Survey of the management of patients with bronchiectasis: a pilot investigation in Asian populations.

BACKGROUND/AIMS: Although international guidelines for bronchiectasis management have been published in Western countries, there is a lack of data about their application in Asian populations including patients with different phenotypes. We aimed to investigate the current status of bronchiectasis management in Asian populations. METHODS: A nationwide questionnaire survey was performed of Asian respiratory specialists from South Korea, Japan, Taiwan, Singapore, Vietnam, and Sri Lanka. Participants were invited by e-mail to answer a questionnaire comprising 25 questions based on international guidelines for the management of bronchiectasis. RESULTS: A total of 221 physicians participated in the survey. About half of them were Korean (50.2%), with the next most common nationalities being Japanese (23.1%), Taiwanese (13.6%), and Singaporean (7.7%). Only 18 (8.1%) responders had local guidelines for bronchiectasis. While 85 (38.5%) responders checked sputum acid-fast bacillus smear/culture about 1 to 3 times per year, only a small proportion of responders routinely performed a serum immunoglobulin test (36/221, 16.3%) or evaluated for allergic bronchopulmonary aspergillosis (41/221, 18.6%). Less than half (43.4%) of responders performed eradication treatment in patients with drug-sensitive Pseudomonas aeruginosa infection, mainly due to the limited availability of inhaled antibiotics (34.8%). In addition, 58.6% of responders considered physiotherapy such as airway clearance and pulmonary rehabilitation. CONCLUSION: Discrepancies might exist between guideline recommendations and practice for bronchiectasis management in Asian populations, partly due to the limited availability of treatment in each country. The development of local guidelines that consider the phenotypes and situation will help to standardize and improve the management of bronchiectasis.

Discovery of a novel anticancer agent with both anti-topoisomerase I and II activities in hepatocellular carcinoma SK-Hep-1 cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine for various applications. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human hepatocellular carcinoma SK-Hep-1 cell line. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase-3 and caspase-9, increase in the DNA content in sub-G1, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments, suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2, prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against SK-Hep-1 cells is accompanied by downregulations of NF-κB-binding activity, inflammatory responses involving cyclooxygenase-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and volume of acidic compartments. Similar effects (including all of the above-mentioned effects) were found in other tested cell lines, including human hepatocellular carcinoma Hep 3B, lung adenocarcinoma A549, squamous cell carcinoma NCI-H520, colorectal adenocarcinoma COLO 205, and T-lymphoblastic MOLT-3 (results not shown). Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

High-resolution computed tomography in assessment of patients with emphysema.

OBJECTIVE: To assess whether high-resolution computed tomography (HRCT) variables are as good as other known clinical variables in grading emphysema patients. METHODS: A detailed clinical history was taken and physical examination performed. We performed serum study, lung function testing, and HRCT scanning to assess emphysema. Mean lung density, the attenuation value separating the least 15% of pixels (PERC15), the percentage of the relative area of the lungs with attenuation values < -950 Hounsfield units (HU) (RA950), and histogram analysis were calculated from computerized data. RESULTS: The final analysis was based on data from 92 subjects, and they were moderately emphysematous (mean lung density was -877 ± 23 HU, PERC15 was -953 ± 21 HU, and RA950 was 16 ± 5%). There was a significant difference regarding subjective emphysema severity in the St George's Respiratory Questionnaire, smoking history, FEV1, C-reactive protein, age, and body mass index (P < .001). There was a significant correlation between the 3 objective image variables and the 6 objective clinical variables (St George's Respiratory Questionnaire, smoking history, FEV1, C-reactive protein, age, and body mass index) (P < .001). CONCLUSIONS: This study shows the possible important role of HRCT in the diagnosis and quantification of pulmonary emphysema.

Diallyl sulfide protects against ultraviolet B-induced skin cancers in SKH-1 hairless mouse: analysis of early molecular events in carcinogenesis.

