Developmental Biology - Asthma
Fatty Tissue In Lungs Causes Asthma
First evidence that fat accumulates in the lungs of overweight and obese people...
For the first time research finds fatty tissue accumulates in airway walls, particularly in people who are overweight or obese. Scientists already know people who are overweight or obese are more likely to suffer with wheezing and asthma, but the reasons for this have not been completely explained.
In a new study, published in the European Respiratory Journal, research suggests this fatty tissue alters the structure of people's airways and could be one reason behind their increased risk for asthma.
"Our research team studies the structure of the airways within our lungs and how these are altered in people with respiratory disease. Looking at samples of lung, we spotted fatty tissue that had built up in the airway walls. We wanted to see if this accumulation correlated with body weight."
John Elliot PhD, West Australian Sleep Disorders Research Institute, Department of Pulmonary Physiology and Sleep Medicine, Senior Research Officer, Sir Charles Gairdner Hospital, Nedlands, Western Australia; School of Human Sciences, University of Western Australia, Crawley, Western Australia, Australia; and author of the study.
Researchers examined post-mortem samples of lung tissue donated for research and stored in the Airway Tissue Biobank. Samples were from 52 people, including 15 with no reported asthma, 21 with asthma but death by other causes, and 16 who died of asthma.
Using dyes to help visualise the structures of 1373 airways under a microscope, they identified and quantified any fatty tissue present. They compared this data with each person's body mass index (BMI).
The study revealed fatty tissue does accumulate in the walls of airways. Further analysis revealed the amount of fat present increases in line with an increasing BMI or Body Mass Index. The research also suggests this increase in fat alters normal airway structure, leading to inflammation of the lungs.
"Being overweight or obese has already been linked to having asthma or having worse asthma symptoms. Researchers have suggested that the link might be explained by the direct pressure of excess weight on the lungs or by a general increase in inflammation created by excess weight.
"This study suggests that another mechanism is also at play. We've found that excess fat accumulates in the airway walls where it takes up space and seems to increase inflammation within the lungs.
"We think this is causing a thickening of the airways limiting the flow of air in and out of the lungs, and could at least partly explain an increase in asthma symptoms."
Peter Noble PhD, Associate Professor, School of Human Sciences, University of Western Australia, Crawley, Western Australia, Australia and study co-author.
The team are looking for new ways to study and measure fatty tissue in the lungs. They want to confirm the relationship with respiratory disease and to find out whether the effect can be reversed by weight loss therapy.
Professor Thierry Troosters is President of the European Respiratory Society (not involved in the study) adds: "This is an important finding on the relationship between body weight and respiratory disease because it shows how being overweight or obese might be making symptoms worse for people with asthma. This goes beyond the simple observation that patients with obesity need to breathe more with activity and exercise hence adding to their ventilatory burden. The observation points at true airway changes that are associated with obesity.
"We need to investigate this finding in more detail and particularly whether this phenomenon can be reversed with weight loss. In the meantime, we should support asthma patients to help them achieve or maintain a healthy weight."
Epidemiological studies report that overweight or obese asthmatic subjects have more severe disease than those of a healthy weight. We postulated accumulation of adipose tissue within the airway wall may occur in overweight patients and contribute to airway pathology. Our aim was to determine the relationship between adipose tissue within the airway wall and body mass index (BMI) in individuals with and without asthma.
Transverse airway sections were sampled in a stratified manner from post-mortem lungs of control subjects (n=15) and cases of nonfatal (NFA, n=21) and fatal (FA, n=16) asthma. The relationship between airway adipose tissue, remodelling and inflammation was also assessed. The areas of the airway wall and adipose tissue were estimated by point count and expressed as area per mm of basement membrane perimeter (Pbm). The number of eosinophils and neutrophils were expressed as area densities.
BMI ranged from 15 to 45 (kg·m-2) and was greater in NFA (p<0.05). Adipose tissue was identified in the outer wall of large airways (Pbm>6 mm), but was rarely seen in small airways (Pbm<6 mm). Adipose tissue area correlated positively with BMI and airway wall thickness in all groups. Densities of neutrophils correlated with adipose tissue area in control subjects (Pbm>6 mm, p=0.04) and both neutrophils and eosinophils in FA (Pbm>12 mm, p<0.01).
These data show that adipose tissue is present within the airway wall and is related to BMI, wall thickness and the number of inflammatory cells. The accumulation of airway adipose tissue in overweight individuals may therefore contribute to airway pathophysiology.
John G. Elliot, Graham M. Donovan, Kimberley C.W. Wang, Francis H.Y. Green, Alan L. James and Peter B. Noble.
Funding: Health Canada; Sir Charles Gairdner and Osborne Park Health Care Group Research Advisory Committee; National Health and Medical Research Council of Australia, the Early Career Research Fellowship 1090888.
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Micrographs (x200) from fatal asthma patient. Outer airway wall
- between Airway Smooth Muscle (ASM) layer and Airway Adventitia
(dashed line) showing Adipose [fat]
tissue and Mucous glands
and inner airway wall (submucosa), between basement membrane and ASM layer (dashed line)
Inflammatory cells were counted within the inner airway wall.
CREDIT European Respiratory Journal