Hyperoxemia and hypoxemia impair cellular oxygenation: a study in healthy volunteers.

INTRODUCTION: Administration of oxygen therapy is common, yet there is a lack of knowledge on its ability to prevent cellular hypoxia as well as on its potential toxicity. Consequently, the optimal oxygenation targets in clinical practice remain unresolved. The novel PpIX technique measures the mitochondrial oxygen tension in the skin (mitoPO2) which allows for non-invasive investigation on the effect of hypoxemia and hyperoxemia on cellular oxygen availability. RESULTS: During hypoxemia, SpO2 was 80 (77-83)% and PaO2 45(38-50) mmHg for 15 min. MitoPO2 decreased from 42(35-51) at baseline to 6(4.3-9)mmHg (p < 0.001), despite 16(12-16)% increase in cardiac output which maintained global oxygen delivery (DO2). During hyperoxic breathing, an FiO2 of 40% decreased mitoPO2 to 20 (9-27) mmHg. Cardiac output was unaltered during hyperoxia, but perfused De Backer density was reduced by one-third (p < 0.01). A PaO2 < 100 mmHg and > 200 mmHg were both associated with a reduction in mitoPO2. CONCLUSIONS: Hypoxemia decreases mitoPO2 profoundly, despite complete compensation of global oxygen delivery. In addition, hyperoxemia also decreases mitoPO2, accompanied by a reduction in microcirculatory perfusion. These results suggest that mitoPO2 can be used to titrate oxygen support.

Echocardiography and pulmonary hypertension in patients with chronic obstructive pulmonary disease undergoing lung transplantation evaluation.

BACKGROUND: The use of echocardiography in pulmonary hypertension (PH) in advanced chronic obstructive pulmonary disease (COPD) is understudied. We aimed to compare the performance of echocardiography with right heart catheterization (RHC) in the diagnosis of PH in COPD patients undergoing lung transplant evaluation. METHODS: We included 111 patients with severe COPD who underwent RHC in a single center as part of lung transplantation evaluation. COPD-PH and severe COPD-PH were defined based on RHC per the 6th world symposium on pulmonary hypertension. Echocardiographic probability of PH was described according to the European Society of Cardiology guidelines. Summary and univariate analyses were performed. RESULTS: The mean age (±SD) was 62 (8) and 47% (n=52) were men. A total of 82 patients (74 %) had COPD-PH. The sensitivity, specificity, positive predictive, and negative predictive values of echocardiography in diagnosing COPD-PH were 43 %, 83 %, 88 %, and 34 % respectively and for severe COPD-PH were 67 %, 75 %, 50 %, and 86 % respectively. Echocardiography was consistent with RHC in ruling in/out PH in 53% (n=59) of patients. After controlling for age, sex. BMI, pack year, echocardiography-RHC time difference, GOLD class, FVC, and CT finding of emphysema, higher TLC decreased consistency (parameter estimate=-0.031; odds ratio: 0.97, 95%CI 0.94-0.99; p=0.037) and higher DLCO increased consistency (parameter estimate=0.070; odds ratio: 1.07, 95%CI 0.94-0.99; p=0.026). CONCLUSIONS: Echocardiography has high specificity but low sensitivity for the diagnosis of PH in advanced COPD. Its performance improves when ruling out severe COPD-PH. This performance correlates inversely with lung hyperinflation.

Fatal venous air embolism in the setting of hemodialysis and pulmonary hypertension: A point of care ultrasound diagnosis.

Air emboli are rare and often difficult to diagnose. Transesophageal echocardiography remains the most definitive method of diagnosis, but this is not feasible in emergencies. We present a case of fatal air embolism in the setting of hemodialysis with recent evidence of pulmonary hypertension. The diagnosis was made by visualizing air in the right ventricle using bedside point of care ultrasound (POCUS). While POCUS is not routinely used for the diagnosis of air embolism, its accessibility makes it a powerful yet practical emerging tool for the diagnosis of respiratory and cardiovascular emergencies.

A simulation of skin mitochondrial Po2 in circulatory shock.

