Program Head, Respiratory Health
BScEnv (Hons) PhD
Associate Professor Alexander Larcombe began work at the Telethon Institute in 2005 and is now a Senior Research Fellow, Head of the Respiratory Environmental Health team and Head of the Respiratory Health Program.
During his time at the Institute Associate Professor Larcombe has led many research projects, primarily investigating the physiological and developmental consequences of exposure to a range of environmental insults including:
- allergen exposure (particularly ovalbumin and house dust mite as models of allergic airways disease),
- respiratory viral infection (including rhinovirus and influenza)
- pollutants (including electronic cigarette aerosols, tobacco smoke, diesel/biodiesel exhaust and arsenic)
- climate change (including the impacts of increased atmospheric CO2)
Associate Professor Larcombe's research has shown how exposure to such insults in early-life (including in utero) can have significant impacts on lung growth and lung function, and lead to life-long respiratory disease.
The goals of his research are to establish and employ relevant models of respiratory dysfunction which can be easily manipulated to identify mechanisms of disease. Once likely mechanisms are fully identified, Associate Professor Larcombe employs interventional studies with the ultimate goal of reducing the impact of early-life respiratory system insults on lung function which, in the long term, will improve the health of children and families.
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Projects
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Publications
January 2021
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.
Published research Respiratory Environmental Health Subsite: WalyanJune 2020Pharmacological 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
Asthma Published research Respiratory Environmental HealthMay 2020The 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
Published research Respiratory Environmental HealthApril 2020Editorial 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
Published research Respiratory Environmental HealthDecember 2019Confounding 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
Published research Respiratory Environmental HealthNovember 2019Early-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
Published research Respiratory Environmental HealthOctober 2019Soy 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
Published research Airway Epithelial Research Respiratory Environmental HealthAugust 2019Mechanical 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
Published research Respiratory Environmental HealthFebruary 2019Nicotine 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
Published research Respiratory Environmental HealthJanuary 2019Maternal 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
Published research Cardiometabolic Sunhealth Respiratory Environmental HealthNovember 2018Transplacental 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
Published research Experimental Immunology Human Immunology Respiratory Environmental HealthMay 2018Effects 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
Asthma Published research Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthFebruary 2018Independent 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
Published research Respiratory Environmental HealthFebruary 2018Visualisation 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.
Published research Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthJanuary 2018Foetal 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
Published research Respiratory Environmental HealthJanuary 2018Fragranced 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
Asthma Published research Respiratory Environmental HealthOctober 2017Increased 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
Published research Respiratory Environmental HealthAugust 2017Vitamin 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.
Published research Inflammation Cardiometabolic Sunhealth Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthJuly 2017The 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.
Published research Respiratory Environmental HealthMay 2017Optical 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
Published research Respiratory Environmental HealthJanuary 2016Biodiesel 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
Published research Airway Epithelial Research Respiratory Environmental HealthOctober 2016Effect 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
Published research Systems Immunology Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthJanuary 2016Early 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
Published research Airway Epithelial Research Respiratory Environmental HealthJuly 2015Biodiesel 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...
Published research Airway Epithelial Research Respiratory Environmental HealthMarch 2015Respiratory 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,...
Published research Respiratory Environmental HealthJanuary 2015Influence 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.
Published research Children's Lung Health Respiratory Environmental HealthNovember 2014House 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...
Published research Vitamin D and Sunlight Airway Epithelial Research P4 Respiratory Health for Kids Respiratory Environmental HealthNovember 2014Persistent 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...
Published research Influenza Experimental Immunology Human Immunology Respiratory Environmental HealthJuly 2014Biodiesel 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...
Published research Airway Epithelial Research Respiratory Environmental HealthMay 2014Route 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...
Published research Airway Epithelial Research Respiratory Environmental HealthMarch 2014Rhinovirus 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...
Asthma Published research Airway Epithelial Research Respiratory Environmental HealthJanuary 2014The 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.
Published research Respiratory Environmental HealthAugust 2013Early 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...
Published research Early Childhood Development Respiratory Environmental HealthMay 2013The 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...
Published research Respiratory Environmental HealthFebruary 2013In 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...
Published research Systems Immunology Respiratory Environmental HealthFebruary 2013In 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.
Published research Respiratory Environmental HealthDecember 2011Physiological 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...
Published research Respiratory Environmental HealthNovember 2012Factors 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.
Published research Respiratory Environmental HealthOctober 2012The 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...
Asthma Published research Respiratory Environmental HealthSeptember 2012Acute 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.
Published research Influenza Respiratory Environmental HealthMay 2012Defective 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...
Asthma Published research Experimental Immunology Human Immunology Respiratory Environmental HealthJanuary 2012Sensitizing 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.
Asthma Published research Child Allergy & Immunology Human Immunology Respiratory Environmental HealthMarch 2011Sexual 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...
Published research Influenza Respiratory Environmental HealthFebruary 2011In 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...
Asthma Published research Respiratory Environmental HealthJanuary 2011Boosting 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.
Asthma Published research Experimental Immunology Human Immunology Respiratory Environmental HealthJanuary 2011Self-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...
Published research Respiratory Environmental Health -
Education and Qualifications
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Awards/Honours
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Recent Research Support