The methylation patterns of a disintegrin and metalloproteinase 33 gene (ADAM33) in adult asthma.

BACKGROUND: Asthma is a common chronic inflammatory respiratory disease. Previous studies have suggested that the pathogenesis of asthma may be affected by epigenetic regulation. The purpose of this study is to characterize the effect of the methylation of each CpG site in the ADAM33 (a disintegrin and metalloproteinase 33) gene in adult asthma. METHODS: A human CpG island microarray was used to examine 4 asthmatic cases and 4 healthy controls, and the results suggested that there might be differences in methylation within exon 9 of the ADAM33 gene. Therefore, we designed a case-control study with 50 asthmatic patients and 50 age- and sex-matched healthy controls to examine the relationship between the CpG methylation of the ADAM33 gene and asthma using bisulfite deoxyribonucleic acid modification and sequencing. RESULTS: Bisulfite sequencing experiments showed that the 14 CpG sites in exon 9 of the ADAM33 gene were highly methylated (100%) in all individuals. The proportions of methylation of the 14 CpG sites in ADAM33 in the case group were not different from those of the control group. The methylation of exon 9 of this locus was not associated with age, sex, IgE levels, or lung function. This study found no association between the methylation of CpG sites in exon 9 of the ADAM33 gene and adult asthma. CONCLUSIONS: The 14 CpG sites were highly methylated in the case and control groups. Further investigation of exon 9 in ADAM33 in a larger population is needed to evaluate its role in asthma.

The association between adult asthma and superoxide dismutase and catalase gene activity.

BACKGROUND: Adult asthma is caused by interaction effects of multiple genetic and environmental factors. Some studies have suggested that antioxidant enzyme activity and gene polymorphisms may play important roles in the context of asthma. Therefore, our study objectives were to investigate the association between asthma, antioxidant activities and the polymorphisms of manganese superoxide dismutase (Mn-SOD) or catalase (CAT). MATERIALS AND METHODS: A case-control study, for which we recruited 250 asthmatic adults and 250 age- and sex-matched controls. All subjects completed a questionnaire. Waist and hip circumference measurements, a lung function test and DNA genotyping were performed. In total, 50 incident cases and 50 matched controls who were non-smokers or had quit smoking for at least 1 year were selected in order to investigate SOD and CAT activity levels. RESULTS: In our study, we did not find a significant association between Mn-SOD Ala16Val, CAT C-262T and asthma. The level of SOD activity in new-onset asthma patients was significantly lower than in control subjects (p < 0.0005). The level of CAT activity in new-onset asthma patients was significantly higher than in control subjects (p < 0.0005). CONCLUSIONS: The levels of SOD and CAT activity were significantly related to adult asthma. SOD and CAT activity may be good tools to differentiate potential asthma sufferers. This would enable us to further investigate the mechanism of defective antioxidant enzymes in the context of asthma pathogenesis.

Effect of carbon dioxide on pulmonary vascular tone at various pulmonary arterial pressure levels induced by endothelin-1.

There have been contradictory reports suggesting that CO(2) may constrict, dilate, or have no effect on pulmonary vessels. Permissive hypercapnia has become a widely adopted ventilatory technique used to avoid ventilator-induced lung injury, particularly in patients with acute respiratory distress syndrome (ARDS). On the other hand, respiratory alkalosis produced by mechanically induced hyperventilation is the mainstay of treatment for newborn infants with persistent pulmonary hypertension. It is important to clarify the vasomotor effect of CO(2) on pulmonary circulation in order to better evaluate the strategies of mechanical ventilation in intensive care. In the present study, pulmonary vascular responses to CO(2) were observed in isolated rat lungs (n = 32) under different levels of pulmonary arterial pressure (PAP) induced by various doses of endothelin-1 (ET-1). The purposes of this study were to investigate (1) the vasodilatory effect of 5% CO(2) in either N(2) (hypoxic-hypercapnia) or air (normoxic-hypercapnia) at different PAP levels induced by various doses of endothelin-1, and (2) the role of nitric oxide (NO) in mediating the pulmonary vascular response to hypercapnia, hypoxia, and ET-1. The results indicated that (1) CO(2) produces pulmonary vasodilatation at high PAP under ET-1 and hypoxic vasoconstriction; (2) the vasodilatory effect of CO(2) at different pressure levels varies in accordance with the levels of PAP, the dilatory effect tends to be more evident at higher PAP; and (3) endogenous NO attenuates ET-1 and hypoxic pulmonary vasoconstriction but does not augment the CO(2)-induced vasodilatation.

