The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
John Widdicombe - One of the best experts on this subject based on the ideXlab platform.
-
Workshop: Tuning the 'Cough Center'
Pulmonary pharmacology & therapeutics, 2011Co-Authors: John Widdicombe, Milos Tatar, Giovanni A. Fontana, Hanácek J, Paul W. Davenport, Federico Lavorini, Donald C. BolserAbstract:The Workshop considered the mechanisms whereby the 'Cough Center' could be tuned by various afferent inputs. There were particular presentations on the effects of inputs from the nose, mouth, respiratory tract and lungs, cerebral cortex, somatic tissues and the pharynx. From all these sites Cough induced from the lungs could be increased or decreased in its strength or modified in its pattern. Thus 'tuning' of Cough could be due to the interaction of afferent inputs, or to the sensitization or desensitization of brainstem neural pathways. The pattern of response depended on the 'type' of Cough being studied and, in some instances, on the timing of the sensory input into the brainstem. Cough inputs could also affect various 'non-Cough' motor outputs from the brain, although this was not the main theme of the Workshop. The main conclusion was that Cough is not a stereotyped output from the medullary 'Cough Center', but that its pattern and strength depend on many afferent inputs acting on the 'Cough Center'.
-
Clinical Cough V: complementary and alternative medicine: therapy of Cough.
Handbook of experimental pharmacology, 2009Co-Authors: John Widdicombe, E. ErnstAbstract:We review the actions of complementary and alternative medicines (CAMs) in the treatment of Cough and of the conditions associated with it; in particular asthma and upper respiratory tract infections. These therapies may work (1) peripherally, at the sites in the airways and lungs at which Cough is being activated, (2) in the brainstem, where the neural “Cough Center” is situated, or (3) at the cerebral cortex, where Cough can be initiated, suppressed or modified by conscious or unconscious controls. Of the large number of trials of CAMs against Cough, most are inadequate in design. It may be difficult to randomize selection. Blinding is often impossible both for the patient and the therapist, and adequate placebo controls may be difficult to devise. The patient can usually identify the “active“ treatment by the taste or smell of a medicine, or from the approach and apparatus being used. Pure chemicals can be extracted from many of the herbs used as antitussives, and can be shown to be effective in randomized, blind, and controlled trials, but it does not follow that the herb itself, used in the recommended formula and shown to be antitussive, acts by this agency unless a placebo effect is ruled out. A few herbs are identified where the evidence points to a true antitussive action. Of nonherbal treatments, the few positive results are usually outweighed by the larger number of negative ones. Thus, in general, CAMs for Cough are welcomed enthusiastically by the patient but lack sound evidence for their efficacy. Antitussive chemicals can be extracted from many herbs, but it is no more than a reasonable hypothesis that the herb itself acts through this pathway.
Donald C. Bolser - One of the best experts on this subject based on the ideXlab platform.
-
Workshop: Tuning the 'Cough Center'
Pulmonary pharmacology & therapeutics, 2011Co-Authors: John Widdicombe, Milos Tatar, Giovanni A. Fontana, Hanácek J, Paul W. Davenport, Federico Lavorini, Donald C. BolserAbstract:The Workshop considered the mechanisms whereby the 'Cough Center' could be tuned by various afferent inputs. There were particular presentations on the effects of inputs from the nose, mouth, respiratory tract and lungs, cerebral cortex, somatic tissues and the pharynx. From all these sites Cough induced from the lungs could be increased or decreased in its strength or modified in its pattern. Thus 'tuning' of Cough could be due to the interaction of afferent inputs, or to the sensitization or desensitization of brainstem neural pathways. The pattern of response depended on the 'type' of Cough being studied and, in some instances, on the timing of the sensory input into the brainstem. Cough inputs could also affect various 'non-Cough' motor outputs from the brain, although this was not the main theme of the Workshop. The main conclusion was that Cough is not a stereotyped output from the medullary 'Cough Center', but that its pattern and strength depend on many afferent inputs acting on the 'Cough Center'.
Hisashi Ida - One of the best experts on this subject based on the ideXlab platform.
