Long-term variability of impulse oscillometry and spirometry in stable COPD and asthma.

BACKGROUND: While optimizing spirometry is a challenge for lung function labs, long-term variability if any between IOS (impulse oscillometry) parameters and spirometry is not clearly known in stable COPD (chronic obstructive pulmonary disease) and chronic asthma. The forced oscillation technique is increasingly employed in routine lung function testing. Our aim in this study was to determine the variability in oscillometric parameters between clinic visits over weeks or months in two patient groups during a period of clinical stability. Moreover, the research assessed relationships between IOS parameters long-term variability and COPD severity. METHODS: We used data from 73 patients with stable COPD and 119 patients with stable asthma at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Patients were included if they had three or more clinic visits where spirometry and IOS were performed during a clinically stable period. Data recorded from the first three visits were used. The standard deviation (SDbv), the coefficient of variation (COV), intraclass correlation coefficient (ICC) and the coefficient of repeatability (COR) were calculated, Wilcoxon Mann-Whitney test was used for data that did not conform to normality of distributions, Kruskal Wallis test was used to compare with multiple groups, post hoc comparison was analyzed by Bonferroni, Spearman correlation coefficients for non-parametric data, the multiple regression analyses to determine the relationship between long-term variability and airflow obstruction. RESULTS: (1) The repeatability of IOS resistance parameters with ICC values > 0.8 was high in COPD and asthma. ICC values of IOS resistance parameters were higher than IOS reactance parameters; (2) the repeatability of spirometry parameters with ICC values < 0.8 was lower than IOS resistance parameters in different GOLD (the Global Initiative for Chronic Obstructive Lung Disease) stages, the higher the stage the worse the repeatability; (3) the severity of airflow obstruction was correlated with long-term variability of R5 (R at 5 Hz) (P < 0.05) in GOLD4, not with long-term variability of R20 (R at 20 Hz) (P > 0.05) and R5-R20 (P > 0.05). CONCLUSION: IOS resistance parameters have good long-term repeatability in asthma and COPD. Additionally, repeatability of spirometry parameters is lower than IOS resistance parameters in different GOLD stages.

Variation of PetCO2 during incremental exercise and severity of IPAH and CTEPH.

BACKGROUND AND OBJECTIVE: End-tidal PCO2 (PetCO2) patterns during exercise testing as well as ventilatory equivalents for CO2 have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO2 change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET). METHODS: 164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls. RESULTS: PetCO2 was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO2 did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO2 value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO2 in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO2 at peak. PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PeakVO2%pred correlated significantly with PetCO2 at rest (r = 0.477, P < 0.001), AT (r = 0.609, P < 0.001) and peak exercise (r = 0.576, P < 0.001) in IPAH. N-terminal natriuretic peptide type-B (NT-proBNP) also correlated markedly with PetCO2, with a correlation coefficient of - 0.326 to - 0.427 (all P < 0.001). Additionally, PetCO2 at rest, at AT and at peak correlated positively with peakVO2%pred and showed an inverse correlation with NT-proBNP in CTEPH patients (all P < 0.05). CONCLUSIONS: PetCO2 during exercise in IPAH and CTEPH patients was significantly different from normal subjects. Moreover, PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PetCO2 was progressively more abnormal with increasing disease severity according to peakVO2%pred and WHO-Fc.

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.

Survival in severe pulmonary hypertension due to chronic lung disease: influence of in-hospital platelet distribution width.

Platelet distribution width has been recognized as risk predictors of idiopathic pulmonary arterial hypertension. This study aims to investigate whether in-hospital platelet distribution width would be useful to predict all-cause death in patients with severe pulmonary hypertension due to chronic lung diseases (CLD-PH). Early in-hospital platelet distribution width was measured in 67 severe CLD-PH patients who were confirmed by right heart catheterization and followed up. Event-free survival was estimated using the Kaplan-Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the association between the platelet distribution width level and all-cause death. During median of 2.4 (2.5, 3.7) years of follow-up, 44 patients died. A significant association was noted between in-hospital platelet distribution width level and the adjusted risk of all-cause mortality (hazard ratio: 1.245; 95% confidence interval: 1.117-1.386, P < 0.001). Compared with those with platelet distribution width <16.1%, the hazard ratio for all-cause death increased by 5.278 (95% confidence interval: 2.711-10.276, P < 0.0001) among patients with platelet distribution width ≥16.1%. Higher levels of platelet distribution width were also associated with increased risk of all-cause death. In-hospital platelet distribution width was independently associated with all-cause death in patients with severe CLD-PH. This potentially could be used to estimate the severity of severe CLD-PH.