Successful weaning predictors in a respiratory care center in Taiwan.

Respiratory care centers (RCCs) provide effective care for patients who have been in intensive care and have undergone prolonged mechanical ventilation. Between February 2002 and December 2005, 891 patients who met the admission criteria of RCCs were referred to our RCC at Kaohsiung Medical University Hospital in southern Taiwan for attempted weaning. We recorded demographic and clinical data, including variables identified previously as predictive of weaning success among highly selected populations. The common causes of respiratory failure at RCC admission were neuromuscular disease (29.2%), pneumonia (27.5%), cancer (18.0%), cardiovascular disease (10.1%), sepsis (5.7%) and post-surgery (1.6%). The percentage of patients successfully weaned was 40.2%, while 59.8% remained dependent on ventilators. In a stepwise multivariate logistic regression analysis, significant predictors of weaning success included neuromuscular disease (odds ratio [OR], 2.64), APACHE II score (OR, 0.93) and blood urea nitrogen level at RCC admission (OR, 0.99). The results could be helpful in the accreditation of medical care quality and may provide guidelines for future research and education programs.

Gastro-intestinal metastasis of primary lung carcinoma: clinical presentations and outcome.

Symptomatic gastro-intestinal (GI) metastasis in lung carcinomas is extremely rare and only a few case reports have been published. Here we review all of the cases of lung cancer from January 2003 to April 2005 in a tertiary teaching hospital in Taiwan. A total of six patients (1.77%, 6/339) with primary lung cancer demonstrated symptomatic gastro-intestinal metastasis. Three patients had squamous cell carcinoma, one had adenocarcinoma, and two had small cell carcinoma. Three patients with gastric metastasis were diagnosed via gastro-endoscopy while one with cecal involvement was diagnosed via colon fiberscopy. Two patients with small bowel perforation and intussusception were diagnosed via laparotomy. We presented these rare cases and made a review of the literature.

Spontaneous pneumothorax as a complication of septic pulmonary embolism in an intravenous drug user: a case report.

Infective endocarditis has been the major cause of morbidity and mortality among intravenous drug users (IDUs) with infections, mostly involving the tricuspid valve and presenting multiple septic pulmonary embolisms. Numerous pulmonary complications of septic pulmonary embolism have been described, but only a few have reported spontaneous pneumothorax. Our patient, a 23-year-old heroin addict, was hospitalized for tricuspid endocarditis and septic pulmonary embolism. Acute onset of respiratory distress occurred on his seventh hospital day and rapidly resulted in hypoxemia. Immediate bedside chest radiograph demonstrated left pneumothorax. It was thought to be a spontaneous pneumothorax, because he had not undergone any invasive procedure before the occurrence of pneumothorax. His clinical condition improved after the insertion of an intercostal chest tube. He later underwent surgery to replace the tricuspid valve as a result of the large size of the vegetation and poor control of infection. He ultimately survived. Pneumothorax is a possible lethal complication of septic pulmonary embolism in IDUs with right-sided endocarditis and should be considered in such patients when respiratory distress occurs acutely during their hospitalization.

Expression and regulation of the macrophage inflammatory protein-1 alpha gene by nicotine in rat alveolar macrophages.

