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Background Toll‐like receptor (TLR)‐7‐associated rhinovirus (RV) activation is involved in the pathogenesis of asthma. Plasmacytoid dendritic cells (pDCs) are the main interferon‐α‐producing cells against viruses. Objective To determine whether asthmatic patients and control subjects differ in terms of interferon‐α expression in pDCs under TLR‐7 or RV stimulation. Methods pDCs were identified in BDCA‐2+ and HLA‐DR+ peripheral blood mononuclear cells. Interferon‐α expression of pDCs was analyzed after TLR‐7 stimulation with or without interleukin 4 (IL‐4)/IL‐13 pretreatment. Interferon‐α expression was also analyzed after RV stimulation over periods of 24, 48, or 96 h with or without IL‐4 pretreatment. RV detection and molecular typing were assayed from throat swabs. Results Following TLR‐7 stimulation, the expression of intracellular interferon‐α was higher in the pDCs of normal subjects than those of asthmatic patients; however, pretreatment with IL‐4 was shown to reduce this effect. After 48‐ and 96‐h RV stimulation, we observed a notable increase in the production of interferon‐α of pDCs in normal subjects but not in asthmatic patients. Baseline interferon‐α expression in pDCs and the incidence of asthma exacerbation to emergency was higher among the 13% of patients identified as rhinovirus+ than among their RV counterparts. Conclusion Our study discovered the response to TLR‐7 stimulation in pDCs was compromised and the sustainability of interferon‐α expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings. Further research is required for the modulatory effect of IL‐4 on TLR‐7 stimulated pDCs., Our study discovered the response to TLR‐7 stimulation in pDCs was compromised and the sustainability of interferon‐a expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings.

Differences in the clinical phenotypes and outcomes of fungus-associated asthma remain unclear. We aimed to investigate the presentation of asthmatics with fungal sensitization and/or positive fungal isolates.Clinical characteristics, pulmonary function, microbiological data, allergy test reports, emergency department (ED) visits and hospitalizations were retrieved from the Chang Gung Research Database between 2010 and 2018; the largest electronic medical record-based database in Taiwan. Follow-up care was provided to each patient for 3 years.A total of 30,754 asthmatics were enrolled, and 7976 were eligible for analysis after applying the exclusion criteria. Of these patients, 694 had sputum examinations for fungi. The patients were divided into four groups: group 1, neither fungal sensitization nor fungal isolates in the sputum (n = 386); group 2, positive fungal sensitization (n = 58); group 3, positive fungal isolates (n = 217); and group 4, concomitant positive fungal sensitization and positive fungal isolates (n = 33). Asthmatic patients with fungal sensitization (groups 2 and 4) demonstrated significantly higher IgE levels compared with those without (groups 1 and 3). Group 4 patients had a higher frequency of hospitalization. Amongst patients under Global Initiative for Asthma (GINA) step 4-5 therapies, group 4 asthmatics possessed significantly higher incidence of respiratory failure.The prevalence of fungal sensitization and fungal isolates from sputum were even across asthmatic severities, but the clinical impact of fungi may be more significant among patients with more severe disease.

Background The bronchiectasis severity index (BSI) and FACED score are currently used in predicting outcomes of non-cystic fibrosis bronchiectasis (NCFB). Distance-saturation product (DSP), the product of distance walked, and lowest oxygen saturation during the 6-min walk test showed strong predictive power of mortality in non-CF bronchiectasis patients. This study aimed to compare the efficacy of these scores and DSP in predicting mortality. Methods and Patients Our retrospective study included NCFB patients from January 2004 to December 2017. We recorded the basic data, pulmonary function, radiologic studies, sputum culture results, acute exacerbations (AE), emergency department (ED) visits, hospitalization, and mortality. Results A total 130 NCFB patients were analysed. The mean BSI score, FACED score, and DSP were 8.8 ± 4.9, 3.4 ± 1.7, and 413.1 ± 101.5 m%, respectively. BSI and FACED scores had comparable predictive power for AE (p=.011; p=.010, respectively). The BSI score demonstrated a significant correlation with ED visits (p=.0003). There were 12 deaths. Patients were stratified using a DSP cut-off value of 345 m% according to the best area under receiver operator characteristic curve (AUC) value in mortality. DSP was not correlated with AE and ED visits. BSI, FACED scores, and DSP demonstrated statistically significant correlations with hospitalization (p

