Sequential development of diffuse panbronchiolitis and myasthenia gravis after thymectomy for thymic neoplasm: a case report.

BACKGROUND: Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature. CASE PRESENTATION: A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections. CONCLUSIONS: To our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG.

A Clinical Breathomics Dataset.

This study entailed a comprehensive GC‒MS analysis conducted on 121 patient samples to generate a clinical breathomics dataset. Breath molecules, indicative of diverse conditions such as psychological and pathological states and the microbiome, were of particular interest due to their non-invasive nature. The highlighted noninvasive approach for detecting these breath molecules significantly enhances diagnostic and monitoring capacities. This dataset cataloged volatile organic compounds (VOCs) from the breath of individuals with asthma, bronchiectasis, and chronic obstructive pulmonary disease. Uniform and consistent sample collection protocols were strictly adhered to during the accumulation of this extensive dataset, ensuring its reliability. It encapsulates extensive human clinical breath molecule data pertinent to three specific diseases. This consequential clinical breathomics dataset is a crucial resource for researchers and clinicians in identifying and exploring important compounds within the patient's breath, thereby augmenting future diagnostic and therapeutic initiatives.

Treatment Response Evaluation by Computed Tomography Pulmonary Vasculature Analysis in Patients With Chronic Thromboembolic Pulmonary Hypertension.

OBJECTIVE: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters. MATERIALS AND METHODS: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD). RESULTS: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% (P < 0.001), 13.3% (P = 0.028), and 39.3% (P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio (P = 0.042). The BV5/TBV ratio was negatively correlated with PVR (r = -0.26; P = 0.035) and positively correlated with CI (r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP (r = -0.56; P = 0.001), PVR (r = -0.64; P < 0.001), and CI (r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV (P = 0.004) and positively associated with 6MWD (P = 0.013). CONCLUSION: Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters.

Pulmonary hypertension complicating unilateral absence of pulmonary artery and coronary-pulmonary artery fistula: Report of a case and review of the literature.

This is a case report of a 53-year-old woman who presented to our hospital in 2011 with an intermittent cough and dyspnea for 5 years. The chest X-ray showed a prominent left hilum and a smaller right lung. Computed tomography (CT) of the chest confirmed the absence of the right pulmonary artery (PA) and the right cardiac catheterization showed a mean PA pressure of 34 mmHg. Concomitant asthma and unilateral absence of pulmonary artery (UAPA) were diagnosed. In the following years, her functional class remained stable under medications including low-dose sildenafil and spironolactone. In 2020, she developed mild intermittent chest tightness and the coronary angiography showed a fistula between the proximal left circumflex coronary artery and right pulmonary circulation. She declined further intervention for her coronary-pulmonary artery fistula (CPAF) and her symptoms improved spontaneously. To our knowledge, only 16 similar cases with combined UAPA and CPAF in adults have been reported in the literature, of which, pulmonary hypertension was documented in nine patients (56.3%).

Comparing Clinical Outcomes of Tiotropium/Olodaterol, Umeclidinium/Vilanterol, and Indacaterol/Glycopyrronium Fixed-Dose Combination Therapy in Patients with Chronic Obstructive Pulmonary Disease in Taiwan: A Multicenter Cohort Study.

Background: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan. Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics. Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period. Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

Switching from omalizumab to mepolizumab therapy improved extra-pulmonary abdominal and cutaneous vasculitis symptoms in a patient with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis of small-to-medium-sized vessels. Both eosinophilic infiltration and vasculitis are thought to contribute to multi-organ damage. Some biologics have been used to reduce the required dose of corticosteroids in EGPA, but no single agent can ensure a complete control of this disease. Here, we describe a patient with anti-neutrophil cytoplasmic antibodies-negative relapsing EGPA whose asthma control was improved by omalizumab, but she continued to develop flares of abdominal and cutaneous vasculitis symptoms. After switching to mepolizumab therapy, her blood hypereosinophilia and extra-pulmonary symptoms were significantly improved. Moreover, the dose of daily maintenance corticosteroid could be tapered off. The experience from our case suggests that biologics targeting interleukin-5 may be more effective than omalizumab in the management of extra-thoracic manifestations in EGPA.

Treatment of electronic cigarette or vaping product use-associated lung injury (EVALI) by corticosteroid and low-dose pirfenidone: Report of a case.