Circulatory shock is the inadequacy to supply mitochondria with enough oxygen to sustain aerobic energy metabolism. A novel noninvasive bedside measurement was recently introduced to monitor the mitochondrial oxygen tension in the skin (mitoPo2). As the most downstream marker of oxygen balance in the skin, mitoPo2 may provide additional information to improve shock management. However, a physiological basis for the interpretation of mitoPo2 values has not been established yet. In this paper, we developed a mathematical model of skin mitoPo2 using a network of parallel microvessels, based on Krogh's cylinder model. The model contains skin blood flow velocity, heterogeneity of blood flow, hematocrit, arteriolar oxygen saturation, and mitochondrial oxygen consumption as major variables. The major results of the model show that normal physiological mitoPo2 is in the range of 40-60 mmHg. The relationship of mitoPo2 with skin blood flow velocity follows a logarithmic growth curve, reaching a plateau at high skin blood flow velocity, suggesting that oxygen balance remains stable while peripheral perfusion declines. The model shows that a critical range exists where mitoPo2 rapidly deteriorates if skin perfusion further decreases. The model intuitively shows how tissue hypoxia could occur in the setting of septic shock, due to the profound impact of microcirculatory disturbance on mitoPo2, even at sustained cardiac output. MitoPo2 is the result of a complex interaction between all factors of oxygen delivery and microcirculation. This mathematical framework can be used to interpret mitoPo2 values in shock, with the potential to enhance personalized clinical trial design.NEW & NOTEWORTHY This is the first paper to simulate mitochondrial oxygen tension in skin in circulatory shock. The relationships of mitoPo2 with parameters of (microcirculatory) oxygen delivery aid in the understanding of noninvasive bedside measurement of mitoPo2 values and show that mitochondrial oxygen tension is two orders of magnitude higher than classically assumed. The model can be used to enhance clinical trial design investigating mitoPo2 as a resuscitation target in circulatory shock.

Role of Transbronchial Lung Cryobiopsy in the Diagnosis of Interstitial Lung Disease: A Meta-analysis of 68 Studies and 6300 Patients.

BACKGROUND: Diagnosis of interstitial lung disease (ILD) is based on multidisciplinary team discussion (MDD) with the incorporation of clinical, radiographical, and histopathologic information if available. We aim to evaluate the diagnostic yield and safety outcomes of transbronchial lung cryobiopsy (TBLC) in the diagnosis of ILD. METHODS: We conducted a meta-analysis by comprehensive literature search to include all studies that evaluated the diagnostic yields and/or adverse events with TBLC in patients with ILD. We calculated the pooled event rates and their 95% confidence intervals (CIs) for the diagnostic yield by MDD, histopathologic diagnostic yield, and various clinical adverse events. RESULTS: We included 68 articles (44 full texts and 24 abstracts) totaling 6386 patients with a mean age of 60.7±14.1 years and 56% men. The overall diagnostic yield of TBLC to achieve a definite or high-confidence diagnosis based on MDD was 82.3% (95% CI: 78.9%-85.2%) and histopathologic diagnosis of 72.5% (95% CI: 67.7%-76.9%). The overall rate of pneumothorax was 9.6% (95% CI: 7.9%-11%), while the rate of pneumothorax requiring drainage by a thoracostomy tube was 5.3% (95% CI: 4.1%-6.9%). The rate of moderate bleeding was 11.7% (95% CI: 9.1%-14.9%), while the rate of severe bleeding was 1.9% (95% CI: 1.4%-2.6%). The risk of mortality attributed to the procedure was 0.9% (95% CI: 0.7%-1.3%). CONCLUSION: Among patients with undiagnosed or unclassified ILD requiring tissue biopsy for diagnosis, transbronchial cryobiopsy represents a reliable alternative to surgical lung biopsy with decreased incidence of various clinical adverse events.

Prevalence and Characteristics of Hyperthyroidism Among Patients With Sarcoidosis in the United States.

