Background: Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life. Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument to assess the efficacy of the treatments following COPD exacerbations is lacking nowadays. The COPD Assessment Test (CAT) is an 8-item questionnaire designed to assess and quantify health status and symptom burden in COPD patients. We hypothesize that the change in CAT score is related to the treatment response following COPD exacerbations. Methods: 78 inpatients with clinician-diagnosed acute exacerbation of COPD (AECOPD) completed the CAT, St George's Respiratory Questionnaire (SGRQ) and modified Medical Research Council (mMRC) Dyspnea Scale both at exacerbation and the 7th day of therapy, and a subgroup of 39 patients performed the pulmonary function test. Concentrations of serum C-reactive protein (CRP) and plasma fibrinogen were assayed at the same time. Correlations between the CAT and other measurements were examined. Results: After 7 days' therapy, the CAT and SGRQ scores, mMRC grades, as well as the concentrations of CRP and fibrinogen all decreased significantly (P < 0.001). Meanwhile, the FEV1% predicted had a significant improvement (P < 0.001). The CAT scores were significantly correlated with concurrent concentrations of CRP and fibrinogen, SGRQ scores, FEV1% predicted and mMRC grades (P < 0.05). The change in CAT score was positively correlated with the change of CRP (r = 0.286, P < 0.05), SGRQ score (r = 0.725, P < 0.001) and mMRC grades (r = 0.593, P < 0.001), but not with fibrinogen (r = 0.137, P > 0.05) or FEV1% predicted (r = −0.101, P > 0.05). No relationship was found between the changes of SGRQ score and CRP and fibrinogen (P>0.05).

Airway barrier damage and excessive inflammation induced by influenza A virus (IAV) are associated with disease progression and prognosis. ResolvinD1 (RvD1) is a promising lipid mediator with critical protection against infection in the lung. However, whether RvD1 protects against IAV-induced injury and the underlying mechanisms remain elusive. In this study, primary normal human bronchial epithelial (pNHBE) cells were isolated and co-cultured with IAV and/or RvD1. Then, the expressions of E-cadherin, Zonula occludins-1, inflammatory mediators and proteins in Nrf2-dependent pathway were detected. To further explore the mechanisms, Nrf2 short hairpin RNA (Nrf2 shRNA) was applied in pNHBE cells. Furthermore, mice were infected with IAV, and were subsequently treated with RvD1. We found that IAV downregulated expressions of E-cadherin, Zonula occludins-1, Nrf2 and HO-1, upregulated the phosphorylation of NF κ B p65 and IKBα, levels of IL-8 and TNF-α, as well as ROS production. RvD1 reversed these damaging effects induced by IAV. However, when Nrf2 expression was suppressed with shRNA in pNHBE cells, the protective effects of RvD1 on IAV-induced injury were inhibited. In vivo studies further demonstrated that RvD1 could alleviate barrier protein breakdown and reduce airway inflammatory reactions. Collectively, the study demonstrated that RvD1 could play dual beneficial roles in protecting airway epithelium barrier function and reducing inflammation via the Nrf2 pathway, which may provide a better treatment option for influenza A virus infection.

Background and objectivesCognitive impairment is a common extrapulmonary comorbidity in COPD patients. The default mode network (DMN) plays a critical role in maintaining the normal activities of humans, and its function can be evaluated by resting state functional magnetic resonance imaging. The aim of this study was to investigate the correlations between cognition and function changes of the DMN in COPD patients.MethodsOne hundred and thirteen eligible participants including 30 control subjects and 83 COPD patients matched for demographic characteristics were recruited. All participants performed cognitive function tests and underwent resting state functional magnetic resonance imaging.ResultsThe total cognitive function scores of COPD patients were significantly different from those of control subjects (P<0.05) and worsened with the degree of airflow obstruction. The activated brain regions in the DMN of COPD patients were less than those of normal controls. Six activated brain regions in the DMN were found to develop significantly different functional connectivity (FC) values among the subjects. Meanwhile, the FC values of the left posterior cingulate cortex and left hippocampus correlated well with cognitive functions and pulmonary function.ConclusionCOPD patients have cognitive impairments that correlate well with disease severity. FC changes in activated brain regions in the DMN may predict cognitive impairment, and the left posterior cingulate cortex and left hippocampus may be important brain regions related to cognitive impairment in COPD patients.

NADPH oxidase 4 (Nox4) is an important source of reactive oxygen species (ROS) production, and its expression is increased in lipopolysaccharide- (LPS-) stimulated lung epithelial cells. Polymerase δ-interacting protein 2 (Poldip2) has been proved to bind Nox4 and participates in oxidative stress and inflammation. However, the role of Poldip2/Nox4 in LPS-induced oxidative stress and inflammation in lung epithelial cells remains unclear. Cell viability was measured via MTT assays. The expression of Poldip2, Nox4, heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2), AKT, and p-AKT was detected by Western blotting and/or immunofluorescence. Poldip2 and Nox4 interaction was analyzed via coimmunoprecipitation (Co-IP) assay. NADPH enzymatic activity and production of ROS, prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were assessed simultaneously. The small interfering RNA (siRNA) or plasmid targeting Nox4 was used to downregulate or upregulate Nox4, and the lentiviral vector encoding Poldip2 was used to downregulate or upregulate Poldip2. The present study demonstrated that LPS stimulation significantly increased the protein levels of Poldip2 and Nox4 and proved that Poldip2 interacted with Nox4 proved by Co-IP. Importantly, Poldip2 acted as an upstream regulator of Nox4. The increased expression of Nox4 and COX-2; NADPH enzymatic activity; production of ROS, PGE2, TNF-α, and IL-1β; and decreased HO-1 expression were significantly suppressed by lentiviral Poldip2 shRNA downregulation but were increased by lentiviral upregulation of Poldip2. Furthermore, inhibiting of PI3K-AKT signaling notably attenuated LPS-induced Poldip2/Nox4 activation. Our study demonstrated that Poldip2 mediates LPS-induced oxidative stress and inflammation via interaction with Nox4 and was regulated by the PI3K-AKT signaling. Targeting Poldip2 could be a beneficial therapeutic strategy for the treatment of ALI.

SARS-CoV-2 outbreak has attracted global attention. Verifying the presence of viral RNA is the gold standard for the diagnosis of COVID-19. However, RT-qPCR diagnosis often fails to catch infected patients, because of inconsistent swab sample collection. Here we report a case that showed 5 consecutive negative and 1 low-viral- dose RT-qPCR results during illness spanning over 20 days. Clinical symptoms suggest SARS-CoV-2 infection with typical ground glass like a lung in computed tomography. SARS-CoV-2 infection was serologically confirmed by the presence of anti-SARS-CoV-2 specific antibodies in patients' serum. Finally, a high level of protective IgG was produced after the patient recovered. Surprisingly, as a barber and a housewife staying at home for the first 2 weeks after the onset of illness, none of the close contacts were infected, showing a case of low viral load and low infectivity in this patient.