Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling. AIM OF THE STUDY: This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice. MATERIALS AND METHODS: To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically (i.g.) administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)-NF-E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro. RESULTS: SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Moreover, SH capsule dose-dependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice. CONCLUSION: Our study demonstrates that SH capsule ameliorates airway inflammation-associated PIC in mice through activating AhR-Nrf2 pathway and consequently alleviating inflammatory responses and oxidative stress.

Anti-inflammatory, expectorant, and antitussive properties of Kyeongok-go in ICR mice.

CONTEXT: Kyeongok-go (KOG) is a traditional mixed herb preparation consisting of Panax ginseng CA Meyer (Araliaceae), Poria cocos Wolf (Polyporaceae), Rehmannia glutinosa (Gaertner) Liboschitz ex Steudel (Orobanchaceae), and honey. Various pharmacological effects of KOG are reported, but the efficacy on respiratory diseases has not been evaluated. OBJECTIVE: The anti-inflammatory, expectorant, and antitussive properties of KOG were examined using animal models of respiratory diseases. MATERIALS AND METHODS: KOG (100, 200, and 400 mg/kg) was orally administered to ICR mice (n = 8) once a day for 11 days. Anti-inflammatory effects of vehicle, xylene, KOG and DEXA (1 mg/kg) were determined by monitoring edoema and redness of treated ears, and measuring the relative and absolute weight of each ear. Expectorant properties of vehicle, KOG and AM (250 mg/kg) were evaluated by observing body surface redness, and the amount of mucous secreted by the trachea. The antitussive potential of vehicle, NH4OH, KOG and TB (50 mg/kg) was evaluated by monitoring changes in the number of coughs (for 6 min). RESULTS: KOG (400 mg/kg) treated mice showed 31.29% and 30.72% (p < 0.01) decreases in the relative and absolute weights of each ear relative to xylene control mice, 39.06% increases (p < 0.01) in TLF OD values relative to intact vehicle control mice, and 59.53% decrease (p < 0.01) in coughing compared to NH4OH control mice. Dose-dependent changes were observed in all experimental models. CONCLUSIONS: KOG may be a potential therapeutic agent for the treatment of various respiratory diseases, particularly those caused by environmental toxins.

Effects of smoking on the optimal effect-site concentration of remifentanil required for preventing cough during anesthetic emergence in male patients undergoing laparoscopic or robotic cholecystectomy.

ABSTRACT: Target-controlled infusion of remifentanil is known to reduce cough effectively during emergence from general anesthesia. The effect of smoking on emergence cough remains controversial. Therefore, we aimed to investigate the effect-site concentration (Ce) of remifentanil in the male patients undergoing laparoscopic or robotic cholecystectomy for suppressing emergence cough in smokers and non-smokers.Twenty smokers and 24 non-smokers (sex, male; age range, 20-65 years) were enrolled in this study. Anesthesia was maintained using sevoflurane and remifentanil. The Ce of remifentanil in 50% (EC50) and 95% (EC95) of the patients required for suppressing emergence cough were determined for each group (smokers and non-smokers) using Dixon up-and-down method and isotonic regression method with a bootstrapping approach.Dixon up-and-down method revealed that the EC50 value was significantly higher in smokers (3.51 ±â€Š0.60 ng/mL) than in non-smokers (2.71 ±â€Š0.30 ng/mL) (P < 0.001). In smokers and non-smokers, isotonic regression revealed EC50 to be 4.40 (83% CI, 4.17-4.58) ng/mL and 2.58 (83% CI, 2.31-2.87) ng/mL, respectively, and EC95 to be 4.76 (95% CI, 4.73-4.78) ng/mL and 3.15 (95% CI, 3.04-3.18) ng/mL, respectively.The Ces of remifentanil required to prevent cough during emergence were significantly higher in smokers than in non-smokers. Therefore, clinicians should pay attention to the smoking history of a patient to prevent cough during emergence.

Tachyphylaxis and Dependence in Pharmacotherapy for Unexplained Chronic Cough.

