Citations

Abstract Low-grade inflammation associated with metabolic syndrome (MS) triggers alterations in several organs, but its effects on pulmonary functional and immunological response in older adults are unknown. This cross-sectional study investigated such responses in older adults with and without MS. The study consisted of 77 older adults with MS (68 ± 3 years old) and without MS (67 ± 3 years old). Impulse oscillometry (IOS) was used to evaluate airway and tissue resistance and reactance. Biomarkers of systemic and pulmonary inflammation and fibrosis were studied. Total resistance of respiratory system (R5Hz; p < 0.009), and resistance of proximal (R20Hz; p < 0.001) and distal (R5Hz-R20Hz; p < 0.004) airways were impaired in MS individuals compared to those without MS. The levels of pro-inflammatory (leptin; IL-1beta; IL-8, p < 0.001; TNF-alpha, p < 0.04) and pro-fibrotic (VEGF, p < 0.001) factor increased in MS, while reduced levels of anti-inflammatory cytokines (adiponectin; IL-1ra; IL-10; p < 0.001), and anti-fibrotic (relaxin 1; relaxin 3; Klotho, p < 0.001) factors were found. We conclude that MS accelerates lung function and mechanics impairment in older adults in detriment of an imbalance between pro and anti-inflammatory and fibrotic mediators. Furthermore, this study shows that the lungs also are a target organ in MS, deserving clinical assessment in older adults’ population.

Abstract Background Anaemia is a frequent complication in patients with Crohn’s disease and ulcerative colitis (UC), and patients who respond to treatment generally show improvement in anaemia. Decrease in haemoglobin (Hgb) levels and anaemia may be associated with Janus kinase (JAK) inhibitors. Upadacitinib (UPA), an oral JAK1 selective inhibitor, has demonstrated favourable dose-dependent efficacy in patients with moderately to severely active UC.1 This analysis of data from the U-ACHIEVE study addressed effects of UPA treatment on Hgb levels in patients with UC. Methods U-ACHIEVE (NCT02819635) was a randomised, double-blind, placebo (PBO)-controlled phase 2b clinical trial. Adults with moderately to severely active UC were randomised to receive 7.5, 15, 30, or 45 mg UPA or PBO once daily (QD) for 8 weeks. Hgb levels were measured for all groups at baseline (BL) and weeks 2, 4, 6, and 8. Mean change from BL was calculated for each group. p-values for comparison between UPA and PBO groups were calculated using one-way ANOVA; no multiplicity adjustment was applied. Percentage of patients with Hgb values grade 2 (15–20 g/l Hgb decrease from BL), grade 3 (&lt;80 g/l Hgb level or 21–29 g/l Hgb decrease from BL), and grade 4 (&lt;70 g/l Hgb level or &gt;29 g/l Hgb decrease BL) anaemia were determined for all treatment groups using the Common Terminology Criteria for Adverse Events version 5. Adverse events (AE) were reported by investigators. Results Included in the analysis were 250 patients (mean age ± SD, 42.3 ± 14.2 years; disease duration, 8.2 ± 2.5 years). At BL, most treatment groups had similar mean Hgb levels, except for the 15 mg UPA group, which had significantly lower Hgb levels vs. PBO group (Table). Increased or stable mean levels of Hgb at week 8 vs. BL were observed in most UPA treatment groups. The PBO group had the greatest decrease in Hgb vs. BL at week 8 compared with UPA treatment groups (Figure). Grade ≥2 anaemia was reported in 17.4% of patients receiving PBO and 14.4% of all patients receiving UPA (14.9%, 12.2%, 12.0%, and 17.9% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). Grade ≥3 anaemia was reported in 8.7% of patients receiving PBO and 5% of all patients receiving UPA (6.4%, 6.1%, 6.0%, and 1.8% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). One subject receiving 7.5 mg QD UPA had grade 4 anaemia. AE of anaemia was reported in 6.5% of patients receiving PBO and in 2.1%, 8.2%, and 3.8% of patients receiving 7.5, 15, and 30 mg UPA, respectively, but not in the 45 mg UPA group. Conclusion Decreased Hgb levels over time were observed more frequently in the PBO group. The maintenance of Hgb levels in patients receiving UPA was likely because of improvement of underlying UC. Reference