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BackgroundAdult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity.MethodsEnvironmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case–control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables.FindingsIn the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28–3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108–0.311, p2.5exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (pInterpretationThese results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.

Idiopathic pulmonary fibrosis (IPF) is a rare and chronic fibrosing interstitial lung disease. However, the clinical features and outcomes of IPF in Taiwan have not been well studied. In addition, the survival difference between patients with IPF alone and combined pulmonary fibrosis and emphysema (CPFE) remains controversial.Patients diagnosed with IPF between 2006 and 2016 were retrospectively enrolled in this study. IPF was defined according to the 2011 American Thoracic Society/European Respiratory Society guideline. The clinical features, comorbidities, and outcomes of CPFE group and IPF-alone group were compared. The extents of emphysema and fibrosis were evaluated.In total, 114 patients with IPF were enrolled, and 86.8% of them were men with a mean age of 77.8 years. The median survival was 3.33 years in all patients with IPF. Moreover, 30 patients (26.3%) met the CPFE criteria. The CPFE group had a higher percentage of smokers (90% vs 50%, p0.001), higher forced vital capacity (82% vs 59%, p0.001), and lower fibrosis scores (8.5 ± 2.9 vs 10 ± 3.2, p = 0.022) than did the IPF-alone group. The baseline room air saturation and percentage of pulmonary hypertension were similar between the two groups. The survival time was not significantly different between the CPFE and IPF-alone groups (median survival, 3.58 vs 2.39 years, p = 0.163). In the multivariate analysis, higher fibrosis score, room air saturation90%, and lung cancer were significant factors associated with mortality.Our study showed that emphysema had no significant effect on the survival of patients with IPF. The outcome of IPF was mainly determined by the baseline disease severity and other comorbidities.

Background: Adult asthma is phenotypically heterogeneous with unclear etiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. Methods: Environmental risk was evaluated by assessing the records of National Health Insurance Research database (NHIRD) and residence-based air pollution [PM2.5 and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)], integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-SNE integrating 18 clinical and demographic variables. Findings: In the NHIRD dataset, a modest increase in the relative risk with time-lag effect for emergency (N=209,837) and outpatient visits (N=638,538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH originated from multiple sources, posing a significant risk for current asthma and its severity, correlating with the level of oxidative stress markers, notably Ne-(hexanoyl)-lysine (HEL) as a marker of response in both cases and controls. Further, levels of circulating sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) were found to discriminate asthma, correlating with the levels of exposure to PAH and metals, respectively, and both correlating with a panel of circulating inflammatory markers. Stratification of the combined datasets by 6 phenotypic clusters among 1,163 asthmatic subjects and those with comorbid T2DM revealed cluster-selective environmental risks and biosignatures. Interpretation: These results suggest the potential contribution of environmental factors, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity. Funding Information: This work was supported, in part, by grants from National Health Research Institutes, Taiwan (EOPP10-014, EOSP07-014 and NHRI-102A1-PDCO-03010201) and Ministry of Health, Taiwan (EODOH01), National Science Council (NSC 102-2314-B-037-052), Ministry of Health (EODOH01), Ministry of Science and Technology (MOST 103-2320-B-110-001), and Academic Sinica (BM-102021170), Taiwan. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: All eligible subjects were enrolled in the study after signing the informed consent approved by the respective recruitment hospitals.

We proposed a modification of the ACR Lung Imaging Reporting and Data System (Lung-RADS) to clarify the characteristics of subsolid nodules with categories 1-11, and to compare the diagnostic accuracy with Lung-RADS and National Lung Screening Trial criteria in an Asian population with high prevalence of adenocarcinoma.We analyzed a retrospective cohort of 1978 consecutive healthy subjects (72.8% nonsmoker) who underwent low-dose computed tomography from August 2013 to October 2014 (1084 men, 894 women). Lung-RADS categories 2 and 3 were modified to include subcategories of 2A/2B/2C and 3A/3B/3C, respectively. Clinical information and nodule characteristics were recorded. Receiver operating characteristic curves were used to compare diagnostic accuracy at different cutoffs.Thirty-two subjects (30 nonsmokers) had pathology-proven adenocarcinoma spectrum lesions in the follow-up period (1.6 ± 0.5 years). Modified Lung-RADS, using modified Lung-RADS category 2C as cutoff, had an area under the curve (AUC) of 0.973 in predicting adenocarcinoma spectrum lesions (sensitivity of 100%, specificity of 89.3%), which was significantly higher than that of Lung-RADS (AUC = 0.815, P .001) and National Lung Screening Trial (AUC = 0.906, P .001). Furthermore, modified Lung-RADS showed an AUC of 0.992 in predicting invasive adenocarcinoma (sensitivity of 95%, specificity of 97.8%) when category 3B was used as cutoff.Modified Lung-RADS may substantially improve sensitivity while maintaining specificity for detection of adenocarcinoma spectrum lesions in an Asian population. Compared to Lung-RADS, it has enhanced ability to differentiate invasive from indolent adenocarcinoma by more refined subclassification of subsolid nodules using two cutoff values of category 2C and 3B. The effect of using modified Lung-RADS in clinical practice must be carefully studied in prospective large cohort studies.

