Voluntary suppression of cough induced by inhalation of capsaicin in healthy volunteers

AbstractThe aim of the present study was to investigate the voluntary suppression of cough in response to capsaicin inhalation in healthy volunteers, and to determine if the dose-response curve to capsaicin was significantly altered when volunteers were asked to suppress their cough response. The quantification of the degree of voluntary suppression of induced cough could provide a new methodology for screening antitussive agents as antitussives may act by influencing voluntary control of cough.Cough was induced by inhalation of capsaicin. Two challenges were given 5 min apart, each comprising five ascending concentrations of capsaicin (1 × 10−5m−3·33 × 10−4m). During one of these challenges the volunteer was allowed to cough when required, and during the other they were asked to suppress cough. These two conditions were given in random order. The cough response was recorded by means of a microphone with the integrated sound trace displayed on a chart recorder.A dose-response relationship was obtained on administration of ascending concentrations of capsaicin. In the non-suppressed challenge 2324 subjects coughed on inhalation of capsaicin (3·33 × 10−4m) with a mean number of coughs of 2·92 ± 0·34, whereas in the suppressed challenge only 324 subjects coughed with a mean number of coughs of 0·29 ± 0·18 (P < 0·001).These results demonstrate that cough induced by inhalation of capsaicin can be voluntarily suppressed. The mechanism of voluntary suppression of cough is discussed in relation to capsaicin challenge and the screening of antitussive medications

Chronic cough: new insights and future prospects

Chronic cough is defined in adults as a cough that lasts for ≥8 weeks. When it proves intractable to standard-of-care treatment, it can be referred to as refractory chronic cough (RCC). Chronic cough is now understood to be a condition of neural dysregulation. Chronic cough and RCC result in a serious, often unrecognized, disease burden, which forms the focus of the current review.The estimated global prevalence of chronic cough is 2-18%. Patients with chronic cough and RCC report many physical and psychological effects, which impair their quality of life. Chronic cough also has a significant economic burden for the patient and healthcare systems. RCC diagnosis and treatment are often delayed for many years as potential treatable triggers must be excluded first and a stepwise empirical therapeutic regimen is recommended.Evidence supporting most currently recommended treatments is limited. Many treatments do not address the underlying pathology, are used off-label, have limited efficacy and produce significant side-effects. There is therefore a significant unmet need for alternative therapies for RCC that target the underlying disease mechanisms. Early clinical data suggest that antagonists of the purinergic P2X3 receptor, an important mediator of RCC, are promising, though more evidence is needed

COPD in young patients: A pre-specified analysis of the four-year trial of tiotropium (UPLIFT)

SummaryWhilst recent large-scale studies have provided much evidence on the natural history and therapeutic response in patients with chronic obstructive pulmonary disease (COPD), relatively little is known about the effect in younger patients.We report a pre-specified post-hoc analysis of 356 patients with COPD ≤ 50 years old from the four year randomised, double blind placebo controlled Understanding Potential Long Term Impact on Function with Tiotropium (UPLIFT) trial. Inclusion criteria included a post-bronchodilator forced expiratory volume in 1 s (FEV1) of ≤70%, FEV1/FVC < 0.70, age ≥40 years, and smoking history of ≥10 pack years.Younger patients had a mean FEV1 of 1.24 L (39% predicted) and an impaired health-related quality of life (St. George’s Respiratory Questionnaire (SGRQ)) compared to the entire UPLIFT population. There were 40.2% women and 51.1% current smokers in the younger age group. Tiotropium was associated with a sustained improvement in spirometry and SGRQ. Mean decline in post-bronchodilator FEV1 was 58 ml/year (placebo) vs. 38 ml/year (tiotropium) (p = 0.01). Corresponding values for pre-bronchodilator FEV1 were 41 ml/year (placebo) compared with 34 ml/year (tiotropium) (p = 0.34). The hazard ratio (95%CI) for an exacerbation in the younger age group was 0.87(0.68, 1.13)). The rate of exacerbations was reduced by tiotropium (rate ratio (95%CI) = 0.73(0.56, 0.95)).Tiotropium resulted in sustained bronchodilation, improved quality of life, and a decreased exacerbation rate in younger patients. Tiotropium also resulted in a significant reduction in the decline in post-bronchodilator FEV1, suggesting possible disease modification by tiotropium in younger patients with COPD

Effects of stoichiometric doping in superconducting Bi-O-S compounds.

Newly discovered Bi-O-S compounds remain an enigma in attempts to understand their electronic properties. A recent study of Bi4O4S3 has shown it to be a mixture of two phases, Bi2OS2 and Bi3O2S3, the latter being superconducting (Phelan et al 2013 J. Am. Chem. Soc. 135 5372-4). Using density functional theory, we explore the electronic structure of both the phases and the effect of the introduction of extra BiS2 bilayers. Our results demonstrate that the S2 layers dope the bismuth-sulphur bands and this causes metallisation. The bands at the Fermi level are of clear two-dimensional character. One band manifold is confined to the two adjacent, square-lattice bismuth-sulphur planes, a second manifold is confined to the square lattice of sulphur dimers. We show that the introduction of extra BiS2 bilayers does not influence the electronic structure. Finally, we also show that spin-orbit coupling does not have any significant effect on the states close to the Fermi level at the energy scale considered

Absorption imaging of a quasi 2D gas: a multiple scattering analysis

Absorption imaging with quasi-resonant laser light is a commonly used technique to probe ultra-cold atomic gases in various geometries. Here we investigate some non-trivial aspects of this method when it is applied to in situ diagnosis of a quasi two-dimensional gas. Using Monte Carlo simulations we study the modification of the absorption cross-section of a photon when it undergoes multiple scattering in the gas. We determine the variations of the optical density with various parameters, such as the detuning of the light from the atomic resonance and the thickness of the gas. We compare our results to the known three-dimensional result (Beer-Lambert law) and outline the specific features of the two-dimensional case.Comment: 22 pages, 5 figure

Theobromine for the treatment of persistent cough: A randomised, multicentre, double-blind, placebo-controlled clinical trial

© Journal of Thoracic Disease. Background: To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods: This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results: At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P < 0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (-12.2±23.28 in BC1036 group and -11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions: This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration: ClinicalTrials.gov: NCT01656668

Slow light propagation in trapped atomic quantum gases

We study semi-classical slow light propagation in trapped two level atomic quantum gases. The temperature dependent behaviors of both group velocity and transmissions are compared for low temperature Bose, Fermi, and Boltzman gases within the local density approximation for their spatial density profile.Comment: 9 pages, 2 figure