High Transcriptional Activity and Clinical Correlations in Eosinophils of Patients with Late-Onset Asthma.

Background: The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA. Methods: Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed. Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function. Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.

Overall Survival Improvement in Patients with Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer and Bone Metastasis Treated with Denosumab.

The impact of an initial skeletal-related event (SRE) and denosumab adjuvant treatment on the survival outcome of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with bone metastasis remains unclear. This retrospective study included 400 metastatic EGFR-mutated NSCLC patients. Among 190 bone metastasis patients, 61 had initial SREs and 73 received denosumab. We analyzed patient characteristics, SRE-free survival (SRE-FS), and overall survival (OS). In metastatic EGFR-mutated NSCLC, bone metastasis was associated with a poorer OS (21.7 vs. 33.0 months; p < 0.001). Bone metastasis patients with initial SREs at diagnosis had an even shorter OS, compared with those without initial SRE (15.4 vs. 23.6 months; p = 0.026). Denosumab reduced SRE incidence (hazard ratio (HR) 0.57 (95% confidence interval (CI) 0.34−0.94; p = 0.027) and was associated with improved OS (26.6 vs. 20.1 months; p = 0.015). A multivariate analysis demonstrated that denosumab treatment was correlated with a lower incidence of SRE (HR 0.61 (95% CI 0.37−0.98); p = 0.042) and better OS (HR 0.60 (95% CI 0.41−0.88); p = 0.008). In subgroup analyses, denosumab prolonged SRE-FS (HR 0.36 (95% CI 0.19−0.79); p = 0.009) in patients without initial SREs and was related to a better OS (25.3 vs. 12.9 months; p = 0.016) in patients with initial or pre-existing SREs. Osteonecrosis of the jaw was diagnosed in two patients (2.74%) receiving denosumab. Our study confirmed the association between initial SREs and a worse outcome and provided novel evidence of the survival benefit of denosumab for EGFR-mutated NSCLC patients with bone metastasis.

Interaction Between CD34+ Fibrocytes and Airway Smooth Muscle Promotes IL-8 Production and Akt/PRAS40/mTOR Signaling in Asthma.

Background: The circulating progenitor cells of fibroblasts (fibrocytes) have been shown to infiltrate the airway smooth muscle compartment of asthma patients; however, the pathological significance of this discovery has yet to be elucidated. This study established a co-culture model of airway smooth muscle cells (ASMCs) and fibrocytes from asthmatic or normal subjects to evaluate innate cytokine production, corticosteroid responses, and signaling in ASMCs. Methods: CD34+ fibrocytes were purified from peripheral blood of asthmatic (Global Initiative for Asthma treatment step 4-5) and normal subjects and cultured for 5∼7 days. In a transwell plate, ASMCs were co-cultured with fibrocytes at a ratio of 2:1, ASMCs were cultured alone (control condition), and fibrocytes were cultured alone for 48 h. Measurements were obtained of interleukin-8 (IL-8), IL-6, IL-17, thymic stromal lymphopoietin, and IL-33 levels in the supernatant and IL-33 levels in the cell lysate of the co-culture. Screening for intracellular signaling in the ASMCs after stimulation was performed using condition medium from the patients' co-culture (PtCM) or IL-8. mRNA and western blot analysis were used to analyze AKT/mTOR signaling in ASMCs stimulated via treatment with PtCM or IL-8. Results: Compared with ASMCs cultured alone, IL-8 levels in the supernatant and IL-33 levels in the ASMCs lysate were significantly higher in samples co-cultured from asthmatics, but not in those co-cultured from normal subjects. Corticosteroid-induced suppression of IL-8 production was less pronounced in ASMCs co-cultured with fibrocytes from asthma patients than in ASMCs co-cultured from normal subjects. ASMCs stimulated using PtCM and IL-8 presented elevating activated AKT substrate PRAS40. Treatment with IL-8 and PtCM increased mRNA expression of mTOR and P70S6 kinases in ASMCs. Treatment with IL-8 and PtCM also significantly increased phosphorylation of AKT and mTOR subtract S6 ribosomal protein in ASMCs. Conclusion: The interaction between ASMCs and fibrocytes from asthmatic patients was shown to increase IL-8 and IL-33 production and promote AKT/mTOR signaling in ASMCs. IL-8 production in the co-culture from asthmatic patients was less affected by corticosteroid than was that in the co-culture from normal subjects. Our results elucidate the novel role of fibrocytes and ASMCs in the pathogenesis of asthma.