Cardiac radiotherapy is rarely used in clinical practice because of concern of adverse effects on the heart. We present a case of a 64-year-old man with advanced small cell lung cancer (SCLC) treated with chemo-radiotherapy who attained partial remission initially but had disease progression to bulky cardiac metastasis and significant pericardial effusion. Severe heart failure with hepatic failure was found. Chemotherapy and pericardiocentesis were contraindicated because of the associated high risk and bleeding tendency. Emergent palliative cardiac radiotherapy resulted in rapid improvements of dyspnea, liver function, and urine output. Pericardiocentesis was performed 5 days later and effusion cytology confirmed metastatic SCLC. To our knowledge, this is the first case of effective cardiac radiotherapy for SCLC with life-threatening cardiac metastasis. Palliative cardiac radiotherapy may be an effective alternative treatment for radiosensitive malignancy with cardiac metastasis in cases of multiple organ dysfunction and unsuitability for chemotherapy and pericardiocentesis.

CD14+ monocytes contain precursors for macrophages and fibrocytes, known to be involved in regulating airway remodeling in human asthma and distinguishable by the PM-2K marker. We sought to identify circulating subsets of PM-2K+ macrophage-like cells and evaluate their relationships to lung function, severity and control status. Circulating PM-2K+ macrophage-like cells and fibrocytes could be identified and distinguished between normal individuals (N = 152) and asthmatic subjects (N = 133) using multi-parametric flow cytometry. PM-2K+ macrophage-like cells were found to be significantly lower in asthmatic subjects, particularly noted for the CD14−PM-2K+ subset and PM-2K+CCR7−CD86+ cells in subjects with poor lung function (FEV%/FVC% −CD86+ subset distribution was significantly different in subjects with varying severity. Moreover, exogenous transforming growth factor beta 1 (TGF-β1) was found to inhibit the generation of PM-2K+ macrophage-like cells, but promote the growth of fibrocytes, from CD14+ monocytes, and monocyte-derived TGF-β1 was found to correlate with the lung function, severity and control status in asthmatic patients. Collectively, aberrant differentiation of monocytes into PM-2K+ macrophage-like cell subsets and fibrocytes, together with increased monocyte-derived TGF-β1, characterized patients with severe asthma.

Background: Among respiratory predictors, rapid shallow breathing index (RSBI) has been a commonly used respiratory parameter to predict extubation outcomes. However, the outcome of prediction remains inconsistent. Regarding nonrespiratory predictors, serum albumin, hemoglobin, bicarbonate, and patients’ alertness have been reported to be associated with successful weaning or extubation. We aimed to develop an integrative index combining commonly used predictors in the adult medical intensive care units (MICUs) and to compare the predictability of the index with RSBI. Methods: This prospective observational study with retrospective data collection of planned extubations was conducted in a 14-bed adult MICU. We enrolled patients who received mechanical ventilation via an endotracheal tube in the adult MICU for >24 hours and passed a 2-hour spontaneous breathing trial and underwent extubation. Extubation failure was defined as reinstitution of invasive mechanical ventilation within 48 hours of extubation. Respiratory parameters and Glasgow Coma Scale (GCS) scores of patients were recorded prospectively. Nonrespiratory parameters were recorded retrospectively. Logistic regression was used to determine significant predictors of extubation outcomes. Results: Fifty-nine patients comprising 70 extubations were enrolled. Extubation failure was significantly and positively associated with lower serum albumin (albumin < 2.6 g/dL, odds ratio [OR] = 5.1; 95% confidence interval [CI], 1.04-24.66), lower hemoglobin (hemoglobin < 10.0 g/dL, OR = 10.8; 95% CI, 2.00-58.04), and lower GCS scores (GCS score ≤ 8, OR = 6.1; 95% CI = 1.15-32.34). By using an integrative index combining the 3 parameters together, the sensitivity and specificity to predict extubation outcomes were 78.6% and 75.9%, respectively. The area under the receiver operating characteristic curve of the index was significantly higher than RSBI (0.84 vs 0.61, P = .026). Conclusion: The integrative index combining serum albumin, hemoglobin, and GCS scores could predict extubation outcomes better than RSBI in an adult MICU.

