Trajectory of smoking behaviour during the first 6 months after diagnosis of lung cancer: A study from Taiwan.

AIMS: To identify different classes of change pattern/ trajectory of tobacco smoking behaviour after diagnosis of lung cancer using multi-wave data and to explore factors associated with the class membership. DESIGN: This is a multi-wave observational study. METHODS: Smoking behaviour data were collected at diagnosis and then every month for 6 months from 133 newly diagnosed people with lung cancer who had recently quit smoking or continued to smoke at diagnosis. These patients were recruited from three medical centres and data were collected from May 2014 to January 2017. Smoking behaviour was assessed based on patients' self-reports on whether they smoked during the last month (yes/no) for a total of seven times. Mixture latent Markov model and logistic regression were used to analyse data. RESULTS: Two latent classes of smoking trajectory were identified among recent quitters or current smokers of people with lung cancer, namely "perseverance for abstinence" and "indecisive for abstinence." Patients who were younger age (OR = 0.95, p = 0.026), exposure to second-hand smoke (OR = 3.35, p = 0.012) and lower self-efficacy for not smoking (OR = 0.96, p = 0.011) were more likely to belong to the class of "indecisive for abstinence." CONCLUSIONS: Heterogeneous classes of smoking trajectory existed in newly diagnosed people with lung cancer. The risk factors associated with a less favourable smoking trajectory can be incorporated into tailored smoking-cessation programs for patients newly diagnosed with lung cancer. IMPACT: The dynamic trajectory of smoking behaviour had not been adequately explored among newly diagnosed people with lung cancer. Two classes of smoking trajectory and the predictors associated with the class membership were identified. These findings suggest that the diagnosis of cancer is a teachable moment for smoking cessation. Patients with younger age, lower self-efficacy of not smoking and exposure to second-hand smoke at home need special attention.

Rare Concurrence of Two Congenital Disorders: Miller-Dieker Syndrome and T-Cell Lymphopenia.

Miller-Dieker syndrome (MDS; OMIM 247200) is a rare contiguous gene deletion syndrome associated with lissencephaly and characteristic facial dysmorphism. T-cell lymphopenia is an immunodeficiency disorder which can be early detected by newborn blood screening, and all live vaccines should be avoided. We report a 2.32-Mb microdeletion at chromosome 17p13.3p13.2 and T-cell lymphopenia in a 6-month-old male infant with MDS. This is, to our knowledge, the first description of these 2 conditions co-occurring in the same patient.

Measuring (1,3)-ß-D-glucan in tracheal aspirate, bronchoalveolar lavage fluid, and serum for detection of suspected Candida pneumonia in immunocompromised and critically ill patients: a prospective observational study.

BACKGROUND: While Candida pneumonia is life-threatening, biomarker measurements to early detect suspected Candida pneumonia are lacking. This study compared the diagnostic values of measuring levels of (1, 3)-ß-D-glucan in endotracheal aspirate, bronchoalveolar lavage fluid, and serum to detect suspected Candida pneumonia in immunocompromised and critically ill patients. METHODS: This prospective, observational study enrolled immunocompromised, critically ill, and ventilated patients with suspected fungal pneumonia in mixed intensive care units from November 2010 to October 2011. Patients with D-glucan confounding factors or other fungal infection were excluded. Endotracheal aspirate, bronchoalveolar lavage fluid and serum were collected from each patient to perform a fungal smear, culture, and D-glucan assay. RESULTS: After screening 166 patients, 31 patients completed the study and were categorized into non-Candida pneumonia/non-candidemia (n = 18), suspected Candida pneumonia (n = 9), and non-Candida pneumonia/candidemia groups (n = 4). D-glucan levels in endotracheal aspirate or bronchoalveolar lavage were highest in suspected Candida pneumonia, while the serum D-glucan level was highest in non-Candida pneumonia/candidemia. In all patients, the D-glucan value in endotracheal aspirate was positively correlated with that in bronchoalveolar lavage fluid. For the detection of suspected Candida pneumonia, the predictive performance (sensitivity/specificity/D-glucan cutoff [pg/ml]) of D-glucan in endotracheal aspirate and bronchoalveolar lavage fluid was 67%/82%/120 and 89%/86%/130, respectively, accounting for areas under the receiver operating characteristic curve of 0.833 and 0.939 (both P < 0.05), respectively. Measuring serum D-glucan was of no diagnostic value (area under curve =0.510, P = 0.931) for the detection of suspected Candida pneumonia in the absence of concurrent candidemia. CONCLUSIONS: D-glucan levels in both endotracheal aspirate and bronchoalveolar lavage, but not in serum, provide good diagnostic values to detect suspected Candida pneumonia and to serve as potential biomarkers for early detection in this patient population.

Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor Treatment and Salvage Chemotherapy in EGFR-Mutated Elderly Pulmonary Adenocarcinoma Patients.

BACKGROUND: Lung cancer is frequently a disease of elderly patients. However, these patients are often treated less actively owing to a higher comorbidity rate and poor performance status. The efficacy of different treatments in elderly patients with epidermal growth factor receptor (EGFR)-mutated lung cancer is still unknown. MATERIALS AND METHODS: We retrospectively reviewed the records of our pulmonary adenocarcinoma patients treated between 2010 and 2013. Data on patient age, type of tumor EGFR mutation, response to first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, type of salvage chemotherapy, and efficacy of EGFR-TKI and salvage chemotherapy were collected. RESULTS: In all, 473 of 1,230 stage IV adenocarcinoma patients had an EGFR mutation, and 330 of them received first-line TKI treatment. Of the 330 patients, 160 were ≥70 years old (elderly group) and 170 were <70 years old (younger group). The response rate and progression-free survival (PFS) with first-line TKI treatment were not significantly different. The elderly group had shorter median survival. A total of 107 patients received salvage chemotherapy after first-line EGFR-TKI treatment: 45 in the elderly group and 62 in the younger group. Their response rate and PFS were not significantly different; however, the younger group had longer median survival. Additional subgroup analysis showed that younger patients who received platinum-based chemotherapy or combination chemotherapy had better median survival than did the elderly patients. The PFS was longer among younger patients receiving a platinum-based regimen than that among the elderly patients. CONCLUSION: Elderly patients with disease progression after first-line EGFR-TKI treatment can receive chemotherapy and have a response rate similar to that of younger patients. IMPLICATIONS FOR PRACTICE: The aim of the present study was to investigate the efficacy of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in elderly patients and the outcomes of subsequent salvage chemotherapy after disease progression. The most important finding was that elderly patients with disease progression after first-line EGFR-TKI treatment can receive salvage chemotherapy and have a response rate similar to that of younger patients who received salvage chemotherapy.

Sleep Apnea and Risk of Panic Disorder.

PURPOSE: Epidemiological studies have identified a trend in the development of depressive and anxiety disorders following a diagnosis of sleep apnea. The relationship between sleep apnea and subsequent panic disorder, however, remains unclear. METHODS: Using a nationwide database, the Taiwan National Health Insurance Research Database, patients with sleep apnea and age-, sex-, income-, and urbanization-matched control patients who did not have sleep apnea were enrolled between 2000 and 2010. Patients with a prior diagnosis of panic disorder before enrollment were excluded. The 2 cohorts were observed until December 31, 2010. The primary endpoint was occurrence of newly diagnosed panic disorder. RESULTS: A total of 8,704 sleep apnea patients and 34,792 control patients were enrolled. Of the 43,496 patients, 263 (0.60%) suffered from panic disorder during a mean follow-up period of 3.92 years, including 117 (1.34%) from the sleep apnea cohort and 146 (0.42%) from the control group. The Kaplan-Meier analysis revealed a predisposition of patients with sleep apnea to develop panic disorder (log-rank test, P <.001). After multivariate adjustment, the hazard ratio for subsequent panic disorder among the sleep apnea patients was 2.17 (95% confidence interval, 1.68-2.81; P <.001). CONCLUSIONS: Sleep apnea appears to confer a higher risk for future development of panic disorder.

