Shiyue Li

The Role of Cryptococcus in the Immune System of Pulmonary Cryptococcosis Patients

Objectives To investigate the role of Cryptococcus in the immune system of immunocompetent patients with pulmonary cryptococcosis (PC) by analysing the dynamic changes of patients’ immune status before and after antifungal therapy. Methods The level of the serum interferon-γ (IFN-γ) and interleukin (IL)-2, -4, -10 and -12 was measured before and after 6-months of treatment. Peripheral blood samples were obtained from 30 immunocompetent PC patients and 30 age- and gender-matched healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated and incubated with recombinant human IL-12 (rhIL-12) for 48 h. Then the concentrations of IFN-γ and IL-4 in the supernatant were analysed. Results Baseline serum IFN-γ level was significantly lower in the PC patients as compared with the control group (P < 0.001). The serum IL-2 and IFN-γ of PC patients were significantly increased after appropriate treatments (P < 0.05 and P < 0.001 when compared to their baseline levels). The productions of IFN-γ in the culture supernatant of PBMCs showed no significant difference between the control and PC patients both before and after antifungal treatments. RhIL-12 is a potent stimulus for IFN-γ production. Culture PBMCs collected from PC patients before treatments had a smaller increase of IFN-γ production in the present of rhIL-12 than the control (P < 0.01); PBMCs from PC patients completing 6-months of treatment showed a comparable increase of IFN-γ production by rhIL-12 stimulation to the control group. Conclusions In apparently immunocompetent patients with PC, a normalization of serum IFN-γ was achieved after recovery from infection. This suggests that Cryptococcus infection per se can suppress the immune system and its elimination contributes to the reestablishment of an immune equilibrium.

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.

Optical coherence tomography in imaging of peripheral pulmonary arteries

BACKGROUND To establish an optical coherence tomography (OCT)-based method for imaging peripheral pulmonary arteries. METHODS We recruited eight patients (five men; average age, 48±12 years; peripheral pulmonary artery thrombosis, three patients; idiopathic pulmonary hypertension, three patients; interstitial lung disease, two patients) who underwent OCT of the peripheral pulmonary arteries in the First Affiliated Hospital of Guangzhou Medical University and Guangzhou Institute of Respiratory Diseases, between September 2009 and September 2010. OCT was performed using both the conventional OCT imaging method (COI) and the improved pulmonary artery imaging method (IPI). In the IPI, contrast agent was used as an indicator of balloon inflation meanwhile increases in flushing speed of the replacement fluid. The percentage of optimal images, inflation pressure, flushing speeds and complications were compared between the two methods. RESULTS We performed OCT of 33 vessel segments by both methods. IPI produced more optimal images than COI (88% vs. 24%). Mean inflation pressure and flushing speed were higher during IPI than COI (0.62±0.15 vs. 0.43±0.08 atm; 1 atm =101.3 kPa; 0.82±0.10 vs. 0.42±0.06 mL/s; both P<0.01). Decreased blood oxygen saturation (SaO2) was associated with 9% and 30% segments (P<0.01) in the COI (mean decrease, 8.4%±3.6%) and IPI groups (mean decrease, 12.1%±5.3%; P<0.05) respectively. SaO2 recovered to pre-imaging levels after oxygen inhalation. CONCLUSIONS IPI is safe and effective for OCT of peripheral pulmonary arteries.

Incidence and Predictors of Tracheobronchial Tuberculosis in Pulmonary Tuberculosis: A Multicentre, Large-Scale and Prospective Study in Southern China

Background: Patients with pulmonary tuberculosis (PTB) have a high risk of concomitant tracheobronchial tuberculosis (TBTB), which commonly causes severe complications such as tracheobronchial stenosis. The prevalence and predictors of TBTB in China remain unclear due to the lack of prospective and large-scale studies. Objectives: To investigate the incidence of TBTB in PTB patients in southern China, and elucidate the predictors of TBTB and related tracheobronchial stenosis. Methods: We prospectively performed bronchoscopy in PTB patients to diagnose TBTB at four medical centres in southern China from September 2015 to August 2016. Clinical and epidemiological data were recorded and analysed to determine predictors of TBTB and related tracheobronchial stenosis. Results: A total of 345 (23.9%) of the 1,442 PTB patients undergoing bronchoscopy were diagnosed with TBTB. Female sex (OR 2.53), age < 50 years (OR 1.88), living in urban (OR 2.19), diabetes (OR 1.84), coughing (OR 2.61), and symptoms ≥4 weeks (OR 1.66) were predictors of PTB concomitant with TBTB. About 59.7% TBTB patients developed tracheobronchial stenosis, of which 23.3% cases presented severe airway narrowing. Female sex (OR 2.27), age < 50 years (OR 2.11), shortness of breath (OR 1.97), and symptoms ≥4 weeks (OR 1.71) were predictors of TBTB-related tracheobronchial stenosis. Conclusions: About 23.9% of PTB patients undergoing bronchoscopy present with TBTB in Guangdong province, southern China. Young and middle-aged females with symptoms persisting for ≥4 weeks (the main predictors of TBTB and related tracheobronchial stenosis) should receive bronchoscopy immediately when diagnosed with PTB.