Correction: S100A9+ MDSC and TAM-mediated EGFR-TKI resistance in lung adenocarcinoma: the role of RELB.

[This corrects the article DOI: 10.18632/oncotarget.24146.].

S100A9+ MDSC and TAM-mediated EGFR-TKI resistance in lung adenocarcinoma: the role of RELB.

BACKGROUND: Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. RESULTS: Blood monocytic S100A9+ MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS). S100A9+ MDSCs in PBMC were well correlated to tumor infiltrating CD68+ and S100A9+ cells, suggesting an origin of TAMs. Patient's MDMs, mostly from S100A9+ MDSC, similar to primary alveolar macrophages from patients, both expressed S100A9 and CD206, attenuated EGFR-TKI cytotoxicity. Microarray analysis identified up-regulation of the RELB signaling genes, confirmed by Western blotting and functionally by RELB knockdown. CONCLUSIONS: In conclusion, blood S100A9+ MDSC is a predictor of poor treatment response to EGFR-TKI, possibly via its derived TAMs through activation of the non-canonical NF-κB RELB pathway. METHODS: Patients with activating EGFR mutation lung adenocarcinoma receiving first line EGFR TKIs were prospectively enrolled. Peripheral blood mononuclear cells (PBMCs) were collected for MDSCs analysis and for monocyte-derived macrophages (MDMs) and stored tissue for TAM analysis by IHC. A transwell co-culture system of MDMs/macrophages and H827 cells was used to detect the effect of macrophages on H827 and microarray analysis to explore the underlying molecular mechanisms, functionally confirmed by RNA interference.

The efficacy of 40 mg versus dose de-escalation to less than 40 mg of afatinib (Giotrif) as the first-line therapy for patients with primary lung adenocarcinoma harboring favorable epidermal growth factor mutations.

The choice of a first-line therapy for lung cancer is a crucial decision that can impact the survival as well as the quality of life of a patient. Inhibitors of epidermal growth factor receptor (EGFR) such as afatinib, erlotinib, and gefitinib have previously been used to treat non-small cell lung cancer harboring favorable EGFR mutations. Although afatinib has greater efficacy than other EGFR inhibitors, adverse events related to its use can result in the discontinuation of the therapy. In this study, we compared the therapeutic efficacy in lung cancer patients of a regimen of 40 mg/day of afatinib with that of a lower dose regimen of <40 mg/day resulting either from a lower starting dose of 30 mg/day or dose adjustment. Seventy-nine patients were treated with 40 mg/day and 67 received de-escalated doses of <40 mg/day. There was no significant difference in the clinical characteristics of the two groups except that the proportion of patients with a body weight of 50 kg or more was greater in the 40 mg/day group. Otherwise, there were no significant differences between the two groups in the average time to treatment failure (TTF), the rates at which the administration of a second-line therapy was necessary, or the frequency and severity of adverse events. Overall, these results suggest that it is possible to calibrate the dosage of afatinib to suit individual patient parameters such as low body weight, and that such calibration can be advised based on the given patient's individual experience of the drug.

The Role of Pulmonary Veins in Cancer Progression from a Computed Tomography Viewpoint.

Background. We studied the role of pulmonary veins in cancer progression using computed tomography (CT) scans. Methods. We obtained data from 260 patients with pulmonary vein obstruction syndrome (PVOS). We used CT scans to investigate pulmonary lesions in relation to pulmonary veins. We divided the lesions into central and peripheral lesions by their anatomical location: in the lung parenchymal tissue or pulmonary vein; in the superior or inferior pulmonary vein; and by unilateral or bilateral presence in the lungs. Results. Of the 260 PVOS patients, 226 (87%) had central lesions, 231 (89%) had peripheral lesions, and 190 (75%) had mixed central and peripheral lesions. Among the 226 central lesions, 93% had lesions within the superior pulmonary vein, either bilaterally or unilaterally. Among the 231 peripheral lesions, 65% involved bilateral lungs, 70% involved lesions within the inferior pulmonary veins, and 23% had obvious metastatic extensions into the left atrium. All patients exhibited nodules within their pulmonary veins. The predeath status included respiratory failure (40%) and loss of consciousness (60%). Conclusion. CT scans play an important role in following tumor progression within pulmonary veins. Besides respiratory distress, PVOS cancer cells entering centrally can result in cardiac and cerebral events and loss of consciousness or can metastasize peripherally from the pulmonary veins to the lungs.

