There is growing evidence that rheumatoid arthritis (RA) originates in mucosal surfaces, including the lungs.
Jeffrey A. Sparks, MD, MSc, a rheumatologist and Assistant Professor of Medicine in the Division of Rheumatology, Inflammation and Immunity, Elena Losina, PhD, Robert W. Lovett professor of Orthopedic Surgery in the Department of Orthopedic Surgery at Brigham and Women’s Hospital, 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 a disease’s association with RA. The new data appear in Seminars in Arthritis and Rheumatism.
Using the Mass General Brigham Biobank, the researchers identified all incident RA cases occurring during follow-up (625 RA patients) and matched each to three control subjects without RA based on the age at RA clinical diagnosis (for controls, age at matched date), sex, and length of the availability of electronic health records. The analysis was limited to participants with at least seven years of preceding medical record data. A median of 13 years of records prior to RA diagnosis or index date for controls were extracted.
Respiratory Diseases and Overall Risk for RA
69% of RA patients and 52% of controls had a respiratory tract disease in the timeframe before RA diagnosis. In a multivariable analysis, respiratory tract diseases overall were not associated with RA. However, certain 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 during which they were associated with RA diagnosis (or matched date for controls):
- Acute sinusitis—The association with RA was greatest (aOR, 3.90) during the period >5 to 10 years before the diagnosis of RA/matched date
- Acute pharyngitis— aOR, 2.13 for the period >10 years before the diagnosis of RA/matched date and 1.85 for the period >0 to 5 years before diagnosis/matched date
- COPD—aOR, 1.93 for the period >10 years before RA/matched date
- Chronic sinusitis—aOR, 1.88 for the period >10 years before RA/matched date
- Pneumonia—aOR, 1.73 for the period >0 to 5 years before RA/matched date
- Asthma—aOR, 1.53 for the period >5 to 10 years before RA/matched date
- Any respiratory tract disease—aOR, 1.42 for the period >10 years before RA/matched date
Other Key Findings
Seropositivity was defined as positivity for either rheumatoid factor and/or anti-citrullinated protein antibodies, while seronegativity was defined as negative for both of these biomarkers. Several respiratory tract diseases were more strongly associated with seronegative RA than seropositive RA, including chronic sinusitis.
Ever-smokers exhibited stronger associations between respiratory tract diseases and RA than never-smokers, and those associations tended to be stronger for acute and earlier-onset diseases.
Implications for the Clinic
The RA disease process may begin years—perhaps even decades—before clinical diagnosis. Patients and clinicians should be aware of the associations between smoking and respiratory tract diseases in regard to the future development of RA.