-
The nonnarcotic antitussive drug dimemorfan: a review
Clinical therapeutics, 1997Co-Authors: Hisashi IdaAbstract:The antitussive dimemorfan phosphate was discovered through extensive screening of morphinic derivatives and was introduced in Japan in 1975. The majority of studies on dimemorfan have been published in Japanese, and this review aims to make these data more generally available. The antitussive action of dimemorfan appears to be directly on the Cough Center in the medulla. Dimemorfan does not induce any significant physical or psychologic dependence, and its antitussive action is not affected by the opioid-receptor blocker levallorphan. Dimemorfan is therefore considered a nonnarcotic antitussive. Studies of antitussive effects in animal models indicate that dimemorfan is up to three times more potent than codeine and is equivalent to dextromethorphan. Three major comparative clinical trials and postmarketing surveillance studies showed that dimemorfan is equally or slightly more efficacious than dextromethorphan, benproperine phosphate, or placebo for the control of Coughing. Several animal and clinical studies have confirmed the efficacy and safety of dimemorfan. Dimemorfan was effective in the majority of patients. In contrast to the narcotic antitussives, dimemorfan caused no serious problems with the digestive system, such as constipation and disorders of the bile duct, caused no dependence or tolerance, and was unlikely to have clinical analgesic effects. Minor side effects, such as loss of appetite, nausea, and drowsiness, were seen in less than 10% of patients. A syrup formulation of dimemorphan that retains its efficacy and safety is also available. Overall, these data indicate that dimemorfan is an effective nonnarcotic antitussive agent with a low incidence of adverse events.
Peter V. Dicpinigaitis - One of the best experts on this subject based on the ideXlab platform.
-
Prevalence of urinary incontinence in women seeking evaluation for chronic Cough
Monitoring airway disease, 2020Co-Authors: Peter V. DicpinigaitisAbstract:Purpose: Cough is the most common symptom for which patients in the United States and elsewhere seek medical attention. Chronic Cough (>8 weeks duration) is associated with quality of life disruption, including physical discomfort, depression, anxiety and social isolation. It is known that urinary incontinence (UI) is frequently associated with chronic Cough in women, however, little information is available in the medical literature regarding the actual prevalence of this condition among women suffering from chronic Cough. Methods: Consecutive women presenting to the Montefiore Cough Center (New York, USA) for evaluation of chronic Cough provided data regarding occurrence of UI associated specifically and temporally with Cough. Additional data collected included age, duration of Cough, duration of UI, body mass index (BMI) and relationship of UI onset to Cough onset. Results: To date, 112 of 180 consecutive women (62.2%) presenting for evaluation of chronic Cough have reported the presence of UI associated with episodes of Cough. In all but five subjects (96%), Cough predated onset of UI. Women with UI were older (age 60.2±12.5(SD) yr vs. 55.5±18.2 yr; p=0.04) and had a significantly greater BMI: 30.0±7.2 kg/m2 vs. 26.8±6.3 kg/m2; p=0.003. Although duration of Cough was greater in subjects with UI (50.3±76.6 months vs. 46.4±63.8 months), this difference was not statistically significant. Conclusions: UI is experienced by the majority of women suffering from chronic Cough. In the vast majority of cases, onset of UI followed onset of chronic Cough, and UI occurred exclusively and immediately following an episode of Cough.
-
Incidence of Arnold's nerve reflex in patients with chronic Cough
1.13 Clinical Problems - Other, 2016Co-Authors: Peter V. DicpinigaitisAbstract:Background: In animals and man, Cough can only be induced by stimulation of a structure innervated by the vagus nerve or one of its branches. The auricular branch of the vagus nerve (Arnold9s nerve) supplies the external acoustic meatus. Induction of Cough by manipulation of the ear is known as Arnold9s nerve reflex or ear-Cough reflex. Three previous studies evaluating a total of 1702 outpatients presenting to an otorhinolaryngologist revealed an incidence of Arnold9s Cough reflex of 2.64%. To our knowledge, the incidence of the ear-Cough reflex in patients with chronic Cough has not been previously studied. Methods: Patients presenting to a specialty Cough Center (Montefiore Cough Center, New York, USA) for evaluation of chronic Cough (>8 weeks duration) underwent physical examination that included the insertion of a cotton-tipped swab (bud) into the external acoustic meatus of each ear and mechanical stimulation of its circumference. Cough occurring within 10 seconds of stimulation was considered induced by the intervention. Results: To date, 33 (24 female, 9 male) of a planned 100 consecutive subjects have been evaluated. Overall incidence of Arnold9s nerve reflex was 11/33 (33 %), with a significant gender difference: 42 % (10/24) in women; 11 % (1/9) in men. Conclusion: The incidence of Arnold9s nerve reflex is much higher in patients with chronic Cough than in other populations previously studied. Such hypersensitivity of a branch of the vagus nerve is consistent with the recently-proposed concept of the Cough Hypersensitivity Syndrome, in which sensory hypersensitivity is the presumed mechanism by which chronic refractory Cough arises and persists in a population of predisposed individuals.
-
Thoughts on One Thousand Chronic Cough Patients
Lung, 2012Co-Authors: Peter V. DicpinigaitisAbstract:Cough is the most common complaint for which patients seek medical attention. Although most cases of acute Cough, due to viral upper respiratory tract infection, are transient and self-limited, chronic Cough often poses a diagnostic and therapeutic challenge. A subgroup of patients suffering from chronic Cough will elude a diagnosis despite appropriate evaluation, and will prove refractory to all therapeutic intervention. Having personally evaluated 1000 individuals presenting to a specialty Cough Center, the author shares insights regarding the demographic composition of this unique group of patients, as well as clinical observations and opinions on currently unmet needs requiring further research.