Continuous epidermal growth factor receptor-tyrosine kinase inhibitor administration in primary lung adenocarcinoma patients harboring favorable mutations with controlled target lung tumors dose not hinder survival benefit despite small new lesions.

BACKGROUND: In this study, we investigated the efficacy of continuous epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) administration in lung adenocarcinoma patients harboring favorable mutations regarding the progressive disease (PD) status with appearance of indolent new lesions. METHODS: From June 2010 to October 2012, 102 patients with lung adenocarcinoma, harboring favorable EGFR mutations and treated with EGFR-TKI were analyzed. Definite new lesions were detected during EGFR-TKI therapy, even though the primary target tumors were controlled. RESULTS: Of the 102 patients, 57 continued and 45 discontinued EGFR-TKI therapy. The median overall survival was 529 days for the discontinuation group and 791 days for the continuation group (p = 0.0197). Median survival time after the discontinuation of EGFR-TKI was 181 days and 115 days in the discontinuation and continuation groups, respectively (p = 0.1776), whereas median survival time after the appearance of indolent new lesions was 204 days and 262 days, respectively (p = 0.0237). CONCLUSION: Continuous EGFR-TKI administration in favorable EGFR-mutative lung adenocarcinoma patients with controlled primary tumors did not hinder the survival benefit, despite the appearance of new lesions.

Long-Term Effectiveness of Combined Treatment with Traditional Chinese Medicine and Western Medicine on the Prognosis of Patients with Lung Cancer.

OBJECTIVES: The study aim was to compare the long-term effect of Western medicine and combined treatment with Traditional Chinese Medicine (TCM) and Western medicine on the prognosis (survival rate, symptom distress, physical function, and quality of life) of patients with lung cancer. DESIGN: Longitudinal study. SETTING/LOCATION: Two medical centers, one each in Northern and Southern Taiwan. PATIENTS: Patients newly diagnosed with lung cancer and treated with Western medicine (n = 54) or TCM plus Western medicine (n = 30). OUTCOME MEASURES: Symptom distress, physical function, and quality of life were measured by using the Symptom Distress Scale, Eastern Cooperative Oncology Group-Performance Status Rating, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ-C30 and EORTC QLQ-LC13), respectively. Data on these measures were collected at baseline (before treatment) and 1, 3, 6, and 12 months after starting treatment. Survival was estimated by Kaplan-Meier curves. Group differences in outcomes were analyzed by generalized estimating equations. RESULTS: Treatment groups did not differ significantly at baseline for demographic information; disease severity; symptom distress; or EORTC QLQ-C30 and QLQ-LC13 scores, except for pain and dyspnea. After adjustment for these baseline effects, the combined-treatment group had better physical function and role function than the Western medicine group at 6 months (p < 0.05). The combined treatment group had better cumulative survival, but this difference did not reach significance. CONCLUSIONS: To more precisely estimate the long-term effectiveness of combined treatment on the prognosis of patients with lung cancer, future studies should standardize the number of TCM visits; increase the number of participants by continuous recruitment; and ask patients to complete daily logs with single-item measures of outcomes, such as symptom distress, quality of life, and physical function. Similar studies are suggested in patients with different cancers to develop a collaborative model using Western medicine and TCM.

The Impact of Sequence of Chemotherapy and EGFR-TKI Treatment on Different EGFR Mutation Lung Adenocarcinoma.

OBJECTIVES: Chemotherapy as first-/second-line treatment in different epidermal growth factor receptor (EGFR) mutation lung adenocarcinoma remains controversial. METHODS: Consecutive patients were collected between 2009 and 2012. Patients were divided into two groups (1st-line chemotherapy: n = 56 and 2nd-line chemotherapy: n = 55). Their outcomes profiles were analyzed. RESULTS: The overall survival (OS) of all patients (390 versus 662 days, p < 0.0001), as well as both progression-free survival (PFS, 151 versus 252 days, p = 0.0001) and OS (308 versus 704 days, p = 0.0001) of patients with L858R mutation (n = 63), who received 2nd-line chemotherapy, was significantly poor. By univariate and multivariate analysis, 2nd-line chemotherapy, and L858R mutation were significantly related to poor PFS and OS. CONCLUSION: In advanced lung adenocarcinoma, L858R mutation and 2nd-line chemotherapy caused a poor outcome. It is a consideration to choice of 1st-line chemotherapy in these subjects. A prospective design is warranted to confirm this finding.

