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.

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.

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.

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.

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.

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.

A Randomized, Placebo-Controlled Phase 2 Trial of CNTO 6785 in Chronic Obstructive Pulmonary Disease.

Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.

Factors responsible for poor sleep quality in patients with chronic obstructive pulmonary disease.

BACKGROUND: Sleep disturbance is a common complaint in patients with chronic obstructive lung disease (COPD). However, the factors resulting in sleep disturbance remain unclear. This retrospective, observational, multicenter study aimed to identify the factors associated with sleep disturbance in patients with COPD. METHODS: The study was a retrospective, observational, and multicenter research. Data including age, sex, body mass index, smoking status, COPD inhaler prescribed, clinical symptoms, pulmonary function tests, medical history of comorbidities, and questionnaires were collected. Parameters including demographics, symptoms, medication, severity, functional classification, and comorbidities were correlated with sleep quality scores. RESULTS: Among 377 patients with COPD, 200 (53 %) patients experienced poor sleep quality (Pittsburg Sleep Quality Index scores > 5). A significant difference in sleep quality, as measured by PSQI scores, was noted between groups based on the 2011 Global Initiatives for Chronic Obstructive Lung Disease (GOLD) classification system. The most common sleep disturbances included "getting up to use the bathroom" (70.3 %), "wake up at night or early morning" (40.3 %), and "cough and snore loudly at night" (15.9 %). The use of inhaled corticosteroids, the presence of wheezing, COPD Assessment Test (CAT) scores, and Modified Medical Research Council (mMRC) dyspnea scale scores positively correlated with poor sleep quality (odds ratio: 1.51, 1.66, 1.09, and 1.30, respectively). Upon multivariate analysis, the CAT score was an independent factor for poor sleep quality in these patients. With the exception of sleep problem items, based on the CAT questionnaire, phlegm was significantly higher in COPD patients with poor sleep quality. CONCLUSIONS: Poor sleep quality is common among patients with COPD and symptoms including wheeze, phlegm, and inhaled corticosteroid use may contribute to poor sleep quality. The CAT score is a good indicator of poor sleep quality in patients with COPD.

Acute Respiratory Distress Syndrome in Patients Discharged From a Tertiary Hospital in Taiwan: Long-Term Survival and Prognostic Factors.

BACKGROUND: Acute respiratory distress syndrome (ARDS) carries significant morbidity and mortality. No previous studies have investigated the long-term outcomes of ARDS patients in Taiwan. OBJECTIVE: This study aimed to investigate the survival of ARDS patients after discharge from the hospital in Taiwan. METHODS: Medical records from 150 ARDS patients discharged alive from the intensive care unit from January 2004 to June 2009 were reviewed. Survival of these patients was followed for 5 years, and prognostic factors were identified. RESULTS: Cumulative survival rates were 81.4% at 6 months, 79.0% at 1 year, 67.2% at 2 years, and 45.7% at 5 years. Independent prognostic factors influencing both 1- and 5-year survival rates were age, previous lung disease, and disposition after discharge. For 5-year survival, renal disease was also an independent risk factor. DISCUSSION: The mortality rate of ARDS survivors after intensive care unit discharge is still high in Taiwan. Three independent risk factors were found to affect the overall survival of these patients.

Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis.

INTRODUCTION: The effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model. RESULTS: Eight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, -0.28; 95% confidence interval (CI), -0.53 to -0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, -0.01; 95% CI, -0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27). CONCLUSIONS: The effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.

2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the Management of Pulmonary Arterial Hypertension.

UNLABELLED: Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan's domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. KEY WORDS: Pulmonary arterial hypertension; Taiwan guidelines.

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.

Different trigemino-vascular responsiveness between adolescent and adult rats in a migraine model.