Electronic (e)-cigarette or vaping product use-associated lung injury (EVALI) is a novel and potentially lethal disease first reported in the United States. We report the case of a 56-year-old man who presented to our hospital with dyspnoea and cough lasting for 2 months after using an e-cigarette for approximately 50 puffs over 2 weeks. Physical examination revealed crackles in the left lower lung. High-resolution computed tomography (HRCT) showed consolidation and ground-glass opacities in both lungs. The baseline forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were 65.7% and 63.9% of the predicted, respectively. Lung biopsy revealed organizing pneumonia with focal fibrosis. In addition to prednisolone, he was treated with a low-dose pirfenidone (200 mg three times per day) due to the persistence of a mild cough, exertional dyspnoea and basal crackles after discharge. His symptoms and FVC significantly improved, but the recovery of the DLCO was slow. The follow-up HRCT demonstrated only minimal fibrotic changes. To our knowledge, this was the first reported case of EVALI successfully treated with a combination of corticosteroid and antifibrotic agents.

End-Expiratory Lung Volumes During Spontaneous Breathing Trials in Tracheostomized Subjects on Prolonged Mechanical Ventilation.

BACKGROUND: The role of end-expiratory lung volume (EELV) during a spontaneous breathing trial (SBT) in patients who were tracheostomized and on prolonged mechanical ventilation is unclear. This study aimed to assess EELV during a 60-min SBT and its correlation with weaning success. METHODS: Enrolled subjects admitted to a weaning unit were measured for EELV and relevant parameters before and after the SBT. RESULTS: Of the 44 enrolled subjects, 29 (66%) were successfully liberated, defined as not needing mechanical ventilation for 5 d. The success group had fewer subjects with chronic kidney disease (41% vs 73%, P = .044), stronger mean ± SD maximum inspiratory pressure (41.6 ± 10.4 vs 34.1 ± 7.1 cm H2O; P = .02) and mean ± SD maximum expiratory pressure (46.9 ± 11.7 vs 35.3 ± 16.9 cm H2O; P = .01) versus the failure group. Toward the end of the SBT, the success group had a significant increase in the mean ± SD EELV (before vs after: 1,278 ± 744 vs 1,493 ± 867 mL; P = .040) and a decrease in the mean ± SD rapid shallow breathing index (83.8 ± 39.4 vs 66.3 ± 29.4; P = .02), whereas there were no significant changes in these 2 parameters in the failure group. The Cox regression analysis showed that, at the beginning of SBT, a greater difference between EELV with a PEEP of 0 cm H2O and with a PEEP of 5 cm H2O was significantly correlated to a higher likelihood of weaning success. Toward the end of the SBT, a greater EELV level at a PEEP of 0 cm H2O was also correlated with weaning success. Also, the greater difference of EELV at a PEEP of 0 cm H2O between the beginning and the end of the SBT was also correlated with a shorter duration to weaning success. CONCLUSIONS: The change in EELV during a 60-min SBT may be of prognostic value for liberation from prolonged mechanical ventilation in patients who had a tracheostomy. Our findings suggest a model to understand the underlying mechanism of failure of liberation from mechanical ventilation in these patients.

The Value of Heart Rhythm Complexity in Identifying High-Risk Pulmonary Hypertension Patients.

Pulmonary hypertension (PH) is a fatal disease-even with state-of-the-art medical treatment. Non-invasive clinical tools for risk stratification are still lacking. The aim of this study was to investigate the clinical utility of heart rhythm complexity in risk stratification for PH patients. We prospectively enrolled 54 PH patients, including 20 high-risk patients (group A; defined as WHO functional class IV or class III with severely compromised hemodynamics), and 34 low-risk patients (group B). Both linear and non-linear heart rate variability (HRV) variables, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE), were analyzed. In linear and non-linear HRV analysis, low frequency and high frequency ratio, DFAα1, MSE slope 5, scale 5, and area 6-20 were significantly lower in group A. Among all HRV variables, MSE scale 5 (AUC: 0.758) had the best predictive power to discriminate the two groups. In multivariable analysis, MSE scale 5 (p = 0.010) was the only significantly predictor of severe PH in all HRV variables. In conclusion, the patients with severe PH had worse heart rhythm complexity. MSE parameters, especially scale 5, can help to identify high-risk PH patients.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. METHODS: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. RESULTS: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia. CONCLUSION: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

Acute Exacerbation of a Chronic Obstructive Pulmonary Disease Prediction System Using Wearable Device Data, Machine Learning, and Deep Learning: Development and Cohort Study.

