Asthma, COPD Increase Rheumatoid Arthritis Risk

Julia Ford, MD

Asthma and chronic obstructive pulmonary disease (COPD) were both associated with an increased risk for incident rheumatoid arthritis, regardless of smoking status and other confounders, new study findings showed.

Julia Ford, MD, and colleagues from Brigham and Women’s Hospital investigated whether asthma or COPD were associated with rheumatoid arthritis. The findings suggested that chronic airway inflammation could be crucial in rheumatoid arthritis pathogenesis.

Ford, from the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women’s Hospital, and the investigative team identified women with self-reported physician-diagnosed asthma or COPD. The women were enrolled in the Nurses’ Health Study (1988-2014) or NHSII (1991-2015). Women in the study were nurses between 25-55 years old who completed baseline and biennial questionnaires about lifestyle; health behaviors; medications; and diseases.

Participants who reported a physician diagnosis of asthma were sent a previously validated supplemental respiratory questionnaire about their symptoms, medications, and diagnostic testing. The questionnaire also helped validate participants who self-reported physician diagnosis of emphysema or chronic bronchitis. Nurses who self-reported COPD had confirmed COPD if the criteria for a probable or definite case was met.

Those who self-reported a new rheumatoid arthritis diagnosis were mailed a CTD Screening Questionnaire. Two rheumatologists reviewed the medical records of such participants so they could identify cases that met the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism RA classification criteria.

Ford and the team selected covariates as possible confounders associated with asthma, COPD, and rheumatoid arthritis. The investigators included sociodemographic covariates such as age; race; geographic region; and household incomes. Reproductive confounders were parity/total breastfeeding duration, menopausal status, postmenopausal hormone use.

During the baseline questionnaire, participants reported their smoking status—never, past, or current—and age they started smoking. Current smokers needed to report the number of cigarettes smoked per day, while past smokers indicated the age they stopped and the number of cigarettes they smoked per day before quitting.

The investigators derived smoking pack-years by multiplying the packs of cigarettes smoked per day (20 cigarettes per pack) with number of years smoked.

Overall, 196,409 participants were included in the asthma analysis and 205,153 were in the COPD analysis. The investigators identified 15,148 women with confirmed asthma, 3573 women with confirmed COPD, and 1060 incident rheumatoid arthritis cases (63% seropositive) during nearly 4.4 million person-years of follow-up (median 23.9 [IQR, 18.3-24.5] years for asthma analysis; median 24 [IQR, 20-24.5] years for COPD analysis).

The women in the COPD group were older with a mean age of 52.7 years old, compared to 42.5 years old in the asthma group and 44.4 years old in the no asthma or COPD group. What’s more, participants in the COPD group were more likely to be postmenopausal (70.3% in the COPD group, 30.4% in the asthma group, and 34.6% in the no asthma or COPD group).

The multivariable-adjusted HR for developing rheumatoid arthritis was 1.53 (95% CI, 1.24-1.88) among women with asthma compared to those without asthma or COPD. What’s more, asthma was linked to seropositive and seronegative rheumatoid arthritis.

Asthma was associated with all rheumatoid arthritis among never-smokers (HR, 1.52; 95% CI, 1.14-2.05) and seronegative rheumatoid arthritis (HR, 1.9; 95% CI, 1.22-2.96), but not with seropositive rheumatoid arthritis (HR, 1.32; 95% CI, .88-1.96) compared to participants without 1 of the conditions. For ever-smokers, asthma had HRs for all rheumatoid arthritis of 1.49 (95% CI, 1.1-2.02), for seropositive rheumatoid arthritis of 1.5 (95% CI, 1.04-2.18), and for seronegative rheumatoid arthritis of 1.48 (95% CI, .87-2.5).

Rheumatoid arthritis risk was significantly increased in prevalent asthma (HR, 1.46; 95% CI, 1.06-2.01) and incident asthma (HR, 1.61; 95% CI, 1.23-2.09).

The HR for developing rheumatoid arthritis was 1.89 (95% CI, 1.31-2.75) among women with COPD compared to those without COPD or asthma. The condition also significantly increased the risk for seropositive rheumatoid arthritis (HR, 2.07; 95% CI, 1.31-3.25), but not seronegative rheumatoid arthritis (HR, 1.59; 95% CI, .83-3.05).

There was a bigger association between COPD and seropositive rheumatoid arthritis (HR, 2.85; 95% CI, 1.63-4.99) among ever-smokers >55 years old. For those who had confirmed COPD and never self-reported asthma, the condition was linked with rheumatoid arthritis (HR, 2.57; 95% CI, 1.51-4.39).

Providers who care for patients with such conditions should be aware of the increased risk of rheumatoid arthritis and have a low threshold to evaluate for the conditions in that patient population, the study investigators concluded.

The study, “Asthma, Chronic Obstructive Pulmonary Disease, and Subsequent Risk for Incident Rheumatoid Arthritis among Women: A Prospective Cohort Study,” was published online in the journal Arthritis & Rheumatology.