Lowest Concentration Of Capsaicin Research Articles

Increased Sensitivity of Cough Reflex is Not the Mechanism of Cough Attributed to Laryngopharyngeal Reflux

In laryngopharyngeal reflux (LPR) patients acid reaches laryngopharyngeal area and stimulates/sensitizes respiratory nerve terminals mediating cough. We addressed several hypothesis: if stimulation of respiratory nerves is responsible for coughing then acidic LPR should correlate with coughing and proton pump inhibitor (PPI) treatment should reduce both LPR and coughing. If sensitization of respiratory nerves is responsible for coughing then cough sensitivity should correlate with coughing and PPI should reduce both coughing and cough sensitivity. In this prospective single center study, patients with positive reflux symptom index (RSI > 13) and/or reflux finding score (RFS > 7) and ≥1 LPR episode/24 hours were enrolled. We evaluated LPR by dual channel 24-hour pH/impedance. We determined number of LPR events with pH drop at levels 6.0, 5.5, 5.0, 4.5, and 4.0. Cough reflex sensitivity was determined as lowest capsaicin concentration causing at least 2/5 coughs (C2/C5) by single breath capsaicin inhalation challenge. For statistical analysis C2/C5 values were -log transformed. Troublesome coughing was evaluated on the scale 0-5. We enrolled 27 LPR patients. The number of LPR events with pH 6.0, 5.5, 5.0, 4.5, and 4.0 was 14[8-23],4[2-6],1[1-3],1[0-2] and 0[0-1], respectively. There was no correlation between number of LPR episodes at any pH level and coughing (Pearson range -0.34 to 0.21, P = NS). There was no correlation between cough reflex sensitivity C2/C5 and coughing (R = -0.29 to 0.34, P = NS). Of patients that completed PPI treatment, 11 had RSI normalized (18.36 ± 2.75 vs. 7 ± 1.35, P < 0.01). There was no change in cough reflex sensitivity in PPI-responders. C2 threshold was 1.41 ± 0.19 vs. 1.2 ± 0.19 (P = 0.11) before and after PPI. No correlation between cough sensitivity and coughing and no change in cough sensitivity despite improvement of coughing by PPI argue that an increased cough reflex sensitivity is not mechanism of cough in LPR. We identified no simple relationship between LPR and coughing suggesting that this relationship is more complex.

Changes in Cough Reflex Sensitivity in Children After Removal of Hypertrophied Adenoid Tissue.

PurposeThe co-occurrence of adenoids and chronic cough is common in children. The goal of this research was to specify changes in cough reflex sensitivity as a result of adenoid tissue removal.Patients and MethodsThe sample group consisted of 17 children (six boys and 11 girls, aged 4–12 years, mean age 6.24 years), all of them possessing symptoms of chronic cough and adenoids, confirmed by nasal fiberoptic endoscopy. This sample group underwent cough reflex sensitivity assessment, which took place both prior to and after endoscopic adenoidectomy. The definition of the cough reflex sensitivity is the lowest capsaicin concentration that caused two (C2) or five (C5) coughs. Capsaicin aerosol in ascending concentrations (from 0.61 to 1250 µmol/L) was inhaled by a single-breath method (KoKo DigiDoser), with the addition of an inspiratory flow regulator valve (RIFR).ResultsConcentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Cough sensitivity (geometric mean with 95% CI) for C2 was 31.86 (12.98–78.18) µmol/L preoperatively and 11.97 (6.16–23.26) µmol/L postoperatively (P=0.064). Cough sensitivity for C5 was 234.91 (97.19–567.77) µmol/L preoperatively and 69.13 (29.08–164.35) µmol/L postoperatively (P=0.022). The children’s pulmonary function was within the normal range.ConclusionIn our study, adenoidectomy significantly increased cough reflex sensitivity in non-atopic children suffering from chronic cough.

Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma

BackgroundWhether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.MethodsNinety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.ResultsThe median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05).ConclusionsMontelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar.Trial registration ClinicalTrials.gov, number NCT01404013.

Enhanced airway sensory nerve reactivity in non-eosinophilic asthma

BackgroundNeural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics.MethodsThirty-eight asthmatics...

Relationship between cough reflex sensitivity and body mass index in children with chronic cough - a pilot study.