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.

Tumor-associated macrophages in stage IIIA pN2 non-small cell lung cancer after neoadjuvant chemotherapy and surgery.

PURPOSE: Most of the patients with stage IIIA pN2 non-small cell lung cancer (NSCLC) develop recurrence after surgery. It is not clear whether post neoadjuvant chemotherapy tumor-associated macrophages is associated with recurrence. PATIENTS AND METHODS: Stage IIIA pN2 NSCLC patients underwent cisplatin/docetaxel neoadjuvant chemotherapy and surgery were retrospectively enrolled. Immunohistochemical staining of CD68 was used to identify macrophages in surgical resected stored tissues. RESULTS: The objective response rate of cisplatin/docetaxel was 68%, overall median disease-free survival (DFS) was 13.1 months and median overall survival (OS) 36.8. months. Multiple Cox regression analysis showed low total macrophage numbers and mediastinal lymph nodes downstaging were independent factors for longer DFS, whereas high islet/stromal macrophages ratio was an independent facto for OS. In patients downstaged to pN0, low total macrophage numbers was also associated with longer DFS. CONCLUSIONS: Low total macrophage number is an independent factor for better DFS in pN2 stage IIIA NSCLC patients receiving neoadjuvant chemotherapy and surgical resection, which association was kept in those downstaged to pN0. Further studies are warrant to confirm the predictive role of TAMs and their potential causative role in tumor recurrence.

Removal of endobronchial malignant mass by cryotherapy improved performance status to receive chemotherapy.

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

Effects of acupressure on fatigue of lung cancer patients undergoing chemotherapy: an experimental pilot study.

BACKGROUND: This study explored the effects of acupressure on fatigue of lung cancer patients undergoing chemotherapy. PATIENTS AND METHODS: For this experimental study, 57 subjects were randomly assigned to three groups: acupressure with essential oils (n=17), acupressure only (n=24), and sham acupressure (n=16). Acupoints were Hegu (LI4), Zusanli (ST36), and Sanyingjiao (SP6). All subjects received acupressure once every morning for 5 months, with each acupoint pressed for 1 min. Fatigue, functional status, anxiety, depression, and sleep quality were measured before initial chemotherapy (T0), on Day 1 of third chemotherapy (T1), and on Day 1 of sixth chemotherapy (T2). Outcome differences between groups were analyzed at T0, T1, and T2 by general estimating equations. RESULTS: After controlling for baseline outcome values, age, and adherence to acupressure, subjects who received acupressure with essential oils and acupressure had significantly less fatigue in daily living activities and sleep better quality at T1 than subjects who received sham acupressure. Subjects who received acupressure with essential oils had significantly better sleep quality at T2 than the sham acupressure group. Subjects who received acupressure with or without essential oils had greater odds of better functional status at T1 than the sham group. CONCLUSION: It is plausible that acupressure with or without essential oils helps lung cancer patients undergoing chemotherapy reduce cancer-related fatigue and increase activity level. Further study is wanted to test this hypothesis.

Elevated circulating levels of tissue factor-positive microvesicles are associated with distant metastasis in lung cancer.

