fibrin and Airway-Obstruction

Topics: Airway Obstruction; Animals; Asthma; Disease Models, Animal; Fibrin; Mice; Mice, Inbred BALB C

Topics: Airway Obstruction; Angiography; Animals; Anticoagulants; Dyspnea; Electrocardiography; Fibrin; Fibrinogen; Fibrinolytic Agents; Heart Auscultation; Heparin; Humans; Ligation; Pulmonary Artery; Pulmonary Embolism; Radionuclide Imaging; Thrombophlebitis; Vena Cava, Inferior

Plastic bronchitis (PB) is a condition characterized by the formation of thick airway casts leading to acute and often life-threatening airway obstruction. PB occurs mainly in pediatric patients with congenital heart disease (CHO) who have undergone staged surgical palliation (Glenn, Fontan), but can also occur after chemical inhalation, H1N1, severe COVID-19, sickle cell disease, severe asthma, and other diseases. Mortality risk from PB can be up to 40%-60%, and no treatment guideline exist. The objectives herein are to develop a standardized evaluation, classification, and treatment guideline for PB patients presenting with tracheobronchial casts, based on our experience with PB at the Children's Hospital of Colorado in Denver.. We describe 11 patients with CHO-associated PB (post-Fontan [n = 9], pre-Fontan [n = 2]) who presented with their initial episodes. We utilized histopathological analysis of tracheobronchial casts to guide treatment in these patients, utilizing our hospital-wide guideline document and classification system.. We found that 100% of post-Fontan PB patients had fibrinous airway casts, while pre-Fontan PB casts were fibrinous only in one of two patients (50%). Utilizing histopathology as a guide to therapy, PB patients with fibrin airway casts were treated with airway-delivered fibrinolytics and anticoagulants, as well as aggressive airway clearance and other supportive care measures. These therapies resulted in successful cast resolution and improved survival in post-Fontan PB patients.. We have shown an improved outcome in PB patients whose treatment plan was based on Denver's PB classification schema and standardized treatment guideline based on tracheobronchial cast histopathology.

Topics: Airway Obstruction; Bronchitis; Child; COVID-19; Fibrin; Fontan Procedure; Humans; Influenza A Virus, H1N1 Subtype; SARS-CoV-2

Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence.. Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin-antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin.. Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid.. Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury.

Topics: Administration, Inhalation; Airway Obstruction; Animals; Blotting, Western; Bronchoalveolar Lavage Fluid; Chemical Warfare Agents; Enzyme-Linked Immunosorbent Assay; Fibrin; Fibrinolysis; Immunoglobulin M; Immunohistochemistry; Indicators and Reagents; Lipoproteins; Male; Microdissection; Mustard Gas; Proteins; Prothrombin; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Respiratory Insufficiency

Sulfur mustard (SM) inhalation causes the rare but life-threatening disorder of plastic bronchitis, characterized by bronchial cast formation, resulting in severe airway obstruction that can lead to respiratory failure and death. Mortality in those requiring intubation is greater than 80%. To date, no antidote exists for SM toxicity. In addition, therapies for plastic bronchitis are solely anecdotal, due to lack of systematic research available to assess drug efficacy in improving mortality and/or morbidity. Adult rats exposed to SM analog were treated with intratracheal tissue plasminogen activator (tPA) (0.15-0.7 mg/kg, 5.5 and 6.5 h), compared with controls (no treatment, isoflurane, and placebo). Respiratory distress and pulse oximetry were assessed (for 12 or 48 h), and arterial blood gases were obtained at study termination (12 h). Microdissection of fixed lungs was done to assess airway obstruction by casts. Optimal intratracheal tPA treatment (0.7 mg/kg) completely eliminated mortality (0% at 48 h), and greatly improved morbidity in this nearly uniformly fatal disease model (90-100% mortality at 48 h). tPA normalized plastic bronchitis-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress (i.e., clinical scores) while decreasing airway fibrin casts. Intratracheal tPA diminished airway-obstructive fibrin-containing casts while improving clinical respiratory distress, pulmonary gas exchange, tissue oxygenation, and oxygen utilization in our model of severe chemically induced plastic bronchitis. Most importantly, mortality, which was associated with hypoxemia and clinical respiratory distress, was eliminated.