Objective Unexplained chronic cough (UCC) is a perplexing condition treated with neuromodulators. Although previous literature describes the effectiveness of neuromodulators, there is little on the development of tachyphylaxis or dependence to neuromodulators over time. Our objective is to capture the experience of a large cohort of patients with UCC over an extended period, looking for these 2 phenomena. Study Design Case series with chart review. Setting Tertiary care hospital. Subjects and Methods We performed a retrospective review of patients diagnosed with UCC from 2010 to 2014. Patient outcomes were measured through percentage improvement scores. Treatment failures were attributed to no benefit, intolerable side effects, or tachyphylaxis. Tachyphylaxis was defined as the need for higher doses of medication following diminishing therapeutic benefit, while dependence was defined as a failure to stop therapy following attempted de-escalation or resurgence following drug cessation. Results Sixty-eight patients were included in the study. Tachyphylaxis was observed among 35% of patients while dependence was observed among 27% of successfully treated patients, together effecting >50% of the cohort. Sixty-eight percent of patients ultimately experienced successful treatment with neuromodulators, demonstrating strikingly distinct responses to different neuromodulator drug classes. Conclusion Tachyphylaxis and dependence occur frequently during UCC treatment and have a major impact on treatment outcomes. Patients sometimes demonstrate distinct responses to different neuromodulator classes. The majority of patients will experience successful treatment for their cough, although several trials may be required.

Antitussive, antispasmodic, bronchodilating and cardiac inotropic effects of the essential oil from Blepharocalyx salicifolius leaves.

ETHNOPHARMACOLOGY RELEVANCE: Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. AIM OF THE STUDY: To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. METHODS: The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca2+) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. RESULTS: Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca2+-CRC, with IC50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a maximal relaxation that was 1.9 times higher than that of papaverine. In the isolated heart, EO-Bs induced a poor negative inotropic response, and did not improve the contractile and energetic recovery after ischemia and reperfusion. In the mouse cough model, EO-Bs (90mg/Kg) was as effective as codeine (30mg/Kg) in reducing cough frequency. CONCLUSIONS: The results indicate that the preparations from Blepharocalyx salicifolius leaves were effective as central antitussive, bronchodilating and antispasmodic agents, suggestive of a mechanism associated with the inhibition of Ca2+ influx into smooth muscle. The EO-Bs displayed only a poor ability to reduce cardiac inotropism, and was devoid of any cardioprotective properties. Thus, the present study validates the traditional use of this South American plant for asthma, cough and bronchospasm, shedding new light into its potency and putative mechanism of action.

The Pharmacokinetics of Morphine and Codeine in Human Plasma and Urine after Oral Administration of Qiangli Pipa Syrup.

Papaveris pericarpium, a natural source of morphine and codeine, is the principal active component in many antitussive traditional Chinese medicines. We herein report the first PK study of papaveris pericarpium in human plasma and urine following oral administration of single (15, 30, 60 mL) and multiple dose (15 mL) of Qiangli Pipa Syrup (MOR 0.1 mg/mL, COD 0.028 mg/mL) by monitoring morphine and codeine using a HPLC-MS/MS method. Their Tmax and t1/2 values are independent of dosages, while the AUC0-t linearly increased with higher dosages, indicating linear PK characteristics. AUC0-t increased obviously after multiple doses, indicating possible risk of accumulative toxicity. Urine studies suggested risks of positive opiate drug tests with a cutoff of 300 ng/mL, which lasted 6-14 h at different doses. These results provide important information for clinical safety, efficacy and rational drug use of Qiangli Pipa Syrup and also guide the related judicial expertise of its administration.

Efficacy and tolerability of a polysaccharide-resin-honey based cough syrup as compared to carbocysteine syrup for children with colds: a randomized, single-blinded, multicenter study.

BACKGROUND: Available pediatric treatments for acute cough are limited by lack of demonstrated efficacy. The objective of this trial is to compare the effects of a polysaccharide-resin-honey based cough syrup, and carbocysteine syrups on nocturnal and daytime cough associated with childhood upper respiratory tract infections (URIs). METHODS: Using a single-blind randomization design, the study recruited children from 4 general pediatric community clinics. Participants included 150 children aged 2 to 5 years with an URI, nocturnal and daytime cough and illness duration of ≤7 days. To be eligible, children had to be free of medication on the day before presentation. A survey was administered to parents on 4 consecutive days beginning from the day of presentation in clinic. Children received the study preparation on the first evening and then 3 times per day for 3 further days. Main outcome measures were cough frequency, cough severity, bothersome nature of cough, and quality of sleep for both child and parent. RESULTS: Both preparations were well tolerated and cough improved over the study period. After one night and on all survey days, there was a significantly better result for polysaccharide-resin-honey (P<0.05) for all the main outcome measures. The trend of improvement over the 4 days was steeper for polysaccharide-resin-honey (P<0.05) with regards to all cough parameters. CONCLUSIONS: Both polysaccharide-resin-honey and carbocysteine cough syrups were well tolerated in children over 2 years of age. The polysaccharide-resin-honey syrup was associated with a more rapid and greater improvement in all clinical cough symptoms measured, beginning from the first night of therapy. Both nocturnal and daytime cough improved, as did sleep quality for both children and parents.

