Article: Fatty airways: Implications for Obstructive Disease
European Respiratory Journal 2019, in press
John G. Elliot,1,2 Graham M. Donovan,3 Kimberley C.W. Wang,2,4 Francis H.Y. Green,5 Alan L.
James,1,6 Peter B. Noble.2
1West Australian Sleep Disorders Research Institute, Department of Pulmonary Physiology and
Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia;
2School of Human Sciences, University of Western Australia, Crawley, Western Australia 6008,
Australia; 3Department of Mathematics, University of Auckland, Auckland, New Zealand;
4Telethon Kids Institute, University of Western Australia, Nedlands, Western Australia 6009,
Australia; 5Department of Pathology and Laboratory Medicine, University of Calgary, Calgary,
Alta, Canada; 6School of Medicine and Pharmacology, University of Western Australia,
Nedlands, Western Australia 6009, Australia.
This work was supported by Health Canada, Sir Charles Gairdner and Osborne Park Health
Care Group Research Advisory Committee (grant: 2017-18/001), National Health and Medical
Research Council of Australia (grant: Early Career Research Fellowship 1090888), Western
Australian Department of Health – Merit Award and a Medical and Health Research
Obesity is known to contribute to reduced lung function and worsened respiratory conditions
such as asthma. This is thought to be true because excess adipose (fatty) tissue may leak out
inflammatory substances and add pressure onto the airways.
This research aims to understand if there is a link between fatty tissue in this area and body
weight (indicated by body mass index – BMI) in those with and without asthma.
Adipose Tissue: An anatomical term that describes a type of connective tissue made up of
adipocytes (fat cells)
Airway inflammation: Triggered in several airway diseases and involves a range of inflammatory
cells and substances that have unique effects on the airways. Usually, airway inflammation has
protective benefits but can also harm surrounding tissue.
Airway remodelling: A main characteristic of asthma that includes thicker airway smooth muscle,
oedema (excess fluid) and fibrosis (thickened, stiff tissue)
Asthma: A condition that produces inflammation in the airways and may cause difficulty
breathing, coughing or chest pain.
Body mass index (BMI): A measure that helps understand if an individual is within a healthy
weight range. It takes into account their height and weight (BMI = kg/m2). A BMI greater than
25 is considered overweight; > 30 is obese
Neutrophils: A type of white blood cell that responds to infections and injuries
Eosinophils: A type of white blood cell that is seen in greater numbers with a parasite infection,
allergic reaction or cancer
Human left lung tissue was taken post-mortem with consent from next-of-kin. The cause of
death in 52 subjects included 16 who died of asthma, 21 who had asthma but died from other
causes and 15 with no history of respiratory illness (controls). The BMI of subjects ranged from
15-45kg/m2 across groups and was used to indicate weight status.
Airway sections were obtained from the lung tissue using a stratified technique. This involves
taking portions of airway at different levels of the lungs which are highly branched. This method
helps ensure similar airway ‘branches’ are sampled across subjects, regardless of their lung size.
Next, the tissue was set in wax blocks and sectioned. Glass slides were prepared with the tissue
and stained with dyes (H&E) to help look at the size and shape of airways under a light
Some of the details that were measured included:
• The airway basement membrane perimeter (Pbm)
• Airway wall area
• Fatty tissue area
• Density of inflammatory cells (eosinophils and neutrophils)
The data collected was compared to the BMI of each subject. Roughly 26 airways were examined
per subject, with a total of 1373 airway samples.
Fatty tissue was discovered in the outer airways of all subject groups and seen most of the time
in medium/large sized airways.
Fatty tissue tended to increase in those with higher BMI and thicker airway walls in all groups.
Inflammatory cells also tended to increase in controls (increased neutrophils) and subjects who
died from asthma (neutrophils and eosinophils).
These findings show that fatty tissue can build up around airways, especially in more
overweight/obese individuals. Fat accumulation in airway walls may also change features such as
airway thickness and bring about a stronger presence of inflammatory cells in this location.
Obesity a growing health concern in Australia, with around two thirds of Australians in a state of
overweight or obesity (Australian Dept of Health). There is a growing body of evidence that
shows a link between obesity and reduced lung function. However, the underlying biological
driver is not clear. This study is a first of its kind and may provide an explanation for why those
of increased weight could have poorer respiratory health.
Animal models, in particular mice and rats, are commonly used to study the effects of obesity.
This study displays a more humane approach to investigating the mechanisms of obesity-related
issues such as asthma or other inflammatory conditions. Similarly, there are key differences
between humans and other animals when inflammation occurs in the body and hence humans
are the best choice to study for this matter.