Children's Lung, Environment and Asthma Research (CLEAR) Group

The Children’s Lung, Environment and Asthma Research (CLEAR) group was established in 2010 under the leadership of Professor Peter Sly who also leads the Children’s Health and Environment Program group. We conduct bench to bedside research that aims to understand the mechanisms underlying chronic childhood lung diseases such as asthma and cystic fibrosis. With research that spans a continuum from basic science, longitudinal cohort studies, clinical trials and translation of findings into clinical practice we work to delay or prevent lung disease, improve its clinical management and halt its progression as children transition to adulthood. 

Members of the CLEAR group have active research collaboration with the Telethon Institute for Child Health Research, National Research Centre for Environmental Toxicology, The Global Change Institute, The Australian Infectious Diseases Research Network, Murdoch Children’s Research Institute, Centre for Ecosystem Management, the School of Population Health UQ and Child and Adolescent Psychiatry, Queensland Health.

The group is funded by research grants from the RCH Foundation, the NHMRC, the Australian Research Council, Cystic Fibrosis Australia, Cystic Fibrosis Foundation Therapeutics, USA, and the University of Queensland. 

2017 Highlights

Industry funding helps to improve treatment for children with cystic fibrosis
Our team was awarded $237,735 by Gilead Sciences, Inc, USA for research that aims to understand how abnormalities in the immune responses of respiratory epithelium increase susceptibility for respiratory infections.

Grant helps us examine the underlying causes of lung disease in cystic fibrosis
A study examining Macrophages, the forgotten cells in cystic fibrosis lung disease was awarded $972,210 by the Cystic Fibrosis Foundation Therapeutics Inc. USA in a bid to understand possible new treatments for children with cystic fibrosis.

Infrastructure funding boosts research precision
Our team received more than $135,000 from The University of Queensland’s Major Equipment and Infrastructure grants for the purchase of specialist laboratory equipment that will address our needs for high nucleic acid quantification accuracy and precision within our research laboratory. The equipment will be situated at the Centre for Children’s Health Research and will benefit other research groups in addition to our own.

Standardising the way we manage discharge for patients with cystic fibrosis
Working in partnership with Professor Claire Wainwright, one of the Lady Cilento Children’s Hospital’s leading clinician-researchers, our team has been funded by the Children’s Hospital Foundation to develop objective criteria for discharge when children with cystic fibrosis are hospitalised for acute pulmonary exacerbation. By standardising discharge criteria, we hope to provide clarity for treating doctors, and peace of mind for families.

Putting immune function under the microscope
Gilead Pty Ltd have made a substantial investment of almost $500,000 to allow our team to address how innate immune cell function is impacted by direct acting antivirals and inhibitors in response to airway infections.

Our Projects

AIR POLLUTION IN VIETNAM

In recent decades, Hanoi has faced serious air pollution; however, few studies of the effects of ambient air pollution on health have been conducted in Vietnam while they have been studied extensively in many developed countries. The aims of this study are to examine the short-term effects of particulate matter (PM) and other air pollutants such as nitrogen dioxide (NO2), sulphur dioxide (SO2), carbon monoxide (CO), and ozone (O3) on hospital admissions for respiratory diseases among young children in Hanoi. Better understanding of the effect of ambient air pollution on children's health in Vietnam will contribute to the improvement of public health and environmental quality.

ELLF

Early Life Lung Function

Respiratory infections are the most commonly experienced illnesses throughout life, but especially during the first two years when infants may have six to eight infections each year. Emerging evidence indicates infections early in life along with other insults to developing airways in susceptible children may contribute to later development of chronic respiratory conditions such as asthma and chronic bronchitis.

We have previously collected detailed information on respiratory infections in the first two years of life for children who have participated in the ORChID study. The purpose of this study is to follow these children in early childhood up to the age of 7 years and track their lung function as a measure of respiratory health, as well as their immune response to common environmental allergens.

Contact: ellf@uq.edu.au

INNATE IMMUNE RESPONSE IN RESPIRATORY EPITHELIUM

Lower respiratory illnesses in the first year or two of life, especially those associated with wheeze and/or fever, are major risk factors for poor respiratory health. Recent data suggests that bacteria and viruses commonly found in the nose in early life may increase the risk of subsequent disease.

