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).

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.

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.

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.

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.

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.

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.

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 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.

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 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).

Intralobar pulmonary sequestration complicating with cryptococcal infection.

INTRODUCTION: Pulmonary sequestration is a rare congenital malformation characterized by accessory lung tissue supplied by an aberrant systemic artery. It often presents with recurrent infections. But fungus infection is exceptional. OBJECTIVES: To help other clinicians deal with patients with pulmonary sequestration complicating with cryptococcal infection. METHODS: We reported a case of pulmonary sequestration complicating with pulmonary and eye cryptococcosis and did literature review. RESULTS: A 20-year-old immunocompetent male patient suffered from eye pain and blurred vision, and received antibiotics and dexamethasone therapy with no improvement. Bacteriology inspection and computerized tomography scan indicated a diagnosis of cryptococcal infection in both eye and lung. Vitrectomy and antifungal agents were administered. Since symptoms fluctuations, lobectomy was operated. The surgery revealed the presence of pulmonary sequestration. Literature review showed that there is no report about pulmonary sequestration complicating with cryptococcal infection so far. CONCLUSIONS: Pulmonary sequestration is a very important but extremely negligent cause for pulmonary cryptococcal infection.

Pulmonary cryptococcosis with trachea wall invasion in an immunocompetent patient: a case report and literature review.

Cryptococcosis causes significant morbidity and mortality in the world. Pulmonary cryptococcosis is a kind of subacute or chronic pulmonary fungal disease. We present a case of pulmonary cryptococcosis with a trachea wall invasion-like malignant tumor in an immunocompetent patient and a literature review. The 44-year-old man, a nonsmoker, suffered from mild dyspnea and white sputum with intermittent blood streaks. A computed tomography (CT) scan of his chest showed two possibly malignant lesions in the right hilum and upper-right field of his lung, which have higher uptake values of fluorodeoxyglucose on positron emission tomography (PET)/CT. Lung biopsy pathology showed scattered fungal spores and positive periodic acid-Schiff (PAS) staining. The immune status and blood tumor markers were all normal in this patient. The titer of Cryptococcus antigen latex agglutination test was 1:1,280. Under fiberoptic bronchoscopy, a prominent new mass on the right wall of the trachea blocked most of the right main bronchus. To reduce the symptoms of airway obstruction, treatment by bronchoscopy, i.e. ablation and endotracheal stent, was used. As his symptoms were aggravated by the use of itraconazole, amphotericin B liposome was used as antifungal treatment. All these methods led to a better prognosis. We conclude that pulmonary cryptococcosis may mimic lung neoplasms radiologically and bronchoscopically, even in immunocompetent patients.

Primary ciliary dyskinesia complicated with diffuse panbronchiolitis: a case report and literature review.

BACKGROUND: Fifty percent of patients with primary ciliary dyskinesia (PCD) have situs inversus. Diffuse panbronchiolitis (DPB) might be one of the characteristic features of the lung in PCD. METHODS: We reported a case of PCD without situs inversus, yet complicated with DPB, and did literature review. RESULTS: A 34-year-old nonsmoking Chinese woman with 6-year primary infertility suffered from recurrent episodes of respiratory tract infections since childhood. Lung auscultation revealed end-inspiratory coarse crackles. Pulmonary function tests demonstrated mild obstructive ventilation functional impairment. Lung biopsy showed respiratory bronchiolitis. Nasal mucosa cilia showed the absence of both outer and inner dynein arms of the microtubules. Saccharin test was positive. Chest images showed bronchiectasis and bronchiolitis but no situs inversus. Paranasal sinus computed tomography (CT) showed maxillary sinusitis and ethmoid sinusitis. A culture of bronchoalveolar lavage fluid was positive for Pseudomonas aeruginosa. Her conditions improved in clinical symptoms and CT images after 2 months of treatment with azithromycin. Literature review revealed that very rare patients were diagnosed as PCD complicated with diffuse DPB, and all of them had situs inversus. CONCLUSIONS: The association of DPB might be one of the characteristic features of the lung in PCD. Further studies on the concurrence of these two diseases are suggested so as to elucidate the mechanism of both.

