Injury to the sinonasal tissues can cause epithelial dysfunction, leading to chronic rhinosinusitis (CRS), a disease characterized by ongoing inflammation and, often, polyp growth.
While an individual’s susceptibility to CRS is not well-understood, specialists believe sinus infections, allergic disease, host immune, and microbiota anomalies may contribute to the disease.
Now, Vanderbilt University Medical Center otolaryngologist Naweed Chowdhury, M.D., is researching the association between CRS and environmental factors, like inhalation of particle pollutants.
“One of the mysteries we face in clinic is why certain people get CRS, because we’re all, in theory, exposed to the same viruses, infections, bacteria and air pollution,” Chowdhury said. “Patients often don’t have a history of infection that they recall, and they may test negative for allergies. My broad goal is to try to identify these triggers and understand how the nasal epithelium responds to chronic injury, so we can develop strategies for primary prevention and effective personalized treatments.”
Particulate Matter Particulars
In 2023, Chowdhury was principal investigator on a prospective study of surgical CRS patients to identify molecular patterns of CRS in those with chronic exposure to elevated levels of ambient particulate matter ≤2.5 μm in diameter (PM2.5).
“This is the first study in humans to provide robust findings comparable to those in lower airway disease.”
To see if associations with PM2.5 mirrored those in asthma and allergic disease, Chowdhury and his team prospectively collected mucus specimens as well as epidemiologic, demographic and clinical data on 308 patients undergoing endoscopic sinus surgery.
They used a geospatial machine learning model to estimate daily local exposure to small particles and found increased odds ratios of nasal polyposis, comorbid asthma and allergic rhinitis (1.41, 1.49 and 1.48, respectively) for each 1 μg/m3 increase in PM2.5 over 12 months.
“The literature on the relationship between small particulate matter and CRS has consisted of a few case studies and observational studies,” Chowdhury said. “This is the first study in humans to provide robust findings comparable to those in lower airway disease.”
Clinical Features of CRS
Chowdhury says the impact of chronic rhinosinusitis on quality of life is frequently underestimated, with symptoms like daily nasal congestion and obstruction, facial pain, hyposmia/anosmia, fatigue, and otalgia often proving debilitating.
Mucosal epithelial tight-junction dysfunction and defective mucociliary clearance are known hallmarks of CRS pathogenesis.
“Chronic mucosal dysfunction, whether from an infection or pollution or allergies, likely starts with a disruption in the barrier lining of the nose,” Chowdhury said. “This allows foreign substances to enter into the mucosal tissues, and that can trigger a massive inflammatory response, including polyp growth.”
First-line treatments include oral and topical steroids and antibiotics. However, around 60 percent of patients are refractory to medical management and need outpatient endoscopic surgical intervention, consisting of polyp removal, flushing of debris, and often removal of some of the nasal lining and bone to widen the sinus cavity.
“Surgery relieves symptoms in about 90 percent of cases, but it is an adjunctive treatment that may need to be repeated periodically,” Chowdhury said. “Sometimes the behavior of the epithelium has changed in a way we can’t reverse, causing new polyps to grow.”
Chowdhury says new biologics are now offered to patients, and while not curative, look promising in extending the polyp-free period.
Cellular Changes
The role of environmental pollutants in human asthma and allergic disease has been linked to inflammatory cytokine upregulation, reactive oxygen species production with increased oxidative stress, and other changes in cellular metabolism.
In rabbit models, inhalation of PM2.5 triggers alterations in the nasal mucosa, including disorganization of ciliary structures and tissue remodeling.
Chowdhury says the lab findings from their study point to a mixed, type-2 dominant CRS inflammatory response being associated with higher levels of PM2.5.
Higher tissue eosinophil counts were also associated with increasing particulate levels in their study. These associations remained after adjusting for age, income, body mass index, rurality, polyps, asthma, and allergic rhinitis.
Multipronged Exploration
Chowdhury is conducting more granular research on the impact of particulate matter exposures, including having patients wear wristbands that will track their exposures, in an effort to overcome the limitations of relying on U.S. Environmental Protection Agency air quality monitoring stations. His lab is investigating discrepancies in transcriptional activity between CRS patients with different levels of pollution exposure.
The team is also treating cultured cells from CRS patients with diesel particles and various other pollutants to measure cellular and gene-level responses.
Further, Chowdhury is probing the nasal microbiota, based on findings that lower levels of healthy nasal microbiota may increase risk of CRS.
“Is CRS related to an overpopulation of bad bacteria in the sinuses? If so, can we borrow from the work in fecal transplants and reverse CRS through a nasal mucus transplant?” he asks. “These are opportunities we want to explore.”
