Nasal polyps – soft, round outgrowths that can appear in the nasal passages and sinuses – can be chronic and relentless. Although noncancerous, these outgrowths can grow large enough to block the nose and sinuses, leading to discomfort, breathing problems and infections. And while they can be surgically removed, they may grow back, sometimes in a matter of days.
Although most patients are happy to be rid of their polyps, for researchers, that tissue is precious: It may hold critical clues about intense, allergic inflammation. Brigham investigators, along with collaborators from the Broad Institute and Massachusetts Institute of Technology, have used some of the most advanced sequencing technology to peer into nasal polyps – gleaning new insights into this condition and the severe form of inflammation that may lead to disorders such as asthma, allergic rhinitis and allergic eczema. Their findings were recently published online in Nature.
“For our patients, one of the most frustrating things about chronic, allergic conditions is that we have no cure. Surgery can relieve discomfort for those with nasal polyps, but in many cases the effect is only temporary,” said co-corresponding author Nora Barrett, MD, of the Division of Rheumatology, Immunology and Allergy. “My group’s goal is to understand why the inflammatory process persists once it begins and to uncover the cause of these conditions.”
Barrett and colleagues obtained samples from 12 patients with nasal polyps or other sinus conditions, collecting a total of 18,036 cells. They compared these to nasal scrapings from healthy individuals. To better understand what genes might be involved in nasal polyps, the team then used a technique called massively parallel, single-cell RNA sequencing, which allows investigators to determine which genes are “turned on” in each cell. Rather than focusing on just one kind of suspected cell, they used this approach to look at every cell type – such as blood cells, skin tissue cells and so forth – found in harvested samples.
What they found surprised them. One of the most striking discoveries the researchers reported was that epithelial progenitor cells – which produce the cells that line the airways – had been permanently altered in the polyp samples. In fact, even when removed from the tissue and grown in the lab, the resulting cells showed marked genetic differences.
“To a dramatic extent, inflammation had changed the basic tissue architecture at the genetic level,” Barrett said. “These lasting changes may be driving the recurrence and persistence of chronic, allergic inflammation for nasal polyps and other allergic conditions.”
The Nature publication offers a global, cellular map of inflamed tissue for what is known as type 2 inflammation – a severe form of inflammation that involves immune cells that have gone rogue, triggering a cascade of immune action. The map points to many pathways that have been altered, and Barrett and colleagues are working through these to identify which ones may be driving inflammation and which ones may be resulting from the inflammatory process.
The research team also tested an antibody that helped restore normal genetic activity – suggesting that it may be possible to develop therapies to prevent nasal polyps from returning by restoring a normal balance to cells that have been altered by inflammation.
The team also hopes to use the new information to develop a genetic signature that would allow clinicians to take a swab of nasal mucosa to test for lung conditions.