Cough Provocation Test Research Articles

Xingbei antitussive granules ameliorate cough hypersensitivity in post-infectious cough guinea pigs by regulating tryptase/PAR2/TRPV1 pathway

Ethnopharmacological relevanceXingbei antitussive granules (XB) is a classic Chinese Medicine prescription for treating post-infectious cough(PIC), based on the Sanao Decoction from Formularies of the Bureau of People’s Welfare Pharmacies in the Song Dynasty and Jiegeng decoction from Essentials of the Golden Chamber in the Han Dynasty. However, the therapeutic effects and pharmacological mechanisms are still ambiguous. In the present study, we endeavored to elucidate these underlying mechanisms. Aims of the studyThis study aimed to explore the potential impact and mechanism of XB on PIC, and provide a scientific basis for its clinical application. Materials and methodsCigarette smoking (CS) combined with lipopolysaccharide (LPS) nasal drops were administered to induce the PIC guinea pig with cough hypersensitivity status. Subsequently, the model guinea pigs were treated with XB and the cough frequency was observed by the capsaicin cough provocation test. The pathological changes of lung tissue were assessed by HE staining, and the levels of inflammatory mediators, mast cell degranulating substances, and neuropeptides were detected. The protein and mRNA expression of transient receptor potential vanilloid type 1(TRPV1), proteinase-activated receptor2(PAR2), and protein kinase C (PKC) were measured by Immunohistochemical staining, Western blot, and RT-qPCR. Changes in the abundance and composition of respiratory bacterial microbiota were determined by 16S rRNA sequencing. ResultsAfter XB treatment, the model guinea pigs showed a dose-dependent decrease in cough frequency, along with a significant alleviation in inflammatory infiltration of lung tissue and a reduction in inflammatory mediators. In addition, XB high-dose treatment significantly decreased the levels of mast cell Tryptase as well as β-hexosaminidase (β-Hex) and downregulated the expression of TRPV1, PAR2, and p-PKC. Simultaneously, levels of neuropeptides like substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and nerve growth factor (NGF) were improved. Besides, XB also can modulate the structure of respiratory bacterial microbiota and restore homeostasis. ConclusionXB treatment alleviates cough hypersensitivity and inflammatory responses, inhibits the degranulation of mast cells, and ameliorates neurogenic inflammation in PIC guinea pigs whose mechanism may be associated with the inhibition of Tryptase/PAR2/PKC/TRPV1 and the recovery of respiratory bacterial microbiota.

Deep Inspiration-Provoked Cough: A Sign of Cough Reflex Arc Hypersensitivity.

Deep inspiration-provoked cough (DIPC) is a form of allotussia. Allotussia is thought to be a manifestation of cough reflex arc hypersensitivity but objective evidence about this is lacking. 36 subjects with chronic cough and 25 healthy subjects underwent mannitol and citric acid cough provocation tests. DIPC was defined as two or more coughs after deep inhalation of an empty mannitol capsule. Citric acid was administered utilizing a dosimetric nebulizer during controlled tidal breathing. Nine subjects demonstrated DIPC, 8/36 subjects with chronic cough and 1/25 healthy subjects (p = 0.048). The concentration of citric acid to provoke five or more coughs (C5) was 23.4 (63.8) mM among subjects with DIPC and 750 (2941) mM among the subjects without it (p = 0.006). The number of deep inspiration-provoked coughs correlated with the citric acid C5 (Rs -0.38, p = 0.002). In conclusion, DIPC, a form of allotussia, is associated with cough reflex arc hypersensitivity.Trial Registration Number.ClinicalTrials.gov database KUH5801136.

Utility of Cough Provocation Tests in Chronic Cough and Respiratory Diseases: A Comprehensive Review and Introduction of New Reference Ranges for the Capsaicin Test.