Background The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. Methods This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). Results The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64–0.97), n = 43) and a desynchronized group (median 0.23 (0.02–0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. Conclusion This is the first result studying the heart–lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Background: Although comorbidites of cardiovascular disease is common in patients with chronic obstructive pulmonary disease (COPD), the interaction between the heart and lungs in COPD patients has yet to be further elucidated. Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Aim: Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. Methods: This is a cross-sectional and a preliminary data from a prospective study, examining 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by six-minute walking test (6MWT).Results: The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64-0.97), n=43) and a desynchronized group (median 0.23 (0.02-0.51), n=12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r=0.42, p=0.001) and distance saturation product (r= 0.41, p=0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis.Conclusion: This is the first result studying the heart-lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Background : Cardiovascular disease is a common comorbidity and cause of mortality among patients with chronic obstructive pulmonary disease (COPD). However, the interaction between the heart and lungs in COPD patients has yet to be fully elucidated.Aim : Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiration flow signals.Methods : This prospective study examined 10 normal subjects and 55 COPD patients. Linear regression and forward stepwise regression were used to determine the correlation between the synchrogram index and the six-minute walking test.Results : K-means clustering analysis was used to separate the 55 COPD patients into a synchronized group (median 0.89 (0.64-0.97), n=43) and a desynchronized group (median 0.23 (0.02-0.51), n=12) based on the synchrogram index. In this study, the synchrogram index was significantly correlated with the six-minute walking distance (r 2 =0.3, sigma T=0.02) and the distance saturation product (r 2 =0.3, sigma T =0.03). Note that age was a significant confounding factor.Conclusion : The synchrogram index shows clinical potential for the stratification of COPD patients for treatment.

Purpose Pseudomonas aeruginosa is associated with pulmonary function decline and high disease severity in non-cystic fibrosis (CF) bronchiectasis. The prevalence of nontuberculous mycobacteria (NTM) in non-CF bronchiectasis patients has increased recently. This study investigated the impact of NTM with or without P. aeruginosa isolates in non-CF bronchiectasis patients. Patients and methods Our retrospective study included 96 non-CF bronchiectasis patients from January 2005 to December 2014. We recorded the presentation, exacerbations, emergency department (ED) visits, hospitalization, serial pulmonary function, radiologic studies, and sputum culture results. All patients were followed up for at least 2 years. Results The 96 patients were divided into four groups: patients with concomitant negative NTM and P. aeruginosa isolates (n=41; group 1), patients with positive NTM isolates (n=20; group 2), patients with positive P. aeruginosa isolates (n=20; group 3), and patients with concomitant positive NTM and P. aeruginosa isolates (n=15; group 4). Compared with group 1 patients, patients in groups 2 and 3 showed a significant decline in forced expiratory volume in 1 second (FEV1). They also had more frequent annual acute exacerbations (AE), ED visits, and hospitalization. Group 4 patients had the greatest FEV1 and forced vital capacity (FVC) decline and the most frequent AE, ED visits, and hospitalization. Conclusion Concomitant NTM and P. aeruginosa isolates in non-CF bronchiectasis are associated with the greatest pulmonary function decline and the worst disease severity. This result suggested that early recognition and prompt treatment of concomitant NTM and P. aeruginosa isolates may improve the outcome in non-CF bronchiectasis patients.

Background: Previous surveillance methods to monitor the prognoses of patients with bronchiectasis are too complex for use in daily practice. The 6-minute walk test (6MWT) is a simple exercise test to predict the prognosis of chronic obstructive airway disease and numerous chronic lung diseases, including idiopathic pulmonary fibrosis. No studies have investigated exercise-induced oxygen desaturation (EID) and distance-saturation product (DSP) of 6MWT to predict the prognoses of patients with bronchiectasis. Methods: This was a prospective study to identify correlations between variables of 6MWT and mortality in patients with bronchiectasis over a 6-year period. The study cohort included 69 patients with stable non-cystic fibrosis (non-CF) bronchiectasis who were regularly evaluated for functional status via 6-minute walk distance (6MWD), spirometry, BODE index, EID, and DSP. Results: Of the 69 patients, 9 (13%) died and 60 (87%) survived during the 6-year follow-up period. The percentage of EID was higher [seven of nine patients (78%) vs . 22 of 60 patients (27%), P=0.003] in the non-survivors group. The 6MWD (467.9±77.1 vs . 363.7±126.7 m, P=0.001) was higher in the survivors group. DSP was significantly lower in the non-survivors group (411.0±78.4 vs . 283.9±90.0 m%, P 280 m% (P Conclusions: DSP is a simple parameter to predict 6-year mortality in patients with non-CF bronchiectasis.

