Cardiopulmonary exercise testing and pulmonary function testing for predicting the severity of CTEPH.

BACKGROUND: Cardiopulmonary exercise testing (CPET) and pulmonary function testing (PFT) are noninvasive methods to evaluate the respiratory and circulatory systems. This research aims to evaluate and monitor chronic thromboembolic pulmonary hypertension (CTEPH) noninvasively and effectively by these two methods. Moreover, the research assesses the predictive value of CPET and PFT parameters for severe CTEPH. METHODS: We used data from 86 patients with CTEPH (55 for test set, and 31 for validation set) at the Shanghai Pulmonary Hospital Affiliated to Tongji University. The clinical, PFT and CPET data of CTEPH patients of different severity classified according to pulmonary artery pressure (PAP) (mm Hg) were collected and compared. Logistic regression analysis was performed to appraise the predictive value of each PFT and CPET parameter for severe CTEPH. The performance of CPET parameters for predicting severe CTEPH was determined by receiver operating characteristic (ROC) curves and calibration curves. RESULTS: Data showed that minute ventilation at anaerobic threshold (VE @ AT) (L/min) and oxygen uptake at peak (VO2 @ peak) (mL/kg/min) were independent predictors for severe CTEPH classified according to PAP (mm Hg). Additionally, the efficacy of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) in identifying severe CTEPH was found to be moderate with the area under ROC curve (AUC) of 0.769 and 0.740, respectively. Furthermore, the combination of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) had a moderate utility value in identifying severe CTEPH with the AUC of 0.843. CONCLUSION: Our research suggests that CPET and PFT can noninvasively and effectively evaluate, monitor and predict the severity of CTEPH.

The screening role of a biomarker panel in BALF among patients with cancer-suspected pulmonary nodules less than 8 mm.

BACKGROUND: It is intractable to differentiate the malignancy from benignancy of cancer-suspected pulmonary nodules less than 8 mm. METHODS: The patients with small pulmonary nodules less than 8 mm which were suspected to be primary lung cancer underwent bronchoscopy and bronchoalveolar lavage. The level of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-ß) and hepatocyte growth factor (HGF) in bronchoalveolar lavage fluid (BALF) were assayed. Then, all patients underwent histopathological examination by means of surgical resection of nodules to determine their benignancy or malignancy. The nodules' benignancy and malignancy suggested by the biomarker panel consisted of VEGF, TGF-ß and HGF in BALF were validated by the histopathological results to determine their screening efficiency. RESULTS: Among 405 patients with pulmonary nodules less than 8 mm, 252 and 153 were predicted to be malignant and benignant, respectively, by using the biomarker panel in BALF. Finally, 180 (71.4%) of 252 and 114 (74.5%) of 153 were validated to be truly malignant and benignant, respectively, according to the histopathological results. In a receiver operating characteristic curve analysis of screening efficiency for pulmonary nodules less than 8 mm, the results demonstrated that the AUC [0.807 (0.658-0.882)] of the biomarker panel in BALF was higher compared with that [0.605 (0.433-0.738)] of the biomarker panel in blood (P = .001). CONCLUSIONS: For patients with cancer-suspected pulmonary nodules less 8 mm, a biomarker panel of VEGF, TGF-ß and HGF in BALF demonstrated more eligible screening efficiency for the preliminary differentiation of malignancy from benignancy, by contrast with their level in blood as well as PET/CT.

Coagulation factor IV is an indicator of symptomatic pulmonary embolism in patients with primary lung cancer.

BACKGROUND: Coagulation factor IV, also known as serum ionised calcium (SIC), participates in coagulative process and tends to elevate in patients with primary lung cancer. It may be an indicator of symptomatic pulmonary embolism (PE) due to primary lung cancer (LC). METHODS: A total of 388 patients who underwent CTPA and/or radionuclide ventilation perfusion scanning due to PE-suspected symptoms were stratified into LCPE (lung cancer and PE) group (n = 95), PE group (n = 99), LC group (n = 98) and control group (n = 96). At admission, the level of SIC and STC (serum total calcium) was compared among four groups. At discharge, the level change of SIC and STC from admission to discharge was compared among four groups. The coefficients analysis between SIC as well as STC and the possibility of PE were performed. RESULTS: The SIC of LCPE group was the highest among four groups at admission (P < 0.001). The level change of SIC from admission to discharge in LCPE group was the highest among four groups (P = 0.001). A ROC curve analysis demonstrated that the sensitivity and specificity of SIC for a diagnosis of PE among LC patients were 71.9% and 86.0%, respectively. The area under curve (AUC) was 0.781. Along with the increase of 0.1 mmol/L in SIC level, the risk ratio for a PE was 2.165 (1.537-2.849) (P < 0.001). CONCLUSIONS: Serum ionised calcium may be an indicator of pulmonary embolism in patients with primary lung cancer.