Obesity is characterized by chronic, low-grade systemic inflammation. Obesity may also be associated with chronic cough. The aim of this pilot study was to clarify relation of cough reflex sensitivity and body mass index (BMI) in children with chronic cough. Altogether 41 children having symptoms of chronic cough were submitted to cough reflex sensitivity measurement. We assessed the relation of cough reflex sensitivity (CKR) due to BMI. Cough reflex sensitivity was defined as the lowest capsaicin concentration which evoked two (C2) or five (C5) coughs. Capsaicin aerosol in doubling concentrations (from 0.61 to 1250 micromol/l) was inhaled by a single breath method (KoKo DigiDoser; nSpire heath Inc, Louisville, CO, USA), modified by the addition of an inspiratory flow regulator valve (RIFR; nSpire heath Inc, Louisville, CO, USA). BMI was calculated. Pulmonary function was within normal range. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Children (22 boys and 19 girls, mean age 6.8 years) cough reflex sensitivity (median, with the Inter-Quartile Range) for C2 was 19.5 (73.4) micromol/l; for C5 it was 78.1 (605.5) micromol/l. We have noticed statistically significant relation of the cough reflex sensitivity (C5) and body mass index (P<0.0001); however, the effect size was small, R2=0.03. Increase of body mass index in one unit is associated with -34.959 micromol/l decrease of C5. We did not find a statistically significant relation between C2 and BMI (P=0.41). The median value of CKR (C2) in boys is not statistically significantly different than the median value of CKR (C2) in girls (P-value 0.5). The median value of CKR (C5) in boys is not statistically significantly different than the median value of CKR (C5) in girls (P-value 0.5). Increase of body mass index in children suffering from chronic cough relates to decrease of cough reflex sensitivity (C5 value).

Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity.

PurposeAn older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients.MethodsWe analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers.ResultsThe mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with cough-variant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 μmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years.ConclusionsIn China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients.Trial RegistrationClinicalTrials.gov Identifier: NCT02591550

Cough physiology in elderly women with nontuberculous mycobacterial lung infections.

Elderly white, thin, nonsmoking women appear to be more susceptible to lung infections with Mycobacterium avium complex and other nontuberculous mycobacteria (NTM). It has been postulated that such disease in women is related to suppression of their cough. We hypothesized that patients with pulmonary NTM (pNTM) infections may have altered cough physiology compared with unaffected control subjects. We used capsaicin-induced cough to assess the cough reflex in pNTM subjects. Eight elderly white women with stable chronic pNTM infections and six unaffected age-matched control subjects were recruited. There was no significant difference between groups in capsaicin-elicited cough motor response, airflow pattern, or cough frequency. The urge-to-cough (UTC) score at the lowest capsaicin concentration was significantly lower in pNTM than control subjects (P < 0.05). There were no significant differences in the UTC score between pNTM and control subjects at >50 μM capsaicin. These results suggest lower UTC sensitivity to the lowest concentration of capsaicin in pNTM than control subjects. In other words, the pNTM subjects do not sense a UTC when the stimulus is relatively small.NEW & NOTEWORTHY This study investigates the cough motor response and cough sensitivity in patients with nontuberculous mycobacteria (NTM) infection. In elderly white female pulmonary NTM subjects, we demonstrated a capacity to produce coughs similar to that of age-matched control subjects but decreased cough sensitivity in response to a low dose of capsaicin compared with control subjects. These findings are important to understand the pathophysiological mechanisms resulting in NTM disease in elderly white women and/or the syndrome developing in elderly white female NTM patients.

Cultivar Variation for Capsaicinoid Content in some Processed Products of Chilli

Determination of capsaicinoids content in various products from seven chilli cultivars was made. Capsaicin, the major element among capsaicinoids, is found primarily in the fruit of Capsicum to which it provides spicy flavor. Extraction of capsaicin in the present study was done using acetonitrile as the solvent, and High Performance Liquid Chromatography was used for its quantification. Whole dried-fruits of 'Bhut Red' (Capsicum chinense) showed the highest concentration of capsaicin (2.59%) and level of pungency (4,40,000 SHU), whereas, salted mash of 'Lemon Drop' (Capsicum baccatum) had the lowest capsaicin concentration (0.07%) and pungency level (12,000 SHU). As capsaicinoids are important in food and pharmaceutical industries, developing products from selected cultivars of chilli with high pungency and high capsaicinoid content will prove useful in order to ensuring health security.