Budesonide/formoterol maintenance and reliever therapy in asthma control: acute, dose-related effects and real-life effectiveness.

BACKGROUND AND OBJECTIVE: The efficacy of budesonide/formoterol maintenance and reliever therapy (BFMRT) in asthma control is well documented in large randomized controlled trials. However, the acute reliever effects and real-life effectiveness are seldom reported. METHODS: This multicenter trial enrolled steroid-naïve, symptomatic asthmatics with baseline exhaled nitric oxide (eNO) of ≥ 40 ppb. There were 120 eligible patients who were randomized and received a dose of inhaled budesonide/formoterol 320/9 µg (lower dose budesonide/formoterol), 640/18 µg (higher dose budesonide/formoterol (HDBF)), or terbutaline (TERB) 1 mg. Inflammatory cells and mediators in induced sputum, eNO and lung function were measured at baseline and 6 h (acute phase). Subsequently, all patients used BFMRT as real-life practice for 24 weeks (maintenance phase). RESULTS: In the acute phase, the degree of post-treatment reduction in total eosinophil counts, interleukin-8 and matrix metalloproteinase-9 in induced sputum were significantly greater in group HDBF (vs TERB, P < 0.05). The increase in forced expiratory volume in first second (FEV1 ) in group HDBF was significantly higher (vs LDBF and TERB, P < 0.05) 3 h after dosing. In the maintenance phase, significant improvement of asthma control (presented by eNO, FEV1 and a five-item asthma control questionnaire) in real-life settings was observed at 4 weeks and sustained to the end of study. The rate of patients who followed scheduled visits declined over time (87% at week 4 and 42% at week 24). CONCLUSIONS: Budesonide/formoterol as reliever exerts acute, dose-related anti-inflammatory effects and FEV1 improvement in symptomatic asthmatics. BFMRT is effective in asthma control. However, the decrease in long-term follow-up rate remains an issue to overcome in real-life settings.

Amyloidosis and the risk of cancer: a nationwide population-based study.

BACKGROUND: The association between amyloidosis and cancer remains unclear. PARTICIPANTS AND METHODS: Using the Taiwan National Health Insurance Research Database we conducted a population-based cohort study. Patients newly diagnosed with amyloidosis between 1997 and 2009 were enrolled. Patients with antecedent cancer were excluded. Standardized incidence ratios (SIR) of cancers were calculated for the study cohort and compared with cancer incidence among the general population. We used a multivariate Cox regression model to evaluate the predictors of cancer development for patients with amyloidosis. RESULTS: The study included 1,693 subjects with median follow-up of 5.63 years. A total of 68 patients developed cancer. The incidence of kidney cancer (SIR 3.42; 95 % CI 1.11-7.97; p = 0.034) and hematologic malignancies (SIR 3.88; 95 % CI 1.86-7.14; p < 0.001) were significantly higher for patients with amyloidosis. CONCLUSION: This is currently the largest study to evaluate cancer risk among patients with amyloidosis. The results indicate that amyloidosis may be associated with an increased risk of kidney cancer and hematologic malignancies.