This project will take advantage of a unique, community-based birth cohort (ELLF), in whom the presence of respiratory viruses and bacteria in the upper airway and respiratory symptoms during the first 2 years of life have been determined from weekly nasal swabs and a daily symptom diary. This project will determine how nasal cells obtained from either adults (asthmatic or healthy) and the children birth cohort respond in laboratory-based culture when infected with bacteria, in addition to assessing the cell response when co-infected with respiratory viruses.

KIDS AND CHEMICALS IN THE HOME

Help us study how Australian children are exposed to chemcials that are commonly found in our homes.
The ‘Kids and Chemicals in the Home Study’ is a Queensland first study, investigating how patterns of chemical use in homes influence children’s exposure to chemicals. 

In recent years researchers have begun focusing more on how the chemicals that we might be exposed to in early life influence our heath.  There is concern that some of the chemicals that are commonly found in products in the home might disrupt the body’s normal functioning and development.  The chemicals that we are specifically investigating are pesticides, specifically pyrethroid and organophosphate insecticides, and flame retardants.  These chemicals are found in all homes in low levels.  However, in Australia in particular, we don’t know a lot about how much of these chemicals babies are exposed to.  We need to know more about how much of these chemicals babies are exposed to before we can study the health effects properly. The aim of this study is to help provide an easy way to figure out what chemicals and how much of those chemicals Australian babies are exposed to in the home.  

In this current study we want to figure out how well an online tool predicts exposure to common pesticides and flame retardants.  The data we are collecting will also provide us with information that will help us determine how much of these chemicals Australian children are exposed to and how they are exposed to these chemicals.  

What does taking part in this study involve?

  1. Take biological samples over a two-day period
  2. Complete a questionnaire

contact: karin.english@uqconnect.edu.au  

LUNG FUNCTION IN PRESCHOOLERS

The preschool years represent a crucial period in lung development. Longitudinal studies have shown that deficits in lung function start in early life with long term consequences into adulthood. This highlights the importance of being able to reliably and accurately measure the lung function of preschool aged children to aid in the diagnosis, treatment and management of children with suspected or known respiratory disease.

Our team, together with the University of Szeged, Hungary have developed a modified version of the Forced Oscillation Technique (FOT) to non-invasively measure the lung function of preschool aged children. This project aims to develop normative reference data for preschool aged children measured using the modified FOT set-up and to develop a more sensitive measure of lung function to detect changes in lung function during the preschool years.

MACROPHAGES IN CYSTIC FIBROSIS

Macrophages are key cells in innate immune responses and play a critical role in orchestrating both initiation and resolution of pulmonary inflammation. In response to immune insults or injury, monocytes originated from bone-marrow migrate to the tissues, differentiate into macrophages (M0) and polarize into pro-inflammatory (classically activated or M1) or inflammation-resolving (alternatively activated or M2) phenotypes. These two compartments are well characterized in mouse model. In human, the border line between M1 and M2 polarization was vague until recently. Therefore macrophage responses in cystic fibrosis (CF) were mostly studied in mouse model. We have developed an ex-vivo model of human macrophages that reliably separates un-polarized (M0), M1 and M2 macrophages. Using this model we recently reported that activation of inflammation-resolving M2 macrophages were impaired in CF. In addition, we observed early expression of pro-inflammatory M1 macrophage markers in monocyte-derived M0 macrophages in patients with CF. Similar M1 and M2 markers expression was observed when macrophages from healthy donors were treated with CFTR channel inhibitor suggesting that defection M2 polarization is CFTR-dependent. We are aiming to study the link between CFTR function and macrophage polarization and functions.

Contact: a.tarique@uq.edu.au

OXIDATIVE STRESS IN CYSTIC FIBROSIS

WOUND HEALING IN ASTHMA

Injury to the airway epithelium occurs frequently as it comes in direct contact with external stimuli that cause damage and force repair. The first and most important event occurring after wounding is cell migration, and in asthma it is known to be structurally and functionally abnormal. Growing airway epithelial cells in vitro at air-liquid interface (ALI) allows for a representative model of the airways. This study will determine the key mechanisms involved in airway epithelium wound healing and establish the baseline characteristics.

