137 results found
Johnson CL, Rogers DF, 2016, WHY IS ERDOSTEINE RECOMMENDED AS A TREATMENT FOR ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS? A SYSTEMATIC REVIEW OF CLINICAL TRIALS, THORAX, Vol: 71, Pages: A157-A157, ISSN: 0040-6376
Ha EVS, Rogers DF, 2016, Novel Therapies to Inhibit Mucus Synthesis and Secretion in Airway Hypersecretory Diseases, PHARMACOLOGY, Vol: 97, Pages: 84-100, ISSN: 0031-7012
Tildy BE, Rogers DF, 2015, Therapeutic Options for Hydrating Airway Mucus in Cystic Fibrosis, PHARMACOLOGY, Vol: 95, Pages: 117-132, ISSN: 0031-7012
Seagrave J, Albrecht HH, Hill DB, et al., 2012, Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells, Respiratory Research, Vol: 13, ISSN: 1465-993X
BackgroundTherapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC.MethodsAfter IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10–300 μM) in the continued presence of IL-13. Cellular and secreted MUC5AC, mucociliary transport rates (MTR), mucus rheology at several time points, and the antioxidant capacity of the drugs were assessed.ResultsIL-13 increased MUC5AC content (~25%) and secretion (~2-fold) and decreased MTR, but only slightly affected the G’ (elastic) or G” (viscous) moduli of the secretions. GGE significantly inhibited MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 μM, respectively). NAC or Amb were less effective. All drugs increased MTR and decreased G’ and G” relative to IL-13 alone. Cell viability was not affected and only NAC exhibited antioxidant capacity.ConclusionsThus, GGE effectively reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus rheology, and may therefore be useful in treating airway mucus hypersecretion and mucostasis in airway diseases.
Madge NJ, Donnelly LE, Rogers DF, 2012, Effect of neutrophil supernatants on ex vivo small airway contractility in COPD, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Lai H, Rogers DF, 2010, New Pharmacotherapy for Airway Mucus Hypersecretion in Asthma and COPD: Targeting Intracellular Signaling Pathways, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Vol: 23, Pages: 219-231, ISSN: 1941-2711
Lai H, Rogers DF, 2010, Mucus hypersecretion in asthma: intracellular signalling pathways as targets for pharmacotherapy, CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 10, Pages: 67-76, ISSN: 1528-4050
ROGERS DF, ALTON E, DEWAR A, et al., 2009, IMPAIRED STIMULUS-EVOKED MUCUS SECRETION IN CYSTIC-FIBROSIS BRONCHI, EXPERIMENTAL LUNG RESEARCH, Vol: 19, Pages: 37-53, ISSN: 0190-2148
Foster KA, Adams EJ, Rogers DF, 2009, Understanding botulinum neurotoxin mechanism of action and structure to enhance therapeutics and improve care, Botulinum Toxin: Therapeutic Clinical Practice & Science, Editors: Jankovic, Albanese, Atassi, Dolly, Hallett, Mayer
Rousseau K, Kirkham S, Johnson L, et al., 2008, Proteomic analysis of polymeric salivary mucins: no evidence for MUC19 in human saliva, BIOCHEMICAL JOURNAL, Vol: 413, Pages: 545-552, ISSN: 0264-6021
Donnelly LE, Rogers DF, 2008, Novel targets and drugs in inflammatory lung disease, CURRENT OPINION IN PHARMACOLOGY, Vol: 8, Pages: 219-221, ISSN: 1471-4892
Rogers DF, 2008, Airway mucus hypersecretion in asthma and COPD: not the same?, Asthma and COPD: Basic Mechanisms and Clinical Management, 2nd Edition, Editors: Barnes, Drazen, Rennard, Thomson
Rogers DF, 2008, Mucus and mucociliary clearance in asthma and allergic rhinitis, Allergy and Allergic Diseases, 2nd Edition, Editors: Kay, Kaplan, Bousquet, Holt
Grandhi S, Donnelly LE, Rogers DF, 2007, Phytoceuticals: the new 'physic garden' for asthma and chronic obstructive pulmonary disease., Expert Rev Respir Med, Vol: 1, Pages: 227-246
Phytoceuticals (non-nutritional but beneficial plant chemicals) merit investigation as pharmacotherapy for asthma and chronic obstructive pulmonary disease (COPD). Although asthma is mostly treated adequately, COPD is not. Thus, there is a need for new drugs with improved therapeutic benefit, especially in COPD. Recent interest in herbal remedies has redirected attention towards plants as sources of improved treatments for lung disease. Phytoceuticals from a variety of plants and plant products, including butterbur, English ivy, apples, chocolate, green tea and red wine, demonstrate broad-spectrum pharmacotherapeutic activities that could be exploited in the clinic. Well-designed clinical trials are required to determine whether these beneficial activities are reproduced in patients, with the prospect that phytoceuticals are the new physic garden for asthma and COPD.