Nocturnal stem cell mobilization in patients with obstructive sleep apnoea: a pilot study.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) experience repetitive cessation of breathing during sleep, leading to intermittent hypoxaemia, excessive oxidative stress and systemic inflammation. These insults may damage the vasculature and provoke the corresponding repair response, such as stem cell mobilization to peripheral blood. This study aimed to investigate nocturnal mobilization of stem cells in OSA. METHODS: Thirty-five patients with OSA and thirteen healthy controls were enrolled. Polysomnography was performed, and severity of OSA was defined by apnoea-hypopnoea index (AHI). Peripheral venous blood was drawn after and before sleep for measurement of CD34+ cell and SDF-1α level. Stem cell mobilization was gauged by ratios of the CD34+ level in the morning to that at night or by their difference. Correlation analysis was performed to identify factors related to stem cell mobilization. RESULTS: Compared to controls, the nocturnal ratios and difference of CD34+ cell levels were larger in patients with OSA (ratios: 1·141 vs. 0·896, P = 0·036; difference: 340 vs. -166/cc blood, P = 0·036), suggestive of stem cell mobilization. The mobilization ratios were related to AHI, body mass index (BMI), SpO2 nadir, oxygen desaturation index and time sustaining hypoxaemia. After adjusting age, gender and BMI, AHI (r = 0·357, P = 0·016) and hypoxaemia-related parameter remained significant. Paired nocturnal differences in CD34+ cell count (P = 0·009) and SDF-1α (P = 0·001) were also significant in patients with OSA, but not in controls. After CPAP therapy for 6 months, the elevated mobilization ratios in patients with OSA tended to decline (P = 0·059). CONCLUSION: CD34+ stem cell mobilization during sleep was observed in OSA.

Sleep apnoea patients have higher mortality when confronting sepsis.

BACKGROUND: Sleep is essential for the maintenance of an intact immune function. Patients with sleep apnoea experience frequent sleep interruption due to apnoea-related arousals, possibly adversely impacting their immunity and affecting their outcomes when confronting sepsis. This case-control study aimed to compare the outcomes of sepsis patients with and without sleep apnoea. METHODS: From 2000 to 2009, 168 sleep apnoea patients who were first admitted for sepsis were identified from the Taiwan National Health Insurance Research Database. Also, 672 sepsis patients without sleep apnoea, who were matched by age, gender and Charlson's comorbidity index scores, served as controls. Hospital outcomes of the two groups were compared. Binary logistic regression was employed for multivariate analysis. RESULTS: The mortality rates of sepsis patients with and without sleep apnoea were 60.1% and 47.9%, respectively (P = 0. 005). After multivariate adjustment, sleep apnoea (OR: 1.805, 95% CI: 1.227-2.656, P = 0.003), presence of shock (OR: 3.600, 95% CI: 2.144-6.046, P < 0.001) and number of organs with dysfunction (OR: 1.591, 95% CI: 1.087-2.329, P = 0.017) were found to be independently associated with mortality. Sleep apnoea patients who needed continuous positive airway pressure treatment had an even higher risk of mortality. CONCLUSIONS: Sepsis patients with sleep apnoea may have poorer hospital outcomes than those without sleep apnoea.

[The use of systematic review to develop a self-management program for CKD].

BACKGROUND: Chronic kidney disease (CKD) has become a public health issue of international concern due to its high prevalence. The concept of self-management has been comprehensively applied in education programs that address chronic diseases. In recent years, many studies have used self-management programs in CKD interventions and have investigated the pre- and post-intervention physiological and psychological effectiveness of this approach. However, a complete clinical application program in the self-management model has yet to be developed for use in clinical renal care settings. PURPOSE: A systematic review is used to develop a self-management program for CKD. METHOD: Three implementation steps were used in this study. These steps include: (1) A systematic literature search and review using databases including CEPS (Chinese Electronic Periodical Services) of Airiti, National Digital Library of Theses and Dissertations in Taiwan, CINAHL, Pubmed, Medline, Cochrane Library, and Joanna Briggs Institute. A total of 22 studies were identified as valid and submitted to rigorous analysis. Of these, 4 were systematic literature reviews, 10 were randomized experimental studies, and 8 were non-randomized experimental studies. (2) Empirical evidence then was used to draft relevant guidelines on clinical application. (3) Finally, expert panels tested the validity of the draft to ensure the final version was valid for application in practice. RESULTS: This study designed a self-management program for CKD based on the findings of empirical studies. The content of this program included: design principles, categories, elements, and the intervention measures used in the self-management program. This program and then was assessed using the content validity index (CVI) and a four-point Liker's scale. The content validity score was .98. The guideline of self-management program to CKD was thus developed. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study developed a self-management program applicable to local care of CKD. It is hoped that the guidelines developed in this study offer a reference for clinical caregivers to improve their healthcare practices.

Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.

Amiodarone and the risk of cancer: a nationwide population-based study.

BACKGROUND: In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy. METHODS: Using the Taiwan National Health Insurance Research database, the authors conducted a population-based cohort study. Patients who were treated with amiodarone between 1997 and 2008 were enrolled. Those with antecedent cancer were excluded. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. A multivariate Cox regression model was used to evaluate the association between cumulative defined daily doses (cDDDs) of amiodarone and cancer occurrence. RESULTS: The study included 6418 subjects, with a median follow-up of 2.57 years. A total of 280 patients developed cancer. The risk of cancer increased with borderline significance (SIR, 1.12; 95% confidence interval [95% CI], 0.99-1.26 [P = .067]). Male patients had a higher risk (SIR, 1.18; 95% CI, 1.02-1.36 [P = .022]). The total cohort of patients and the male patients with > 180 cDDDs within the first year were found to have SIRs of 1.28 (95% CI, 1.00-1.61; P = .046) and 1.46 (95% CI, 1.11-1.89; P = .008), respectively. After adjustment for age, sex, and comorbidities, the hazards ratio was 1.98 (95% CI, 1.22-3.22; P = .006) for the high tertile of cDDDs compared with the low tertile. CONCLUSIONS: The results of the current study indicate that amiodarone may be associated with an increased risk of incident cancer, especially in males, with a dose-dependent effect.

Jugular venous reflux and plasma endothelin-1 are associated with cough syncope: a case control pilot study.

BACKGROUND: Jugular venous reflux (JVR) has been reported to cause cough syncope via retrograde-transmitted venous hypertension and consequently decreased cerebral blood flow (CBF). Unmatched frequencies of JVR and cough syncope led us to postulate that there should be additional factors combined with JVR to exaggerate CBF decrement during cough, leading to syncope. The present pilot study tested the hypothesis that JVR, in addition to an increased level of plasma endothelin-1 (ET-1), a potent vasoconstrictor, is involved in the pathophysiology of cough syncope. METHODS: Seventeen patients with cough syncope or pre-syncope (Mean[SD] = 74.63(12.37) years; 15 males) and 51 age/gender-matched controls received color-coded duplex ultrasonography for JVR determination and plasma ET-1 level measurements. RESULTS: Multivariate logistic analysis showed that the presence of both-side JVR (odds ratio [OR] = 10.77, 95% confident interval [CI] = 2.40-48.35, p = 0.0019) and plasma ET-1 > 3.43 pg/ml (OR = 14.57, 95% CI = 2.95-71.59, p = 0.001) were independently associated with the presence of cough syncope/ pre-syncope respectively. There was less incidence of cough syncope/ pre-syncope in subjects with the absence of both-side JVR and a plasma ET-1 ≦3.43 pg/ml. Presence of both side JVR and plasma ET-1 level of > 3.43 pg/ml, increased risk for cough syncope/pre-syncope (p < 0.001). CONCLUSIONS: JVR and higher plasma levels of ET-1 are associated with cough syncope/ pre-syncope. Although sample size of this study was small, we showed a synergistic effect between JVR and plasma ET-1 levels on the occurrence of cough syncope/pre-syncope. Future studies should confirm our pilot findings.

Bile acids increase alveolar epithelial permeability via mitogen-activated protein kinase, cytosolic phospholipase A2 , cyclooxygenase-2, prostaglandin E2 and junctional proteins.

