Endobronchial Ultrasound for the Screening of Pulmonary Embolism in Patients with Suspected Lung Cancer: A Prospective Cohort Study.

BACKGROUND: Patients with lung cancer exhibit increased risk of pulmonary embolism (PE). While the contrast phase of computed tomography of the chest in the diagnostic work-up of suspected chest malignancy does not allow reliable detection of PE, it may be feasible to screen for present PE during endobronchial ultrasound (EBUS) examination. OBJECTIVES: The aim of this study was to establish if screening during EBUS for PE in patients with suspected lung cancer is feasible and if positive findings are predictive of PE. METHODS: Patients undergoing EBUS due to suspicion of malignancy of the chest were prospectively enrolled. The pulmonary arteries were assessed during EBUS using a standardized protocol. Patients in whom PE suspicion was raised were referred to confirmatory imaging. RESULTS: From December 2020 to August 2021, 100 patients were included. Median time for vascular assessment during EBUS was 2 min (Q1-Q3: 1-3 min). EBUS identified two suspected PEs (2%), and the number needed to scan was 50. The positive predictive value of EBUS for PE was 100%. CONCLUSION: EBUS for PE screening seems feasible and with limited time use. The PPV of positive findings for the diagnosis of PE is high, but the utility is somewhat limited by a high number needed to scan even in a high-risk population. Based on our findings, we believe that EBUS assessment of the pulmonary vasculature may have a role as a routine screening tool for PE. The assessment for PE should be implemented in EBUS training programmes, as operators should be able to recognize incidental PEs.

Inter-rater reliability and prognostic value of baseline Radiographic Assessment of Lung Edema (RALE) scores in observational cohort studies of inpatients with COVID-19.

OBJECTIVES: To reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes. SETTING: Hospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems. PARTICIPANTS: 425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set. PRIMARY AND SECONDARY OUTCOMES: We measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host-response biomarkers, SARS-CoV-2 RNA load and clinical outcomes. RESULTS: Inter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). In the discovery cohort, the required level of respiratory support at the time of CXR acquisition (supplemental oxygen or non-invasive ventilation (n=178); invasive-mechanical ventilation (n=234), extracorporeal membrane oxygenation (n=13)) was significantly associated with RALE scores (median (IQR): 20.0 (14.1-26.7), 26.0 (20.5-34.0) and 44.5 (34.5-48.0), respectively, p<0.0001). Among invasively ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, soluble receptor of advanced glycation end-products and soluble tumour necrosis factor receptor 1 (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted HR 1.04 (1.02-1.07), p=0.002). We replicated the significant associations of RALE scores with baseline disease severity and mortality in the independent validation data set. CONCLUSIONS: With a reproducible method to measure radiographic severity in COVID-19, we found significant associations with clinical and physiologic severity, host inflammation and clinical outcomes. The incorporation of radiographic severity assessments in clinical decision-making may provide important guidance for prognostication and treatment allocation in COVID-19.

Morphological and functional findings in COVID-19 lung disease as compared to Pneumonia, ARDS, and High-Altitude Pulmonary Edema.

Coronavirus disease-2019 (COVID-19) may severely affect respiratory function and evolve to life-threatening hypoxia. The clinical experience led to the implementation of standardized protocols assuming similarity to severe acute respiratory syndrome (SARS-CoV-2). Understanding the histopathological and functional patterns is essential to better understand the pathophysiology of COVID-19 and then develop new therapeutic strategies. Epithelial and endothelial cell damage can result from the virus attack, thus leading to immune-mediated response. Pulmonary histopathological findings show the presence of Mallory bodies, alveolar coating cells with nuclear atypia, reactive pneumocytes, reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates, micro-abscesses, microthrombus, hyaline membrane fragments, and emphysema-like lung areas. COVID-19 patients may present different respiratory stages from silent to critical hypoxemia, are associated with the degree of pulmonary parenchymal involvement, thus yielding alteration of ventilation and perfusion relationships. This review aims to: discuss the morphological (histopathological and radiological) and functional findings of COVID-19 compared to acute interstitial pneumonia, acute respiratory distress syndrome (ARDS), and high-altitude pulmonary edema (HAPE), four entities that share common clinical traits, but have peculiar pathophysiological features with potential implications to their clinical management.