OBJECTIVE: We aimed to determine the prevalence and clinical characteristics of self-reported hyperthyroidism in patients with sarcoidosis. METHODS: A national registry-based study investigating 3836 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire in the period between June 2014 and August 2019 was conducted. This registry is generated from a web-based questionnaire that is self-reported by patients with sarcoidosis. We compared patients with sarcoidosis who had hyperthyroidism with those who did not. We used multivariate logistic regression analysis to study the association between hyperthyroidism and different cardiac manifestations in patients with sarcoidosis. RESULTS: Three percent of the study respondents self-reported having hyperthyroidism and were generally middle-aged Caucasian women. Compared with patients without hyperthyroidism, patients with hyperthyroidism had more sarcoidosis-related comorbidities (59% vs 43%, P = .001) and more steroid-related comorbidities (56% vs 44%, P = .01), but there was no difference in the sarcoidosis-specific treatments they received, which included corticosteroids. Patients with hyperthyroidism reported sarcoidosis involvement of the heart (26.6% vs 14.9%, P = .005), kidneys (14.9% vs 8%, P = .033) and sinuses (17.7% vs 10.2%, P = .030) more frequently. Cardiac manifestations that were more frequently reported in patients with hyperthyroidism included atrial arrhythmias (11.3% vs 6.3%, P = .046), ventricular arrhythmias (17.2% vs 7.5%, P < .001), congestive heart failure (10.4% vs 5%, P = .017), and heart block (9.4% vs 4.7%, P = .036). CONCLUSION: Hyperthyroidism is infrequent in patients with sarcoidosis but is potentially associated with different cardiac manifestations. We suggest considering routine screening for hyperthyroidism in patients with sarcoidosis, especially in those with cardiac involvement. Further studies are needed to investigate the impact of identifying and treating hyperthyroidism in patients with sarcoidosis.

Pre-Existing Psychiatric Illness Is Associated With an Increased Risk of Delirium in Patients With Acute Respiratory Distress Syndrome.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) are highly susceptible to developing delirium for a multitude of reasons. Previous studies have linked pre-existing depression with an increased risk of postoperative delirium in patients undergoing cardiac and non-cardiac surgery. However, the evidence regarding the association between pre-existing psychiatric illnesses and delirium in ARDS patients is unknown. In this study, we aim to determine the relationship between pre-existing psychiatric illness and the risk of development of delirium amongst ARDS patients. STUDY DESIGN AND METHODS: We performed a retrospective study of a mixed group of patients admitted to the intensive care unit (ICU) between January 2016 and December 2019 with a diagnosis of ARDS per the Berlin definition. The study group was divided into 2 cohorts: subjects with delirium and subjects without delirium. Comparison between the 2 groups was conducted to examine the impact of pre-existing psychiatric illnesses including major depressive disorder (MDD), generalized anxiety disorder (GAD), bipolar disorder, schizophrenia, or post-traumatic stress disorder. Multivariable logistic regression analysis was performed adjusting for benzodiazepine use, sedatives, analgesics, sequential organ failure assessment score, and corticosteroid use to determine the association between pre-existing psychiatric disorders and delirium. RESULTS: 286 patients with ARDS were identified; 124 (43%) of whom were diagnosed with ICU delirium. In patients diagnosed with ICU delirium, 49.2% were found to have preexisting psychiatric illnesses, compared to 34.0% without any preexisting psychiatric illness (OR = 1.94, P = 0.01). In a subgroup analysis of individual psychiatric illnesses, GAD and MDD were associated with the development of delirium (OR = 1.88, P = 0.04 and OR = 1.76, P = 0.05 respectively). INTERPRETATION: ARDS patients with preexisting psychiatric illnesses, particularly GAD and MDD are associated with an increased risk of developing ICU delirium. Clinicians should be aware of the effect of psychiatric co-morbidities on developing delirium in critically ill patients.