BACKGROUND AND OBJECTIVE: Bile acid (BA) aspiration is associated with various lung diseases. It was hypothesized that BA may induce changes in alveolar epithelium permeability and contribute to the pathogenesis of lung injury. METHODS: Human alveolar epithelial cells were grown in monolayer and stimulated with a major component of BA, chenodeoxycholic acid (CDCA). Transepithelial electrical resistance (TER) and paracellular fluxes were measured to assess permeability alteration. Prostaglandin E2 ( PGE2 ) production was measured, and its effect on TER and junctional proteins (JP) was also examined. Reverse transcription polymerase chain reaction and Western blots were used to investigate the expression of messenger RNA and JP. RESULTS: CDCA induced significant p38 and c-Jun N-terminal kinase (JNK) phosphorylation, cytosolic phospholipase A2 (cPLA2 ) and cyclooxygenase-2 (COX-2) messenger RNA expression, PGE2 production, TER reduction and decay of JP (including occludin, zonula occludens-1 (ZO-1) and E-cadherin, in which ZO-1 had maximal change). CDCA also increased paracellular fluxes, which was abolished by dexamethasone. Both CDCA and PGE2 contributed to TER reduction in an identical trend and a dose-response manner. PGE2 also reduced ZO-1 expression, which was similar to that observed by CDCA stimulation. Pretreatment with inhibitors of p38 (SB203580), JNK (SP600125), cPLA2 (mepacrine) and COX-2 (NS398) as well as dexamethasone reversed the CDCA-induced PGE2 production, TER reduction and decay of ZO-1. CONCLUSIONS: The increase in alveolar permeability was associated with decay of JP. BA may induce permeability alteration through the upregulation of mitogen-activated protein kinase, cPLA2 , COX-2, PGE2 and JP, which may contribute to the pathogenesis of BA-associated lung injury.

Abnormal renal resistive index in patients with mild-to-moderate chronic obstructive pulmonary disease.

BACKGROUND: Arterial rigidity and endothelial dysfunction are systemic manifestations of chronic obstructive pulmonary disease (COPD). The decrease in renal vascular resistance in order to adapt the increase in glomerular filtration rate after oral protein loading is known as normal renal functional reserve. We tested the hypothesis that COPD patients, even in those with mild-to-moderate airflow obstruction, are affected by systemic inflammation associated with abnormal renal functional reserve. MATERIALS AND METHODS: The study enrolled 24 current smokers with a cigarette smoking history ≥ 25 pack-years and 8 nonsmokers with normal spirometry as control. Doppler sonography detected the renal resistive index (RRI) before and after oral protein loading to determine the renal functional reserve. Pulmonary function and serum tumor necrosis factor α (TNF-α) levels were analyzed to compare with the renal functional reserve. RESULTS: The smokers were stratified into 3 groups (Group 1: smokers with normal spirometry, Group 2: mild COPD, Group 3: moderate COPD); nonsmokers as Group 4. The baseline RRI levels were similar in Group 1 and Group 4. After protein loading, the RRI elevated in all smoking groups; moreover, Group 3 had the highest RRI and with longer duration than other groups. The smokers with higher serum TNF-α levels had a longer RRI elevation. Multiple linear regression revealed forced expiratory volume in one second (FEV1), serum TNF-α levels and aging were independently predictive factors of impaired renal functional reserve. CONCLUSIONS: A greater impairment in renal functional reserve of COPD patients was correlated with more severe airway obstruction and inflammation.

Long-acting ß2 agonists and corticosteroids restore the reduction of histone deacetylase activity and inhibit H2O2-induced mediator release from alveolar macrophages.

BACKGROUND: Treatment of COPD with a combination of long-acting ß(2) agonists and corticosteroids is currently used worldwide. The mechanisms of the anti-inflammatory effects and their associations with histone deacetylase (HDAC) activity remain unclear. METHODS: Human alveolar macrophages were isolated and stimulated with H(2)O(2) in the presence of varying concentrations of long-acting ß(2) agonists and corticosteroids. Supernatants were collected for IL-8 and MMP-9 measurements. Cell lysates were analyzed for HDAC (mainly HDAC1/HDAC2) activity. Quantitative real-time PCR was performed to determine the levels of IL-8 and MMP-9 mRNA. RESULTS: Both long-acting ß(2) agonists, salmeterol and formoterol, and corticosteroids, fluticasone and budesonide, showed anti-inflammatory effects to a certain extent on H(2)O(2)-induced IL-8 and MMP-9 release in alveolar macrophages. Combinations of long-acting ß(2) agonists and corticosteroids exerted greater effects to suppress mediator release, and both transcription and translation of IL-8 and MMP-9 were inhibited. It seemed that the levels of IL-8 and MMP-9 after H(2)O(2) stimulation were inversely associated with the activity of HDAC. H(2)O(2) stimulation resulted in a significant decrease in HDAC activity and was associated with an increase in mediator release. In contrast, treatment with long-acting ß(2) agonists, corticosteroids or theophylline restored the H(2)O(2)-induced decrease in HDAC activity and inhibited mediator release. CONCLUSION: Combinations of long-acting ß(2) agonists and corticosteroids exerted greater effects on the suppression of mediator release in relation to the enhancement of HDAC activity. This supports at least in part the likely contribution of anti-inflammatory effects of long-acting ß(2) agonists and corticosteroids to the clinical benefits seen in COPD patients.