BACKGROUND: The World Health Organization has projected that by 2030, chronic obstructive pulmonary disease (COPD) will be the third-leading cause of mortality and the seventh-leading cause of morbidity worldwide. Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with an accelerated decline in lung function, diminished quality of life, and higher mortality. Accurate early detection of acute exacerbations will enable early management and reduce mortality. OBJECTIVE: The aim of this study was to develop a prediction system using lifestyle data, environmental factors, and patient symptoms for the early detection of AECOPD in the upcoming 7 days. METHODS: This prospective study was performed at National Taiwan University Hospital. Patients with COPD that did not have a pacemaker and were not pregnant were invited for enrollment. Data on lifestyle, temperature, humidity, and fine particulate matter were collected using wearable devices (Fitbit Versa), a home air quality-sensing device (EDIMAX Airbox), and a smartphone app. AECOPD episodes were evaluated via standardized questionnaires. With these input features, we evaluated the prediction performance of machine learning models, including random forest, decision trees, k-nearest neighbor, linear discriminant analysis, and adaptive boosting, and a deep neural network model. RESULTS: The continuous real-time monitoring of lifestyle and indoor environment factors was implemented by integrating home air quality-sensing devices, a smartphone app, and wearable devices. All data from 67 COPD patients were collected prospectively during a mean 4-month follow-up period, resulting in the detection of 25 AECOPD episodes. For 7-day AECOPD prediction, the proposed AECOPD predictive model achieved an accuracy of 92.1%, sensitivity of 94%, and specificity of 90.4%. Receiver operating characteristic curve analysis showed that the area under the curve of the model in predicting AECOPD was greater than 0.9. The most important variables in the model were daily steps walked, stairs climbed, and daily distance moved. CONCLUSIONS: Using wearable devices, home air quality-sensing devices, a smartphone app, and supervised prediction algorithms, we achieved excellent power to predict whether a patient would experience AECOPD within the upcoming 7 days. The AECOPD prediction system provided an effective way to collect lifestyle and environmental data, and yielded reliable predictions of future AECOPD events. Compared with previous studies, we have comprehensively improved the performance of the AECOPD prediction model by adding objective lifestyle and environmental data. This model could yield more accurate prediction results for COPD patients than using only questionnaire data.

Efficacy and safety of balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Data on the efficacy and safety of balloon pulmonary angioplasty (BPA) in Taiwanese patients with chronic thromboembolic pulmonary hypertension (CTEPH) are lacking. In this study, we evaluated the effects of BPA on clinical parameters including hemodynamics, echocardiography and functional status in patients with inoperable CTEPH in Taiwan. METHODS: We retrospectively collected the clinical data of inoperable CTEPH patients who underwent ≥3 BPA sessions. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-min walk distance and World Health Organization (WHO) functional class were collected and analyzed before and after BPA treatment. RESULTS: A total of 59 BPA sessions were performed in 13 inoperable CTEPH patients. No periprocedural deaths or major complications requiring tracheal intubation with mechanical ventilation occurred. WHO functional class significantly improved in all 13 patients (P < 0.001), and 6-min walk distance improved from 344 ± 147 to 450 ± 120 m (P = 0.014). Additionally, the plasma level of N-terminal pro-brain natriuretic peptide significantly decreased (P = 0.007). Hemodynamic data were available in 11 patients after ≥3 BPA sessions. Both mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased from 44.6 ± 11.7 mmHg to 32.6 ± 5.1 mmHg (P = 0.005) and 745 ± 389 dyn·s·cm-5 to 366 ± 120 dyn·s·cm-5 (P = 0.002), respectively. Cardiac output also increased from 3.69 ± 1.12 L/min to 4.33 ± 0.94 L/min (P = 0.021). CONCLUSION: BPA improved both clinical symptoms and hemodynamic data in inoperable CTEPH Taiwanese patients without major periprocedural complications.

Kinetics of oxygen uptake during unassisted breathing trials in prolonged mechanical ventilation: a prospective pilot study.

