Fabrication of sac-like hydrogel membranes for replicating curved tissue barriers on chips.

Current organ-on-a-chip (OOC) systems cannot mimic in vivo tissue barriers that feature curved geometries and rhythmic movement. This is due to the lack of a relevant membrane that can reproduce the natural biochemical and physical properties of a basement membrane, especially the characteristic sac-like structure possessed by multiple tissue barriers. To address this challenge, a sac-like hydrogel membrane is fabricated here using a one-step simple methodology inspired by soap bubble formation. Di-acrylated Pluronic® F127 (F127-DA) is a hydrogel that exhibits excellent mechanical properties, stably withstanding rhythmic mechanical stretching and fluid flow for at least 24 h. Using this hydrogel to make a membrane, a complex lung-on-a-chip device is successfully constructed, effectively replicating the alveolar-capillary barrier and demonstrating cellular function under physiological respiratory conditions. This membrane offers a crucial platform for replicating sac-like tissue barriers.

Bronchoalveolar lavage fluid polymerase chain reaction for invasive pulmonary aspergillosis among high-risk patients: a diagnostic meta-analysis.

BACKGROUND: Polymerase chain reaction (PCR) assays are perceived to facilitate the diagnosis of fungal infections. However, due to lack of standardization, the value of bronchoalveolar lavage (BAL) fluid PCR in diagnosis of invasive pulmonary aspergillosis (IPA) remains unclear. METHODS: We conducted a systematic meta-analysis to evaluate the accuracy of BAL fluid PCR in IPA diagnosis among high-risk patients. All studies involving patients at risk for IPA were included. The sensitivity, specificity, positive and negative likelihood ratios of BAL fluid PCR were summarized for diagnosis of proven/probable IPA, or proven IPA only. Potential heterogeneity was assessed by subgroup analyses and meta-regression. RESULTS: Forty-one studies involving 5668 patients were analyzed. The summary sensitivity, specificity, positive and negative likelihood ratios of BAL fluid PCR for proven/probable IPA were 0.75 (95% CI = 0.67-0.81), 0.94 (95% CI = 0.90-0.96), 11.8 (95% CI = 7.7-18.1) and 0.27 (95% CI = 0.20-0.36), respectively. Whereas for proven IPA only, sensitivity and specificity were 0.91 (95% CI = 0.68-0.98) and 0.80 (95% CI = 0.74-0.85) in fourteen studies involving 2061 patients. Significant heterogeneity was present due to the underlying disease, antifungal treatment and differences in DNA extraction techniques and choice of PCR assay. Compared to patients with hematological malignancies (HM) and hematopoietic stem cell/solid organ transplantation (HSCT/SOT), sensitivity was higher in the population with disease such as chronic obstructive pulmonary disease, solid tumor, autoimmune disease with prolonged use of corticosteroids, etc. (0.88 vs. 0.68, P < 0.001), which was related to the concurrent use of antifungal prophylaxis among patients with HM and HSCT/SOT. CONCLUSION: BAL fluid PCR is a useful diagnostic tool for IPA in immunocompromised patients and is also effective for diagnosing IPA in patients without HM and HSCT/SOT. Furthermore, standard protocols for DNA extraction and PCR assays should be focused on to improve the diagnostic accuracy. Trial registration PROSPERO, registration number CRD42021239028.

Detection of Viruses by Multiplex Real-Time Polymerase Chain Reaction in Bronchoalveolar Lavage Fluid of Patients with Nonresponding Community-Acquired Pneumonia.

Background: Nonresponding pneumonia is responsible for the most mortality of community-acquired pneumonia (CAP). However, thus far, it is not clear whether viral infection plays an important role in the etiology of nonresponding CAP and whether there is a significant difference in the clinical characteristics between viral and nonviral nonresponding CAP. Methods: From 2016 to 2019, nonresponding CAP patients were retrospectively enrolled in our study. All patients received bronchoalveolar lavage (BAL) and virus detection in BAL fluid by multiplex real-time polymerase chain reaction (PCR), and clinical, laboratory, and radiographic data were collected. Results: A total of 43 patients were included. The median age was 62 years, and 65.1% of patients were male. Overall, 20 patients (46.5%) were identified with viral infection. Of these viruses, influenza virus (n = 8) and adenovirus (n = 7) were more frequently detected, and others included herpes simplex virus, human enterovirus, cytomegalovirus, human coronavirus 229E, rhinovirus, and parainfluenza virus. Compared with nonviral nonresponding CAP, only ground-glass opacity combined with consolidation was a more common imaging manifestation in viral nonresponding CAP. However, no obvious differences were found in clinical and laboratory findings between the presence and the absence of viral infections. Conclusions: Viral infections were particularly frequent in adults with nonresponding CAP. The ground-glass opacity combined with consolidation was a specific imaging manifestation for viral nonresponding CAP, while the clinical and laboratory data showed no obvious differences between viral and nonviral nonresponding CAP.

