The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Multidetector CT findings of primary pleural angiosarcoma : a systematic review, an additional cases report.

BACKGROUND: To demonstrate and analyze the relatively common imaging findings in this rare primary pleural angiosarcoma (PPA). CASE PRESENTATION: Three cases of PPA, proven by video-assisted thoracic surgery biopsies are retrospectively reviewed. Patients were all male. Age ranges from 65 to 75 years old age (mean; 69). Major chief complaints were dyspnea and chest pain. One has a history of colon cancer, the other has a tuberculosis history and the other has no known history. Multidetector chest CT and PET CT were all done. Immunohistochemical studies were performed including CD31, CD34, or factor VIII-related antigen, vimentin, and cytokeratin. We also review the literatures on recently published PPA. All masses were from 1 to 10 cm. All three patients had multiple pleural based masses, which were ovoid in shape with relatively sharp margin in unilateral hemithorax. Multiple small circumscribed pleural masses are limited in the pleural space in two patients, whereas two, huge lobulated masses about up to 10 cm were present with pleural and extrapleural involvement in one patient. In two patients with pleural mass only, multiple pleural masses were only seen in parietal pleura in one patient and were in both visceral and parietal pleura in one patient. Pleural effusion were found in one side in one patient and in both sides in one patient. One angiosarcoma was arised from chronic tuberculotic pleurisy sequelae. All pleural masses are heterogenous with irregular internal low densities in all patients. Hematogenous metastases were found in liver, vertebra, rib in one patient, and were in lungs with mediastinal lymph node metastases in the other patient. Three patients survived for longer than 3months after diagnosis, but continued to deteriorate rapidly. Two patients underwent chemotherapy after surgical excision, and the other one with multiple metastases treated chemotherapy after CT-guided biopsy, but eventually all died. As a result of comparative analysis of a total of 13 patients' images including 10 cases previously published, there was pleural effusion in all except 2 cases. CONCLUSIONS: PPA were all necrotic without any vascularized enhancing nature, and manifested as unilateral circumscribed or localized pleural-based masses.

Effects of low-dose pirfenidone on survival and lung function decline in patients with idiopathic pulmonary fibrosis (IPF): Results from a real-world study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. METHODS: This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. RESULTS: Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48-0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37-0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. CONCLUSIONS: Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.

The association between serum apolipoprotein B and fractional exhaled nitric oxide in bronchial asthma patients.

BACKGROUND: Asthma and lipid metabolism are associated with systemic inflammation. However, the studies about the relationship between lipid profile, fractional exhaled nitric acid (FeNO) and pulmonary function test (PFT) results are currently lacking. METHODS: We enrolled asthma patients who had serum lipid profiles including apolipoprotein levels from March 1, 2019 to December 31, 2019. We classified the asthma patients into two groups according to the diagnosis method: (I) patients who were diagnosed based on clinical symptoms/signs and PFT results and (II) patients diagnosed with clinical symptoms/signs. Clinical characteristics including age, underlying diseases, smoking status, allergy test results and treatment agents were compared between the two groups. The associations between blood cholesterol levels including apolipoprotein and pulmonary functions were analyzed. Moreover, patients were divided into two groups according to the median value of apolipoprotein B (Apo B), and lung function test results were compared between the patients who had high and low Apo B levels. RESULTS: Among the 167 patients, 93 (55.7%) were PFT-proven asthma patients. In PFT-proven asthma patients, the levels of total cholesterol (TC) (r =0.37, P=0.03), low-density lipoprotein (LDL) (r =0.46, P=0.01) and Apo B (r =0.38, P=0.02) showed a significant correlation with FeNO, which had no statistical significance in physician-diagnosed asthma group. In multivariate regression analysis, log (FeNO) showed a significant correlation with Apo B (P<0.01) after adjustment for presence of PFT-proven asthma (P=0.01) and current smoking (P=0.01). Patients with high Apo B levels had a lower post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (69.8 vs. 74.9, P=0.02) and lower post-BD FEV1 (%) (77.5 vs. 85.0, P=0.04) compared with those showing low Apo B levels. CONCLUSIONS: The levels of Apo B and FeNO had positive correlations and high Apo B levels were associated with severe airflow obstruction and low FEV1 (%). Apo B could reflect the uncontrolled status of bronchial asthma and poor lung function.