Clinical profiles of 12 Chinese patients with diffuse panbronchiolitis.

BACKGROUND: Diffuse panbronchiolitis (DPB) is an uncommon idiopathic inflammatory disease, characterized by chronic sinusitis, respiratory bronchiolitis and progressive airway obstruction. Without correct diagnosis and treatment, DPB may progress to bronchiectasis, respiratory failure and even death. OBJECTIVE: To help other clinicians deal with DPB. METHODS: Twelve Chinese patients (six women;mean (SD) age 50(14.7) years) who were diagnosed as DPB were assessed retrospectively for clinical, radiological, lung function, microbiological, and other "characteristic" laboratory parameters. RESULTS: Most patients presented with chronic cough, copious purulent sputum production, and exertional dyspnoea, end-inspiratory crackles, and a history of sinusitis. Unlike DPB cases from Japan, cold agglutination test in 11 out of 12 patients were negative, and the CD4/CD8 lymphocyte ratio in all patients were normal or low. All patients had moderate to severe small airway disfunction and hypoxemia. The mean values of FEV1/FVC, and RV/TLC were 58.9%, and 41.5%, respectively. The most common HRCT findings from this cohort of patients were bronchiectasis and bronchiolitis, with nodular shadows distributed in a centrilobular pattern. Morphological examination revealed peribronchiolar and bronchiolar wall inflammation composed of lymphocytes, plasma cells, and histocytes. Few cases were not confirmed by diagnostic criteria from Japan but clinically diagnosed as DPB due to satisfied treatment response and typical clinical features. CONCLUSIONS: More DPB cases need to be analyzed from Chinese population due to different presentations compared to Japanese population. This experience should help other clinicians in the investigation and management of DPB in non-Japanese patients.

A case report of pulmonary cryptococcosis presenting as endobronchial obstruction.

Cryptococcosis presenting as endobronchial obstruction was scarce. We report a case of patient with cryptococcosis. A chest CT scan showed masses in the right upper lobe and right hilar, with evidence of narrowing of the right upper lobe bronchus. PET-CT scans showed the mass in the bronchus with the high mSUVs. A biopsy specimen was taken from the mass by lung puncture biopsy and showed cryptococcus infection. Culture of lung tissue was C. neoformans. The serum was positive for cryptococcal antigen, with a titer of more than 1(:)1,280. He was successfully treated using amphotericin B liposome. This case is worth discussing because it was cryptococcosis presenting as endobronchial obstruction that is often considered tumor.

Aspergillus fumigatus conidia upregulates NOD2 protein expression both in vitro and in vivo.

AIM: To determine if NOD2 is involved in host recognition of Aspergillus fumigatus (Af) conidia. METHODS: An Af conidia pulmonary infection murine model was established by intranasal inoculation of Af conidia suspensions. Protein levels of NOD2 in lung tissue were determined by immunohistochemistry. A549 and phorbol-12-myristate 13-acetate (PMA)-activated THP-1 cell lines were treated with heat-killed Af conidia, then the presence of NOD2 protein in these cell lines was detected by Western blotting. The ability of muramyl dipeptide (MDP) to induce the secretion of TNF-alpha after incubation with heatkilled Af conidia was measured by enzyme-linked immunosorbent assay. RESULTS: The expression of NOD2 protein in lung tissue increased after Af conidia infection. Heat-killed Af conidia significantly upregulated NOD2 protein expression in A549 cells and PMA-activated THP-1 cells. Additionally, Af conidia in conjuction with MDP, significantly increased the secretion of TNF-alpha in A549 cells and PMA-activated THP-1 cells. CONCLUSION: Af conidia upregulates NOD2 protein expression in vitro and in vivo. These findings indicate that NOD2 protein may respond to Af conidia.

A comparative study of clinical manifestations caused by tuberculosis in immunocompromised and non-immunocompromised patients.