Comparison among different presentations of venous thromboembolism because of lung cancer.

INTRODUCTION: Venous thromboembolism (VTE) because of lung cancer has been sufficiently studied, nevertheless, little is known regarding the discrepancy of clinical characteristics and predictive factors among different presentations of VTE because of lung cancer. OBJECTIVES: This study was designed to investigate the distinction of clinical characteristics and predictive factors among different presentations of VTE because of lung cancer. METHODS: All patients concomitant lung cancer and VTE were stratified into three groups: pulmonary embolism (PE) group in which patients had sole PE, deep vein thrombosis (DVT) group with sole DVT and concomitance group with both PE and DVT. RESULTS: Concomitance of PE and DVT (28.2 days) mostly occurred at the early stage after the diagnosis of lung cancer, by contrast with DVT (63.6 days) which did at the latest stage, whereas PE (36.7 days) generally developed intermediately in between (P = .02). In a Kaplan-Meier analysis, the cumulative survival rate of DVT group was higher than that of concomitance group, whereas the rate of PE group lied in between. (P = .002) The strongest correlated factors with the development of DVT, PE and concomitance were adenocarcinoma (HR 3.27, P = .003), chemotherapy (HR 2.62, P = .005) and D-Dimer (HR 3.88, P < .001), respectively. The strongest correlated factors with the mortality of DVT, PE and concomitance were comorbidity (HR 2.32, P = .003), metastasis (HR 3.12, P < .001), and metastasis (HR 4.29, P < .001), respectively. CONCLUSION: Concomitance of DVT and PE represents the severest state of lung cancer, the earliest occurrence of VTE, and the worst survival rate, whereas DVT stands for the mildest condition of lung cancer and stablest pattern of VTE.

Characteristics of cardiopulmonary exercise testing of patients with borderline mean pulmonary artery pressure.

BACKGROUND: Pulmonary hypertension patients with mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg had impaired cardiopulmonary exercise testing (CPET). Borderline mean pulmonary pressures (boPAP; 21-24 mm Hg) represent early pulmonary vasculopathy. The CPET characteristics of boPAP are a matter of discussion. We aimed to determine the CPET profile of such borderline hemodynamics. METHODS: A matched case-control study was conducted on consecutive boPAP patients at the Shanghai Pulmonary Hospital between Jan 2012 and Jan 2017. Hemodynamics, echocardiography, the pulmonary function test (PFT) and CPET parameters were compared between boPAP patients and normal mPAP patients which were matched 1:1 by sex and age. Conditional logistic regression analysis was performed to determine the efficacy of CPET in detecting boPAP. RESULTS: A total of 48 patients underwent RHC and CPET (24 Normal, 24 boPAP). There were no differences in the demographics, echocardiography and PFT. BoPAP patients had significantly decreased VO2 at the anaerobic threshold and peak VO2 /kg (858.4 ± 246.5 mL/min vs 727.9 ± 228.0 mL/min, P = 0.037; 21.1 ± 6.4 mL/min/kg vs. 15.5 ± 5.6 mL/min/kg, P = 0.001, respectively). Significant differences were not observed in ventilation efficiency. A trend of impaired oxygen pulse and submaximal exercise tolerance were observed in boPAP patients. Conditional logistical regression analysis revealed the risk of boPAP increased by 2.493 (95% confident interval: 1.388 to 4.476, P = 0.002) with every 5 mL/min/kg decrease in peak VO2 /kg. CONCLUSIONS: Patients with boPAP have a greater prevalence of exercise intolerance, a trend of impaired oxygen pulse and submaximal exercise tolerance.

Impact of Pituitary-Gonadal Axis Hormones on Pulmonary Arterial Hypertension in Men.