Radiographic features of cardiogenic pulmonary oedema in cats with left-sided cardiac disease: 71 cases.

OBJECTIVES: The aims of this study were to describe the radiographic features of cardiogenic pulmonary oedema (CPE) in a large group of cats with left-sided cardiac disease, and to determine the association between the radiographic features of CPE and the underlying cardiac disease. METHODS: Thoracic radiographs of cats with CPE and echocardiographic evidence of left-sided cardiac disease and left atrial enlargement (LAE) were reviewed, and cardiac silhouette, pulmonary vessels and pulmonary parenchyma evaluation were performed. Interstitial and/or alveolar patterns were classified according to their distribution (ie, diffuse, multifocal or focal) and location (ie, craniodorsal, cranioventral, caudodorsal, caudoventral and perihilar). A Student's t-test and Mann-Whitney U-test, or the two-proportion z-test, were used to compare continuous or categorical variables, respectively, between cats affected by the two most represented cardiac diseases, namely hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM). RESULTS: Seventy-one cats were included; among them, 46 (64.7%) and 13 (18.3%) had presented for HCM and RCM, respectively. Subjective and objective cardiomegaly, and subjective and objective LAE were detected in 97.2% and 91.9% of cats and in 80.3% and 40.6% of cats, respectively. Pulmonary artery abnormalities, in particular caudal pulmonary artery dilation, were found in 77.5% of cats. Pulmonary artery to pulmonary vein ratio = 1 was found in 71.8% and 55% cats on right lateral and ventrodorsal or dorsoventral views, respectively. Interstitial (57.8%) and mixed interstitial-alveolar (38%) pattern, multifocal (84.5%) and symmetrical (75%) distribution with prevalent ventrocaudal (65.6% of cats) and ventrocranial (60.9% of cats) locations were most frequently observed. No difference was found for any of these radiographic features between cats with HCM and RCM. CONCLUSIONS AND RELEVANCE: Moderate-to-severe cardiomegaly and LAE, caudal pulmonary artery and vein dilation, as well as a ventral, multifocal and symmetrical interstitial pulmonary pattern, were the main radiographic features of CPE in evaluated cats. Underlying cardiac disease did not influence the aforementioned radiographic features.

Lung ultrasound assessment of pulmonary edema in neonates with chronic lung disease before and after diuretic therapy.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is characterized by lung injury with varying degrees of disrupted alveolarization, vascular remodeling, inflammatory cell proliferation, and pulmonary edema. Diuretics are often used to ameliorate the symptoms or progression of BPD. Our primary objective was to use lung ultrasound (LUS) to determine if diuretics decrease pulmonary edema in infants with BPD. The secondary objective was to assess changes in respiratory support during the first week after initiation of diuretics. METHODS: Premature infants requiring noninvasive respiratory support and starting diuretic therapy for evolving BPD were compared with a similar group of infants not receiving diuretics (control). For the diuretic group, LUS exams were performed before and on Days 1, 3, and 6 after initiation of treatment. For the control group, LUS was performed at equivalent time points. A composite pulmonary edema severity (PES) score of 0-5 was calculated based on the total number of B-lines in six scanned areas. Respiratory support parameters (FiO2 , nasal cannula flow, or CPAP) were also recorded. RESULTS: Infants in the diuretic (n = 28) and control (n = 23) groups were recruited at median corrected gestational ages of 34.2 (33.3-35.9) and 34.0 (33.4-36.3) weeks, respectively (p = 0.82). PES scores, FiO2 , and respiratory flow support decreased significantly from Days 0 to 6 (p < 0.0001, p = 0.001, and p = 0.01, respectively) in the diuretic group, but not in the control group. CONCLUSION: Diuretic use is associated with decreased pulmonary edema and improved oxygenation in infants with BPD during the first week of treatment.

