Respiratory Tract Diseases May Increase Risk of RA Years Before Onset

Close up of hands affected by rheumatoid arthritis

There’s growing evidence that rheumatoid arthritis (RA) originates in mucosal surfaces, including the lungs.

Now, Elena Losina, PhD, Robert W. Lovett professor of Orthopedic Surgery in the Department of Orthopedic Surgery at Brigham and Women’s Hospital, Jeffrey A. Sparks, MD, MSc, a rheumatologist and assistant professor of Medicine in the Division of Rheumatology, Immunology and Allergy, Vanessa L. Kronzer, MD, of the Mayo Clinic, and colleagues have demonstrated that the timing of respiratory tract disease diagnosis significantly affects the strength of specific disease’s association with RA. The new data appear in Seminars in Arthritis and Rheumatism.


Using the Mass General Brigham Biobank, the researchers matched each of 625 RA patients to three control subjects based on age at RA clinical diagnosis (for controls, age at matched date), sex, and length of the availability of records in the accompanying electronic health records system.

The analysis was limited to participants with at least seven years of preceding medical record data, and a median of 13 years of records were extracted.

Respiratory Diseases and Overall RA Risk

69% of RA patients and 52% of controls had a respiratory tract disease before RA diagnosis. In a multivariable analysis, respiratory tract diseases overall were not associated with RA. However, certain individual diseases were linked to an increased risk of RA:

  • Acute sinusitis—adjusted OR [aOR], 1.91
  • Acute pharyngitis—aOR, 1.74
  • Chronic obstructive pulmonary disease (COPD)—aOR, 1.56

Timing of Respiratory Tract Diseases and RA

Several specific respiratory tract diseases studied had a time window when it was associated with RA:

  • Acute sinusitis—The association with RA was greatest (aOR, 3.90) during the period >5 to 10 years before RA was diagnosed
  • Acute pharyngitis— aOR, 2.13 for the period >10 years before RA and 1.85 for the period >0 to 5 years before
  • COPD—aOR, 1.93 for the period >10 years before RA
  • Chronic sinusitis—aOR, 1.88 for the period >10 years before RA
  • Pneumonia—aOR, 1.73 for the period >0 to 5 years before RA
  • Asthma—aOR, 1.53 for the period >5 to 10 years before RA
  • Any respiratory tract disease—aOR, 1.42 for the period >10 years before RA

Other Key Findings

Several respiratory tract diseases were more strongly associated with seronegative RA than seropositive RA, and the interaction was statistically significant for chronic sinusitis. Seropositivity was defined as positivity for either rheumatoid factor and/or anti-citrullinated protein antibodies.

Ever-smokers exhibited stronger associations between respiratory tract diseases and RA than never-smokers did, and those associations tended to be stronger for acute and recent-onset diseases.

Implications for the Clinic

The RA disease process may begin years—perhaps even decades—before autoantibody production. Patients and clinicians should be aware of the associations between smoking and respiratory tract diseases with the future onset of RA.

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