Background: The published data on the association between β2-adrenergic receptor gene polymorphisms and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed.Methods: A literature search was conducted in PubMed, Web of Science, EMBASE, Wanfang, and the China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to calculate the strength of the association. A sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates, and funnel plots and Egger’s tests were used for indications of publication bias.Results: Seventy three studies with three single nucleotide polymorphisms (SNP) (rs1042713, c.G46A, p.Gly16Arg; rs1042714, c.G79C, p.Gln27Glu; rs1042711, c.T-47C, p.Cys19Arg) were finally identified. For the rs1042713 polymorphism, no significant association with asthma risk was found in the overall population. However, a significant protective association was found in the Indian population in the dominant model comparison (OR = 0.72, 95% CI = 0.59–0.87, I² = 25%, studies = 5, cases = 1190, controls = 1241). A significant risk association was found in the Arab population in the dominant model comparison (OR = 1.75, 95% CI = 1.14–2.70, I² = 0%, studies = 2, cases = 307, controls = 361) and the homozygote model comparison (OR = 1.88, 95% CI = 1.17–3.02, I² = 0%, studies = 2, cases = 307, controls = 361), and in the Hispanic-Latino population in the dominant model comparison (OR = 1.68, 95% CI = 1.10–2.55, I² = 77%, studies = 5, cases = 1026, controls = 1412). For the rs1042714 polymorphism, we found a significant association in the recessive model comparison (OR = 0.83, 95% CI = 0.70–0.98, I² = 44%, studies = 52, cases = 8242, controls = 16,832), the homozygote genotype comparison (OR = 0.84, 95% CI = 0.72–0.98, I² = 25%, studies = 52, cases = 8242, controls = 16,832) and the allelic genetic model (OR = 0.91, 95% CI = 0.83–0.99, I² = 59%, studies = 52, cases = 8242, controls = 16,832) in the overall population. When stratified by age, a significant association was also found in children in the recessive model comparison (OR = 0.59, 95% CI = 0.39–0.88, I² = 58%, studies = 18, cases = 2498, controls = 2510) and the homozygote genotype comparison (OR = 0.63, 95% CI = 0.43–0.92, I² = 46%, studies = 18, cases = 2498, controls = 2510), but not in adult. For the rs1042711 polymorphism, no significant associations were found in the any genetic model.Conclusion: The meta-analysis suggests that the ADRB2 rs1042714 polymorphism has a protective association with asthma in the overall population and the pediatric subgroup.

Lung cancer has been the leading cause of cancer-related death for many years worldwide. Pemetrexed, either as monotherapy or combined with other agents, is the preferred chemotherapy regimen for lung adenocarcinoma. However, both de novo and acquired resistance against pemetrexed frequently occur and lead to poor prognosis of patients. The underlying mechanisms remain poorly characterized. Here, RNA-seq analysis is utilized to compare gene expression levels in an adenocarcinoma cell line A549 with those in its pemetrexed-resistant counterpart, A549/PEM. We show that SRC3 is one of the most significantly upregulated genes in pemetrexed-resistant cells. SRC3 specifically enhances pemetrexed resistance in cultured adenocarcinoma cells. In addition, SRC3 increases pemetrexed resistance by decreasing chemotherapy-induced apoptosis via downregulating ROS level. Mechanistically, SRC3 enhances pemetrexed resistance via regulating Nrf2 and AKT signaling pathway. High SRC3 expression is positively correlated with decreased responsiveness to pemetrexed rather than other chemotherapeutic agents and predicts a poorer clinical outcome in lung adenocarcinoma patients. These data indicate that knockdown of SRC3 may be useful to treat pemetrexed-resistant lung cancer and may also provide a specific biomarker to predict pemetrexed responsiveness in lung cancer.

This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants’ residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM_2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . The results showed a relationship between PM_2.5, lung function and IOS parameters. An increase of 10 µg/m³ in PM_2.5 was associated with a decline of 2.083% (95% CI: −3.047 to − 1.103) in forced expiratory volume in one second /predict (FEV₁%pred), a decline of 193 ml/s (95% CI: −258 to − 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: −1.518 to − 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (F_res), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z₅) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R₅). Compared to patients in the central district, those in the southern district had lower FEV₁/FVC, FEV₁%pred, PEF, FEF_75%, MMEF, X₅, and higher F_res, Z₅ and R₅ (p < 0.05). Short-term exposure to PM_2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM_2.5, the more severe of COPD.

The Role of Human Leukocyte Antigen-DR in Regulatory T Cells in Patients with Virus-Induced Acute Exacerbation of Chronic Obstructive Pulmonary Disease - Article abstract #928051

Objective: The aim was to evaluate the associations of short-term exposure to main constituents of PM_2.5 with lung function and impulse oscillometry system in China. Methods: A four-year observational cohort study based on hospital outpatient visits between January 1, 2016 to December 31, 2019 was conducted in northern China. A total of 2151 outpatients were randomly selected from four hospitals in Beijing (who were divided into patients with acute exacerbation of COPD (AECOPD) (1348 cases) and without AECOPD (803 cases)). Multivariable linear regression models were used to obtain differences of lung function index and impulse oscillometry system (IOS) parameters associated with PM_2.5, adjusting for sex, smoking history,education level, age, body mass index (BMI), mean temperature, and relative humidity. Results: Significant associations were found between lung function and IOS with PM_2.5 in AECOPD patients in Beijing, China. An increase of 10 ug/m³ in PM_2.5 was associated with a decline of 2.08% (95% CI: −3.05 to −1.10) in FEV₁/pred, a decline of 0.19 L/s (95% CI: −0.26 to −0.04) in PEF and a decline of 0.93% (95% CI: −1.52 to −0.34) in MMEF_25-75%. An increase of 10 ug/m³ in PM_2.5 was associated with an increase of 0.73 Hz (95% CI: 0.31 to 1.15) in Fres, an increase of 0.04 Kpa/(L/s) (95% CI: 0.01 to 0.06) in Z5 and an increase of 0.03 Kpa/(L/s) (95% CI: 0.00 to 0.05) in R5. And the more heavily PM_2.5 of the district, the greater harm the impact. Conclusion: Our findings suggested that short-term PM_2.5 exposure may primarily affect both airway function and IOS in COPD patients.