remain scarce. Here, we performed metagenomic sequencing of 704 longitudinal nasal swabs from infants with and without cystic fibrosis (CF) to construct and characterize a non-redundant gene atlas of the infant nasal microbiome. We aimed to determine how the nasal microbiome is perturbed by early therapies, as CF is commonly treated with inhaled hypertonic saline to improve mucociliary clearance.

Trajectories of prematurity-associated lung disease: lifelong lung health

Preterm birth is increasingly recognised as adversely influencing lifelong lung function. This Series paper on prematurity-associated lung disease reviews studies reporting longitudinal lung function measurements in individuals who were born preterm. Evidence suggests that preterm birth alters lung function trajectories from early life onwards, with implications for future respiratory morbidity. We propose that this population needs rigorous follow up that should include systematic monitoring of lung function across the lifespan, starting in childhood.

Population-specific heterogeneity in ontogeny of the broadly-conserved blood transcriptional program during the first week of life

Previous research has shown that immune development during the first week of life, i.e. ontogeny, is progressive, consistent and robust, involving large numbers of differentially expressed genes at each sampled time point.

Proteomic Insights into Intrauterine Growth Restriction and Its Role in Asthma Pathogenesis

Intrauterine growth restriction (IUGR) increases risk of developing respiratory diseases such as asthma later in life. This study aims to characterize the effects of maternal hypoxia-induced IUGR on the lung proteome and identify key altered pathways relevant to asthma development in male and female adult offspring.

Applying spirometry phenotypes to a longitudinal cohort born very preterm

To better characterise prematurity-associated lung disease, adult spirometry phenotype classifications (obstructive lung disease, preserved ratio impaired spirometry and dysanapsis) have been applied to children born preterm. It is unknown how these phenotypes track over time.

Carbon dioxide overload, detected in human blood, suggests a potentially toxic atmosphere within 50 years

Anthropogenic activities are increasing the amount of carbon dioxide (CO2) in the atmosphere. There is mounting experimental evidence that lifetime exposure to these increasing atmospheric CO2 levels can negatively impact the normal physiology of organisms. However, directly assessing this in humans is very difficult. 

Early life exposure to an episode of extreme air pollution and lung function later in childhood: the Hazelwood early life follow-up (ELF) study

Children are particularly vulnerable to air pollution, but the effects of early life exposure to acute, high-intensity pollution on later lung function remain poorly understood. We assessed the association between prenatal or infant exposure to fire-related fine particulate matter (PM2.5) from a six-week coal mine fire and subsequent lung function. 

What goes up must come down: dynamics of type 1 interferon signaling across the lifespan

Type 1 interferons (T1IFNs) are typically expressed in low concentrations under homeostatic conditions, but upon pathogenic insult or perturbation of the pathway, these critical immune signaling molecules can become either protectors from or drivers of pathology. While essential for initiating antiviral defense and modulating inflammation, dysregulation of T1IFN signaling can contribute to immunopathology, making it and its associated pathways prime targets for immune evasion and disruption by pathogens. 

Marked Variation in Paediatric Problematic Severe Asthma Services Across Australia and New Zealand

Asthma affects > 10% of children in Australia and New Zealand (NZ), with up to 5% of those having severe disease, presenting a management challenge. We aimed to survey tertiary paediatric respiratory services across Australia and NZ using a custom-designed questionnaire, to conduct a cross-sectional observational study of the numbers of children with problematic severe asthma seen, the number treated with biologic therapy, outpatient clinic/multidisciplinary team services available, investigations and tools routinely used and approaches utilised for transition to adult care.

Suppression of TGF-β/SMAD signaling by an inner nuclear membrane phosphatase complex

Cytokines of the TGF-β superfamily control essential cell fate decisions via receptor regulated SMAD (R-SMAD) transcription factors. Ligand-induced R-SMAD phosphorylation in the cytosol triggers their activation and nuclear accumulation. We determine how R-SMADs are inactivated by dephosphorylation in the cell nucleus to counteract signaling by TGF-β superfamily ligands.