Eosinopenia | |
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An eosinophil in peripheral blood | |
Specialty | Hematology |
Eosinopenia is a condition where the number of eosinophils, a type of white blood cell, in circulating blood is lower than normal. [1] Eosinophils are a type of granulocyte and consequently from the same cellular lineage as neutrophils, basophils, and mast cells. [1] [2] Along with the other granulocytes, eosinophils are part of the innate immune system and contribute to the defense of the body from pathogens. The most widely understood function of eosinophils is in association with allergy and parasitic disease processes, though their functions in other pathologies are the subject of ongoing research. [3] The opposite phenomenon, in which the number of eosinophils present in the blood is higher than normal, is known as eosinophilia.
The definition of eosinopenia varies in clinical practice, and normal eosinophil levels vary among the population. [4] One common definition is an absolute eosinophil count of less than 50 cells/μLiter of blood. [5] [6] [7] Other definitions include less than 10 cells/μLiter, while some clinical laboratories classify 0 cells/μLiter as within the acceptable range. [3] The diagnosis of eosinopenia is challenging due to the low number of eosinophils normally present in blood and the fluctuations in eosinophil levels throughout the day. [1] [4]
Eosinopenia is associated with several disease states and conditions, including inflammation and sepsis, endogenous catecholamines, and use of glucocorticoids. [1] There are also medications that deliberately target eosinophils in order to treat eosinophil-mediated diseases, causing drug-induced eosinopenia. [8]
Unlike other granulocytes, eosinophil count decreases in response to release of catecholamines. [1] A hypothesized mechanism contributing to this change is decreased eosinophil production by the bone marrow in response to catecholamines. Epinephrine is also believed to stimulate receptors through the β-adrenergic pathway to decrease eosinophils in peripheral blood. [1]
Use of glucocorticoids has been known to affect several blood components, including decreasing eosinophils. [1] This cause of this effect is multifactorial. Glucocorticoids decrease the number of eosinophils in the circulation by causing them to exit the bloodstream and move into the tissue. The number of eosinophils released by the bone marrow is suppressed by glucocorticoids. It has also been theorized that glucocorticoids eliminate eosinophils in the blood by causing them to undergo apoptosis. [1]
Due to the harmful role of eosinophils in diseases such as eosinophilic asthma and eosinophilic granulomatosis with polyangiitis, drugs have been developed to purposefully diminish eosinophils in order to alleviate symptoms. [8] Some examples of these drugs include mepolizumab, reslizumab, and benralizumab. [9]
Although eosinopenia has long been recognized as a laboratory marker for infection, the mechanism for this phenomenon is currently unknown. [2] [10] One potential explanation is that eosinopenia may be an indication of immune dysregulation. [5] In the body's response to a pathogen, the immune system activates "type 1 inflammation" which mobilizes certain immune cells to clear pathogens. This response can produce collateral damage of host tissue. To balance this, eosinophils are one component of "type 2 inflammation" that can begin to mend the tissue. As a result, eosinopenia may be a sign that the body has not mounted an appropriate type 2 inflammation response, so it may be doing more damage than normal to surrounding tissue. [5] Another theory postulates that eosinophils in sepsis travel out of the blood and may contribute to tissue damage, causing relative eosinopenia in the blood with elevated eosinophils in affected tissue. [5] Eosinophils have been shown to have a cytotoxic effect on bacteria, which contributes to surrounding tissue damage. [2] [3]
Persistent eosinopenia in sepsis is independently associated with worse clinical outcomes, including increased mortality and increased rates of hospital readmission. [5] It is unknown if eosinophils contribute directly to clearing pathogens in sepsis or if their absence is only an indicator that the immune system is dysregulated. [5] The causative role of eosinopenia to poor survival in sepsis, if it exists, has yet to be established. [5]
The use of eosinopenia as a diagnostic tool in sepsis is debatable. [10] Although there is a high incidence of eosinopenia in sepsis, it is not more effective as a biomarker than more commonly utilized indicators of sepsis, such as procalcitonin (PCT) and C-reactive protein (CRP). [10] One advantage it does have compared these biomarkers is that it is generally a faster and cheaper test. [10]