Exposure to polycyclic aromatic hydrocarbons (PAHs) associated with ambient air particulate matter (PM) poses significant health concerns. Several modeling approaches have been developed for simulating ambient PAHs, but no hourly intra-urban spatial data are currently available. The aim of this study is to develop a new modeling strategy in simulating, on an hourly basis, grid-scale PM2.5-PAH levels. PM and PAHs were collected over a one-year time frame through an established air quality monitoring network within a metropolitan area of Taiwan. Multivariate linear regression models, in combination with correlation analysis and PAH source identification by principal component analysis (PCA), were performed to simulate hourly grid-scale PM2.5-PAH concentrations, taking criteria pollutants and meteorological variables selected as possible predictors. The simulated levels of 72-h personal exposure were found to be significantly (R=0.729**, p

Chronic exposure to ambient polycyclic aromatic hydrocarbons (PAHs) is associated with asthma, but its regulatory mechanisms remain incompletely defined. We report herein that elevated levels of urinary 1-hydroxypyrene, a biomarker of PAH exposure, were found in asthmatic subjects (n = 39) as compared to those in healthy subjects (n = 43) living in an industrial city of Taiwan, where indeno[1,2,3-cd]pyrene (IP) was found to be a prominent PAH associated with ambient PM2.5. In a mouse model, intranasal exposure of mice with varying doses of IP significantly enhanced antigen-induced allergic inflammation, including increased airway eosinophilia, Th2 cytokines, including IL-4 and IL-5, as well as antigen-specific IgE level, which was absent in dendritic cell (DC)-specific aryl hydrocarbon receptor (AhR)-null mice. Mechanistically, IP treatment significantly altered DC’s function, including increased level of pro-inflammatory IL-6 and decreased generation of anti-inflammatory IL-10. The IP’s effect was lost in DCs from mice carrying an AhR-mutant allele. Taken together, these results suggest that chronic exposure to environmental PAHs may pose a significant risk for asthma, in which IP, a prominent ambient PAH in Taiwan, was shown to enhance the severity of allergic lung inflammation in mice through, at least in part, its ability in modulating DC’s function in an AhR-dependent manner.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. Preclinical studies have suggested that uncommon G719X, L861Q, and S768I mutations are also sensitive to EGFR-TKIs. However, the efficacy of EGFR-TKIs in patients with these uncommon mutations remains unclear.A nationwide survey was performed to collect data from gefitinib and erlotinib treatment outcomes of patients with stage IIIB/IV lung adenocarcinoma bearing EGFR G719X/L861Q/S768I mutations. The results were compared with those regarding patients with exon 19 deletions or L858R mutations.One hundred and sixty-one patients with uncommon EGFR mutations were enrolled from 18 institutes throughout Taiwan. Mutations of G719X, L861Q, S768I, G719X + L861Q, and G719X + S768I were observed in 78, 57, 7, 9, and 10 patients, respectively. After receiving EGFR-TKI treatment, patients with uncommon mutations exhibited a significantly inferior tumor response rate (41.6% vs. 66.5%; p0.001) and progression-free survival (median, 7.7 vs. 11.4 months; p0.001) than patients with common mutations. Among the patients who used EGFR-TKIs as first-line treatment, there was a significant difference in overall survival between these two groups of patients (median, 24.0 vs. 29.7 months; p = 0.005).Gefitinib and erlotinib are active in patients with G719X/L861Q/S768I mutations; however, less effective than in those with common mutations.

