Clinical application of endobronchial ultrasonography-guided transbronchial needle aspiration biopsy-a single center, large sample, real-world study.

BACKGROUND: Endobronchial ultrasonography-guided transbronchial needle aspiration biopsy (EBUS-TBNA) has been used for more than 10 years in China. Its clinical application and diagnostic value in different diseases with large sample was lack of report. METHODS: A retrospective analysis was performed about the application and diagnostic value of EBUS-TBNA in different disease of patients in Respiratory Intervention Center of Guangzhou Institute of Respiratory Health from January 2012 to July 2020. RESULTS: A total 5758 patients were included with 182 patients excluded for lack of information. Finally, data of 5576 patients (3798 males and 1778 females) were analyzed. For anesthetize, most patients were undergoing general anesthesia of intravenous with spontaneous breathing (69.4%), followed by general anesthesia of intravenous and inhalation with tracheal intubation and mechanical ventilation (17.9%) and conscious sedation and analgesia (12.8%). Lymph nodes were the main sites of biopsy obtained (76.4%). Tumors accounted for the highest proportion of disease (66.4%), followed by infection diseases (9.9%), sarcoidosis (3.9%), lymphoma (1.1%), and others (18.7%). The sensitivity of EBUS-TBNA for diagnosis of tumor was 89.7%, and 40.8% for infection diseases. There were significant differences in the puncture site and proportions of diseases between male and females (both p < 0.05). Higher diagnostic value was found in male patients (p < 0.05). CONCLUSION: EBUS-TBNA has good diagnostic value for different mediastinal and central pulmonary space-occupying lesions diseases, with highest sensitivity for tumors. Higher diagnostic value was found in male patients.

Long-term efficacy and safety of the Dumon stent for treatment of benign airway stenosis.

BACKGROUND: The long-term efficacy of the Dumon stent in the treatment of benign airway stenosis is unclear. OBJECTIVE: The objective of this study was to evaluate the long-term efficacy and safety of the Dumon stent in patients with benign airway stenosis. METHODS: We retrospectively reviewed patients with benign airway stenosis who were treated with a Dumon stent at the First Affiliated Hospital of Guangzhou Medical University between March 2014 and October 2021. We included patients with successful removal of silicone stents after implantation. The clinical data and information on bronchoscopic interventional procedures and related complications were collected and analyzed. RESULTS: Ninety-nine patients with benign airway stenosis were included. The stent was placed mainly in the trachea (44.4%) and left main bronchus (43.4%). The main type of stenosis was post-tuberculosis bronchial stenosis (57.6%). The overall cure rate was 60.6%. Stent-related complications included retention of secretions (70.7%), granuloma formation (67.7%), stent angulation (21.2%), and stent migration (12.1%). The stent was less effective for left main bronchus stenosis (p = 0.012). Multivariate logistic regression analysis identified that stent placement for more than 13 months, a stent-intervention number of ⩽ 1 predicted a favorable outcome. CONCLUSION: The efficacy and safety of the Dumon stent for benign airway stenosis need improvement. The stent is less effective for left main bronchus stenosis; regular follow-up is required in such cases. Stent placement for > 13 months and no more than once stent intervention within a 6-month period were associated with a favorable outcome.

Endobronchial optical coherence tomography or computed tomography for evaluating progression of bronchiectasis.

