Rheumatoid arthritis and changes on spirometry by smoking status in two prospective longitudinal cohorts.

OBJECTIVE: To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators. METHODS: We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5-7 years. RA was identified based on self-report and disease-modifying antirheumatic drug use; non-RA comparators reported neither. The primary outcomes were annual changes in the per cent-predicted forced expiratory volume in 1 s (FEV1%) and per cent predicted forced vital capacity (FVC%). Statistical comparisons were performed using multivariable linear regression. The analysis was stratified based on baseline smoking status and the presence of obstructive pattern (FEV1/FVC <0.7). RESULTS: Among participants who underwent baseline and follow-up spirometry, we identified 233 patients with RA and 37 735 non-RA comparators. Among never-smoking participants without an obstructive pattern, RA was significantly associated with more FEV1% decline (ß=-0.49, p=0.04). However, in ever smokers with ≥10 pack-years, those with RA exhibited significantly less FEV1% decline than non-RA comparators (ß=0.50, p=0.02). This difference was more pronounced among those with an obstructive pattern at baseline (ß=1.12, p=0.01). Results were similar for FEV1/FVC decline. No difference was observed in the annual FVC% change in RA versus non-RA. CONCLUSIONS: Smokers with RA, especially those with baseline obstructive spirometric patterns, experienced lower FEV1% and FEV1/FVC decline than non-RA comparators. Conversely, never smokers with RA had more FEV1% decline than non-RA comparators. Future studies should investigate potential treatments and the pathogenesis of obstructive lung diseases in smokers with RA.

Myeloid Cells and Sphingosine-1-Phosphate Are Required for TCRαß Intraepithelial Lymphocyte Recruitment to the Colon Epithelium.

Intraepithelial lymphocytes (IELs) are T cells important for the maintenance of barrier integrity in the intestine. Colon IELs are significantly reduced in both MyD88-deficient mice and those lacking an intact microbiota, suggesting that MyD88-mediated detection of bacterial products is important for the recruitment and/or retention of these cells. Here, using conditionally deficient MyD88 mice, we show that myeloid cells are the key mediators of TCRαß+ IEL recruitment to the colon. Upon exposure to luminal bacteria, myeloid cells produce sphingosine-1-phosphate (S1P) in a MyD88-dependent fashion. TCRαß+ IEL recruitment may be blocked using the S1P receptor antagonist FTY720, confirming the importance of S1P in the recruitment of TCRαß+ IELs to the colon epithelium. Finally, using the TNFΔARE/+ model of Crohn's-like bowel inflammation, we show that disruption of colon IEL recruitment through myeloid-specific MyD88 deficiency results in reduced pathology. Our results illustrate one mechanism for recruitment of a subset of IELs to the colon.