FCGR2A rs1801274 和MUC5B rs35705950 变异与肺炎易感性的相关性。
- 作者列表："Shi X","Ma Y","Li H","Yu H
BACKGROUND:Herein, we collected currently published data to comprehensively evaluate the impact of the FCGR2A (Fc fragment of IgG receptor IIa) rs1801274 and MUC5B (mucin 5B, oligomeric mucus/gel-forming) rs35705950 variations on susceptibility to pneumonia diseases. METHODS:We retrieved case-control studies from three online databases and applied the statistical approach of meta-analysis for a series of pooling analyses. RESULTS:A total of fourteen case-control studies were included for FCGR2A rs1801274; while thirty-one case-control studies were included for MUC5B rs35705950. No significant difference between pneumonia cases and controls for FCGR2A rs1801274 was found. However, MUC5B rs35705950 was significantly associated with pneumonia susceptibility in the whole population under the genetic models of allelic T vs. G [OR (odds ratio) =3.78], carrier T vs. G (OR = 3.31), TT vs. GG (OR = 13.66), GT vs. GG (OR = 4.78), GT + TT vs. GG (OR = 5.05), and TT vs. GG + GT (OR = 6.47) (all P < 0.001, Bonferroni-adjusted P < 0.006; false discovery rate-adjusted P < 0.0010). Furthermore, we observed a similar positive result for subgroup analyses of "Caucasian", "Asian", "population-based control", and "idiopathic pulmonary fibrosis". CONCLUSIONS:MUC5B rs35705950, but not FCGR2A rs1801274, increases susceptibility to clinical pneumonia, especially to idiopathic pulmonary fibrosis, in both the Caucasian and Asian populations.
背景: 在此，我们收集了目前发表的数据，以全面评估FCGR2A (IgG受体IIa的Fc片段) rs1801274 和MUC5B (粘蛋白 5B，寡聚粘液/凝胶形成) 的影响rs35705950 对肺炎疾病易感性的变异。 方法: 我们从三个在线数据库中检索病例对照研究，并应用meta分析的统计方法进行一系列汇集分析。 结果: 共纳入 14 个关于FCGR2A rs1801274 的病例-对照研究; 同时纳入 31 个关于MUC5B rs35705950 的病例-对照研究。肺炎病例和对照之间未发现FCGR2A rs1801274 的显著差异。然而，在等位基因T vs. G的遗传模型下，MUC5B rs35705950 与整个人群的肺炎易感性显著相关 [OR (比值比) = 3.78]，携带者T对G (or = 3.31)，TT对GG (or = 13.66)，GT对GG (or = 4.78)，GT + TT vs GG (OR = 5.05)，TT与GG + GT (OR = 6.47)，差异均有统计学意义 (均P < 0.001，Bonferroni调整P < 0.006; 错误发现率校正P < 0.0010).此外，我们观察到 “高加索人”，“亚洲人”，“基于人群的对照” 和 “特发性肺纤维化” 的亚组分析的类似阳性结果。 结论: MUC5B rs35705950，而不是FCGR2A rs1801274，增加了白种人和亚洲人群对临床肺炎的易感性，尤其是特发性肺纤维化。
METHODS::The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.
METHODS::Pneumonia is a common respiratory infectious disease that involves the inflammation of the pulmonary parenchyma. Periodontal disease is widespread and correlated with pneumonia. However, the relationship between periodontal treatment and clinical infectious outcomes in patients with pneumonia has remained undetermined. The aim of this study was to investigate the association between periodontal treatment and the risk of pneumonia events in the Taiwanese population. A nationwide population-based cohort study was conducted using data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 49,400 chronic periodontitis patients who received periodontal treatment from 2001 to 2012 were selected. In addition, 49,400 healthy individuals without periodontal diseases were picked randomly from the general population after propensity score matching according to age, gender, monthly income, urbanization, and comorbidities. The Cox proportional hazard regression analysis was adopted to assess the hazard ratio (HR) of pneumonia between the periodontal treatment cohort and the comparison cohort. The average ages of the periodontal treatment and comparison groups were 44.25 ± 14.82 years and 44.15 ± 14.5 years, respectively. The follow up durations were 7.66 and 7.41 years for the periodontal treatment and comparison groups, respectively. We found 2504 and 1922 patients with newly diagnosed pneumonia in the comparison cohort and the periodontal treatment cohort, respectively. The Kaplan-Meier plot revealed that the cumulative incidence of pneumonia was significantly lower over the 12 year follow-up period in the periodontal treatment group (using the log-rank test, p < 0.001). In conclusion, this nationwide population-based study indicated that the patients with periodontal treatment exhibited a significantly lower risk of pneumonia than the general population.
METHODS:OBJECTIVE:To describe the treatment of community-acquired pneumonia (CAP) in children under five years in Tanzania. METHODS:Between January and December 2017, children aged 2-59 months with chest radiography-confirmed CAP were enrolled. The parents were interviewed to collect information on the patients and home-based medication. Clinical information was derived from the patient files. Nasopharyngeal swab and blood samples were collected for isolation of the causative pathogens. Swab samples were analysed by quantitative PCR whereas blood samples were tested using BacT/Alert 3D. RESULTS:Overall, 109 children with CAP were included in this analysis. Provision of care to most children was delayed (median = 4.6 days). A quarter (26.6%) were given unprescribed/leftover antibiotics at home. Only one child had positive bacterial culture. Referrals were associated with nasopharyngeal carriage of Streptococcus pneumoniae (p = 0.003) and Haemophilus influenzae (p = 0.004). Of all admitted children, more than a quarter (n = 29) did not need to be hospitalised and inappropriately received injectable instead of oral antibiotics. CONCLUSION:We found high rates of home treatment, particularly with antibiotics. Appropriate health care was delayed for most children because of home treatment. Efforts are needed at the community level to improve awareness of antimicrobial resistance.