Associate Professor Alexander Larcombe

A pilot study into assessing the danger of heated-tobacco-products

Chemical analysis of new and “aged” e-liquids: Development of a rapid toxicological screening approach

Lung function in a model of a paediatric metabolic disease

Future Child Health

Using Systems Biology to understand asthma exacerbations and develop better treatments

Understanding how viral infection in early life impacts on lung function in adulthood

The health effects of electronic cigarettes

Is acamprosate safe to use in pregnancy, and can it mitigate the effects of alcohol consumption in pregnant mice?

Investigating the effects of macrolides on excessive synthesis and secretion of airway mucins using novel ex vivo and in vivo approaches

Fetal alcohol exposure, nutritional status and epigenetic disruption – exploring the links

Development of a screening tool to identify safer biodiesels

Computational fluid-particle dynamic and pharmacokinetic assessment of electronic cigarette aerosols for improved understanding of their potential to impact health

Chronic carbon dioxide exposure: an unrecognised health risk of climate change?

The epigenetic origin of alcohol-induced disorders: a cross-species study

Long-term derangement of antigen presenting cell populations in the respiratory tract following Influenza A infection

This project investigates how different populations of cells within the respiratory tract immune system are altered during a viral infection.

Alcohol pharmacotherapy dispensing trends in Australia between 2006 and 2023

This study aimed to investigate acamprosate and naltrexone dispensing patterns in Australia.

Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure resembling common patterns of alcohol consumption in pregnancy in humans. 

Hidden in plain sight: how vaping manufacturers exploit legislative loopholes

The respiratory health effects of acute in vivo diesel and biodiesel exhaust in a mouse model

Biodiesel, a renewable diesel fuel that can be created from almost any natural fat or oil, is promoted as a greener and healthier alternative to commercial mineral diesel without the supporting experimental data to back these claims. The aim of this research was to assess the health effects of acute exposure to two types of biodiesel exhaust, or mineral diesel exhaust or air as a control in mice.

Mucopolysaccharidosis (MPS IIIA) mice have increased lung compliance and airway resistance, decreased diaphragm strength, and no change in alveolar structure

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. 

Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model

Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model.

A rapid semi-quantitative screening method to assess chemicals present in heated e-liquids and e-cigarette aerosols

Electronic cigarettes (e-cigarettes) lack regulatory status as therapeutic products in all jurisdictions worldwide. They are potentially unsafe consumer products, with significant evidence they pose a risk to human health. Therefore, developing rapid, economical test methods to assess the chemical composition of e-liquids in heated and unheated forms and the aerosols produced by e-cigarettes is crucial.

Respiratory Health Effects of In Vivo Sub-Chronic Diesel and Biodiesel Exhaust Exposure

Biodiesel, which can be made from a variety of natural oils, is currently promoted as a sustainable, healthier replacement for commercial mineral diesel despite little experimental data supporting this. The aim of our research was to investigate the health impacts of exposure to exhaust generated by the combustion of diesel and two different biodiesels.

Electronic Cigarette Usage Patterns and Perceptions in Adult Australians

Despite their increasing popularity, and Australia's unique regulatory environment, how and why Australian adults use e-cigarettes and their perceptions of their safety, efficacy and regulation have not been extensively reported before. In this study, we screened 2217 adult Australians with the aim of assessing these questions in a sample of current or former e-cigarette users.

Switching from tobacco cigarettes in very early pregnancy: The effects of in utero e-cigarette exposure on mouse offspring neurodevelopment and behaviour

Electronic cigarettes (e-cigarettes) are often perceived to be safer than smoking, which has led to some women switching to e-cigarettes during pregnancy. However, the effects of switching from smoking to e-cigarettes on both pregnancy outcomes and the foetus are largely unknown. This study aimed to investigate the effects of switching from tobacco smoking to e-cigarette use in very early pregnancy on birth outcomes, neurodevelopment and behaviour of the offspring.

Genome Sequences of Two Lytic Staphylococcus aureus Bacteriophages Isolated from Wastewater

Two lytic double-stranded DNA (dsDNA) bacteriophages, belonging to the family Herelleviridae, were isolated from wastewater in Western Australia. Biyabeda-mokiny 2 appears to belong to the genus Kayvirus, and Koomba-kaat 1 to Silviavirus.