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.

Changed hemodynamics in acute vasoreactivity testing: prognostic predictors in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is similar to pulmonary arterial hypertension (PAH) in its pathogenesis. Changed hemodynamic parameters in acute vasoreactivity testing (AVT) have proved to be prognostic predictors of PAH. We wanted to determine whether these changed indices also impacted the prognosis of CTEPH. Data was retrieved for 86 CTEPH patients who underwent right heart catheterization (RHC) with AVT at Shanghai Pulmonary Hospital from 2009 to 2018 and following up for 20 ± 15 months for event. Cox proportional hazards models were performed to determine the predictors of independent event-free survival. Receiver operating characteristic curve was plotted to determine the cut-off value of independent parameters in CTEPH. Kaplan-Meier method and log-rank test were used to perform the Survival analyses. Forty seven patients had an event. Many hemodynamic indices improved after AVT. The event-free group had better mean right atrial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance (PVR) and oxygen saturation of mixed venous blood (SvO2) both at baseline and after AVT. The event-free group also showed higher cardiac output (CO) and cardiac index (CI) after AVT. Among the changed hemodynamic parameters during the AVT, ΔCO, ΔCO/baseline CO, ΔCI, ΔCI/baseline CI and ΔPVR/baseline PVR were significantly higher in the event-free group. Foremost, ΔPVR/baseline PVR, PVR after AVT and baseline SvO2 were independent predictors for event-free survival. Patients with SvO2 ≥ 61.65% at baseline or PVR < 8.09 WU after AVT or ΔPVR/baseline PVR ≥ 0.054 had significantly better survival. Hemodynamic indices both at baseline and after AVT as well as the changes in these indices reflected the severity of CTEPH. Baseline SvO2, PVR after AVT, and ΔPVR/baseline PVR could be used as independent predictors to estimate the outcomes of CTEPH patients.

Variable predictors of acute pulmonary embolism recurrence with duration of follow-up.

BACKGROUND: Acute pulmonary embolism (PE) is a critical disease and often leads to a high mortality and morbidity. Several studies have identified predictors of PE recurrence, but whether these predictors have prognostic value and how they vary during varied follow-up periods remain unclear. METHODS: We retrospectively assessed the occurrence of recurrent PE and the survival time of patients with a diagnosis of acute PE at Shanghai Pulmonary Hospital from May 2007 to May 2018. Potential predictors of recurrent PE were evaluated at different points (1, 3, 6, 12, 24, 60 and 120-month) during a long-term follow-up for each patient. Patients were stratified into two groups by gender to analyze the impact of sex in period-guided prognostic prediction. Receiver operating characteristic curve analysis, survival analysis and multivariate Cox proportional hazards analysis were implemented as statistical analysis methods. RESULTS: In total, 597 acute PE patients were included, of whom 62 reported a PE recurrence. Male patients tend to have a lower risk of PE recurrence than female patients during 3- to 60-month follow-up period but have a higher risk of PE recurrence than female patients during 120-month follow-up period. The independent predictors of recurrence-free survival varied among different follow-up periods: In all patients, diabetes was an independent predictor only within 30 days follow-up period and female was considered as an independent predictor during 3- to 120-month follow-up period. Among male patients, hyperlipidemia and Log D-dimer (cut-off value =3.436) was observed as a predictor of recurrent PE within 6-month and over 12-month follow-up respectively. However, there is no unified independent prognostic indicator for female patients identified. CONCLUSIONS: In the early stage of follow-up, male PE patients have better prognosis, but with the extension of follow-up, female PE patients have better prognosis. The independent predictors of recurrence-free survival vary in different follow-up periods in PE patients when stratified based on gender and associated medical conditions.

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.

Value of heart rate recovery in female patients with pulmonary arterial hypertension due to systemic lupus erythematosus.

