Albumin level as an independent predictive factor for adverse outcomes in COVID-19 patients: a retrospective cohort study.

INTRODUCTION: Research on the association between albumin (ALB) level and clinical outcomes of coronavirus disease 2019 (COVID-19) are limited. This study aimed to investigate the relationship between albumin level at the time of admission and adverse outcomes in patients with COVID-19. METHODOLOGY: This was a retrospective cohort study with 199 COVID-19 patients from five designated hospitals in Fujian Province who were enrolled between 22 January and 27 February, 2020. Clinical characteristics and laboratory values at the time of admission were collected. Adverse outcomes were defined as meeting at least one of the following criteria: development of acute respiratory distress syndrome (ARDS), respiratory failure, shock, multiple organ failure (MOF), intensive care unit (ICU) admission and in-hospital mortality event. The univariate and multivariate linear regression models and generalized additive models (GAM) were used to analyze the relationship between ALB and adverse outcomes. RESULTS: A non-linear relationship with an inflection point of 32.6g/L was detected between ALB and adverse outcomes after adjusting for potential confounders. The odds ratio and the confidence intervals on the left and right sides of the inflection point were 0.204 (0.061-0.681) and 0.908 (0.686-1.203), respectively. This suggested that ALB was negatively correlated with adverse outcomes when ALB was less than 32.6 g/L, and for every 1 unit increase in ALB, the risk of adverse outcomes was reduced by 79.6%. CONCLUSIONS: The relationship between ALB and adverse outcomes of COVID-19 is non-linear. ALB level is an independent predictive factor for adverse outcomes in COVID-19 patients.

Lack of STAT6 enhances murine acute lung injury through NLRP3/p38 MAPK signaling pathway in macrophages.

BACKGROUND: Signal transducer and activator of transcription 6 (STAT6) is an intracelluar transcriotion factor and NLRP3 (Nod-like receptor containing a pyrin domain 3) is a component of NLRP3 inflammasome in pyroptotic cells. There was increased activation of STAT6 and expression of NLRP3 in mice with murine acute lung injury (ALI). However, it is unknown their roles in the development of murine ALI. We in this study, investigated the effects of STAT6 signaling on murine ALI and pyroptosis in STAT6 knock-out (KO) mice and macrophages. RESULTS: STAT6 was activated in the lung tissues of mice 2 days after intratracheal treatmemt with 5 mg/kg LPS. Lack of STAT6 expression in KO mice induced more severe lung inflammation, associated with elevated neutrophil influx and expression of TNF-alpha, IL-6 and IL-1beta in the inflamed lung tissues. In addition, the expression of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD), p-p38 MAPK (p38 mitogen-activated protein kinase) and ratio of LC3-II/I (microtubule-associated protein-1 light chain-3) was increased, accompanied with the increased polarization of Siglec-F(-) subtype macrophages in KO mice with ALI. Further studies in bone marrow-derived macrophages (BMDMs) revealed that lack of STAT6 increased the expression of NLRP3 and p-p38 MAPK, in association with elevated expression of TNF-alpha, IL-1beta and Calreticulin in LPS-treated KO BMDMs. CONCLUSIONS: Lack of STAT6 exacerbated murine ALI through improving the expression of NLRP3 and activation of p38 MAPK in macrophages. STAT6 has an immune suppressive role in the development of ALI and would be a promising therapeutic target in the treatment of ALI and possibly among patients with acute respiratory distress syndrome (ARDS).

Resveratrol attenuates inflammation and apoptosis through alleviating endoplasmic reticulum stress via Akt/mTOR pathway in fungus-induced allergic airways inflammation.

