Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial.

Background: The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2.

Methods: Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18-80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids).

A phase 2 multiple ascending dose study of the inhaled pan-JAK inhibitor nezulcitinib (TD-0903) in severe COVID-19.

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Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: a prospective cohort study.

The association of autoimmune disease (AI) with transplant-free survival in the setting of Group 3 pulmonary hypertension and pulmonary fibrosis remains unclear. We report cases of severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg right ventricular dysfunction) and extensive pulmonary fibrosis after pulmonary arterial hypertension-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival.

A 75-Year-Old Man With Organizing Pneumonia Presenting With Worsening Dyspnea.

A 75-year-old man was referred to our institution for worsening dyspnea, decreased activity tolerance, myalgias, and an increase in oxygen requirement. Nine months before the initial referral, the patient presented to an outside hospital for acute hypoxemic respiratory failure requiring a right-sided video-assisted thoracoscopic surgery (VATS) lung biopsy that disclosed organizing pneumonia (OP). He was treated with a prolonged steroid course starting at 1 mg/kg daily and tapered over 6 months to a baseline of 20 mg of prednisone daily and continuous oxygen (2 L/min).

Comparison of Fixed-Dose Inhaled Epoprostenol and Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome in Critically Ill Adults.

Purpose: Several reports have demonstrated similar effects on oxygenation between inhaled epoprostenol (iEPO) compared to inhaled nitric oxide (iNO) for acute respiratory distress syndrome (ARDS). Previous studies directly comparing oxygenation and clinical outcomes between iEPO and iNO exclusively in an adult ARDS patient population utilized a weight-based dosing strategy. The purpose of this study was to compare the clinical and economic impact between iNO and fixed-dosed iEPO for ARDS in adult intensive care unit (ICU) patients.

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension.

Objective: We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH).

Methods: Two pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc-PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquantitatively assessed in areas of preserved lung architecture.

A review of exercise pulmonary hypertension in systemic sclerosis.

In general, pulmonary vascular disease has important negative prognostic implications, regardless of the associated condition or underlying mechanism. In this regard, systemic sclerosis is of particular interest as it is the most common connective tissue disease associated with pulmonary hypertension, and a well-recognized at-risk population. In the setting of systemic sclerosis and unexplained dyspnea, the concept of using exercise to probe for underlying pulmonary vascular disease has acquired significant interest.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Use and Costs in the Critically Ill.

Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin in the ICU.

BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension.

Background: Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. BOLA3 (BolA Family Member 3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined.

Right Ventricular Functional Reserve in Early-Stage Idiopathic Pulmonary Fibrosis: An Exercise Two-Dimensional Speckle Tracking Doppler Echocardiography Study.

Background: The most important determinant of long-term survival in patients with idiopathic pulmonary fibrosis is the right ventricular (RV) adaptation to the increased pulmonary vascular resistance. Our aim was to explore RV contractile reserve during stress echocardiography in early-stage IPF.

Methods: Fifty early-stage patients with IPF and 50 healthy control patients underwent rest and stress echocardiography, including RV two-dimensional speckle tracking echocardiography.

The Right Heart International Network (RIGHT-NET): Rationale, Objectives, Methodology, and Clinical Implications.

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

Pulmonary Hypertension Related to Chronic Obstructive Pulmonary Disease and Diffuse Parenchymal Lung Disease: A Focus on Right Ventricular (Dys)Function.

Diffuse pulmonary lung disease and chronic obstructive pulmonary disease is a heterogeneous population that can manifest pulmonary hypertension. These subgroups are classified as primarily World Health Organization group 3. Available data suggest that the impact of pulmonary hypertension targeted therapy in diffuse pulmonary lung disease and chronic obstructive pulmonary disease is limited and survival is poor despite attempted treatment.

Pulmonary Hypertension: The Role of Lung Transplantation.

Despite advances in targeted medical therapy, pulmonary arterial hypertension (PAH) remains a fatal disease because of progressive right ventricular dysfunction. For patients who are refractory to medical therapy, heart-lung and lung transplantation are important treatment options. Because of longer waiting time, surgical interventions including extracorporeal lung support and atrial septostomy can be used in PAH patients bridging to transplantation.

Stressing the Cardiopulmonary Vascular System: The Role of Echocardiography.

The cardiopulmonary vascular system represents a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for assessing pulmonary hemodynamics, a comprehensive noninvasive evaluation including left and right ventricular reserve and function and cardiopulmonary interactions remains highly attractive. Stress echocardiography is crucial in the evaluation of many cardiac conditions, typically coronary artery disease but also heart failure and valvular heart disease.

Exercise-Induced Pulmonary Hypertension: Translating Pathophysiological Concepts Into Clinical Practice.

Exercise stress testing of the pulmonary circulation for the diagnosis of latent or early-stage pulmonary hypertension (PH) is gaining acceptance. There is emerging consensus to define exercise-induced PH by a mean pulmonary artery pressure > 30 mm Hg at a cardiac output < 10 L/min and a total pulmonary vascular resistance> 3 Wood units at maximum exercise, in the absence of PH at rest. Exercise-induced PH has been reported in association with a bone morphogenetic receptor-2 gene mutation, in systemic sclerosis, in left heart conditions, in chronic lung diseases, and in chronic pulmonary thromboembolism.

Sarcoidosis and colon cancer: a possible association.

Sarcoidosis is a multisystem inflammatory disease characterized by non-caseating granulomas which mainly affect the pulmonary lymphatic system and lungs; although any organs can be interested. The association between sarcoidosis and cancer is still controversial, but many studies demonstrated an increased risk of cancer in patients with sarcoidosis, whereas few cases of sarcoidosis occurring after cancer have been reported. This report outlines and describes clinical, biologic and radiologic features of 3 patients with a history of surgical treatment and adjuvant chemotherapy for colon cancer, followed by a diagnosis of sarcoidosis some years later.

An official European Respiratory Society statement: pulmonary haemodynamics during exercise.

There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the scientific evidence in this field in order to provide a basis for future recommendations.Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise.

Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension.

Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1).

Editor's Choice-Biomarkers of acute cardiovascular and pulmonary diseases.

Acute cardiothoracic and respiratory diseases frequently remain a challenge to diagnose and differentiate in the emergency setting. The main diseases that manifest with chest pain include ischaemic heart disease, myocarditis, acute pericarditis, aortic dissection/rupture and pulmonary embolism (PE). Diseases that primarily present with dyspnoea include heart failure (HF), acute respiratory distress syndrome (ARDS), pneumonia, asthma exacerbations and chronic obstructive pulmonary disease.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience.

Rationale: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes.

Objectives: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction.

Methods: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109).

Matrix Remodeling Promotes Pulmonary Hypertension through Feedback Mechanoactivation of the YAP/TAZ-miR-130/301 Circuit.

Pulmonary hypertension (PH) is a deadly vascular disease with enigmatic molecular origins. We found that vascular extracellular matrix (ECM) remodeling and stiffening are early and pervasive processes that promote PH. In multiple pulmonary vascular cell types, such ECM stiffening induced the microRNA-130/301 family via activation of the co-transcription factors YAP and TAZ.