The association of sex hormone (estradiol, testosterone, and progesterone) with cardiopulmonary disease has already attracted great attention, especially in pulmonary arterial hypertension (PAH). However, the impact of sex hormones and their pituitary stimulators (follicle-stimulating hormone and luteinizing hormone) on PAH in men remains unclear. We conducted a prospective cohort study recruiting 95 patients with idiopathic PAH from 2008 to 2014 and following up for a median of 65 months for death. Compared with control, abnormal plasma levels of sex hormones were more common in patients with PAH. Higher estradiol and estradiol/testosterone levels were associated with risk of PAH diagnosis (odds ratio per ln estradiol, 3.55; P<0.001; odds ratio per ln estradiol/testosterone, 4.30; P<0.001), whereas higher testosterone and progesterone were associated with a reduced risk (odds ratio per ln testosterone, 0.48; P=0.003; odds ratio per ln progesterone, 0.09; P<0.001). Fifty patients died during follow-up. Men with higher estradiol had increased mortality (hazard ratio per ln estradiol, 2.02; P=0.007), even after adjustment for baseline characteristics and PAH treatment. According to receiver operating characteristic analysis, patients with PAH with higher estradiol level (≥145.55 pmol/L) had worse 5-year survival rate compared with those with lower estradiol (38.6% versus 68.2%; log-rank test P=0.001). Therefore, our data show higher estradiol, estradiol/testosterone ratio, lower testosterone, and progesterone were associated with increased risk of PAH. Meanwhile, higher estradiol was independently associated with higher mortality in men with PAH. Further studies are needed to explain the origin of these hormonal derangements and their potential pathophysiological implications in PAH.

Clinical and hemodynamic characteristics of pulmonary hypertension associated with interstitial lung disease in China.

BACKGROUND: Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD). The aim of the present study was to investigate characteristics and prognosis of ILD associated PH in a predominantly Chinese patient cohort. METHODS: Consecutive patients with ILD associated PH, confirmed by right heart catheterization at shanghai pulmonary hospital were included in the study. Characteristics at baseline and during follow-up, as well as survival, were analyzed. RESULTS: This observational study was conducted in 26 patients with a mean age of 60.0 ± 12.2 y old. The 6-min walking distance was 335.0 ± 190.9 m. The mean pulmonary arterial pressure (PAP) was 42.9 ± 10.9 mmHg, cardiac output was 4.4 ± 1.0 L/min, and pulmonary vascular resistance (PVR) was 8.6 ± 4.1 Wood Units. The mean PAP was ≥35 mmHg in 69.2% of cases. There were no difference in lung function parameters between ILD with PH and ILD without PH. The overall survival rate was 92% at 1 y, 82% at 3 y, and 62% at 5 y. PVR was the only variable significantly associated with death. CONCLUSIONS: Severe hemodynamic impairment along with PH can occur in patients with ILD. These patients have more severely impaired exercise capacity and cardiac function than ILD patients without PH. PVR was the only prognostic factor identified in this group of patients.

The relationship between tumor markers and pulmonary embolism in lung cancer.

BACKGROUND: Tumor markers (TMs) and D-Dimer are both hallmarks of severity and prognosis of lung cancer. Tumor markers could be related to pulmonary embolism (PE) in lung cancer. RESULTS: The number of abnormal tumor markers of lung cancer patients with pulmonary embolism (3.9 ± 1.1vs1.6 ± 0.6,P 0.005) was more than that in patients without pulmonary embolism. TMs panel (P trend < 0.001), CEA (R2 0.735, P0.003) and CYFRA21-1 (R2 0.718, P0.005) were positively correlated with D-Dimer in patients with pulmonary embolism. The multivariate logistic regression analysis showed that, for tumor markers, TMs panel (OR5.98, P < 0.001) had the strongest correlation with pulmonary embolism. The AUC (area under curve) of TMs panel and CEA were 0.82 [95%CI (0.71-0.95), P < 0.001] and 0.71 [95%CI (0.62-0.84), P 0.002] by ROC (receiver operating characteristic) curve analysis, respectively. MATERIALS AND METHODS: Tumor markers were compared between lung cancer patients complicated with pulmonary embolism and those without pulmonary embolism Then the correlation between each tumor marker as well as panel of combined TMs and D-Dimer as well as pulmonary embolism were analyzed for patients with pulmonary embolism. CONCLUSIONS: There is a relationship between tumor markers and pulmonary embolism in patients with lung cancer. The panel of combined tumor markers is a valuable diagnostic marker for pulmonary embolism in lung cancer.

