Global trends in the incidence and mortality of asthma from 1990 to 2019: An age-period-cohort analysis using the global burden of disease study 2019.

Background: Asthma is a major global health challenge. The global strategic management and prevention of asthma report has been published, but health system planning for asthma requires a careful assessment of asthma epidemiology. This study described the incidence and mortality of global asthma from 1990 to 2019. Methods: Based on data from the global burden of disease study (GBD) 2019, we present spatial and temporal trends in asthma incidence and mortality for the world and its 204 countries and territories from 1990 to 2019. Meanwhile, age-period-cohort analysis was used to explore factors influencing asthma incidence and mortality. Results: From 1990 to 2019, the incidence of asthma decreased from 601.20 per 1,00,000 to 477.92 per 1,00,000, and the mortality of asthma decreased from 8.60 per 1,00,000 to 5.96 per 1,00,000. High sociodemographic index (SDI) areas have higher age-standardised asthma incidence and low sociodemographic index areas have higher age-standardised asthma mortality. The age-period-cohort analysis results showed that the relative risk (RR) of incidence was high in children and the RR of mortality was high in elderly individuals. The RR of both asthma incidence and mortality showed a decreasing trend over time. The RR of asthma incidence in the recent birth cohort was higher than that in the previous birth cohort. The RR of asthma mortality continued to decline with the change in the birth cohort. Conclusions: Global asthma incidence and mortality decreased from 1990 to 2019. The decline in asthma incidence was mainly attributed to age effects and period effects, and the decline in asthma mortality was mainly attributed to period effects and cohort effects. Focusing on the risk of incidence in children and the risk of mortality in the elderly, promoting healthy lifestyles and controlling environmental risk factors can help to better control asthma.

Myeloid-derived Suppressor Cells Activate Liver Natural Killer Cells in a Murine Model in Uveal Melanoma.

OBJECTIVE: Elevated myeloid-derived suppressor cells (MDSCs) in many malignancies are associated with the increased risk for metastases and poor prognosis. Therefore, a mouse model of intraocular melanoma was established to explore how MDSCs influence liver metastases. METHODS: In this study, murine B16LS melanoma cells were transplanted into the posterior compartment (PC) of the eye of C57BL/6 mice. Leucocytes from the liver of naive mice and mice bearing melanoma liver metastasis were isolated using isotonic Percoll centrifugation, examined by flow cytometry for their expression of Gr1, CD11b, F4/80, RAE-1, and Mult-1, and further isolated for MDSCs and natural killer (NK) cells. The effects of MDSCs on NK cells were tested by coculturing and assessing the ability of NK cells to produce interferon-gamma (IFN-γ) by ELISA and NK cell cytotoxicity by 3H-thymidine incorporation assay. The impact of IFN-γ on liver metastases was examined via selectively depleting IFN-γ in vivo. RESULTS: The results showed that mice with liver metastases had increased levels of CD11b+Gr1+F4/80+ as well as CD11b+Gr1+F4/80- MDSCs. MDSCs significantly enhanced the generation of IFN-γ together with the cytotoxicity of the NK cells. Furthermore, these effects were cell-cell contact-dependent. Although IFN-γ was not of a toxic nature to the melanoma cells, it profoundly inhibited B16LS cell proliferation. Depleting IFN-γ in vivo led to increased liver metastases. CONCLUSION: All these findings first revealed that MDSCs accumulated in liver metastasis of intraocular melanoma could activate the NK cells to produce an effective anti-tumor immune response. Thus, the MDSCs' performance in different tumor models would need more investigation to boost current immunotherapy modalities.