Cigarette smoking causes inflammation mainly confined to the airway and lung. Nicotine is one of the primary constituents in cigarette smoke. Alveolar macrophages apparently play a pivotal role in mediating pulmonary inflammation via the production of chemokines. Macrophage inflammatory protein-1 alpha (MIP-1 alpha), a member of CC chemokines, has been shown to contribute to monocyte/macrophage and neutrophil chemotaxis and activation. Our previous work demonstrated that MIP-1 alpha mRNA expression in macrophages is induced by a variety of stimuli. In the present study, we further investigate whether nicotine can regulate the gene expression of MIP-1 alpha in macrophages and determine the mechanism leading to increased expression. A rat alveolar macrophage (RAM) cell line, NR8383, was treated with nicotine at a dose of 3.1, 31, 310 microM, or 3.1 mM. Northern blot analysis showed that the induction of MIP-1 alpha mRNA expression was dose-dependent. To define the time course of the inflammatory response, RAM cells were exposed to 31 microM nicotine, MIP-1 alpha mRNA was induced as early as 1 h after treatment, was maximally expressed at 4 and 6 hours, and reduced by 8 hours. Western blot analysis demonstrated a single band with an estimated molecular weight of 10 kD for MIP-1 alpha which was induced after nicotine treatment, suggesting that expression of MIP-1 alpha mRNA could reflect in protein synthesis. In addition. the increase in MIP-1 alpha mRNA expression induced by nicotine was attenuated by co-treatment with the antioxidant N-acetylcysteine (NAC), at doses of 10 and 20 mM, suggesting that the induction of MIP-1 alpha mRNA is mediated via the generation of reactive oxygen species (ROS). To further investigate transcriptional regulation of the MIP-1 alpha gene expression, RAM cells were exposed to nicotine. MIP-1 alpha mRNA levels were significantly increased in nuclear RNA preparations, indicating that transcriptional activation is involved in increased expression of MIP-1 alpha mRNA. Moreover, we performed RNA decay assay by measuring the half-life of MIP-1 alpha mRNA. Treatment of RAM cells with the transcriptional inhibitor actinomycin D following exposure to nicotine revealed that the half-life of MIP-1 alpha mRNA was markedly increased by nicotine treatment, supporting a role of post-transcriptional stabilization in MIP-1 alpha gene expression. These observations indicate that nicotine can induce MIP-1 alpha mRNA expression and protein synthesis in RAM cells, mediating, at least in part, via the generation of ROS. In addition, the increase in MIP-1 alpha mRNA level involves, both transcriptional activation and post-transcriptional stabilization.

A subset of clinical status of pulmonary tuberculosis in Southern Taiwan.

The aims of this study were to present the clinical status of pulmonary tuberculosis in Southern Taiwan and to analyze the reasons for failure of antituberculosis treatment in order to achieve a higher rate of success after treatment. Two hundred and senventeen adult patients, aged 15 to 90 years old who presented to the Chest Division, Kaohsiung Medical University Hospital from 1999 to 2002 with a diagnosis of Pulmonary Tuberculosis, were retrospectively studied. We compared the rate of recurrence of pulmonary tuberculosis by dividing the cases into 2 groups: those who completed treatment and those who did not. We also determined the age distributions for when initial diagnosis of pulmonary tuberculosis was made among these 217 cases. In 90 culture proven cases, antituberculosis drug susceptibility was tested to determine the rate of drug resistance. We also assessed the reasons for failure of treatment. Age distribution analysis showed that initial infection began at a young age, was widely spread, and occurred regardless of age. There were 116 cases that completed antituberculosis treatment and 101 cases that did not. Of the 116 cases, only 16 relapsed, whereas 79 of the 101 cases relapsed. In cases where completely treated patients relapsed, the period before recurrence was indefinite. Most of the cases of incompletely treated patients relapsed earlier. In the 90 culture proven cases in which antituberculosis drug susceptibility was tested, 39 patients showed resistance to at least one drug, 9 patients were resistant to only one drug, 9 patients were resistant to two drugs and 21 patients were resistant to more than 3 drugs. The common reasons for failure of treatments were: 1) poor patient compliance to medication: 50 cases, 2) multiple drug resistance: 30 cases, 3) delayed treatment: 19 cases. Some cases included a combination of the above.

Do pulmonary hemodynamics change after effective lung volume reduction surgery for emphysema?

The improvement in lung function, exercise test, blood gas levels, and symptoms in emphysema patients after volume reduction surgery is a result of improvements in breathing mechanics. The question is, is the improvement in the condition related to pulmonary hemodynamics? Few studies have examined pre- and postoperative pulmonary pressure. This paper examines whether there is any significant change in systolic and diastolic pulmonary pressure after effective volume reduction surgery. From October 1999 to October 2002, 12 emphysema patients who underwent volume reduction surgery were studied. Systolic and diastolic pulmonary pressures were measured 2 days before surgery through cardiac catheterization and 2 days after removal of the chest tubes through Swan Ganz catheters placed in the operating room just before surgery. Patients were stable and breathed without assistance during the postoperative pressure measurement. Blood gas analysis, lung function tests, and a 6-minute walk test were performed preoperatively and 3 months postoperatively. The two sets of data were compared using the Wilcoxon signed rank test. There was no significant change in pulmonary hemodynamics, although pulmonary function improved. The improvement in pulmonary function after volume reduction surgery is not related to pulmonary hemodynamics.