OBJECTIVE: To characterize the differences between clinical manifestations in immunocompromised patients (ICPs) and non-immunocompromised patients (non-ICPs) with tuberculosis. METHODS: Underlying diseases, clinical presentations, misdiagnosis, treatment and prognosis, etc, were analyzed retrospectively in 115 tuberculosis patients, including 39 ICPs and 76 non-ICPs. RESULTS: Compared with non-ICPs, the individuals who were ICP had more expectoration (64.1% vs 35.5%), pulmonary moist rale (41.0% vs 9.2%), miliary pulmonary tuberculosis (30.8% vs 2.6%), pleural effusion (48.7% vs 25.0%) and lymphadenopathy (18.0% vs 4.0%). ICPs had less lung cavity (15.4% vs 22.4%) and pleural thickening (15.4% vs 23.7%) compared to non-ICPs. Pulmonary tuberculosis in ICPs was prone to be misdiagnosed as pneumonia (23.1% vs 6.6%). Pulmonary tuberculosis was found in the apicoposterior segment (SI + SII) in more cases in non-ICPs (21.7%, 10/46) than ICPs (10.3%, 3/29). The diagnostic value of tuberculin skin test and adenosine deaminase in pleural effusions was limited in ICPs. ICPs had significantly poorer prognoses than non-ICPs. CONCLUSION: The clinical manifestations of ICPs with tuberculosis are atypical, misdiagnosis often occurs, resulting in a worse prognosis.

[A control study on bacterial resistance and clinical features of lower respiratory tract infection with Pseudomonas aeruginosa in medical intensive care unit and general ward].

OBJECTIVE: To compare the bacterial resistance and clinical features of lower respiratory tact infection with Pseudomonas aeruginosa (PA) in medical intensive care units (MICU) and general wards (GW) and to analyze the predisposing factors to PA infection. METHODS: Three hundred and twenty three patients with lower respiratory tract PA infection, aged from 30 to 91 years, admitted into Shanghai Zhongshan hospital from May 1997 to December 2001 (163 in MICU and 160 in GW) were included in this retrospective study. The predisposing factors, underlying diseases, clinical presentations, laboratory data, treatment and outcome of these patients were analyzed. On the other hand, the susceptibility patterns to antibiotics of 1 387 PA strains (879 from MICU and 508 from GW) from the recorders of the bacteria culture chamber were investigated. RESULTS: The underlying diseases of the patients mainly were chronic obstructive pulmonary disease (23.3% of patients in MICU and 12.5% in GW) and malignant tumor (14.7% in MICU and 14.4% in GW). A relatively high resistant rates of PA strains to common antibiotics were found in both groups: cefoperazone/sulbactam 1.0% (MICU: 1.0%, GW: 1.1%), piperacillin/tazobactam 2.5% (MICU: 1.0%, GW: 5.0%), amikacin 6.1% (MICU: 7.0%, GW: 4.5%), ceftazidime 9.2% (MICU: 11.6%, GW: 2.7%), cefepime 11.3% (MICU: 12.2%, GW: 10.8%), imipenem 13.5% (MICU: 6.8%, GW: 25.2%), piperacillin 13.8% (MICU: 17.8%, GW: 6.9%), cefoperazone 16.4% (MICU: 22.1%, GW: 6.6%), ticarcillin/clavulanic acid 17.2% (MICU: 21.2%, GW: 17.3%), cidomycin 18.5% (MICU: 20.5%, GW: 14.9%), ciprofloxacin 20.2% (MICU: 27.2%, GW: 8.1%), ceftriaxone 44.4% (MICU: 53.6%, GW: 28.4%). Most of the resistant rates of strains from MICU were higher than those from GW. The susceptibilities of PA to ceftazidime and piperacillin changed little during the past 5 years and were above 80.00%. Since 1988, especially from 2000, the susceptibility of PA to most antibiotics became remarkably lower. With selected antibiotic treatment of the infections 196 patients were cured, 79 patients died in hospital. The mortality of patients in GW (16.25%, 26/160) was lower than that in MICU (32.52%, 53/163). CONCLUSION: Precautions to PA infection is important in patients with predisposing factors. Patients with Lower respiratory tract PA infection in MICU had different clinical features, laboratory data and outcome compared to GW patients. The PA isolated from MICU patients had a higher resistant rate to many antibiotics than that from GW patients. It is important to perform antibiotic sensitivity test timely to help correct selection of drugs, especially for MICU patients.