BACKGROUND: Resveratrol has shown pleiotropic effects against inflammation and oxidative response. The present study aimed to investigate the effects and mechanisms of resveratrol on fungus-induced allergic airway inflammation. METHODS: Female BALB/c mice were injected intraperitoneally with Aspergillus fumigatus (Af) extract emulsified with aluminum on day 0 and 7 and intranasally challenged with Af extracts on day 14 and 15. Resveratrol or dexamethasone or a vehicle was injected intraperitoneally 1 h before each challenge. Mice were sacrificed for serum, bronchoalveolar lavage fluid (BALF), and lungs 24 h after the last challenge. The control group was administered with saline. BEAS-2B was used for the experiments in vitro that Af-exposed airway epithelial cells. RESULTS: Resveratrol and dexamethasone attenuated the airway inflammation and eosinophilia, and reduced not only the production of IL-4, IL-5, and IL-13 in the BALF and lung tissues but also the mRNA levels of lung IL-6, TNF-α, and TGF-ß induced by Af challenge (P < 0.05). Furthermore, Af-induced lung endoplasmic reticulum (ER) stress-related proteins PERK, CHOP, and GRP78 and the apoptosis markers including cleaved caspase-3 and cleaved caspase-7 were both suppressed significantly by resveratrol (P < 0.05). In vitro, activation of ER stress and the Akt/mTOR pathway in Af-exposed BEAS-2B cells were effectively ameliorated by resveratrol. Inhibition of the Akt/mTOR pathway using LY294002 suppressed the ER stress while ER stress inhibitor 4-PBA decreased the apoptosis in Af-exposed BEAS-2B cells. CONCLUSIONS: Our findings collectively revealed that resveratrol alleviated the Af-exposed allergic inflammation and apoptosis through inhibiting ER stress via Akt/mTOR pathway, exerting therapeutic effects on the fungus-induced allergic lung disorder.

Clinical characteristics of allergic bronchopulmonary aspergillosis in patients with and without bronchiectasis.

OBJECTIVE: Allergic bronchopulmonary aspergillosis (ABPA) is classified radiologically as serologic ABPA (ABPA-S) or ABPA with central bronchiectasis (ABPA-CB). This retrospective case series study aimed to describe and compare the clinical characteristics of both forms of ABPA. METHODS: Patients with ABPA treated in the hospital between February 2011 and June 2019 were enrolled and were divided into ABPA-S and ABPA-CB groups based on whether their cases were complicated with central bronchiectasis. Demographic data, symptoms, laboratory values, comorbidities, and image findings were collected. ABPA-S patients were followed up retrospectively through medical records. RESULTS: Ninety-three (93) patients were enrolled, including 74 ABPA-CB patients and 19 ABPA-S patients. The most common predisposing condition was asthma (36.6%), with a median course of 30 years (IQR 13-42.5) prior to ABPA diagnosis. Patients of 54.8% had been misdiagnosed, with ABPA-S more likely than ABPA-CB to have been misdiagnosed as asthma (p < 0.01). Obstructive ventilation dysfunction and mixed ventilation dysfunction were found in 21 patients (22.6%) and 16 patients (17.2%), respectively. Compared with ABPA-S, ABPA-CB had a higher median blood eosinophil count (880 vs. 700 cells/µl), serum IgE (2957 vs. 2616 IU/ml), and Aspergillus fumigatus specific-IgE (20.6 vs. 7.31 kUA/L), although these findings were not statistically significant. Three ABPA-S patients developed bronchiectasis during follow-up and experienced relapses more than twice. CONCLUSIONS: Our findings suggested that the clinical characteristics between ABPA-CB and ABPA-S were mostly similar. ABPA-S had a relatively lower immunological activity level than ABPA-CB but was still immunologically active and could develop bronchiectasis.

Ameliorative effects of eosinophil deficiency on immune response, endoplasmic reticulum stress, apoptosis, and autophagy in fungus-induced allergic lung inflammation.

BACKGROUND: Respiratory fungal exposure is known to be associated with various allergic pulmonary disorders. Eosinophils have been implicated in tissue homeostasis of allergic inflammation as both destructive effector cells and immune regulators. What contributions eosinophils have in Aspergillus fumigatus (Af)-induced allergic lung inflammation is worthy of investigating. METHODS: We established the Af-exposed animal asthmatic model using eosinophil-deficient mice, ∆dblGATA1 mice. Airway inflammation was assessed by histopathological examination and total cell count of bronchoalveolar lavage fluid (BALF). The protein level in BALF and lung mRNA level of type 2 cytokines IL-4, IL-5, and IL-13 were detected by ELISA and qRT-PCR. We further studied the involvement of endoplasmic reticulum (ER) stress, apoptosis, and autophagy by western blots, qRT-PCR, immunofluorescence, TUNEL, or immunohistochemistry. RNA-Seq analysis was utilized to analyze the whole transcriptome of Af-exposed ∆dblGATA1 mice. RESULTS: Hematoxylin and eosin (HE) staining and periodic acid-Schiff staining (PAS) showed that airway inflammation and mucus production were alleviated in Af-challenged ∆dblGATA1 mice compared with wild-type controls. The protein and mRNA expressions of IL-4, IL-5, and IL-13 were reduced in the BALF and lung tissues in Af-exposed ∆dblGATA1 mice. The results demonstrated that the significantly increased ER stress markers (GRP78 and CHOP) and apoptosis executioner caspase proteases (cleaved caspase-3 and cleaved caspase-7) in Af-exposed wild-type mice were all downregulated remarkably in the lungs of ∆dblGATA1 mice with Af challenge. In addition, the lung autophagy in Af-exposed ∆dblGATA1 mice was found elevated partially, manifesting as higher expression of LC3-II/LC3-I and beclin1, lower p62, and downregulated Akt/mTOR pathway compared with Af-exposed wild-type mice. Additionally, lung RNA-seq analysis of Af-exposed ∆dblGATA1 mice showed that biological processes about chemotaxis of lymphocytes, neutrophils, or eosinophils were enriched but without statistical significance. CONCLUSIONS: In summary, eosinophils play an essential role in the pathogenesis of Af-exposed allergic lung inflammation, whose deficiency may have relation to the attenuation of type 2 immune response, alleviation of ER stress and apoptosis, and increase of autophagy. These findings suggest that anti-eosinophils therapy may provide a promising direction for fungal-induced allergic pulmonary diseases.

