Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor-dependent and independent pathways.

BACKGROUND AND OBJECTIVE: The roles of bile acid microaspiration and bile acid-activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation. METHODS: Human AECs and normal or IPF-derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The AECs injury indices, epithelial-mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR-independent pathways in bile acid-induced profibrotic effects were also investigated. RESULTS: LCA, DCA and CDCA reduced cell viability and increased intracellular reactive oxygen species (ROS) production in A549 cells. They all induced EMT, as shown by enhanced α-SMA and vimentin and decreased E-cadherin levels. LCA directly induced differentiation of lung fibroblasts to myofibroblasts. All three bile acids promoted cellular migration but not proliferation of lung fibroblasts. FXR expression was upregulated in IPF lungs, and inhibition of FXR restrained the bile acid-induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid-stimulated A549 cells, which contained increased levels of profibrotic factors. TGF-ß/Smad3 signaling was also involved in the bile acid-induced EMT and lung fibroblast differentiation. CONCLUSION: Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR-dependent and independent pathways.

Occupational inhalational exposure and serum GM-CSF autoantibody in pulmonary alveolar proteinosis.

OBJECTIVES: Although the serum granulocyte-macrophage colony stimulating factor autoantibody (GMAb) levels have been recognised as a diagnostic marker in primary pulmonary alveolar proteinosis (PAP), their role in PAP with occupational inhalational exposure (PAPo) remains unclear. METHODS: Forty-five consecutive patients with PAP were enrolled. Each patient with PAP was assessed for baseline clinical characteristics, chest high-resolution CT (HRCT), serum GMAb and occupational exposure. Fifty healthy controls were included to define normal ranges for GMAb levels. Ninety-seven hospital controls with other respiratory diseases were included to establish prevalence of a history of occupational inhalation exposure. RESULTS: According to the serum GMAb cut-off value of 2.39 µg/mL, 84.4% of the recruited patients with PAP had positive serum GMAb with a median level of 28.7 µg/mL, defined as autoimmune PAP, and the remaining 15.6% had negative serum GMAb with a median level of 0.16 µg/mL, defined as non-autoimmune PAP. Also, 34.2% of patients with autoimmune PAP had a history of occupational inhalational exposure, which was not significantly higher than that of hospital controls (34.2% vs 19.6%, p=0.072). Four patients with PAPo showed negative GMAb. Their arterial oxygen tension, pulmonary function parameters and chest HRCT features were significantly different when compared with patients with autoimmune PAP (p<0.05). These four non-autoimmune occupational lung disease cases culminated in 3 deaths and a lung transplant. CONCLUSIONS: A number of patients with PAP who may have occupational inhalational exposure and negative serum GMAb represent a high possibility of silicoproteinosis and very poor survival.

Meta-analysis of the adverse effects of long-term azithromycin use in patients with chronic lung diseases.

The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.

[The clinicopathological features of acute fibrinous and organizing pneumonia].

OBJECTIVE: To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP). METHODS: The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized. RESULTS: Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement. CONCLUSIONS: AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.

[Expressions of caveolin-1 and extracellular matrix in lung tissues of patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the expressions of caveolin-1, collagen-I, α-smooth muscle actin (α-SMA) and Smad in lung tissues of patients with idiopathic pulmonary fibrosis (IPF) and therefore to explore their potential roles in the pathogenesis of the disease. METHODS: Six patients with IPF confirmed pathologically by open lung biopsy in Department of Pulmonary Medicine, Affiliated Drum Tower Hospital of Nanjing University from January 2005 to December 2008 were studied. Diagnosis of IPF was made in accordance with the American Thoracic Society/European Respiratory Society Consensus Statement. At the same period, 6 normal lung samples were also obtained from patients with lung cancer by surgical resections as the control group. The level of caveolin-1 mRNA and protein, collagen-I, α-SMA and Smads in lung tissues were detected by RT-PCR, Western blot and immunohistochemistry. RESULTS: Compared with the control group, significantly reduced levels of caveolin-1 mRNA and protein (0.66 ± 0.19 vs 0.05 ± 0.02; 0.81 ± 0.11 vs 0.16 ± 0.05, P < 0.05) were observed in the lungs of patients with IPF. However, collagen-I (0.85 ± 0.11 vs 0.16 ± 0.04) and α-SMA (0.78 ± 0.08 vs 0.14 ± 0.05) proteins in the lung tissues of IPF patients were significantly increased as compared to the controls (P < 0.05). The expressions of p-Smad2 and p-Smad3 proteins were significantly increased (0.78 ± 0.08 vs 0.17 ± 0.04; 0.86 ± 0.07 vs 0.14 ± 0.04, respectively, P < 0.05), while that of Smad7 protein decreased (0.22 ± 0.05 vs 0.78 ± 0.08, P < 0.05) in the lungs of patients with IPF as compared with the control groups. CONCLUSION: The reduced expression of caveolin-1 in lung tissues of IPF may be related to the development and progress of pulmonary fibrosis.

