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.

Peripheral venous pressure changes during exercise are associated with adverse Fontan outcomes.

OBJECTIVE: Elevated central venous pressure (CVP) plays an important role in the development of adverse Fontan outcomes. Peripheral venous pressure (PVP) has been validated as a surrogate for CVP in Fontan patients. We hypothesised that PVP in response to exercise will be associated with a greater prevalence of Fontan morbidity. METHODS: Adult Fontan patients had cardiopulmonary exercise testing (CPET) with PVP monitoring in the upper extremity between 2015 and 2018. PVP at rest, during unloaded cycling and at peak exercise was compared between those with and without adverse Fontan outcomes including arrhythmia, unscheduled hospital admissions, heart failure requiring diuretics, need for reintervention and a composite outcome of the above morbidities, heart transplantation and death. RESULTS: Forty-six patients with a mean age at CPET of 26.9±9.5 years. During exercise, PVP increased from 13.6±3.5 mm Hg at rest, to 16.5±3.9 mm Hg during unloaded cycling, to 23.0±5.5 mm Hg at peak exercise. Unloaded and peak PVP were more strongly associated than resting PVP with all adverse outcomes, except reintervention (composite outcome: resting PVP: OR 2.8, p=0.023; unloaded PVP: OR 6.1, p=0.001; peak PVP: OR 4.0, p<0.001). Cut-offs determined using ROC curve analysis had high specificity for the composite outcome (88% unloaded PVP ≥18 mm Hg; 89% peak PVP ≥25 mm Hg). CONCLUSION: Higher PVP at unloaded and peak exercise was strongly associated with a higher prevalence of adverse Fontan outcomes. Minimally invasive PVP monitoring during CPET may serve as a useful tool for risk stratifying individuals with a Fontan.