Vitamin C, Thiamine, and Hydrocortisone in the Treatment of Sepsis: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: There is a conflicting body of evidence regarding the benefit of vitamin C, thiamine, and hydrocortisone in combination as an adjunctive therapy for sepsis with or without septic shock. We aimed to assess the efficacy of this treatment among predefined populations. METHODS: A literature review of major electronic databases was performed to include randomized controlled trials (RCTs) evaluating vitamin C, thiamine, and hydrocortisone in the treatment of patients with sepsis with or without septic shock in comparison to the control group. RESULTS: Seven studies met our inclusion criteria, and 6 studies were included in the final analysis totaling 839 patients (mean age 64.2 ± 18; SOFA score 8.7 ± 3.3; 46.6% female). There was no significant difference between both groups in long term mortality (Risk Ratio (RR) 1.05; 95% CI 0.85-1.30; P = 0.64), ICU mortality (RR 1.03; 95% CI 0.73-1.44; P = 0.87), or incidence of acute kidney injury (RR 1.05; 95% CI 0.80-1.37; P = 0.75). Furthermore, there was no significant difference in hospital length of stay, ICU length of stay, and ICU free days on day 28 between the intervention and control groups. There was, however, a significant difference in the reduction of SOFA score on day 3 from baseline (MD -0.92; 95% CI -1.43 to -.41; P < 0.05). In a trial sequential analysis for mortality outcomes, our results are inconclusive for excluding lack of benefit of this therapy. CONCLUSION: Among patients with sepsis with or without septic shock, treatment with vitamin C, thiamine, and hydrocortisone was not associated with a significant reduction in mortality, incidence of AKI, hospital and ICU length of stay, or ICU free days on day 28. There was a significant reduction of SOFA score on day 3 post-randomization. Further studies with a larger number of patients are needed to provide further evidence on the efficacy or lack of efficacy of this treatment.

Sarcoidosis among US Hispanics in a Nationwide Registry.

BACKGROUND: Sarcoidosis has been well studied in multiple races and ethnic groups. However, there is a paucity of data that describes sarcoidosis in Hispanics. We aimed to determine the prevalence of Hispanic ethnicity, clinical characteristics and impact of sarcoidosis among Hispanics from a US based national registry. METHODS: We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures questionnaire. This registry is a web-based, self-reported questionnaire that provides data related to demographics, diagnostics, organ involvement, treatment modalities, and the physical and psychosocial impact of sarcoidosis. We compared Hispanic patients to non-Hispanics. We performed multivariate logistic regression analysis adjusting for age, gender, education, income and insurance status and looked at the association between Hispanic ethnicity with depression, chronic pain syndrome, chronic fatigue syndrome, impact on family finances, employment-based disability and job termination. RESULTS: Nine percent of the patients reported a Hispanic ethnicity and the majority of these patients self-identified as white women. The most common organs involved were the lungs (74.9%), central lymph nodes (53.8%), and peripheral lymph nodes (37.1%). Hispanics reported more peripheral nerves and peripheral lymph nodes involvement than non-Hispanics. Hispanics experienced more depression, sleep apnea, and chronic pain syndrome than non-Hispanics. The use of mobility assistive devices was more common among Hispanics, as well as employment-based disability, and disease-related job termination compared to non-Hispanics. The majority of Hispanics reported significantly more pain that interfered with the enjoyment of life than non-Hispanics. On multivariate logistic regression analysis, Hispanic ethnicity was associated with depression (adjusted odds ratio (aOR) = 1.5; 95% CI: 1.01-2.2), chronic pain syndrome (aOR = 1.7; 1.1-2.6), job termination due to sarcoidosis (aOR = 1.7; 1.1-2.7) and higher impact on family finances (aOR = 1.7; 1.1-2.5). CONCLUSION: The clinical presentation of sarcoidosis in Hispanic patients differs from that in non-Hispanic patients living in the United States. These differences should be considered when managing Hispanic patients with sarcoidosis. We encourage more studies that investigate phenotyping among Hispanics with sarcoidosis.

Clinical Characteristics of Sarcoidosis Patients with Self-Reported Lymphoma: A US Nationwide Registry Study.