Background: The early radiological signs of progression in bronchiectasis remain unclear. The objective of the present study was to compare endobronchial optical coherence tomography (EB-OCT) and chest computed tomography (CT) for the evaluation of radiological progression of bronchiectasis via stratification of the presence (TW+) or absence (TW-) of thickened-walled bronchioles surrounding dilated bronchi in patients with bronchiectasis based on CT, and determine the risk factors. Methods: In this prospective cohort study, we performed both chest CT and EB-OCT at baseline and 5-year follow-up, to compare changes in airway calibre metrics. We evaluated bacterial microbiology, sputum matrix metalloproteinase-9 levels and free neutrophil elastase activity at baseline. We compared clinical characteristics and airway calibre metrics between the TW+ and TW- groups. We ascertained radiological progression at 5 years via CT and EB-OCT. Results: We recruited 75 patients between 2014 and 2017. At baseline, EB-OCT metrics (mean luminal diameter (p=0.017), inner airway area (p=0.005) and airway wall area (p=0.009) of seventh- to ninth-generation bronchioles) were significantly greater in the TW+ group than in the TW-group. Meanwhile, EB-OCT did not reveal bronchiole dilatation (compared with the same segment of normal bronchioles) surrounding nondilated bronchi on CT in the TW- group. At 5 years, 53.1% of patients in the TW+ group progressed to have bronchiectasis measured with EB-OCT, compared with only 3.3% in TW- group (p<0.05). 34 patients in the TW+ group demonstrated marked dilatation of medium-sized and small airways. Higher baseline neutrophil elastase activity and TW+ bronchioles on CT predicted progression of bronchiectasis. Conclusion: Thickened-walled bronchioles surrounding the dilated bronchi, identified with EB-OCT, indicates progression of bronchiectasis.

Airway morphological abnormalities of bronchiolitis assessed by endobronchial optical coherence tomography.

BACKGROUND: A few studies have reported the medium-sized and small airway morphological abnormalities of bronchiolitis. Whether spirometry or impulse oscillometry (IOS) is correlated with airway remodeling of bronchiolitis remains unclear. OBJECTIVES: Aiming to demonstrate the airway morphological abnormalities of bronchiolitis obliterans (BO) and diffuse panbronchiolitis (DPB) assessed by endobronchial optical coherence tomography (EB-OCT), and elucidate whether spirometric and IOS parameters have correlation with the airway remodeling of bronchiolitis. METHODS: We recruited 18 patients with bronchiolitis (BO, n = 9; DPB, n = 9) and 17 control subjects. Assessments of clinical features, St. George's respiratory questionnaire (SGRQ), chest computed tomography (CT), spirometry, IOS, and EB-OCT were performed in all enrolled subjects. The correlation between EB-OCT and lung function parameters was studied and analyzed. RESULTS: The magnitude of abnormalities of spirometric and IOS parameters was significantly greater in patients with bronchiolitis than that in control subjects (p < 0.05). Patients with BO had notably lower forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, maximal mid-expiratory flow (MMEF)% pred and higher resonant frequency (Fres), and area of reactance (AX) than those with DPB (p < 0.05). The EB-OCT measurement among patients with bronchiolitis and between the bronchus in the left and the right lung demonstrated a heterogeneous distribution of airway calibers, presenting a high intra- and inter-individual variability. Patients with bronchiolitis had notably greater airway wall area (p < 0.05) compared with control, while BO presented greater magnitude of airway abnormalities than DPB. Fres and the difference in airway resistance at 5 and 20 Hz (R5-R20) correlated negatively with medium-sized and small airway inner area, and correlated positively with airway wall area (p < 0.05), whose correlation coefficients were higher than those of spirometric parameters. CONCLUSION: Bronchiolitis, BO and DPB, manifested a heterogeneous distribution of airway calibers with significant intra- and inter-individual variability. IOS parameters, rather than spirometry, correlated better with medium-sized and small airway remodeling in bronchiolitis assessed by EB-OCT measurement.

Deep Learning-Based Segmentation of Airway Morphology from Endobronchial Optical Coherence Tomography.

