Cough Reflex Sensitivity In Patients Research Articles

Decreased capsaicin cough reflex sensitivity predicts hospitalisation due to COPD

IntroductionPatients with chronic obstructive pulmonary disease (COPD) are often hospitalised due to severe acute exacerbation (AE) or community-acquired pneumonia (CAP). Previous studies revealed the association of cough reflex sensitivity with...

P9‐24: Hydrogen sulfide in serum or sputum supernatant as a biomarker for cough reflex sensitivity in patients with asthma

P9‐24: Hydrogen sulfide in serum or sputum supernatant as a biomarker for cough reflex sensitivity in patients with asthma

Tiotropium Attenuates Refractory Cough and Capsaicin Cough Reflex Sensitivity in Patients with Asthma

Asthmatic cough is often refractory to standard treatments such as inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA). Tiotropium may modulate cough reflex sensitivity of acute viral cough, but its efficacy in asthmatic cough remains unknown. To evaluate whether tiotropium improves cough and cough reflex sensitivity in patients with asthma refractory to ICS/LABA. Seventeen consecutive patients with asthma with chronic cough despite the use of ICS/LABA (13 women; 43.4 ± 19.0 years; average ICS dose, 651 ± 189 μg/d; fluticasone equivalent) were additionally treated with tiotropium (5 μg/d) for 4 to 8 weeks to examine its effects on pulmonary function and capsaicin cough reflex sensitivity (cough thresholds C2 andC5). Cough severity, cough-specific quality of life, and asthma control were also evaluated using cough visual analog scales (VASs), the Japanese version of Leicester Cough Questionnaire (J-LCQ), and Asthma Control Test (ACT), respectively. Patients with an improved cough VAS score of 15 mm or more were considered responders to tiotropium. Tiotropium significantly improved cough VAS, J-LCQ, and ACT scores, but not FEV1. Changes in cough VAS score correlated with those in C2 (r=-0.58; P= .03), C5 (r=-0.58; P= .03), and ACT scores (r=-0.62; P= .02), but not in FEV1 in the overall patients. When analyses were confined to the 11 responders, tiotropium significantly improved capsaicin cough reflex sensitivity within the subgroup (C2: P= .01 and C5: P= .02) and versus the nonresponders (C2: P= .004 and C5: P= .02). Tiotropium may alleviate asthmatic cough refractory to ICS/LABA by modulating cough reflex sensitivity but not through bronchodilation.

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.

Effect of an Orally Active Th2 Cytokine Inhibitor, Suplatast Tosilate, on “Atopic Cough”

"Atopic cough" is a new clinical entity that presents with isolated chronic bronchodilator-resistant cough accepted in the Japanese Respiratory Society Guidelines for Management of Cough. The essential features are eosinophilic tracheobronchitis, increased cough reflex sensitivity and an atopic constitution. It has been suggested that activated helper T lymphocytes and the cytokines which are produced by these cells are involved in the pathogenesis, but the relationship between helper T cell-derived cytokines and the airway cough reflex sensitivity remains unknown. The effect of an orally active Th2 cytokine inhibitor, suplatast tosilate (CAS 94055-76-2, IPD; 300 mg/day), on the cough response to inhaled capsaicin (CAS 404-86-4) was examined in ten patients with atopic cough. The 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. The serum total immunoglobulin E (IgE) level and the peripheral blood eosinophil count were also determined after treatment with suplatast tosilate. The cough threshold measured after four weeks of treatment with suplatast tosilate was significantly increased compared to the value obtained with placebo, along with a decrease of the serum IgE level and peripheral eosinophil count. Th2 cytokines may increase the airway cough reflex sensitivity in patients with atopic cough. Oral administration of suplatast tosilate may be a novel therapy for atopic cough.

GERD-related Chronic Cough

GERD-related Chronic Cough

Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patients with sinobronchial syndrome

BackgroundSinobronchial syndrome is a cause of chronic productive cough. Inflammatory mediators are involved in the pathophysiology of chronic productive cough. Accumulating evidences indicate that cyclooxygenase (COX)-2, one of the inducible isoforms of COX, is a key element in the pathophysiological process of a number of inflammatory disorders. However, little is known about the role of COX-2 in chronic productive cough in patients with sinobronchial syndrome known as neutrophilic bronchial inflammation.MethodsThe effect of etodolac, a potent COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 15 patients with sinobronchial syndrome in a randomized, placebo-controlled cross-over study. 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.ResultsThe cough threshold was significantly (p < 0.03) increased after two-week treatment with etodolac (200 mg twice a day orally) compared with placebo [37.5 (GSEM 1.3) vs. 27.2 (GSEM 1.3) μM].ConclusionsThese findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in patients with sinobronchial syndrome.

