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Chest Jan 2020Massive hemoptysis is a medical emergency with high mortality presenting several difficult diagnostic and therapeutic challenges. The origin of bleeding and underlying... (Review)
Review
Massive hemoptysis is a medical emergency with high mortality presenting several difficult diagnostic and therapeutic challenges. The origin of bleeding and underlying etiology often is not immediately apparent, and techniques for management of this dangerous condition necessitate an expedient response. Unlike hemorrhage in other circumstances, a small amount of blood can rapidly flood the airways, thereby impairing oxygenation and ventilation, leading to asphyxia and consequent cardiovascular collapse. Of paramount importance is early control of the patient's airway and immediate isolation of hemorrhage in an attempt to localize and control bleeding. A coordinated team response is essential to guarantee the best chances of patient survival. Prompt control of the airway and steps to limit the spread of hemorrhage take precedence. Bronchial artery embolization, rigid and flexible bronchoscopy, and surgery all serve as potential treatment options to provide definitive control of hemorrhage. Several adjunctive therapies described in recent years may also assist in the control of bleeding; however, their role is less defined in life-threatening hemoptysis and warrants additional studies. In this concise review, we emphasize the steps necessary for a systematic approach in the management of life-threatening hemoptysis.
Topics: Bronchoscopy; Checklist; Diagnosis, Differential; Diagnostic Imaging; Electrocoagulation; Embolization, Therapeutic; Fibrinolytic Agents; Hemoptysis; Humans; Iatrogenic Disease; Intubation, Intratracheal; Prognosis
PubMed: 31374211
DOI: 10.1016/j.chest.2019.07.012 -
Seminars in Immunology Dec 2019Asthma is a chronic airway disease, which affects more than 300 million people. The pathogenesis of asthma exhibits marked heterogeneity with many phenotypes defining... (Review)
Review
Asthma is a chronic airway disease, which affects more than 300 million people. The pathogenesis of asthma exhibits marked heterogeneity with many phenotypes defining visible characteristics and endotypes defining molecular mechanisms. With the evolution of novel biological therapies, patients, who do not-respond to conventional asthma therapy require novel biologic medications, such as anti-IgE, anti-IL-5 and anti-IL4/IL13 to control asthma symptoms. It is increasingly important for physicians to understand immunopathology of asthma and to characterize asthma phenotypes. Asthma is associated with immune system activation, airway hyperresponsiveness (AHR), epithelial cell activation, mucus overproduction and airway remodeling. Both innate and adaptive immunity play roles in immunologic mechanisms of asthma. Type 2 asthma with eosinophilia is a common phenotype in asthma. It occurs with and without visible allergy. The type 2 endotype comprises; T helper type 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), IgE-secreting B cells and eosinophils. Eosinophilic nonallergic asthma is ILC2 predominated, which produces IL-5 to recruit eosinophil into the mucosal airway. The second major subgroup of asthma is non-type 2 asthma, which contains heterogeneous group of endoypes and phenotypes, such as exercise-induced asthma, obesity induced asthma, etc. Neutrophilic asthma is not induced by allergens but can be induced by infections, cigarette smoke and pollution. IL-17 which is produced by Th17 cells and type 3 ILCs, can stimulate neutrophilic airway inflammation. Macrophages, dendritic cells and NKT cells are all capable of producing cytokines that are known to contribute in allergic and nonallergic asthma. Bronchial epithelial cell activation and release of cytokines, such as IL-33, IL-25 and TSLP play a major role in asthma. Especially, allergens or environmental exposure to toxic agents, such as pollutants, diesel exhaust, detergents may affect the epithelial barrier leading to asthma development. In this review, we focus on the immunologic mechanism of heterogenous asthma phenotypes.