PURPOSE: Microvesicles (MV) in the blood stream are associated with distant metastasis in cancer. Platelet or endothelial cell-related MV actively participate in thrombogenesis, which is an important step in cancer metastasis. This study investigated the correlations between MV levels of platelet-poor plasma and distant metastasis in lung cancer. METHODS: Platelet-poor plasma from 44 treatment-naive lung cancer (23 with distant metastasis) and 19 normal subjects was used to determine the levels of glycoprotein Iß (CD42) + platelet MV (PMV), P-selectin (CD62P) + PMV, VE-cadherin (CD144) + endothelial MV (EMV), tissue factor (CD142) + MV, thrombin-antithrombin complex and vascular endothelial growth factor (VEGF). RESULTS: The level of CD142 + MV was significant (odds ratio 5.86, 95 % confidence interval 1.31-38.3) in predicting distant metastasis in lung cancer, and a cutoff value of 2.668 (after logarithm transformation) in the ROC curve had a specificity of 90 % and a sensitivity of 59 %. The presence of distant metastasis showed a significant correlation between CD144 + EMV and VEGF, but not between CD144 + EMV and CD42 + PMV or CD62P + PMV in lung cancer subjects. CONCLUSIONS: The finding of CD142 + MV in platelet-poor plasma may be useful for suggesting distant metastasis in lung cancer. In addition to thrombogenesis, interaction between VE-cadherin and VEGF may be needed for successful metastasis in lung cancer.

Overall response to first-line tyrosine kinase inhibitor and second-line chemotherapy is predictive of survival outcome in epidermal growth factor receptor-mutated adenocarcinoma.

BACKGROUND: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for the treatment of lung adenocarcinoma with an EGFR-sensitizing mutation, but resistance is inevitable. Chemotherapy is widely used in the second-line setting. The outcome following this treatment scheme has not been thoroughly evaluated. METHODS: From 2007 to 2011, consecutive patients with mutated EGFR receiving first-line TKI and second-line chemotherapy were retrospectively reviewed. The overall response was categorized into double responder, single responder and double nonresponder. RESULTS: Following this treatment scheme, baseline Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (HR 0.60; 95% CI 0.37-0.98; p = 0.041) and double responder (HR 0.24; 95% CI 0.07-0.78; p = 0.018) were independent predictors of overall survival. Absence of pleural metastasis independently predicted the response to first-line TKI (OR 2.60; 95% CI 1.13-5.99; p = 0.025). In TKI responders, ECOG performance status 0-1 before chemotherapy (OR 4.95; 95% CI 1.15-21.28; p = 0.006), an exon 19 deletion (OR 4.74; 95% CI 1.30-17.21; p = 0.018) and progression-free survival (PFS) on first-line TKI (OR 1.02; 95% CI 1.01-1.09; p = 0.049) independently predicted the response to second-line chemotherapy. A moderate linear relationship (Pearson's r = 0.441; p = 0.001) existed between the PFS of this treatment scheme in TKI responders. CONCLUSION: The status of double responder to first-line TKI and second-line chemotherapy was predictive of improved survival in EGFR-mutated adenocarcinoma.

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

BACKGROUND: Obstructive 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. METHODS: Patients 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. RESULTS: A 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). CONCLUSION: The 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 potential regimen of target-controlled infusion of propofol in flexible bronchoscopy sedation: a randomized controlled trial.

OBJECTIVES: Target-controlled infusion (TCI) provides precise pharmacokinetic control of propofol concentration in the effect-site (Ce), eg. brain. This pilot study aims to evaluate the feasibility and optimal TCI regimen for flexible bronchoscopy (FB) sedation. METHODS: After alfentanil bolus, initial induction Ce of propofol was targeted at 2 µg/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 µg/ml, respectively) to maintain stable sedation levels and vital signs. Adverse events, frequency of adjustments, drug doses, and induction and recovery times were recorded. RESULTS: The study was closed early due to significantly severe hypoxemia events (oxyhemoglobin saturation <70%) in the group titrated at 0.5 µg/ml. Forty-nine, 49 and 46 patients were enrolled into the 3 respective groups before study closure. The proportion of patients with hypoxemia events differed significantly between groups (67.3 vs. 46.9 vs. 41.3%, p = 0.027). Hypotension events, induction and recovery time and propofol doses were not different. The Ce of induction differed significantly between groups (2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 µg/ml, p = 0.005) and the Ce of procedures was higher at 0.5 µg/ml titration (2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 µg/ml, p = 0.006). The adjustment frequency tended to be higher for titration at 0.1 µg/ml but was not statistically significant (2 (0∼6) vs. 3 (0∼6) vs. 3 (0∼11)). Subgroup analysis revealed 14% of all patients required no further adjustment during the whole sedation. Comparing patients requiring at least one adjustment with those who did not, they were observed to have a shorter induction time (87.6±34.9 vs. 226.9±147.9 sec, p<0.001), a smaller induction dose and Ce (32.5±4.1 vs. 56.8±22.7 mg, p<0.001; 1.76±0.17 vs. 2.28 ±0.41, p<0.001, respectively), and less hypoxemia and hypotension (15.8 vs.56.9%, p = 0.001; 0 vs. 24.1%, p = 0.008, respectively). CONCLUSION: Titration at 0.5 µg/ml is risky for FB sedation. A subgroup of patients required no more TCI adjustment with fewer complications. Further studies are warranted to determine the optimal regimen of TCI for FB sedation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01101477.