Rationale: IgG4-related disease is a rare and novel disease entity that tends to involve multiple organs. The pulmonary manifestation of this disease is highly variable and may mimic lung cancer, pneumonia, interstitial lung disease (ILD), sarcoidosis, and so forth. Small airway disease is rarely reported in IgG4-related lung disease (IgG4-RLD). In the current study, we describe a rare case of IgG4-RLD with patterns of ILD and bronchiolitis. Patient concern: A 43-year-old man had chronic cough and dyspnea on exertion for 4 years. Initial chest radiography showed diffuse interstitial infiltration. Follow-up chest computed tomography 4 years later revealed bilateral diffuse centrilobular nodules with tree-in-bud pattern, bronchial wall thickening, and mediastinal lymph nodes. Bilateral diffuse multifocal ground-glass opacities and mosaic attenuation were also observed. Pulmonary function test revealed mixed restrictive and obstructive ventilatory impairment. Diagnoses: Video-assisted thoracoscopic surgery (VATS) lung biopsy showed interstitial fibrosis with lymphoplasmacytic infiltration rich in IgG4-positive plasma cells. Serum IgG4 level also showed remarkable elevation. Therefore, IgG4-RLD is confirmed. Intervention: VATS wedge resection of right upper lobe and mediastinal lymph node. Outcomes: The patient responded well to steroid and immunosuppression therapy, and was regular followed-up in outpatient clinic. Lessons: IgG4-RLD should be considered not only in ILD, but also in small airway disease. Serum IgG4 level may be a useful tool for screening.

Background: The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients. Methods: This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared. Results: Among the 253 randomized subjects, 244 patients were evaluable (119 in the BDP/F group and 125 in the FP/S group). A significant improvement from baseline to the end of treatment period was observed in both BDP/F and FP/S groups in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), morning and evening peak expiratory flow (PEF), Asthma Control Test (ACT) score and the use of rescue medication. FVC increase from pre-dose was significant after 5 min post inhalation in the BDP/F group only, while statistically significant within group improvement was not achieved until 30 min post inhalation in the FP/S group. Conclusion: The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F. Keywords: Asthma, Combination therapy, Inhaled corticosteroid, Long acting beta2-agonist, Pulmonary hyperinflation

Unplanned extubation (UE) may cause considerable adverse effects in patients receiving mechanical ventilation (MV). Previous literature showed inconsistent prognosis in patients with UE. This study aimed to evaluate the clinical implications and outcomes of UE.The intubated adult patients with MV support in our hospital were enrolled, and they were divided into the UE and non-UE groups. Demographic data, admission unit, MV duration, overall weaning rate, and mortality rates were compared. The outcomes of UE in ordinary ward and intensive care unit (ICU) were also assessed.Totally 9245 intubated adult patients were included. UE occurred in 303 (3.5%) patients, and the UE events were 0.27 times/100 MV days. Old age, nonoperation related MV cause, and admission out of the ICU were significant factors associated with UE events. UE patients showed a trend of better overall weaning rate (71.9% vs 66.7%, P = .054) than non-UE. However, the in-hospital mortality rate (25.7% vs 24.8%, P = .713) were similar between the UE and non-UE patients. The reintubation rate of UE patients was 44.1% (142/322). Successful UEs were associated with patients in weaning process (52.8% vs 38.7%, P = .012), and patients received non-invasive positive pressure ventilation (NIPPV) support after UE (19.4% vs 3.5%, P < .001). Patients with successful UE had significantly shorter MV days, higher overall weaning rate, and lower mortality than those with unsuccessful UE. Outcomes of UE in ordinary ward and in ICU had similar MV duration, reintubation rate, overall weaning rate, and in-hospital mortality rate.The overall weaning rate and in-hospital mortality rates of the UE and non-UE patients were similar. UE occurred in ordinary ward had similar outcomes to those in ICU. Patients receiving MV should be assessed daily for weaning indications to reduce delayed extubation, and therefore, may decrease UE occurrence. Once the UE happened, NIPPV support may reduce the reintubation rate.