Topics: Asthma; Cytokines; Eosinophils; Humans; Hypersensitivity; Immunity, Innate; Immunoglobulin E; Phenotype; Th17 Cells; Th2 Cells
PubMed: 31703832
DOI: 10.1016/j.smim.2019.101333 -
Allergology International : Official... Oct 2019Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss syndrome) is a rare form of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis... (Review)
Review
Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg-Strauss syndrome) is a rare form of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small to medium-size vessel vasculitis associated with bronchial asthma and eosinophilia. Its rarity and unique features such as eosinophilic inflammation have delayed progress of research regarding EGPA for several years, compared to other forms of ANCA-associated vasculitis. However, recently, attention to EGPA as a research subject has been gradually increasing. To resolve problems in existing criteria for EGPA, new classification criteria for EGPA generated by a large international cohort will be launched and is being expected to accelerate future studies. Pathogenesis and roles of ANCA in EGPA are still largely unknown; however, it has been reported that glomerulonephritis is more frequent in ANCA-positive patients than in ANCA-negative patients, while heart failure is more frequent in ANCA-negative patients than in ANCA-positive patients. In addition, a recent genome-wide association study has suggested the presence of two genetically distinct subgroups of EGPA, which correspond to ANCA-positive and -negative subgroups. Although responses to glucocorticoids in EGPA are generally good, patients with EGPA often experience a relapse. Currently, there is no standard therapy for EGPA based on accumulation of clinical trial results. Recently, clinical benefits of mepolizumab for EGPA were proved by a randomized controlled trial and mepolizumab was approved for EGPA. In addition, various new drugs are under evaluation. To find optimal use of these drugs and to resolve unmet needs, such as relapse prevention, will be needed in future.
Topics: Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Biopsy; Diagnosis, Differential; Disease Susceptibility; Eosinophilia; Eosinophils; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Phenotype
PubMed: 31266709
DOI: 10.1016/j.alit.2019.06.004 -
The Surgical Clinics of North America Jun 2022Massive hemoptysis is appropriately defined as life-threatening hemoptysis that causes airway obstruction, respiratory failure, and/or hypotension. Patients with this... (Review)
Review
Massive hemoptysis is appropriately defined as life-threatening hemoptysis that causes airway obstruction, respiratory failure, and/or hypotension. Patients with this condition die from asphyxiation, not hemorrhagic shock. Any patient who presents with life-threatening hemoptysis requires immediate treatment to secure the airway and stabilize hemodynamics. Early activation and coordinated response from a multidisciplinary team is critical. Once the airway is secure and appropriate resuscitation is initiated, priorities are to localize the source of the bleeding and gain hemorrhage control. Nonsurgical control of hemorrhage is superior to surgery in the acute situation.
Topics: Bronchoscopy; Diagnostic Imaging; Embolization, Therapeutic; Hemoptysis; Hemorrhage; Humans
PubMed: 35671767
DOI: 10.1016/j.suc.2021.11.002 -
Chest May 2023Tranexamic acid (TA) is used to control bleeding in patients with hemoptysis. However, the effectiveness of the different routes of TA administration has not been... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tranexamic acid (TA) is used to control bleeding in patients with hemoptysis. However, the effectiveness of the different routes of TA administration has not been studied.
RESEARCH QUESTION
Does the nebulized route of TA administration reduce the amount of hemoptysis compared with the IV route in patients presenting to the ED with hemoptysis?
STUDY DESIGN AND METHODS
This was a pragmatic, open-label, randomized, parallel, single-center, pilot trial of nebulized TA (500 mg tid) vs IV TA (500 mg tid) in adult patients presenting to the ED with active hemoptysis. The primary outcome was cessation of bleeding at 30 min. Secondary outcomes included amount of hemoptysis at 6, 12, and 24 h; interventional procedures; and side effects of TA. Patients who were hemodynamically unstable or requiring immediate interventional procedure or mechanical ventilation were excluded from the study.