Pulmonary edema in a pediatric cancer patient after anesthetic induction.

Negative pressure pulmonary edema (NPPE) in the context of anesthesia is a rare condition, although pediatric patients are at higher risk. This case stands out for the severe respiratory clinic that quickly developed in a child with a cancer history whose radiological and clinical presentation suggested multiple differential diagnoses, including tumor recurrence with metastasis or pulmonary tuberculosis. NPPE is a well-described, but a probably underrecognized clinical syndrome, that occurs after intense inspiratory effort against an obstructed airway. In clinical practice, when unexplained pulmonary edema takes place, NPPE should be considered in the differential diagnosis. NPPE usually has a favorable prognosis but pediatricians, radiologists, and anesthesiologists should be aware of this complication.

Fatal noncardiogenic pulmonary edema related to nonionic, iso-osmolar iodine contrast medium: one case report.

BACKGROUND: Noncardiogenic pulmonary edema (NCPE) is a rare and life-threatening allergy-like reaction to the intravascular injection of a nonionic radiographic agent. We first describe a very rare case of fatal NCPE after the intravenous injection of nonionic, iso-osmolar iodine contrast media. Case presentation A 55-year-old male patient was admitted to the hospital with esophageal cancer. After the intravenous administration of 100 mL iodixanol, the patient first exhibited digestive tract symptoms, including abdominal pain, diarrhea, and vomiting, with no dyspnea, rash, itching, or throat edema. He received anti-allergy treatment, but his symptoms did not improve; instead, he further developed pulmonary edema. Arterial blood gas analysis results were as follows: pH, 7.08; PO2, 70 mm Hg; PCO2, 40 mm Hg; and SaO2, 52%. Then, the patient received emergent tracheal intubation and ventilation to assist breathing, and he was transferred to the intensive care unit (ICU) for further treatment. In the ICU, the patient developed shock and respiratory and circulatory failure; therefore, he received shock resuscitation, acidosis correction, muscle relaxants to lower the work of breathing, and cardiotonic therapy. The patient eventually died. During the ICU period, emergency bedside color ultrasound showed a diffuse B line in both lungs, and the size of the cardiac cavity was normal, but the ventricular rate was extremely fast. Chest radiography showed pulmonary edema with a normal cardiac silhouette, and the brain natriuretic peptide (BNP) level was in the normal range. CONCLUSIONS: NCPE is a rare and critical allergy-like reaction to the use of a nonionic iso-osmolar radiocontrast contrast medium. Clinicians should pay very close attention to digestive tract manifestations during the medical observation of patients, as gastrointestinal manifestations may be the prodromal symptoms of NCPE caused by iso-osmolar contrast medium injection.

Comparison of artificial intelligence to the veterinary radiologist's diagnosis of canine cardiogenic pulmonary edema.

Application of artificial intelligence (AI) to improve clinical diagnosis is a burgeoning field in human and veterinary medicine. The objective of this prospective, diagnostic accuracy study was to determine the accuracy, sensitivity, and specificity of an AI-based software for diagnosing canine cardiogenic pulmonary edema from thoracic radiographs, using an American College of Veterinary Radiology-certified veterinary radiologist's interpretation as the reference standard. Five hundred consecutive canine thoracic radiographs made after-hours by a veterinary Emergency Department were retrieved. A total of 481 of 500 cases were technically analyzable. Based on the radiologist's assessment, 46 (10.4%) of these 481 dogs were diagnosed with cardiogenic pulmonary edema (CPE+). Of these cases, the AI software designated 42 of 46 as CPE+ and four of 46 as cardiogenic pulmonary edema negative (CPE-). Accuracy, sensitivity, and specificity of the AI-based software compared to radiologist diagnosis were 92.3%, 91.3%, and 92.4%, respectively (positive predictive value, 56%; negative predictive value, 99%). Findings supported using AI software screening for thoracic radiographs of dogs with suspected cardiogenic pulmonary edema to assist with short-term decision-making when a radiologist is unavailable.

