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The internal anatomy of our lungs is surprisingly variable, and some of those variations are associated with a greater risk of chronic obstructive pulmonary disease (COPD), a new study led by researchers at 黑料不打烊 University and the has found.

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

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听smoking, commonly after they have quit smoking, but is increasingly recognized in those who have never smoked.

Benjamin Smith, an assistant professor in 黑料不打烊鈥檚 Department of Medicine and the study鈥檚 first author, noticed that variations in the large airways of lungs had been reported in old autopsy studies. 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.

Extra and missing branches

鈥淲e 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,鈥� said Smith, who is also a scientist at the Research Institute of the 黑料不打烊 University Health Centre (RI-MUHC). 鈥淚nterestingly, 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.鈥�

About 16 percent of people possess an extra airway branch in the lung, about 6 percent are missing a branch,听and another 4 percent have a combination of variants or other patterns. The results were in the Proceedings of the National Academy of Sciences.

鈥淭he amount of lung variation high up in the airway tree was quite a surprise to us,鈥� says R. Graham Barr, MD, PhD, chief of general medicine at Columbia University Irving Medical Center and the study鈥檚 senior author. 鈥淭hese changes are occurring at a branching level equivalent to your fingers鈥搒o it鈥檚 like a quarter of us having four or six fingers instead of five.鈥�

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 findings were replicated in a second study of almost 3,000 patients with and without COPD.

These airway tree variations are identifiable on 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. Before CT scans are used outside of this group for the identification of airway variants in clinical practice, the study authors say more research will be needed to confirm that preventive or therapeutic interventions based on the presence of airway tree variations can improve patients鈥� outcomes.

Quitting smoking remains best antidote

In the meantime, the researchers say they will be investigating another important finding 鈥� 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 said 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. 鈥淚f proven,鈥� he said, 鈥渢his would represent a novel mechanism of COPD among non-smokers.鈥�

Smith emphasized 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.

About the study

The study, titled 鈥淗uman Airway Branch Variation and Chronic Obstructive Pulmonary Disease,鈥� was published Jan. 16 ahead of print in Proceedings of the National Academy of Sciences.
DOI:

Other authors: Hussein Traboulsi (黑料不打烊 Univ.), John H.M. Austin (Columbia), Ani Manichaikul (Univ. of Virginia), Eric A. Hoffman (Univ. of Iowa), Eugene R. Bleecker (Univ. of Arizona), Wellington V. Cardoso (Columbia), Christopher Cooper (UCLA), David J. Couper (UNC-Chapel Hill), Stephen M. Dashnaw (Columbia), Jia Guo (Columbia), MeiLan K. Han (Univ. of Michigan), Nadia N. Hansel (Johns Hopkins), Emlyn W. Hughes (Columbia), David R. Jacobs Jr. (Univ. of Minnesota), Richard E. Kanner (Univ. of Utah), Joel D. Kaufman (Univ. of Washington), Eric Kleerup (UCLA), Ching-Long Lin (Univ. of Iowa), Kiang Liu (Northwestern), Christian M. Lo Cascio (Columbia), Fernando J. Martinez (Cornell Univ.), Jennifer N. Nguyen (Univ. of Virginia), Martin R. Prince (Cornell Univ.), Stephen Rennard (Univ. of Nebraska), Stephen S. Rich (Univ. of Virginia), Leora Simon (黑料不打烊 Univ.), Yanping Sun (Columbia), Karol E. Watson (UCLA), Prescott G. Woodruff (UCSF), and Carolyn J. Baglole (黑料不打烊 Univ.).

Financial support was provided by the National Institutes of Health, 黑料不打烊 University Health Center Research Institute, and the Fonds de recherche du Qu茅bec 鈥� Sant茅 (FRQS).

One co-author (EAH) is co-founder and shareholder in Vida Diagnostics, which was used to assess some, but not the main, lung measures in the study.

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