PURPOSE: Little is known about the association between sarcoidosis and lymphoma. We aim to determine the prevalence of lymphoma in US sarcoidosis patients and compare the clinical characteristics of patients with and without lymphoma. METHODS: Using a national registry-based study investigating 3560 respondents to the Foundation for Sarcoidosis Research Sarcoidosis Advanced Registry for Cures Questionnaire (FSR-SARC) completed between June 2014 and August 2019, we identified patients who reported the diagnosis of lymphoma following sarcoidosis and randomly selected a computer-generated control sample of sarcoidosis patients with no reported lymphoma with a 2:1 ratio. RESULTS: Among 3560 patients with sarcoidosis, 43 (1.2%) reported developing lymphoma following their sarcoidosis diagnosis. Patients with lymphoma were more likely to be diagnosed with sarcoidosis at a younger age (median, IQR) 40 (27-50) vs 45 (34.8-56, p = 0.017) years, were more likely to be African-Americans OR 95% CI 3.9 (1.6-9.6, p = 0.002), and have low annual income (OR 2.7, 1.1-6.4 p = 0.026). The sarcoidosis-lymphoma group were more likely to have salivary gland (16% vs 5%, p = 0.026) (OR 4; 1.1-14.5) and cutaneous (46% vs 23%, p = 0.023) (OR 2.9; 1.1-7.3) sarcoidosis. They also reported more chronic fatigue (42% vs 23%, p = 0.029), chronic pain (37% vs 13%, p = 0.001), and depression (42% vs 22%, p = 0.019). CONCLUSION: The prevalence of lymphoma reported in sarcoidosis patients is higher than the general population which further supports the possible increased risk of lymphoma in sarcoidosis. Diagnosis of sarcoidosis at a younger age, African-American race, cutaneous, and salivary glands sarcoidosis were associated with lymphoma. Sarcoidosis patients who developed lymphoma reported higher disease burden and more non-organ-specific manifestations.

Utility of bronchoscopic intra-tumoral alcohol injection to restore airway patency.

BACKGROUND: In cases of malignant airway obstruction, achieving airway patency using conventional bronchoscopic modalities can be challenging and may not be satisfactory. We aim to present our experience of using intra-tumoral alcohol injection (ITAI) to help achieve airway patency in malignant airway obstruction. METHODS: A retrospective study of adult patients presenting with malignant airway obstruction who underwent bronchoscopy with ITAI at a university center between 2015 and 2020 was conducted. We present procedural and patients' characteristics along with any additional bronchoscopic or systemic interventions received. Patients were classified based on airway patency response (assessed qualitatively by an interventional pulmonologist) into those with good response (≥50% improvement in airway patency) vs. those with low response (<50% improvement in airway patency). RESULTS: Forty-two patients underwent ITAI, of which 34 (81%) had at least two bronchoscopies to evaluate response. The patient median age was 65.5 [interquartile range (IQR) 57.8-72]. Most patients had stage IV malignancy at the time of the bronchoscopy (57.1%) and had Eastern Cooperative Oncology Group (ECOG) performance status score of between 2-3. Eighty-two percent of the patients achieved good airway patency response at the conclusion of the procedures. The procedures were generally well-tolerated and only one patient had significant bleeding that was not directly related to ITAI and required intensive care unit monitoring for 24 hours after the procedure. CONCLUSIONS: Dehydrated alcohol is readily available, inexpensive and a safe drug that can be potentially injected directly in malignant airway obstructive lesions in a multimodality approach to achieve airway patency when traditional modalities reach their limitation. Further studies are warranted to determine whether ITAI is superior to other interventional methods, explore its utilization to treat peripheral malignant tumors, as well as to standardize the treatment protocol and determine the effects of ITAI on patient symptoms and quality of life.

A 57-Year-Old Man With Stridor and Critical Tracheal Narrowing.

CASE PRESENTATION: A 57-year-old man with a history of polysubstance use presented with shortness of breath, wheezing, productive cough, subjective fever, and chills of 3-day duration. Additionally, he reported worsening shortness of breath for the last 3 months. Of note, the patient was reported to have had, in the previous 6 months, two episodes of pneumonia that was treated with antibiotics and steroids. He was also diagnosed several years prior with adult-onset asthma due to intermittent wheezing and was prescribed an albuterol inhaler. The albuterol did not help relieve his wheezing, and he stopped refilling it.