Levofloxacin degradation under visible-LED photo-catalyzing by a novel ternary Fe-ZnO/WO3 nanocomposite.

As semiconductor photocatalysts showing their efficient redox ability upon illumination, new development of materials to enhance the pollution degradation is gaining popularity, especially on their oxidation ability. In this study, a highly stable ternary Fe-ZnO/WO3 nanocomposite photocatalyst has been synthesized in order to improve charge transfer of photocatalytic oxidation under 30W LED light (425-470 nm) to efficiency degrade the Levofloxacin (LVF) in the solution. This catalyst was characterized and analyzed by XRD, FE-SEM, HR-TEM, X-ray XPS, UPS, PL, TRPL, LSV, EIS, and Photocurrent. Various important factors for the photodegradation were investigated, including Fe content, initial LVF concentration, catalyst dosage, and solution pH. The optimal conditions were Fe 1.0 wt%, LVF 10 mg L-1, Fe-ZnO/WO3 dosage 0.5 g L-1, and pH 7 for LVF photodegradation up to 96% with a kinetic rate constant of 0.0342 min-1 and were stable in photodegradation efficiency (90%) after five test cycles. In the visible LED light, the activation bandgap was estimated to be 2.75 eV with high electron-hole pair separation and charge transfer from Fe-ZnO to WO3 that could enhance the generation of active species of •OH. Moreover, the more effective charge separation of Fe-ZnO/WO3 were confirmed by lower PL intensity and longer charge carrier lifetime. Fe-ZnO/WO3 also demonstrated the excellent electrochemical properties with high photocurrent and small resistance. For the LVF degradation, 3 possible pathways were proposed with 12 intermediate products. This study demonstrated that the synthesized Fe-ZnO/WO3 could serve as a reliable visible-light responsive photocatalysts with the potential for degrading antibiotics in solution.

Association between sugary drinks consumption and dental caries incidence among Taiwanese schoolchildren with mixed dentition.

OBJECTIVES: Dental caries is a multifactorial disease, and a sugary diet can generate an acidic plaque environment that advances its development. However, the specific effect of sugary drinks on the subsequent oral health of schoolchildren with mixed dentition is unclear. In this study, we investigated the association between the consumption of sugary drinks and 1 year incidence rate of caries in permanent teeth among Taiwanese schoolchildren with mixed dentition. METHODS: A longitudinal 1 year follow-up study was conducted among Taiwanese schoolchildren aged 8-9 years. A questionnaire collected information regarding the parents' oral health status and their children's demographic background, oral health-related behaviours and consumption habits of sugary drinks, including handmade drinks (specifically bubble tea and pearl milk tea) and carbonated drinks. Dental caries was recorded through standardized oral examinations. The number of dental services received was retrieved from the Taiwan National Health Insurance Research Database. Multivariate Cox proportional hazards models and zero-inflated negative binomial models were used to estimate the association between the consumption of sugary drinks and the incidence rate of caries in permanent teeth after 1 year. RESULTS: The study involved 494 children. During the 1 year follow-up period, 117 children developed new dental caries in their permanent teeth, yielding a caries incidence rate of 0.183 per person-year. After adjustments for confounding factors, children who preferred having sugar-rich beverages were associated with having a 4.3 times higher (95% confidence interval [CI] = 1.2-15.7) risk of developing caries than did those who preferred nonsugary drinks (P < .05). Additionally, children who often consumed handmade drinks were associated with having a 1.7 times higher (95% CI = 1.1-2.9) risk of developing caries than those who seldom consumed (P < .05). CONCLUSIONS: The findings suggest that the consumption of sugary drinks during the mixed dentition stage might be a major etiological factor for caries in permanent teeth. These findings could be valuable to paediatricians, dentists, nutritionists and policymakers.