Rogers DF, 2007, Mucoactive agents for airway mucus hypersecretory diseases, 39th Conference of the Respiratory-Care-Journal, Pages: 1176-1197
Airway mucus hypersecretion is a feature of a number of severe respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). However, each disease has a different airway inflammatory response, with consequent, and presumably linked, mucus hypersecretory phenotype. Thus, it is possible that optimal treatment of the mucus hypersecretory element of each disease should be disease-specific. Nevertheless, mucoactive drugs are a longstanding and popular therapeutic option, and numerous compounds (eg, N-acetyleysteine, erdosteine, and ambroxol) are available for clinical use worldwide. However, rational recommendation of these drugs in guidelines for management of asthma, COPD, or CF has been hampered by lack of information from well-designed clinical trials. In addition, the mechanism of action of most of these drugs is unknown. Consequently, although it is possible to categorize them according to putative mechanisms of action, as expectorants (aid and/or induce cough), mucolytics (thin mucus), mucokinetics (facilitate cough transportability), and mucoregulators (suppress mechanisms underlying chronic mucus hypersecretion, such as glueocorticosteroids), it is likely that any beneficial effects are due to activities other than, or in addition to, effects on mucus. It is also noteworthy that the mucus factors that favor mucociliary transport (eg, thin mucus gel layer, "ideal" sol depth, and elasticity greater than viscosity) are opposite to those that favor cough effectiveness (thick mucus layer, excessive sol height, and viscosity greater than elasticity), which indicates that different mucoactive drugs would be required for treatment of mucus obstruction in proximal versus distal airways, or in patients with an impaired cough reflex. With the exception of mucoregulatory agents, whose primary action is unlikely to be directed against mucus, well-designed clinical trials are required to unequivocally determine the e
Rogers DF, 2007, Physiology of airway mucus secretion and pathophysiology of hypersecretion, RESPIRATORY CARE, Vol: 52, Pages: 1134-1149, ISSN: 0020-1324
Rogers DF, 2007, Physiology of airway mucus secretion and pathophysiology of hypersecretion, 39th Conference of the Respiratory-Care-Journal, Pages: 1134-1149
Mucus secretion is the first-line defense against the barrage of irritants that inhalation of approximately 500 L of air an hour brings into the lungs. The inhaled soot, dust, microbes, and gases can all damage the airway epithelium. Consequently, mucus secretion is extremely rapid, occurring in tens of milliseconds. In addition, mucus is held in cytoplasmic granules in a highly condensed state in which high concentrations of Ca2+ nullify the repulsive forces of the highly polyanionic mucin molecules. Upon initiation of secretion and dilution of the Ca2+, the repulsion forces of the mucin molecules cause many-hundred-fold swelling of the secreted mucus, to cover and protect the epithelium. Secretion is a highly regulated process, with coordination by several molecules, including soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) proteins, myristoylated alanine-rich C kinase substrate (MARCKS), and Munc proteins, to dock the mucin granules to the secretory cell membrane prior to exocytosis. Because mucus secretion appears to be such a fundamental airway homeostatic process, virtually all regulatory and inflammatory mediators and interventions that have been investigated increase secretion acutely. When given longer-term, many of these same mediators also increase mucin gene expression and mucin synthesis, and induce goblet cell hyperplasia. These responses induce (in contrast to the protective effects of acute secretion) long-term, chronic hypersecretion of airway mucus, which contributes to respiratory disease. In this case the homeostatic, protective function of airway mucus secretion is lost, and, instead, mucus hypersecretion contributes to pathophysiology of a number of severe respiratory conditions, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Rogers DF, 2007, Mucoactive agents for airway mucus hypersecretory diseases, RESPIRATORY CARE, Vol: 52, Pages: 1176-1197, ISSN: 0020-1324