Genome Sequence of a Lytic Staphylococcus aureus Bacteriophage Isolated from Breast Milk

We identified a double-stranded DNA (dsDNA) bacteriophage appearing to belong to Herelleviridae, genus Kayvirus. The bacteriophage, Biyabeda-mokiny 1, was isolated from breast milk using a clinical isolate of Staphylococcus aureus.

The effects of acamprosate on maternal and neonatal outcomes in a mouse model of alcohol use disorders

Despite the teratogenic effects of alcohol, little is known about the safety of pharmacotherapies such as acamprosate for the treatment of alcohol use disorders in pregnancy. The aims of this study were to investigate, in a mouse model, the effects of maternally administered acamprosate on maternal and neonatal health, offspring neurodevelopment and behaviour, as well as examine whether acamprosate reduces the neurological harm associated with alcohol consumption in pregnancy.

Biodiesel feedstock determines exhaust toxicity in 20% biodiesel: 80% mineral diesel blends

To address climate change concerns, and reduce the carbon footprint caused by fossil fuel use, it is likely that blend ratios of renewable biodiesel with commercial mineral diesel fuel will steadily increase, resulting in biodiesel use becoming more widespread.

Toxicity of different biodiesel exhausts in primary human airway epithelial cells grown at air-liquid interface

Biodiesel is created through the transesterification of fats/oils and its usage is increasing worldwide as global warming concerns increase. Biodiesel fuel properties change depending on the feedstock used to create it.

Azithromycin inhibits mucin secretion, mucous metaplasia, airway inflammation, and airways hyperresponsiveness in mice exposed to house dust mite extract

Excessive production, secretion, and retention of abnormal mucus is a pathological feature of many obstructive airways diseases including asthma. Azithromycin is an antibiotic that also possesses immunomodulatory and mucoregulatory activities, which may contribute to the clinical effectiveness of azithromycin in asthma.

In Vitro primary human airway epithelial whole exhaust exposure

The method outlined in this article is a customization of the whole exhaust exposure method generated by Mullins et al. (2016) using reprogrammed primary human airway epithelial cells as described by Martinovich et al. (2017). It has been used successfully to generate recently published data (Landwehr et al. 2021). The goal was to generate an exhaust exposure model where exhaust is collected from a modern engine, real-world exhaust concentrations are used and relevant tissues exposed to assess the effects of multiple biodiesel exposures.

Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence

Prenatal alcohol exposure is associated with a range of adverse offspring neurodevelopmental outcomes. Several studies suggest that PAE modifies DNA methylation in offspring cells and tissues, providing evidence for a potential mechanistic link to Fetal Alcohol Spectrum Disorder.

Exacerbation of chronic cigarette-smoke induced lung disease by rhinovirus in mice

A significant proportion of chronic obstructive pulmonary disease exacerbations are strongly associated with rhinovirus infection (HRV). In this study, we combined long-term cigarette smoke exposure with HRV infection in a mouse model.

Long-term exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in young adulthood

Atmospheric carbon dioxide (CO2) levels are currently at 418 parts per million (ppm), and by 2100 may exceed 900 ppm. The biological effects of lifetime exposure to CO2 at these levels is unknown. Previously we have shown that mouse lung function is altered by long-term exposure to 890 ppm CO2. Here, we assess the broader systemic physiological responses to this exposure.

What doctors should consider before prescribing e-liquids for e-cigarettes

Chemical analysis of fresh and aged Australian e-cigarette liquids

To assess the chemical composition of electronic cigarette liquids (e-liquids) sold in Australia, in both their fresh and aged forms. Design, setting: Gas chromatography–mass spectrometry analysis of commercial e-liquids sold in Australia (online and physical stores).

Phage therapy for multi-drug resistant respiratory tract infections

The emergence of multi-drug resistant (MDR) bacteria is recognised today as one of the greatest challenges to public health. As traditional antimicrobials are becoming ineffective and research into new antibiotics is diminishing, a number of alternative treatments for MDR bacteria have been receiving greater attention. Bacteriophage therapies are being revisited and present a promising opportunity to reduce the burden of bacterial infection in this post-antibiotic era.

Previous Influenza Infection Exacerbates Allergen Specific Response and Impairs Airway Barrier Integrity in Pre-Sensitized Mice

In this study we assessed the effects of antigen exposure in mice pre‐sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression.

