A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

INTRODUCTION: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. METHODS AND ANALYSIS: A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. PRIMARY OUTCOME: Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. DISCUSSION: This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. TRIAL REGISTRATION: NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Construct validity of the anglicised FACE-Q skin cancer module.

OBJECTIVES: The FACE-Q Skin Cancer module is a patient-reported outcome measure (PROM) for facial skin cancer. It has been anglicised for the UK population and undergone psychometric testing using classical test theory. In this study, further evaluation of construct validity using Rasch measurement theory and hypothesis testing was performed. METHODS: Patients were prospectively recruited to the Patient-Reported Outcome Measures In Skin Cancer Reconstruction (PROMISCR) study and asked to complete the anglicised FACE-Q Skin Cancer module. The scalability and unidimensionality of the data were assessed with a Mokken analysis prior to Rasch analysis. Response thresholds, targeting, fit statistics, local dependency, and internal consistency were examined for all items and subscales. Four a priori hypotheses were tested to evaluate the convergent and divergent validity. We additionally hypothesised that the median 'cancer worry' score would be lower in post-operative than pre-operative patients. RESULTS: 239 patients self-completed the questionnaire between August 2017 and May 2019. Of the ten subscales assessed, five showed relative fit to the Rasch model. Unidimensionality was present for all five subscales, with most demonstrating ordered item thresholds and appropriate fit statistics. Two items in the 'cancer worry' subscale had either disordered or very close response thresholds. Subscales of the FACE-Q Skin Cancer module demonstrated convergent and divergent validity with relevant Skin Cancer Index comparators (p < 0.001). Median 'cancer worry' was lower in post-operative patients (44 vs 39, p < 0.001). CONCLUSION: The anglicised FACE-Q Skin Cancer module shows psychometric validity through hypothesis testing, and both classical and modern test theory.

The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

Health sequelae of human cryptosporidiosis-a 12-month prospective follow-up study.

To investigate long-term health sequelae of cryptosporidiosis, with especial reference to post-infectious irritable bowel syndrome (PI-IBS). A prospective cohort study was carried out. All patients with laboratory-confirmed, genotyped cryptosporidiosis in Wales, UK, aged between 6 months and 45 years of age, over a 2-year period were contacted. Five hundred and five patients agreed to participate and were asked to complete questionnaires (paper or online) at baseline, 3 and 12 months after diagnosis. The presence/absence of IBS was established using the Rome III criteria for different age groups. Two hundred and five of 505 cases completed questionnaires (40% response rate). At 12 months, over a third of cases reported persistent abdominal pain and diarrhoea, 28% reported joint pain and 26% reported fatigue. At both 3 and 12 months, the proportion reporting fatigue and abdominal pain after Cryptosporidium hominis infection was statistically significantly greater than after C. parvum. Overall, 10% of cases had sufficient symptoms to meet IBS diagnostic criteria. A further 27% met all criteria except 6 months' duration and another 23% had several features of IBS but did not fulfil strict Rome III criteria. There was no significant difference between C. parvum and C. hominis infection with regard to PI-IBS. Post-infectious gastrointestinal dysfunction and fatigue were commonly reported after cryptosporidiosis. Fatigue and abdominal pain were significantly more common after C. hominis compared to C. parvum infection. Around 10% of people had symptoms meriting a formal diagnosis of IBS following cryptosporidiosis. Using age-specific Rome III criteria, children as well as adults were shown to be affected.

Patient-reported outcome measures for facial skin cancer: a systematic review and evaluation of the quality of their measurement properties.

