Mast Cell and Muscle Interactions in Animals and Man
William J. Snape, Stephen M. Collins in Effects of Immune Cells and Inflammation on Smooth Muscle and Enteric Nerves, 2020
Diarrhea is a cardinal symptom of Inflammatory Bowel Disease (IBD) and is likely to result, at least in part, from changes in motility. These changes in motility may result from a series of immunophysiological interactions which occur between immunocompetent cells and the smooth muscle and nerves of the gut1. Mast cells have been implicated in the pathophysiology of IBD; mast cells are present in the gut muscle of patients with non-inflammatory bowel disease and are increased in numbers in IBD patients2,3. There is evidence of mast cell degranulation in close proximity to the smooth muscle and nerves in inflamed segments of Crohn’s disease3. Altered functional activity of mast cells in IBD is suggested from studies on mast cells isolated from the bowel epithelium of IBD patients4; mast cells isolated from the mucosa of patients with Crohn’s disease release significantly more histamine and prostaglandins than control when challenged with preparations of epithelial cell complexes or anti-human IgE4. Reports have shown that in some cases treatment with disodium cromoglycate, a mast cell stabilizer, has improved IBD symptoms5,6.
Allergic Diseases of the Eye
Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial in Textbook of Allergy for the Clinician, 2021
For patients presenting with acute symptoms, it is usual to prescribe a moderately potent topical steroid with low ocular penetration, such as fluorometholone or loteprednol, three or four times a day for around two weeks. Along with this a mast cell stabilizer or a dual action drug is started as a preventive medication, intended for long term instillation (Mantelli et al. 2007). Prophylactic treatment is usually continued through the expected period of allergen exposure. As drugs such as olopatadine and alcaftadine are available as once-a-day preparations for this purpose, compliance is usually good.
Main Classes of Drugs
Jerome Z. Litt, Neil H. Shear in Litt's Drug Eruption & Reaction Manual, 2017
Mast cell stabilizerCromolynLodoxamideNedocromilPemirolast
Pharmacological treatments for eosinophilic esophagitis: current options and emerging therapies
Published in Expert Review of Clinical Immunology, 2020
Alfredo J Lucendo
Despite EoE being recognized as an allergic disease that shares many common physiological and clinical aspects with other Th2-type atopic diseases, the effect of antiallergic drug treatments on EoE has been disappointing. Thus, cromolyn, a mast cell stabilizer with poor absorption and almost nonexistent side effects, prevents the release of inflammatory mediators such as histamine from mast cells. In systemic mastocytosis, cromolyn is of choice to treat associated gastrointestinal symptoms, and in asthma, cromolyn significantly decreases activated eosinophils in bronchial mucosa, similarly to fluticasone propionate and better than placebo or beta-2 agonists [114,115]. However, no benefit from cromolyn on symptoms or inflammation was described for children with EoE in early case reports [116]. Recently, an RCT that assessed viscous oral cromolyn for EoE in 16 children showed no changes in esophageal or blood eosinophilia after 8-week treatment, and no significant benefit over symptoms compared to placebo was noted [117].
Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial
Published in Gut Microbes, 2022
Lucas Wauters, Luka Van Oudenhove, Alison Accarie, Karlien Geboers, Hannelore Geysen, Joran Toth, Anja Luypaerts, Kristin Verbeke, Tamara Smokvina, Jeroen Raes, Jan Tack, Tim Vanuytsel
Interestingly, preclinical studies have identified increased intestinal permeability as the potential link between psychological stress and mucosal immune activation via enhanced passage of antigens,10 with improvement after probiotics.11,12 Increased intestinal permeability has been demonstrated in IBS and IBD with mucosal eosinophil and/or mast cell activation.13,14 We showed that a social-evaluative stressor (public speech) and intravenous administration of CRH increased small intestinal permeability quantified by the urinary lactulose-to-mannitol ratio (LMR) in healthy students. This effect was abolished after pre-treatment with the mast cell stabilizer disodium-cromoglycate (DSCG).15 Recent studies demonstrated that both commensal and lactic acid-producing bacteria can enhance mucosal barrier integrity in mice inflammation models, with a similar protective effect of L. rhamnosus CNCM I-3690 compared to Faecalibacterium prausnitzii A2–165.16 Furthermore, anti-inflammatory effects were reported for L. rhamnosus in these models,17,18 making this an important candidate for further human research. However, no studies have investigated the potential role of bacteria in general or L. rhamnosus in particular for increased permeability during psychological stress in humans.
Pharmacotherapeutic Options for Chronic Refractory Cough
Published in Expert Opinion on Pharmacotherapy, 2020
Woo-Jung Song, Kian Fan Chung
Sodium cromoglycate was not initially developed for cough, but a novel inhaled high-dose formulation, PA101 (now RVT-1601), has recently shown promising anti-tussive effects in patients with idiopathic pulmonary fibrosis (IPF). Historically, cromoglycate was classified as a mast cell stabilizer because of its activity to inhibit mast cell degranulation, but the mechanisms of action are likely to be complex [76]. It has an inhibitory effect on airway sensory nerve activation, probably via the G-protein coupled receptor GPR35 [77,78]. In a recent PoC placebo-controlled trial, a 2-week treatment with PA101 significantly reduced objective daytime cough frequency (31.1%; p = 0.024) in patients with IPF, but not in patients with CRC (p = 0.31), suggesting that the antitussive effect of PA101 is likely to be disease-specific [79] (Table 2). Interestingly, there were no significant improvements in PROs, such as LCQ score (least square [LS] mean difference of 1.1; 95% CI of −0.18 to 2.33; p = 0.09) and cough severity VAS score (LS mean difference of −8.5; 95% CI of −19.65 to 2.70; p = 0.13) in IPF patients (Figure 1), although both daytime cough frequency ≥ 15 coughs/hour and cough VAS ≥ 40 mm were required for the patient inclusion. Meanwhile, there were no significant differences in patient characteristics, such as age, sex, cough duration, IPF duration, or the proportion of patients receiving IPF treatment, between responders and nonresponders in the IPF group (responder defined as a reduction in daytime cough frequency greater than 30%). There were also no serious adverse events reported during the trial [79]. Currently, a larger phase 2b dose-ranging trial in patients with IPF-associated cough is ongoing (EudraCT Number: 2018-004447-23).
Related Knowledge Centers
- Allergic Conjunctivitis
- Allergic Rhinitis
- Asthma
- Degranulation
- Histamine
- Immunoglobulin E
- Allergy
- Mast Cell
- Medication
- Mastocytosis