Prevalence and characteristics of self-reported hypothyroidism and its association with nonorgan-specific manifestations in US sarcoidosis patients: a nationwide registry study.

Little is known about the prevalence, clinical characteristics and impact of hypothyroidism in patients with sarcoidosis. We aimed to determine the prevalence and clinical features of hypothyroidism and its relation to organ involvement and other clinical manifestations in patients with sarcoidosis. We conducted a national registry-based study investigating 3835 respondents to the Sarcoidosis Advanced Registry for Cures Questionnaire between June 2014 and August 2019. This registry is based on a self-reported, web-based questionnaire that provides data related to demographics, diagnostics, sarcoidosis manifestations and treatment. We compared sarcoidosis patients with and without self-reported hypothyroidism. We used multivariable logistic regression and adjusted for potential confounders to determine the association of hypothyroidism with nonorgan-specific manifestations. 14% of the sarcoidosis patients self-reported hypothyroidism and were generally middle-aged white women. Hypothyroid patients had more comorbid conditions and were more likely to have multiorgan sarcoidosis involvement, especially with cutaneous, ocular, joints, liver and lacrimal gland involvement. Self-reported hypothyroidism was associated with depression (adjusted odds ratio (aOR) 1.3, 95% CI 1.01-1.6), antidepressant use (aOR 1.3, 95% CI 1.1-1.7), obesity (aOR 1.7, 95% CI 1.4-2.1), sleep apnoea (aOR 1.7, 95% CI 1.3-2.2), chronic fatigue syndrome (aOR 1.5, 95% CI 1.2-2) and was borderline associated with fibromyalgia (aOR 1.3, 95% CI 1-1.8). Physical impairment was more common in patients with hypothyroidism. Hypothyroidism is a frequent comorbidity in sarcoidosis patients that might be a potentially reversible contributor to fatigue, depression and physical impairment in this population. We recommend considering routine screening for hypothyroidism in sarcoidosis patients especially in those with multiorgan sarcoidosis, fatigue and depression.

Attitudes and Knowledge of the Harmful Effects of Waterpipe Tobacco Smoking among university students: A study from Jordan.

Waterpipe tobacco smoking (WTS) is an emerging behavior worldwide, especially among the youth. It continues to spike in the Middle-Eastern region. WTS is associated with many harmful health-related outcomes.Objective: Herein, the attitude, knowledge, and factors affecting the knowledge of university students toward the detrimental effects of WTS were examined. This was a cross-sectional study where university students filled an online questionnaire that was available between October 2019 and May 2020. A total of 966 questionnaires were filled. About 40% of participants were current waterpipe smokers. Around 30% of participants stated that WTS is not addictive, and about third of them indicated that smoking waterpipe is an essential part of social gathering and is socially accepted behavior. Half of participants (55.8%) were knowledgeable about the major harmful consequences of WTS. Older students were more knowledgeable as compared to younger ones. In contrast, students from non-medical colleges and waterpipe smokers were less knowledgeable in comparison to those in medical colleges and non-smokers, respectively. More targeted health campaigns to control the use of WTS among university students should be implemented.

Cyclophosphamide for the treatment of Acute Exacerbation of Interstitial Lung Disease: A Review of the Literature.

Acute exacerbation of interstitial lung disease is a serious and life-threatening event but little is known about its treatment. Cyclophosphamide has been proposed in randomized clinic trials as a treatment option in progressive cases of systemic sclerosis related interstitial lung disease. However, in acute exacerbation of interstitial lung disease, we found only small case series, and retrospective studies, mostly with no comparative groups which described the role of cyclophosphamide. Results of these studies showed mixed outcomes, with no robust evidence that cyclophosphamide adds any benefit in treating acute exacerbations of interstitial lung disease. More well-designed studies including randomized clinical trials are needed to better understand the role of cyclophosphamide during exacerbations of interstitial lung disease. In this review article, we summarize the current evidence on the use of cyclophosphamide in interstitial lung disease with a focus on the acute exacerbation events.