RESULTS
Of the 55 patients in each arm, hemoptysis cessation at 30 min following TA administration was significantly higher in the nebulization arm (n = 40) compared with the IV arm (n = 28): χ (1, n = 110) = 5.55; P = .0019. Also, hemoptysis amount was reduced significantly in the nebulization arm at all time periods of observation (P value at 30 min = .011, at 6 h = .002, 12 h = .0008, and at 24 h = .005). Fewer patients in the nebulization arm required bronchial artery embolization (13 vs 21; P = .024) and thereby had higher discharge rates from the ED (67.92% vs 39.02%; P = .005). Two patients in the nebulization arm had asymptomatic bronchoconstriction that resolved after short-acting beta-agonist nebulization. No patient discharged from the ED underwent any interventional procedure or revisited the ED with rebleed during the 72 h follow-up period.
INTERPRETATION
Nebulized TA may be more efficacious than IV TA in reducing the amount of hemoptysis and need for ED interventional procedures. Future larger studies are needed to further explore the potential of nebulized TA compared with IV TA in patients with mild hemoptysis.
CLINICAL TRIAL REGISTRATION
Clinical Trials Registry-India; No.: CTRI/2019/05/019337; URL: http://ctri.nic.in/Clinicaltrials/advancesearchmain.php.
Topics: Adult; Humans; Tranexamic Acid; Antifibrinolytic Agents; Pilot Projects; Hemoptysis; Patient Discharge
PubMed: 36410494
DOI: 10.1016/j.chest.2022.11.021 -
American Family Physician Feb 2022Hemoptysis is the expectoration of blood from the lower respiratory tract, usually from bronchial arteries. The most common causes are acute respiratory infections,...
Hemoptysis is the expectoration of blood from the lower respiratory tract, usually from bronchial arteries. The most common causes are acute respiratory infections, cancer, bronchiectasis, and chronic obstructive pulmonary disease. No cause is identified in 20% to 50% of cases. Hemoptysis must be differentiated from pseudohemoptysis, which is blood that originates from nasopharyngeal or gastrointestinal sources. The initial evaluation includes determining the severity of bleeding and stability of the patient and may require bronchoscopy for airway protection. Mild hemoptysis comprises more than 90% of cases and has a good prognosis, whereas massive hemoptysis has a high mortality rate. A history and physical examination can assist in identifying an etiology, but diagnostic testing is often required. Chest radiography is a good initial test, but it has limited sensitivity for determining the site and etiology of the bleeding. Computed tomography and computed tomography angiography of the chest with intravenous contrast are the preferred modalities to determine the etiology of bleeding; however, bronchoscopy may also be needed. In addition to supportive medical treatment, management should include treatment of the underlying etiology because recurrence often takes place in the absence of treatment of the identified cause. Bronchial arterial embolization is used to treat massive hemoptysis, particularly when an involved artery is noted on computed tomography angiography. Surgery is reserved for patients whose medical treatment and embolization are not effective.