The relationship between immunosuppressive therapy and clinical isolates for patients diagnosed with dermatomyositis-related interstitial lung diseases.

BACKGROUND: Immunosuppressive therapy is the main treatment for patients with interstitial lung diseases (ILD) secondary to dermatomyositis (DM). Microbial colonization or infection might be very common for these patients. However, the relationship between immunotherapy and microorganism isolates are not fully understood in these patients. OBJECTIVES: This study retrospectively analyzed on the clinical features in DM-ILD patients who had positive microbiological results during immunosuppressive therapy in our hospital. METHODS: Patients were divided into two groups, according to the result of microbiological study. Comparisons in infection-related data in various contexts were carried out. RESULTS: As a result, patients who had positive microbiological findings were manifested as higher fever degree [p = 0.01; positive group: mean ± SEM: 38.83 ± 0.15 °C, N = 28; negative group: mean ± SEM: 38.27 ± 0.15 °C; N = 28], higher serum C-reactive protein (CRP) [p less than 0.001, positive group (mean ± SEM: 31.6 ± 5.2 mg/L; N = 43); negative (mean ± SEM: 11.1 ± 1.6 mg/L; N = 86)], and lower CD3+CD4+ T cells counts than that of negative populations [p = 0.03, positive group (mean ± SEM: 0.27 ± 0.05 × 109/L; N = 31); negative group (mean ± SEM: 0.400 ± 0.03 × 109/L; N = 44)]. Longer hospital stay [p = 0.005; 21/36 vs 31/99] and higher serum FK506 concentrations [p = 0.02, positive group: 9.80 ± 1.87 ng/ml; N = 7; negative group: 5.76 ± 0.73 ng/ml; N = 27] were related to the occurrence of microorganism in the airway. Meanwhile, short-term investigation of in-hospital mortality related to airway microbial carry had no statistical difference between the both groups [p = 0.21, Log-rank (Mantel-Cox) Test]. CONCLUSIONS: Occurrence of positive isolates in DM-ILD patients may relate to higher inflammatory markers CRP, lower CD4 + T cells counts, high concentration of serum FK-506, and longer hospital stay.

Idiopathic pleuroparenchymal fibroelastosis confirmed by pathology: a case report.

The case of a patient with cough and asthma after activity that each had a 1-month duration is reported. Chest high-resolution computed tomography (HRCT) showed visceral pleural thickening in both upper lungs (especially the right lung), which was accompanied by fibrous strips and patches near the pleura, and these were accompanied by distraction bronchiectasis. Idiopathic pleuropulmonary elastosis was confirmed by thoracoscopic lung biopsy. The patient was treated with acetylcysteine, but their asthma worsened after activity and their lung function decreased significantly after 10 months. Idiopathic pleuroparenehymal fibroelastosis is a rare new type of idiopathic interstitial pneumonia, which has no effective treatment except for lung transplantation.

Activating transcription factor 3 involved in Pseudomonas aeruginosa PAO1-induced macrophage senescence.

