Chang-Hao Zhong

Validation of human small airway measurements using endobronchial optical coherence tomography

BACKGROUND Small airway remodeling is the cardinal feature underlying chronic airway diseases. There is no modality which identifies small airway pathological changes, which is crucial for early diagnosis, efficacy and prognostic assessment. OBJECTIVE To evaluate the usefulness of endobronchial optical coherence tomography (EB-OCT) in assessing small airways morphology in vivo. METHODS Twelve patients with pulmonary nodules scheduled for lung resection underwent spirometry, multi-detector computed tomography (MDCT) and EB-OCT. We measured D(mean) (mean luminal diameter), Ai (inner luminal area), Aw (airway wall area) and Aw% [Aw/(Ai + Aw) × 100%] from the 3rd to 5th generation bronchi of RB9 segment by MDCT. D(mean), Ai, Aw and Aw% from the 3rd to 9th generation bronchi of RB9 segment were measured by EB-OCT and histology. Correlations of these parameters, measured by three different methods, were evaluated. We recruited 4 COPD patients to determine if EB-OCT could identify peripheral airway remodeling. RESULTS The 4 parameters, measured by CT and EB-OCT, correlated significantly [D(mean) (r = 0.991), Ai (r = 0.997), Aw (r = 0.997), Aw% (r = 0.991), all P < 0.01]. Significant correlation were found for these parameters, measured by histology and EB-OCT, from the 3rd to 5th generation bronchi [D(mean) (r = 0.989), Ai (r = 0.997), Aw (r = 0.999), Aw% (r = 0.988), all P < 0.01], and from the 6th to 9th generation bronchi [D(mean) (r = 0.979), Ai (r = 0.997), Aw (r = 0.994) and Aw% (r = 0.988), all P < 0.01]. Significant small airways morphological abnormalities were observed in COPD patients. CONCLUSIONS EB-OCT, a minimally invasive imaging modality with high-resolution, is useful and clinically practical for assessing proximal and distal airways of human compared with CT and histology.

A canine model of tracheal stenosis induced by cuffed endotracheal intubation

Postintubation tracheal stenosis is a complication of endotracheal intubation. The pathological mechanism and risk factors for endotracheal intubation-induced tracheal stenosis remain not fully understood. We aimed to establish an animal model and to investigate risk factors for postintubation tracheal stenosis. Beagles were intubated with 4 sized tubes (internal diameter 6.5 to 8.0 mm) and cuff pressures of 100 to 200 mmHg for 24 hr. The status of tracheal wall was evaluated by bronchoscopic and histological examinations. The model was successfully established by cuffed endotracheal intubation using an 8.0 mm tube and an intra-cuff pressure of 200 mmHg for 24 hr. When the intra-cuff pressures were kept constant, a larger sized tube would induce a larger tracheal wall pressure and more severe injury to the tracheal wall. The degree of tracheal stenosis ranged from 78% to 91% at 2 weeks postextubation. Histological examination demonstrated submucosal infiltration of inflammatory cells, hyperplasia of granulation tissue and collapse of tracheal cartilage. In summary, a novel animal model of tracheal stenosis was established by cuffed endotracheal intubation, whose histopathological feathers are similar to those of clinical cases of postintubation tracheal stenosis. Excessive cuff pressure and over-sized tube are the risk factors for postintubation tracheal stenosis.

Needle-based confocal laser endomicroscopy in the diagnosis of peripheral pulmonary nodule: a preliminary report

Lung cancer is one of the most fatal cancers in the world. To early distinguish benign and malignant pulmonary nodule is critical for disease prognosis. Confocal laser endomicroscopy (CLE) can be used to explore bronchus mucous membrane, alveolar elastic fiber structures and microvessels, and could be helpful for the diagnostic imaging and for the localization guidance. In this report, we presented two cases of peripheral pulmonary nodule. Under the guidance of X-ray and endobronchial ultrasound, needle-based confocal laser endomicroscopy (nCLE) could directly approach the peripheral pulmonary nodule via an exploratory puncture needle. The results indicated that the utility of the nCLE is helpful to precise positioning and characterize the peripheral pulmonary nodule. This report presents for the first time the application of nCLE for positioning the peripheral extraluminal nodule and describe the different confocal imaging features between adenocarcinoma and tuberculosis.

The efficacy and safety of airway foreign body removal by balloon catheter via flexible bronchoscope in children – A retrospective analysis

OBJECTIVES To investigate the efficacy and safety of the airway foreign body removal by balloon catheter via flexible bronchoscope in children. METHODS Retrospective analysis was performed of 26 cases of airway foreign body removal in children by balloon catheter via flexible bronchoscope in the First Affiliated Hospital of Guangzhou Medical University between December 2006 and December 2014. RESULTS There were 14 males and 12 females, aging between 1 and 12 years (median age: 25 months). The clinical course ranged from 0.5h to 60 days (median: 3 days). The foreign bodies consisted of peanuts (16 cases), soybeans (3 cases), pumpkin seeds (3 cases), porcine bone (1 case), olive nut (1 case), and a plant-based object (1 case). All foreign bodies were successfully removed. The operation duration ranged from 3 to 15 (5.3±2.9)min. No complication was observed such as hemorrhage, pneumothorax, or airway laceration. CONCLUSIONS Balloon catheter via flexible bronchoscope is a safe, effective, and easily performed method of removing airway non-sharp foreign bodies in children.

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.

Bronchiectasis after bronchial thermoplasty

Bronchial thermoplasty (BT) is used in the treatment of severe refractory asthma. It has been found to be beneficial to long-term improvements in the rate of asthma exacerbation, quality of life questionnaire answers (AQLQ), hospitalization, and emergency room visits. Atelectasis and lung abscess as direct complication of BT, but not bronchiectasis, have been reported previously. In this study, we report bronchiectasis after BT in what we believe may be the first case, combined with optical coherence tomography (OCT) and a 3-year follow-up of chest computed tomography (CT), to evaluate a patient with severe persistent asthma. We describe a 49-year-old Chinese male who complained of recurrent wheezing lasting over 5 years. His chest CT scan was normal before BT, but one month thereafter, he presented with mild central bronchiectasis on high-resolution CT, which persisted for more than 4 years. It remains unclear why this patient developed bronchiectasis so early post-BT treatment. This case highlights the need for short-term and long-term safety data on BT.

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.

Validation of human small-airway measurements using endobronchial optical coherence tomography: an observational study

Abstract Background Small-airway remodelling is the cardinal pathological feature underlying chronic obstructive pulmonary disease (COPD). Identification of early-stage pathological changes is crucial for the diagnosis, treatment, and prognosis of respiratory diseases. Our study aimed to investigate the usefulness of endobronchial optical coherence tomography (EB-OCT) in assessment of small-airways morphology in patients with pulmonary nodules who were scheduled for lung resection surgery (four had COPD, four were smokers with normal lung function, and four were life-long non-smokers). Patients with respiratory diseases other than COPD were excluded. Methods 12 patients with pulmonary nodules scheduled for lung resection underwent spirometry, multidetector CT (MDCT), and EB-OCT. We measured mean luminal diameter (D mean ), inner luminal area (Ai), airway wall area (Aw), and Aw% [Aw/(Ai+Aw)×100%] from the third to fifth generation bronchi of RB9 segment by MDCT. D mean , Ai, Aw, and Aw% from the third to nineth generation bronchi of RB9 segment were measured by EB-OCT and histology. The correlations of these four parameters, measured by MDCT, EB-OCT, and histology, were studied. The study protocol was approved by the ethics committee of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China, and written informed consent was obtained before the study. This study was registered with the Chinese Clinical Trial Register, number ChiCTR-DOD-14005734. Findings EB-OCT was well tolerated. The four parameters measured by CT correlated significantly with their respective parameters measured by EB-OCT (D mean r=0·991, Ai r=0·997, Aw r=0·997, Aw% r=0·991; all p mean r=0·989 [p mean r=0·979, Ai r=0·997, Aw r=0·994, Aw% r=0·988; all p Interpretation EB-OCT, a direct and minimally invasive imaging modality with high resolution, is useful for assessment of proximal and distal airways compared with CT (for larger airways) and histology. Funding None.