Topics: Angiography; Bronchial Arteries; Bronchoscopy; Embolization, Therapeutic; Hemoptysis; Humans
PubMed: 35166503
DOI: No ID Found -
Thorax Feb 2021The heterogeneity of chronic obstructive pulmonary disease (COPD) creates many diagnostic, prognostic, treatment and management challenges, as the pathogenesis of COPD... (Review)
Review
The heterogeneity of chronic obstructive pulmonary disease (COPD) creates many diagnostic, prognostic, treatment and management challenges, as the pathogenesis of COPD is highly complex and the underlying cellular and molecular mechanisms remain poorly understood. A reliable, easy-to-measure, clinically relevant biomarker would be invaluable for improving outcomes for patients. International and national guidance for COPD suggests using blood eosinophil counts as a biomarker to help estimate likely responsiveness to inhaled corticosteroids (ICS) and, potentially, to aid effective management strategies. However, with the mechanism underlying the association between higher eosinophil levels and ICS effect unknown, use of the blood eosinophil count in COPD continues to be widely debated by the respiratory community.Two international meetings involving respiratory medicine specialists, immunologists and primary and secondary care clinicians were held in November 2018 and March 2019, facilitated and funded by GlaxoSmithKline plc. The aims of these meetings were to explore the role of eosinophils in the disease processes of COPD and as prognostic and diagnostic markers, and to identify areas of deficient knowledge that warrant further research. The consensus views of the attendees on key topics, contextualised with current literature, are summarised in this review article, with the aim of aiding ongoing research into the disease processes of COPD and the development of biomarkers to aid clinical management.Under certain conditions, eosinophils can be recruited to the lung, and increasing evidence supports a role for eosinophilic inflammation in some patients with COPD. Infiltration of eosinophils across the bronchial vascular epithelium into the airways is promoted by the actions of immunoregulatory cells, cytokines and chemokines, where eosinophil-mediated inflammation is driven by the release of proinflammatory mediators.Multiple studies and two meta-analyses suggest peripheral blood eosinophils may correlate positively with an increased likelihood of exacerbation reduction benefits of ICS in COPD. The studies, however, vary in design and duration and by which eosinophil levels are viewed as predictive of an ICS response. Generally, the response was seen when eosinophil levels were 100-300 cells/µL (or higher), levels which are traditionally viewed within the normal range. Some success with interleukin-5-targeted therapy suggests that the eosinophilic phenotype may be a treatable trait.The use of biomarkers could help to stratify treatment for COPD-the goal of which is to improve patient outcomes. Some evidence supports eosinophils as a potential biomarker of a treatable trait in COPD, though it is still lacking and research is ongoing. A unified consensus and a practical, accessible and affordable method of utilising any biomarker for COPD was thought to be of most importance. Challenges around its utilisation may include presenting a clear and pragmatic rationale for biomarker-driven therapy, guidance on ICS withdrawal between primary and secondary care and a lack of financial incentives supporting broad application in clinical practice. Future treatments should, perhaps, be more targeted rather than assuming the primary disease label (COPD or asthma) will define treatment response.
Topics: Adrenal Cortex Hormones; Biomarkers; Eosinophils; Humans; Prognosis; Pulmonary Disease, Chronic Obstructive
PubMed: 33122447
DOI: 10.1136/thoraxjnl-2020-215167 -
Seminars in Respiratory and Critical... Feb 2021Life-threatening hemoptysis (LTH) is any amount of hemoptysis that causes significant hemodynamic decompensation or respiratory distress which may lead to death if left... (Review)
Review
Life-threatening hemoptysis (LTH) is any amount of hemoptysis that causes significant hemodynamic decompensation or respiratory distress which may lead to death if left untreated. While the amount of hemoptysis that qualifies as massive hemoptysis has continued to be debated, any amount between 100 to 1,000 mL/day is considered significant. Up to 15% cases of hemoptysis are LTH and need urgent life-saving intervention. Understanding of pulmonary vascular anatomy is of paramount importance to manage LTH. The goal of treatment lies in airway protection, appropriate oxygenation, and prevention of exsanguination. Once the airway is stabilized, a quick diagnosis and control of bleeding site is targeted. This chapter highlights current practices and approach to LTH including medical management, bronchoscopic approach, and advanced therapies such as bronchial artery embolization and surgical resection. We review situations, such as bronchiectasis, vascular malformation, diffuse alveolar hemorrhage, and tracheostomy bleed and specific approach to management of these conditions in a systematic and evidence-based manner.