Pulmonary alveolar proteinosis: A single center retrospective analysis of 14 cases

Introduction: Pulmonary alveolar proteinosis (PAP) is a rare lung disease, characterized by abnormal alveolar accumulation of enlarged foamy macrophages and periodic acid-Schiff (PAS)-positive materials. Knowledge of the disease characteristics is still lacking.ObjectiveTo help clinicians gain a better understanding of this rare disease.MethodsWe undertook a retrospective analysis of 14 adult patients with PAP, treated in Zhongshan Hospital, Fudan University.ResultsSerum lactate dehydrogenase (LDH) was correlated with the arterial partial pressure of oxygen (PaO2) and diffusion capacity for carbon monoxide (DLCO). Transbronchial lung biopsy (TBLB) established a definitive diagnosis for a positive rate of 100%. The patients underwent whole lung lavage (WLL) and exhibited varying degrees of remission. The patients with mild symptoms received only supportive care and observation, and remained stable during follow-up.ConclusionLDH may correlate with disease severity. Bronchoscopy is sufficiently sensitive for a definite diagnosis. Conventional bilateral whole lung lavage proved a reliable treatment for indicated patients, but selective unilateral lung lavage or observation may be a rational choice in certain patients. (AU)

Introducción: La proteinosis alveolar pulmonar (PAP) es una enfermedad pulmonar rara, caracterizada por una acumulación alveolar anormal de macrófagos espumosos agrandados y materiales periódicos de ácido-Schiff (PAS). Todavía se carece de la cognición de las características de la enfermedad.ObjetivoPara ayudar a los médicos a comprender mejor esta enfermedad rara.MétodosRealizamos un análisis retrospectivo de 14 pacientes adultos con PAP, tratados en el Hospital Zhongshan, Universidad de Fudan.ResultadosLa lactato deshidrogenasa (LDH) sérica se correlacionó con la presión parcial de oxígeno arterial (PaO2) y la capacidad de difusión del monóxido de carbono (DLCO). La biopsia pulmonar transbronquial (TBLB) que establece un diagnóstico definitivo para una tasa positiva del 100%. Los pacientes recibieron lavado pulmonar completo (WLL) y exhibieron diferentes grados de remisión. Los pacientes con síntomas leves aceptaron solo atención de apoyo y observaciones, se mantuvieron estables durante el seguimiento.ConclusiónLa LDH puede correlacionarse con la gravedad de la enfermedad. La broncoscopia es suficientemente sensible para un diagnóstico definitivo. El lavado pulmonar bilateral convencional demostró ser un tratamiento confiable para los pacientes indicados, pero el lavado selectivo unilateral u observación pulmonar puede ser una opción racional en ciertos pacientes. (AU)

Reversible bronchial dilatation in adults.

Bronchiectasis is characterized by the destruction of bronchial wall and persistent irreversible bronchiectasis due to respiratory infection and bronchial obstruction. Reversible bronchiectasis is rarely reported in adults. The study aims to evaluate dynamic changes in chest computed tomography (CT) findings and relevant factors affecting improvement or reversal of bronchiectasis. A total of 239 patients with bronchiectasis admitted to our hospital from January 2009 to December 2019 were retrospectively analyzed. 23 patients (group A) with bronchiectasis reversion or improvement confirmed by chest CT were matched with patients in group B according to gender and age (difference <5 years). 23 patients (group B) with bronchiectasis progression or no obvious improvement confirmed by chest CT were selected from the remaining patients. The clinical features and imaging findings of the two groups were compared. The duration of disease in group A was less than that in group B, and the stable period was longer (p < 0.05). There was no significant difference in other clinical features between the two groups. In contrast to the traditional concept of "Bronchiectasis", our results suggested that some adult bronchiectasis can be improved and completely radiologically reversed.