Acute Pulmonary Edema Due to Arteriovenous Shunt Placement After Lung Transplantation.

Lung transplant recipients often have complications of immunosuppressant-induced nephropathy, which may require renal replacement therapy. We report a case of unilateral lung edema and pulmonary hypertension due to arteriovenous fistula placement in a patient with unilateral chronic lung allograft dysfunction after bilateral living-donor lobar lung transplantation. Lung transplant recipients with limited residual vascular beds, such as lobar graft or severe deviation in lung perfusion, are vulnerable to the acute increase in blood flow due to arteriovenous fistula placement and pulmonary edema can easily develop regardless of the left ventricular function. Hence, careful volume control is required.

LUCAS (lung ultrasonography in cardiac surgery) score to monitor pulmonary edema after congenital cardiac surgery in children.

AIM: Cardiopulmonary bypass (CPB) generates a systemic capillary leak syndrome with pulmonary edema. Lung ultrasound (LUS) could be useful to monitor it. Primary objective was to compare sensitivity, specificity, positive and negative predictive values of chest X-ray and LUS to detect pulmonary edema using a new score (LUCAS). Secondary objectives were to evaluate correlation between LUCAS score and respiratory and inotropic support. METHODS: Prospective intervention study including patients <2 months admitted to the Pediatric Intensive Care Unit after CPB. LUS was performed with a lineal probe, screening 3 points in each lung (parasternal, anterolateral and posterior area), pre and post-CPB. Pulmonary edema was evaluated clinically, through LUCAS score and with X-ray. RESULTS: 17 patients were included. LUS achieved higher sensitivity than X-ray to detect pulmonary edema (91.7 versus 44.0%) and greater predictive negative value (88.2 versus 53.3%). There was correlation between higher LUCAS score prior to surgery and longer mechanical ventilation. High values of LUCAS score after surgery correlated with longer CPB time, inotropic support, and FiO2 need. CONCLUSION: LUS detected pulmonary edema better than chest X-ray, with greater sensitivity and negative predictive value. LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.Key notesCardiopulmonary bypass during cardiac surgery, generates a systemic capillary leak syndrome with pulmonary edema.In this prospective study performed in the Pediatric Intensive Care Unit, lung ultrasound detected pulmonary edema better than X-ray, with greater sensitivity and negative predictive value.LUCAS score was useful to predict more inotropic support and longer mechanical ventilation.

Unilateral Pulmonary Edema After Robotically Assisted Mitral Valve Repair Requiring Veno-Venous Extracorporeal Membrane Oxygenation.

Unilateral pulmonary edema (UPE) is an uncommon yet potentially life-threatening complication of minimally invasive cardiac surgery (MICS). Most frequently described after robotically assisted mitral valve (MV) repair, it is characterized by right lung edema, hypoxemia, hypercapnia, pulmonary hypertension, and hemodynamic instability beginning minutes-to-hours after separation from cardiopulmonary bypass (CPB). The authors describe a severe case with refractory hypoxemia requiring veno-venous (VV) extracorporeal membrane oxygenation (ECMO) after robotically assisted MV repair.

Risk of Acute Lung Injury after Esophagectomy.