Clinical significance of microbial colonization identified by initial bronchoscopy in patients with lung cancer requiring chemotherapy.

BACKGROUND: There are limited data on the association between bronchial colonization and respiratory infections in people with lung cancer requiring cytotoxic chemotherapy. We investigated whether bronchial colonization in initial bronchoscopy specimens can predict the development of pneumonia after chemotherapy in patients with lung cancer. METHODS: Four hundred thirteen patients with lung cancer included in the Catholic Medical Center lung cancer registry were enrolled from March 2015 to August 2018. Demographic data, microbiology results, development of pneumonia after chemotherapy, and clinical information about lung cancer were analyzed retrospectively. RESULTS: A total of 206 lung cancer patients treated with chemotherapy were included in the analysis. Forty patients (19.4%) had positive results for the bronchial washing culture during the initial evaluation of lung cancer. The most common organisms were Klebsiella pneumoniae (n=14) and Streptococcus pneumoniae (n=6) in the surveillance culture, and Pneumocystis jirovecii (n=12) and Staphylococcus aureus (n=8) at the time of pneumonia development. Eighty-nine patients (43.2%) had pneumonia after chemotherapy, but the occurrence of pneumonia did not differ according to the colonization. There were no patients for whom the initial isolated organism was a causative microbe for the development of pneumonia after or during chemotherapy. The pneumonia group had poorer prognosis than the non-pneumonia group (378 vs. 705 days, P=0.0004). CONCLUSIONS: Microbial colonization in bronchoscopy specimens was not associated with pneumonia development or mortality after chemotherapy for lung cancer. This finding suggests that testing surveillance culture may not be helpful for predicting pneumonia or improving survival in lung cancer patients with chemotherapy.

Comparing attenuations of malignant and benign solitary pulmonary nodule using semi-automated region of interest selection on contrast-enhanced CT.

BACKGROUND: The purpose of this study was to determine whether semi-automated region of interest (ROI) measurement of CT attenuations of solitary pulmonary nodule (SPN) is an accurate approach in differentiating malignant from benign SPN. METHODS: Ninety cases of pathologically proven SPN were retrospectively reviewed. CT attenuations of SPN before and after contrast injection were measured using semi-automated ROI selection method. Attenuations within a range of -100 to 200 Hounsfield units (HU) as soft tissue density range were set. The ROI included the entire SPN regardless of its internal soft tissue contents after automatic elimination of airs, calcific, or bony densities. RESULTS: There were 42 (46.7%) malignant SPN and 48 (53.3%) benign SPN, which were grouped into A (18 tuberculoma, 13 fungus), B (5 focal organizing pneumonia, 5 abscess), and C (7 other benign tumors). The malignant SPN showed significantly higher mean attenuations of enhancement and net-enhancement than all benign SPN (P<0.001). Using the area under the receiver operating characteristic curve (AUC), the cut-off net-enhancement of 15 HU gave 83% sensitivity, 65% specificity and 73% accuracy for predicting malignancy. Malignant SPN (mean 67.9 HU) had significantly higher enhancement than group A (mean 52.6 HU, P<0.001, 95% CI: 8.73, 21.81) and group B (mean 57.0 HU, P=0.025, 95% CI: -1.43, 20.34) while group C showed no significant difference (mean 68.1 HU, P=0.97). Net enhancements were higher in group B (mean 18.8 HU) than in group A (mean 8.8 HU) (P<0.001, 95% CI: 11.8, 23.18). CONCLUSIONS: The semi-automated ROI measurement of SPN's attenuations on CT is an accurate approach in distinguishing indeterminate SPN.

Interstitial pneumonia with autoimmune features show better survival and less exacerbations compared to idiopathic pulmonary fibrosis.