Beraprost, a stable analog of prostacyclin, enhances cough reflex sensitivity to capsaicin in bronchitic patients

ABSTRACTAims: Inflammatory mediators are involved in the pathophysiology of neutrophilic bronchial disorders presenting with chronic productive cough. Accumulating evidence indicates that prostanoids are key elements in the pathophysiology of these disorders. However, little is known about the role of prostacyclin in neutrophilic bronchial inflammation. Methods: The effect of beraprost, a chemically and biologically stable analog of prostacyclin, on cough response to inhaled capsaicin was examined in 14 patients with chronic bronchitis, a neutrophilic bronchial disorder, in a randomized, placebo-controlled crossover study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of the airway cough reflex sensitivity. Results: After a 2-week treatment with beraprost (80 μg twice a day orally), the cough threshold was significantly (P < .05) decreased as compared with placebo [12.2 (geometric standard error of the mean [GSEM] 1.5) μM vs. 24.4 (GSEM 1.3)]. Conclusions: These findings indicate that prostacyclin is involved in the pathophysiology of cough reflex sensitivity in patients with chronic bronchitis, a frequently encountered neutrophilic bronchial disorder presenting with chronic productive cough.

Cough Reflex Sensitivity Testing in Asthmatic Patients and Healthy Volunteers

Abstract Asthma and allergic diseases are complex conditions caused by a combination of genetic and environmental factors. Cough is a major symptom in some people with asthma. Cough reflex sensitivity (CRS) test with capsaicin is one of the most important method for cough studying. Cough reflex sensitivity was defined as the lowest concentration of capsaicin that elicited 2 or more (C2) and 5 or more coughs (C5). The aim of this study was to find out a cough reflex sensitivity in patients with asthma bronchiale and in healthy volunteers. In the present study we conclude that cough reflex sensitivity was significantly increased in asthmatic adult patients compared with healthy adult volunteers.

LOW-PUNGENT SWEET PEPPER SELECTED UNDER CONTINUOUS FLUORESCENT ILLUMINATION

‘Shishito’ (Capsicum annuum L.) is a group of sweet pepper cultivars. Fruits are small, green and non-pungent, but pungent fruits sometimes occur. In our previous study, plants of ‘Shishito’ grew well and bore abundant fruits under continuous fluorescent illumination, however, pungent fruit strongly increased. In this study, mutation was induced and screening for low-pungent variants in M2-M3 was conducted under continuous fluorescent illumination. Seeds of ‘Shishi-Homare’ were treated with a 30 Gy 220 MeV 12C5+ beam. Self-fertilized M2 seeds were harvested from M1 plants individually. First screening was conducted in the field and 126 plants were selected from 762 plants. Second screening was conducted in a growth chamber under continuous fluorescent illumination, in which the concentration of the pungent compound capsaicin in the fruit placenta was determined with HPLC. One plant with the lowest capsaicin concentration was selected and self-pollinated. M3 plants were grown under continuous fluorescent illumination. The capsaicin concentration of M3 plants under continuous fluorescent illumination was lower than that of M2 plants however, plants with high capsaicin level still existed. One plant with the lowest capsaicin concentration was selected and self-pollinated. The capsaicin concentration of M4 plants under continuous fluorescent illumination was much lower than that of wild type ‘Shishi-Homare’; the average concentration of M4 plants was about one sixth of that of the wild type.

Th2 cytokine inhibition and cough in asthmatic and bronchitic patients

BACKGROUND: Activated T helper lymphocytes are present in the airway and their production of cytokines is important in the pathogenesis of asthma, however, the relationship between T helper lymphocyte‐derived cytokines and airway cough reflex sensitivity remains unknown. METHODS: The effect of the orally active Th2 cytokine inhibitor suplatast tosilate on cough response to inhaled capsaicin was examined in eleven patients with stable atopic asthma and compared with patients having non‐atopic asthma and chronic bronchitis (the latter of which is not related to Th2 cytokines). Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. Concentration of serum total IgE level was also measured after treatment with suplatast tosilate. RESULTS: The cough threshold after two weeks treatment with suplatast tosilate was significantly greater than the value with placebo accompanied by decrease of serum IgE level in atopic asthmatics. This significance was not observed in patients with non‐atopic asthma or chronic bronchitis. CONCLUSIONS: Th2 cytokines may be possible modulators augmenting airway cough reflex sensitivity in atopic asthmatic airways but not in non‐atopic asthmatic or bronchitic airways.