Pseudomonas aeruginosa (PA) is one of the most prevalent pathogens that cause nosocomial infection in critical patients. Previously, we reported PA induced macrophage to senescence under the circumstance of infection. As an oxidative stress responsiveness element, activating transcription factor 3 (ATF3) might be involved in the macrophage senescence process. To test this presumption, we manipulated the expression of ATF3 in macrophage by using a PAO1 infection system. In the present study, ATF3 expression in macrophage was increased, following the duration and colony counts of PAO1 infection. Knockdown of ATF3 in macrophage resulted in increased percentage of senescent macrophage under PAO1 infection, while overexpressing ATF3 partly blocked PAO1-induced macrophage senescence. In accordance with the senescent phenotype, elevated reactive oxygen species (ROS) production was shown in ATF3 knockdown macrophages. Also, capacity of phagocytosis was also affected by manipulation of ATF3 expression in macrophages, and increased phagocytosed fluorescent beads was found in ATF3 knockdown macrophage. ATF3 might regulate the senescence process through influence on NF-κB translocation. During infection, the overexpression or downregulation of ATF3 in macrophage negatively modulated the translocation of NF-κB p65 and its phosphorylation at Ser-536. As a result, IL-6 and TNFα was elevated, while IL-10 decreased in case of ATF3 knockdown. In conclusion, ATF3 negatively regulates NF-κB translocation and activation, and participates in PA-induced macrophage senescence. As oxidative stress and inflammation induced element, ATF3 may modulate macrophage-related host defense.

Northern pig-tailed macaques ( Macaca leonina) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has become an unprecedented global health emergency. At present, SARS-CoV-2-infected nonhuman primates are considered the gold standard animal model for COVID-19 research. Here, we showed that northern pig-tailed macaques ( Macaca leonina, NPMs) supported SARS-CoV-2 replication. Furthermore, compared with rhesus macaques, NPMs showed rapid viral clearance in lung tissues, nose swabs, throat swabs, and rectal swabs, which may be due to higher expression of interferon (IFN)-α in lung tissue. However, the rapid viral clearance was not associated with good outcome. In the second week post infection, NPMs developed persistent or even more severe inflammation and body injury compared with rhesus macaques. These results suggest that viral clearance may have no relationship with COVID-19 progression and SARS-CoV-2-infected NPMs could be considered as a critically ill animal model in COVID-19 research.

[Expression of caveolin-1 and extracellular matrix induced by transforming growth factor beta1 in human fetal lung fibroblasts].

OBJECTIVE: To investigate the expressions of caveolin-1, collagen-I and alpha-SMA in human fetal lung fibroblasts induced by transforming growth factor beta(1) (TGF-beta(1)). METHODS: Human fetal lung fibroblasts (HFLF) were cultured in vitro, and exposed to TGF-beta(1) with different final concentrations (2, 5, 10 microg/L). Cells without TGF-beta(1) exposure served as the control. Caveolin-1 mRNA and protein, collagen-I and alpha-SMA proteins in cell (at least 5 x 10(8)) lysates, were detected at different points after the treatment of TGF-beta(1), by RT-PCR, Western blot and Immunohistochemistry. Each experiment was repeated 3 times. One-way analysis of variance (ANOVA) was used to compare data among groups, and linear regression was established for correlation analysis. RESULTS: TGF-beta(1) reduced caveolin-1 mRNA and protein expressions in a dose- and time-dependent manner, measured by integral optical density. Compared with the control group (1.22 +/- 0.12 and 1.45 +/- 0.06), caveolin-1 mRNA and protein expressions (0.59 +/- 0.06 and 0.53 +/- 0.04) were significantly reduced, with statistical significance (F = 29.279 and F = 95.786, P < 0.01), in cells exposed to TGF-beta(1) (5 microg/L) for 12 h. The collagen-I and alpha-SMA protein expressions (1.35 +/- 0.09 and 0.75 +/- 0.06) measured by integral optical density increased after stimulation, peaked at 24 h in 5 microg/L TGF-beta(1) group. At that time point, the collagen-I and alpha-SMA protein expressions were 4.2 and 4.8 times of the control group (0.28 +/- 0.04 and 0.18 +/- 0.04), F = 81.221 and F = 65.477, P < 0.01. Caveolin-1 expression had a negative correlation with collagen-I (r = -0.923, P < 0.05) and alpha-SMA protein expression (r = -0.793, P < 0.05). CONCLUSION: The reduced caveolin-1, which was negatively correlated with expressions of collagen-I and alpha-SMA proteins in HFLF cells exposed to TGF-beta(1), may be related to the development and progress of pulmonary fibrosis.

[Report of 2 cases of novel influenza A (H1N1) virus infection complicated with pneumonia and hypoxemia].