BACKGROUND: Patients with interstitial lung disease (ILD) who show features related to autoimmunity without meeting criteria for a defined connective tissue disease are categorized as interstitial pneumonia with autoimmune features (IPAF). The present study compared clinical characteristics and clinical outcomes of patients with IPAF to patients with connective tissue disease related-interstitial lung disease (CTD-ILD) and patients with idiopathic pulmonary fibrosis (IPF). METHODS: ILD patients who were consecutively enrolled in a single institution ILD cohort between 2008 and 2015 were evaluated for the study. Clinical data had been prospectively collected, while radiologic imaging and pathologic findings were re-reviewed for the present study. RESULTS: Out of 305 patients with ILD, 54 (17.7%) patients met the classification of IPAF, 175 (57.4%) patients had IPF, and 76 (24.9%) patients were diagnosed with CTD-ILD. Compared to IPF, incidences of acute exacerbations in 1,3 and 5 years were significantly less in the IPAF group (p = 0.022, p = 0.026 and p = 0.007, respectively). From multivariate analysis for mortality, age (p = 0.034, HR 1.022, 95% CI: 1.002-1.044), FVC (p < 0.001, HR 0.970, 95% CI: 0.955-0.984), ILD exacerbation (p = 0.001, HR 2.074, 95% CI: 1.366-3.148), and ILD type (p = 0.047, HR 0.436, 95% CI: 0.192-0.984 (IPAF vs IPF), respectively) showed significant association. CONCLUSIONS: Compared to the other ILD groups, IPAF showed distinct clinical characteristics. The IPAF group showed better survival and less episodes of exacerbation when compared to the IPF group.

Clinical significance of Glasgow Prognostic Score in patients with tuberculous pleurisy.

BACKGROUND: The Glasgow Prognostic Score (GPS) reflects the host systemic inflammatory response and is a validated, independent prognostic factor for various malignancies. We investigated the clinical significance of the GPS in patients with tuberculosis (TB) pleurisy, focusing on treatment outcomes including paradoxical response (PR). METHODS: This was a retrospective study performed between January 2010 and December 2015 in two referral and university hospitals in South Korea, with intermediate incidences of TB. In all, 462 patients with TB pleurisy were registered in the study. The patients were classified into three groups based on GPS score, as follows: (I) GPS of 2, elevated CRP level (>1.0 mg/dL) and hypoalbuminemia (<3.5 g/dL); (II) GPS of 1, elevated CRP level or hypoalbuminemia; and (III) GPS of 0, neither elevated CRP level nor hypoalbuminemia. RESULTS: A total of 367 patients with TB pleurisy were finally included. PR occurred in 102 (27.8%) patients after a mean of 75 days following initiation of anti-TB treatment. The proportion of PR occurrence was significantly lower in the GPS 2 group (P=0.007). Successful treatment outcomes including cure and completion were also significantly lower in the GPS 2 group (P=0.001), while all-cause mortality and TB-specific mortality were higher in the GPS 2 group (P=0.001 and <0.001, respectively). Old age over than 65 years old was an independent predicting factor for high mortality and lower PR occurrence. However, the TB relapse rate was not different among the three GPS groups. CONCLUSIONS: Higher GPS value and elderly age were identified as prognostic factors for poor outcomes in TB pleurisy and as predicting factors for lower PR occurrence. More prospective studies are needed to clarify the utility of GPS in patients with TB pleurisy.

Inhibiting IGF-1R attenuates cell proliferation and VEGF production in IGF-1R over-expressing EGFR mutant non-small cell lung cancer cells.