BACKGROUND: Pediatric migraine displays different clinical features from adult migraine. Because the trigemino-vascular system (TGVS) plays a pivotal role in migraine pathophysiology, this study compared TGVS responses in a migraine model induced by intracisternal (i.c.) instillation of capsaicin in adolescent and adult rats. METHODS: TGVS responses measured included c-Fos-protein-expressing neurons in the trigeminal cervical complex (TCC), calcitonin gene-related peptide (CGRP) expression in the trigeminal ganglia (TG) and dura mater, and dural protein extravasation. The formulas for estimating total numbers of activated TCC neurons were established based on the c-Fos-positive neuronal numbers in three sample sections, +0.6, -1.2 and -9 mm and +0.6, -0.6 and -6 mm, from the obex in adult and adolescent rats, respectively. RESULTS: After capsaicin instillation, adolescent rats had comparable TCC neurons activated as adult rats, but less TGVS peripheral responsiveness than adults, including CGRP immunoreactivity in the TG, and protein extravasation and CGRP depletion (inversely reflected by CGRP immunoreactivity) in the dura mater. CONCLUSIONS: Age-dependent differences in TGVS responsiveness in the i.c. capsaicin-induced migraine model of rats are reminiscent of less severe migraine in pediatric patients. This finding may provide new insight into the pathophysiology of migraine and guide the development of new anti-migraine drugs for children.

Calcitonin gene-related peptide and size of the atrial septal defect in new-onset migraine after transcatheter closure: results of a preliminary study.

BACKGROUND: New-onset migraine headache attacks (MHAs) can occur after atrial septal device implantation in patients without previous migraine. Plasma calcitonin gene-related peptide (CGRP), which plays a crucial role in migraine pathophysiology, has shown to be released from specific cardiac tissues. METHODS AND RESULTS: We prospectively collected patients before and after closure and measured plasma CGRP levels using enzyme-linked immunosorbent assay. Forty atrial septal defect (ASD) patients who had no migraine previously were enrolled. Four (23.5%) of the 17 consecutive patients whose CGRP levels were checked before ASD closure had new-onset MHAs. The patients with MHAs had bigger ASD size (20 ± 0.9 vs 16 ± 1 mm, P = .009) and lower CGRP levels before closure (21.1 ± 3.9 vs 90.1 ± 27.1 pg/mL, P = .042) than those without. Among the 5 patients with blood samplings both during and between attacks, a paired comparison revealed a significantly increased level during attack (257.2 ± 45.5 vs 45.6 ± 25.5 pg/mL, P = .03). CONCLUSION: Bigger ASD size and lower plasma CGRP levels before closure can be a potential predictor of new-onset MHAs. Furthermore, a significant increase of CGRP levels during migraine attack implies that the occurrences of new-onset MHAs after ASD closure correlate with the release of CGRP. This suggests CGRP sensitization from a lower baseline may be involved in the occurrence of new-onset MHAs after ASD closure.

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.

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.

Quantitative determination of isoniazid in biological samples by cation-selective exhaustive injection-sweeping-micellar electrokinetic chromatography.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, infects approximately one third of the current world population. Isoniazid is one of the most frequently used first-line anti-TB drugs. In this study, we developed a sensitive cation-selective exhaustive injection-sweeping-micellar electrokinetic chromatography method (CSEI-Sweep-MEKC) for analyzing isoniazid in human plasma. Parameters including acetonitrile (ACN) percentage in the separation buffer; the injection time, and concentration of the high-conductivity buffer; sodium dodecyl sulfate (SDS) concentration; phosphate concentration in the sample matrix; and the sample injection time were all optimized to obtain the best analytical performance. The optimal background electrolyte comprised 50 mM phosphate buffer, 100 mM SDS, and 15% ACN. Non-micelle background electrolyte, containing 75 mM phosphate buffer and 15% ACN, was first injected into the capillary, followed by a short plug of 200 mM phosphate (high-conductivity buffer). Run-to-run repeatability (n=3) and intermediate precision (n=3) of peak area ratios were found to be lower than 8.7% and 11.4% RSD, respectively. The accuracy of the method was within 98.1-106.9%. The limit of detection of isoniazod in human plasma was 9 ng mL(-1). Compared with conventional MEKC, the enhancement factor of the CSEI-Sweep-MEKC method was 85 in plasma samples. The developed method was successfully used to determine isoniazid concentration in patient plasma. The results demonstrated that CSEI-Sweep-MEKC has the potential to analyze isoniazid in human plasma for therapeutic drug monitoring and clinical research.

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.