Gwilt CR, Donnelly LE, Rogers DF, 2007, The non-neuronal cholinergic system in the airways: An unappreciated regulatory role in pulmonary inflammation?, PHARMACOLOGY & THERAPEUTICS, Vol: 115, Pages: 208-222, ISSN: 0163-7258
Rogers DF, 2007, Composition and function of airway mucus, The Pulmonary Epithelium
Rogers DF, Rubin BK, 2007, Mucolytics for COPD, Chronic Obstructive Pulmonary Disease, Editors: Stockley, Rennard, Rabe, Celi
Holder E, Griesenbach U, Li S, et al., 2006, Intravenously administered oligonucleotides can be delivered to conducting airway epithelium via the bronchial circulation, GENE THERAPY, Vol: 13, Pages: 1628-1638, ISSN: 0969-7128
Foster KA, Adams EJ, Durose L, et al., 2006, Re-engineering the target specificity of clostridial neurotoxins - a route to novel therapeutics, NEUROTOXICITY RESEARCH, Vol: 9, Pages: 101-107, ISSN: 1029-8428
Rogers DF, Barnes PJ, 2006, Treatment of airway mucus hypersecretion, ANNALS OF MEDICINE, Vol: 38, Pages: 116-125, ISSN: 0785-3890
Rogers DF, 2005, The role of airway secretions in COPD: pathophysiology, epidemiology and pharmacotherapeutic options., COPD, Vol: 2, Pages: 341-353, ISSN: 1541-2555
Often considered an aggravating but otherwise benign component of chronic obstructive pulmonary disease (COPD), airway mucus hypersecretion is now recognised as a potential risk factor for an accelerated loss of lung function in COPD and is a key pathophysiological feature in many patients, particularly those prone to respiratory tract infection. Consequently, it is important to develop drugs that inhibit mucus hypersecretion in these susceptible patients. Conventional therapy including anticholinergics, beta2-adrenoceoptor agonists, alone or in combination with corticosteroids, mucolytics and macrolide antibiotics are not entirely or consistently effective in inhibiting airway mucus hypersecretion in COPD. Novel pharmacotherapeutic targets are being investigated, including inhibitors of nerve activity (e.g., BK(Ca) channel activators), tachykinin receptor antagonists, epoxygenase inducers (e.g., benzafibrate), inhibitors of mucin exocytosis (e.g., anti-MARCKS peptide and Munc-18B blockers), inhibitors of mucin synthesis and goblet cell hyperplasia (e.g., EGF receptor tyrosine kinase inhibitors, p38 MAP kinase inhibitors, MEK/ERK inhibitors, hCACL2 blockers and retinoic acid receptor-alpha antagonists), inducers of goblet cell apoptosis (e.g., Bax inducers or Bcl-2 inhibitors), and purinoceptor P(2Y2) antagonists to inhibit mucin secretion or P(2Y2) agonists to hydrate secretions. However, real and theoretical differences delineate the mucus hypersecretory phenotype in COPD from that in other hypersecretory diseases of the airways. More information is required on these differences to identify therapeutic targets pertinent to COPD which, in turn, should lead to rational design of anti-hypersecretory drugs for specific treatment of airway mucus hypersecretion in COPD.
Culpitt SV, Rogers DF, Traves SL, et al., 2005, Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma, RESPIRATORY MEDICINE, Vol: 99, Pages: 703-710, ISSN: 0954-6111
Rogers DF, 2005, Mucociliary dysfunction in COPD: effect of current pharmacotherapeutic options, PULMONARY PHARMACOLOGY & THERAPEUTICS, Vol: 18, Pages: 1-8, ISSN: 1094-5539
Rogers DF, 2005, Airway mucus in COPD: pathophysiology and treatment, Chronic Obstructive Pulmonary Disease: Cellular and Molecular Mechanisms, Editors: Barnes
Rogers DF, 2004, Airway mucus hypersecretion in asthma: an undervalued pathology?, CURRENT OPINION IN PHARMACOLOGY, Vol: 4, Pages: 241-250, ISSN: 1471-4892
Rogers DF, 2004, Overview of Airway Mucus Clearance, Therapy for Mucus-Clearance Disorders, Editors: Rubin, van, New York, Publisher: Marcel Dekker, Pages: 1-27, ISBN: 9780824707163
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