Pulmonary alveolar proteinosis: A single center retrospective analysis of 14 cases.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare lung disease, characterized by abnormal alveolar accumulation of enlarged foamy macrophages and periodic acid-Schiff (PAS)-positive materials. Knowledge of the disease characteristics is still lacking. OBJECTIVE: To help clinicians gain a better understanding of this rare disease. METHODS: We undertook a retrospective analysis of 14 adult patients with PAP, treated in Zhongshan Hospital, Fudan University. RESULTS: Serum lactate dehydrogenase (LDH) was correlated with the arterial partial pressure of oxygen (PaO2) and diffusion capacity for carbon monoxide (DLCO). Transbronchial lung biopsy (TBLB) established a definitive diagnosis for a positive rate of 100%. The patients underwent whole lung lavage (WLL) and exhibited varying degrees of remission. The patients with mild symptoms received only supportive care and observation, and remained stable during follow-up. CONCLUSION: LDH may correlate with disease severity. Bronchoscopy is sufficiently sensitive for a definite diagnosis. Conventional bilateral whole lung lavage proved a reliable treatment for indicated patients, but selective unilateral lung lavage or observation may be a rational choice in certain patients.

Airway microbiota is associated with the severity of non-CF bronchiectasis.

BACKGROUND: Airway microbiota are associated with several chronic respiratory diseases. However, limited studies examined microbiota in non-cystic fibrosis (non-CF) bronchiectasis, especially its relationship with severity and immunology. OBJECTIVES: We characterized the microbiota of patients with different severities of bronchiectasis and examined the correlation between microbiota and the immunological indices. MATERIALS AND METHODS: The microbiota of 63 sputum samples from 40 patients with bronchiectasis were analyzed by 16S rRNA gene sequencing. Blood tests and related immunological indices were detected. RESULTS: According to the baseline data of patients with bronchiectasis, we found that more severe bronchiectasis was accompanied by lower prealbumin levels. The 16S rRNA sequencing analyses demonstrated that Pseudomonas-dominated microbiota produced lower levels of interleukin-4 (IL-4) and transforming growth factor-ß (TGF-ß) compared to other-dominated microbiota. The airway microbiota of patients with mild bronchiectasis clustered apart from those of patients with severe bronchiectasis, which correlated with IL-4 and other clinical indices. CONCLUSION: There are differences in the airway microbiota between patients with mild and severe bronchiectasis. The airway microbiota was related to some clinical indices that represent effects on the immune system.

Clinical characteristics of 199 discharged patients with COVID-19 in Fujian Province: A multicenter retrospective study between January 22nd and February 27th, 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has quickly spread throughout the country and the world since first broke out in Wuhan, China. The outbreak that started from January 22, 2020, in Fujian Province has been controlled as the number of indigenous cases has not increased since March. We aimed to describe the clinical characteristics of patients with COVID-19 in Fujian Province, China. METHODS: In this retrospective, multicenter study, we collected and analyzed the epidemiological, clinical, and laboratory data of all cases confirmed by nucleic acid tests in five designated hospitals in Fujian Province between January 22 and February 27, 2020. All patients were followed up until discharge. COVID-19 severity was classified as mild, moderate, severe, or critical. RESULTS: Of 199 discharged patients with COVID-19, 105 patients were male, with a median age of 46.3 years, and 17 patients were severe, and 5 patients were critical on admission. Hypertension and diabetes were the most common comorbidities. The symptoms at illness onset were mainly fever (76.4%), cough (60.8%), and myalgia or fatigue (27.6%). A total of 96.5% of patients had abnormal imaging findings on chest computed tomography. Lymphopenia (37.2%) and hypoxemia (13.6%) were observed. Acute respiratory distress syndrome and respiratory failure occurred in 9 patients (4.5%) and 8 patients (4.0%) respectively. One patient died and the others were cured and discharged with the median hospital stay of 19 days. Old age was negatively correlated with lymphocyte count (r = - 0.296, p < 0.001) and oxygenation index (r = - 0.263, p = 0.001). Bivariate regression analysis revealed that old age (≥ 75 years), hypertension, diabetes, and lymphopenia were correlated with the severity of COVID-19. CONCLUSIONS: Patients in Fujian Province were mostly nonsevere cases with mild or moderate symptoms, and had a lower mortality than patients in Wuhan (4.3%-15%). Older age, hypertension, diabetes, and lymphopenia were risk factors for severity of COVID-19.

Induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNß from pyroptotic macrophages.

Mesenchymal stem cells (MSCs) have been used in cell-based therapies for a variety of disorders. Some factors such as inflammatory mediators in the diseased area might damage the survival of MSCs and affect their efficacy. Pyroptosis is a form of programmed necrosis as a response for immune cells to cytosolic pathogenic stimuli. Whether MSCs develop pyroptosis under pathological stimulation, its underlying mechanism and biological significance are still unclear. Here, we found that LPS, flagellin, dsDNA, nigericin (NIG), or LPS combined with nigericin (LPS/NIG) could not induce pyroptosis in adipose-tissue-derived mesenchymal stem cells (ASCs). However, when applied the culture media collected from LPS/NIG-induced pyroptotic bone marrow-derived macrophages (BMDMs) to incubate ASCs, ASCs developed pyroptosis. Inhibition of caspases or deletion of Caspase-1/11 in ASCs did not affect the pyroptotic macrophage media-triggered ASC pyroptosis while ablation of Caspase-1/11 abolished BMDM pyroptosis induced by LPS/NIG. Media collected from LPS/NIG stimulated Gsdmd-/- or Caspase-1/11-/- BMDMs could not induce pyroptosis of ASCs. In addition, RNA-seq analysis showed that interferon (IFN)-stimulated genes were upregulated in pyroptotic ASCs. Adding IFNß could boost LPS/NIG stimulated BMDM media-induced ASC pyroptosis. Surprisingly, the pyroptotic ASCs had a lower bactericidal ability to P. Aeruginosa. Taken together, induction of ASC pyroptosis requires gasdermin D or caspase-1/11-dependent mediators and IFNß from pyroptotic macrophages.

The association between serum albumin/prealbumin level and disease severity in non-CF bronchiectasis.

Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disease that can lead to malnutrition. Serum prealbumin and albumin level are related to inflammatory and nutritional status. Thus, we aimed to confirm our hypothesis that low serum albumin and prealbumin level, as well as body mass index (BMI), is correlated to severe non-CF bronchiectasis. We conducted a retrospective cross-sectional study of 128 patients, including 75 patients with prealbumin test and 79 patients with albumin test. Detailed medical history was recorded, including pulmonary function tests and high-resolution computed tomography. bronchiectasis severity index (BSI) and FACED scores were calculated. Leicester Cough Questionnaire, Quality of Life Questionnaire-Bronchiectasis, chronic obstructive pulmonary disease (COPD) assessment test and Patient Health Questionnaire-9 questionnaires were used to assess patients' clinical symptoms. Correlation analysis showed that BSI score was more correlated to patients' clinical symptoms than FACED. Thus, patients were divided into three groups of different severity based on BSI score. Albumin, prealbumin and BMI showed a significant difference between three groups. Correlation and multivariable linear regression analysis showed that serum albumin and prealbumin level were correlated to BSI, FACED and questionnaires. The analysis between three indices and PFT/high-resolution computed tomography (HRCT) showed that prealbumin, albumin and BMI could reflect the PFT and modified Reiff score in non-CF bronchiectasis. In conclusion, BMI, albumin and prealbumin showed a significant correlation with the BSI, FACED, as well as patients' clinical symptoms. Among them, serum albumin was the indicator most strongly associated with the BSI and questionnaires, while prealbumin could better reflect lung function decline and radiological severity.

Clinical characteristics of allergic bronchopulmonary aspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease caused by a hypersensitivity reaction to Aspergillus colony in the airways. Due to the diversity of disease manifestations and physicians' incomplete knowledge of ABPA, patients with ABPA are often misdiagnosed and given poor prognosis. OBJECTIVES: To investigate the clinical characteristics, treatment and prognosis status among patients with ABPA. METHODS: We retrospectively analyzed 75 patients diagnosed as ABPA in Zhongshan Hospital, Fudan University between October 2008 and June 2018. RESULTS: Among 75 patients, 28% had asthma as the predisposing condition and 69% suffered from misdiagnosis before ABPA diagnosis was made, among which 21% were misdiagnosed as tuberculosis. About 34% of patients had eosinophil count below 500 cells/µL and 25% had total serum IgE level <1000 IU/mL. Nearly half of patients did not meet the diagnostic criteria of ABPA and all the patients who overlapped with invasive pulmonary aspergillosis (IPA) did not meet the diagnostic criteria of standard ABPA. Patients who did not fully meet the diagnostic criteria were more likely treated with inhaled corticosteroids (ICS) and antibiotics, but more difficult to attain response and remission and easier to develop advanced ABPA. CONCLUSIONS: This study demonstrates an unsatisfactory situation of diagnosis, treatment and prognosis of ABPA, including a high misdiagnosis rate, uncertainty in the diagnosis of ABPA, lack of standardization in treatment and relatively poor prognosis.

