Increased bronchiectasis risk and related risk factors in inflammatory bowel disease: a 10-year Korean national cohort study.

Background: The association between inflammatory bowel disease (IBD) and an increased risk of bronchiectasis, as well as contributing factors, remains unclear. Additionally, whether bronchiectasis increases disease burden in IBD remains unknown. Therefore, this study aimed to: 1) assess whether IBD increases the risk of incident bronchiectasis; 2) compare the risk of bronchiectasis between individuals with Crohn's disease (CD) and those with ulcerative colitis (UC); 3) identify risk factors for bronchiectasis in individuals with IBD; and 4) examine the disease burden in individuals with IBD and bronchiectasis versus those without. Methods: We conducted a population-based matched cohort study involving adults aged ≥20 years with IBD, using data acquired from the Korean National Health Insurance Service-National Sample Cohort database between 2002 and 2012. Results: During the mean follow-up of 9.6 years, the incidence rate of bronchiectasis was 419.63 out of 100 000 person-years (PY) and 309.65 out of 100 000 PY in the IBD and matched cohorts (adjusted hazard ratio (aHR) 1.21, 95% CI 1.05-1.39), respectively. UC was associated with increased bronchiectasis risk (aHR 1.42, 95% CI 1.19-1.69), but CD was not. Multivariate Cox regression analyses showed that age, male sex, medical aid, underweight status, COPD and diabetes mellitus were associated with an increased risk of bronchiectasis in the IBD cohort (p<0.05). The mortality, emergency department visit and hospitalisation rates were significantly higher for individuals with IBD and bronchiectasis compared with those without bronchiectasis (p<0.05). Conclusion: IBD is associated with increased risk of bronchiectasis, which results in a greater disease burden in individuals with IBD.

FRMD6 determines the cell fate towards senescence: involvement of the Hippo-YAP-CCN3 axis.

Cellular senescence, a hallmark of aging, is pathogenically linked to the development of aging-related diseases. This study demonstrates that FRMD6, an upstream component of the Hippo/YAP signaling cascade, is a key regulator of senescence. Proteomic analysis revealed that FRMD6 is upregulated in senescent IMR90 fibroblasts under various senescence-inducing conditions. Silencing FRMD6 mitigated the senescence of IMR90 cells, suggesting its requirement in senescence. Conversely, the overexpression of FRMD6 alone induced senescence in cells and in lung tissue, establishing a causal link. The elevated FRMD6 levels correlated well with increased levels of the inhibitory phosphorylated YAP/TAZ. We identified cellular communication network factor 3 (CCN3), a key component of the senescence-associated secretory phenotype regulated by YAP, whose administration attenuated FRMD6-induced senescence in a dose-dependent manner. Mechanistically, FRMD6 interacted with and activated MST kinase, which led to YAP/TAZ inactivation. The expression of FRMD6 was regulated by the p53 and SMAD transcription factors in senescent cells. Accordingly, the expression of FRMD6 was upregulated by TGF-ß treatment that activates those transcription factors. In TGF-ß-treated IMR90 cells, FRMD6 mainly segregated with p21, a senescence marker, but rarely segregated with α-SMA, a myofibroblast marker, which suggests that FRMD6 has a role in directing cells towards senescence. Similarly, in TGF-ß-enriched environments, such as fibroblastic foci (FF) from patients with idiopathic pulmonary fibrosis, FRMD6 co-localized with p16 in FF lining cells, while it was rarely detected in α-SMA-positive myofibroblasts that are abundant in FF. In sum, this study identifies FRMD6 as a novel regulator of senescence and elucidates the contribution of the FRMD6-Hippo/YAP-CCN3 axis to senescence.

Mammalian adaptation risk in HPAI H5N8: a comprehensive model bridging experimental data with mathematical insights.

Understanding the mammalian pathogenesis and interspecies transmission of HPAI H5N8 virus hinges on mapping its adaptive markers. We used deep sequencing to track these markers over five passages in murine lung tissue. Subsequently, we evaluated the growth, selection, and RNA load of eight recombinant viruses with mammalian adaptive markers. By leveraging an integrated non-linear regression model, we quantitatively determined the influence of these markers on growth, adaptation, and RNA expression in mammalian hosts. Furthermore, our findings revealed that the interplay of these markers can lead to synergistic, additive, or antagonistic effects when combined. The elucidation distance method then transformed these results into distinct values, facilitating the derivation of a risk score for each marker. In vivo tests affirmed the accuracy of scores. As more mutations were incorporated, the overall risk score of virus heightened, and the optimal interplay between markers became essential for risk augmentation. Our study provides a robust model to assess risk from adaptive markers of HPAI H5N8, guiding strategies against future influenza threats.

Impacts of regular physical activity on hospitalisation in chronic obstructive pulmonary disease: a nationwide population-based study.

INTRODUCTION: Studies that comprehensively evaluate the association between physical activity (PA) levels, particularly by quantifying PA intensity, and healthcare use requiring emergency department (ED) visit or hospitalisation in patients with chronic obstructive pulmonary disease (COPD) are limited in Korea. METHODS: The risk of all-cause and respiratory ED visit or hospitalisation according to the presence or absence of COPD and the level of PA was evaluated in a retrospective nationwide cohort comprising 3308 subjects with COPD (COPD cohort) and 293 358 subjects without COPD (non-COPD cohort) from 2009 to 2017. RESULTS: The COPD group exhibited a higher relative risk of all-cause and respiratory ED visit or hospitalisation across all levels of PA compared with the highly active control group (≥1500 metabolic equivalents (METs)-min/week). Specifically, the highest risk was observed in the sedentary group (adjusted HR (aHR) (95% CI) = 1.70 (1.59 to 1.81) for all-cause ED visit or hospitalisation, 5.45 (4.86 to 6.12) for respiratory ED visit or hospitalisation). A 500 MET-min/week increase in PA was associated with reductions in all-cause and respiratory ED visit or hospitalisation in the COPD cohort (aHR (95% CI) = 0.92 (0.88 to 0.96) for all-cause, 0.87 (0.82 to 0.93) for respiratory cause). CONCLUSIONS: Compared with the presumed healthiest cohort, the control group with PA>1500 METs-min/week, the COPD group with reduced PA has a higher risk of ED visit or hospitalisation.