Downregulation of the cough reflex by aclidinium and tiotropium in awake and anesthetized rabbits.

Long-acting muscarinic receptor antagonists (LAMAs) have been reported to attenuate cough in preclinical and clinical studies. The present study was performed on rabbits to compare aclidinium and tiotropium efficacy in the downregulation of the cough reflex. This reflex was evoked by citric acid inhalation in unanesthetized animals and by both citric acid inhalation and mechanical stimulation of the tracheobronchial tree in anesthetized animals 90 min following the inhalation of each drug (nebulizer output always at 1 mL/min). Aclidinium 4 mg/mL and tiotropium 200 µg/mL inhaled in 1 min proved to have similar protective effect on methacholine-induced bronchoconstriction in anesthetized animals. The total dosage employed for aclidinium and tiotropium was 4 mg and 200 µg, respectively. In awake animals, similar reductions in the cough number were observed following 10-min inhalation of each drug with a slight, not significant tendency to higher antitussive effects for aclidinium. In anesthetized animals, 1-min inhalation of each drug caused similar depressant effects on cough responses induced by both mechanical and chemical stimulation. A complete suppression of cough responses to mechanical stimuli was seen in some preparations. The results strongly suggest that the LAMA-induced downregulation of cough may be mediated not only by transient receptor potential vanilloid type 1 channels, as already reported, but also by acid-sensing ion channels and mechanoreceptors. The route of administration along with the more rapid hydrolysis of aclidinium into inactive metabolites minimize potential systemic side effects and give to this drug a very favorable safety profile.

Nonmedical Use of Cough Syrup Among Secondary Vocational School Students: A National Survey in China.

Nonmedical use of cough syrup (NUCS) among secondary vocational school (SVS) students has been an increasing concern for public health in China, but no data were available. This cross-sectional study aimed to investigate the epidemiological characters of NUCS as well as its risk factors among SVS students in China.From September 2013 to December 2014, a total of 13,614 SVS students were purposively selected through multistage sampling in 6 cities of China. Information on NUCS, demographics, family background, smoking and alcohol consumption, impulsiveness, sensation seeking, and parental monitoring were collected. Logistic regression was used to explore factors related to NUCS.The 12,923 (94.9%) valid responses (16.3 ±â€Š1.0 years old, and 52.6% men) reported 3.47% (95% confidence interval: 3.15-3.79%) lifetime NUCS. Logistic regression indicated that smoking, part-time job experience, high level of impulsiveness, and sensation seeking were risk factors for NUCS, whereas urban living and high parental monitoring were protective ones.NUCS was prevalent among SVS students. Interventions that target on smoking, impulsiveness and sensation seeking control, improvement on parental monitoring may have considerable impact on NUCS among SVS students.

Modifying Post-Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence.

OBJECTIVE: Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax. METHODS: Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC)). RESULTS: The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts. CONCLUSIONS: In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data.

Use of Cough and Cold Medications in Severe Bronchiolitis before and after a Health Advisory Warning against Their Use.

We compared the use of cough and cold medications in 2 multicenter studies of young children hospitalized with bronchiolitis before and after the 2008 Food and Drug Administration cough and cold medications advisory. Although cough and cold medication use decreased after the advisory, nearly 20% of children age 12-23.9 months with severe bronchiolitis received cough and cold medications.

Noscapine Increases the Sensitivity of Drug-Resistant Ovarian Cancer Cell Line SKOV3/DDP to Cisplatin by Regulating Cell Cycle and Activating Apoptotic Pathways.