Summary Purpose Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which has demonstrated a survival benefit in non-small-cell lung cancer (NSCLC) patients. An open label phase II study was conducted in Taiwanese patients with NSCLC to evaluate its efficacy. Methods Patients with proven stage IIIB/IV NSCLC who had received at least one line of standard chemotherapy or radiotherapy were enrolled into this study. All patients were given oral erlotinib, 150 mg/day till disease progression. Results From May 2005 to July 2006, 300 patients were entered from 14 hospitals in Taiwan. This analysis was based on 299 patients who received at least one dose of erlotinib. The best response rates were a 29% partial response and 44% stable disease in 273 patients who had response data available. Non-smoking (p = 0.033), adenocarcinoma/BAC (p = 0.0027), female (p = 0.0013), aged less than 65 years (p = 0.0115), stage IV (p = 0.0492), patients with skin rash (p = 0.0216), and a higher grade of skin rash (p = 0.003) were significantly correlated with response to treatment. Skin rash was a common adverse event (any grade: 84%, Gr 3–4: 16%). The median time to disease progression was 5.6 months. Cox regression model for progression free survival showed patients most at risk of early progression were males of low performance status having squamous cell carcinoma. Conclusions This was the largest multicenter prospective clinical study of NSCLC in Taiwan. The results demonstrated the excellent response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese NSCLC patients who had been previously treated with chemotherapy or radiotherapy.

Schwannoma is the most common nerve sheath tumor in the posterior mediastinum, whereas intrathoracic paraspinal malignant peripheral nerve sheath tumor (MPNST) is quite rare. Both benign and malignant nerve sheath tumors may be symptomatic, rendering clinical differentiation of limited utility. On radiographic imaging, erosion of the ribs and vertebral bodies, irregularity in contour, and inhomogeneity in attenuation are not sufficiently reliable for diagnosis of MPNST. Histologically, MPNSTs reveal hypercellularity, nuclear atypia, and mitotic activity. Surgical resection is the main modality of treatment. Postoperative radiation therapy for MPNST has led to a significant reduction in local recurrence. The prognosis is unfavorable. Herein, we present an unusual case of a posterior mediastinal mass in a 50-year-old female with delayed diagnosis of 2 years. After surgical intervention, the histologic finding was MPNST. Postoperative radiation therapy was applied because of incomplete resection. The follow-up chest computed tomography 5 months later revealed a residual soft tissue mass with significant reduction in size over the parathoracic spine area. No neurologic sequelae were identified after surgery.

A 77-year-old man with a progressively dry cough (two months duration) was admitted with hemoptysis. Chest computed tomography (CT) revealed left lingular lobe consolidation and one thick-walled cavity lesion over the left lower lobe, which was accompanied by satellite micro-nodules in a tree-in-bud pattern. CT-guided biopsy confirmed mycobacterial infection, and subsequent culture yielded Mycobacterium avium complex (MAC). Unremitting hemoptysis was present despite treatment (14 days) with ethambutol, rifampin, clarithromycin, and streptomycin. Initial CT angiography (CTA) to determine the source of the hemoptysis revealed a suspected aneurysm in the consolidated left lingular lobe; however, this could not be localized via catheter angiography during the pulmonary and bronchial arterial phases. Two weeks later, a massive hemoptysis episode led to haemodynamic instability and serious consequences. Follow-up CTA confirmed the previously detected aneurysm, and glue embolization was performed successfully. This case report highlights a rare but catastrophic MAC-associated pseudoaneurysm and relevant treatment options.

A 59-year-old woman presented to our clinic with a dry cough and dull pain over her entire back that had persisted for more than 1 week. The patient had no sputum production, fever, sore throat or prior history of tuberculosis, and she had not travelled recently. On examination, she was tachypnoeic and hypoxaemic, with dry crackles in both lower lungs. Her oxygenation saturation was 90% when …