Cough provocation tests (CPTs) are an objective measurement of the sensitivity of the cough reflex arc. However, they are not established in clinical practice because a large variability of response in healthy subjects limits their diagnostic value. There is a paucity of studies that have investigated CPT reference ranges in healthy subjects. This systematic review describes the variability of the responses to CPTs in healthy subjects and factors that influence it. A new analysis of 134 healthy subjects was conducted to create reference ranges for single-breath capsaicin CPT by calculating the interquartile ranges for the provocative concentration of capsaicin to induce 2 and 5 coughs. Female subjects had a more sensitive cough reflex than male counterparts. The ability of CPTs to distinguish various respiratory diseases from healthy subjects was also reviewed. Cough sensitivity was consistently heightened in the following groups: unselected patients with chronic, refractory, or recurrent cough, unexplained chronic cough, gastro-esophageal reflux-associated cough, cough-variant asthma, lower airway symptoms induced by chemical irritants, and fibrotic interstitial lung diseases. In the following groups, hypersensitivity of the cough reflex was present in those individuals whose symptom profile was predominated by cough: asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and sarcoidosis. In the following conditions, patients usually cough in order to expectorate mucus from their airways, not because of a hypersensitive cough reflex arc: productive cough, asthma, upper airway cough syndrome, COPD, bronchiectasis, cystic fibrosis, and chronic respiratory infections. CPTs have the potential to identify patients with chronic respiratory symptoms due to cough reflex hypersensitivity, thereby providing a targeted approach for therapy.

Cough-provocation tests with hypertonic aerosols.

Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

Comparison of mannitol and citric acid cough provocation tests.

Citric acid has been used as a cough provocation test for decades. However, the methods of administration have not been standardized. Inhaled mannitol is a novel cough provocation test, which has regulatory approval and can be performed utilizing a simple disposable inhaler in a standardized manner. To compare the mannitol and citric acid cough provocation tests with respect to their ability to identify subjects with chronic cough and their tolerability. Subjects with chronic cough (n = 36) and controls (n = 25) performed provocation tests with mannitol and citric acid. Both tests were video recorded. Cough sensitivity was expressed as coughs-to-dose ratios (CDR) and the cumulative doses to mannitol or concentration to citric acid evoking 5 coughs (C5). Forced expiratory volume in 1 s (FEV1), visual analogue scales (VAS), test completion rates and the total cough frequencies were analysed. Mannitol and citric acid CDR both effectively separated those with cough and the control subjects (AUC 0.847 and 0.803, respectively) as did C5 (AUC 0.823 and 0.763, respectively). There was a good correlation between the cough sensitivity provoked by the two stimuli, either expressed as CDR (r = 0.65, p < 0.001) or C5 (r = 0.53, p = 0.001). Both tests were similarly tolerated in terms of VAS, although more patients discontinued the mannitol test early, primarily due to cough. Mannitol and citric acid tests correlated well, equally identified subjects with chronic cough and their tolerability was similar. The feasibility issues, strict standardisation and regulatory approval may favour mannitol to be used in clinical cough research.

Clinical application of capsaicin cough challenge test

The capsaicin cough provocation test is the most commonly used test to objectively evaluate cough sensitivity.The mechanism is simple and the test can be accepted by a lot of patients, which could evaluate the degree of cough, guide medicine, promote new drug development, seek for the cause.This article mainly reviews the clinical application of capsaicin cough test to assess degree of cough and guide treatment. Key words: Capsaicin; Diagnostic techniques, respiratory system; Nasal provocation tests; Cough; Technology assessment, biomedical; Diagnosis; Therapeutic uses; Review