BACKGROUND: Skin cancer is the commonest malignancy worldwide, often occurring on the face. Both the condition and treatment can lead to scarring and facial disfigurement, affecting a patient's health-related quality of life (HRQoL), which can be measured using patient-reported outcome measures (PROMs). OBJECTIVES: This systematic review identifies PROMs for facial skin cancer and appraises their methodological quality and psychometric properties using up-to-date methods. METHODS: MEDLINE, Embase, PsycINFO, Cochrane and CINAHL were searched systematically in accordance with PRISMA guidelines, identifying all PROMs designed for or validated in facial skin cancer. Methodological quality and evidence of psychometric properties were assessed using the COnsensus-based Standards for the Selection of Health Measurement INstruments (COSMIN) checklist and criteria proposed by Terwee and colleagues. A best-evidence synthesis and assessment of instrument focus on post-resection reconstruction was also performed. RESULTS: We included 24 studies on 11 PROMs. Methodological quality and psychometric evidence was variable, with the Patient Outcome of Surgery - Head/Neck (POS-H/N), Skin Cancer Index (SCI), Skin Cancer Quality of Life Impact Tool (SCQOLIT) and Essers and colleagues demonstrating the greatest level of validation. None scored well in their relevance to post-skin cancer reconstruction of the face. CONCLUSIONS: This systematic review critically appraises PROMs for facial skin cancer using internationally accepted criteria. The identified PROMs demonstrate a variation in the quality of validation performed, with a need to improve this across all PROMs in the field. Only through improving the quality of available PROMs and their focus on the post-treatment aesthetic and functional outcome will we be able to truly appreciate the concerns of our patients and improve the management of facial skin cancer.

Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study.

BACKGROUND: Little is known regarding the recognition of anxiety in children and young people (CYP) in primary care. This study examined trends in the presentation, recognition and recording of anxiety and of anxiolytic and hypnotic prescriptions for CYP in primary care. METHOD: A population-based retrospective electronic cohort of individuals aged 6-18 years between 2003 and 2011 within the Secure Anonymised Information Linkage (SAIL) Databank primary care database was created. Incidence rates were calculated using person years at risk (PYAR) as a denominator accounting for deprivation, age and gender. RESULTS: We identified a cohort of 311,343 registered individuals providing a total of 1,546,489 person years of follow up. The incidence of anxiety symptoms more than tripled over the study period (Incidence Rate Ratio (IRR)=3.55, 95% CI 2.65-4.77) whilst that of diagnosis has remained stable. Anxiolytic/hypnotic prescriptions for the cohort as a whole did not change significantly over time; however there was a significant increase in anxiolytic prescriptions for the 15-18 year age group (IRR 1.62, 95% CI 1.30-2.02). LIMITATIONS: There was a lack of reliable information regarding other interventions available or received at a primary, secondary or tertiary level such as psychological treatments. CONCLUSIONS: There appears to be a preference over time for the recording of general symptoms over diagnosis for anxiety in CYP. The increase in anxiolytic prescriptions for 15-18 year olds is discrepant with current prescribing guidelines. Specific guidance is required for the assessment and management of CYP presenting with anxiety to primary care, particularly older adolescents.

Protocol for a prospective multicentre cohort study to develop and validate two new outcome measures for patients with inflammatory bowel disease.

INTRODUCTION: Most of the health-related quality of life (HRQoL) measures for patients with inflammatory bowel disease (IBD) were designed to be used in outpatient settings and are therefore not suitable for use in acute inpatient settings. None of the currently used clinical severity indices for patients with IBD have been properly validated. The aim of this study was to describe the development of a new HRQoL questionnaire and a clinical severity index for patients with ulcerative colitis or Crohn's disease that were short, valid and suitable at any stage of their disease. The new HRQoL and disease severity index will be easily used at the point of care, and invaluable monitoring tools for clinical care, audit and research. METHODS AND ANALYSIS: This is a prospective multisite validation study of two new outcome measures, the Crohn's and Colitis quality of life (CCQ) questionnaire and the Clinical IBD severity score (CISS). We plan to recruit patients with ulcerative colitis or Crohn's disease. The questionnaire items will be selected through extensive literature review and a focus group involving patients, methodologists, statisticians and IBD specialists. The CCQ questionnaire will be completed by patients attending IBD clinics, having endoscopy procedures or when admitted to hospital. CISS will be completed by clinicians while assessing patients with IBD. Psychometric analysis will be carried out to test the validity and reliability of the questionnaires and to determine the potential to produce shorter versions of CISS and CCQ. The construct validity of CCQ will be tested against short form-12 and the European Quality of Life Five Dimensions. The construct validity of CISS will be tested against biochemical markers, clinical and endoscopic indices to assess severity. ETHICS: This study was approved by the South East Wales Research Ethics Committee (Ref 11/WA/0239).

A Randomised, Cross-Over, Placebo-Controlled Study of Aloe vera in Patients with Irritable Bowel Syndrome: Effects on Patient Quality of Life.