Exercise Training for Patients Pre- and Postsurgically Treated for Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis examined the effects of exercise training on length of hospital stay, postoperative complications, exercise capacity, 6-minute walking distance (6MWD), and health-related quality of life (HRQoL) in patients following resection of non-small cell lung cancer (NSCLC). METHODS: This review searched PubMed, EMBASE, and the Cochrane Collaboration data base up to August 16, 2015. It includes 15 studies comparing exercise endurance and quality of life before versus after exercise training in patients undergoing lung resection for NSCLC. RESULTS: This review identified 15 studies, 8 of which are randomized controlled trials including 350 patients. Preoperative exercise training shortened length of hospital stay; mean difference (MD): -4.98 days (95% CI = -6.22 to -3.74, P < .00001) and also decreased postoperative complications for which the odds ratio was 0.33 (95% CI = 0.15 to 0.74, P = .007). Four weeks of preoperative exercise training improved exercise capacity; 6MWD was increased to 39.95 m (95% CI = 5.31 to 74.6, P = .02) .While postoperative exercise training can also effectively improve exercise capacity, it required a longer training period; 6MWD was increased to 62.83 m (95% CI = 57.94 to 67.72) after 12 weeks of training ( P < .00001). For HRQoL, on the EORTC-QLQ-30, there were no differences in patients' global health after exercise, but dyspnea score was decreased -14.31 points (95% CI = -20.03 to -8.58, P < .00001). On the SF-36 score, physical health was better after exercise training (MD = 3 points, 95% CI = 0.81 to 5.2, P = .007) while there was no difference with regard to mental health. The I2 statistics of all statistically pooled data were lower than 30%. There was a low amount of heterogeneity among these studies. CONCLUSIONS: Evidence from this review suggests that preoperative exercise training may shorten length of hospital stay, decrease postoperative complications and increase 6MWD. Postoperative exercise training can also effectively improve both the 6MWD and quality of life in surgical patients with NSCLC, but requiring a longer training period.

Clinical characteristics of pulmonary hypertension in bronchiectasis.

Pulmonary hypertension (PH), as a complication of bronchiectasis, is associated with increased mortality. However, hemodynamic characteristics and the efficacy of pulmonary arterial hypertension (PAH) therapies in patients with bronchiectasis and PH remain unknown. Patients with bilateral bronchiectasis and concurrent PH were included in the study. Patient characteristics at baseline and during follow-up, as well as survival, were analyzed. This observational study was conducted in 36 patients with a mean age of 51.5 years (range, 17‒74 years). The 6 min walking distance was 300.8 ± 3.3 m. The mean pulmonary arterial pressure (PAP) was 41.5 ± 1.7 mmHg, cardiac output was 5.2 ± 1.4 L/min, and pulmonary vascular resistance was 561.5 ± 281.5 dyn∙s∙cm(-5). The mean PAP was > 35 mmHg in 75% of the cases. Mean PAP was inversely correlated with arterial oxygen saturation values (r =-0.45, P = 0.02). In 24 patients who received oral PAH therapy, systolic PAP was reduced from 82.4 ± 27.0 mmHg to 65.5 ± 20.9 mmHg (P = 0.025) on echocardiography after a median of 6 months of follow-up. The overall probability of survival was 97.1% at 1 year, 83.4% at 3 years, and 64.5% at 5 years. Given the results, we conclude that PH with severe hemodynamic impairment can occur in patients with bilateral bronchiectasis, and PAH therapy might improve hemodynamics in such patients. Prospective clinical trials focusing on this patient population are warranted.

Diagnose of occult bronchial foreign body: A rare case report of undetected Chinese medicine aspiration for 10 long years.

BACKGROUND: Occult bronchial foreign body can be very difficult to diagnose early in an adult patient without acute symptoms. This report describes a rare case of undetected Chinese medicine "Coptis chinensis" aspiration for 10 long years. METHODS: A case was reported that a female patient complained of a 10-year history of productive cough. A battery of tests were given to confirm the diagnosis. RESULTS: Chest computed tomography (CT) showed extensive bronchiectasis and multiple nodules, along with stenosis of left lower lobar bronchus. An extensive solid lesion with surrounding inflammatory granulation tissue was seen on her first bronchoscopy and biopsy revealed chronic mucosal inflammation. A neglected history of Coptis chinensis regularly kept in-mouth while sleeping for the last 10 years in this patient provided clues for a final diagnosis. Confirmatory diagnosis of bilateral tracheobronchial foreign bodies caused by recurrent inhalation of Coptis chinensis was made by a second bronchoscopy. CONCLUSIONS: This case clearly demonstrates that a precise medical history is often overlooked. A high index of suspicion, a precise medical history, radiographic features of chronic respiratory symptoms not explained by other conditions were keys to diagnosing this case.