Long-term prognosis of chronic cough: a prospective, observational cohort study

BackgroundThe long-term prognosis of chronic cough and its determinants need to be clarified.MethodsThis is a prospective, observational cohort study. Eighty-nine unselected subjects with chronic (> 8 weeks’ duration) cough were carefully investigated: Clinical examination, symptom questionnaire, Leicester Cough Questionnaire (LCQ), skin prick tests, ambulatory peak expiratory flow monitoring, spirometry before and after 0.4 mgs of salbutamol, exhaled nitric oxide concentration measurement, hypertonic saline cough provocation test, and histamine bronchial provocation test. After five years, a letter was sent to the subjects containing questions about continuation of cough, smoking, indoor exposures, presence of co-morbidities, and current medication. It also contained LCQ and Cough Clinic diagnostic questionnaire. Sixty-eight subjects (76%) responded.ResultsAt five years, continuing regular cough was present in 31 (46%) of the subjects and continuing impairment in cough-related quality of life (less than 1.3 points’ improvement in LCQ) in 32 (47%). Continuing regular cough was associated with presence of chronic rhinitis or esophageal reflux disease, baseline mild airway responsiveness to histamine, and baseline strong cough responsiveness to hypertonic saline. Continuing impairment in cough-related quality of life was associated with high body mass index, absence of atopy, absence of pets, and high number of background disorders (esophageal reflux disease, asthma, or chronic rhinitis).ConclusionsAlmost half of subjects with chronic cough suffered of the disorder at five years from initial assessment. Several possible determinants of poor prognosis could be identified.

Now is the Right Time to Establish a New Strategy for Managing Chronic Cough as a Neuropathic Disorder.

Now is the Right Time to Establish a New Strategy for Managing Chronic Cough as a Neuropathic Disorder.

Airway oxidative stress in chronic cough

BackgroundThe mechanisms of chronic cough are unclear. Many reactive oxygen species affect airway sensory C-fibres which are capable to induce cough. Several chronic lung diseases are characterised by cough and oxidative stress. In asthma, an association between the cough severity and airway oxidative stress has been demonstrated. The present study was conducted to investigate whether airway oxidative stress is associated with chronic cough in subjects without chronic lung diseases.MethodsExhaled breath condensate samples were obtained in 43 non-smoking patients with chronic cough and 15 healthy subjects. Exclusion criteria included a doctor’s diagnosis of any lung disorders and any abnormality in lung x-ray. The concentration of 8-isoprostane was measured. In addition, the patients filled in Leicester Cough Questionnaire and underwent hypertonic saline cough provocation test, spirometry, ambulatory peak flow monitoring, nitric oxide measurement, and histamine airway challenge. In a subgroup of patients the measurements were repeated during 12 weeks’ treatment with inhaled budesonide, 800 ug/day.ResultsThe 8-isoprostane concentrations were higher in the cough patients than in the healthy subjects (24.6 ± 1.2 pg/ml vs. 10.1 ± 1.7 pg/ml, p = 0.045). The 8-isoprostane concentration was associated with the Leicester Cough Questionnaire total score (p = 0.044) but not with the cough sensitivity to saline or other tests. Budesonide treatment did not affect the 8-isoprostane concentrations.ConclusionsChronic cough seems to be associated with airway oxidative stress in subjects with chronic cough but without chronic lung diseases. This finding may help to develop novel antitussive drugs.Trial registrationThe study was registered in ClinicalTrials.gov database (KUH5801112), identifier NCT00859274.

Capability of hypertonic saline cough provocation test to predict the response to inhaled corticosteroids in chronic cough: a prospective, open-label study

