fibrin and Bronchitis

Topics: Age Factors; Bronchitis; Chronic Disease; Collagen; Fibrin; Heterozygote; Humans; Kinins; Leukocytes; Lung; Microbial Collagenase; Phenotype; Plasminogen; Pulmonary Emphysema; Trypsin Inhibitors

Plastic bronchitis (PB) is a rare and deadly condition that is characterized by the formation of airway casts. It most frequently occurs in children with underlying congenital heart disease that has been surgically palliated by the Fontan procedure. The Fontan circulation results in above-normal central venous pressure, and it has been hypothesized that the formation of airway casts is due to lymph leak. Knowledge of plastic bronchitis pathogenesis is poor and stems mostly from published case reports.. To garner information about cast pathogenesis by characterizing inflammatory cell phenotypes in existing formalin-preserved, paraffin-embedded samples and generating protein and cytokine-chemokine profiles of airway cast homogenates.. We used immunofluorescence confocal microscopy, state-of-the-science proteomics, and a cytokine array assay to immunophenotype cellular content and to generate protein and cytokine profiles of plastic bronchitis airway casts, respectively.. Neutrophils, eosinophils, macrophages, and B lymphocytes were identified in cast samples; there were notably fewer T lymphocytes. Fibrin(ogen) was an abundant protein in the cast proteome. Histone H4 was also abundant, and immunofluorescence microscopy demonstrated it to be mostly extracellular. The cytokine profile of plastic bronchitis casts was proinflammatory.. Plastic bronchitis airway casts from children with Fontan physiology are composed of fibrin and are cellular and inflammatory in nature, providing evidence that their formation cannot be explained simply by lymph leak into the airways. Consequences of cellular necrosis including extracellular histones and the apparent low number of T cells indicate that a derangement in inflammation resolution likely contributes to cast formation.

Topics: Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Child; Cytokines; Fibrin; Fontan Procedure; Heart Defects, Congenital; Histones; Humans; Immunity, Cellular; Immunophenotyping; Proteomics

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

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

Plastic bronchitis (PB) is a rare disease that often occurs in patients with congenital heart disease (CHD) who have undergone staged single-ventricle palliation. It is characterized by the formation of rubbery "casts" in the airways. PB treatment frequently includes inhaled tissue plasminogen activator (tPA). However, the efficacy of tPA to reduce cast burden is unknown. This is further complicated by our lack of knowledge of cast composition. We obtained spontaneously expectorated PB casts from children (n = 4) with CHD and one adult patient with idiopathic PB. Pathological assessment was made from paraffin-preserved samples. Casts were treated with phosphate-buffered saline (PBS) or tPA. Cast response to tPA was assessed by changes in cast weight and the production of fibrin D-dimer. Independent of dose, tPA reduced cast weight compared with PBS-treatment (P = 0.001) and increased D-dimer levels. Histological staining showed that PB casts from all patients were composed of fibrin and contained notable numbers of lymphocytes. Cast composition did not change over time. Collectively, these data support that in our PB patients, casts are composed of fibrin and are responsive to tPA treatment. This makes inhaled tPA a potentially viable option for symptomatic relief of PB while we work to unravel the complexity of PB pathogenesis.

Topics: Administration, Inhalation; Bronchi; Bronchitis; Child; Child, Preschool; Female; Fibrin; Fibrinolytic Agents; Fontan Procedure; Heart Defects, Congenital; Humans; Immunohistochemistry; Infant; Male; Paraffin Embedding; Prospective Studies; Tissue Plasminogen Activator

Assessing state of various hemostasis levels in patients having pulmonary diseases caused by dust, in accordance with respiratory failure severity, enables to diagnose early changes confirming hypoxia. The most reliable parameters are changes in vascular and platelet hemostasis and in fibrinolysis system.

Topics: Biomarkers; Bronchitis; Disease Progression; Early Diagnosis; Fibrin; Hemostasis; Humans; Hypoxia; Lung Diseases; Middle Aged; Occupational Exposure; Particulate Matter; Platelet Function Tests; Respiratory Insufficiency; Thrombin

Burn patients often develop respiratory distress and ARDS several days after injury. An ovine model allows experimental study of this problem. In sheep the injury is characterized by intense acute inflammation in the trachea and bronchi from 3 to 48h after injury, with accumulation of neutrophils, fibrin and other plasma proteins, and mucus in airway lumens. We have carried out immunostaining for multiple cytokines in this model, including interleukin-8 (IL-8), Interleukin-1 beta (IL-1beta), interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF). All of these show intense immunostaining in airway mucous glands. IL-1beta and VEGF show substantial constitutive staining in the serous cells of mucous glands, while IL-8, IL-1alpha, and TNF-alpha show substantially increased expression after injury. This pattern of expression of cytokines in mucous glands, and the apparent release of cytokines into the lumen after injury, are considered potentially highly significant in the progression of injury in this model. In addition, a proinflammatory function of mucous glands might prove to be important in chronic lung diseases such as chronic bronchitis and asthma.