Outcomes of the patients in the respiratory care center are not associated with the seniority of the caring resident.

Although many studies show that the experience level of physicians is significantly associated with the outcomes of their patients, little evidence exists to show whether junior residents provide worse care than senior residents. This study was conducted to analyze whether the experience level of residents may affect the outcomes of patients cared for in a well-organized setting. We conducted a 7-year retrospective study utilizing statistical data from a respiratory care center (RCC) in a medical center between October 2004 and September 2011. In addition to the two medical residents who had been trained in the intensive care unit (ICU), the RCC team also included attending physicians in charge, a nurse practitioner, a case manager, a dietitian, a pharmacist, a social worker, registered respiratory therapists, and nursing staff. Weaning from mechanical ventilation was done according to an established weaning protocol. The 84 months analyzed were classified into five groups according to the levels of the two residents working in the RCC: R2 + R1, R2 + R2, R3 + R1, R3 + R2, and R3 + R3. The monthly weaning rate and mortality rate were the major outcomes, while the mean ventilator days, rate of return to the ICU, and nosocomial infection incidence rate were the minor outcomes. The groups did not differ significantly in the monthly weaning rate, mortality rate, mean ventilator days, rate of return to the ICU, or nosocomial infection incidence rate (p > 0.1). Further analysis showed no significant difference in the monthly weaning rate and mortality rate between months with a first-year resident (R1) and those with two senior residents (p > 0.2). Although the weaning rate in the RCC gradually improved over time (p < 0.001), there was no significant difference in the monthly weaning rate between the groups after adjusting for time and disease severity (p > 0.7). Thus, we concluded that in a well-organized setting, the levels (experiences) of residents did not significantly affect patient outcomes. This result may be attributed to the well-developed weaning protocol and teamwork processes in place, which avoid a large effect from any single factor and provide stable and high-quality care to the patients.

Aortobronchial fistula after esophagectomy for esophageal cancer -- a very rare complication.

Most aorto-respiratory fistulas are related to aortic pathology or procedures, but fistula formation after esophageal resection has never been reported in the literature. We are now reporting a case of hemoptysis that occurred after esophagectomy for locally advanced esophageal cancer. Aortobronchial fistula was detected by computed tomography scan. The patient was finally saved by emergency surgery-Dacron graft interposition of the descending thoracic aorta. There was no malignant cell in the postoperative specimen of the fistula. The erosion of the ligaclips (Johnson & Johnson) might be responsible for the aortobronchial fistula formation. For esophageal surgery, avoidance of trauma to aortic wall and careful using of ligaclips are important to circumvent this complication.

The effects of the self-efficacy method on adult asthmatic patient self-care behavior.

BACKGROUND: The prevalence of asthma and associated mortality is higher among adults than among children, as are associated morbidity and hospital readmission rates. The literature shows that promoting patient self-care behaviors and self-efficacy helps reduce recurrence and hospital readmission rates. Therefore, self-care behaviors and self-efficacy represent critical issues in successful asthma management. PURPOSE: This study was developed to investigate the effects of a self-efficacy intervention on (a) the self-care behaviors of adult asthma patients and (b) the self-efficacy of adult asthmatic patients. The study used a pretest-posttest experimental design. METHODS: A total of 60 asthma outpatients who visited the chest medicine division of a medical center in Kaohsiung City between March 2, 2009, and January 31, 2010, were assessed. Patients were randomly divided into two groups (experimental and control), with 30 patients assigned to each. Experimental group participants received the self-efficacy intervention program, which included watching a 15- to 20-minute DVD, received a healthcare booklet on self-efficacy for adult asthmatic patients, were asked to share their illness experience with support groups, and received medical follow-ups by telephone. Control group patients received conventional health education administered by the outpatient department. Study instruments included a self-care behavior scale for adult asthmatic patients (content validity index = .95, Cronbach's α = .82) and a self-efficacy scale for adult asthmatic patients (content validity index = .98, Cronbach's α = .82). RESULTS: The two key findings of this study were as follows: (a)There was a significant improvement in the self-care behaviors of patients who received self-efficacy intervention in terms of medication adherence (p= .008), self-monitoring (p= .000), avoidance of antigens (p = .001), regular follow-up visits (p = .000), and regular exercise (p = .016); and (b) the program improved participant self-efficacy in terms of both asthma attack prevention (p = .030) and management during asthma attacks (p = .017). CONCLUSIONS: On the basis of these results, self-efficacy intervention has been demonstrated a beneficial addition to adult asthmatic patient self-care regimens.

