Yu Lun Lo

Diagnostic Value of EBUS-TBNA for Lung Cancer with Non-Enlarged Lymph Nodes: A Study in a Tuberculosis-Endemic Country

Background In tuberculosis (TB)-endemic areas, contrast-enhanced computed tomography (CT) and positron emission tomography (PET) findings of lung cancer patients with non-enlarged lymph nodes are frequently discrepant. Endobronchial ultrasound-guided transbronchial aspiration (EBUS-TBNA) enables real-time nodal sampling, and thereby improves nodal diagnosis accuracy. This study aimed to compare the accuracy of nodal diagnosis by using EBUS-TBNA, and PET. Methods We studied 43 lung cancer patients with CT-defined non-enlarged mediastinal and hilar lymph nodes and examined 78 lymph nodes using EBUS-TBNA. Results The sensitivity, specificity, positive predictive value, and negative predictive value of EBUS-TBNA were 80.6%, 100%, 100%, and 85.7%, respectively. PET had low specificity (18.9%) and a low positive predictive value (44.4%). The diagnostic accuracy of EBUS-TBNA was higher than that of PET (91% vs. 47.4%; p<0.001). Compared to CT-based nodal assessment, PET yielded a positive diagnostic impact in 36.9% nodes, a negative diagnostic impact in 46.2% nodes, and no diagnostic impact in 16.9% nodes. Patients with lymph nodes showing negative PET diagnostic impact had a high incidence of previous pulmonary TB. Multivariate analysis indicated that detection of hilar nodes on PET was an independent predictor of negative diagnostic impact of PET. Conclusion In a TB-endemic area with a condition of CT-defined non-enlarged lymph node, the negative diagnostic impact of PET limits its clinical usefulness for nodal staging; therefore, EBUS-TBNA, which facilitates direct diagnosis, is preferred.

Feasibility of Bispectral Index-Guided Propofol Infusion for Flexible Bronchoscopy Sedation: A Randomized Controlled Trial

Objectives There are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists. Methods After administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation. Results The proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group. Conclusions BIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference. Trial Registration ClinicalTrials. gov NCT00789815

Reduced nuclear factor-κB repressing factor: a link toward systemic inflammation in COPD

Chronic systemic inflammation is implicated in the systemic manifestations and, probably, the excess mortality risk of chronic obstructive pulmonary disease (COPD). The role of nuclear factor (NF)-&kgr;B repressing factor (NRF), a DNA-binding, protein-inhibiting NF-&kgr;B response gene, in human diseases has not been explored. We hypothesised that the NRF-negative regulatory mechanism is impaired in COPD peripheral blood mononuclear cells (PBMCs) leading to excessive interleukin (IL)-8/CXCL8 production. NRF expression, NF-&kgr;B activation, IL-8/CXCL8 release and intracellular oxidative stress were assessed in PBMCs of normal subjects and stable COPD patients. Primary PBMCs with NRF overexpression, NRF knockdown and exposure to H2O2 were used to elucidate the mechanisms. Stable COPD patients, especially those with severe COPD, showed decreased NRF expression, enhanced NF-&kgr;B activation and increased IL-8/CXCL8 release in PBMCs compared with normal subjects. This was associated with reduced NRF and increased RNA polymerase II occupancy at the IL-8/CXCL8 promoter. NRF knockdown enhanced IL-8/CXCL8 production in normal PBMCs, whilst NRF overexpression attenuated IL-8/CXCL8 production. Intracellular oxidative stress was increased in COPD PBMCs. H2O2-decreased NRF expression and -enhanced IL-8/CXCL8 production was augmented in COPD PBMCs. NRF expression is reduced in PBMCs of stable COPD patients, probably through oxidative stress, leading to increased production of IL-8/CXCL8 and potentially chronic systemic inflammation.

Bispectral Index in Evaluating Effects of Sedation Depth on Drug-Induced Sleep Endoscopy.