Topics: Bronchial Arteries; Bronchiectasis; Embolization, Therapeutic; Hemoptysis; Hemorrhage; Humans
PubMed: 32862418
DOI: 10.1055/s-0040-1714386 -
Frontiers in Immunology 2023Prosperous advances in understanding the cellular and molecular mechanisms of chronic inflammation and airway remodeling in asthma have been made over the past several... (Review)
Review
Prosperous advances in understanding the cellular and molecular mechanisms of chronic inflammation and airway remodeling in asthma have been made over the past several decades. Asthma is a chronic inflammatory disease of the airways characterized by reversible airway obstruction that is self-resolving or remits with treatment. Around half of asthma patients are "Type-2-high" asthma with overexpression of type 2 inflammatory pathways and elevated type 2 cytokines. When stimulated by allergens, airway epithelial cells secrete IL-25, IL-33, and TSLP to derive a Th2 immune response. First ILC2 followed by Th2 cells produces a series of cytokines such as IL-4, IL-5, and IL-13. T cells control IgE synthesis by secreting IL-4 to allergen-specific B cells. IL-5 promotes eosinophil inflammation, while IL-13 and IL-4 are involved in goblet cell metaplasia and bronchial hyperresponsiveness. Currently, "Type-2 low" asthma is defined as asthma with low levels of T2 biomarkers due to the lack of reliable biomarkers, which is associated with other Th cells. Th1 and Th17 are capable of producing cytokines that recruit neutrophils, such as IFN-γ and IL-17, to participate in the development of "Type-2-low" asthma. Precision medicine targeting Th cells and related cytokines is essential in the management of asthma aiming at the more appropriate patient selection and better treatment response. In this review, we sort out the pathogenesis of Th cells in asthma and summarize the therapeutic approaches involved as well as potential research directions.
Topics: Humans; Cytokines; Immunity, Innate; Interleukin-13; Interleukin-4; Interleukin-5; Asthma; Inflammation; Allergens; Th17 Cells
PubMed: 37377958
DOI: 10.3389/fimmu.2023.1149203 -
Allergy May 2024Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus-1 (DEL-1), an extracellular matrix protein, is a...
BACKGROUND
Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus-1 (DEL-1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation.
METHODS
Levels of DEL-1 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL-1 modulation of neutrophil adhesion and transepithelial migration was examined in a co-culture model in vitro. The effects of DEL-1-adenoviral vector-mediated overexpression on ovalbumin/lipopolysaccharide (OVA/LPS)-induced neutrophilic asthma were studied in mice in vivo.
RESULTS
DEL-1 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL-1 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1 ± 75.3 vs. 276.8 ± 29.36 pg/mL, p < .001) and were negatively correlated to blood neutrophils (r = -0.2881, p = .0384) and neutrophil-to-lymphocyte ratio (NLR) (r = -0.5469, p < .0001). DEL-1 concentrations in the EBC of severe asthmatic patients (113.2 ± 8.09 pg/mL) were also lower than normal subjects (193.0 ± 7.61 pg/mL, p < .001) and were positively correlated with the asthma control test (ACT) score (r = 0.3678, p = .0035) and negatively related to EBC IL-17 (r = -0.3756, p = .0131), myeloperoxidase (MPO) (r = -0.5967, p = .0055), and neutrophil elastase (NE) (r = -0.5488, p = .0009) expression in asthma patients. Neutrophil adhesion and transepithelial migration in asthma patients were associated with LFA-1 binding to ICAM-1 and inhibited by DEL-1. DEL-1 mRNA and protein expression in human bronchial epithelial cells were regulated by IL-17. Exogenous DEL-1 inhibited IL-17-enhanced neutrophil adhesion and migration. DEL-1 expression was decreased while neutrophil infiltration was increased in the airway of a murine model of neutrophilic asthma. This was prevented by DEL-1 overexpression.
CONCLUSIONS
DEL-1 down-regulation leads to increased neutrophil migration across bronchial epithelial cells and is associated with neutrophilic airway inflammation in asthma.
Topics: Animals; Female; Humans; Mice; Asthma; Calcium-Binding Proteins; Cell Adhesion; Cell Adhesion Molecules; Disease Models, Animal; Inflammation; Neutrophils; Transendothelial and Transepithelial Migration
PubMed: 37681299
DOI: 10.1111/all.15882