Role of flexible bronchoscopic cryotechnology in diagnosing endobronchial masses.

BACKGROUND: Endobronchial masses obstruct the central airway, and cryotechnology is reportedly a feasible means of managing such masses. However, few reports have explored the role of cryotechnology in diagnosing endobronchial masses. METHODS: All endobronchial masses were sampled for pathologic diagnosis by forceps biopsy and cryotechnology, performed during flexible bronchoscopy. The diagnostic accuracy of forceps biopsy and that of cryotherapy were compared by the χ(2) test, and the obtained specimen sizes were compared by the t test. RESULTS: Between 2007 and 2011, 75 patients with a median age of 64 years (interquartile range [IQR], 49-76; 48 men; 27 women; and 52 smokers [69.3%]) were diagnosed with endobronchial masses. The sites of these masses included the trachea (n = 17), left main bronchus (n = 16), right main bronchus (n = 11), right upper lobe bronchus (n = 11), right intermediate bronchus (n = 8), right lower lobe bronchus (n = 4), left upper lobe bronchus (n = 3), left lower lobe bronchus (n = 3), and right middle lobe bronchus (n = 2). Fifty-nine lesions were malignant, and 16 were benign. Lung squamous cell carcinoma (n = 23) was the leading cause of malignancy, and endobronchial tuberculosis (n = 9) was the most common benign disease. The diagnostic accuracy of cryotechnology was significantly higher than that of forceps biopsy (100% vs 69.3%, p < 0.0001). The specimen size obtained by cryotechnology was also significantly larger than that obtained by forceps biopsy (13.8 ± vs 1.9 ± 0.6 mm, p < 0.0001). CONCLUSIONS: The current study supports the view that cryotechnology is a good tool for diagnosing endobronchial masses. Cryotechnology also provides a better diagnostic specimen and has greater diagnostic accuracy than traditional forceps biopsy.

Endobronchial mucosa invasion predicts survival in patients with small cell lung cancer.

BACKGROUND: Current staging system for small cell lung cancer (SCLC) categorizes patients into limited- or extensive-stage disease groups according to anatomical localizations. Even so, a wide-range of survival times has been observed among patients in the same staging system. This study aimed to identify whether endobronchial mucosa invasion is an independent predictor for poor survival in patients with SCLC, and to compare the survival time between patients with and without endobronchial mucosa invasion. METHODS: We studied 432 consecutive patients with SCLC based on histological examination of biopsy specimens or on fine-needle aspiration cytology, and received computed tomography and bone scan for staging. All the enrolled patients were assessed for endobronchial mucosa invasion by bronchoscopic and histological examination. Survival days were compared between patients with or without endobronchial mucosa invasion and the predictors of decreased survival days were investigated. RESULTS: 84% (364/432) of SCLC patients had endobronchial mucosal invasion by cancer cells at initial diagnosis. Endobronchial mucosal involvement (Hazard ratio [HR], 2.01; 95% Confidence Interval [CI], 1.30-3.10), age (HR, 1.04; 95% CI, 1.03-1.06), and extensive stage (HR, 1.39; 95% CI, 1.06-1.84) were independent contributing factors for shorter survival time, while received chemotherapy (HR, 0.32; 95% CI, 0.25-0.42) was an independent contributing factor better outcome. The survival days of SCLC patients with endobronchial involvement were markedly decreased compared with patients without (median 145 vs. 290, p<0.0001). Among SCLC patients of either limited (median 180 vs. 460, p<0.0001) or extensive (median 125 vs. 207, p<0.0001) stages, the median survival duration for patients with endobronchial mucosal invasion was shorter than those with intact endobronchial mucosa, respectively. CONCLUSION: Endobronchial mucosal involvement is an independent prognostic factor for SCLC patients and associated with decreased survival days.