To develop a new approach for identifying acute lung injury (ALI) in surgical ward setting and to assess incidence rate, clinical outcomes, and risk factors for ALI cases after esophagectomy. We also compare the degree of lung injury between operative and non-operative sides. Consecutive esophageal cancer patients (n=1022) who underwent esophagectomy from Dec 2012 to Nov 2018 in our hospital were studied. An approach for identifying ALI was proposed that integrated radiographic assessment of lung edema (RALE) score to quantify degree of lung edema. Stepwise logistic regression identified risk factors for postoperative ALI incidence. The degree of bilateral lung injury was compared using the RALE score. The approach for identifying ALI in surgical ward setting was defined as acute onset, PaO2/FiO2≤300 mmHg, bilateral opacities on bedside chest radiograph with a RALE score≥16, and exclusion of cardiogenic pulmonary edema. Incidence rate of ALI was estimated to be 9.7%. ALI diagnosis was associated with multiple clinical complications, prolonged hospital stay, higher medical bills, and higher perioperative mortality. Nine risk factors including BMI, ASA class, DLCO%, duration of surgery, neutrophil percentage, high-density lipoprotein, and electrolyte disorders were identified. The RALE score of the lung lobes of the operative side was higher than the non-operative side. A new approach for identifying ALI in esophageal cancer patients receiving esophagectomy was proposed and several risk factors were identified. ALI is common and has severe outcomes. The lung lobes on the operative side are more likely to be affected than the non-operative side.

Development of an Image-Based HCS-Compatible Method for Endothelial Barrier Function Assessment.

The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the COVID-19 pandemic. Despite decades of laboratory and clinical study, no efficient pharmacological therapy for ARDS has been found. An increase in endothelial permeability is the primary event in ARDS onset, causing the development of pulmonary edema that leads to respiratory failure. Currently, the detailed molecular mechanisms regulating endothelial permeability are poorly understood. Therefore, the use of the PDD approach in the search for efficient ARDS treatment can be more productive than classic target-based drug discovery (TDD), but its use requires a new cell-based assay compatible with high-throughput (HTS) and high-content (HCS) screening. Here we report the development of a new plate-based image cytometry method to measure endothelial barrier function. The incorporation of image cytometry in combination with digital image analysis substantially decreases assay variability and increases the signal window. This new method simultaneously allows for rapid measurement of cell monolayer permeability and cytological analysis. The time-course of permeability increase in human pulmonary artery endothelial cells (HPAECs) in response to the thrombin and tumor necrosis factor α treatment correlates with previously published data obtained by transendothelial resistance (TER) measurements. Furthermore, the proposed image cytometry method can be easily adapted for HTS/HCS applications.

Lung Ultrasound Surface Wave Elastography for Assessing Patients With Pulmonary Edema.

B-Mode ultrasound insonation of lungs that are dense with extravascular lung water (EVLW) produces characteristic reverberation artifacts termed B-lines. The number of B-lines present demonstrates reasonable correlation to the amount of EVLW. However, analysis of B-line artifacts generated by this modality is semi-quantitative relying on visual interpretation, and as a result, can be subject to inter-observer variability. The purpose of this study was to translate the use of a novel, quantitative lung ultrasound surface wave elastography technique (LUSWE) into the bedside assessment of pulmonary edema in patients admitted with acute congestive heart failure. B-mode lung ultrasound and LUSWE assessment of the lungs were performed using anterior and lateral intercostal spaces in the supine patient. 14 patients were evaluated at admission with reassessment performed 1-2 days after initiation of diuretic therapy. Each exam recorded the total lung B-lines, lung surface wave speeds (at 100, 150, and 200 Hz) and net fluid balance. The patient cohort experienced effective diuresis (average net fluid balance of negative 2.1 liters) with corresponding decrease in pulmonary edema visualized by B-mode ultrasound (average decrease of 13 B-Lines). In addition, LUSWE demonstrated a statistically significant reduction in the magnitude of wave speed from admission to follow-up. The reduction in lung surface wave speed suggests a decrease in lung stiffness (decreased elasticity) mediated by successful reduction of pulmonary edema. In summary, LUSWE is a noninvasive technique for quantifying elastic properties of superficial lung tissue that may prove useful as a diagnostic test, performed at the bedside, for the quantitative assessment of pulmonary edema.