BACKGROUND: Manual measurement of endobronchial optical coherence tomography (EB-OCT) images means a heavy workload in the clinical practice, which can also introduce bias if the subjective opinions of doctors are involved. OBJECTIVE: We aim to develop a convolutional neural network (CNN)-based EB-OCT image analysis algorithm to automatically identify and measure EB-OCT parameters of airway morphology. METHODS: The ResUNet, MultiResUNet, and Siamese network were used for analyzing airway inner area (Ai), airway wall area (Aw), airway wall area percentage (Aw%), and airway bifurcate segmentation obtained from EB-OCT imaging, respectively. The accuracy of the automatic segmentations was verified by comparing with manual measurements. RESULTS: Thirty-three patients who were diagnosed with asthma (n = 13), chronic obstructive pulmonary disease (COPD, n = 13), and normal airway (n = 7) were enrolled. EB-OCT was performed in RB9 segment (lateral basal segment of the right lower lobe), and a total of 17,820 OCT images were collected for CNN training, validation, and testing. After training, the Ai, Aw, and airway bifurcate were readily identified in both normal airway and airways of asthma and COPD. The ResUNet and the MultiResUNet resulted in a mean dice similarity coefficient of 0.97 and 0.95 for Ai and Aw segmentation. The accuracy Siamese network in identifying airway bifurcate was 96.6%. Bland-Altman analysis indicated there was a negligible bias between manual and CNN measurements for Ai (bias = -0.02 to 0.01, 95% CI = -0.12 to 0.14) and Aw% (bias = -0.06 to 0.12, 95% CI = -1.98 to 2.14). CONCLUSION: EB-OCT imaging in conjunction with ResUNet, MultiResUNet, and Siamese network could automatically measure normal and diseased airway structure with an accurate performance.

Hierarchical clock-scale hand-drawn mapping as a simple method for bronchoscopic navigation in peripheral pulmonary nodule.

BACKGROUND: A feasible and economical bronchoscopic navigation method in guiding peripheral pulmonary nodule biopsy is lacking. OBJECTIVE: To investigate the utility of hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. METHODS: We developed a hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation in peripheral pulmonary nodules. Patients with peripheral pulmonary nodules were recruited and assigned to two groups in this retrospective study, subjects in VBN group received conventional bronchoscopy in conjunction with virtual bronchoscopic navigation (VBN) and radial probe endobronchial ultrasound (RP-EBUS) for biopsy (VBN group), while HBN group underwent ultrathin bronchoscopy and RP-EBUS under the guidance of hand-drawn bronchoscopic navigation (HBN). The demographic characteristics, procedural time, operating cost and diagnostic yield were compared between these two groups. RESULTS: Forty-eight patients with peripheral pulmonary nodule were enrolled in HBN group, while 42 in VBN group. There were no significant differences between VBN and HBN groups in terms of age, gender, lesion size, location and radiographic type. The time of planning pathway (1.32 vs. 9.79 min, P < 0.001) and total operation (23.63 vs. 28.02 min, P = 0.002), as well as operating cost (758.31 ± 125.21 vs.1327.70 ± 116.25 USD, P < 0.001) were markedly less in HBN group, compared with those in VBN group. The pathological diagnostic efficiency of benign and malignant disease in HBN group appeared similar with those in VBN group, irrespective of the size of pulmonary lesion (larger or smaller than 20 mm). The total diagnostic yield of HBN had no marked difference from that of VBN (75.00% vs. 61.90%, P = 0.25). CONCLUSIONS: Hierarchical clock-scale hand-drawn mapping for bronchoscopic navigation could serve as a feasible and economical method for guiding peripheral pulmonary nodule biopsy, providing a comparable diagnostic yield in comparison with virtual bronchoscopic navigation.

A clinical and canine experimental study in small-airway response to bronchial thermoplasty: Role of the neuronal effect.

BACKGROUND: The effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear. METHODS: We recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs' lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT. RESULTS: Patients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)-positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment. CONCLUSIONS: BT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.

Feasibility and Safety of Radiofrequency Ablation Guided by Bronchoscopic Transparenchymal Nodule Access in Canines.

