Rheumatoid arthritis and risk of chronic obstructive pulmonary disease or asthma among women: A marginal structural model analysis in the Nurses’ Health Study

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Objective Rheumatoid arthritis (RA) is postulated to originate at mucosal surfaces, particularly the airway mucosa. To investigate this hypothesis, we determined the association between RA and asthma, passive smoke exposure, and age at start of smoking. Methods For this case–control study, we identified 1,023 cases of RA (175 incident) within a single‐center biobank population, using a rules‐based algorithm that combined self‐report with 2 diagnostic codes. Exposures were self‐reported on biobank questionnaires. Logistic regression models were used to calculate the association of exposures with RA, adjusting for potential confounders. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results After adjustment for allergies, urban environment, and passive smoke exposure, asthma was found to be associated with RA in the full cohort (OR 1.28 [95% CI 1.04–1.58; P = 0.02]) but not the incident RA cohort (OR 1.17 [95% CI 0.66–2.06; P = 0.60]). History of allergic disease was associated with RA in both the full cohort (OR 1.30 [95% CI 1.12–1.51; P < 0.001]) and the incident RA cohort (OR 1.61 [95% CI 1.11–2.33; P = 0.01]), especially food allergy, which was significantly associated with RA in the full cohort (OR 1.38 [95% CI 1.08–1.75; P = 0.01]) and showed a trend toward significance in the incident RA cohort (OR 1.83 [95% CI 0.97–3.45; P = 0.06]). Passive smoke exposure at home or work was not associated with RA. Finally, age at start of smoking was not associated with increased odds of developing RA in either the full cohort (OR 1.03 [95% CI 1.00–1.06; P = 0.03]) or the incident RA cohort (OR 1.00 [95% CI 0.92–1.08; P = 0.98]). Conclusion Asthma and allergies may be associated with increased risk of RA. Passive smoke exposure and early age at start of smoking do not appear to influence risk of RA.

Section: Discussionsupporting

confidence: 63%

Investigating Asthma, Allergic Disease, Passive Smoke Exposure, and Risk of Rheumatoid Arthritis

Kronzer

Crowson

Sparks

et al. 2019

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“…Importantly, MAA adducts demonstrated marked colocalization with citrulline, CD19+ B cells, and type II collagen, most frequently observed in RA-ILD lung tissue. This study is among the first to characterize a biomarker for RA-ILD that has leveraged a comparator population incorporating RA patients with other chronic lung diseases that may be overrepresented in RA (33). Taken together, our findings suggest that MAA-modified proteins and resulting immune responses may serve as useful biomarkers for RA-ILD and that MAA-modified proteins may contribute to the pathogenesis of RA-ILD.…”

Section: Discussionmentioning

confidence: 69%

Malondialdehyde–Acetaldehyde Adducts and Antibody Responses in Rheumatoid Arthritis–Associated Interstitial Lung Disease

England

Duryee

Roul

et al. 2019

Objective To compare serum anti–malondialdehyde–acetaldehyde (anti‐MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis–associated interstitial lung disease (RA‐ILD) to those found in controls. Methods Anti‐MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA‐ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti‐MAA antibody with RA‐ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA‐ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. Results Among 1,823 RA patients, 90 had prevalent RA‐ILD. Serum IgA and IgM anti‐MAA antibody concentrations were higher in RA‐ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti‐MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11–3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19–4.15]) were significantly associated with the presence of RA‐ILD. MAA expression in RA‐ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA‐ILD. Conclusion Serum IgA and IgM anti‐MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA‐ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA‐ILD.

“…Prior studies have demonstrated a positive association between RA and subsequent risk of developing COPD . However, we identified only 2 studies examining COPD as an RA risk factor, neither of which were prospective.…”

Section: Discussionmentioning

confidence: 99%

Asthma, Chronic Obstructive Pulmonary Disease, and Subsequent Risk for Incident Rheumatoid Arthritis Among Women: A Prospective Cohort Study

Ford

Liu

Chu

et al. 2020

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Objective. Inflamed airways are hypothesized to contribute to rheumatoid arthritis (RA) pathogenesis due to RA-related autoantibody production, and smoking is the strongest environmental RA risk factor. However, the role of chronic airway diseases in RA development is unclear. We undertook this study to investigate whether asthma and chronic obstructive pulmonary disease (COPD) were each associated with RA.Methods. We performed a prospective cohort study of 205,153 women in the Nurses' Health Study (NHS, 1988(NHS, -2014 and NHSII (1991NHSII ( -2015. Exposures were self-reported physician-diagnosed asthma or COPD confirmed by validated supplemental questionnaires. The primary outcome was incident RA confirmed by medical record review by 2 rheumatologists. Covariates (including smoking pack-years/status) were assessed via biennial questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for RA were estimated using Cox regression.Results. We identified 15,148 women with confirmed asthma, 3,573 women with confirmed COPD, and 1,060 incident RA cases during 4,384,471 person-years (median 24.0 years/participant) of follow-up in the NHS and NHSII. Asthma was associated with increased RA risk (HR 1.53 [95% CI 1.24-1.88]) compared to no asthma/COPD after adjustment for covariates, including smoking pack-years/status. Asthma remained associated with increased RA risk when analyzing only never-smokers (HR 1.53 [95% CI 1.14-2.05]). COPD was also associated with increased RA risk (HR 1.89 [95% CI 1.31-2.75]). The association of COPD with RA was most pronounced in the subgroup of eversmokers age >55 years (HR 2.20 [95% CI 1.38-3.51]).Conclusion. Asthma and COPD were each associated with increased risk of incident RA, independent of smoking status/intensity and other potential confounders. These results provide support for the hypothesis that chronic airway inflammation may be crucial in RA pathogenesis.