Background. Irritable bowel syndrome (IBS) is a chronic, difficult to treat condition. The efficacy of Aloe vera in treating IBS symptoms is not yet proven. The purpose of this study was to determine if Aloe vera is effective in improving quality of life. Methods. A multicentre, randomised, double-blind, cross-over placebo controlled study design. Patients were randomised to Aloe vera, wash-out, placebo or placebo, washout, Aloe vera. Each preparation (60 mL) was taken orally twice a day. Patient quality of life was measured using the Gastrointestinal Symptoms Rating Score, Irritable Bowel Syndrome Quality of Life, EuroQol and the Short-Form-12 at baseline and treatment periods 1 and 2. Results. A total of 110 patients were randomised, but only 47 completed all questionnaires and both study arms. Statistical analysis showed no difference between the placebo and Aloe vera treatment in quality of life. Discussion. This study was unable to show that Aloe vera was superior to placebo in improving quality of life. Drop outs and other confounding factors may have impacted on the power of the study to detect a clinically important difference. Conclusion. This study failed to find Aloe vera superior to placebo in improving quality of life proven Irritable Bowel Syndrome patients.

Adaptation of the Manchester-Minneapolis Quality of Life instrument for use in the UK population.

INTRODUCTION: The availability of health-related quality of life (HRQL) measures that are reliable, valid, brief and comprehensible and appropriate for use with UK children is limited. We report the validation of a HRQL measure suitable for UK use in healthy children, children with chronic disease conditions and socially disadvantaged children. PATIENTS: A total of 1238 children took part in the study, including healthy children as controls (n = 824) and five exemplar groups: children diagnosed with asthma (n = 87), diabetes (n = 103) or inflammatory bowel disease (IBD; n = 69), children in remission from cancer (n = 68) and children in public care (n = 87). METHODS: In phase I, the Manchester-Minneapolis Quality of Life instrument (MMQL) Child Form was translated into UK English. In phases II and III, the questionnaire was shortened and validated. RESULTS: MMQL was anglicised and shortened to five components comprising 29 items. Good internal reliability was found with alpha reaching at least 0.69 for all subscales. Construct validity was established through moderate correlations with comparable PedsQL subscales (Pearson's r ranged from 0.38 to 0.58, p<0.01). Discriminant validity was also demonstrated in children with asthma and IBD, children in remission from cancer and children in public care, all of whom reported significantly lower HRQL than healthy children. Children with diabetes showed similar HRQL to their healthy peers. Good reproducibility and moderate responsiveness were demonstrated for the new measure. CONCLUSIONS: The anglicised and shortened MMQL was shown to be valid and reliable and could be a valuable new tool for the assessment of HRQL in children.

Can randomised trials rely on existing electronic data? A feasibility study to explore the value of routine data in health technology assessment.

OBJECTIVES: To estimate the feasibility, utility and resource implications of electronically captured routine data for health technology assessment by randomised controlled trials (RCTs), and to recommend how routinely collected data could be made more effective for this purpose. DATA SOURCES: Four health technology assessments that involved patients under care at five district general hospitals in the UK using four conditions from distinct classical specialties: inflammatory bowel disease, obstructive sleep apnoea, female urinary incontinence, and total knee replacement. Patient-identifiable, electronically stored routine data were sought from the administration and clinical database to provide the routine data. REVIEW METHODS: Four RCTs were replicated using routine data in place of the data already collected for the specific purpose of the assessments. This was done by modelling the research process from conception to final writing up and substituting routine for designed data activities at appropriate points. This allowed a direct comparison to be made of the costs and outcomes of the two approaches to health technology assessment. The trial designs were a two-centre randomised trial of outpatient follow-up; a single-centre randomised trial of two investigation techniques; a three-centre randomised trial of two surgical operations; and a single-centre randomised trial of perioperative anaesthetic intervention. RESULTS: Generally two-thirds of the research questions posed by health technology assessment through RCTs could be answered using routinely collected data. Where these questions required analysis of NHS resource use, data could usually be identified. Clinical effectiveness could also be judged, using proxy measures for quality of life, provided clinical symptoms and signs were collected in sufficient detail. Patient and professional preferences could not be identified from routine data but could be collected routinely by adapting existing instruments. Routine data were found potentially to be cheaper to extract and analyse than designed data, and they also facilitate recruitment as well as have the potential to identify patient outcomes captured in remote systems that may be missed in designed data collection. The study confirmed previous evidence that the validity of routinely collected data is suspect, particularly in systems that are not under clinical and professional control. Potential difficulties were also found in identifying, accessing and extracting data, as well as in the lack of uniformity in data structures, coding systems and definitions. CONCLUSIONS: Routine data have the potential to support health technology assessment by RCTs. The cost of data collection and analysis is likely to fall, although further work is required to improve the validity of routine data, particularly in central returns. Better knowledge of the capability of local systems and access to the data held on them is also essential. Routinely captured clinical data have real potential to measure patient outcomes, particularly if the detail and precision of the data could be improved.