BACKGROUND: The treatment of pulmonary malignancies remains a challenge. The efficacy and safety of bronchoscopic radiofrequency ablation (RFA) for the treatment of lung cancer are not well elucidated. OBJECTIVE: This study aimed to evaluate the feasibility and safety of RFA guided by bronchoscopic transparenchymal nodule access (BTPNA) in vivo. METHODS: In an attempt to determine the parameters of RFA, we first performed RFA in conjunction with automatic saline microperfusion in the lung in vitro with various ablation energy (10, 15, 20, 25, and 30 W) and ablation times (3, 5, 8, and 10 min). The correlation between ablated area and RFA parameter was recorded and analyzed. Further, we conducted a canine study with RFA by BTPNA in vivo, observing the ablation effect and morphological changes in the lung assessed by chest CT and histopathologic examination at various follow-up time points (1 day, n = 3; 30 days, n = 4; 90 days, n = 4). The related complications were also observed and recorded. RESULTS: More ablation energy, but not ablation time, induced a greater range of ablation area in the lung. Ablation energy applied with 15 W for 3 min served as the appropriate setting for pulmonary lesions ≤1 cm. RFA guided by BTPNA was performed in 11 canines with 100% success rate. Inflammation, congestion, and coagulation necrosis were observed after ablation, which could be repaired within 7 days; subsequently, granulation and fibrotic scar tissue developed after 30 days. No procedure-related complication occurred during the operation or in the follow-up periods. CONCLUSION: The novel RFA system and catheter in conjunction with automatic saline microperfusion present a safe and feasible modality in pulmonary parenchyma. RFA guided by BTPNA appears to be well established with an acceptable tolerance; it might further provide therapeutic benefit in pulmonary malignancies.

Hybrid stenting with silicone Y stents and metallic stents in the management of severe malignant airway stenosis and fistulas.

BACKGROUND: Airway stenting is frequently used in the palliative treatment of patients with advanced tumor-induced airway stenosis and fistulas. However, there is paucity of studies regarding the use of airway stents in restoring patency. The aim of the study was to assess the efficacy and safety of hybrid silicon Y stents and covered self-expanding metal stents (SEMS) and in reestablishing patency in airway stenoses and fistulas. METHODS: This retrospective study included 31 patients between January 2016 to December 2019 with inoperable complex malignant airway stenoses and fistulas, managed with Silicone Y stents, and covered SEMS. The clinical details, clinical outcomes and complications up to 6 months were extracted from medical records. The improvement of performance was assessed based on modified British Medical Research Council (mMRC) dyspnea scores (t=6.892, P<0.001), Karnofsky Performance Scores (KPS) (t=-11.653, P<0.001), and performance status (PS) (t=3.503, P<0.001). RESULT: A total of 31 silicon Y stents and 35 covered SEMSs were inserted. Of the 31 patients (M:F 20:11; age: 54.64±9.57), 25/31 (80.6%) experienced immediate relief of symptoms following stent placement. Patients' mMRC dyspnea scores, KPS, and PS showed significant improvement following stenting. The mean duration of stent placement was 146.3±47.7 days, and 17/31 (55%) patients were alive at 6 months. No major complications related to hybrid stenting were observed during the follow-up period. CONCLUSIONS: Hybrid stenting is a feasible and safe palliative treatment for malignant airway stenosis and fistulas to improve quality of life and can be performed without major complications.

Self-expanding covered metallic stents as a transition to silicone stent implantation in management of severe post-tuberculosis bronchial stenosis.