PURPOSE: The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells. MATERIALS AND METHODS: Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot. The concentrations of vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Cell growth in PC9 and HCC827 cells was synergistically suppressed by co-treatment with gefitinib and linsitinib. Gefitinib did not affect H1975 cell growth; however, linsitinib suppressed cell proliferation. Co-treatment with gefitinib and linsitinib inhibited pAKT and pERK, and linsitinib treatment profoundly reduced IGF-1-induced pIGF-1R expression in PC9 and HCC827 cells. Dual treatment increased the number of Annexin-V-positive HCC827 and H1975 cells, and expression of cleaved caspase 3 and cleaved PARP increased in H1975 cells following linsitinib treatment. Gefitinib inhibited HIF-1α and VEGF expression in HCC827 cells, and linsitinib inhibited VEGF production in H1975 cells. CONCLUSION: IGF-1R TKIs had modest anti-tumor efficacy and their effects were explained by blocking the EGFR and IGF-1R pathway in IGF-1R expressing EGFR-sensitive cells. IGF-1R TKI had pro-apoptotic activity and inhibited cellular growth in EGFR-resistant cells.

Clinical outcomes of extracorporeal membrane oxygenation support in patients with hematologic malignancies.

BACKGROUND/AIMS: The clinical outcomes of patients with hematologic malignancies who were treated with extracorporeal membrane oxygenation (ECMO) after the failu re of optimal conventional therapy were determined. METHODS: The medical records of all patients administered ECMO during their stay in a medical intensive care unit of Seoul St. Mary's Hospital between February 2010 and July 2013 were reviewed retrospectively. RESULTS: In total, 15 patients with hematologic malignancies were compared to 33 immunocompetent patients with documented cardiorespiratory failure. Underlying hematologic malignancies were significantly associated with lower overall survival (0.0% vs. 24.2%, p = 0.044). Mortality was significantly associated with a higher 24 hours ECMO inspired fraction of oxygen (0.71 ± 0.24 vs. 0.47 ± 0.13, p = 0.015), the development of infection after ECMO (87.5% vs. 25.0%, p = 0.001), and the presence of hyperbilirubinemia (70.0% vs. 0.0%, p < 0.001). Matching of the patients based on their Acute Physiology and Chronic Health Evaluation II scores confirmed the greater risk of mortality in patients with hematologic malignancies (survival: 0.0% vs. 40.0%, p = 0.017). The mean difference in inotropic-equivalent scores after ECMO was significantly lower in the immunocompetent patients than in those with hematologic malignancies (-59.22 ± 97.83 vs. 53.87 ± 164.46, p = 0.026). CONCLUSIONS: Patients with hematologic malignancies who require ECMO for respiratory support have poor outcomes. The incidence of complications in these patients did not significantly differ from that in immunocompetent patients.

Malignant solitary fibrous tumor of the pleura slowly growing over 17 years: case report.

Although a solitary fibrous tumor of the pleura (SFTP) is a rare disease, and usually has a benign course, it has a malignant potential. We report a case of malignant SFTP treated surgically. A 75-year-old female was admitted with a chief complaint of hemoptysis of two weeks duration. Computed tomography of the chest imaged a large mass in the right hemithorax, which compressed adjacent organs; however, there was no evidence of invasion. We reviewed the patient's medical records and found that the mass had been presented for 17 years. Complete resection was achieved through a right thoracotomy and histopathologic examination confirmed a malignant SFTP.

A Case of Pulmonary MALT Lymphoma Arising from Lymphocytic Interstitial Pneumonitis.

Pulmonary mucosa-associated lymphoid tissue-derived (MALT) lymphoma is a rare disease. This disorder is considered to be a model of antigen-driven lymphoma, which is driven either by autoantigens or by chronic inflammatory conditions. Low-grade B-cell MALT lymphoma may develop from a nonneoplastic pulmonary lymphoproliferative disorder, such as lymphocytic interstitial pneumonitis (LIP). A recent estimate predicts that less than 5% of LIP patients acquire malignant, low-grade, B-cell lymphoma. In Korea, there has been no previous report of malignant low-grade, B-cell lymphoma, acquired from LIP. Here, we present the case of a patient with LIP that developed into pulmonary MALT lymphoma, six years after diagnosis.

Pulmonary cryptococcosis mimicking primary lung cancer with multiple lung metastases.