BackgroundMany patients with chronic cough respond to treatment with inhaled corticosteroids but it is difficult to predict which patients are likely to respond. The primary aim of the present study was to define the capability of hypertonic saline cough provocation test to predict the responsiveness to inhaled corticosteroids in chronic cough. The secondary aim was to assess the ability of the saline test to monitor the healing of cough during corticosteroid treatment.MethodsForty-three patients with chronic cough were recruited. Before therapy, spirometry, ambulatory peak flow monitoring, nitric oxide measurement, histamine airway challenge, and saline test were performed. Those responding to the first saline test repeated it and the nitric oxide measurement during the subsequent visits. The patients used inhaled budesonide, 400 ug twice daily, for twelve weeks. The treatment response was assessed by Leicester Cough Questionnaire at baseline, and at one, four, and twelve weeks.ResultsSeventy-seven % of the patients demonstrated the minimal important difference in the Leicester Cough Questionnaire indicating a symptomatic response. Neither the response magnitude nor the speed was predicted by the saline test. Histamine challenge showed the strongest predictive ability: The maximal improvement in Leicester Cough Questionnaire total score was 5.08 (3.76 – 6.40) points in the histamine positive and 2.78 (1.55 – 4.01) points in the histamine negative subjects (p = 0.006). Baseline nitric oxide level also associated with the improvement in Leicester Cough Questionnaire total score (p = 0.02). During the treatment, the cough sensitivity to saline gradually decreased among the budesonide responders but not in the non-responders. Nitric oxide levels decreased very rapidly among the responders.ConclusionsSaline test cannot predict the responsiveness to inhaled corticosteroids in chronic cough but it may be utilized to monitor the effect of this treatment.Trial registrationThe study was registered in ClinicalTrials.gov database (KUH5801112). ClinicalTrials.gov Identifier: NCT00859274

Determinants of asthma control and quality of life in stable asthma: evaluation of two new cough provocation tests

Asthma control and quality of life are poorly associated with traditional asthma biomarkers. In the present study, we evaluated two new cough provocation tests in this respect. Asthma Control Questionnaire and Leicester Cough Questionnaire were completed by 36 stable asthmatics. Cough provocation tests with hypertonic saline and isocapnic hyperpnoea of dry air were performed, as well as spirometry, ambulatory peak expiratory flow (PEF) monitoring and exhaled nitric oxide (eNO) measurement. Leicester Cough Questionnaire score correlated closely with cough responsiveness to hypertonic saline and isocapnic hyperpnoea (R = -0.66, P < 0.001 and R = -0.49, P = 0.002, respectively). Asthma Control Questionnaire score also correlated with the cough responsiveness to these tests (R = 0.52, P = 0.001 and R = 0.43, P = 0.008, respectively). Forced expiratory volume in 1 s (%predicted), diurnal PEF variation and eNO did not correlate with cough-related quality of life but showed some association with asthma control. There was a significant correlation between Leicester Cough Questionnaire and Asthma Control Questionnaire (R = -0.54, P = 0.001). Asthma control and cough-related quality of life are more closely associated with cough responsiveness to the investigated cough provocation tests than to eNO and traditional indices of bronchial obstruction. Cough is a major contributor to poor asthma control.

Asthmatic cough and airway oxidative stress

The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma.Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements.Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03–0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects.Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma.

The Cough Receptor TRPV1 Agonists 15(S)-HETE and LTB4 in the Cough Response to Hypertonicity

Asthmatic patients are hypersensitive to the cough-provoking effect of hypertonic aerosols. 15- hydroxyeicosatetraenoic acid (15(S)-HETE) and leukotriene (LT) B4 are asthma-related mediators which can be released upon hypertonic stimuli, and both are potent agonists of the transient receptor potential vanilloid subfamily member 1 (TRPV1), a major cough receptor. Therefore, they are potential mediators for hypertonicity-provoked cough. Twenty-six asthmatic and ten healthy subjects underwent a hypertonic saline cough provocation test. Exhaled breath condensate was collected before and after the test, and the concentrations of 15(S)-HETE and LTB4 were analysed. Neither the baseline concentrations of these mediators nor the saline test-induced changes in them were associated with cough responsiveness to hypertonicity. High baseline 15(S)-HETE was associated with aspirin hypersensitivity and high LTB4 with male sex and large variability in ambulatory peak flow measurements. The TRPV1 agonists 15(S)-HETE and LTB4 seem not to be involved in the cough response to hypertonicity in asthmatic patients.