Pulmonary cryptococcosis coexisting with adenocarcinoma: a case report and review of the literature.

BACKGROUND: Pulmonary cryptococcosis is a common fungal infection frequently seen in immunocompromised patients. Owing to its nonspecific clinical and radiographic features, the differential diagnosis with secondary tuberculosis, malignant tumor, and bacterial pneumonia is sometimes difficult. Many case reports have focused on misdiagnosis of pulmonary cryptococcosis as a malignant tumor. But to the best of our knowledge, the coexistence of pulmonary cryptococcosis and malignant tumor is rarely presented. CASE PRESENTATION: A 52-year-old immunocompetent Han Chinese woman was presented to our emergency department complaining of headache and vomiting accompanied by postural changes. She was diagnosed with pulmonary cryptococcosis according to results of laboratory tests, computed tomography, and percutaneous lung biopsy. Owing to the poor therapeutic effects of 6-month fluconazole treatment, she underwent a second percutaneous lung biopsy and was diagnosed with pulmonary cryptococcosis coexisting with adenocarcinoma. Delayed treatment of malignant tumor resulted in lymph node metastasis, higher pathologic stage, and probably poorer prognosis. CONCLUSIONS: Our patient's case serves as a reminder not to misdiagnose pulmonary cryptococcosis coexisting with adenocarcinoma.

Overexpression of Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin in Dendritic Cells Protecting against Aspergillosis.

BACKGROUND: Dendritic cells (DCs) play an important role in host defense against pathogen infection. DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (SIGN) is a group II C-type lectin receptor and specifically expressed on the surface of DCs. This study aimed to determine whether DC-SIGN affects intracellular signaling activation, Th1/Th2 imbalance and aspergillus immune evasion in aspergillus infection, and explore the application of DC-SIGN-modified DCs in immunotherapy. METHODS: DCs were first obtained from the mononuclear cells of peripheral blood. The interferon (IFN)-γ and dexamethasone (Dex) were used to stimulate DCs. The expression of DC-SIGN, Th1 and Th2 cytokines, and the capacity of DCs in stimulating T cells proliferation and phagocytosis, and nuclear factor (NF)-κB activation were analyzed. In addition, adenovirus expression vector Ad-DC-SIGN was generated to transfect DCs. Mannan was used to block DC-SIGN signaling for confirming the involvement of DC-SIGN function in Aspergillus fumigatus (Af)-induced DCs maturation. The unpaired, two-tailed Student's t-test was used in the comparisons between two groups. RESULTS: Exogenous IFN-γ could activate Af-induced DCs and promote the Th0 cells toward Th1 profile (interleukin [IL]-12 in IFN-γ/Af group: 50.96 ± 4.38 pg/ml; control/Af group: 29.70 ± 2.00 pg/ml, t = 10.815, P < 0.001). On the other hand, Dex inhibited the secretion of Th2 cytokines (IL-10 in Dex/Af group: 5.27 ± 0.85 pg/ml; control/Af group: 15.14 ± 1.40 pg/ml, t = 14.761, P < 0.001)), and successfully caused immunosuppression. After transfection with Ad-DC-SIGN, DCs have improved phagocytosis (phagocytosis rates in Ad-DC-SIGN group: 74.0% ± 3.4%; control group: 64.7% ± 6.8%, t = 3.104, P = 0.013). There was more Th1 cytokine secreted in the Af-induced DC-SIGN modified DCs (IL-12 in Ad-DC-SIGN/Af group: 471.98 ± 166.31 pg/ml; control/Af group: 33.35 ± 5.98 pg/ml, t = 6.456, P = 0.001), correlated to the enhanced NF-κB activation. CONCLUSION: Overexpressing DC-SIGN in DCs had a protective function on aspergillosis.

Pulmonary alveolar proteinosis with peripheral adenocarcinom.