BACKGROUND: Diallyl sulfide (DAS) has been shown to have a preventive effect against various cancers. AIMS AND OBJECTIVES: We evaluated the protective effects of DAS in regression of ultraviolet B (UVB)-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers. METHODS: We examined the efficacy of DAS in UVB light-induced skin lesion in SKH-1 hairless mice and the associated molecular events. RESULTS: Mice irradiated with UVB at 180mJ/cm(2) twice per week elicited 100% tumor incidence at 20 weeks. The topical application of DAS before UVB irradiation caused a delay in tumor appearance, multiplicity, and size. The topical application of DAS before and immediately after a single UVB irradiation (180mJ/cm(2) ) resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells, together with an increase in p53 and p21/Cip1-positive cell population in the epidermis. Simultaneously, DAS also significantly inhibited nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. CONCLUSIONS: The protective effect of DAS against photocarcinogenesis is accompanied by the down-regulation of cell-proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, and up-regulation of p53, p21/Cip1 to prevent DNA damage and facilitate DNA repair.

Predicted postoperative product and diffusion heterogeneity index in the evaluation of candidates for lung resection.

OBJECTIVES: The primary objective of this retrospective study was to evaluate whether abnormal predicted postoperative variables and predicted postoperative product are useful in predicting postoperative complications. The secondary objective was to assess whether an abnormal diffusion heterogeneity index is associated with increased postoperative complications. METHODS: In this retrospective study we evaluated the medical records of 57 patients who underwent lung resection for lung cancer. Calculations of the predicted postoperative variables were done using preoperative testing data, including the extent of the resected lung segments. Predicted postoperative product was obtained by multiplying the predicted postoperative percent-of-predicted FEV(1) by the predicted postoperative percent-of-predicted single-breath diffusing capacity of the lung for carbon monoxide (D(LCO)). The measured product was obtained by multiplying FEV(1) by D(LCO). We derived diffusion heterogeneity index from measurements of the single-breath D(LCO) with the 3-equation method, as a measure of the heterogeneity of the distribution of gas exchange in the lung. RESULTS: Patients with complications had lower predicted postoperative FEV(1) (P < .001), lower predicted postoperative D(LCO) (P < .001), lower predicted postoperative maximal oxygen uptake (P < .001), lower predicted postoperative increase in percent-of-predicted D(LCO) at 70% work load from at-rest percent-of-predicted D(LCO) (ΔD(LCO)%) (P < .001), lower predicted postoperative product (P < .001), and lower measured product (P = .004). Interestingly, diffusion heterogeneity index increased with exercise in [corrected] patients with complications but decreased with exercise in [corrected] patients without complications. CONCLUSIONS: The predicted postoperative variables, predicted postoperative product, measured product, and diffusion heterogeneity index are potentially useful predictors of complications in candidates for lung resection.

The effects of a swimming intervention for children with asthma.

BACKGROUND AND OBJECTIVE: Asthma is a common paediatric airway disease with increasing prevalence. Studies comparing swimming with other sports have found that swimming is unlikely to provoke unstable asthma but possible benefits are not defined. This study investigated the benefits of a 6 week swimming intervention on pulmonary function tests (PFT), PEF and severity of asthma in children. METHODS: Young asthmatics were randomly assigned to the experimental or the control group, with 15 subjects in each group. In addition to regular treatment for asthma, the experimental group received swimming training for 6 weeks. PFT, PEF and severity of asthma were measured. RESULTS: There was a significant improvement (P < 0.01) in PEF in the experimental group compared with the control group (330 L/min, 95% CI: 309-351 vs. 252 L/min, 95% CI: 235-269) after the swimming intervention. There was also a significant improvement (P < 0.05) in the severity of asthma in the experimental group compared with the control group. CONCLUSIONS: These data suggest that a swimming programme for asthmatic children can improve some disease parameters (PEF and the severity of asthma). Swimming may be an effective non-pharmacological intervention for the child or adolescent with asthma.

Improved lung function after thoracocentesis in patients with paradoxical movement of a hemidiaphragm secondary to a large pleural effusion.