The Role of Nitrosative Stress in the Pathogenesis of Unexplained Chronic Cough with Cough Hypersensitivity

Unexplained chronic cough is a common condition without specific causes. A hyperreactivity of the cough reflex has been suggested as a mechanism for inducing chronic cough. We hypothesized that nitrosative stress in the upper airway might play a role in cough hypersensitivity by causing neurochemical abnormalities. Fifty-one patients with unexplained chronic cough and 27 controls were enrolled. A capsaicin cough provocation test was performed to determine cough sensitivity. Nitrosative stress in the upper airway was assessed by quantifying 3-nitrotyrosine (3-NT) immunostaining in nasal epithelial cells (NECs) and measuring nasal nitric oxide (nNO). The effect of NO on airway epithelium was investigated by measuring the levels of substance P (SP) in nasal lavage fluid and evaluating SP expression in airway epithelial cells. Based on the results of the capsaicin test, patients were divided into two groups: a cough hypersensitivity (CHS) group and a normal cough sensitivity (NCS) group. The levels of 3-NT immunoreactivity in NECs were significantly higher in CHS (49 ± 2.9%) than in NCS (27 ± 3.3%) and controls (12 ± 1.6%), a pattern that was also reflected in the values of nNO (350 ± 43, 215 ± 23, and 138 ± 23 ppb in CHS, NCS, and controls, respectively). SP concentration was also elevated in nasal lavage fluids from CHS (746 ± 28 pg/mL) compared with that from NCS (624 ± 40 pg/mL) and controls (526 ± 41 pg/mL). SP expression in airway epithelial cells was greatly enhanced by exposure to NO donor, which was attenuated by pretreatment with either NO scavenger or NO synthase inhibitor. Increased nitrosative stress in the upper airway may play a role in the pathogenesis of unexplained chronic cough with CHS through enhanced secretion of SP.

The utility of the mannitol challenge in the assessment of chronic cough: a pilot study

There is a need for more objective outcome measures for chronic cough. In this pilot study we sought to investigate the utility of the mannitol challenge as a cough-provocation test in non-asthmatic chronic cough. We studied 16 healthy controls and 13 subjects with chronic cough. We assessed cough severity using a visual analogue score, capsaicin cough sensitivity, health status using the Leicester Cough Questionnaire and the dose of mannitol to cause 2 (C2) or 5 (C5) coughs. In all of the subjects with chronic cough and 6 of the controls we assessed the 1-week repeatability of the mannitol challenge. We found that in those subjects with chronic cough the geometric mean (logSEM) mannitol C2 and C5 was heightened compared to controls (C2: 4 (0.2) versus 16 (0.1); p = 0.04 and C5: 63 (0.1) versus 251 (0.1); p = 0.04). Cough visual analogue score, capsacin-induced cough sensitivity and health status were also altered in chronic cough compared to healthy controls, but in those subjects with chronic cough none of these outcomes was correlated with the mannitol C2 or C5. The repeatability of the mannitol challenge assessed by intraclass correlation was C2 = 0.53 and C5 = 0.59. A cut-off in the dose of mannitol of 62 mg/ml for C2 and 550 mg/ml for C5 had a sensitivity of 69 and 62% and specificity of 69 and 81% respectively to distinguish chronic coughers from healthy controls. In conclusion, the mannitol challenge my have potential as a novel cough challenge test and further work is required to extend our findings and to assess whether it has utility in different causes of chronic cough.