The roles of transforming growth factor-ß1 and vascular endothelial growth factor in the tracheal granulation formation.

BACKGROUND: Acquired tracheal stenosis is common in patients with a long-term tracheostomy and granulation is one of the most commonly observed lesions in benign airway stenosis. The aim of this study was to investigate the mechanisms of tracheal granulation formation and find the potential therapeutic targets to prevent the granulation formation. RESULTS: In granulation tissue obtained from patients during interventional bronchoscopy for the relief of airway obstruction, increased expression of transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF), as well as increased numbers of fibroblasts, was found by immunohistochemical staining. TGF-ß1 expression was detected in both the epithelial and submucosal layers. The highest levels of VEGF and vimentin expression occurred in the submucosal layers. In comparison with the control, significantly increased numbers of small vessels were observed in the submucosal layers of the granulation tissue. In vitro, TGF-ß1 stimulated production of VEGF by cultured fibroblasts at both the mRNA and protein level. VEGF siRNA treatment resulted in a significant decrease of TGF-ß1-induced VEGF production. SIS3, a selective Smad3 inhibitor, and UO126 both inhibited p44/42 MAP kinase phosphorylation and attenuated subsequent VEGF production by fibroblasts. A low concentration of erythromycin (1 µg/ml), but not dexamethasone (100 µM), inhibited TGF-ß1-induced VEGF production. CONCLUSION: This study provides important information that facilitates an understanding, at least in part, of the mechanisms of granulation formation. Targeting these mediators and cells may help to prevent the formation of granulation tissue in long-term tracheostomy or prolonged endotracheal intubation patients.

Characteristics of pncA mutations in multidrug-resistant tuberculosis in Taiwan.

BACKGROUND: Pyrazinamide (PZA) is an important first-line drug in multidrug-resistant tuberculosis (MDRTB) treatment. However, the unreliable results obtained from traditional susceptibility testing limits its usefulness in clinical settings. The detection of pncA gene mutations is a potential surrogate of PZA susceptibility testing, especially in MDRTB isolates. The impact of genotypes of M. tuberculosis in pncA gene mutations also remains to be clarified. METHODS: MDRTB isolates were collected from six hospitals in Taiwan from January 2007 to December 2009. pncA gene sequencing, pyrazinamidase activity testing, and spoligotyping were performed on all of the isolates. PZA susceptibility was determined by the BACTEC MGIT 960 PZA method. The sensitivity and specificity of pncA gene analysis were estimated based on the results of PZA susceptibility testing. RESULTS: A total of 66 MDRTB isolates, including 37 Beijing and 29 non-Beijing strains, were included for analysis. Among these isolates, 36 (54.5%) were PZA-resistant and 30 (45.5%) were PZA-susceptible. The PZA-resistant isolates were more likely to have concomitant resistance to ethambutol and streptomycin. Thirty-seven mutation types out of 30 isolates were identified in the pncA gene, and most of them were point mutations. The sensitivities of pncA gene sequencing for PZA susceptibility in overall isolates, Beijing and non-Beijing strains were 80.6%, 76.2%, and 86.7% respectively, and the specificities were 96.7%, 93.8%, and 100% respectively. CONCLUSIONS: More than half of the MDRTB isolates in this study are PZA-resistant. Analysis of pncA gene mutations helped to identify PZA-susceptible MDRTB isolates, especially in non-Beijing strains.