The development of constrictive bronchiolitis obliterans in patients who have ingested Sauropus androgynus juice has not been previously reported. We describe four patients with S. androgynus-associated constrictive bronchiolitis obliterans who underwent open lung biopsies for histopathological analysis. This article aims to recognize the possible pathogenesis of the disease. The spectrum of histologic changes ranged from slight bronchiolar inflammation and fibrosis to marked submucosal fibrosis causing complete cicatricial obliteration of the lumen. A dense eosinophil infiltrate was noted in the bronchiolar submucosa or fibrotic tissue of the completely obliterated bronchioles in two patients. Immunohistochemical studies revealed that lymphocytic infiltrate consisted mainly of T lymphocytes in all patients. Immunofluorescent stains for immunoglobulin (Ig)G, IgA, IgM, C1q, C3, and C4 were negative. Electron microscopy disclosed no immune complex deposition in the specimens examined. Although the role of antibody- and complement-mediated reaction is not supported by the negative results of immunofluorescent and electron microscopic studies, the common finding of the predominant T-lymphocytic infiltrate suggests that a T-cell mediated immune response is involved in the pathogenesis of the disease. Furthermore, the finding of a heavy lymphocytic infiltrate in many bronchioles without significant collagen deposition suggests that the lymphocytic infiltrate may precede the tissue fibrosis. In addition, the presence of a dense eosinophil infiltrate may combine with lymphocytes and other immunologic and mesenchymal cells to promote antigen-specific stimulation of lymphocytes and induction of fibrosis.

Background The CYFRA 21–1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21–1 is a sensitive and specific tumor marker for non-small cell lung cancer. Methods CYFRA 21–1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21–1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer. Results The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21–1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21–1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21–1 assay has the highest sensitivity. The median level of CYFRA 21–1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p 0.1). Conclusion For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21–1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.

Intrathoracic extramedullary haematopoiesis (EMH) is a rare entity that is usually asymptomatic. A 44 year old man with alpha-thalassaemia is described who developed dyspnoea and massive left sided haemothorax. The haemoglobin disorder was established by Hgb H staining and haemoglobin electrophoretic studies. The DNA analysis revealed it to be a case of double heterozygous terminal codon mutation with the genotype alphaalphaCS/alphaalphaT. Computed tomographic scanning and magnetic resonance imaging of the thorax showed multiple paravertebral masses which were found by thoracoscopic biopsy to be extramedullary haematopoiesis. Although no additional sclerosing pleurodesis or low dose radiation therapy was given, the lung expanded well and there has been no recurrence of haemothorax to date.

Churg-Strauss syndrome (CSS) is a rare disorder characterized by the histopathological triad of systemic necrotizing vasculitis, extravascular granuloma, and eosinophilic infiltrate, occurring in individuals with asthma or a history of allergy. We report a case of CSS with rare presentation of diffuse pulmonary hemorrhage. A transbronchial lung biopsy showed necrotizing vasculitis, pulmonary capillaritis, and prominent eosinophilic infiltrate. At autopsy, necrotizing granuloma and diffuse alveolar hemorrhage were found in the lungs. Laboratory data showed hypereosinophilia, disseminated intravascular coagulopathy, and positive anti-proteinase 3 antineutrophil cytoplasmic antibody (ANCA). This case emphasize that CSS should be considered in the differential diagnosis of ANCA-positive vasculitis with diffuse alveolar hemorrhage.

Summary Background In August, 1995, there was an outbreak in Taiwan of rapidly progressive respiratory distress associated with consumption of uncooked Sauropus androgynus , a vegetable with a claimed yet unconfirmed effect on weight control. We report on 23 patients with strikingly similar clinical presentations. Methods A structured questionnaire for clinical manifestations was completed. Radiographic findings, pulmonary physiological changes, immunological and microbiological studies, and pathological examination were evaluated. Findings All patients were young and middle-aged women (mean age 39 years [range 21–52]). They took uncooked S androgynus juice, generally mixed with guava or pineapple juice, for a mean duration of 10 weeks. Progressive dyspnoea and persistent cough were the main symptoms on presentation. Pulmonary function testing uniformly revealed moderate to severe airflow obstruction with mean forced expiratory volume in 1 s (FEV 1 ) of 0·66 L (26% of predicted). No bronchodilator response was observed. Room-air arterial blood gas analysis showed hypoxaemia (mean PaO 2 9·6 [SD 1·6] kPa). Chest radiographs were essentially normal. High-resolution computed tomography showed bilateral bronchiectasis and patchy low attenuation of lung parenchyma with mosaic perfusion. Ventilation-perfusion scintigraphic findings were compatible with obstructive lung disease. Histopathology of open lung biopsy specimens in four patients confirmed the presence of bronchiolitis obliterans. Immunohistochemical stains of the open lung biopsy specimens showed predominance of T cells over B cells. Immunofluorescent stains for IgG, IgM, IgA, C1q, C3, and C4 were negative. Serum concentrations of tumour necrosis factor a were higher than those of normal controls. Clinical response to prednisolone was limited. Interpretation We describe an unusual association between bronchiolitis obliterans and ingestion of the vegetable S androgynus. T-cell mediated immunity may be involved in the pathogenesis.