BACKGROUND AND AIMS: Post-tuberculosis bronchial stenosis (PTBS) is one of the most common complications of tracheobronchial tuberculosis. Silicone stent serves as a major treatment for maintaining airway patency. However, silicone stent placement remains a large challenge in patients with severe cicatricial PTBS. Our objective was to evaluate the efficacy and safety of covered, self-expanding, metallic stents (SEMSs) as a transition to silicone stent implantation for treating severe PTBS. METHODS: We retrospectively reviewed the data of patients with severe PTBS who received airway stenting in the First Affiliated Hospital of Guangdong Medical University between September 2015 and May 2019. The types of the stent, intervention procedures, bronchoscopic findings, clinical outcomes and related complications were collected and analyzed. RESULTS: Fifty-eight cases with severe PTBS were included in this study. Thirteen (22.4%) of the patients received bronchial silicone stent implantation immediately after dilations. For the remaining 45 (77.6%) patients, silicone stents could not be deployed after dilations and SEMSs implantation was implemented as a bridge to silicone stenting. The SEMSs were placed for an interval of 28.4 ± 11.1 days. All of the silicone stents were inserted successfully following the removal of SEMSs. No SEMS-related complication occurred. The subgroup analysis showed that patients who received transitional SEMSs had less luminal caliber but fewer transbronchial dilations before silicone stent implantation (p < 0.05). CONCLUSION: Covered SEMS placement as a transition to silicone stenting could serve as a feasible procedure to reduce complications and improve the success rate of silicone stent implantation in patients with severe PTBS.The reviews of this paper are available via the supplemental material section.

Long-term efficacy and safety of the Dumon stent for benign tracheal stenosis: a meta-analysis.

BACKGROUND: The short-term efficacy of Dumon stent has been well demonstrated. Across years, however, due to insufficient sample size and absent of the randomized controlled trial, no reliable conclusion could be reach for Dumon stent's long-term efficacy. So, we conducted the first meta-analysis to evaluate the long-term efficacy and safety of the Dumon stent for benign tracheal stenosis. METHODS: Data on related trials were obtained by doing a literature search in PubMed, Web of Science and Cochrane Library. Random-effect and fixed-effect models were used to calculate the efficacy and incidence of complication of Dumon stent placement. RESULTS: A total of 395 patients from 8 studies were included in this study, revealing that the stability rate was 41.12% (95% CI, 34.85-48.52%) of Dumon stenting. Further, a curative rate of 40.74% (95% CI, 34.92-47.53%), and efficacy of 75.49% (95% CI, 70.89-80.39%) were obtained from this study. Analysis of the incidence of complications indicated 25.04% of migration (95% CI, 17.52-35.79%), 15.66% granulation (95% CI, 9.39-26.11%) and 23.82% of mucus retention 23.82% (95% CI, 13.77-41.20%). CONCLUSIONS: Dumon stent has a moderate efficacy for treating benign tracheal stenosis with approximately 20% incidence of complication, regular bronchoscopy follow-up should be conducted. Thus, further research is required to modified Dumon stenting.

Postintubation Tracheal Stenosis Evaluated by Endobronchial Optical Coherence Tomography: A Canine Model Study.

BACKGROUND: The predictors and airway morphological changes during the development of postintubation tracheal stenosis (PITS) have not been well elucidated. OBJECTIVES: To elucidate the validation of endobronchial optical coherence tomography (EB-OCT) in assessing the airway morphological changes in PITS. METHODS: We performed oral endotracheal intubation in 12 beagles to establish the PITS model. EB-OCT was performed respectively before modeling and on the 1st, 7th, and 12th day after extubation in 9 canines, and was conducted consecutively in 3 canines during the development of PITS. Histological findings and the thickness and gray-scale value of the tracheal wall assessed by EB-OCT measurements were analyzed and compared. RESULTS: The tracheal wall edema, granulation tissue proliferation, cartilage destruction in PITS, and airway wall thickening detected by EB-OCT were in concordance with the histopathological measurements. The consecutive EB-OCT observation of the airway structure demonstrated the tracheal wall thickness significantly increased from 344.41 ± 44.19 µm before modeling to 796.67 ± 49.75 µm on the 9th day after modeling (p < 0.05). The airway wall gray-scale values assessed by EB-OCT decreased from 111.19 ± 14.71 before modeling to 74.96 ± 4.08 on the 9th day after modeling (p < 0.05). The gray-scale value was negatively correlated with the airway wall thickness (r = -0.945, p = 0.001). CONCLUSION: The EB-OCT imaging, in concordance with the histopathological finding, was validated for assessing the airway morphological changes during the development of PITS. The EB-OCT evaluation of cartilage damage and gray-scale value measurement might help predict the development and prognosis of PITS.

Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with Tracheal Stenosis.

BACKGROUND: Hydrogen-oxygen mixture (H2-O2) may reduce airway resistance in patients with acute severe tracheal stenosis, yet data supporting the clinical use of H2-O2 are insufficient. OBJECTIVES: To evaluate the efficacy and safety of breathing H2-O2 in acute severe tracheal stenosis. METHODS: Thirty-five consecutive patients with severe acute tracheal stenosis were recruited in this prospective self-control study. Air, H2-O2 and O2 inhalation was given in 4 consecutive breathing steps: air for 15 min, H2-O2 (6 L per min, H2:O2 = 2: 1) for 15 min, oxygen (3 L per min) for 15 min, and H2-O2 for 120 min. The primary endpoint was inspiratory effort as assessed by diaphragm electromyography (EMGdi); the secondary endpoints were transdiaphragmatic pressure (Pdi), Borg score, vital signs, and impulse oscillometry (IOS). The concentration of H2 in the ambient environment was obtained with 12 monitors. Adverse reactions during the inhalation were recorded. RESULTS: The mean reduction in the EMGdi under H2-O2 was 10.53 ± 6.83%. The EMGdi significantly decreased during 2 H2-O2 inhalation steps (Steps 2 and 4) compared with air (Step 1) and O2 (Step 3) (52.95 ± 15.00 vs. 42.46 ± 13.90 vs. 53.20 ± 14.74 vs. 42.50 ± 14.12% for Steps 1 through 4, p < 0.05). The mean reduction in the Pdi under H2-O2 was 4.77 ± 3.51 cmH2O. Breathing H2-O2 significantly improved the Borg score and resistance parameters of IOS but not vital signs. No adverse reactions occurred. H2 was undetectable in the environment throughout the procedure. CONCLUSIONS: Breathing H2-O2 may reduce the inspiratory effort in patients with acute severe tracheal stenosis and can be used for this purpose safely.

Significances of spirometry and impulse oscillometry for detecting small airway disorders assessed with endobronchial optical coherence tomography in COPD.

BACKGROUND: Spirometry confers limited value for identifying small-airway disorders (SADs) in early-stage COPD, which can be detected with impulse oscillometry (IOS) and endobronchial optical coherence tomography (EB-OCT). Whether IOS is useful for reflecting small-airway morphological abnormalities in COPD remains unclear. OBJECTIVES: To compare the diagnostic value of spirometry and IOS for identifying SADs in heavy-smokers and COPD based on the objective assessment with EB-OCT. METHODS: We recruited 59 COPD patients (stage I, n=17; stage II, n=18; stage III-IV, n=24), 26 heavy-smokers and 21 never-smokers. Assessments of clinical characteristics, spirometry, IOS and EB-OCT were performed. Receiver operation characteristic curve was employed to demonstrate the diagnostic value of IOS and spirometric parameters. RESULTS: More advanced staging of COPD was associated with greater abnormality of IOS and spirometric parameters. Resonant frequency (Fres) and peripheral airway resistance (R5-R20) conferred greater diagnostic values than forced expiratory volume in one second (FEV1%) and maximal (mid-)expiratory flow (MMEF%) predicted in discriminating SADs in never-smokers from heavy-smokers (area under curve [AUC]: 0.771 and 0.753 vs 0.570 and 0.558, respectively), and heavy-smokers from patients with stage I COPD (AUC: 0.726 and 0.633 vs 0.548 and 0.567, respectively). The combination of IOS (Fres and R5-R20) and spirometric parameters (FEV1% and MMEF% predicted) contributed to a further increase in the diagnostic value for identifying SADs in early-stage COPD. Small airway wall area percentage (Aw% 7-9), an EB-OCT parameter, correlated significantly with Fres and R5-R20 in COPD and heavy-smokers, whereas EB-OCT parameters correlated with FEV1% and MMEF% in advanced, rather than early-stage, COPD. CONCLUSIONS: IOS parameters correlated with the degree of morphologic abnormalities of small airways assessed with EB-OCT in COPD and heavy-smokers. Fres and R5-R20 might be sensitive parameters that reliably reflect SADs in heavy-smokers and early-stage COPD.