Cisplatin is a first-line chemotherapy drug against ovarian cancer. However, its strong toxic side effects and the development of cisplatin resistance in human cancer cells seriously influence the effects of chemotherapy and quality of life in patients. Noscapine (Nos), a non-toxic benzylisoquinoline alkaloid extracted from opium, has been recently reported to have anti-cancer activity, but the mechanism of that effect has not been clearly established. In the present study, we investigated cytotoxicity of Nos in combination with cisplatin (DDP) in drug-resistant human ovarian cancer cell line SKOV3/DDP in vitro and in vivo null mice xenograft model. Cell proliferation was measured by MTT assay, flow cytometry was used to analyze cell cycle and apoptosis, protein expression of several apoptotic factors was investigated by flow cytometry and immunohistochemical method, and their mRNA expression levels were determined by real-time PCR. In vitro experiments showed that Nos significantly inhibited proliferation of SKOV3/DDP cells. DDP/Nos-combined treatment notably enhanced DDP-induced inhibition of cell proliferation and increased the pro-apoptotic effect of DDP in SKOV3/DDP cells. DDP/Nos administration increased the proportion of G2/M cells, reduced both protein and mRNA expression of anti-apoptotic factors XIAP, surviving and NF-kB, and augmented protein and mRNA levels of pro-apoptotic caspase-3. In vivo experiments revealed that Nos/DDP treatment increased the apoptotic rate of xenograft tumors in null mice. Tumor volume decreased from 1.733 ± 0.155 g in mice treated with DDP alone to 1.191 ± 0.106 g in animals treated with Nos/DDP. These observations suggest that Nos increases the anti-cancer activity of DDP against the drug-resistant ovarian cancer cell line SKOV3/DDP by modulating the cell cycle and activating apoptotic pathways. The study provides a new chemotherapy strategy for the treatment of DDP-resistant human ovarian cancer.

Does the type of anesthetic agent affect remifentanil effect-site concentration for preventing endotracheal tube-induced cough during anesthetic emergence? Comparison of propofol, sevoflurane, and desflurane.

STUDY OBJECTIVE: To investigate whether the type of anesthetic agent administered affects the antitussive effect of remifentanil. DESIGN: Prospective randomized study. SETTING: Operating room of a university hospital. PATIENTS: 78 ASA physical status 1 and 2 women, aged 20 to 65 years, who were scheduled to undergo a thyroidectomy. INTERVENTIONS: Patients were randomly assigned to three groups to receive anesthesia with propofol (Group P), sevoflurane (Group S), or desflurane (Group D). The main anesthetics were titrated to maintain a target Bispectral Index for hypnosis of 40 to 60. Remifentanil was administered via effect-site target-controlled infusion (TCI). To determine the effective remifentanil effect-site concentration (Ce) to suppress coughing in each group, the up-and-down sequential allocation design was used. MEASUREMENTS: The half maximal effective concentration (EC50) values of remifentanil for preventing coughing in the groups were estimated using isotonic regression and compared among the groups. MAIN RESULTS: The EC50 of remifentanil for cough suppression in Group P [1.60 ng/mL (98.3% CI, 0.92-1.75 ng/mL)] was statistically lower than in Group D [1.96 ng/mL (98.3% CI, 1.81-2.50 ng/mL)]. The EC50 in Group S was 1.75 ng/mL (98.3% CI, 1.39-2.13 ng/mL), which was higher than in Group P and lower than in Group D, but did not differ significantly from either group. CONCLUSIONS: Remifentanil administration for cough suppression during emergence should be customized to the anesthetic agent.

Enhanced noscapine delivery using estrogen-receptor-targeted nanoparticles for breast cancer therapy.

Noscapine (Nos), an orally available plant-derived antitussive alkaloid, is in phase II clinical trials for cancer chemotherapy. It has extensively been shown to inhibit tumor growth in nude mice bearing human xenografts of hematopoietic, breast, lung, ovarian, brain, and prostate origin. However, high tumor-suppressive Nos dosages encumber the development of oral controlled-release formulations because of a short biological half-life (<2 h), poor absorption, low aqueous solubility, and extensive first-pass metabolism. Here, we present the design, fabrication, optimization, characterization, and biological evaluation of estrone-conjugated noscapine-loaded gelatin nanoparticles (Nos-ES-GN) for targeting estrogen-receptor-positive breast cancer MCF-7 cells. Gelatin nanoparticles (GN) were a uniformly compact size, stable at physiological pH, and showed a drug entrapment efficiency of 66.1±5.9 and 65.2±5.6% for Nos-GN and Nos-ES-GN, respectively. The secondary structure of gelatin nanocoacervates was predicted using circular dichroism and in-silico molecular modeling. Our data suggest that ethanol-fabricated GN retained the α-helical content of gelatin, whereas acetone favored the formation of random coils. The conjugation of estrone to Nos-GN did not affect the release rate of the drug, and both formulations followed first-order release kinetics with an initial burst, followed by a slow release. The IC50 value of Nos-ES-GN was 21.2 µmol/l, which was ∼50% lower than the free drug (43.3 µmol/l), suggesting targeted drug delivery. Our cell uptake study carried out in an estrogen-receptor-positive (MCF-7) and negative (MDA-MB-231) cancer cell lines showed greater accumulation of Nos-ES-GN in MCF-7 cells instead of MDA-MB-231 cells. Our data indicated that estrone-conjugated nanoparticles may potentially be used for targeting breast cancer cells.