Pulmonary hypertension in eosinophilic versus noneosinophilic COPD.

BACKGROUND: The eosinophilic COPD phenotype is associated with greater airway remodelling, exacerbation risk and steroid responsiveness. However, little is known about the prevalence and characteristics of pulmonary hypertension (PH) in this patient population. METHODS: We retrospectively evaluated a cohort of COPD patients with right heart catheterisation (RHC) data at a university hospital between January 2011 and May 2019 and compared the pulmonary vascular profile and prevalence of PH between eosinophilic and noneosinophilic patients using a definition of eosinophilic COPD as at least three blood eosinophil values ≥300 cells·µL-1. We used multivariable logistic regression analyses to examine the association between eosinophilic COPD and various PH categories adjusting for age, sex, body mass index, forced expiratory volume in 1 s (%), smoking status and use of supplemental oxygen. RESULTS: Among 106 COPD patients with RHC data and at least three blood eosinophil values, 25% met the definition of eosinophilic COPD. Fewer patients among the eosinophilic group required long-term oxygen therapy (69% versus 93%, p=0.001) and total lung capacity was significantly lower in the eosinophilic group (p=0.006). This group had higher mean pulmonary arterial pressure (mPAP) (median (interquartile range) 30 (27-41) mmHg versus 25 (22-30) mmHg, p=0.001) and pulmonary vascular resistance (PVR) (4 (2.8-5.1) Wood units versus 2.9 (2.1-4.1) Wood units, p=0.018). On multivariable logistic regression analyses, eosinophilic phenotype was associated with PH (adjusted (a)OR 6.5, 95% CI 1.4-30.7; p=0.018) and pre-capillary PH (aOR 3.2, 95% CI 1.1-9; p=0.027), but not severe PH (aOR 2.1, 95% CI 0.6-7.2; p=0.219). CONCLUSION: Eosinophilic COPD was associated with higher mPAP and PVR and increased likelihood of PH. More studies are needed to further explore this finding.

Novel CineECG enables anatomical 3D localization and classification of bundle branch blocks.

AIMS: Ventricular conduction disorders can induce arrhythmias and impair cardiac function. Bundle branch blocks (BBBs) are diagnosed by 12-lead electrocardiogram (ECG), but discrimination between BBBs and normal tracings can be challenging. CineECG computes the temporo-spatial trajectory of activation waveforms in a 3D heart model from 12-lead ECGs. Recently, in Brugada patients, CineECG has localized the terminal components of ventricular depolarization to right ventricle outflow tract (RVOT), coincident with arrhythmogenic substrate localization detected by epicardial electro-anatomical maps. This abnormality was not found in normal or right BBB (RBBB) patients. This study aimed at exploring whether CineECG can improve the discrimination between left BBB (LBBB)/RBBB, and incomplete RBBB (iRBBB). METHODS AND RESULTS: We utilized 500 12-lead ECGs from the online Physionet-XL-PTB-Diagnostic ECG Database with a certified ECG diagnosis. The mean temporo-spatial isochrone trajectory was calculated and projected into the anatomical 3D heart model. We established five CineECG classes: 'Normal', 'iRBBB', 'RBBB', 'LBBB', and 'Undetermined', to which each tracing was allocated. We determined the accuracy of CineECG classification with the gold standard diagnosis. A total of 391 ECGs were analysed (9 ECGs were excluded for noise) and 240/266 were correctly classified as 'normal', 14/17 as 'iRBBB', 55/55 as 'RBBB', 51/51 as 'LBBB', and 31 as 'undetermined'. The terminal mean temporal spatial isochrone contained most information about the BBB localization. CONCLUSION: CineECG provided the anatomical localization of different BBBs and accurately differentiated between normal, LBBB and RBBB, and iRBBB. CineECG may aid clinical diagnostic work-up, potentially contributing to the difficult discrimination between normal, iRBBB, and Brugada patients.