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Biomolecules Jul 2021Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic... (Review)
Review
Neutrophil elastase (NE) is a major inflammatory protease released by neutrophils and is present in the airways of patients with cystic fibrosis (CF), chronic obstructive pulmonary disease, non-CF bronchiectasis, and bronchopulmonary dysplasia. Although NE facilitates leukocyte transmigration to the site of infection and is required for clearance of Gram-negative bacteria, it also activates inflammation when released into the airway milieu in chronic inflammatory airway diseases. NE exposure induces airway remodeling with increased mucin expression and secretion and impaired ciliary motility. NE interrupts epithelial repair by promoting cellular apoptosis and senescence and it activates inflammation directly by increasing cytokine expression and release, and indirectly by triggering extracellular trap release and exosome release, which magnify protease activity and inflammation in the airway. NE inhibits innate immune function by digesting opsonins and opsonin receptors, degrading innate immune proteins such as lactoferrin, and inhibiting macrophage phagocytosis. Importantly, NE-directed therapies have not yet been effective in preventing the pathologic sequelae of NE exposure, but new therapies are being developed that offer both direct antiprotease activity and multifunctional anti-inflammatory properties.
Topics: Animals; Chronic Disease; Humans; Leukocyte Elastase; Lung; Lung Diseases; Neutrophils
PubMed: 34439732
DOI: 10.3390/biom11081065 -
Respiratory Medicine Jan 2021Idiopathic pulmonary hemosiderosis (IPH) is an uncommon cause of diffuse alveolar hemorrhage (DAH). Patients with IPH usually present with hemoptysis, and the diagnosis... (Review)
Review
Idiopathic pulmonary hemosiderosis (IPH) is an uncommon cause of diffuse alveolar hemorrhage (DAH). Patients with IPH usually present with hemoptysis, and the diagnosis is often delayed by years. Patients often present with intermittent episodes of hemoptysis interspersed between periods of relative normalcy. However, massive hemorrhage resulting in acute respiratory failure and non-remitting hemoptysis have also been described. The classic triad includes hemoptysis, radiologic lung infiltrate, and iron deficiency anemia. Several hypotheses regarding the pathogenesis of IPH have been proposed. These risk factors include an autoimmune, allergic or genetic predisposition, and possible environmental exposure. Since IPH appears to be responsive to corticosteroids, the autoimmune hypothesis is considered to play a crucial role. A diagnosis of IPH requires exclusion of other etiologies of DAH, including infection, medications, toxic inhalation, vasculitis, and anti-glomerular basement membrane disease, among others. Histologically, IPH is characterized by the presence of hemosiderin-laden macrophages in the alveolar space without any evidence of vasculitis or immunocomplex deposition. Corticosteroid therapy represents the primary modality of treatment. Other immunosuppressive medications have also been used with varying success, especially in the setting of steroid-refractory disease. The prognosis of IPH in adults is somewhat better compared to the pediatric population. The severity of the initial presentation does not predict future outcomes. Which risk factors and patient characteristics are associated with a poor outcome are also unknown. More research is necessary to elucidate the pathophysiology and appropriate treatment.
Topics: Adrenal Cortex Hormones; Anemia, Iron-Deficiency; Autoimmunity; Child; Delayed Diagnosis; Female; Genetic Predisposition to Disease; Hemoptysis; Hemosiderosis; Humans; Immunosuppressive Agents; Lung; Lung Diseases; Magnetic Resonance Imaging; Male; Middle Aged; Prognosis; Radiography, Thoracic; Risk Factors; Severity of Illness Index; Hemosiderosis, Pulmonary
PubMed: 33246295
DOI: 10.1016/j.rmed.2020.106234 -
International Journal of Molecular... Jan 2021Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication in patients with hematologic malignancies or systemic autoimmune disorders. Pathologic... (Review)
Review
Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication in patients with hematologic malignancies or systemic autoimmune disorders. Pathologic findings show pulmonary capillaritis, bland hemorrhage, diffuse alveolar damage, and hemosiderin-laden macrophages, but in the majority of cases, pathogenesis remains unclear. Despite the severity and high mortality, the current treatment options for DAH remain empirical. Systemic treatment to control inflammatory activity including high-dose corticosteroids, cyclophosphamide, and rituximab and supportive care have been applied, but largely unsuccessful in critical cases. Activated recombinant factor VII (FVIIa) can achieve rapid local hemostasis and has been administered either systemically or intrapulmonary for the treatment of DAH. However, there is no randomized controlled study to evaluate the efficacy and safety, and the use of FVIIa for DAH remains open to debate. This review discusses the pathogenesis, diverse etiologies causing DAH, diagnosis, and treatments focusing on hemostasis using FVIIa. In addition, the risks and benefits of the off-label use of FVIIa in pediatric patients will be discussed in detail.
Topics: Adrenal Cortex Hormones; Cyclophosphamide; Factor VIIa; Hemorrhage; Hemostasis; Humans; Inflammation; Lung Diseases; Pulmonary Alveoli; Recombinant Proteins; Rituximab
PubMed: 33466873
DOI: 10.3390/ijms22020793 -
Pneumologie (Stuttgart, Germany) Mar 2023Haemoptysis describes the expectoration of blood originating from the tracheobronchial tree and lung. Its presentation varies from mild to massive haemoptysis, the...
Haemoptysis describes the expectoration of blood originating from the tracheobronchial tree and lung. Its presentation varies from mild to massive haemoptysis, the latter entailing the risk of asphyxia and thus requiring rapid intervention that spans multiple specialties.
Topics: Humans; Hemoptysis; Lung; Lung Neoplasms; Bronchi; Sputum
PubMed: 36918017
DOI: 10.1055/a-1854-3022 -
Journal of Thrombosis and Haemostasis :... Sep 2020The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated... (Review)
Review
The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID-19. The clinical presentation of COVID-19-associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D-dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial-sepsis-associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID-19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID-19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.
Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; COVID-19; Cytokines; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Inflammation; Lung; Lymphocytes; Partial Thromboplastin Time; Protease Inhibitors; Prothrombin Time; Sepsis; Thrombosis
PubMed: 32558075
DOI: 10.1111/jth.14975 -
Annals of Cardiac Anaesthesia 2022Pulmonary thromboendarterectomy surgery is the recommended treatment for patients with chronic thromboembolic pulmonary hypertension. Massive intraoperative pulmonary...
Pulmonary thromboendarterectomy surgery is the recommended treatment for patients with chronic thromboembolic pulmonary hypertension. Massive intraoperative pulmonary haemorrhage with bleeding into the airway is a rare complication, and it typically presents as cardiopulmonary bypass flow is reduced and blood begins to flow through the pulmonary circulation. Immediate management includes maintaining extracorporeal circulation to reduce blood flow through the pulmonary circulation, isolation of the affected lung, while the surgeon identifies and repairs the site of haemorrhage.
Topics: Endarterectomy; Hemorrhage; Humans; Hypertension, Pulmonary; Infant, Newborn; Lung Diseases; Pulmonary Embolism
PubMed: 35417969
DOI: 10.4103/aca.aca_247_20 -
Lung Apr 2021Diffuse alveolar hemorrhage (DAH) is a rare condition with reported mortality ranging between 20 and 100%. There are many etiologies of DAH. Cardiac diseases are likely... (Review)
Review
Diffuse alveolar hemorrhage (DAH) is a rare condition with reported mortality ranging between 20 and 100%. There are many etiologies of DAH. Cardiac diseases are likely underreported causes of DAH. Heart failure and mitral valve diseases are the most common cardiac causes of DAH. The DAH results from pulmonary venous hypertension leading to stress failure of the pulmonary capillaries. There is also a contribution of the bronchial circulation. The Alveolar-capillary membrane or blood-gas barrier is an extremely thin structure that allows rapid and passive diffusion of oxygen from the inhaled air to the pulmonary capillaries while preventing pulmonary edema and DAH with chronic elevation of the transmural hydrostatic pressure. The purpose of this manuscript is to inform the clinician about this rare cause of DAH, which may be overlooked unless specifically sought after. We also discuss the pathophysiologic aspects of DAH and the safety mechanisms in place to prevent such occurrences.
Topics: Heart Diseases; Hemorrhage; Humans; Lung Diseases; Pulmonary Alveoli
PubMed: 33709230
DOI: 10.1007/s00408-021-00433-x -
Molecules (Basel, Switzerland) Nov 2022Although critical for development of novel therapies, understanding altered lung function in disease models is challenging because the transport and diffusion of gases... (Review)
Review
Although critical for development of novel therapies, understanding altered lung function in disease models is challenging because the transport and diffusion of gases over short distances, on which proper function relies, is not readily visualized. In this review we summarize progress introducing hyperpolarized Xe imaging as a method to follow these processes in vivo. The work is organized in sections highlighting methods to observe the gas replacement effects of breathing (Gas Dynamics during the Breathing Cycle) and gas diffusion throughout the parenchymal airspaces (3). We then describe the spectral signatures indicative of gas dissolution and uptake (4), and how these features can be used to follow the gas as it enters the tissue and capillary bed, is taken up by hemoglobin in the red blood cells (5), re-enters the gas phase prior to exhalation (6), or is carried via the vasculature to other organs and body structures (7). We conclude with a discussion of practical imaging and spectroscopy techniques that deliver quantifiable metrics despite the small size, rapid motion and decay of signal and coherence characteristic of the magnetically inhomogeneous lung in preclinical models (8).
Topics: Xenon Isotopes; Magnetic Resonance Imaging; Lung; Respiration; Erythrocytes
PubMed: 36500430
DOI: 10.3390/molecules27238338 -
The Lancet. Neurology Nov 2023Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining... (Randomized Controlled Trial)
Randomized Controlled Trial
Intracranial pressure monitoring with and without brain tissue oxygen pressure monitoring for severe traumatic brain injury in France (OXY-TC): an open-label, randomised controlled superiority trial.
BACKGROUND
Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months.
METHODS
We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed.
FINDINGS
Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest.
INTERPRETATION
After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission.
FUNDING
The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.
Topics: Humans; Oxygen; Intracranial Pressure; Brain Injuries, Traumatic; Brain; France; Hematoma; Death
PubMed: 37863590
DOI: 10.1016/S1474-4422(23)00290-9 -
Portuguese Journal of Cardiac Thoracic... Oct 2022A 16-year-old female, without relevant previous medical history, presented with 1 year episodic and progressive hemoptysis. CT scan revealed an abnormal blood supply...
A 16-year-old female, without relevant previous medical history, presented with 1 year episodic and progressive hemoptysis. CT scan revealed an abnormal blood supply from the descending thoracic aorta to the left lower lobe, the later presenting with significant signs of hyperperfusion. Therapy consisted of ligation of the anomalous vessel followed by left lower lobe lobectomy. Lung sequestration is a rare congenital pulmonary malformation, mostly diagnosed in childhood. The typical symptoms are recurrent pulmonary infections or productive cough and only in rare situations severe hemoptysis occurs. Preoperative planning with CT or MR angiography is important to identify the aberrant blood supply. The treatment of choice is surgical ligation of the feeding vessel in combination with lung resection.
Topics: Adolescent; Angiography; Bronchopulmonary Sequestration; Female; Hemoptysis; Humans; Lung; Thorax
PubMed: 36197824
DOI: 10.48729/pjctvs.282