Theophylline inhibits the cough reflex through a novel mechanism of action.

BACKGROUND: Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. Determining how theophylline inhibits cough might lead to the development of optimized compounds. OBJECTIVE: We sought to investigate the inhibitory activity of theophylline on vagal sensory nerve activity and the cough reflex. METHODS: Using a range of techniques, we investigated the effect of theophylline on human and guinea pig vagal sensory nerve activity in vitro and on the cough reflex in guinea pig challenge models. RESULTS: Theophylline was antitussive in a guinea pig model, inhibited activation of single C-fiber afferents in vivo and depolarization of human and guinea pig vagus in vitro, and inhibited calcium influx in airway-specific neurons in vitro. A sequence of pharmacological studies on the isolated vagus and patch clamp and single-channel inside-out experiments showed that the effect of theophylline was due to an increase in the open probability of calcium-activated potassium channels. Finally, we demonstrated the antitussive activity of theophylline in a cigarette smoke exposure model that exhibited enhanced tussive responses to capsaicin. CONCLUSION: Theophylline inhibits capsaicin-induced cough under both normal and "disease" conditions by decreasing the excitability of sensory nerves through activation of small- and intermediate-conductance calcium-activated potassium channels. These findings could lead to the development of optimized antitussive compounds with a reduced side effect potential.

Codeine-associated pediatric deaths despite using recommended dosing guidelines: three case reports.

This report describes the deaths of three children ages 4-10 years due to codeine toxicity at home. All three children were overweight or obese; however, the codeine doses were within recommended dose ranges for adjusted lean weight. Codeine's analgesic effect depends on its metabolic conversion to morphine in the liver via the drug-metabolizing enzyme CYP2D6. Genetic variation may result in poor analgesia, opioid toxicity, or oversedation. Caregivers must be warned about risks associated with comorbidities including obesity and polypharmacy. Codeine should no longer be prescribed to children due to its poor analgesic effect and risk of opioid toxicity and oversedation.

Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in chronic cough.

INTRODUCTION: Chronic cough is a common clinical problem and there is a shortage of effective treatments for it. Within the group of transient receptor potential ion channels a receptor for the cooling substance menthol has been identified. This study aimed to assess whether pre-inhalation of dissolved, nebulised menthol could increase capsaicin cough thresholds and influence spirometric values. METHODS: Fourteen patients with chronic cough and airway sensitivity to environmental irritants and 15 control subjects were tested on three occasions. Each one inhaled a 1 mL of nebulised menthol solution of 0.5% or 1% or placebo (saline with 0.05% menthol) at each visit in a randomized and double-blind order. They were then provoked by capsaicin inhalation. RESULTS: Patients' cough thresholds differed significantly from the controls' on all three provocations (P < 0.0001). After inhalation of 1% menthol, the patients' cough thresholds were significantly higher (P < 0.02) compared to after placebo inhalation and to after 0.5% menthol inhalation (P < 0.05). The patients' peak inspiratory flows were significantly reduced after inhalation of the placebo (saline) (P < 0.05) but not after inhalation of 0.5% or 1% menthol. Forced inspiratory flows 50% were lowered after inhalation of placebo and of 0.5% menthol (P < 0.05) but not after 1% menthol. Among the controls, forced inspiratory flows 50% were lowered after only placebo inhalation (P < 0.05). CONCLUSIONS: In patients with chronic cough, pre-inhalation of menthol reduces cough sensitivity to inhaled capsaicin and influences inspiratory flows. The findings may provide scientific support for the common practice of using menthol as a reliever for variant airway discomfort. The use of menthol in different cigarette brands could be questioned since it could conceal the natural irritation following smoking.

Personal construction of cough medicine among young substance abusers in Hong Kong.

Although cough medicine abuse is a growing problem in many places, there is no study examining the views of young substance abusers toward cough medicine. The objective of this study was to examine personal constructions of cough medicine abusers via the repertory grid tests (N = 11). Several observations are highlighted from the study. First, personal constructions of cough medicine were mixed, including the benefits and harmful effects of its abuse. Second, although the informants perceived cough medicine to be addictive and harmful, they perceived cough medicine to be less addictive and less harmful than did heroin. Third, while the informants construed cough medicine to be similar to ketamine and marijuana, they also perceived cough medicine to possess some characteristics of heroin. Fourth, relative to the construed similarity between heroin and the gateway drugs (cigarette, beer, and liquor), the informants construed cough medicine to be more similar to the gateway drugs. Finally, a higher level of perceived dissimilarity between cough medicine and gateway drugs was related to a higher level of perceived harm of cough medicine abuse.