Cough sensitivity in atopic dermatitis

The aim of study was to investigate the cough sensitivity (C2) to capsaicin (CAPS) in patients with atopic dermatitis without clinical respiratory symptoms. Cough sensitivity (C2) is defined as the lowest CAPS concentration, which evokes two or more coughs. Forty eight dermatological patients (21 M, 27 F; mean age 44 yr) and 24 healthy volunteers (14 M, 10 F; mean age 37 yr) inhaled deep breath (2 l) of CAPS aerosol in doubled concentrations (from 0.02 to 200 μmol/l) (Pari Provokationstest I, PARI WERK; mass median diameter 1.2 μm). Cough sensitivity (C2) expressed as geometric mean (95% CI) of CAPS concentration was 0.13 μmol/l (0.06–0.31) in 26 patients with atopic dermatitis (10 M, 16 F; mean age 41 yr), 5.51 μmol/l (1.33–22.90) in 22 patients with psoriasis (11 M, 11 F; mean age 46 yr) and 4.29 μmol/l (2.54–7.26) in 24 controls. There is significant difference of cough sensitivity (C2) between patients with atopic dermatitis and healthy volunteers ( p<0.001) and also between patients with atopic dermatitis and psoriasis ( p<0.001). Cough sensitivity (C2) in atopic dermatitis patients without clinical respiratory symptoms is significantly increased. In patients with psoriasis cough sensitivity (C2) is not significantly changed.

Thromboxane antagonism and cough in chronic bronchitis

BACKGROUND. The increased eicosanoid synthesis has been suggested as the underlying mechanism of chronic productive cough in patients with chronic bronchitis. METHOD: The effects of the orally active thromboxane A2 (TxA2) receptor antagonist seratrodast and the cysteinyl leukotrienes (cLTs) receptor antagonist pranlukast on cough response to inhaled capsaicin were examined in sixteen patients with stable chronic bronchitis. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough sensitivity. RESULTS: The cough threshold was significantly increased compared with placebo after four-week treatment with seratrodast, but not after treatment with pranlukast. CONCLUSIONS: TxA2, but not cLTs, may be a possible modulator augmenting airway cough sensitivity in chronic bronchitis. Thromboxane antagonism may be considered to be one of the therapeutic options for the treatment of chronic productive cough.

Comparison between tidal breathing and dosimeter methods in assessing cough receptor sensitivity to capsaicin

Dosimeter method and tidal breathing method have been used to assess cough sensitivity to inhaled capsaicin, a C-fibre ending stimulator. The aim of the present study was to evaluate the repeatability of and the agreement between the two methods. Cough threshold, the lowest concentration of capsaicin causing five or more coughs, was measured twice 1-3 weeks apart by each method in 26 normal subjects. Increasing concentrations of capsaicin were inhaled by a single breath in the dosimeter method or by 15 s tidal breathing in the tidal breathing method in 1 min intervals. Coefficients of repeatability of the cough threshold measurement were 1.89 and 2.71 doubling concentration in the tidal breathing method and the dosimeter method, respectively, suggesting good repeatability in the cough threshold measurement by both methods. The cough threshold was significantly (P < 0.0001) greater by 1.75 doubling concentration on the dosimeter method than the tidal breathing method. The coefficient of agreement between the two methods was 2.53 doubling concentration. Five subjects complained of burning sensation in the throat in the dosimeter method but no patient complained about the tidal breathing method (P < 0.05). Although the agreement between the two methods was considered to be good, higher concentrations of capsaicin solution were required to determine the cough threshold in the dosimeter method, resulting in an unpleasant sensation in the throat.

Airway cough sensitivity to inhaled capsaicin and bronchial responsiveness to methacholine in asthmatic and bronchitic subjects.

The objective of this study was to evaluate the effect of chronic airway inflammation on airway cough sensitivity and non-specific bronchial responsiveness, and the relationship between them. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, and non-specific bronchial responsiveness, defined as the methacholine concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1) (PC20-FEV1), were measured in 18 asthmatic, 13 bronchitic (sinobronchial syndrome) and 28 healthy non-atopic subjects. All subjects were non-smoking men. The geometric mean values (mumol) of the cough threshold were 18.9 (GSEM 1.29), 8.69 (GSEM 1.29) and 27.6 (GSEM 1.31) in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly lower (P << 0.02) than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.48 mg/ml (GSEM 1.38)) was significantly lower than that in bronchitic subjects (18.5 mg/ml (GSEM 1.75)) (P << 0.001). There was no correlation between cough threshold and PC20-FEV1 values (correlation coefficient (r) = 0.155). These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma, and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.