BACKGROUND AND OBJECTIVES: Previous studies have shown little or no improvement in pulmonary function and arterial blood oxygenation after therapeutic thoracocentesis. This study investigated changes in pulmonary function, arterial blood gases and dyspnoea after therapeutic thoracocentesis in patients with paradoxical movement (PM) of a hemidiaphragm due to pleural effusion. METHODS: Twenty-one patients with pleural effusion and PM of a hemidiaphragm and 41 patients with pleural effusion but without paradoxical movement (NPM) were studied before and 24 h after thoracocentesis. Lung function measurements included lung mechanics, blood gas exchange and the Borg dyspnoea scale. RESULTS: At thoracocentesis a mean of 1,220 mL of pleural fluid was removed from the PM group and 1,110 mL from the NPM group. Post-thoracocentesis the PM group showed small but significant improvement (P < 0.05) in FEV(1) (63% vs 73%), FVC (67% vs 77%), PaO(2) (66 mm Hg vs 73 mm Hg), A-a O(2) gradient (38 mm Hg vs 30 mm Hg), and the Borg scale (5.1 vs 2.1). The NPM group showed no significant change in any parameter. CONCLUSIONS: Statistically significant improvement in pulmonary function following thoracocentesis was observed in patients with pleural effusion and PM of the hemidiaphragm. Patient selection may therefore explain the different outcomes of thoracocentesis reported in previous studies.

Effect of lung resection on exercise capacity and on carbon monoxide diffusing capacity during exercise.

OBJECTIVE: To evaluate the effect of lung resection on lung function and exercise capacity values, including diffusion capacity of the lung for carbon monoxide (Dlco), during exercise, and to determine whether postoperative lung function, including exercise capacity and Dlco during exercise, could be predicted from preoperative lung function and the number of functional segments resected. DESIGN: Prospective study. SETTING: Clinical pulmonary function laboratory in a university teaching hospital. PATIENTS: Twenty-eight patients undergoing lung resection at Vancouver General Hospital from October 1998 to May 1999, were studied preoperatively and 1-year postoperatively. INTERVENTIONS: We determined FEV(1) and FVC, and maximal oxygen uptake (Vo(2)max) and maximal workload (Wmax) achieved during incremental exercise testing. We used the three-equation modification of the single-breath Dlco technique to determine Dlco at rest (RDlco) and during steady-state exercise at 70% of Wmax, and the increase in Dlco from rest to exercise (ie, the mean increase in Dlco percent predicted at 70% of Wmax from resting Dlco percent predicted [(70%-R)Dlco]). We calculated the predicted postoperative (PPO) values for all the above parameters using the preoperative test data and the extent of functioning bronchopulmonary segments resected, and compared the results with the actual 1-year postoperative results. RESULTS: Following lung resection, there was a significant reduction in FEV(1), FVC, and Dlco with decreases of 12%, 13%, and 22% predicted, respectively. There were also significant decreases in Vo(2)max per kilogram of 2.1 mL/min/kg (8% of predicted Vo(2)max) and in Wmax of 12 W (7% of predicted Wmax). However, (70%-R)Dlco did not significantly decrease after lobectomy but decreased after pneumonectomy. The calculated PPO values significantly underestimated postoperative values after pneumonectomy but were acceptable for lobectomy. CONCLUSIONS: Exercise tests may be better indicators of functional capacity after lung resection than measurements of FEV(1) and FVC or RDlco. PPO results calculated by estimating the functional contribution of the resected segments, are comparable with those obtained using ventilation-perfusion lung scanning and significantly underestimate postoperative lung function after pneumonectomy, but are acceptable for lobectomy.

Pulmonary function tests in preoperative pulmonary evaluation.

Pulmonary function testing (PFT) has been used to evaluate the risk for postoperative complications since the 1950s. PFT including spirometry, lung volumes, diffusing capacity, oximetry, and arterial blood gases has been used to assess the postoperative risk of lung resection. In selected cases, additional evaluation may include radionuclide lung scanning, exercise testing, invasive pulmonary hemodynamic measurements, and risk stratification analysis. A new index, predicted postoperative product (PPP), was found to have strong predictive ability for mortality. We defined a new useful index, measured product (MP), to predict postoperative complications; MP had similar advantages of PPP. Since diffusing capacity at rest has been shown to be a good predictor of postoperative complications following lung resection, and since exercise testing has been also useful in preoperative evaluation prior to lung resection, we reasoned that evaluation of the effect of exercise on diffusing capacity would be helpful to evaluate the ability of the pulmonary capillary bed to expand and increase its capacity to transfer gas during exercise.