OBJECTIVE To evaluate the effect of sedation depth on drug-induced sleep endoscopy (DISE). METHODS Ninety patients with obstructive sleep apnea (OSA) and 18 snorers underwent polysomnography and DISE under bispectral index (BIS)-guided propofol infusion at two different sedation levels: BIS 65-75 (light sedation) and 50-60 (deep sedation). RESULTS For the patients with OSA, the percentages of velopharynx, oropharynx, hypopharynx, and larynx obstructions under light sedation were 77.8%, 63.3%, 30%, and 33.3%, respectively. Sedation depth was associated with the severity of velopharynx and oropharynx obstruction, oropharynx obstruction pattern, tongue base obstruction, epiglottis anteroposterior prolapse and folding, and arytenoid prolapse. In comparison, OSA severity was associated with the severity of velopharynx obstruction, severity of oropharynx obstruction, and arytenoid prolapse (odds ratio (95% confidence interval); 14.3 (4.7-43.4), 11.7 (4.2-32.9), and 13.2 (2.8-62.3), respectively). A good agreement was noted between similar DISE findings at different times and different observers (kappa value 0.6 to 1, respectively). A high percentage of arytenoid prolapse (46.7% among the patients with OSA under light sedation) was noted. CONCLUSIONS Greater sedative depth increased upper airway collapsibility under DISE assessment. DISE under BIS-guided propofol infusion, and especially a level of 65-75, offers an objective and reproducible method to evaluate upper airway collapsibility. Some findings were induced by drug sedation and need careful interpretation. Specific arytenoid prolapse patterns were noted for which further investigations are warranted. CLINICAL TRIALS REGISTRATION http://www.clinicaltrials.gov, identifier: NCT01100554. COMMENTARY A commentary on this article appears in this issue on page 965.

Associated bone mineral density and obstructive sleep apnea in chronic obstructive pulmonary disease

Background Osteoporosis is an important issue for patients with chronic obstructive pulmonary disease (COPD). Worse systemic inflammation and reduced exercise capacity have been reported in COPD patients with obstructive sleep apnea (OSA), implying that OSA may be an independent factor for osteoporosis in COPD patients. Methods A total of 66 patients with bone mineral density (BMD) and polysomnography results from a previous COPD cohort (January 2008 to January 2013) were retrospectively enrolled. Clinical characteristics such as medication, pulmonary function, BMD, and results of polysomnography were analyzed. Results The BMD in those with OSA was significantly lower than in those without OSA (−1.99±1.63 versus −1.27±1.14, P=0.045). In univariate analysis, body mass index, forced expiratory volume in 1 second, percentage of predicted value, incremental shuttle walk test, apnea–hypopnea index, and oxygen desaturation index (ODI) were significantly associated with BMD. After multivariate linear regression analysis, the ODI was still an independent factor for BMD. In addition, smaller total lung capacity is significantly associated with higher ODI and lower BMD, which implies that lower BMD might cause severer OSA via decreased total lung capacity. Conclusion OSA may be an independent factor for BMD in patients with COPD, which implies a possible vicious cycle takes place in these patients.

Endobronchial ultrasound-guided transbronchial biopsy and brushing: a comparative evaluation for the diagnosis of peripheral pulmonary lesions

OBJECTIVES The diagnosis of peripheral pulmonary lesions (PPLs) often involves endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB), washing and brushing. Certain echoic features of PPL have been associated with biopsy yield. This study compared yields of TBB and bronchial washing (TBBW) with those of TBBW plus bronchial brushing and analysed the associations between clinical and echoic features and yield. METHODS We performed a retrospective review of 271 patients undergoing TBB for PPL. TBBW was performed in 139 patients and 132 underwent TBBW plus brushing. RESULTS The diagnostic yield of TBBW plus brushing was superior to that of TBBW (80.3 vs 66.2%, P < 0.01). In TBBW patients, lesions <3 cm (57.1 vs 73.7%, P < 0.05), EBUS probe adjacent to the lesion (47.6 vs 74.2%, P < 0.01), continuous margin (56.5 vs 75.7%, P < 0.01) and homogeneous echogenicity (51.0 vs 75.0%, P < 0.01) predicted lower yields, but adding bronchial brushing rendered the diagnostic yields similar, irrespective of EBUS echoic features, leaving lesion size of <3 cm (odds ratio 2.81; 95% confidence interval 1.08-7.31, P < 0.05) as the single independent predictor of lower yield by multivariate regression analysis. TBB plus brushing was not inferior to TBBW plus brushing (78.8 vs 80.3%, P = 0.88). CONCLUSIONS Bronchial brushing boosted diagnostic yields, particularly for PPLs with echoic features previously associated with a reduced biopsy yield.