Sarcoidosis: a long-term follow up study.

BACKGROUND AND AIM OF WORK: The study investigated the occurrence, time and mode of presentation, clinical features, course of pulmonary disease and prognosis of all patients with sarcoidosis looked after by one physician in a district general hospital during the period 1965-1996. The hospital covered a catchment population of 150,000. METHODS: A detailed review of 212 patient notes was carried out with the aid of a purposely designed structured data collection form. Postal questionnaires were sent to those patients not currently attending to determine survival/state of health. Death certificates were analysed to determine the cause of death. RESULTS: A diagnosis of sarcoidosis was based on clinical grounds in 63 of the 212 cases, with histological proof confirming sarcoidosis in 149 cases. There was a slightly higher incidence in females than males, with four familial instances documented. There was pulmonary involvement in 192 cases classified in the usual way at presentation and the course of these patients was studied. Patients with Stage 1 and 2 disease had resolution rates in excess of 80%, and Stage 3 50%. For the remainder, two patterns emerged: one group with persistent infiltration or fibrosis but little disability or disease progression, and another with advancing disease refractory to steroid therapy with a bad prognosis. CONCLUSIONS: The good prognosis of patients with Stage 1 disease was confirmed. There were fewer patients presenting with Stage 2 and 3 disease and their prognosis was better than in other published studies. Overall, the numbers of patients progressing from one stage to another was small. Although there was a small group of patients with steroid-refractory, progressive, fibrosis with a bad prognosis, the mortality rate from sarcoidosis in this study was small.

Population requirement for adult critical-care beds: a prospective quantitative and qualitative study.

BACKGROUND: The provision of adult critical-care facilities is not based on a rational or scientific assessment of need. We aimed to define the numbers of adult critical-care beds required for a population of 500000. METHODS: In five hospitals in Wales, UK, we classified patients who might be suitable for critical care in intensive-care or high-dependency units. On every 12th day for 1 calendar year, we counted the numbers of such patients admitted in a defined geographical population. A panel of ten intensivists made consensus decisions about whether individual patients were in the appropriate unit. The data were used to predict the numbers of beds and units required for the population. FINDINGS: 4058 patients were suitable for critical care, of whom 3028 lived in the study area. 56.4% were in general wards, 22.3% in high-dependency units, and 21.3% in intensive-care units. The mean risk of death was 22.0% and the in-hospital death rate 17.3%. According to the masked consensus, 41.3% of patients required high-dependency beds and 21.5% intensive-care beds. Mean risk of death increased from general wards (14.7%) to high-dependency units (19.2%) to intensive care (37.0%). Based on the consensus decisions, the average daily requirement of intensive-care beds was 21 and of high-dependency beds 43; to meet needs 95% of times required 30 and 55 beds, respectively, in a single critical-care unit. INTERPRETATION: We estimated, scientifically, numbers of adult critical-care beds required to meet population needs. Studies are necessary periodically to track changes in admissions requiring critical care.

SF-36 scores vary by method of administration: implications for study design.

BACKGROUND: Previous research suggests that people respond differently to health status measures when data are collected by interview or self completion of a questionnaire. The objective of this study was to determine whether SF-36 health status scores differ systematically by method of administration. METHOD: A randomized cross-over study was carried out on 210 new attenders at general medicine, endocrinology, gastroenterology and urological out-patient departments. The outcome was the difference in SF-36 profiles comparing clinic based interviews with self completion at home by the same subjects. RESULTS: For seven of the eight variables of the SF-36 scores were lower in the self assessment, the differences being statistically significant in four of the eight comparisons. The largest differences were in role limitations due to emotional problems (difference 14.74, 95 per cent confidence interval (CI) 7.76-21.7) and social function (difference 7.21, 95 per cent CI 3.19-11.23). CONCLUSIONS: Clinic based interviews systematically exaggerate health status compared with self assessment. The difference is sufficiently large to underestimate the effectiveness of health service interventions when a clinic based pre-intervention and postal self completed follow-up design is used, unless adjustment is made for this systematic bias.