Relationship of carbon monoxide pulmonary diffusing capacity to postoperative cardiopulmonary complications in patients undergoing pneumonectomy.

This retrospective analytic study evaluated whether abnormal diffusing capacity for carbon monoxide (DLCO) is a predictor of postoperative morbidity and mortality in patients undergoing pneumonectomy for lung cancer. The medical records of patients undergoing pneumonectomy at Vancouver General Hospital between January 1992 and December 1997 were reviewed. Postoperative complications occurring within 30 days of resection were classified into mortality, and cardiovascular, pulmonary, and technical complications. A total of 151 pneumonectomy cases were reviewed. There were 100 men (66%) and 51 women (34%) with a mean age of 61 years. Complications occurred in 73 patients (48%), including mortality in eight (5%), cardiovascular morbidity in 50 (33%), pulmonary morbidity in 30 (20%), and technical morbidity in 22 (15%). Arrhythmia (21%) and pulmonary edema (13%) were the two major cardiovascular complications. Patients with complications had a greater smoking history, a longer hospital stay, a lower forced expiratory volume in 1 second (FEV1), a lower FEV1/forced vital capacity (FVC) ratio, a lower DLCO, and a lower DLCO/alveolar volume (VA) ratio than patients without complications. A DLCO of 70% predicted was the best functional predictor of postoperative complications, with a complication rate of 94% in patients with a DLCO of less than 70% predicted compared with 27% in patients with a DLCO of at least 70% predicted (sensitivity, 62%; specificity, 96%). However, technical morbidity was not related to preoperative lung function variables, including DLCO. Patients with a DLCO of at least 70% predicted had a low postpneumonectomy complication rate. Although cardiac arrhythmia was the major cause of morbidity, pulmonary edema was the major cause of mortality.

Relationship of predicted postoperative product to postpneumonectomy cardiopulmonary complications.

BACKGROUND: This retrospective analytic study was to evaluate diffusing capacity of the lung for carbon monoxide (DLCO) and predicted postoperative product (PPP) as predictors of postpneumonectomy cardiopulmonary complications. METHODS: One-hundred fifty-one patients underwent pneumonectomy at Vancouver General Hospital from January 1992 to December 1997. The PPP was obtained by multiplying the predicted postoperative (ppo) FEV1 by the ppo DLCO, both expressed as % of predicted. The ppo FEV1 and DLCO were derived by calculating the proportional loss of functional lung from the resected lung. We also evaluated a new index, the measured product (MP), obtained by multiplying the measured preoperative FEV1 by DLCO, both expressed as % of predicted. RESULTS: Patients with complications had lower FEV1, lower DLCO, lower MP, lower ppo FEV1, lower ppo DLCO, and lower PPP than patients without complications. DLCO at 70% of predicted was the best predictor of postoperative complications, while PPP at 1400 was similar to MP at 5000 and ppo DLCO at 40% of predicted in predicting postoperative complications. The complication rate was 88% in patients with DLCO < 70% of predicted, compared with a complication rate of 19% in patients with DLCO > or = 70% of predicted (sensitivity = 68%, specificity = 93%), while the complication rate was 66% in patients with PPP < 1400, compared with a complication rate of 25% in patients with PPP > or = 1400 (sensitivity = 63%, specificity = 78%). CONCLUSIONS: DLCO < 70% of predicted is associated with increased risk of complications following pneumonectomy. PPP determined preoperatively allows a patient with a critically low value (< 40% of predicted) for one variable (either ppo FEV1 or ppo DLCO) to be accepted for surgery on the basis of a good value in the other. Patients with PPP > or = 1400 have a relatively low postpneumonectomy complication rate.