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.

Fuel feedstock determines biodiesel exhaust toxicity in a human airway epithelial cell exposure model

Biodiesel is promoted as a sustainable replacement for commercial diesel. Biodiesel fuel and exhaust properties change depending on the base feedstock oil/fat used during creation. The aims of this study were, for the first time, to compare the exhaust exposure health impacts of a wide range of biodiesels made from different feedstocks and relate these effects with the corresponding exhaust characteristics.

Editorial overview: The physiology of the diseased lung

Exposomes and metabolic health through a physical activity lens: a narrative review

In this narrative review, we provide an overview of the role of physical activity as part of differing exposomes (our combined non-genetic exposures from conception onwards) and environmental influences on metabolic health. We discuss 'beneficial' exposomes (green/natural outdoor spaces, sun exposure, healthy diets and features of built environments) that could synergise with physical activity to prevent metabolic dysfunction, particularly that related to lifestyle diseases of obesity, type 2 diabetes and metabolic syndrome.

Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling

Climate change models predict that atmospheric carbon dioxide [CO2] levels will be between 700 and 900 ppm within the next 80yrs. In this study we aimed to assess the respiratory structure and function effects of long-term exposure to 890ppm CO2 from preconception to adulthood using a mouse model.

Pharmacological ablation of the airway smooth muscle layer—Mathematical predictions of functional improvement in asthma

Findings provide further proof of concept that pharmacological targeting of airway smooth muscle thickness will be beneficial and may be facilitated by azithromycin

The Evolving Landscape of e-Cigarettes: A Systematic Review of Recent Evidence

This review focuses on smokers and nonsmokers and evaluates the most recent data regarding the potential health effects of e-cigarettes

Editorial overview: Endocrine and metabolic adaptations to extreme environments: Living life to the extreme – insights into the limits of life and transitions to disease

The need to understand responses to extreme environments has prompted this edition of Current Opinion in Endocrine and Metabolic Research

Confounding effects of gavage in mice: Impaired respiratory structure and function

It is therefore clear that gavage can have significant impacts on experimental animals in terms of their stress response and overall morbidity and mortality

Early-life exposure to electronic cigarettes: cause for concern

There are a multitude of ways that, with respect to early-life exposures and health, electronic nicotine delivery systems are a cause for concern

Soy Biodiesel Exhaust is More Toxic than Mineral Diesel Exhaust in Primary Human Airway Epithelial Cells

Exposure to biodiesel exhaust resulted in significantly greater cell death and a greater release of immune mediators compared to both air controls and ULSD exhaust

Mechanical Abnormalities of the Airway Wall in Adult Mice After Intrauterine Growth Restriction

We propose that mechanical abnormalities of the airway wall acquired through disrupted fetal growth impact susceptibility to disease

Nicotine and other potentially harmful compounds in "nicotine-free" e-cigarette liquids in Australia

The aim of our investigation was to assess the chemical composition of a range of e-liquids available in Australia, focusing on nicotine and other potentially harmful compounds

Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams

While maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring

Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention

Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma

This study demonstrates novel intrinsic differences in tight junctions gene and protein expression between airway epithelial cells of children with and without asthma

Independent and combined effects of airway remodelling and allergy on airway responsiveness

There was a positive relationship between the thickness of the airway smooth muscle layer with airway responsiveness, which was shifted upward in the presence of allergy

Visualisation of Multiple Tight Junctional Complexes in Human Airway Epithelial Cells

Apically located tight junctions in airway epithelium perform a fundamental role in controlling macromolecule migration through paracellular spaces.

Foetal growth restriction in mice modifies postnatal airway responsiveness in an age and sex-dependent manner

Our data demonstrate changes in airway responsiveness as a result of intrauterine growth restriction that could influence susceptibility to asthma development

Fragranced consumer products: effects on asthmatic Australians

Most asthmatics would prefer workplaces, healthcare facilities, and environments that are fragrance-free, which could help reduce adverse effects

Increased heterogeneity of airway calibre in adult rats after hypoxia-induced intrauterine growth restriction

The rat model demonstrates that intrauterine growth restriction leads to a more heterogeneous distribution of airway lumen calibre in adulthood

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

In disease settings, vitamin D may be important for maintaining optimal lung epithelial integrity and suppressing inflammation, but less is known of its effects prior to disease onset.