Performance evaluation of detecting circulating tumor cells and tumor cells in bronchoalveolar lavage fluid in diagnosis of peripheral lung cancer.

BACKGROUND: To evaluate the diagnostic performances of detecting circulating tumor cells (CTCs) and tumor cells in bronchoalveolar lavage fluid (BALF) for peripheral lung cancer. METHODS: A total of 247 patients with lung cancer and 70 cases with benign lung disease were recruited in this study. Peripheral blood and BALF samples were collected, in which the tumor cells were enriched by negative immunomagnetic selection and detected by fluorescence in situ hybridization (FISH) of chromosome enumeration probe 8 (CEP8). The levels of tumor-associated markers (e.g., CEA, CA125, and NSE) in peripheral blood plasma were measured by using electrochemiluminescence. RESULTS: The numbers of CTCs detected in peripheral blood were significantly higher in patients with lung cancer than those with benign lung disease (5.78±0.57 vs. 1.13±0.39, Z=-8.64, P<0.01). Similarly, tumor cells count in BALF of malignancy were higher than that of benign lesions (6.76±0.89 vs. 0.89±0.23, Z=-6.254, P<0.01). However, as for patients with lung cancer and benign lung disease, the numbers of tumor cells in peripheral blood were comparable with those in BALF (both P>0.05). Detecting CTCs and tumor cells in BALF had similar areas under curves (AUC =0.871 and 0.963, respectively; P>0.05) in discriminating benign lesions from lung cancer (sensitivity 83.8% and 92.6%, specificity 86.5% and 99.9%, respectively), both of which were larger than those of NSE, CEA, and CA125 (AUC =0.564, 0.512 and 0.554, respectively; all P<0.05). The diagnostic performances of discriminating benign lesions and lung cancer in BALF and peripheral blood were both in concordance with that of histopathology (kappa values 0.662 and 0.569, respectively; both P<0.001). CONCLUSIONS: Detecting tumor cells in peripheral blood and BALF may sensitive to identify benign and malignant peripheral lung lesions and be of value for early diagnosis of lung cancer.

Serum KL-6 in pulmonary alveolar proteinosis: China compared historically with Germany and Japan.

BACKGROUND: KL-6 is a biomarker of the severity of pulmonary alveolar proteinosis (PAP). We noticed a significant difference in the mean serum KL-6 level between Japanese and Caucasian patients. To assess the clinical value of serum KL-6 in Chinese PAP patients, and to compare the differences in serum KL-6 levels in Chinese patients and patients of other ethnicities. METHODS: From 2014-2016, we prospectively examined 37 Chinese Han patients with PAP, measured their serum KL-6 levels, evaluated the correlation between initial KL-6 levels and clinical variables, and compared our results with studies from Japan and Germany (similar methods were used). We searched dbSNP for the MUC1 568 (rs4072037) genotype or allele frequency distributions in China, Japan, and Germany. RESULTS: Initial serum KL-6 levels were significantly correlated with baseline PaO2, A-aDO2, DLCO, FVC, and LDH levels (all P<0.001). Compared with Chinese PAP patients, the mean serum KL-6 level was significantly lower in German PAP patients (P<0.001) but not in Japanese PAP patients (P>0.4). In the rs4072037 allele frequency distributions, the frequency of the A/A genotype was significantly higher while that of the G/G genotype was significantly lower in Chinese and Japanese cohorts than in Caucasian cohorts (both P<0.001). CONCLUSIONS: Serum KL-6 can be used as a biological indicator for disease monitoring in Chinese patients. The difference in serum KL-6 level among Chinese, German, and Japanese PAP patients may be associated with the distribution of the rs4072037 genotype.