OBJECTIVE: This study intended to explore the relation between heart rate recovery at 1 minutes (HRR1) during the recovery phase of cardiopulmonary exercise test (CPET) and exercise capacity in female systemic lupus erythematosus associated pulmonary arterial hypertension (SLE-PAH) patients. METHODS: Twenty-one female SLE-PAH patients underwent right heart catheterization (RHC), pulmonary function test (PFT) and CPET. Forty-two healthy subjects matched with SLE-PAH patients in age, sex and BMI were recruited as a control group. The correlations between HRR1 with clinical and CPET parameters were performed. RESULTS: Peak HR, ΔHR, HRR1, Peak HR-warm HR1min , Peak HR-warm HR2min and CR were significantly lower in SLE-PAH than in controls (P < .01). Increased incidence of CRI was seen in SLE-PAH. Except for the Peak PET O2 , which was higher in controls, all other CPET parameters were lower in SLE-PAH. SLE-PAH patients with HRR1 ≥ 16 had longer 6MWD, lower NT-proBNP, better percent of predicted gas transfer index or diffusing capacity for carbon monoxide (DLco% pred) as well as better CO and CI. Peak HR, ΔHR, HRR1, Peak HR-warm HR1min , Peak HR-warm HR2min , CR, Peak Load, Peak VO2 , Peak PET CO2 , OUEP and OUES were lower and duration of exercise was shorter in patients with HRR1 < 16. HRR1 had positive correlation with 6MWD, DLco% pred, CO, CI and some key CPET parameters. CONCLUSIONS: HRR1 is an easily obtained auxiliary parameter in SLE-PAH patients to reflect an altered autonomic tone. SLE-PAH patients with HRR1 < 16 have more severe hemodynamics, worse clinical findings and marked oxygen uptake inefficiency than those with HRR1 ≥ 16.

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.

A modified risk score in one-year survival rate assessment of group 1 pulmonary arterial hypertension.

BACKGROUND: Risk assessment of pulmonary arterial hypertension (PAH) contributes to its management. Unfortunately, the existing risk assessment approaches are defective for clinicians to practice in daily clinical settings to some extent. METHODS: We designed a modified Risk Assessment Score of PAH (mRASP) comprising four non-invasive variables which were World Health Organization functional class(WHO FC), 6-min walk distance (6MWD), N-terminal of the pro-hormone brain natriuretic peptide(NT-pro BNP), and right atrial area(RAA), then validated it in the prediction of one-year survival rate for patients with PAH by contrast with the REVEAL risk score. RESULTS: For the validation cohort(n = 216), the predicted one-year survival rate were 95-100%, 90-95%, and < 90% in the mRASP risk score strata of 0-2, 3-5, and 6-8, respectively; meanwhile, the observed one-year survival rates were 97.1, 92.6, and 52.2%, in each corresponding stratum, respectively. The mRASP (c-index = 0.727) demonstrated similar predictive power in contrast with the REVEAL risk assessment score (c-index = 0.715) in the prediction of one-year survival rate. CONCLUSION: The mRASP is an eligible risk assessment tool for the prognostic assessment of PAH. In contrast with the REVEAL score, it demonstrated similar predictive power and accuracy, with extra simplicity and convenience.

The influence of anemia on one-year exacerbation rate of patients with COPD-PH.

BACKGROUND: Anemia is prevalent not only in COPD but also in pulmonary hypertension. We postulated that anemia may have certain prognostic value in COPD concomitant with PH due to COPD (COPD-PH). METHODS: We performed a 12-month prospective investigation to follow up COPD patients with or without PH assessed by right heart catheterization. Eligible patients were enrolled, stratified into COPD-PH-anemia group (n = 40), COPD-PH group (n = 42), COPD-anemia group (n = 48), and COPD group(n = 50), and then followed up for 12 months. RESULTS: After the follow-up, for both of the actual variation value and variation rate, the increase of NT-pro BNP (P<0.001; P = 0.03) and CAT score (P = 0.001; 0.002), as well as the decrease of PaO2 (P = 0.03; 0.086) and Peak VO2 (P = 0.021; 0.009) in COPD-PH-anemia group were highest among four groups. The cumulative one-year survival rates were similar among four groups (P = 0.434). The cumulative exacerbation-free rate was lowest in COPD-PH-anemia group among four groups (P<0.001). Hemoglobin was an independent promoting factor for the probability of hospitalization due to exacerbation ≧ 1/year in patients with COPD-PH-anemia [HR 3.121(2.325-5.981); P<0.001]. CONCLUSIONS: Anemia is a promoting factor for the worsening of exercise capacity, deterioration of hypoxemia, declining of life quality, and aggravation of exacerbations in patients with COPD-PH-anemia, by contrast with COPD-PH, COPD-anemia, and COPD.