Background/Objective Tumor necrosis factor-α (TNF-α) antagonists have become increasingly popular in the treatment of psoriasis. However, the increased risk of latent tuberculosis infection (LTBI) reactivation has also become an important issue in clinical practice. The aim of this study was to evaluate serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing for detecting LTBI among a cohort of psoriatic patients vaccinated with bacille Calmette-Guerin in a country with an intermediate burden of TB during long-term treatment with TNF-α antagonists. Methods We enrolled psoriatic patients treated with TNF-α antagonists who also accepted yearly serial QFT-GIT testing and regular chest X-ray examinations before and during the anti-TNF-α treatment from January 2010 to August 2014. Patients diagnosed with LTBI received chemoprophylaxis, and QFT-GIT testing was performed in these patients after completion of chemoprophylaxis. Results In this retrospective study, 101 patients had completed baseline and at least 1 year of follow-up. Among these patients, 60 had continued TNF-α antagonists therapy and received examinations in the 2 nd year, whereas 18 had continued the therapy until the 3 rd year. The conversion rate among these patients was 14.29% (13/91). In this study, 23 patients were diagnosed with LTBI according to the positive results obtained in the QFT-GIT test, with 19 of them having completed chemoprophylactic therapy. Follow-up QFT-GIT testing revealed reversion in 11 patients (57.89%) and decreased interferon-γ (IFN-γ) levels (68.42%) in 13 patients. Patients over 45 years of age tended to have a persistent positive result. Conclusion This study demonstrated that 14.29% of psoriatic patients undergoing long-term TNF-α antagonist therapy had a QFT-GIT conversion. Although a decreased IFN-γ level and QFT-GIT reversion were observed in most cases following prophylactic therapy, the value of QFT-GIT for evaluating the effect of LTBI prophylaxis remains controversial.

Background: Neutrophils sequestrated in the lung and release of proinflammatory mediators, including neutrophil defensin are responsible for sepsis-induced micro vascular permeability and alveolar epithelial cell damage. Objective: To investigate whether Neutrophil defensin might indirectly contribute to lung injury through their capacity to induce synthesis of IL-8 in epithelial cells, A549 epithelial cells were incubated with Neutrophil defensin (human neutrophil peptide; 1, 5 and 10 mg/ml) for 30 minutes, 2 hours and 6 hours. Methods: The IL-8 was analyzed by ELISA or by RT-PCR to measure IL-8 synthesis capacity. The mitogen-activated protein kinase (MAPK) activities were detected by western blot analysis. Results: Neutrophil defensin dose-dependently increased IL-8 release from cultured A549 epithelial cells. The MAPK, ERK, was up regulated by Neutrophil-defensin. Activator protein-1 (AP-1) but not nuclear transcriptional factor-kappa B (NF-kB) was also activated. Specific inhibitors of ERK inhibitor, PD 98059, but not NF-kB inhibitor, PDTC, significantly inhibited defensin-induced IL-8 release and mRNA expression. The specific tyrosine kinase (TK) inhibitor, genistein, or protein kinase C (PKC) inhibitor, Go 6976 also inhibited IL-8 release and mRNA expression.

Introduction The prognostic value of epidermal growth factor receptor (EGFR) mutations and the correlation between EGFR mutations and the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histological classification remain controversial. The current study aimed to investigate the pure prognostic role of EGFR mutations in treatment-naive patients with resected stage I lung adenocarcinoma. Methods We retrospectively reviewed 373 patients with stage I pulmonary non-small-cell lung cancer who underwent complete surgical resection between January 2010 and May 2014. The tumors were classified according to IASLC/ATS/ERS criteria. EGFR mutation status was determined by established methods. Results A total of 120 patients were included for analysis; 87 had tumors with EGFR mutations and 33 had wild-type tumors. More low- and intermediate-grade tumors had EGFR mutations, and nearly half of the high-grade tumors were wild-type (75.7% versus 46.2%, p = 0.041). Patients with low-grade tumors had significantly greater median disease-free survival (DFS) (76.8 versus 13 months, p < 0.0001) and better overall survival (OS) (median OS not reached, p = 0.0003) than those with intermediate- and high-grade tumors. Tumor recurrence was 41.4% and 30.3% in mutant and wild-type patients. The 5-years survival rate was 54% and 71.2%. Multivariate analysis revealed that the new histological classification and the pathologic stage were independent predictors of both DFS and OS. EGFR mutation status had no prognostic implications. Conclusion Low grade tumors according to IASLC/ATS/ERS histological classification and the pathologic stage IA tumors of resected stage I lung adenocarcinomas independently predict better DFS and OS. EGFR mutations were frequently seen in histologically low- and intermediate-grade tumors but not a prognostic factor.

