Secular trend and risk factors of 30-day COPD-related readmission in Beijing, China.

Readmission due to chronic obstructive pulmonary disease (COPD) exacerbation contributes significantly to disease burden. Trend in readmission rate among COPD patients in China is not well characterized. We described the secular trend and identify risk factors of COPD-related 30-day readmission in Beijing during 2012-2017. In this retrospective cohort study, we used data from a citywide hospital discharge database in Beijing. We included patients ≥ 40 years with a primary diagnosis of COPD from 2012 to 2017. A total of 131 591 index admissions were identified. COPD-related 30-day readmission was defined as the initial admission with a primary diagnosis of COPD that occurs within 30 days from the discharge date of an index admission. Overall and annual 30-day readmission rates were calculated in the total population and subgroups defined by patient characteristics. We used multivariable logistic models to investigate risk factors for readmission and in-hospital mortality within 30 days. The overall 30-day COPD-related readmission rate was 15.8% (n = 20 808). The readmission rate increased from 11.5% in 2012 to 17.2% in 2017, with a multivariable-adjusted OR (95% CI) for annual change to be 1.08 (1.06-1.09) (P trend < 0.001). The upward trend in readmission rate levelled off at about 17% since 2014. The readmission rate of men was higher and increased faster than women. Comorbid osteoporosis, coronary heart disease, congestive heart failure, and cancer were associated with an increased risk of 30-day COPD-related readmission. The 30-day COPD-related readmission rate in Beijing showed an overall increasing trend from 2012 to 2017. Future efforts should be made to further improve care quality and reduce early readmissions of COPD patients.

Analysis of lncRNA and mRNA Repertoires in Lung From BAFF-R-Deficient Pneumocystis-Infected Mice.

Background: Pneumocystis pneumonia (PCP) is a common medical issue in immunosuppressive patients. Increasing evidence supports that B cells may play an essential role in PCP individuals. The present study aims to integrate lncRNA and mRNA expression profiles and further investigate the molecular function of mature B cells in PCP. Methods: The lung tissue of wild-type (WT) mice and B-cell-activating factor receptor-deficient (mature B-cell deficiency, BAFF-R-/-) mice were harvested at 3 weeks after being infected with pneumocystis. After total RNAs were extracted, transcriptome profiling was performed following the Illumina HiSeq 3000 protocol. lncRNA-targeted miRNA pairs were predicted using the online databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment pathways were analyzed to functionally annotate these differentially expressed genes. Additionally, the immune-related lncRNA-miRNA-mRNA-ceRNA network was subsequently performed. The quantitative real-time PCR (RT-PCR) analysis was conducted to evaluate the lncRNA and mRNA expression profiles in WT-PCP mice and BAFF-R-/- PCP mice. Results: Compared with the control group, 166 mRNAs were observed to be aberrantly expressed (fold change value ≥2; P <0.05) in the BAFF-R-/- PCP group, including 39 upregulated and 127 downregulated genes, while there were 69 lncRNAs differently expressed in the BAFF-R-/- PCP group, including 15 upregulated and 54 downregulated genes. In addition, GO and KEGG pathway analyses showed that BAFF-R deficiency played an important role in the primary and adaptive immune responses in PCP. Furthermore, the lncRNA and mRNA co-expression network was established. We noted that the core network of lncRNA-TF (transcription factor) pairs could be classified into the categories including infection and immunity pathways. Conclusion: In summary, in this study, we further explored the role of mature B cells in the pathogenesis and progression of PCP and the data demonstrated that BAFF-R deficiency could play a significant role in immune regulation in the PCP population.

PD-1 Deficiency Promotes Macrophage Activation and T-Helper Cell Type 1/T-Helper Cell Type 17 Response in Pneumocystis Pneumonia.

Pneumocystis is an unusual, opportunistic fungal pathogen capable of causing Pneumocystis pneumonia (PCP) in immunocompromised hosts. Although PCP was discovered >100 years ago, its pathogenesis remains unclear. The inhibitory receptor PD-1 (programmed death 1), a negative regulator of activated T cells, has been reported to take part in tumor escape, immune tolerance, and infection immunity. In this study, we examined the role of the PD-1/PD-L1 (programmed death-ligand 1) pathway in patients with PCP and in mice. The expression levels of PD-1/PD-L1 in patients with PCP and in mice were measured by real-time PCR and flow cytometry. The effects of PD-1 deficiency are demonstrated using wild-type and PD-1-/- mice. Our data show that Pneumocystis infection promotes PD-1/PD-L1 expression; PD-1 deficiency enhances the phagocytic function of macrophages and the pulmonary T-helper cell type 1 (Th1)/Th17 response, which might contribute to Pneumocystis clearance; and PD-1 deficiency affects the polarization of macrophages. PCP mice treated with anti-PD-1 antibody showed improved pulmonary clearance of Pneumocystis. Collectively, our results demonstrate that the PD-1/PD-L1 pathway plays a role in regulating the innate and adaptive immune responses, suggesting that manipulation of this pathway may constitute an immunotherapeutic strategy for PCP.

IL-10-producing B cells regulate Th1/Th17-cell immune responses in Pneumocystis pneumonia.

Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells play an important role in infectious diseases. In the present study, the immune regulatory role of mature B cells in host defense to Pneumocystis was evaluated. Pneumocystis infection resulted in a decrease in B cells in patients and mice, and the Pneumocystis burden in B cell-deficient mice also progressively increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was delayed in B cell-activating factor receptor (BAFF-R)-deficient mice (BAFF-R-/- mice), which had few B cells and Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild-type (WT) mice. There were fewer effector CD4+ T cells and higher percentages of T helper (Th)1/Th17 cells in BAFF-R-/- mice than in WT mice. Adoptive transfer of naive B cells, mRNA sequencing, and IL-1ß neutralization experiments indicated that IL-1ß is a likely determinant of the IL-10-producing B cell-mediated suppression of Th1/Th17-cell immune responses in BAFF-R-/- PCP mice. Our data indicated that B cells play a vital role in the regulation of Th cells in response to Pneumocystis infection.

Diagnosis of Pneumocystis jirovecii pneumonia with serum cell-free DNA in non-HIV-infected immunocompromised patients.

Conventional respiratory tract specimens, such as bronchoalveolar lavage (BAL) fluid and induced sputum for diagnosing Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients are difficult to obtain. Besides, bronchoscopy is an invasive procedure that carries the risk of causing rapidly progressive respiratory insufficiency. By contrast, serum cell-free DNA (cfDNA) is easy to obtain and has been proven useful in diagnosing cancer, pregnancy associated complications, parasite infection and sepsis. In this study, we performed quantitative polymerase chain reaction (qPCR) to assess the diagnostic efficiency of using serum cfDNA, BAL fluid, and sputum DNA for PCP. Seventy-one patients (35 PCP patients and 36 non-PCP patients) were enrolled according to the clinical PCP diagnostic criteria. The sensitivity, specificity, positive predictive value, and negative predictive value of PCR using serum cfDNA were 68.6% (95% CI, 50.7-83.1), 97.2% (95% CI, 85.5-99.9), 96.0%, and 76.1%, respectively. PCR using BAL fluid and sputum had a high sensitivity (97.1% and 91.4%, respectively) but relatively low specificity (86.1% and 86.1%, respectively). The combination of the sputum PCR OR serum cfDNA PCR yielded a sensitivity of 97.1%.These results indicated that serum cfDNA might be a valuable method in PCP diagnosis.