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Nasal Polyps in CRS Found to Influence Risk of Past, Current Proton Pump Inhibitor Use


Incidence of chronic rhinosinusitis (CRS) was associated with a higher rate of current and past proton pump inhibitor (PPI) use, in which elevated risk of PPI use and prescription duration were only found in those with CRS who did not have nasal polyps.

An elevated rate of past and current proton pump inhibitor (PPI) use and prescription duration were shown in patients with chronic rhinosinusitis (CRS), although the presence of nasal polyps may lessen the risk of PPI usage. Study findings were published recently in Scientific Reports.

As the routine treatment of gastroesophageal reflux diseases (GERD), acid suppression therapy with PPIs is not recommended for patients with CRS. However, the frequent co-occurrence of GERD and CRS has led to wide use of PPIs in patients with CRS, which has been associated with anti-inflammatory effects.

“Whether GERD could be a contributing factor for CRS in some patients has been disputed for decades. However, it was reported that patients with CRS had a significantly higher incidence of GERD than normal controls,” said the study authors. “As CRS is a multifactorial inflammatory disease comorbid with GERD, it is reasonable to investigate the association between PPI therapy and CRS, which was rarely studied.”

They conducted a nested case-control study of data derived from the Korean National Health Insurance Service-Health Screening Cohort between 2002 and 2013 to determine whether PPI prescription history and duration of treatment affected CRS risk.

A total of 7194 patients with CRS and 28,776 controls matched 1:4 by random order for age, sex, income group, region of residence, and index date were included in the analysis. Participants were assessed for PPI prescription history, prescription duration, and prescription duration for PPI generation. First-generation PPIs included lansoprazole, omeprazole, and pantoprazole, and second-generation PPIs included dexlansoprazole, esomeprazole, ilaprazole, and rabeprazole. Subgroup analyses were performed according to age and sex.

International Classification of Diseases, 10th Revision, codes defined CRS, and claim codes defined previous PPI use. Conditional logistic regression analyzed the crude and adjusted ORs (aORs) with 95% CI.”

Across a mean (SD) follow-up of 94.8 (42.5) and 93.5 (43.0) months for patients with CRS and controls, respectively, a higher rate of patients with CRS were reported as current (33.8%) and past (26.3%) PPI users than PPI nonusers (19.1%; P < .001). Fewer PPI nonusers and more past and current PPI users were in the CRS group vs the control group.

For PPI prescription duration, there were also more patients with CRS in all the usage periods (< 30 days, 30-89 days, ≥ 90 days), and the PPI prescription days were longer in CRS, regardless of the PPI generation.

A statistically higher risk of CRS was shown overall in current PPI users (aOR, 1.71; 95% CI, 1.46-2.02; P < .001) and past PPI users (aOR, 1.28; 95% CI, 1.16-1.41; P < .001). Several variables were shown to influence the risk of CRS for current and past PPI usage:

  • PPI prescription was associated with the risk of CRS without nasal polyps, with a significant risk increase in current PPI users (aOR, 2.07; 95% CI, 1.68-2.54; P < .001) and past PPI use (aOR, 1.50; 95% CI, 1.33-1.71; P < .001)
  • CRS with nasal polyps was not associated with PPI prescription history or prescription duration
  • irrespective of PPI prescription days, PPI use was associated with higher CRS occurrence (aOR, 1.46; 95% CI, 1.26-1.69; P < .001) in the 30-to-89-day PPI user group
  • Risk for CRS was increased the first-generation PPI prescription group (aOR, 2.45; 95% CI, 1.59-3.76; P < .001), but not in the second-generation PPI prescription group (aOR, 1.08; 95% CI, 0.59-1.99; P > .05)

The subgroup analyses of age and sex groups consistently showed an elevated risk of CRS in PPI users vs controls.

“Considering diverse indications for PPI prescription, our findings highlight the need for clinicians to be aware of the risk associated with PPI use in patients, irrespective of the age or sex of their patients. Further research on the pathophysiological link between PPI use and CRS is required,” concluded the4 researchers.


Choi HG, Kong IG. The association between chronic rhinosinusitis and proton pump inhibitor use: a nested case–control study using a health screening cohort. Sci Rep. Published online June 10, 2022. doi:10.1038/s41598-022-13271-5

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