James L. Ellis - One of the best experts on this subject based on the ideXlab platform.
-
Antitussive activity of sigma-1 receptor agonists in the guinea-pig
British Journal of Pharmacology, 2003Co-Authors: Claire Brown, Malika Fezoui, William M. Selig, Carl E Schwartz, James L. EllisAbstract:Current antitussive medications have limited efficacy and often contain the opiate-like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits Cough is ill defined. DEX displays affinity at both NMDA and sigma receptors, suggesting that the antitussive activity may involve central or peripheral activity at either of these receptors. This study examined and compared the antitussive activity of DEX and various putative sigma receptor agonists in the guinea-pig citric-acid Cough model. Intraperitoneal (i.p.) administration of DEX (30 mg kg−1) and the sigma-1 agonists SKF-10,047 (1–5 mg kg−1), Pre-084 (5 mg kg−1), and carbetapentane (1–5 mg kg−1) inhibited citric-acid-induced Cough in guinea-pigs. Intraperitoneal administration of a sigma-1 antagonist, BD 1047 (1–5 mg kg−1), reversed the inhibition of Cough elicited by SKF-10,047. In addition, two structurally dissimilar sigma agonists SKF-10,047 (1 mg ml−1) and Pre-084 (1 mg ml−1) inhibited Cough when administered by aerosol. Aerosolized BD 1047 (1 mg ml−1, 30 min) prevented the antitussive action of SKF-10,047 (5 mg kg−1) or DEX (30 mg kg−1) given by i.p. administration and, likewise, i.p. administration of BD 1047 (5 mg kg−1) prevented the antitussive action of SKF-10,047 given by aerosol (1 mg ml−1). These results therefore support the argument that antitussive effects of DEX may be mediated via sigma receptors, since both systemic and aerosol administration of sigma-1 receptor agonists inhibit citric-acid-induced Cough in guinea-pigs. While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated 90%) across mammalian species/tissues (Barnes et al., 1992; Schuster et al., 1995), does not display homology to any other known receptors, although it does share 30% homology with a fungal sterol isomerase (Moebius et al., 1996). Sigma receptors have a single transmembrane region (Prasad et al., 1998; Yamamoto et al., 1999), are 18–26 kDa molecular weight proteins, and there are at least two subtypes (σ1 and σ2) (McCann et al., 1994; Vilner et al., 1995; Bergeron & Debonnel, 1997). To date, only the sigma-1 receptor has been cloned (Kekuda et al., 1996; Seth et al., 1998; Mei & Pasternak, 2001) with cloning of the sigma-2 receptor proving difficult. Initially, the sigma receptor was thought to be an opioid receptor due to high-affinity enantiomer selective binding of various opiates as well as steroids and psychoactive drugs to the sigma receptor (Martin et al., 1976). This misnomer still persists, despite the re-classification as a nonopioid receptor and the effects of these opiates being insensitive to the opioid antagonist naltrexone (Vaupel, 1983). Sigma receptors are found in various tissues throughout the body; however, the density is not uniform. The highest concentration of receptors is seen mainly in limbic and motor areas of the CNS, followed by the periphery (liver, spleen, endocrine, GI tract, and lung) (Roman et al., 1989; Wolfe et al., 1989; 1997; Whitlock et al., 1996; Alonso et al., 2000). The endogenous ligand for the sigma receptor is not yet known, but has been hypothesized to be progesterone (Meyer et al., 1998). While the specific function of the sigma receptor remains elusive, sigma receptors are present in high concentrations in areas of the CNS related to sensory processing such as the dorsal root ganglia and the nucleus tractus solitarus (NTS) (Walker et al., 1990; Alonso et al., 2000). The NTS is a site where the airway afferent fibers first synapse and an area very close to the Cough Center in the brainstem. This region, therefore, seems ideally placed to function as a ‘gate' for the Cough reflex, and therefore antitussives acting through the sigma receptor could conceivably modulate afferent activity prior to reaching the Cough Center. The role of sigma receptors in mediating the antitussive effects of DEX has not been systematically examined. Existing literature, which indicates the possible involvement of sigma-1 receptors, has all been conducted in the rat (Kamei et al., 1992a), a species in which it is difficult to measure Cough consistently. To our knowledge, no one has investigated the role of sigma receptors using the guinea-pig, which, owing to the higher propensity to Cough than rats, is a much preferred species to conduct antitussive research. The objective of this study was to further investigate whether DEX, as well as other putative sigma receptor agonists, inhibit citric-acid-induced Cough in guinea-pigs.