Few studies have investigated the measurement of oxygen uptake ([Formula: see text]O2) in tracheostomized patients undergoing unassisted breathing trials (UBTs) for liberation from mechanical ventilation (MV). Using an open-circuit, breath-to-breath method, we continuously measured [Formula: see text]O2 and relevant parameters during 120-min UBTs via a T-tube in 49 tracheostomized patients with prolonged MV, and calculated mean values in the first and last 5-min periods. Forty-one (84%) patients successfully completed the UBTs. The median [Formula: see text]O2 increased significantly (from 235.8 to 298.2 ml/min; P = 0.025) in the failure group, but there was no significant change in the success group (from 223.1 to 221.6 ml/min; P = 0.505). In multivariate logistic regression analysis, an increase in [Formula: see text]O2 > 17% from the beginning period (odds ratio [OR] 0.084; 95% confidence interval [CI] 0.012-0.600; P = 0.014) and a peak inspiratory pressure greater than - 30 cmH2O (OR 11.083; 95% CI 1.117-109.944; P = 0.04) were significantly associated with the success of 120-min UBT. A refined prediction model combining heart rate, energy expenditure, end-tidal CO2 and oxygen equivalent showed a modest increase in the area under the receiver operating characteristic curve of 0.788 (P = 0.578) and lower Akaike information criterion score of 41.83 compared to the traditional prediction model including heart rate and respiratory rate for achieving 48 h of unassisted breathing. Our findings show the potential of monitoring [Formula: see text]O2 in the final phase of weaning in tracheostomized patients with prolonged MV.

Pre-extubation functional residual capacity and risk of extubation failure among patients with hypoxemic respiratory failure.

Hypoxemic respiratory failure is usually accompanied with a certain extent of consolidation and alveolar derecruitment, which may still be present even after the patients have achieved the status of readiness to extubate. Functional residual capacity (FRC) is an indicator of lung aeration. This study aimed to evaluate whether pre-extubation FRC is associated with the risk of extubation failure in patients with hypoxemic respiratory failure. We prospectively included 92 patients intubated for hypoxemic respiratory failure. We used a technique based on a nitrogen multiple breath washout method to measure FRC before the planned extubation. The median FRC before extubation was 25 mL/kg (Interquartile range, 20-32 mL/Kg) per predicted body weight (pBW). After extubation, 20 patients (21.7%) were reintubated within 48 hours. The median FRC was higher in the extubation success group than in the extubation failure group (27 versus 21 mL/Kg, p < 0.001). Reduced FRC was associated with higher risk of extubation failure (odds ratio, 1.14 per each decreased of 1 mL/Kg of FRC/pBW, 95% CI, 1.05-1.23, p = 0.002). In conclusion, pre-extubation FRC is associated with the risk of extubation failure. Reduced FRC may be incorporated into the traditional risk factors to identify patients at high risk for extubation failure.

Riociguat Improves Pulmonary Hemodynamics in Patients with Inoperable Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Few studies have investigated the effects of riociguat on pulmonary hemodynamics in Asian patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this study, we evaluated the effects of riociguat on pulmonary hemodynamics in inoperable CTEPH patients. METHODS: We retrospectively collected the clinical data of 11 inoperable CTEPH patients. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-minute walk distance and World Health Organization (WHO) functional class were assessed at baseline and after riociguat treatment. RESULTS: The median duration of riociguat treatment was 12 months, and all 11 patients tolerated riociguat 7.5 mg/day well after titration. With regards to pulmonary hemodynamic data, both mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased from 41 ± 8 mmHg to 38 ± 9 mmHg (p = 0.045) and 787 ± 417 dyn·s·cm-5 to 478 ± 267 dyn·s·cm-5 (p = 0.007), respectively. With regards to clinical symptoms, WHO functional class significantly improved in nine of the 11 patients, and there was no change in the other two patients (p = 0.004). In addition, the median level of N-terminal pro-brain natriuretic peptide also significantly decreased from 281 (117-5943) pg/ml to 226 (48-1276) pg/ml (p = 0.021). CONCLUSIONS: Riociguat treatment improved both clinical symptoms and pulmonary hemodynamics in the inoperative CTEPH patients in this study.

Heart Rhythm Complexity Impairment in Patients with Pulmonary Hypertension.