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.

Effects of para-toluenesulfonamide intratumoral injection on pulmonary adenoid cystic carcinoma complicating with severe central airway obstruction: a 5-year follow-up study

Pulmonary adenoid cystic carcinoma (ACC) is a rare type of non-small cell lung carcinoma that may develop life-threatening severe malignant airway obstruction (SMAO). Currently, limited therapeutic approaches exist for ACC-SMAO. We investigated the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection for ACC-SMAO. In this phase III, multicenter, non-randomized, single-arm, open-label trial, we recruited eight hospitalized patients with ACC-SMAO between October 2009 and January 2011. Within the first year, patients received PTS injection for 2-3 sessions weekly, with 2 weeks as a single course. Pre- and post-treatment assessments, including vital sign assessment, dyspnea index, chest computed tomography (CT), were performed shortly before PTS injection and at day 30 post-treatment. We extended the observation to 5 years to determine overall survival. The primary endpoint was the CT-assessed airway objective response rate (ORR) at day 30. The key secondary endpoint was the overall survival (OS) at 5 years post-treatment. At baseline, mean airway tumor cross-sectional area was 153.3 mm2 (n=8), and the mean airway obstruction rate was 86.1%. The airway ORR reached 100% (33.3% complete remission and 66.7% partial remission). PTS treatment reduced the airway tumor size from 158.2 to 22.7 mm2 and the average airway obstruction rate decreased from 83.1% to 14.4% (n=6). The 5-year overall survival rate was 50.0%. Median survival duration was 4.98 years (range, 1.39-5.00 years). Four patients (50.0%) had stable disease. Compared with baseline dyspnea index, the transitional dyspnea index increased significantly at 30 days after treatment (mean difference: 5.40; 95% CI, 0.31-10.49; P<0.05). Adverse events were reported in 75% of patients (n=6), of whom 33.3% (n=2) and 66.7% (n=4) were rated as mild and moderate, respectively. No SAE was reported. In conclusion, PTS could rapidly debulk ACC-SMAO, resulting in considerable improvement of five-year survival rate.

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.

Pulmonary Capillary Hemangiomatosis without Pulmonary Hypertension: An Early Stage of Disease?

A 14‐year‐old male visited the First Affiliated Hospital of Guangzhou Medical University with a complaint of a 2‐year history of progressive exertional dyspnea and fingertips cyanosis. Physical examination revealed remarkable desaturation measured by pulse oximetry (80% at rest) and marked cyanosis of lips. The high‐resolution computed tomography scanning revealed no significant abnormality in the lung field [Figure 1a and 1b]. Computed tomography of pulmonary angiography showed no filling defect in trunk or branches of pulmonary arteries, no dilated central pulmonary arteries, and no cardiomegaly [Figure 1c and 1d]. Cardiac catheterization showed a mean right atrial pressure of 6 mmHg, pulmonary artery pressure with mean of 12 mmHg, pulmonary capillary wedge pressure of 9 mmHg, cardiac output of 6.2 L/min, and cardiac index of 4.10 L·min−1·m−2. Pulmonary vascular resistance was slightly elevated at 4.52 wood units. Lung biopsy revealed that lower lobe alveolar spaces were filled with red blood cells or hemosiderin cells, and alveolar septum was wider than normal. Hematoxylin and eosin staining shows that capillary proliferations within alveolar and bronchiolar walls were visible throughout most areas [Figure 2a‐2c]. Immunostaining of lung section was strongly positive for CD34 [Figure 2d], CD31 [Figure 2e], and F8 [Figure 2f]. The clinical manifestations, pathological findings, and immunohistochemistry supported definitive diagnosis of pulmonary capillary hemangiomatosis (PCH) with normal pulmonary artery blood pressure and normal radiological appearance. Because of financial difficulties, the patient abandoned heart–lung transplantation and left hospital without therapeutic intervention. Follow‐up to nearly a years, the patient was stable with no prominent hypoxia on 2 L/min supplemental nasal cannula oxygen at home. Written informed consent was obtained from the parents of patient for publication of this case report and any accompanying images. All patients with PCH usually have elevated pulmonary arterial pressures measured by right heart catheterization with normal or low pulmonary capillary wedge pressure and this have been demonstrated.[1] The infiltration of pulmonary vessel and intrapulmonary shunting caused by uncontrolled proliferation of the pulmonary capillaries might be responsible for the pulmonary hypertension and Pulmonary Capillary Hemangiomatosis without Pulmonary Hypertension: An Early Stage of Disease?