Hypertonic saline cough provocation test with salbutamol pre‐treatment: evidence for sensorineural dysfunction in asthma

Cough is one of the most common symptoms of asthma. However, studies using capsaicin, citric acid, or tartaric acid to document cough threshold have repeatedly failed to show statistically significant differences between asthmatic and healthy subjects. The studies using hypertonic aerosols as the cough stimulant have suggested an enhanced sensitivity in asthmatic subjects but the induced bronchoconstriction has made the interpretation of the results difficult. To determine the cough sensitivity to hypertonicity in healthy subjects, patients with chronic cough, and patients with asthma in a setting where the induction of bronchoconstriction is prevented. Nineteen healthy subjects, 21 non-asthmatic patients with chronic cough, and 26 asthmatic patients with chronic cough underwent an incremental hypertonic saline challenge including a pre-treatment with 0.4 mg of salbutamol. Spirometry was performed before the challenge, after salbutamol, and after the challenge. The patients with cough also underwent skin testing, histamine challenge, exhaled nitric oxide measurement, ambulatory peak flow monitoring, kept cough diary, and filled in the Leicester Cough Questionnaire. Eighteen patients repeated the saline challenge. The challenge did not induce bronchoconstriction in any group. The osmolality to provoke 15 cumulative coughs was significantly smaller in the asthmatic patients than in the healthy subjects (P<0.001) and in the cough patients without asthma (P=0.04). According to multivariate analysis among all the 47 patients with cough, female sex (P<0.001) and large spontaneous peak flow variation in the ambulatory recording (P=0.001) were associated with high sensitivity to saline. The saline challenge response was well repeatable (intraclass correlation coefficient 0.90). The findings of the present study are not affected by induced bronchoconstriction. Asthma or, more specifically, spontaneous, reversible airway obstruction is associated with an enhanced sensitivity to the cough-provoking effect of hypertonic saline. This suggests a pathological function of the sensorineural apparatus in this disorder.

Transvaginal tape lysis for urinary obstruction after suburethral tape placement. When to do an immediate replacement?

To evaluate the interest and the indications of an immediate replacement of a suburethral tape after tape lysis for urinary obstruction is the aim of the study. From 2000 until 2007, a total of 22 patients underwent suburethral tape placement for stress urinary incontinence and developed thereafter a bladder outlet obstruction. These patients had a transvaginal tape lysis under local anesthesia. An immediate replacement of the tape was carried out in those patients who developed leakage under cough provocation test. Twelve patients (group 1) underwent a tape lysis and replacement. Ten patients (group 2) underwent a simple tape lysis. The two groups were demographically comparable. The continence rate was 100% in the two groups. The success rate defined by urodynamics was 75% for the first group and 80% for the second group. The success rate defined by the disappearance of the initial symptoms and improvement of the scores of the questionnaires was 75% for the first group and 90% for the second group.

Simultaneous versus video counting of coughs in hypertonic cough challenges

BackgroundThe coughs occurring during cough provocation tests are usually counted at the same time when the test is being conducted, i.e., simultaneously. It is unknown whether cough counting from video recording might increase the accuracy of the cough counting. During recent years, cough challenges with hypertonic aerosols have been introduced. They often provoke very frequent coughing which may complicate the simultaneous cough counting.ObjectiveTo assess whether cough counting from video recording is superior to simultaneous cough counting in two different hypertonic cough challenges.MethodsThe analysis includes 82 hypertonic saline challenges performed on 66 subjects, providing 1984 observation minutes with both simultaneous and video cough counting. The cough sensitivity was expressed as the osmolality to provoke 15 cumulative coughs (CUM15). The analysis also includes 136 hypertonic histamine challenges performed on 114 subjects providing 5373 observation minutes with both simultaneous and video counting. The cough sensitivity was expressed as the cumulative number of coughs divided by the final histamine concentration administered (CCR). This challenge involved several additional measurements to cough counting.ResultsFor the saline challenge, the mean difference between the counting types was 0.0 coughs per minute with 95% limits of agreement of -1.2 to 1.2 coughs per minute. For the hypertonic histamine challenge the respective figures were 0.3 (-1.9 to 2.5) coughs per minute. At high coughing frequency the video counts tended to outnumber the simultaneous counts. The counting type had no effect on the hypertonic saline CUM15 and only a marginal effect on its repeatability. On the contrary, video counting resulted to significantly higher hypertonic histamine CCR values than simultaneous counting (p < 0.001).ConclusionThe agreement between simultaneous and video counting of coughs is generally good. However, as the coughing frequency increases, simultaneous counting may miss coughs, especially if the nurse has to share his/her attention to several activities simultaneously. Video recording is advisable for the hypertonic histamine challenge but unnecessary for the hypertonic saline challenge. To ensure reliable simultaneous cough counting, cough provocation tests should be performed in a quiet environment, applying as little unnecessary equipment and measurements as possible.