Eosinopenia is a possible laboratory finding in patients who present with COVID-19 and is associated with disease severity, though it is not pathognomonic. [3] One study found that 53% of patients admitted for COVID-19 had eosinopenia at time of admission; in another study of fatal COVID-19 cases, 81% of patients had eosinopenia. [8] In patients with eosinopenia who present with COVID-19, eosinophil counts usually return to normal levels as they recover. [3] [8] In fatal cases of COVID-19, eosinophil counts remain low for the duration of the disease. [3] It is unclear if this eosinopenia contributes to the disease course. [8] The presence of eosinopenia has been included in several risk stratification scores, such as the COVID-19-REAL score and PARIS score, which both use different definitions of eosinopenia as part of several factors to screen for COVID-19. [3] Eosinopenia has also been proposed as a marker for distinguishing COVID-19 from influenza virus infection, since patients diagnosed with COVID-19 have slightly lower eosinophil counts than patients diagnosed with influenza. [3]
Though the most widely known role of eosinophils is in regards to allergy and parasitic infections, recent research has found evidence for an antiviral function of eosinophils. [3] [8] Research has shown that mice that were genetically modified to have more eosinophils than normal were able to combat RSV infection more effectively than normal mice, while genetically eosinophil-depleted mice were less effective. [8] The precise mechanism for this function is undetermined, though some elements of the eosinophil response to viruses include nitric oxide production and inactivation of viruses. [3] [8] Though there is early research on the role of eosinophils in response to respiratory viruses, this function is still uncertain and requires additional research in order to define the extent to which eosinophils participate in antiviral immune response as well as clinical relevancy. [8]
The cause of eosinopenia in COVID-19 infection is also unknown at this time. Some proposed contributory mechanisms include increased movement of eosinophils out of the blood into tissue, decreased generation or output of eosinophils from the bone barrow, and shorter lifespan within the blood. [3] One aspect of severe COVID-19 that may contribute to eosinopenia is the cytokine storm. In this disorder, cytokines may interact with eosinophils and modulate their activity, movement, or survival. [3]
In patients admitted to the hospital with exacerbations of chronic obstructive pulmonary disease (COPD), eosinopenia is associated with increased mortality, increased rate of ventilation, and longer hospital stays. [2] Eosinopenia is one of the five components included as part of the DECAF score, which predicts short-term mortality in patients with acute exacerbations of COPD. [7] [11] This score has been used as a specific screening tool for stratifying low- and high-risk patients, supporting the value of monitoring eosinopenia during management of exacerbations of COPD. [2] [11]
Inflammation is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function.
Sputum is mucus that is coughed up from the lower airways. In medicine, sputum samples are usually used for a naked eye examination, microbiological investigation of respiratory infections and cytological investigations of respiratory systems. It is crucial that the specimen does not include any mucoid material from the nose or oral cavity.
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply.
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 5×108/L (500/μL). Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 × 109/L (i.e. 1,500/μL). The hypereosinophilic syndrome is a sustained elevation in this count above 1.5 × 109/L (i.e. 1,500/μL) that is also associated with evidence of eosinophil-based tissue injury.
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte and how they work is not fully understood. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, and heparin that prevents blood clotting, although there are less than that found in mast cell granules. Mast cells were once thought to be basophils that migrated from the blood into their resident tissues, but they are now known to be different types of cells.
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis, is an extremely rare autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy).
Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath.
