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Our lungs aren’t all identical

Our lungs’ internal anatomy is surprisingly variable and some of these anatomical variations are associated with a higher risk of chronic obstructive pulmonary disease (COPD), a new study indicates.

The variations occur in large airway branches in the lower lobes of the lungs and can be readily detected with standard CT scans. The findings suggest that people with certain variations might, in the future, need more personalized treatments.

“These changes are occurring at a branching level equivalent to your fingers—so it’s like a quarter of us having four or six fingers instead of five.”

COPD is a progressive lung disease that causes airway inflammation, makes breathing more difficult, and is the fourth leading cause of death in the world. COPD usually occurs in people with a history of smoking, commonly after they have quit smoking, but is increasingly recognized in those who have never smoked.

Benjamin Smith, an assistant professor in McGill University’s medicine department and the study’s first author, noticed that old autopsy studies had been reported variations in the large airways of lungs. So, he and the other researchers set out to see how common those variations are in the general population, and if they were associated with COPD.

For the study, the researchers examined CT scans from more than 3,000 people in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

‘Like having four fingers’

“We found that central airway branches of the lungs, which are believed to form early in life, do not follow the textbook pattern in one quarter of the adult population and these non-textbook variations in airway branches are associated with higher COPD prevalence among older adults,” says Smith, who is also a scientist at the Research Institute of the McGill University Health Centre.

“Interestingly, one of the airway branch variants was associated with COPD among smokers and non-smokers. The other was associated with COPD, but only among smokers.”

About 16 percent of people possess an extra airway branch in the lung, about 6 percent are missing a branch, and another 4 percent have a combination of variants or other patterns.

“The amount of lung variation high up in the airway tree was quite a surprise to us,” says R. Graham Barr, chief of general medicine at Columbia University Irving Medical Center and the study’s senior author. “These changes are occurring at a branching level equivalent to your fingers—so it’s like a quarter of us having four or six fingers instead of five.”

People with an extra airway branch were 40 percent more likely to have COPD than people with standard anatomy. And people missing a specific airway branch were almost twice as likely to have COPD, but only if they smoked. The researchers replicated the findings in a second study of almost 3,000 patients with and without COPD.

Low-dose screening lung CT scans, which are currently indicated clinically for lung cancer screening in older patients with a history of heavy smoking in the prior 15 years can identify these airway tree variations. Before researchers use CT scans outside of this group for the identification of airway variants in clinical practice, the authors say more research is necessary to confirm that preventive or therapeutic interventions based on the presence of airway tree variations can improve patients’ outcomes.

Family history

In the meantime, the researchers say they will be investigating another important finding—this one around family history. Their study identified a common airway branch variation that occurs within families and is associated with COPD among non-smokers.

Smith says that, while other developmental events that occur within families may be involved, his research team is looking into whether there is a genetic basis for this variant.

“If proven,” he says, “this would represent a novel mechanism of COPD among non-smokers.”

Smith emphasizes that for all the new findings, quitting smoking remains the best antidote to COPD, and smokers trying to quit should seek professional help, if necessary, to succeed.

The researchers report their findings in the Proceedings of the National Academy of Sciences.

Additional authors of the study are from McGill University; Columbia University; the University of Virginia; the University of Iowa; the University of Arizona; the University of California, Los Angeles; the University of North Carolina at Chapel Hill; the University of Michigan; Johns Hopkins University; the University of Minnesota; the University of Utah, the University of Washington; Northwestern University; Cornell University; the University of Nebraska; and the University of California, San Francisco.

Financial support came from the National Institutes of Health, McGill University Health Center Research Institute, and the Fonds de recherche du Québec–Santé (FRQS).

One coauthor (Eric A. Hoffman of the University of Iowa) is cofounder and shareholder in Vida Diagnostics, which the researchers used to assess some, but not the main, lung measures in the study.

Source: McGill University

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