A 17-year-old man was admitted to the emergency department complaining of a mouth full of blood that he had spit out twice since the previous day. A chest radiogram revealed a small right lung and dextroposition of the cardiomediastinal structure (Figure 1). After the man’s condition was stabilized, he underwent an MRI to evaluate a suspected congenital anomaly. After a contrast agent was injected intravenously, 3-dimensional magnetic resonance angiography (MRA) was performed with a 1.5-T scanner while the man held his breath for 10 seconds. Oblique-coronal reconstruction revealed …

Background: Tumor staging remains the most important prognostic predictor in patients with non-small cell lung cancer (NSCLC). However, the prognostic significance of expression of oncoproteins involved in regulation of cellular uncontrolled proliferation remains controversial. Methods: In this retrospective study, we investigated the expression of bcl-2 and p53 oncoproteins in 114 surgically resected NSCLC patients (46 stage I, 39 stage II and 29 stage IIIa) using immunohistochemical analysis and correlated the molecular markers with survival. Results: Positive bcl-2 immunoreactivity was detected in 26 of 114 (22.8%) NSCLC, including 15 of 43 (34.9%) squamous cell carcinoma and 11 of 71 (15.5%) adenocarcinoma cases. Nuclear staining for p53 was observed in 59 of 114 (51.8%) NSCLC, including 26 of 43 (60.5%) squamous cell carcinoma and 33 of 71 (46.5%) adenocarcinoma patients. There was no correlation between pathological staging and expression of bcl-2 and p53. However, the expression frequency of bcl-2 was significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.02). The presence of bcl-2 expression did not provide a favorable prognosis (P = 0.23) and the overexpression of p53 oncoprotein was also not significantly associated with adverse prognosis (P = 0.09). No inverse relationship was found between bcl-2 and p53 expression (P = 0.83). Conclusion: Expressions of bcl-2 and p53 using immunohistochemical staining are not independent prognostic predictors in patients undergoing surgery for NSCLC.

In late April 1995, an outbreak of a poorly defined respiratory illness related to the ingestion of leaves of Sauropus androgynus was observed in southern Taiwan. To further evaluate the association between S. androgynus and bronchiolitis obliterans syndrome, a hospital-based case-control study was conducted with one case group and three different control groups at Veterans General Hospital-Kaohsiung between April and September 1995. A total of 54 cases (50 females, 4 males), 54 age- and sex-matched neighborhood controls, 54 matched routine physical check-up controls, and 54 matched self-referred patron controls (who had ingested S. androgynus yet without obstructive physiology) were interviewed for clinical symptoms, history of S. androgynus consumption, and potential confounding factors. All 54 cases (100%) ingested S. androgynus compared with only five (9%) neighborhood controls (matched odds ratio (OR) incalculable, p0.001) and two (4%) physical check-up controls (matched OR incalculable, p0.001). In the univariate analysis of 54 cases and 54 self-referred patron controls, factors associated with an increased risk of bronchiolitis obliterans syndrome were methods of food preparation (uncooked juice vs. stir fried or boiled dishes, matched OR 10.3 (95% confidence interval (CI) 1.3-84.4)); preparer of the S. androgynus-containing food (vendor only vs. patient only or patient plus vendor, matched OR 2.8 (95% CI 1.1-7.1)); total S. androgynus consumption quantity (4,500 vs. 413-2,063 g, matched OR 10.0 (95% CI 1.9-53.0)); duration of consumption (45 vs. 6-24 days, matched OR 2.1 (95% CI 1.2-3.8)); and midterm interruption (2 vs. 2-5 days per week, matched OR 2.6 (95% CI 1.1-6.1)). Additionally, multiple conditional logistic regression analysis of cases and self-referred patron controls revealed that a larger total amount of S. androgynus consumption, preparation of S. androgynus food without cooking, and ingesting S. androgynus food prepared by a vendor were the significant risk factors associated with bronchiolitis obliterans syndrome.