Eosinophilic pneumonia is a disease in which an eosinophil, a type of white blood cell, accumulates in the lungs. These cells cause disruption of the normal air spaces (alveoli) where oxygen is extracted from the atmosphere. Several different kinds of eosinophilic pneumonia exist and can occur in any age group. The most common symptoms include cough, fever, difficulty breathing, and sweating at night. Eosinophilic pneumonia is diagnosed by a combination of characteristic symptoms, findings on a physical examination by a health provider, and the results of blood tests and X-rays. Prognosis is excellent once most eosinophilic pneumonia is recognized and treatment with corticosteroids is begun.
Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus that involves eosinophils, a type of white blood cell. In healthy individuals, the esophagus is typically devoid of eosinophils. In EoE, eosinophils migrate to the esophagus in large numbers. When a trigger food is eaten, the eosinophils contribute to tissue damage and inflammation. Symptoms include swallowing difficulty, food impaction, vomiting, and heartburn.
Stress hormones are secreted by endocrine glands to modify one's internal environment during the times of stress. By performing various functions such as mobilizing energy sources, increasing heart rate, and downregulating metabolic processes which are not immediately necessary, stress hormones promote the survival of the organism. The secretions of some hormones are also downplayed during stress. Stress hormones include, but are not limited to:
Eosinophilic gastroenteritis, also known as eosinophilic enteritis, is a rare and heterogeneous condition characterized by patchy or diffuse eosinophilic infiltration of gastrointestinal (GI) tissue, first described by Kaijser in 1937. Presentation may vary depending on location as well as depth and extent of bowel wall involvement and usually runs a chronic relapsing course. It can be classified into mucosal, muscular and serosal types based on the depth of involvement. Any part of the GI tract can be affected, and isolated biliary tract involvement has also been reported. The stomach is the organ most commonly affected, followed by the small intestine and the colon.
White blood cells, also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes: granulocytes, lymphocytes and monocytes.
Eosinophilic bronchitis (EB) is a type of airway inflammation due to excessive mast cell recruitment and activation in the superficial airways as opposed to the smooth muscles of the airways as seen in asthma. It often results in a chronic cough. Lung function tests are usually normal. Inhaled corticosteroids are often an effective treatment.
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. GOLD 2024 defined COPD as a heterogeneous lung condition characterized by chronic respiratory symptoms due to abnormalities of the airways and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction.
Dupilumab, sold under the brand name Dupixent, is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as atopic dermatitis (eczema), asthma and nasal polyps which result in chronic sinusitis. It is also used for the treatment of eosinophilic esophagitis and prurigo nodularis.
Eosinophilic myocarditis is inflammation in the heart muscle that is caused by the infiltration and destructive activity of a type of white blood cell, the eosinophil. Typically, the disorder is associated with hypereosinophilia, i.e. an eosinophil blood cell count greater than 1,500 per microliter. It is distinguished from non-eosinophilic myocarditis, which is heart inflammation caused by other types of white blood cells, i.e. lymphocytes and monocytes, as well as the respective descendants of these cells, NK cells and macrophages. This distinction is important because the eosinophil-based disorder is due to a particular set of underlying diseases and its preferred treatments differ from those for non-eosinophilic myocarditis.
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Donna Elizabeth Davies is a British biochemist and professor of respiratory cell and molecular biology at the University of Southampton. In 2003, Davies was the co-founder of Synairgen, an interferon-beta drug designed to treat patients with asthma and chronic obstructive pulmonary disease.
Prostaglandin inhibitors are drugs that inhibit the synthesis of prostaglandin in human body. There are various types of prostaglandins responsible for different physiological reactions such as maintaining the blood flow in stomach and kidney, regulating the contraction of involuntary muscles and blood vessels, and act as a mediator of inflammation and pain. Cyclooxygenase (COX) and Phospholipase A2 are the major enzymes involved in prostaglandin production, and they are the drug targets for prostaglandin inhibitors. There are mainly 2 classes of prostaglandin inhibitors, namely non- steroidal anti- inflammatory drugs (NSAIDs) and glucocorticoids. In the following sections, the medical uses, side effects, contraindications, toxicity and the pharmacology of these prostaglandin inhibitors will be discussed.
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