Participate in our Research

We have a number of opportunities for parents and children to participate in our research.

Current studies are listed on the Participate in our Research section of our website, under the respiratory.

Visit Participate in our Research

Clinical Trials

Liberty Asthma Voyage Study

This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of dupilumab in children 6 to < 12 years of age with uncontrolled persistent asthma. The purpose of this study is to assess how safe and effective dupilumab is compared with placebo for the treatment of uncontrolled persistent asthma in children ages 6 to less than 12 years of age and how well it is tolerated. To date dupilumab has been studied in 5 clinical trials and in the 2 completed asthma trials, dupilumab improved breathing and reduced symptoms of asthma.  This study is being funded by Sanofi Australia Pty Ltd.

Asthma is a chronic disease that affects the airways, making them very sensitive to exercise, infections, pollution and other irritants.  These cause the airways to narrow making it difficult to breathe.   Symptoms of asthma include wheezing, shortness of breath, chest tightness and coughing. Symptoms are often worse at night and in the early morning. While there is no cure for asthma, the condition may be controlled. It is hoped that Dupilumab will help these children with asthma control.

In this study the treatment is given for 52 weeks and then followed for 12 weeks without any treatment. The study medication is given as a subcutaneous injection every 2 weeks for 52 weeks. Daily electronic symptom diary and PEF needs to be completed throughout the study. During the study we will be doing tests like spirometry, FeNO and ECG and collecting blood and urine samples at different time points.

The recruitment is open for this study. For enquiries about the study please contact the clinical team on clear@uq.edu.au 

Combat CF

This is a phase 3 multi-centre randomized placebo-controlled study of azithromycin in the primary prevention of radiologically-defined bronchiectasis in infants with cystic fibrosis. The purpose of this study is to see if we can prevent or delay the onset of lung disease in children with Cystic Fibrosis by giving them Azithromycin from when they are very young.

The study is funded by Cystic Fibrosis Foundation Therapeutics in the US and the sponsor for the study is Telethon Kids Institute. There are eight centres across Australia and New Zealand (Perth, Brisbane, Melbourne, Sydney, Adelaide and Auckland). Total of 130 participants have to be recruited for the study. The recruitment is still in progress for the study.

The children diagnosed with cystic fibrosis by New Born Screening can be enrolled in the study by six months of age. They will receive azithromycin or placebo thrice a week till the age of 3 years. There are 14 visits to the hospital with bronchoscopy at the first visit and then at the age of 1 ad 3 years and the CT scans are done at the age of 1 and 3 years.

For enquiries about the study please contact the clinical team on clear@uq.edu.au

Prevention of Asthma in Children

(OM-85 in Prevention of Asthma in Children)

This is a phase 2, single-centre, double blind, randomised, placebo-controlled, study testing the primary prevention of persistent asthma in high risk children by protection against acute respiratory infections during early childhood using OM-85. Persistent asthma is a major problem yet none of the current therapies do more than control the condition. The long-term solution is to prevent asthma from progressing to the persistent form. The purpose of this study is to see if we can prevent asthma by stopping some of the events that happen early in life which may cause asthma. These are events like respiratory tract infections (colds and flu), wheezing and sensitisation to allergens.

OM-85 is an immune-stimulant which primes the immune system so that the body can respond quickly to infections and reduce damage to the lungs to prevent asthma from developing. OM-85 is a capsule and powder from capsule is dissolved in water and given to the child. The child receives OM-85 or placebo as five blocks of 10 days treatment plus 20 days no treatment for two winters and then they are followed up in the third year without any treatment.

This study is funded by the National Health and Medical Research Council and is being conducted at the Lady Cilento Children’s Hospital in Brisbane. Child Health Research Centre at The University of Queensland is the sponsor for the study. The recruitment for this study has been completed and participants are being followed up.

For enquiries about the study please contact the clinical team on clear@uq.edu.au

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Our Staff and Students

Professor Peter Sly is the Director of the Children's Lung, Environment and Asthma Research group.

Meet our team