Topics: Animals; Bronchi; Bronchitis; Connective Tissue Cells; Cytokines; Disease Models, Animal; Epithelial Cells; Female; Fibrin; Goblet Cells; Immunohistochemistry; Inflammation Mediators; Interleukins; Mucins; Neutrophils; Sheep; Smoke Inhalation Injury; Staining and Labeling; Tracheitis; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Topics: Biopsy; Bronchi; Bronchial Diseases; Bronchitis; Bronchoscopy; Chyle; Cough; Dyspnea; Fibrin; Frozen Sections; Humans; Lymphocytes; Lymphography; Male; Middle Aged; Mucus; Oxygen; Triglycerides

Extravascular activation of the coagulation system and consequent fibrin deposition is involved in the pathomechanism of chronic bronchoalveolar inflammatory diseases. The turnover of extravascular fibrin is attenuated by its cross-linking with activated factor XIII (FXIII).. Determination of cellular and plasmatic forms of FXIII and their correlation with D-dimer level in the bronchoalveolar lavage fluid (BALF) from healthy children and from children with bronchoalveolar inflammation.. Highly sensitive immunoassays were used for the quantitation of cellular and plasma FXIII and D-dimer in the BALF of children with recurrent wheezy bronchitis and fibrosing alveolitis. BALF was investigated for FXIII-containing cells by flow cytometry.. In the BALF of controls a low amount of the cellular form of FXIII (FXIII A2) and D-dimer were measured, while plasma FXIII (FXIII A2B2) was absent. Alveolar macrophages represented the single cell population in BALF that contained FXIII. In the BALF of both patients' groups the concentration and the total amount of FXIII A2 was significantly elevated, and plasma FXIII also appeared in the BALF of most patients. The D-dimer concentration was also elevated in the patients' groups and it correlated both with plasma FXIII and neutrophil count. These findings suggest that FXIII A2 is released from activated or injured alveolar macrophages into the bronchoalveolar lining fluid and in bronchoalveolar inflammatory diseases, FXIII A2B2 also leaks out from the capillaries. By cross-linking fibrin and inhibitors of fibrinolysis to fibrin, FXIII might be a key regulator of fibrin turnover in the extravascular compartment.

Topics: Adolescent; Bronchi; Bronchitis; Bronchoalveolar Lavage Fluid; Capillaries; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Factor XIII; Factor XIII Deficiency; Factor XIIIa; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Flow Cytometry; Humans; Infant; Inflammation; Macrophages; Male; Neutrophils; Pulmonary Alveoli; Time Factors

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

Topics: Age Factors; Bronchitis; Bronchoscopy; Child, Preschool; Dyspnea; Fibrin; Humans; Infant

Topics: Adult; Aged; Animals; Antibodies; Aspartate Aminotransferases; Bronchitis; Bronchopneumonia; Erythrocytes; Female; Fibrin; Fibrinogen; Humans; Injections, Intravenous; Iodine Radioisotopes; Leg; Male; Middle Aged; Myocardial Infarction; Sheep; Thrombophlebitis

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

Topics: Anti-Bacterial Agents; Blood Coagulation; Blood Sedimentation; Bronchitis; Bronchography; Child, Preschool; Cough; Dyspnea; Exudates and Transudates; Female; Fibrin; Humans; Infant; Male; Pulmonary Atelectasis

Topics: Asphyxia; Bronchitis; Chloramphenicol; Endoscopy; Fibrin; Hemorrhage; Humans; Mucous Membrane; Tracheal Diseases; Tracheotomy

Topics: Autopsy; Bronchitis; Burns; Embolism, Fat; Fibrin; Humans; Lung; Pneumonia; Pulmonary Alveoli; Pulmonary Artery; Pulmonary Embolism; Pulmonary Veins; Thoracic Injuries