OBJECTIVE: to improve understanding of the novel influenza A (H1N1) virus infection complicated with pneumonia. METHOD: clinical presentations, radiological data, laboratory data and treatments of 2 patients with pneumonia caused by the novel influenza A (H1N1) virus were retrospectively analyzed. RESULTS: one patient was a middle-aged woman, and the other was a young man with a history of asthma. Both patients had fever (temperatures more than 39 degrees C), cough, and dyspnea. At the time of admission, both patients had hypoxemia. Chest computed tomography (CT) scan showed patchy distribution of consolidation and ground-glass opacity mainly in peripheral subpleural regions, as well as peribrochovascular lesions with air-bronchogram. The decreased and lymphocytes, elevated lactate dehydrogenase and creatine kinase were found in both patients. After admission, the patients received oseltamivir with a dose of 75 mg twice a day for a minimum of 5 days. Other treatments included antibiotics and methylprednisolone. One patient needed intermittent non-invasive ventilation for respiratory distress. Both patients recovered and the opacities on their chest CT were almost absorbed. WBC counts increased to normal and the levels of LDH and CK decreased. CONCLUSIONS: patients with the novel influenza A (H1N1) virus infection may develop pneumonia. The manifestations are non-specific. Chest CT scan reveals patchy distribution of consolidation and ground-glass opacity. In addition to antiviral therapy, glucocorticoids may have some effects on the pulmonary lesions and be useful for improving the clinical conditions.

COVID-19-like symptoms observed in Chinese tree shrews infected with SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/ HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here, different aged Chinese tree shrews (adult group, 1 year old; old group, 5-6 years old), which are close relatives to primates, were infected with SARS-CoV-2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days post-inoculation (dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3, 5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Histological analysis of lung tissues from animals at 3 dpi (adult group) and 7 dpi (old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.

Delayed severe cytokine storm and immune cell infiltration in SARS-CoV-2-infected aged Chinese rhesus macaques.

As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b + and CD8 + cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b + cells, and persistent infiltration of CD8 + cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.

[Giant cell interstitial pneumonia associated with hard metals: a case report and review of the literature].

OBJECTIVE: To highlight the clinical, radiological and pathological characteristics of Objective To highlight the clinical, radiological and pathological characteristics of giant cell interstitial pneumonia (GIP) associated with Hard metals. METHOD: The clinical, radiological and pathological data of a patient with hard metal lung disease confirmed by video-assisted thoracoscopic biopsy of the right lung were presented, and relevant literatures were reviewed. RESULTS: A 30-year-old female patient presented with cough and dyspnea on exertion for more than 40 days. She had worked for grinding tungsten rod, with exposure to metal dusts containing cobalt and tungsten for more than 3 years. Chest radiographs and CT demonstrated bilateral ground-glass attenuations and ill-defined small nodules. Lung function studies showed the mixed type of ventilation dysfunction with a low diffusion capacity (DLCO of 39% of predicted). Lung biopsy specimens showed desquamative interstitial pneumonia like reaction with alveolar macrophages and numerous large multinucleated histiocytes that ingested inflammatory cells in alveolar spaces, which was characteristics of GIP. The lung parenchyma also showed patchy chronic inflammatory-cell infiltrates centered predominantly around the bronchioles and interstitial fibrosis. Considering the exposure history and the histological findings of the lung, the diagnosis of hard metal lung disease and GIP associated with hard metals was made. Her cough, dyspnea, and radiological changes showed marked improvement after corticosteroid therapy and avoidance of further exposure to hard metals. CONCLUSION: GIP is almost pathognomonic for hard metal lung disease. Meticulous history taking on occupational exposure is important for the diagnosis and differential diagnosis of suspected interstitial lung disease.

Clinical characteristics and outcomes of hypersensitivity pneumonitis: a population-based study in China.