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma.

BACKGROUND: It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features. METHODS: 30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry. RESULTS: There were no significant differences in atopy and FEV1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls. CONCLUSIONS: Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registration http://www.chictr.org.cn (ChiCTR-OOC-15006221).

Effectiveness of lung ultrasonography for diagnosis of pneumonia in adults: a systematic review and meta-analysis.

BACKGROUND: Pneumonia is usually presented as a forgotten killer, and an early diagnosis could largely improve the prognostic outcomes. Lung ultrasound (LUS) has been universally applied in evaluating multiple pulmonary diseases including pneumonia. However, the diagnosis accuracy of LUS for pneumonia in adults is still uncertain. Hence, we performed a systematic review of the current literature to assess the diagnosis accuracy of LUS for pneumonia in adults. METHODS: PubMed and EMBASE were searched for clinical trials that assessed the detection accuracy of LUS for pneumonia in adult patients. We extracted descriptive and quantitative information from eligible studies that met strict inclusion criteria and calculated pooled sensitivity, specificity and pooled diagnostic likelihood ratios (LR). Summary receiver operating characteristic (sROC) curve was used to assess the overall performance of LUS-based assays. RESULTS: We reviewed 1,072 articles and selected 38 for detailed review. 14 articles containing 1,911 participants met all inclusion criteria and were included in the final analysis. LUS exhibited a pooled sensitivity of 0.904 (0.884-0.921), specificity of 0.884 (0.861-0.904), positive LR of 6.6 (3.7-11.7), negative LR of 0.08 (0.04-0.19) and the area under curve (AUC) was 0.9611. Interestingly, when CT alone, CT combined with clinical presentations, and microbiology was set as the gold standard of pneumonia respectively, LUS demonstrated a pooled sensitivity of 90.9%, 95.0%, 53.3%, and a pooled specificity of 89.7%, 91.3% and 67.9%. In extension, we compared the diagnostic efficiency of LUS for pneumonia with chest X-ray (CXR) in 1,343 patients. The AUC for LUS and CXR was 0.972 and 0.867 respectively and the Z statistic of the two sROC curves was 2.31. CONCLUSIONS: Our study indicated that LUS is a robust diagnostic tool for pneumonia with high accuracy. Utilization of LUS would facilitate the estimation of pneumonia at bedside.

Nuclear erythroid 2 p45-related factor-2 Nrf2 ameliorates cigarette smoking-induced mucus overproduction in airway epithelium and mouse lungs.

BACKGROUND AND OBJECTIVE: Nuclear erythroid 2 p45-related factor-2 (Nrf2) is known to play important roles in airway disorders, whereas little has been investigated about its direct role in airway mucus hypersecretion. The aim of this study is to determine whether this factor could protect pulmonary epithelium and mouse airway from cigarette-induced mucus overproduction. METHODS: Using genetic approaches, the role of Nrf2 on cigarette smoking extracts (CSE) induced MUC5AC expression was investigated in lung A549 cells. Nrf2 deficiency mice were smoked for various periods, and the airway inflammation and mucus production was characterized. RESULTS: Acute smoking exposure induced expression of MUC5AC and Nrf2 in both A549 cells and mouse lungs. Genetic ablation of Nrf2 augmented, whereas overexpression of this molecule ameliorated CSE-induced expression of MUC5AC. Nrf2 knockout mice, after exposure to cigarette smoking, displayed enhanced airway inflammation and mucus production. CONCLUSION: Nrf2 negatively regulated smoking-induced mucus production in vitro and in vivo, suggesting therapeutic potentials of this factor in airway diseases with hypersecreted mucus.

Astragalus Membranaceus prevents airway hyperreactivity in mice related to Th2 response inhibition.

AIM OF THE STUDY: Asthma is recognized as a common pulmonary disease throughout the world. To date, there has been a growing interest in herbal products in Traditional Chinese Medicine, which is considered to be effective to treat asthma. A Chinese herb Astragalus Membranaceus (AM) was found useful in treating allergic diseases. The purpose of this study is to determine whether this herbal injection could suppress allergic-induced AHR and mucus hypersecretion in allergic mice. MATERIALS AND METHODS: A mouse model of chronic asthma was used to investigate AM injection on the airway lesions in compared with glucocorticoids. The study was conducted on mice sensitized and challenged with ovalbumin and the whole body plethsmography was performed to assess AHR. The bronchoalveolar lavage (BAL), histopathology were examined. RESULTS: We found 28-day AM administration significantly decreased inflammatory infiltration and mucus secretion in the lung tissues of allergic mice. 28-day AM administration enhanced Ova-induced decreased IFN-gamma, and the Ova-induced elevations of IL-5 and IL-13 in BALF were prevented by 28-day injection. We also showed 28-day AM injection markedly suppressed increased AHR in allergic mice. CONCLUSIONS: Our results indicate Astragalus Membranaceus has a potential role in treating allergic asthma.