Background: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. Methods: This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. Results: Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. Conclusions: Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide promising effect against non-small-cell lung cancer (NSCLC), although most tumors acquire resistance. Our objective was to assess the survival outcome of patients with NSCLC with or without subsequent chemotherapy after acquired TKI resistance.A total of 114 patients with pathologically confirmed stage IIIB or IV NSCLC who had had disease control with TKIs were retrospectively reviewed. After acquired TKI resistance, patients received either best supportive care (BSC) only or BSC plus subsequent chemotherapy. Both groups were well balanced in regard to performance status, age, sex, histology subtype, and smoking status.Sixty-seven patients (58.8%) received subsequent chemotherapy, and 47 patients (41.2%) received BSC only. The median overall survival (OS) and progression-free survival (PFS) from the time of TKI resistance in the subsequent-chemotherapy group (11.2 months and 3.5 months, respectively) were longer than those of the BSC group (3.8 months and 1.5 months, respectively; P.01). Patients who subsequently received taxane-based chemotherapy exhibited higher a response rate and disease control rate (48.7% and 79.5%, respectively) than patients treated with a nontaxane regimen (21.4% and 53.5%, respectively; P.05). Overall survival and PFS in patients after taxane-based subsequent chemotherapy (12.7 months and 5.1 months, respectively) were longer than those of patients given a nontaxane regimen (7 months and 1.8 months, respectively; P.01).This study suggests that acquired TKI resistance should be managed aggressively. The higher antitumor response and survival outcome with a taxane-based regimen in this retrospective study could encourage further prospective investigation to confirm the efficacy of taxane over nontaxane chemotherapy in patients with NSCLC whose disease progresses with EGFR TKI treatment.

Objectives Aspiration of the lower airways due to foreign body is rare in adults. This study aimed to determine the outcome of patients who received flexible bronchoscopy with different modalities for foreign body removal in the lower airways. Patients and Methods Between January 2003 and January 2014, 94 patients diagnosed with foreign body in the lower airways underwent flexible bronchoscopy with different modalities, which included forceps, loop, basket, knife, electromagnet, and cryotherapy. The clinical presentation, foreign body location and characteristics, and applications of flexible bronchoscopy were analyzed. Results Forty (43%) patients had acute aspiration, which developed within one week of foreign body entry and 54 (57%) had chronic aspiration. The most common foreign bodies were teeth or bone. More patients with chronic aspiration than those with acute aspiration were referred from the out-patient clinic (48% vs. 28%), but more patients with acute aspiration were referred from the emergency room (35% vs. 6%) and intensive care unit (18% vs. 2%). Flexible bronchoscopy with different modalities was used to remove the foreign bodies (85/94, 90%). Electromagnet or cryotherapy was used in nine patients to eliminate the surrounding granulation tissue before foreign body removal. In the nine patients with failed flexible bronchoscopy, eight underwent rigid bronchoscopy instead and one had right lower lung lobectomy for lung abscess. Conclusions Flexible bronchoscopy with multiple modalities is effective for diagnosing and removing foreign bodies in the lower respiratory airways in adults, with a high success rate (90%) and no difference between acute and chronic aspirations.

Background: The alveolar recruitment maneuver (RM) has been reported to improve oxygenation in acute respiratory distress syndrome (ARDS) and may be related to reduced extravascular lung water (EVLW) in animals. This study was designed to investigate the effects of RM on EVLW in patients with ARDS. Methods: An open label, prospective, randomized controlled trial including patients with ARDS was conducted in hospitals in North Taiwan between 2010 and 2016. The patients were divided into 2 groups (with and without RM). The primary endpoint was the comparison of the EVLW index between the 2 groups. Results: Twenty-four patients with ARDS on mechanical ventilator support were randomized to receive ventilator treatment with RM (RM group, n = 12) or without RM (non-RM group, n = 12). Baseline demographic characteristics were similar between the 2 groups. After recruitment, the day 3 extravascular lung water index (EVLWI) (25.3 ± 9.3 vs 15.5 ± 7.3 mL/kg, P = .008) and the arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FiO2) (132.3 ± 43.5 vs 185.6 ± 38.8 mL/kg, P = .003) both improved over that of day 1. However, both EVLWI and PaO2/FiO2 did not significantly change from day 1 to 3 in the non-RM group. Conclusion: RM is a feasible method for improving oxygenation and the EVLW index in patients with ARDS, as well as for decreasing ventilator days and intensive care unit stay duration.