Tension-free vaginal tape: avoiding failure

A prospective, single-centre study to assess the outcome of incontinence surgery in the first 120 consecutive patients who had tension-free vaginal tape (TVT) by a single surgeon. All patients were initially seen at 3 months postsurgery, with a cough provocation test, measurement of residual urine volume and a satisfaction survey. At a mean of 26 months (6-42 months) after surgery, a validated telephone interview was performed. The operation was performed in accordance with the original technique described by Ulmsten et al. [Int Urogynecol J Pelvic Floor Dysfunct 1996; 7: 81-5]. A total of 87 of 120 patients completed the study with the others either not complying or having died. Sixty-three (72.4%) patients were completely dry on cough provocation test. Of these, four (4.5%) had a slow stream and 10 (11.4%) suffered persistent urgency. The remaining 24 patients had varying degrees of leakage (operative failure). Sixteen (18.3%) patients subjectively considered the procedure to have failed at 3 months follow-up, either because leakage occurred once or more a day, and/or the persistence of the preoperative frequency/urgency syndrome. Of these 16 TVT failures, two had previous pelvic radiotherapy, two had double incontinence and eight had TVT for recurrent incontinence. Among the failures, 81.3% had mixed incontinence with predominant urge and nocturia three times per twenty four hours. Our study highlights the need for selection when performing TVT. We recommend that TVT be performed for those who have simple stress incontinence failing conservative measures (pelvic floor exercises and physiotherapy), with no history of incontinence surgery, pelvic radiotherapy, faecal or mixed incontinence.

Elevated substance P levels in nasal lavage fluids from patients with chronic nonproductive cough and increased cough sensitivity to inhaled capsaicin

Background The exact mechanism of a chronic nonproductive cough is sometimes unclear when patients who are without symptoms or signs indicating the major causes of chronic cough remain undiagnosed. Objective We hypothesized that some neurochemical alterations in the sensory nerves in the cough reflex may occur in the upper airway of chronic nonproductive cough patients. Methods We took nasal lavage fluid (NLF) specimens from 38 patients with a chronic nonproductive cough as the sole presenting symptom. All 38 had normal chest radiography, spirometry, and bronchial responsiveness. We likewise took NLF specimens from 14 healthy control subjects. We used a capsaicin cough provocation test to determine cough sensitivity and considered the value of C 5 (the lowest capsaicin concentration inducing 5 consecutive coughs) as an index of cough sensitivity. We measured levels of substance P of NLF specimens by using ELISA. In addition, we evaluated the clinical response of each patient after subsequent therapeutic trials with an antihistamine and decongestant for 2 weeks. Results By using capsaicin cough sensitivity as the basis for grouping the study subjects, we divided the patients into 2 groups: an increased cough sensitivity group (ICS, C 5 <32 μmol/L) and a normal cough sensitivity (NCS) group. Patients with ICS showed an elevated SP concentration in NLF (median value, 408 pg/mL) compared with that of the NCS group (237 pg/mL) and the control subjects (138 pg/mL) ( P < .01). The median value of the percentage of remnant cough after therapeutic trial compared with the cough status before treatment was significantly higher in the ICS subgroup (70%) than that of NCS (25%) ( P < .05). Conclusions Elevated substance P contents in NLF specimens were associated with ICS in patients with chronic nonproductive cough, suggesting a neurochemical abnormality in the upper airway.