by Elise Wachspress
Stop for a minute and breathe, just breathe. Now envision what your lungs are doing.
In your mind’s eye, do you see big pink balloons filling and deflating?
Close. What’s really going on is hundreds of millions of tiny little pink balloons filling and deflating—ten to twenty times a minute, even more often for babies and small children. Your lungs actually look more like foamy, pulsating soap bubbles than balloons.
In between these bubbles—the alveoli—is a flexible web that allows the little sacs to expand and contract, taking in air, grabbing the oxygen, and dispelling the carbon dioxide waste products.
Unless the web starts to harden. That’s what happens in the case of interstitial lung diseases (ILD). Alveolar expansion gets more and more difficult, until patients begin to feel their lungs are made of concrete. The damage is usually progressive and irreversible. In some cases, certain medications can slow ILD, and some people may be candidates for lung transplants. Otherwise, it’s not hard to see where this condition leads. When you can’t breathe, you can’t live.
ILD can be caused by exposure to hazardous materials like asbestos. Sometimes autoimmune diseases, like rheumatoid arthritis, can trigger the disease. Unfortunately, in most cases, especially for a subset of the disease called idiopathic pulmonary fibrosis (IPF), the cause is unknown.
Physician-scientists at the University of Chicago are working to change that—because if you know the causes of disease, you are many steps closer to resolving it. This quest is particularly critical right now, because over the last three decades, mortality from ILD has doubled in the US.
UChicago, one of the few centers of excellence for treating the disease, draws many of the top people interested in studying it. A large team that included clinician-scientists, researchers, and radiologists from UChicago and NorthShore University HealthSystem, recently found some powerful indicators in predicting ILD outcomes—findings which will not only help physicians fine-tune treatments, but also provide clues of the disease’s mechanism.
One indicator involved the lymph nodes, the organs that 2018 Nobel Prize winner Jim Allison describe as like Rick’s Place in Casablanca: where all cells—the good guys, bad guys, reporters, and soldiers—go to hang out.
The team, led by Deji Adegunsoye, Jonathan Chung, Mary Strek, and Anne Sperling, found that when the lymph nodes tucked between the lungs were enlarged—a condition visible on a CT scan—patients had much worse lung function and significantly increased mortality.
They also found these patients had characteristic imbalances in cells and substances associated with the immune system, some of which could be found through a blood test. In fact, patients with large numbers of one specific interleukin—a protein generated by the immune system—circulating in their blood had the worst survival rates.
Taken together, these factors are likely biomarkers of the patient’s prognosis. Both can be monitored via minimally invasive testing, as opposed to the lung biopsies currently used.
Patients who show neither of these indicators likely have a truly different form of ILD, which not only means longer survival, but may also be differentially treatable with certain immunological drugs.
This latest research is only one strand of the many ways UChicago scientists are fighting ILD. The involvement of these immunological factors seems to corroborate what many team members have suspected through years of clinical work: that a variety of triggers—both chemical and microbial—may set up an immune response that attacks the lungs. IPF patients have often reported exposure to substances like organic solvents, stone dust, and/or mold. The Chicago team is looking for funding for a dedicated occupational health consultant to extensively document patients’ life histories in hopes of identifying disease triggers. As with a similar discovery that asbestos exposure causes the universally deadly mesothelioma, they hope to make ILP preventable.
The team is also working to significantly increase their biobank of lungs, which are exceptionally fragile and require a very specialized storage regimen. The lymph node findings were only possible because of the intense support of UChicago’s technical/biobanking staff (who must often respond on a moment’s notice when a patient undergoes a lung transplant) and strong collaboration with NorthShore. The team hopes UChicago can become a regional center of lung biobanking, to drive this kind of research.
And with the help of molecular engineers, the team is also working to develop microfluidic tools to drive that lung research and develop new drugs to address the immunological effects—tools and drugs that can be commercialized for use across the world, with the help of the Polsky Center for Entrepreneurship and Innovation.
For too long, interstitial pulmonary disease, especially IPF, have been a death sentence. It’s way past time for a change.
Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office