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

Abstract

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 three 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 one inpatient or two outpatient codes at least two years before index date of RA clinical diagnosis or matched date. Logistic regression models calculated odds ratios (OR) for RA with 95% confidence intervals (CI), adjusting for confounders. We then stratified by serostatus ("seropositive" was positive rheumatoid factor and/or anti-citrullinated protein antibodies) and smoking. Results We identified 741 RA cases and 2,223 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 pre-index 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 packyears (OR 1.52, 95% CI:1.02,2.27; p=0.10 for interaction). Conclusion Acute/chronic sinusitis and pharyngitis and acute respiratory burden increased RA risk. The mucosal paradigm of RA pathogenesis may involve the upper respiratory tract.

The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice

“…4). This hypothesis is in agreement with previous studies showing the reciprocal association of respiratory tract/lung inflammation with arthritis (Ford et al 2020;Kronzer et al 2022).…”

A Roadmap for Investigating Preclinical Autoimmunity Using Patient-Oriented and Epidemiologic Study Designs: Example of Rheumatoid Arthritis

“…Follow-up studies showed that women with asthma were more likely to have elevated ACPA in pre-RA suggesting that pulmonary mucosal inflammation may influence RA-related autoantibody production prior to RA onset ( 67 , 68 ). Other biomarkers examined in the NHS and NHSII have included inflammatory markers, Epstein-Barr virus antibodies, carotenoids, vitamin D, leukocyte telomere length, metabolomic profiles, and adipokines ( 49 , 69 – 75 ).…”

“…Several large placebo-controlled randomized trials, including the Women’s Health Study (investigating vitamin E and aspirin) ( 141 , 142 ), Women’s Health Initiative (investigating postmenopausal hormones) ( 143 ), and VITAL trial (investigating vitamin D and omega-3 fatty acids) ( 144 ) have investigated RA risk as a secondary outcome, the latter suggesting that vitamin D may have potential protection of incident RA and other autoimmune diseases. Finally, the Mayo Clinic and Mass General Brigham Biobanks have been harnessed to analyze electronic health record ( 145 ) and survey data collected prior to RA onset and will use banked blood for future studies ( 75 , 146 – 149 ).…”

Occupational inhalants, genetics and the respiratory mucosal paradigm for ACPA-positive rheumatoid arthritis

“…Vanessa L Kronzer , 1 Jeffrey A Sparks 2,3 Ever smoking was first identified as a risk factor for rheumatoid arthritis (RA), 1 growing evidence has implicated the respiratory mucosa in RA pathogenesis. [2][3][4] Respiratory exposures now associated with increased risk of RA include air pollution, 5 6 respiratory tract diseases, [7][8][9][10][11] passive smoking, 12 13 and importantly, occupational inhalants 14 such as silica dust and asbestos, 15 textile dust, 16 brick and concrete laying, 17 pesticides 18 and military burn pits. 19 Another revolution in understanding RA pathogenesis occurred when a strong interaction between smoking and human leucocyte antigen shared epitope (HLA-SE) alleles to increase risk of anticitrullinated peptide antibody (ACPA) positive RA by 21-fold.…”

“…Another important finding related to RA pathogenesis was that the individual inhalable agents and their interactions showed a strong association for ACPA-positive RA, but not ACPA-negative RA. On the one hand, this is somewhat surprising since prior studies of both occupational inhalants15–17 and respiratory diseases7 8 showed that they were associated with both ACPA-positive and ACPA-negative RA, approximately equally. On the other hand, smoking has long been known to be associated stronger with ACPA-positive RA 2 20.…”