Transition from Ambrisentan to Bosentan in Pulmonary Arterial Hypertension: A Single-Center Prospective Study.

Background and objective: Two endothelin receptor antagonists (ETRAs), bosentan and ambrisentan, are approved for patients with pulmonary arterial hypertension (PAH). However, there is little information about the transition strategy between these two ETRAs. We aimed to evaluate the safety and efficacy from ambrisentan to bosentan. Methods: Twenty PAH patients were enrolled into the single-center, open-labelled prospective study. Echocardiogram, WHO functional class (WHO-FC), 6-minute walking distance (6MWD), right heart catheterization, and hemotology were collected. After receiving oral 5 mg ambrisentan daily initially for one year, the patients were divided into two arms: eight patients switched to bosentan, while the remaining 12 patients continued ambrisentan. Characteristics at baseline, 1-and 2-year follow-up points were compared. RESULTS: There were no significant differences in echocardiogram, WHO-FC, hemodynamics, demographics and liver function at baseline, 1-and 2-year points in both arms. 6MWD in bosentan group was significantly shorter at baseline. But there were no significant differences of 6MWD at 1- and 2-year points. CONCLUSIONS: It is safe for stable PAH patients to transition from ambrisentan to bosentan without hemodynamic or hematologic deterioration.

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.

Characteristics of exercise capacity in female systemic lupus erythematosus associated pulmonary arterial hypertension patients.

BACKGROUND: To study the oxygen uptake efficiency and determine usefulness of submaximal parameters of oxygen uptake in systemic lupus erythematosus associated pulmonary arterial hypertension (SLE PAH) on performing a cardiopulmonary exercise test (CPET). METHODS: CPET was performed in 21 SLE PAH patients, equal number of idiopathic pulmonary arterial hypertension (IPAH) patients and controls. Peak VO2, anaerobic threshold (AT), oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) and other CPET parameters were examined. All subjects had pulmonary function test (PFT) at rest, which included FEV1, FVC, FEV1/FVC, DLCO measurements. Right heart catheterization (RHC) was also done in SLE PAH and IPAH patients. CPET parameters were compared with RHC parameters to determine potential correlations. RESULTS: Peak VO2, PETCO2 and peak O2 pulse were lower in SLE PAH than IPAH and controls with OUE being lower during all stages of exercise in SLE PAH. DLCO and FVC values were significantly lower in SLE PAH (p < 0.05). Peak O2 pulse and VO2@AT in SLE PAH and IPAH was low (p < 0.05) and significant difference between SLE PAH and IPAH was seen (p < 0.05). PVR correlated with the lowest VE/VCO2, O2 pulse, peak PETCO2 and OUE in SLE PAH patients (all p < 0.05). CONCLUSIONS: SLE PAH patients have cardiopulmonary exercise limitation with reduced oxygen uptake efficiency. VO2@ at AT, peak O2 pulse and O2 pulse at AT were significantly reduced (p < 0.05). Key CPET parameters correlated with elevated pulmonary vascular resistance (PVR). Submaximal parameters of oxygen uptake are equally useful in SLE PAH.

Sex-specific cardiopulmonary exercise testing indices to estimate the severity of inoperable chronic thromboembolic pulmonary hypertension.

Background: Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH) have been revealed in few studies. Although right heart catheterization (RHC) is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH), cardiopulmonary exercise testing (CPET) has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the "sex-specific" CPET indices could estimate the severity of inoperable CTEPH. Methods: Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years) and 40 female (age, mean ± SD =56.3±11.8 years) patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan-Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors. Results: Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE), and end-tidal partial pressure of O2 (PETO2) at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir VE/CO2 were significantly higher in male patients than in female patients (P<0.05). Only oxygen uptake efficiency plateau (OUEP) showed a significantly higher difference in female than male patients (P<0.05). In addition, several CPET indices correlated with hemodynamic parameters, especially pulmonary vascular resistance (PVR), which was distinctly different between the sexes. Nadir VE/CO2 was an independent predictor of PVR in male patients with CTEPH, whereas OUEP was an independent predictor of PVR in female patients with CTEPH. Conclusion: Even after confounding for age and body mass index, different CPET measurements of gas exchange efficiency correlated with PVR differently between male and female patients. This potentially could be used to estimate the severity of CTEPH.

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.