An outbreak of Sauropus androgynus-associated bronchiolitis obliterans occurred in Taiwan in the summer of 1995. We undertook a study of the correlation between high-resolution CT findings and pulmonary function testing in patients from this outbreak.We evaluated inspiratory-expiratory high-resolution CT scans of 24 patients with S. androgynus-associated bronchiolitis obliterans. The presence of bronchiectasis was assessed by two visual scores (a bronchial dilatation score and a bronchiectasis extent score). Extent of air-trapping was assessed visually and given a score. We also used computer software to assess the extent of air-trapping and generate scores of dynamic attenuation. Spirometry, plethysmography, and diffusion capacity of each patient were also obtained.All four scores had statistically significant correlation with forced expiratory volume in 1 sec (FEV1) (p.05 for both bronchiectasis scores; p.001 for both air-trapping scores). The two air-trapping scores had statistically significant correlation with forced vital capacity and diffusion capacity. We found the scores for dynamic attenuation had the greatest correlation with FEV1 (r = .85). We also found that mosaic attenuation was notable on expiratory CT scans alone in nine patients (type 1 air-trapping) and on both inspiratory and expiratory CT scans in 15 patients (type 2 air-trapping). In the latter group, FEV1 was significantly lower (p.01).Findings from high-resolution CT of air-trapping were more important than findings of bronchiectasis when correlating pulmonary function with S. androgynus-associated bronchiolitis obliterans. Type 2 air-trapping suggested a more severe air-flow obstruction than did type 1. Scores for quantitative attenuation generated by computer software were helpful in assessing air-trapping and correlating it with pulmonary function. These findings may apply to patients with bronchiolitis obliterans from other causes.

TPS7614 Background: First-line erlotinib (an EGFR tyrosine-kinase inhibitor) significantly increased progression-free survival (PFS) vs chemotherapy in phase III trials of pts with EGFR mutation-positive NSCLC. Discontinuation of erlotinib on RECIST disease progression (PD) may lead to rapid disease flare-up; continued erlotinib beyond RECIST PD may extend clinical benefit by slowing progression of this life-threatening disease. We describe ASPIRATION, a large, Asian, multicenter, single-arm, open-label, phase II trial (NCT01310036), which will increase understanding of first-line erlotinib and erlotinib continuation beyond RECIST PD in pts with EGFR-mutated NSCLC. Methods: Pts (n=204) ≥18 yrs with stage IV/recurrent NSCLC, ≥1 measurable lesion (≥10mm), ECOG performance status (PS) 0-2 and positive EGFR mutation status established by local pathology laboratory (that underwent voluntarily QA/QC) are eligible. All pts receive erlotinib 150mg/day. Tumor response is evaluated using RECIST (v1.1). The primary endpoint is PFS. At investigator's discretion, pts may continue on erlotinib beyond RECIST PD, e.g. if they have slow PD (>6 months of partial response/stable disease), asymptomatic minimal PD, or new brain metastasis controlled locally. Pts should not continue erlotinib if they have extracranial PD with symptoms; rapid PD and/or worsening of PS; or life-threatening complications. Pts continuing erlotinib who present with second RECIST PD will discontinue. Secondary endpoints include objective response rate, disease control rate, overall survival, and safety. For the exploratory biomarker study, pre-treatment tumor tissue blocks are collected; remaining tissue (after EGFR mutation testing for eligibility) will be analyzed centrally to study the association of biomarkers and clinical outcomes. Pre-treatment and post-treatment plasma and serum samples will be obtained at various time points for biomarker assays, including EGFR mutations and other candidate NSCLC biomarkers. Recruitment began in Apr 2011; the estimated final data collection for the primary endpoint is Dec 2014.

Colonic metastasis from lung cancer is rare and generally asymptomatic. Here, we report a case with lung adenocarcinoma that presented with acute abdominal pain due to intestinal obstruction caused by the metastatic colon tumor. The patient underwent emergency colonoscopy and the pathologic report was adenocarcinoma, which was the same as that for a bronchoscopic biopsy from a large lung mass. Immunohistochemistry was positive for thyroid transcription factor-1 and cytokeratin 7, and negative for cytokeratin 20 and caudal-related homeobox transcription factor 2 on both lung biopsy and colon surgical specimens. Accordingly, we used immunohisto-chemistry for thyroid transcription factor-1, cytokeratin 7, cytokeratin 20 and caudal-related homeobox transcription factor-2 to diagnose primary adenocarcinoma of the lung with colonic metastasis.