Chronic Obstructive Pulmonary Disease in Stage I Non-small Cell Lung Cancer That Underwent Anatomic Resection: The Role of a Recurrence Promoter

Abstract Background: Despite the use of anatomic resection, the post-surgical recurrence rate remains high in early-stage non-small cell lung cancer (NSCLC). Chronic inflammation plays a role in the mechanism that promotes tumor initiation. This study aimed to investigate the association between recurrence outcome and chronic inflammation-related co-morbidities in early-stage resected NSCLC. Methods: A review of medical records for recurrence outcome and co-morbidities, in terms of chronic obstructive pulmonary disease (COPD), DM, asthma and cardiovascular diseases, was performed with 181 patients with stage I NSCLC that underwent anatomic resection. Results: Subjects with T descriptors as T2a disease (49.5 vs. 28.0%, p < 0.05) and the presence of COPD (42.4 vs. 20.7%, p < 0.01) had a higher risk of tumor recurrence. Univariate analysis for recurrence-free survival showed T descriptor as T2a (21.5 months vs. NR, p < 0.05) and the presence of COPD (20.5 months vs. NR, p < 0.01) as significant factors predicting reduced survival. The presence of COPD (HR: 1.98; 95% CI, 1.29–.02, p < 0.01) and T descriptor as T2a (HR: 2.01; 95% CI, 1.04–3.91, p < 0.05) remain independent predictors of reduced recurrence-free survival in the Cox regression model. Patients with COPD were at higher risk of brain recurrence (OR: 7.88; 95% CI, 1.50–41.3, p < 0.01). In contrast, patients without COPD showed a tendency toward recurrence in bone and liver (OR: 4.13; 95% CI, 1.08–15.8, p = 0.05). Conclusion: Subjects with COPD and T2a disease had a higher risk of recurrence. The role of COPD as a recurrence promoter merits further prospective investigation.

Chronic cough and obstructive sleep apnoea in a sleep laboratory-based pulmonary practice

BackgroundObstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough.MethodsPatients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed.ResultsA total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010).ConclusionThe incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.

The safety and efficacy of alfentanil-based induction in bronchoscopy sedation: A randomized, double-blind, controlled trial

Background: Alfentanil in combination with propofol produces a synergistic sedative effect in patients undergoing flexible bronchoscopy (FB). However, the use of this combination is controversial due to the risk of cardiopulmonary depression. The aim of this study was to evaluate the proper induction regimen of alfentanil in propofol target-controlled infusion for FB sedation. Methods: One hundred seventy-three patients were assigned randomly into 5 regimens: Group 1 and 2, alfentanil 2.5 and 5 &mgr;g/kg, respectively, immediately before propofol administration; Group 3 and 4, alfentanil 2.5 and 5 &mgr;g/kg, respectively, 2 minutes before propofol administration; and Group 5, propofol administration alone to achieve the observer assessment of alertness and sedation scale 3∼2. The bronchoscopists, physicians in charge of sedation, and patients were blind to the regimens. Adverse events, drug dose, induction, procedure and recovery time, cough severity, and propofol injection related pain were recorded. Results: The patients in groups 2 and 4 required a lower dose of propofol (P = 0.031 and 0.019, respectively) and shorter time (P = 0.035 and 0.010) than group 5 for induction. Patients in group 2 experienced more hypoxemia than those in group 5 during induction (P = 0.031). The physician in charge of sedation scored a lower severity of cough in the patients in group 4 than in groups 3 and 5. There were no differences in terms of propofol injection related pain among the groups. Conclusion: Alfentanil 5 &mgr;g/kg given immediately before propofol infusion cannot be recommended. Further study is required to define conclusions about alfentanil 2.5 and 5 &mgr;g/kg because of the low power rating of subgroup in the present study.

Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation

AbstractAsthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD.To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ⩽70% and FEV1 less than 80% predicted after inhaled salbutamol (400 &mgr;g). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (&Dgr;IC%) after a 6 minute walk test (6MWT).Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to &Dgr;IC% (rs = 0.404, n = 31, P = 0.024).We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction.