Chronic Sinus Inflammation Linked to Roadway Gases

Exposure to traffic-related gases was associated with increased chronic rhinosinusitis risk, a case-control study showed, supporting a role for pollutants beyond particulate matter.

Each standard deviation increase in exposure to nitrogen dioxide (NO₂, from high-temperature fuel combustion) at one’s home address averaged over 5 years correlated with more than double the odds of chronic rhinosinusitis (adjusted OR [aOR] 2.32, 95% CI 1.09-4.93) independent of demographics, smoking history, use of steroid medication, and comorbidities.

The association was nearly the same with benzene exposure, which comes from gasoline evaporation and incomplete combustion (aOR 2.15 per standard deviation, 95% CI 1.05-4.38), while airborne lead levels had an even stronger association with chronic rhinosinusitis (aOR 3.48, 95% CI 1.36-8.88), Jivianne T. Lee, MD, of the University of California Los Angeles, and colleagues reported in JAMA Otolaryngology–Head & Neck Surgery.

“These findings potentially advance understanding of how distinct pollutants contribute to [chronic rhinosinusitis] heterogeneity and may help inform future directions for targeted prevention, therapeutic innovation, and clinical management,” the researchers wrote.

Nasal and sinus epithelium tissue forms a barrier layer that orchestrates mucosal immunity, but pollutants can disrupt its permeability and trigger epithelial alarmins that drive downstream type 2 inflammatory responses from the likes of interleukins (ILs)-4, -5, and -13.

While airborne particulates have a well-proven link to a wide range of health risks, including chronic rhinosinusitis, the study affirms this latter link extends to traffic-related and industrial-related gases.

Indeed, long-term residential exposure to the pollutants studied was associated with cytokines.

After controlling for chronic rhinosinusitis status and co-pollutant levels, NO₂ exposure was the only one linked to type 2 inflammatory cytokines, “which was consistent with a barrier alarmin type 2 pathway,” according to Lee and colleagues. Each standard deviation higher NO₂ was associated with three-fold increase in IL-4, a 4.6-fold increase in IL-5, a 2.7-fold increase in IL-13, and 6.6-fold increase in tumor necrosis factor α levels. The chronic rhinosinusitis patients had stronger cytokine associations with NO₂ compared with controls.

“In contrast, benzene and lead were associated with cytokine signatures that were characterized by IL-8 and IL-1RA, pointing toward innate, neutrophilic rather than type 2 pathways,” the group added, a diversity “suggesting pollutant-specific pathways that may contribute to heterogeneous chronic rhinosinusitis pathophysiology.”

The case-control study utilized sinonasal epithelial specimens collected at a tertiary referral center in California between March 2017 and August 2021. The 62 patients with chronic rhinosinusitis were undergoing endoscopic sinus surgery, while the 30 control participants had endoscopic transnasal skull-base procedures as the source of their specimens. The controls were free of chronic rhinosinusitis based on clinical history and objective radiographic and endoscopic assessment.

The researchers tested those samples and correlated findings with residential exposure to pollutants according to a validated land use regression model with 5-year mean concentrations at the individual’s residential address before surgery.

Average age was similar among the chronic rhinosinusitis and control participants (48 vs 49), although the rhinosinusitis group had a higher proportion of males (59.7% vs 36.7%) and of prior or current smoking history (41.9% vs 20.0%). Asthma and chronic obstructive pulmonary disease were also more common with chronic rhinosinusitis than among controls (45% vs 3% and 7% vs 0%, respectively).

Cytokine levels did not differ significantly by presurgical use of intranasal steroids, which was more common with chronic rhinosinusitis.

Limitations of the study included inability to infer causality. One reason is that, although chronic rhinosinusitis diagnosis occurred within 5 years of surgery for participants, during the period pollutant exposure was assessed, the exact timing of disease onset remains uncertain, the researchers noted.

Also, exposure data came from ambient levels at geocoded residential addresses, but personal exposure might have been different. The study didn’t have time-activity patterns, indoor or occupational source data, or microenvironmental non-exhaust peaks.