Pulmonary hypertension is a fatal disease, however reliable prognostic tools are lacking. Heart rhythm complexity analysis is derived from non-linear heart rate variability (HRV) analysis and has shown excellent performance in predicting clinical outcomes in several cardiovascular diseases. However, heart rhythm complexity has not previously been studied in pulmonary hypertension patients. We prospectively analyzed 57 patients with pulmonary hypertension (31 with pulmonary arterial hypertension and 26 with chronic thromboembolic pulmonary hypertension) and compared them to 57 age- and sex-matched control subjects. Heart rhythm complexity including detrended fluctuation analysis (DFA) and multiscale entropy (MSE) and linear HRV parameters were analyzed. The patients with pulmonary hypertension had significantly lower mean RR, SDRR, pNN20, VLF, LF, LF/HF ratio, DFAα1, MSE slope 5, scale 5, area 1-5 and area 6-20 compared to the controls. Receiver operating characteristic curve analysis showed that heart rhythm complexity parameters were better than traditional HRV parameters to predict pulmonary hypertension. Among all parameters, scale 5 had the greatest power to differentiate the pulmonary hypertension patients from controls (AUC: 0.845, P < 0.001). Furthermore, adding heart rhythm complexity parameters significantly improved the discriminatory power of the traditional HRV parameters in both net reclassification improvement and integrated discrimination improvement models. In conclusion, the patients with pulmonary hypertension had worse heart rhythm complexity. MSE parameters, especially scale 5, had excellent single discriminatory power to predict whether or not patients had pulmonary hypertension.

2018 TSOC guideline focused update on diagnosis and treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension.

Plasma Calcitonin Gene-Related Peptide: A Potential Biomarker for Diagnosis and Therapeutic Responses in Pediatric Migraine.

Background: Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine. Methods: We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM), and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least 2 weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA. Results: In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, p = 0.001). The mean plasma CGRP level in migraineurs either during (291 ± 60 pg/ml) or between (240 ± 48) attacks was higher than in NM patients (51 ± 5 pg/ml, p = 0.006 and 0.018, respectively) and NH controls (53 ± 6 pg/ml, p = 0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364 ± 62 pg/ml, n = 47) than those not (183 ± 54 pg/ml, n = 21) (p = 0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437 ± 131 pg/ml, n = 14 vs. 67 ± 19 pg/ml, n = 6, p = 0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives. Conclusion: The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.

Age-Dependent Anti-migraine Effects of Valproic Acid and Topiramate in Rats.

Background: Valproic acid (VPA) and topiramate (TPM), initially developed as antiepileptics, are approved for migraine prophylaxis in adults but not children. The differences in their antimigraine mechanism(s) by age remain unclear. Methods: A migraine model induced by intra-cisternal (i.c.) capsaicin instillation in pediatric (4-5 weeks) and adult (8-9 weeks) rats was pretreated with VPA (30, 100 mg/kg) or TPM (10, 30, 100 mg/kg). Noxious meningeal stimulation by the irritant capsaicin triggered trigeminovascular system (TGVS) activation mimicking migraine condition, which were assessed peripherally by the depletion of calcitonin gene-related peptide (CGRP) in sensory nerve fibers of the dura mater, the increased CGRP immunoreactivity at trigeminal ganglia (TG) and centrally by the number of c-Fos-immunoreactive (c-Fos-ir) neurons in the trigeminocervical complex (TCC). Peripherally, CGRP released from dural sensory nerve terminals of TG triggered pain signal transmission in the primary afferent of trigeminal nerve, which in turn caused central sensitization of the TGVS due to TCC activation and hence contributed to migraine. Results: In the VPA-treated group, the central responsiveness expressed by reducing the number of c-Fos-ir neurons, which had been increased by i.c. capsaicin, was significant in pediatric, but not adult, rats. Inversely, VPA was effective in peripheral inhibition of elevated CGRP immunoreactivity in the TG and CGRP depletion in the dura mater of adult, but not pediatric, rats. In TPM group, the central responsiveness was significant in both adult and pediatric groups. Peripherally, TPM significantly inhibited capsaicin-induced CGRP expression of TG in adult, but not pediatric, rats. Interestingly, the capsaicin-induced depletion of CGRP in dura was significantly rescued by TPM at high doses in adults, but at low dose in pediatric group. Conclusion: These results suggest VPA exerted peripheral inhibition in adult, but central suppression in pediatric migraine-rats. In contrast, TPM involves both central and peripheral inhibition of migraine with an optimal therapeutic window in both ages. These findings may clarify the age-dependent anti-migraine mechanism of VPA and TPM, which may guide the development of new pediatric anti-migraine drugs in the future.

The impact of 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines on allocation and pharmacological management of patients with COPD in Taiwan: Taiwan Obstructive Lung Disease (TOLD) study.

BACKGROUND: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan. SUBJECTS AND METHODS: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines. RESULTS: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators. CONCLUSION: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients.