Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perennial rhinitis and asthma are clinical syndromes representing a range of overlapping pathologies; accurate classification should therefore precede any comparison. Although the sinonasal cavities, trachea and bronchi have a common respiratory mucosa, there are also anatomical differences. For example, the nose has a capacitance vessel network and the lower airways possess smooth muscle, both of which are responsive to neurohumoral influences. The prevalence of rhinitis and asthma has increased over the last three decades. Rhinitis occurs in around 75% of allergic asthmatics while 20% of perennial allergic rhinitics develop asthma. Eosinophils, and their associated proteins and cytokines, may play a central role in both perennial rhinitis and asthma with and without atopy. The characteristic pathology of asthma can be summarized as a chronic, desquamating, eosinophilic bronchitis. Non-allergic rhinitis with eosinophilia is recognized, but without consistent evidence of epithelial damage. Eosinophils are also present in rhinosinusitis with polyposis, particularly in patients with aspirin sensitivity, in whom asthma also often occurs. Increased mast cell activation and mediator release is evident in both perennial rhinitis and asthma following allergen challenge. The importance of mast cells in non-atopic asthma and polyposis is also recognized. Adhesion molecules may also be upregulated, with an increased number and activation of TH2 lymphocytes. However, allergen-resultant T-cell activation may be less marked in the nose than in the lung. Autonomic imbalance also plays a role in both conditions via changes in neural tone to effector tissues, release of neuropeptides, and interplay with cellular recruitment. Pharmacological manipulation of rhinitis and asthma also illustrates the pathological similarities and differences.
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PMID:The link between the nose and lung, perennial rhinitis and asthma--is it the same disease? 921 59

Inflammation with infiltrations of eosinophils and mast cells into the walls of airways is considered to increase airway hyperresponsiveness (AHR), which in turn characterizes asthma. We present a child with AHR in whom the clinical course of asthma was related to eosinophilic bronchitis. Our patient was admitted at age 6 months with bronchiolitis and at age 4 years with asthma. Inhaled corticosteroids were begun at age 7 years. At age 8 he developed a meningeal sarcoma. While on chemotherapy, his asthma symptoms resolved and he no longer required prophylactic asthma treatment. After 14 months off all chemotherapy, he again had mild episodic asthma. While receiving chemotherapy for malignancy, he had an admission with a coagulase negative staphylococcal bacteremia. During sputum induction with 4.5% saline, he developed cough, wheeze, and a 20% reduction in peak expiratory flow (220 to 180 L/min) that reversed after treatment with salbutamol. The sputum cell count was 1.7 x 10(6)/ml with 1.1 x 10(6) being neutrophils. Two weeks later and prior to the induction of the second sputum, a 21% increase in FEV1 was recorded after bronchodilator inhalation (82% to 99% of predicted). The second sputum contained 2.7 x 10(6)/ml cells with 1.6 x 10(6)/ml neutrophils. Neither eosinophils nor mast cells were identified in the sputum. A third sputum obtained 14 months after the cessation of chemotherapy showed a sputum cell count of 16 x 10(6)/ml, with 11.6 x 10(6) neutrophils and 0.4 x 10(6) eosinophils; no mast cells were detected. A reversible 15% reduction in FEV1 was detected on hypertonic saline challenge testing. This boy had persistent airway hyperreactivity and reversible airways obstruction on three occasions during and following chemotherapy. When he developed asthma symptoms, his sputum contained neutrophils and eosinophils; while on chemotherapy his sputum did not contain eosinophils and he was symptom-free and off all asthma therapy. One can speculate that chemotherapy for malignancy can induce a remission in asthma symptoms but not AHR, and remission in symptoms is associated with a lack of eosinophilic or mast cell infiltrates in the sputum.
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PMID:Chemotherapy for malignancy induces a remission in asthma symptoms and airway inflammation but not airway hyperresponsiveness. 971 Feb 82

Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.
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PMID:New insights into the relationship between airway inflammation and asthma. 1214 12

In a recent study, the difference between asthma and eosinophilic bronchitis (a condition characterized by cough but not airway hyperresponsiveness or airflow obstruction) was infiltration of airway smooth muscle (ASM) by mast cells. Mast cells produce a variety of lipid mediators, chemokines, cytokines, and enzymes that may interact with ASM cells to cause hyperreactivity to constrictive stimuli and proliferation, and activated ASM can produce stem cell factor and other chemokines, cytokines, and growth factors that may act in recruitment, differentiation, and retention of mast cells. Mast cell infiltration of the airways in asthma is T-cell-dependent, and TH2 cytokines from T cells and other sources act in mast cell expansion from circulating and tissue precursors. The recent data on interactions of mast cells and ASM suggest that this could be an important contributor to airway hyperresponsiveness in asthma. Why this occurs in asthma and how it is sustained remain to be established.
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PMID:The role of the mast cell in asthma: induction of airway hyperresponsiveness by interaction with smooth muscle? 1524 45

Cough variant asthma and the closely related corticosteroid responsive cough syndromes eosinophilic bronchitis and atopic cough are common causes of chronic cough. The diagnosis is often not overt but detailed investigation of airway responsiveness and airway inflammation can be helpful. Cough variant asthma, eosinophilic bronchitis and atopic cough are all associated with eosinophilic airway inflammation, which is similar to that seen in non-cough predominant asthma. However, evidence of activated mast cells and increased concentrations of mast cell products appears to be confined to the conditions associated with cough, suggesting a role for mast cell degranulation in the superficial airway structures in the pathogenesis of cough. Cough variant asthma is typically corticosteroid responsive; leukotriene antagonists and antihistamines also help. Further study of this interesting asthma variant may increase our understanding of the relationship between airway inflammation and airway dysfunction.
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PMID:Cough and asthma. 1556 83

Asthma is characterized by variable airflow obstruction, airway hyperresponsiveness, and airway inflammation. Mast cells have long been thought to play a central role in asthma through their ability to release proinflammatory mediators, but this role has been questioned by the lack of efficacy of antihistamines and so-called mast cell-stabilizing drugs. Recent comparisons between the immunopathology of asthma and eosinophilic bronchitis have led to the re-emergence of the mast cell as a pivotal cell in asthma. Eosinophilic bronchitis is a condition in which patients present with chronic cough, and shares many of the inflammatory features associated with asthma, but without variable airflow obstruction or airway hyperresponsiveness. The only striking pathologic difference between these conditions is that, in asthma, the airway smooth muscle is infiltrated by mast cells. This suggests that interactions between mast cells and airway smooth muscle cells are critical for the development of the disordered airway physiology in asthma.
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PMID:The re-emergence of the mast cell as a pivotal cell in asthma pathogenesis. 1568 13

There is compelling evidence that human mast cells contribute to the pathophysiology of asthma. Mast cells, but not T cells or eosinophils, localize within the bronchial smooth muscle bundles in patients with asthma but not in normal subjects or those with eosinophilic bronchitis, a factor likely to be important in determining the asthmatic phenotype. The mechanism of mast cell recruitment by asthmatic airway smooth muscle involves the CXCL10/CXCR3 axis, and several mast cell mediators have profound effects on airway smooth muscle function. The autacoids are established as potent bronchoconstrictors, whereas the proteases tryptase and chymase are being demonstrated to have a range of actions consistent with key roles in inflammation, tissue remodeling, and bronchial hyperresponsiveness. IL-4 and IL-13, known mast cell products, also induce bronchial hyperresponsiveness in the mouse independent of the inflammatory response and enhance the magnitude of agonist-induced intracellular Ca2+ responses in cultured human airway smooth muscle. There are therefore many pathways by which the close approximation of mast cells with airway smooth muscle cells might lead to disordered airway smooth muscle function. Mast cells also infiltrate the airway mucous glands in subjects with asthma, showing features of degranulation, and a positive correlation with the degree of mucus obstructing the airway lumen, suggesting that mast cells play an important role in regulating mucous gland secretion. The development of potent and specific inhibitors of mast cell secretion, which remain active when administered long-term to asthmatic airways, should offer a novel approach to the treatment of asthma.
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PMID:The role of the mast cell in the pathophysiology of asthma. 1675 Sep 87

Asthma and nonasthmatic eosinophilic bronchitis are among the most common causes of chronic cough, accounting for about 25 and 10% of cases, respectively. Chronic cough due to asthma may present in isolation in which case it is known as cough-variant asthma. Nonasthmatic eosinophilic bronchitis is characterized by the presence of eosinophilic airway inflammation in the absence of variable airflow obstruction or airway hyperresponsiveness. Both conditions share many immunopathological features with the exceptions to date of mast cell infiltration into the airway smooth muscle, increased IL-13 expression, and narrowing and thickening of the airway wall, which are features reserved to asthma. In most cases the trigger that causes the cough is uncertain. However, removal of potential triggers is important to consider, in particular with respect to occupational exposure to known sensitisers. In both conditions there is subjective and objective improvement following treatment with inhaled corticosteroids, which is associated with the presence of an airway eosinophilia. Whether eosinophilic inflammation is the cause of cough or an epiphenomenon is uncertain, but the failure of anti-IL-5 to modify cough in asthma has questioned a causal association. In asthma, beta-agonist theophylline, leukotriene receptor antagonist, and oral corticosteroid therapy improve cough. In noneosinophilic bronchitis, some patients require oral corticosteroids but the benefit of other additional therapies is unknown. In general, response to therapy in both conditions is very good and the limited long-term data available suggest that both usually have a benign course, although in some cases persistent airflow obstruction may occur.
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PMID:Cough due to asthma and nonasthmatic eosinophilic bronchitis. 1966 8

Among the most common causes of chronic cough are asthma (25%) and nonasthmatic eosinophilic bronchitis (10%). In asthma, cough may present as an isolated symptom, in which case it is known as cough variant asthma. Variable airflow obstruction and airway hyper-responsiveness are cardinal features of asthma, which are absent in nonasthmatic eosinophilic bronchitis. The presence of eosinophilic airway inflammation is a common feature of asthma and is a diagnostic criterion for nonasthmatic eosinophilic bronchitis. At a cellular level, mast cell infiltration into the airway smooth muscle bundle, narrowing of the airway wall, and increased interleukin-13 expression are features of asthma and not nonasthmatic eosinophilic bronchitis. In most cases, the trigger that causes the cough is uncertain, but occasionally occupational exposure to a sensitizer is identified, and avoidance is recommended. In both conditions, there is improvement following treatment with inhaled corticosteroids, which is associated with the presence of an airway eosinophilia and increased exhaled nitric oxide. Generally, response to therapy in both conditions is very good, and the limited long-term data available suggest that both usually have a benign course, although in some cases fixed airflow obstruction may occur.
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PMID:Cough due to asthma, cough-variant asthma and non-asthmatic eosinophilic bronchitis. 2017 62

: Although there is much circumstantial evidence implicating eosinophils as major orchestrators in the pathophysiology of asthma, recent studies have cast doubt on their importance. Not only does anti-interleukin-5 treatment not alter the course of the disease, but some patients with asthma do not have eosinophils in their airways, whereas patients with eosinophilic bronchitis exhibit a florid tissue eosinophilia but do not have asthma. In contrast, mast cells are found in all airways and localize specifically to key tissue structures such as the submucosal glands and airway smooth muscle within asthmatic bronchi, irrespective of disease severity or phenotype. Here they are activated and interact exclusively with these structural cells via adhesive pathways and through the release of soluble mediators acting across the distance of only a few microns. The location of mast cells within the airway smooth muscle bundles seems particularly important for the development and propagation of asthma, perhaps occurring in response to, and then serving to aggravate, an underlying abnormality in asthmatic airway smooth muscle function. Targeting this mast cell-airway smooth muscle interaction in asthma offers exciting prospects for the treatment of this common disease.
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PMID:Asthma: eosinophil disease, mast cell disease, or both? 2052 29


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