Background: Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease classified into congenital form, autoimmune form and secondary form. Secondary PAP is caused by underlying conditions including solid malignancies. Few cases reported PAP associated with lung cancers. Objective: To show the clinical features of PAP with adenocarcinom, tried to seek for possible mechanism to explain whole clinical course. Methods: Reported a case of PAP associated with lung adenocarcinom, and also reviewed the relevant literature on PAP. Results: The patient suffered from intermittent cough, fever, shortness of breath, thoracalgia or hemoptysis. Blood gas analysis showed hyoxemia. Spirometric abnormality is mildly restrictive defect. High-resolution computed tomography (HRCT) showed patchy, ground-glass opacities with interlobular septal thickening called as "crazy-paving" pattern. Positron emission tomography/computed tomography (PET/CT) revealed a nodule with characteristics of lobulation and spiculation in the right lung apex section and diffuse consolidation shadow spreading over rest of lung field. Bronchoalveolar lavage fluid (BALF) showed a large amount of amorphous red-dyed materials and a few alveolar macrophages scattered in endoalveolar space with PAS positive. Transbronchial lung biopsy found adenocarcinoma. Wedge resection with mediastinal lymphnode and then 2 cycles of postoperative chemotherapy was carried out. No ground-glass opacities were found in his chest CT pictures in the next nine months. This result may support the theory that lung cancer cells cause quantitative or functional damage to alveolar macrophages, which trend to secondary PAP. Conclusions: The patient had typical clinical features of PAP. PAP may be secondary to lung cancer. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 390-394).

The Expression of Dectin-1, Irak1 and Rip2 During the Host Response to Aspergillus fumigatus.

BACKGROUND: C-type lectin receptors (CLRs), Toll-like receptors (TLRs), and Nod-like receptors (NLRs) have the ability to recognize Aspergillus fumigatus (A. fumigates) and induce innate immune response. Dectin-1 is a well-described CLR, while interleukin-1 receptor-associated kinase 1 (Irak1) and receptor-interacting protein 2 (Rip2) are pivotal adaptor proteins of TLRs and NLRs signaling pathways, respectively. OBJECTIVES: Our primary aim is to elucidate whether Dectin-1 regulates the expression of Irak1 and Rip2, and confirm that CLRs, TLRs, and NLRs pathways act synergistically in response to A. fumigatus infection. METHODS: Pulmonary infection mouse models were established. Myeloid cells were differentiated in cell culture and examined by inverted microscopy, flow cytometry, and scanning electron microscopy. The relative mRNA levels were determined by qRT-PCR. The protein expression levels were determined by immunohistochemistry and Western blot. RESULTS: The expression of Dectin-1, Irak1, Rip2, and phosphorylation level of nuclear factor (NF)-κB p65 were induced by conidia in immunocompetent mice, while their expression and phosphorylation level were inhibited in immunocompromised mice after the administration of conidia. Conidia increased the expression of Dectin-1, Irak1, and Rip2 in myeloid cells, while Dectin-1 silencing significantly reduced their expression. CONCLUSION: Our findings demonstrate that Dectin-1, Irak1, and Rip2 are involved in response to A. fumigatus infection. Dectin-1 modulates the expression of Irak1 and Rip2. Additionally, these three signaling pathways are interconnected, and CLRs pathway plays a dominant role against A. fumigatus invasion.

Analysis of the clinical features of invasive bronchopulmonary aspergillosis.

INTRODUCTION: Early diagnosis of invasive bronchopulmonary aspergillosis (IBPA) is difficult, so the mortality rate is high. OBJECTIVE: To discuss the clinical features of IBPA. METHODS: We retrospectively analyzed the clinical features, imaging findings, laboratory test, diagnosis and treatment of 115 patients with IBPA diagnosed from October 2004 to June 2013 in Zhongshan Hospital, Fudan University. RESULTS: The main clinical manifestations were cough in 58 patients (50.4%), expectoration in 37 patients (32.2%), fever in 18 patients (15.7%), shortness of breath in 26 patients (22.6%), hemoptysis in 26 patients (22.6%) and chest pain in 7 patients (6.0%). The main CT findings were nodules in 35 patients (30.4%), consolidation shadows or patchy shadows in 62 patients (53.9%) and cavity in 14 patients (12.2%). Percutaneous pulmonary biopsy was conducted in 25 patients (21.7%), TBLB in 58 patients (50.4%) and thoracoscopic surgery in 32 patients (27.8%). The positive rate of GM test was 73.5% (72/98). Thirty patients who received lobectomy were followed up for 1-3 years. Fifty-five patients who received monotherapy with antifungal agents were followed up for 1-3 years, and 12 patients were healed. The lesions for 23 patients were obviously absorbed, 10 patients had aggravation and two patients died. CONCLUSIONS: The clinical manifestations of IBPA were unspecific. The main symptoms were cough and expectorate. Patients with different immunologic function had different imaging findings. The halo sign and new moon sign for diagnosis was not as common as reported. Interventional therapy under bronchoscope is very important for patients with ATB.