Topics: Airway Obstruction; Animals; Chemical Warfare Agents; Disease Models, Animal; Fibrin; Fibrinolytic Agents; Humans; Mustard Gas; Rats; Rats, Sprague-Dawley; Respiratory Insufficiency; Tissue Plasminogen Activator

This case illustrates the successful use of orthotopic heart transplantation for the treatment of plastic bronchitis in a 6-year-old boy with hypoplastic left heart syndrome, which developed 2 years after Fontan procedure. Transplantation was undertaken after he failed medical management of airway obstruction. He is currently 1-year post-cardiac transplantation and has no evidence of plastic bronchitis despite weaning of an aggressive airway clearance regimen.

Topics: Airway Obstruction; Bronchitis; Cardiac Surgical Procedures; Child; Fibrin; Heart Transplantation; Humans; Hypoplastic Left Heart Syndrome; Male

Sulfur mustard (SM) is a frequently used chemical warfare agent, even in modern history. SM inhalation causes significant respiratory tract injury, with early complications due to airway obstructive bronchial casts, akin to those seen after smoke inhalation and in single-ventricle physiology. This process with SM is poorly understood because animal models are unavailable.. To develop a rat inhalation model for airway obstruction with the SM analog 2-chloroethyl ethyl sulfide (CEES), and to investigate the pathogenesis of bronchial cast formation.. Adult rats were exposed to 0, 5, or 7.5% CEES in ethanol via nose-only aerosol inhalation (15 min). Airway microdissection and confocal microscopy were used to assess cast formation (4 and 18 h after exposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were done to evaluate vascular permeability.. Bronchial casts, composed of abundant fibrin and lacking mucus, occluded dependent lobar bronchi within 18 hours of CEES exposure. BALF contained elevated concentrations of IgM, protein, and fibrin. Accumulation of fibrin-rich fluid in peribronchovascular regions (4 h) preceded cast formation. Monastral blue dye leakage identified bronchial vessels as the site of leakage.. After CEES inhalation, increased permeability from damaged bronchial vessels underlying damaged airway epithelium leads to the appearance of plasma proteins in both peribronchovascular regions and BALF. The subsequent formation of fibrin-rich casts within the airways then leads to airways obstruction, causing significant morbidity and mortality acutely after exposure.

Topics: Airway Obstruction; Animals; Blotting, Western; Bronchi; Bronchoalveolar Lavage Fluid; Capillary Permeability; Chemical Warfare Agents; Disease Models, Animal; Fibrin; Immunoglobulin M; Inhalation Exposure; Male; Microdissection; Microscopy, Confocal; Mustard Gas; Rats; Rats, Sprague-Dawley

A 69-year-old woman was admitted because of dyspnea. Thereafter, she fell into a state of shock. Resuscitation was attempted but she did not respond to it and died on the second hospital day. According to the autopsy findings, a wide range of area from the larynx to the trachea was covered with pseudomembrane. In the culture of bacteria, alpha Streptococcus and Corynebacterium genus (non-diphtherial) were all that was detected. These findings suggest that pseudomembranous lesion, an endogenous foreign matter of the air passage should be suspected when a patient presents with sudden dyspnea.

Topics: Aged; Airway Obstruction; Autopsy; Bronchitis; Corynebacterium; Death, Sudden; Dyspnea; Female; Fibrin; Humans; Neutrophils; Streptococcus pyogenes

Three cases of life-endangering airway obstruction by fibrin membranes are reviewed which developed in a 17-year-old girl with virus pneumonia, in a 21-year-old girl with a history of thrombopathy after general anaesthesia with naso-tracheal intubation and in a 23-year-old woman after short anaesthesia with orotracheal intubation. Possible causal factors, the clinical symptoms and the therapeutic measures taken by the anaesthetist are discussed. Since these cases are generally in a state of severe respiratory collapse by the time treatment is initiated general anaesthesia with muscle relaxation should be attempted only if the anaesthesist is certain that he can effectively ventilate the patient before and during the operation. Otherwise it is better to apply assisted ventilation with oxygen and halothane via a mask until a clear air passage has been restored. Administration of anticholine drugs and control of shock are essential.

Topics: Adolescent; Adult; Airway Obstruction; Dyspnea; Female; Fibrin; Humans; Intubation, Intratracheal; Pneumonia, Viral; Succinylcholine; Tracheitis; Tracheotomy; Tubocurarine

Topics: Aged; Airway Obstruction; Bronchitis; Bronchoscopy; Chronic Disease; Diagnosis, Differential; Fibrin; Humans; Male