Although malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients in a university-affiliated hospital between 2007 and 2011 were evaluated. Survival curve with or without postcryotherapy chemotherapy and performance status (PS) improvement of these subjects were analyzed using the Kaplan-Meier method. There were 59 patients (42 males), with median age of 64 years (range, 51–76, and median performance status of 2 (interquartile range [IQR], 2-3). Postcryotherapy complications included minor bleeding (n=12) and need for multiple procedures (n=10), while outcomes were relief of symptoms (n=51), improved PS (n=45), and ability to receive chemotherapy (n=40). The survival of patients with chemotherapy postcryotherapy was longer than that of patients without such chemotherapy (median, 534 versus 106 days; log-rank test,P=0.007; hazard ratio, 0.25; 95% confidence interval, 0.10–0.69). The survival of patients with PS improvement postcryotherapy was longer than that of patients without PS improvement (median, 406 versus 106 days; log-rank test,P=0.02; hazard ratio, 0.28; 95% confidence interval, 0.10–0.81). Cryotherapy is a feasible treatment for MEM. With better PS after cryotherapy, further chemotherapy becomes possible for patients to improve survival when MEM caused dyspnea and poor PS.

Study Objectives.The aim of this study is to investigate the correlation between serum high-sensitivity C-reactive protein (hs-CRP) and other clinical tools including high-resolution computed tomography (HRCT) in patients with stable non-CF bronchiectasis.Design.A within-subject correlational study of a group of patients with stable non-CF bronchiectasis, who were recruited from our outpatient clinic, was done over a two-year period.Measurements.Sixty-nine stable non-CF bronchiectasis patients were evaluated in terms of hs-CRP, 6-minute walk test, pulmonary function tests, and HRCT.Results.Circulating hs-CRP levels were significantly correlated with HRCT scores (n=69,r=0.473,P<0.001) and resting oxygenation saturation (r=-0.269,P=0.025). HRCT severity scores significantly increased in patients with hs-CRP level of 4.26 mg/L or higher (mean ± SD28.1±13.1) compared to those with hs-CRP level less than 4.26 mg/L (31.7±9.8,P=0.004). Oxygenation saturation at rest was lower in those with hs-CRP level of 4.26 mg/L or higher (93.5±4.4%) compared to those with hs-CRP level less than 4.26 mg/L (96.4±1.6%,P=0.001).Conclusion.There was a good correlation between serum hs-CRP and HRCT scores in the patients with stable non-CF bronchiectasis.

Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain metastases of lung adenocarcinoma.

To evaluate the association of epidermal growth factor receptor (EGFR) gene copy number with EGFR and k-ras mutation status and tyrosine kinase inhibitor (TKI) sensitivity in non-small cell lung cancer (NSCLC), EGFR gene copy number of 182 NSCLC tumor specimens were analyzed by chromogenic in situ hybridization (CISH). EGFR and k-ras mutation analyses were also performed for, respectively, 176 and 157 of the 182 patients. Additionally, 36 patients in this study had received TKI monotherapy. The tumor was considered to be CISH positive if the gene copy number wasor=5 signals per nucleus inor=40% of tumor cells. CISH-positive tumors were strongly associated with adenocarcinoma (56.8%) compared with squamous cell carcinoma (15.9%) (p0.0001). The CISH-positive tumors were also strongly associated with EGFR mutations (78%) compared with wild type (20.2%) (p0.0001). Only six tumors had k-ras mutations. None had EGFR mutation and only one was CISH positive. In the patients treated with TKI, EGFR mutation was strongly associated with TKI responsiveness (22/25 responders) (p0.0001), but the CISH-positive tumors were only marginally significant (18/25 responders) (p=0.0665). Patients with EGFR mutations or CISH-positive tumors were all associated with longer median survival, although not statistically significant. Our results suggest Increased EGFR copy number was highly correlated with EGFR mutation in adenocarcinoma. Although it is less correlated with TKI responsiveness when compared with EGFR mutations, it still could be a good alternative molecular predictive marker for TKI responsiveness, since CISH can be done on paraffin section and is much quicker than DNA sequencing.

Objectives Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis. Design To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed. Results The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p