The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice

This study shows, for the first time, that exposure to e-cigarette aerosol during adolescence and early adulthood is not harmless to the lungs and can result in significant impairments in lung function.

Optical coherence tomography-based contact indentation for diaphragm mechanics in a mouse model of transforming growth factor alpha induced lung disease

This study tested the utility of optical coherence tomography-based indentation to assess mechanical properties of respiratory tissues in disease

Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells

Canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure

Effect of human rhinovirus infection on airway epithelium tight junction protein disassembly and transepithelial permeability

HRV-1B infection directly alters human airway epithelial TJ expression leading to increased epithelial permeability potentially via antiviral response of IL-15

Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice

Early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice

Biodiesel exhaust: The need for a systematic approach to health effects research

Biodiesel is a generic term for fuel that can be made from virtually any plant or animal oil via transesterification of triglycerides with an alcohol...

Respiratory toxicology of e-cigarettes: effect of vapours on lung function and inflammation

Electronic cigarettes (ECs) have been rapidly gaining ground on conventional cigarettes due to their efficiency in ceasing or reducing tobacco consumption,...

Influence of gestational age on dead space and alveolar ventilation in preterm infants ventilated with volume guarantee

Ventilated preterm infant lungs are vulnerable to overdistension and underinflation.

Persistent and compartmentalised disruption of dendritic cell subpopulations in the lung following influenza A virus infection

Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung...

House dust mite induced lung inflammation does not alter circulating vitamin D levels

We hypothesized that allergic inflammation decreases the level of circulating 25(OH)D and tested this using a mice model of house dust mite (HDM) induced...

Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells

Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared...

Route of exposure alters inflammation and lung function responses to diesel exhaust

In this study, we compared the physiological consequences of short-term exposure to diesel exhaust via inhalation to those due to exposure to the same diesel...

Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice

In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to...

The effect of diesel exhaust exposure on blood-brain barrier integrity and function in a murine model

Epidemiological studies indicate that exposure to diesel exhaust (DE) is associated with vascular-based disorders.

Early life arsenic exposure and acute and long-term responses to influenza A infection in mice

Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase...

The influence of moving walls on respiratory aerosol deposition modelling

This work initially examines particle deposition in a Weibull-type geometry, comparing traditional computational fluid dynamics approaches with a novel...

In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood.

In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice

In utero exposure to arsenic via drinking water increases the risk of lower respiratory tract infections during infancy and mortality from bronchiectasis in...

Physiological and inflammatory responses in an anthropomorphically relevant model of acute diesel exhaust particle exposure are sex and dose-dependent

Diesel exhaust particles (DEP) are an important contributor to suspended particulate matter (PM) in urban areas. While epidemiological evidence exists for a...

Factors influencing the assessment of lung function in mice with influenza-induced lung disease

The constant-phase model (CPM) is commonly fit to respiratory system input impedance (Z rs) to estimate lung mechanics.

The mechanism of deep inspiration-induced bronchoprotection: Evidence from a mouse model

In healthy individuals, deep inspirations (DIs) taken prior to a bronchial challenge reduce the bronchoconstrictor response, which is termed...

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza

Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre-existing respiratory diseases.

Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk

A hallmark of atopic asthma is development of chronic airways hyper-responsiveness (AHR) that persists in the face of ongoing exposure to perennial...

Sensitizing and Th2 Adjuvant Activity of Cysteine Protease Allergens

Here, we report on a model that does not use Th2-skewing adjuvants and yet achieves sensitization solely via the nasal mucosa.

Sexual dimorphism in lung function responses to acute influenza A infection

Males are generally more susceptible to respiratory infections; however, there are few data on the physiological responses to such infections in males and...

In utero cigarette smoke exposure impairs somatic and lung growth in BALB/c mice

The aim of this study was to assess whether in utero tobacco smoke exposure alone affects early-life lung growth and development. Pregnant BALB/c mice...

Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control

The hallmark of atopic asthma is transient airways hyperresponsiveness (AHR) preceded by aeroallergen-induced Th-cell activation.

Self-citation in American Physiological Society Journals

This study investigates the incidence of self-citation (authors citing their own work) for scholarly articles in ten journals published by the American...