Pulmonary Aspergillus Overlap Syndromes.

BACKGROUND: Broadly, there are three main categories in pulmonary aspergillosis: chronic forms of aspergillosis; allergic bronchopulmonary aspergillosis; and invasive aspergillosis (IPA). IPA has been further subdivided into angioinvasive and airway-invasive aspergillosis. Aspergillus overlap syndromes is defined as the occurrence of more than one form aspergillus disease in a single individual. OBJECTIVES: To help clinicians correctly deal with AOS. METHODS: Retrospectively study the clinical findings of nine patients presenting with AOS. RESULTS: Four cases were diagnosed as angioinvasive aspergillosis complicated with ABPA, three cases as IPA overlap aspergilloma, and two cases as ABPA with AWIA. All the patients presented with cough and expectoration. In three patients with IPA overlap aspergilloma, two had hemoptysis, two had wheezing and fever. All of patients with IPA overlap ABPA had wheezing, dyspnea, and fever, three had sputum plugs, two had hemoptysis, and five patients had mucopurulent discharge and rhonchi in auscultation. Their total IgE ranged from 129 to 2124 IU/ml (676.5 ± 557.33 IU/ml). Fungal culture in sputum showed A. Fumigatus in three patients. All the six patients with IPA overlap ABPA applied steroid therapy and antifungal therapy. Three of them received two or more antifungal drugs successively, and three received combinational therapy. All the patients improved except one diagnosed ABPA overlap IPA. CONCLUSIONS: Clinical manifestation of AOS is not typical. Poor first-line therapeutic effects and complicated diagnosis criteria require clinicians to be aware of AOS when facing patients with aspergillosis.

A randomized, open, multicenter clinical study on the short course of intravenous infusion of 750 mg of levofloxacin and the sequential standard course of intravenous infusion/oral administration of 500 mg of levofloxacin for treatment of community-acquired pneumonia.

BACKGROUND: To compare 5-day regimen of levofloxacin 750 mg IV daily with 7-14-day conventional regimen of levofloxacin 500 mg intravenous to oral (IV/PO) daily for treatment of community-acquired pneumonia (CAP) in Chinese population. METHODS: This was a non-inferiority study to assess the difference of clinical efficacy at the end of treatment (EOT) between two regimens. Adult CAP patients with CURB-65 score 0-2 were enrolled from 17 hospitals in China from November 2012 to July 2014. The subjects were randomized into levofloxacin 750 or 500 mg group and the clinical data were collected. Sputum and blood specimens were sent for bacterial culture. The urinary antigen of Streptococcus pneumoniae (S. pneumoniae) was detected as well. At EOT, the clinical efficacy (primary endpoint), microbiological efficacy and safety were evaluated. RESULTS: A total of 457 patients were enrolled. Intent-to-treat (ITT) for primary endpoint analysis and per-protocol set (PPS) populations were 448 and 427 patients respectively. The therapeutic durations were 4.86 and 10.35 days and the mean drug exposure was 3,641.4 and 5,169.6 mg in 750 and 500 mg groups respectively. The clinical efficacy rate was 91.40% (202/221) in 750 mg group and 94.27% (214/227) in 500 mg group (ITT, P=0.2449). The difference in clinical efficacy rate was -2.87 (95% CI: -7.64, 1.90) between the two groups. The non-inferiority hypothesis of two groups was tenable (Δ=10%). The bacterial eradication rate was 100.00% in both groups. The most common drug-related clinical adverse events were injection site and gastrointestinal reactions. The most common drug-related laboratory abnormalities were WBC decrease and ALT/AST elevation. No statistical difference was found between two groups (P>0.05). CONCLUSIONS: The 5-day regimen of levofloxacin 750 mg daily is non-inferior to 7-14-day conventional regimen of 500 mg daily in clinical efficacy for treatment of mild to moderate Chinese CAP population. The short course regimen allows the reduction of antimicrobial drug exposure and is well tolerated.