Association of Sinusitis and Upper Respiratory Tract Diseases With Incident Rheumatoid Arthritis: A Case-control Study

Vanessa L. Kronzer, Weixing Huang, Alessandra Zaccardelli, Cynthia S. Crowson, John M. Davis, Robert Vassallo, Tracy J. Doyle, Elena Losina, Jeffrey A. Sparks

Research output: Contribution to journalArticlepeer-review


Objective. We aimed to determine whether specific respiratory tract diseases are associated with increased rheumatoid arthritis (RA) risk. Methods. This case-control study within the Mass General Brigham Biobank matched newly diagnosed RA cases to 3 controls on age, sex, and electronic health record history. We identified RA using a validated algorithm and confirmed by medical record review. Respiratory tract disease exposure required 1 inpatient or 2 outpatient codes at least 2 years before the index date of RA clinical diagnosis or matched date. Logistic regression models calculated ORs for RA with 95% CIs, adjusting for confounders. We then stratified by serostatus (“seropositive” was positive rheumatoid factor and/or anticitrullinated protein antibodies) and smoking. Results. We identified 741 RA cases and 2223 controls (both median age 55, 76% female). Acute sinusitis (OR 1.61, 95% CI 1.05-2.45), chronic sinusitis (OR 2.16, 95% CI 1.39-3.35), and asthma (OR 1.39, 95% CI 1.03-1.87) were associated with increased risk of RA. Acute respiratory tract disease burden during the preindex exposure period was also associated with increased RA risk (OR 1.30 per 10 codes, 95% CI 1.08-1.55). Acute pharyngitis was associated with seronegative (OR 1.68, 95% CI 1.02-2.74) but not seropositive RA; chronic rhinitis/pharyngitis was associated with seropositive (OR 2.46, 95% CI 1.01-5.99) but not seronegative RA. Respiratory tract diseases tended towards higher associations in smokers, especially > 10 pack-years (OR 1.52, 95% CI 1.02-2.27, P = 0.10 for interaction). Conclusion. Acute and chronic sinusitis, pharyngitis, and acute respiratory burden increased RA risk. The mucosal paradigm of RA pathogenesis may involve the upper respiratory tract.

Original languageEnglish (US)
Pages (from-to)358-364
Number of pages7
JournalJournal of Rheumatology
Issue number4
StatePublished - Apr 1 2022


  • epidemiology
  • pharyngitis
  • rheumatoid arthritis
  • sinusitis
  • smoking

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology


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