Outcome of physical therapy intervention on ventilator weaning and functional status.

Our study aimed to understand the characteristics of ventilator dependence in patients at a respiratory care center and the potential effects of physical therapy on ventilator weaning and patients' functional status. Prospective data collection consisted of the following: (1) demographic data, including name, gender, age, diagnosis, the Acute Physiology and Chronic Health Evaluation as a severity of the disease, modified Glasgow Coma Scale, mobility at the time of admission, and days of hospitalization; (2) Rapid shallow breathing index (RSBI) as a predictive indicator of ventilator weaning, including indicators of ventilator weaning were collected from the respiratory flow sheet; and (3) Barthel index. Between July 1 and December 31, 2007, 126 patients were admitted to the respiratory care center, and those who required mechanical ventilation for more than 14 days were enrolled. Fifty-five subjects received physical therapy. The RSBI in patients who received physical therapy was 75.7 +/- 37.9 before therapy and 80.0 +/- 48.5 afterwards, while the Barthel index increased from 0.8 +/- 1.4 to 1.9 +/- 2.5 (p < 0.05). The RSBI decreased as time of physical therapy lengthened, but not significantly (r = 0.12, p = 0.44). The success rate of ventilator weaning in patients receiving physical therapy intervention versus non-physical therapy intervention was 58.2% and 40.9%, respectively. The results indicated that lengthening the physical therapy intervention time enhanced the ventilator weaning success rate while mobility was not affected (r = -0.11, p = 0.41). Physical therapy may be offered to ventilator-dependent patients in line with their individual needs to improve or maintain basic mobility.

Antiproliferative and antitumorigenic activity of Toona sinensis leaf extracts in lung adenocarcinoma.

Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G(1) peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G(1) arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti-lung cancer drug.

Management of a nosocomial outbreak of Mycobacterium tuberculosis Beijing/W genotype in Taiwan: an emphasis on case tracing with high-resolution computed tomography.

A nosocomial outbreak of Mycobacterium tuberculosis Beijing/W genotype infected 15 healthcare workers (HCWs) in a medical center in Taiwan, where there is a high prevalence of tuberculosis and a high rate of positive tuberculin skin tests. An index patient with laryngeal cancer and a lung abscess was identified by epidemiological investigation and it was found that an M. tuberculosis isolate from his lung tissue sample had an identical IS6110 restriction fragment length polymorphism pattern to the isolates from 3 HCWs. Confirmation of the identity of this strain as Beijing/W genotype was made using spoligotyping. Seven hundred and eighty-five HCWs potentially exposed to the probable index patient received contact investigation and chest X-ray screening. We used chest high-resolution computed tomography (HRCT) to clarify trivial lesions in chest X-rays. Nine HCWs with smear-negative pulmonary tuberculosis were diagnosed by HRCT. Fifteen of the 35 (42.9%) HCWs with documented exposure to the index patient developed pulmonary tuberculosis within 11 months after exposure. The outbreak was successfully controlled by active case finding and enforcement of infection control strategies. Intervention to detect the potential tuberculosis source is helpful in the prevention and control of a nosocomial tuberculosis outbreak. HRCT can be a useful tool for tuberculosis diagnosis of contacts in an outbreak situation.

Clinical and radiographic presentations of pulmonary cryptococcosis in immunocompetent patients.

Pulmonary cryptococcosis is often noted in immunocompromized patients, especially in HIV-seropositive patients and post-transplant patients. Only a few case reports and small-scale studies on pulmonary cryptococcosis in immunocompetent patients have been published in the English literature. However, there are several areas of uncertainty in this group of patients including image presentations and management strategy. This retrospective study including 17 patients is designed to share our 7 y of experience in clarifying the characteristics of pulmonary cryptococcosis in immunocompetent patients, including initial symptoms, diagnostic criteria, pulmonary imaging, treatment and outcome in a tertiary teaching hospital in Taiwan.