BACKGROUNDS: Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) that develops in response to the inhalation of various antigens. The clinical pathologies are very complex and undetermined. The clinical features and outcomes of HP have not been fully elucidated. The aim of this study was to analyze the incidence, clinical features, and outcomes of HP patients and construct a simple clinical model for diagnosing chronic HP (CHP). METHODS: The cohort study included 101 patients with HP admitted to the Nanjing Drum Tower Hospital from January 2009 to December 2017. The patients were categorized into acute HP (AHP, n = 72) and CHP (n = 29) groups according to the updated international criteria. The clinical, imaging, treatment, and follow-up data were retrospectively reviewed. All patients were followed up until December 31, 2017. Statistical analysis was performed, and a clinical scoring system for CHP was constructed by SPSS 20.0 software. RESULTS: The incidence of HP was 2.4% in ILD inpatients in our center. Patients in the CHP group were older (t = -2.212, P = 0.029), had more smokers (χ = 8.428, P = 0.004), and longer duration of symptoms (t = -4.852, P < 0.001) than those in the AHP group. Weight loss, crackles, digital clubbing, and cyanosis were more common in the CHP group than those in the AHP group (χ = 5.862, P < 0.001; χ = 8.997, P = 0.003; χ = 11.939, P = 0.001; and χ = 4.025, P = 0.045, respectively). On chest high-resolution computed tomography (HRCT), reticular patterns, traction bronchiectasis, and accompanying honeycombing were more common in CHP cases than those in AHP cases (χ = 101.000, P < 0.001; χ = 32.048, P < 0.001; and χ = 36.568, P < 0.001, respectively). The clinical scoring system for CHP was established based on the clinical variables (age [A], duration of symptoms [D], smoking history [S], unidentified exposure [U], and chest HRCT [C]; ADSUC) (area under the curve 0.935, 95% confidence interval: 0.883-0.987, P < 0.001). Eleven patients (15.3%) in the AHP group developed CHP, and unidentified exposure was an independent risk factor for the progression of disease (P = 0.038). The survival of patients with CHP, smoking history, unidentified antigens and fibrosis on Chest HRCT were significantly worse (P = 0.011, P = 0.001, P = 0.005, and P = 0.011, respectively) by Kaplan-Meier analysis. Cox multivariate regression analysis revealed that unidentified exposure and total lung volume (TLC pred%) were independent prognostic predictors for HP patients (P = 0.017 and P = 0.017, respectively). CONCLUSIONS: The clinical features and outcomes of the CHP patients differ from those of the AHP patients. ADSUC is a simple and feasible clinical model for CHP. Unidentified exposure is an independent risk factor for the progression of AHP to CHP. Unidentified exposure and a low baseline TLC pred% are independent predictors for survival in HP patients.

Acute exacerbation of idiopathic pulmonary fibrosis: usual interstitial pneumonitis vs. possible usual interstitial pneumonitis pattern.

BACKGROUND: The prognosis of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is very poor with a high mortality. The aim of this study was to describe the clinical features and survival of patients with AE-IPF with usual pulmonary fibrosis (UIP) and possible UIP (P-UIP) pattern on chest high resolution computed tomography (HRCT). METHODS: This retrospective study included 107 patients with AE-IPF admitted to Nanjing Drum Tower Hospital from January 2010 to December 2016. The subjects were divided into UIP (n = 86) and P-UIP group (n = 21) based on chest HRCT. Continuous variables were analyzed using Student's t test or Mann-Whitney U test. Categorical variables were analyzed using χ test. Log-rank test was used for the survival analysis. Cox proportional models evaluated the risk factors for AE occurrence and survival. RESULTS: The male, older patients, previous N-acetylcysteine use, elevated white blood cell (WBC) counts, and microbiology infection were more common in the UIP group than the P-UIP group (χ = 13.567, P < 0.001; z = -2.936, P = 0.003; χ = 5.901, P = 0.015; t = 2.048, P = 0.043; χ = 10.297, P = 0.036, respectively). The percentage of AE with UIP pattern in idiopathic interstitial pneumonia (IIP) was significantly higher than P-UIP pattern (χ = 40.011, P < 0.001). Smoking was the risk factor for AE within 6 months after IPF diagnosis in the UIP group. The cumulative proportion survival of 30-days was significantly higher in the UIP group compared with the P-UIP group (χ = 5.489, P = 0.019) despite of the similar overall survival in the two groups. Multivariate Cox regression analysis indicated WBC count, partial pressure of oxygen in artery (PaO2)/fractional concentration of inspired oxygen (FiO2), and computed tomography (CT) score were the independent predictors for survival in the UIP group (hazard ratio [HR]: 1.070, 95% confidential interval [CI]: 1.027-1.114, P = 0.001; HR: 0.992, 95% CI: 0.986-0.997, P = 0.002; and HR: 1.649, 95% CI: 1.253-2.171, P < 0.001, respectively). CONCLUSIONS: AE occurrence of UIP patients in IIP was significantly more than P-UIP cases. The short-term survival was better in the UIP group despite of the similar overall survival in the two groups. WBC count, PaO2/FiO2, and CT score were the independent predictors for survival in UIP subjects.