Cryptococcosis is an invasive fungal infection, which is more common in immunocompromised patients. However, pulmonary cryptococcosis can occur in immunocompetent patients and should be considered on a differential diagnosis for nodular or mass-like lesions in chest radiograph. Recently, we experienced a patient with pulmonary cryptococcosis, successfully treated with oral fluconazole therapy. A 74-year-old female patient was referred for an evaluation of abnormal images, a large consolidative mass with multiple nodular consolidations and small nodules that mimics primary lung cancer with multiple lung to lung metastases. Computed tomography-guided lung biopsy confirmed the diagnosis of pulmonary cryptococcosis. The follow-up image taken after 4 months with oral fluconazole treatment showed marked improvement.

Effect of tiotropium bromide on airway remodeling in a chronic asthma model.

BACKGROUND: Recent evidence suggests that acetylcholine acting through muscarinic receptors may play an inhibitory role in the mechanisms that drive the structural changes in the airways called airway remodeling. The novel anticholinergic drug tiotropium bromide, which selectively antagonizes muscarinic receptors, especially the M3 subtype, and is long acting, could be beneficial in attenuating airway remodeling in chronic asthma. OBJECTIVE: To investigate the effect of tiotropium bromide on parameters of airway remodeling, including smooth muscle hypertrophy and peribronchial thickening, in a mouse model of chronic asthma. METHODS: To develop the murine models of acute and chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 1 and 3 months, respectively. The effect of tiotropium bromide (0.1mM in 50 µL of phosphate-buffered saline) on pulmonary inflammation and remodeling was evaluated. The expression of muscarinic receptors M2 and M3 was analyzed. RESULTS: In the chronic asthma model, the tiotropium-treated group significantly decreased smooth muscle thickening and peribronchial collagen deposition. As for pulmonary inflammation, the chronic asthma model had a reduction of inflammatory cells and T(H)2 cytokines by tiotropium bromide, but the effects in the asthma acute model were reversed. In the chronic asthma model, expression of the M3 receptor was inhibited and that of the M2 receptor was elevated by the administration of tiotropium bromide. CONCLUSION: This study suggests that tiotropium bromide might have an inhibitory effect on airway remodeling in a murine model of chronic asthma. Differential effects on muscarinic receptor subtypes may explain why tiotropium bromide has different effects on acute and chronic asthma.

The soluble tumor necrosis factor-alpha receptor suppresses airway inflammation in a murine model of acute asthma.

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-alpha blocking strategies are now being tried in asthma patients. This study investigated whether TNF-alpha blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-alpha blocking therapy on cytokine production and adhesion molecule expression. MATERIALS AND METHODS: Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-alpha receptor (sTNFR) during the OVA challenge. RESULTS: There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue. CONCLUSION: These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.

Vaccination with DNA encoding human T-cell epitopes suppresses Der p induced allergic responses in mice.

The apparent complexity of allergen-specific T-cell response in terms of epitope usage in humans is a potential barrier to peptide-based immunotherapy for allergy. A knowledge of cross-reacting T-cell epitopes of common allergens might have an impact on the development of vaccines for immunotherapy. We examined the efficiency of vaccinating with plasmid DNA coding only human T-cell epitopes on the suppression of allergic reactions in mice. BALB/c mice that received an injection of mixed naked DNA plasmids encoding the five classes of human T-cell epitopes on Der p 1 and Der p 2 produced a significant reduction in total and Der p-specific immunoglobulin E (IgE) synthesis. In Der p specific-IgG2a antibody responses, vaccinated mice showed more prominent responses than controls. Higher levels of interferon-gamma, a Th1 cytokine associated with the suppression of IgE production, were found in the sera of vaccinated mice. Histologic studies showed a marked reduction in the infiltration of inflammatory cells in the lung tissues of vaccinated mice vs. controls. These results suggest that vaccination with DNA encoding human T-cell epitopes effectively inhibits allergic responses in mice and might induce cross-regulation on helper T-cell level in vivo.