All CRS patients are different. CRS is a clinical syndrome and patients may present very differently and have variable responses to medical and surgical interventions. —Justin H. Turner, MD
Explore This IssueJuly 2019
She emphasized, however, that this is not an ethnic difference per se, adding that nasal polyps in second generation Asians with CRS living in Northern America or Europe are starting to look molecularly similar to nasal polyps in the populations of these countries. “This observation suggests that environmental exposure plays a critical role in driving the type of immune response contributing to rhinosinusitis,” she said. On the other hand, she cited a 2018 study that found that variations in cut-off levels of eosinophil numbers used to diagnose eosinophilic versus neutrophilic chronic rhinosinusitis may contribute to some of the differences in the percent of eosinophilic versus neutrophilic CRS between eastern and western countries (Curr Allergy Asthma Rep. 2018;18:46). Nonetheless, she added, the 2017 study highlights the fact that not all polyps are the same at a molecular level.
To that end, she said the research is pointing toward the future. “Maybe down the road you can take a biopsy sample that helps us to endotype our patients with chronic sinusitis,” she said.
For Noam A. Cohen, MD, PhD, director of rhinology research in the department of otorhinolaryngology–head and neck surgery at Perelman School of Medicine at the University of Pennsylvania in Philadelphia, another important component of what he sees as a multifactorial approach to explaining CRS is looking at taste receptors and the role they play in the development of the disease.
In studies published in 2012 and 2014, he and his colleagues showed that people with sensitive bitter taste receptors are less likely to develop a subtype of CRS based on the genetically determined function of these taste receptors (J Clin Invest. 2012;122:4145–4159; J Clin Invest. 2014;124:1393–1405). The research showed that one bitter taste receptor detects the molecule secreted by gram-negative bacteria that subsequently stimulate an immediate defense (nitric oxide production) in the cells lining the sinuses, which kills and clears out bacteria that play a common role in sinusitis. “What the receptor triggers is like a switch turned on in response to the bacteria, which not only kills the bacteria but sweeps the dead bugs away,” said Dr. Cohen.
Where this gets interesting, he said, is that there are a lot of genetic differences in the ability of people to taste bitter molecules. “Over the past five to six years, we’ve been able to show that patients in whom this bitter taste receptor doesn’t work are at much higher risk for developing gram-negative sinusitis,” he said.
With this finding, Dr. Cohen and his colleagues then looked at whether you could use the presence or absence of functioning bitter taste receptors to predict surgical outcomes, and they found that a subset of CRS patients without the functioning receptor were at higher risk for sub-optimal surgical outcomes.
Currently, Dr. Cohen and his colleagues are gearing up to launch a clinical trial to see whether it is possible for patients with CRS to forego conventional antibiotics after activation of their multiple bitter taste receptors and natural defense mechanism against the bacteria that cause rhinosinusitis.