Cough‐reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency

The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations. The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C(5)). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period. The study group comprised 45 COPD subjects and 10 controls. Mean log C(5) was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76-1.18) versus 1.26 (95% CI: 0.81-1.71), P = 0.095). In the COPD group, log C(5) was negatively correlated with serum CRP level (r = -0.36, P = 0.02) and significantly associated with the exacerbation frequency (r = -0.38, P = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency (r(2) = 0.15, P = 0.01). Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.

Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro‐oesophageal reflux and chronic cough

Gastro-oesophageal reflux disease (GORD) is one of the most common causes of chronic cough; however, the mechanisms by which GOR initiates coughing are incompletely understood. We address the hypothesis that acidification of oesophagus acutely increases the cough reflex sensitivity in patients with GORD and chronic cough. Nine patients with GORD with chronic cough and 16 patients with GORD without cough were recruited. In a randomized double blind study, saline and acid (HCl, 0.1 mol L(-1)) were separately infused into oesophagus via naso-oesophageal catheter. Cough reflex sensitivity to inhaled capsaicin was determined immediately after completion of each infusion. Infusion of acid into oesophagus increased capsaicin cough reflex sensitivity in patients with GORD and chronic cough. In contrast, acid had no effect on the cough sensitivity in patients with GORD without cough. In a separate study, acid infusion into oesophagus did not affect the cough sensitivity in 18 healthy subjects. We conclude that acid in the oesophagus acutely increases the cough reflex sensitivity to capsaicin in patients with GORD and chronic cough. This phenomenon may contribute to the pathogenesis of cough due to GORD.

Change in bronchial responsiveness and cough reflex sensitivity in patients with cough variant asthma: effect of inhaled corticosteroids

BackgroundCough variant asthma (CVA) is a cause of chronic cough and a precursor of typical asthma. We retrospectively examined the longitudinal change in bronchial responsiveness and cough reflex sensitivity in CVA patients with respect to the effect of long-term inhaled corticosteroids (ICS).MethodsProvocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20-FEV1) and provocative concentration of capsaicin eliciting 5 or more coughs (C5) were measured before treatment and during a follow up period following relief of cough (median; 2.0 (range; 0.5 to 8.0) years after the initial visit) in a total of 20 patients with CVA (7 males and 13 females, mean ± SD age of 49.9 ± 12.9 years).ResultsThree of 8 patients not taking long-term ICS developed typical asthma compared to none of 12 patients taking ICS (p = 0.0171). PC20-FEV1 significantly (p < 0.0001) increased from 1.80 (GSEM, 1.35) to 10.7 (GSEM, 1.63) mg/ml in patients taking ICS but did not change in patients not taking ICS [2.10 (GSEM, 1.47) compared to 2.13 (GSEM, 1.52) mg/ml]. Cough threshold did not change in patients whether taking or not taking ICS.ConclusionLong-term ICS reduces bronchial hyperresponsiveness in CVA as recognized in typical asthma. Cough reflex sensitivity is not involved in the mechanism of cough in CVA.

Impaired Efficacy of Cough in Patients With Parkinson Disease

Aspiration pneumonia, a leading cause of death in patients with Parkinson disease (PD), usually occurs at the advanced stages of the disease. We investigated both motor and sensory components of cough and induced-sputum substance P (SP) concentrations in patients with early and advanced stages of PD to assess whether cough efficacy is impaired in PD. Fifteen female patients with early stages of PD (Hoehn and Yahr stage II-III), 10 patients with advanced stages of PD (Hoehn and Yahr stage IV), and 15 age-matched female control subjects were investigated. The motor component of cough efficacy was assessed by monitoring voluntary maximal cough peak flow. The sensory component of cough efficacy was assessed by measuring cough reflex sensitivity to citric acid inhalation. Sputum SP concentrations were measured in sputum induced by hypertonic saline solution inhalation. The mean (+/- SD) cough peak flow rates in patients with both early PD (230 +/- 74 L/min; p < 0.005) and advanced PD (186 +/- 60 L/min; p < 0.0001) were significantly weaker than that in control subjects (316 +/- 70 L/min). Cough reflex sensitivity in patients with advanced PD (46.7 +/- 49.3 g/L) was significantly lower compared to control subjects (14.5 +/- 16.6 g/L; p < 0.01) and patients with early PD (11.2 +/- 14.8 g/L; p < 0.005). The sputum SP concentration was significantly lower in patients with advanced PD (11.2 +/- 8.4 pg/mL) compared to that in control subjects (35.6 +/- 15.4 pg/mL) and patients with early PD (28.5 +/- 16.4 pg/mL). In the early stages of the disease, mainly the motor component of cough was impaired. In advanced stages of the disease, both the motor and sensory components of cough were impaired. Sputum SP concentration significantly declined in patients with advanced PD. The results suggest that the combination of impaired motor and sensory components of cough may play an important role in the development of aspiration pneumonia in PD.