[Pulmonary sarcoidlike granulomatosis induced by aluminum dust: a case report and literature review].

OBJECTIVE: To highlight the etiological diagnosis of pulmonary granulomatosis. METHODS: The clinical, radiological and pathological data of a patient with sarcoidlike lung granulomatosis confirmed by open lung biopsy were presented, and relevant literatures were reviewed. RESULTS: A 50-year-old female worker presented with intermittent cough and dyspnea for 3 years, after exposure to aluminum dust for 15 years. Radiographs of the chest and high-resolution CT demonstrated bilateral areas of ground-glass attenuation, patchy areas of consolidation, extensive reticular hyper-attenuating areas and traction bronchiectasis. Lung function studies showed a restrictive pattern with a low diffusion capacity. Lung biopsy specimens confirmed the presence of diffuse, noncaseating granulomatous nodules. Scanning electron microscopy and energy-dispersive radiograph analysis revealed large quantities of foreign particles mainly containing aluminum in granulomas. Her cough, dyspnea, radiological shadowing and pulmonary function showed marked improvement after corticosteroid therapy. CONCLUSIONS: With the occupational history, histological and mineralogical studies, the patient was considered to have pulmonary sarcoidlike granulomatosis, most likely related to occupational exposure to aluminum dust. The search for any possible relevant exposure of a patient with suspected sarcoidosis seems mandatory.

[A high-resolution CT and pathological study of nonspecific interstitial pneumonia].

OBJECTIVE: To describe the characteristics of high-resolution CT(HRCT) findings of nonspecific interstitial pneumonia (NSIP) and the correlation with pathological changes. METHODS: The HRCT features of 9 cases (3 men and 6 women) of histopathologically confirmed NSIP were retrospectively analyzed and correlated with the pathological findings. RESULTS: The predominant HRCT features, found in all the cases, were bilaterally patchy areas of ground-glass opacity with or without areas of consolidation. Irregular linear opacities, traction bronchiectasis, and thickening of bronchovascular bundles were also frequently seen. The abnormalities were distributed over the peripheral zones of the middle and lower lungs in most cases. Honeycombing was not a feature in all the cases. Areas of ground-glass opacity with or without irregular linear opacity or traction bronchiectasis corresponded pathologically to areas of interstitial thickening caused by varying degrees of interstitial inflammation and fibrosis showing temporal uniformity. Areas of consolidation were associated with extensive collagen-type interstitial fibrosis and mild interstitial inflammation at the biopsy sites, and occasionally represented the areas of bronchiolitis obliterans organizing pneumonia, foamy cell collections in alveolar spaces, or microscopic honeycombing with mucin stasis. CONCLUSION: The HRCT manifestations of NSIP are characteristic though not specific. In patients with consistent clinical features, the diagnosis of NSIP can be suspected by typical HRCT findings.

[Primary natural killer/T cell lymphoma of the lung: two cases report and clinical analysis].

OBJECTIVE: To describe the clinical and pathological features of primary NK/T cell lymphoma of the lung. METHODS: Two cases of primary NK/T cell lymphoma of the lung were reported, and the clinical, radiological and pathological characteristics of the disease were discussed with literature review of 3 cases. RESULTS: Most patients presented with fever, cough and dyspnea, and antibiotics were ineffective. Radiographic findings included solitary or multiple nodules and consolidation, unilateral orbilateral pleural effusions (4/5), without hilar or mediastinal adenopathy. Ebstein-Barr virus was positive in cases patients (3/5). Histopathology revealed a great deal of abnormal lymphocyte infiltration, which were angio-centric with marked tissue putrescence and angio-destruction. Immunophenotyping showed CD56(+), CD3(+), perform (+), T-cell intracytoplasmic antigen-1(+) and/or GranB(+), but CD20(-). Most patients died of respiratory failure in half a year (4/5). CONCLUSION: Primary NK/T cell lymphoma of the lung is rare, but should be considered when patients present with lung shadows and fever non-responsive to antibiotics, decreased WBC and increased LDH.