The opioid agonist codeine and antagonist naltrexone do not affect voluntary suppression of capsaicin induced cough in healthy subjects.

Opioids exert an analgesic action by mimicking the effects of endogenous neurotransmitter substances in the central nervous system. Opioids are widely used as antitussives, and it is reasonable to assume that endogenous opioids are involved in the control of cough. In order to investigate this hypothesis, a parallel design study was carried out to examine the effects of 50 mg codeine (opioid agonist), 50 mg naltrexone (opioid antagonist) and placebo on capsaicin-induced cough in 80 healthy volunteers (mean age 25 yrs). Volunteers received two capsaicin challenge units (each consisting of five inhalations of different concentrations of capsaicin, 0.00-3.33 x 10(-4) M). On one challenge unit subjects were instructed to suppress cough, and on the other challenge unit subjects coughed freely. Coughs were recorded on a tape cassette player and later played back into a pen recorder to produce integrated sound traces. The number of coughs in the suppression challenge unit was significantly reduced in all three treatment groups compared to that recorded in the non-suppression challenge unit. Comparisons between the three treatment groups showed that there was no statistical difference between the three groups both before and 90 min after treatment for the total coughs in the suppression challenge unit and for the total coughs in the non-suppression challenge unit. These results demonstrate that capsaicin-induced cough can be voluntarily suppressed, but that both suppressed and non-suppressed cough were unaffected by treatment with codeine, naltrexone or placebo. These results do not provide any support for the hypothesis that capsaicin-induced cough is influenced by endogenous opioid substances.

Voluntary cough suppression as an indication of symptom severity in upper respiratory tract infections.

The aim of the present study was to determine whether the ability to suppress cough voluntarily is an index of cough severity in upper respiratory tract infection. Cough was measured by means of a microphone linked to a pen recorder and subjects were instructed to voluntarily suppress cough in order to determine cough suppression time. Subjective scores of symptom severity, mood and psychological parameters were made prior to cough measurements. The baseline frequency of cough showed a distribution towards the higher frequencies, with a median of 2.1 (lower quartile 1.2, upper quartile 3.2) coughs.min-1. The results for cough suppression fell into two distinct groups, one group reaching a breaking point within 12.6 min; and another group which did not cough during the 20 min cough suppression period. In the group of subjects which broke from the cough suppression, there was an inverse relationship between the cough suppression time and the baseline frequency of cough. The median frequency of cough following cough suppression was significantly greater than the baseline median frequency of cough. The subjects who reached a breaking point had a greater baseline frequency of cough and a greater symptom severity score, and they also felt more feeble, clumsy, sad and antagonistic than the group which did not reach a breaking point. The subjects who reached a breaking point had significantly greater scores for the psychology parameter of obsessional symptoms than the group which did not reach a breaking point.(ABSTRACT TRUNCATED AT 250 WORDS)

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

The aim of the present study was to investigate the voluntary suppression of cough in response to capsaicin inhalation in healthy volunteers, and to determine if the dose-response curve to capsaicin was significantly altered when volunteers were asked to suppress their cough response. The quantification of the degree of voluntary suppression of induced cough could provide a new methodology for screening antitussive agents as antitussives may act by influencing voluntary control of cough. Cough was induced by inhalation of capsaicin. Two challenges were given 5 min apart, each comprising five ascending concentrations of capsaicin (1 x 10(-5) M-3.33 x 10(-4) M). During one of these challenges the volunteer was allowed to cough when required, and during the other they were asked to suppress cough. These two conditions were given in random order. The cough response was recorded by means of a microphone with the integrated sound trace displayed on a chart recorder. A dose-response relationship was obtained on administration of ascending concentrations of capsaicin. In the non-suppressed challenge 23/24 subjects coughed on inhalation of capsaicin (3.33 x 10(-4) M) with a mean number of coughs of 2.92 +/- 0.34, whereas in the suppressed challenge only 3/24 subjects coughed with a mean number of coughs of 0.29 +/- 0.18 (P < 0.001). These results demonstrate that cough induced by inhalation of capsaicin can be voluntarily suppressed. The mechanism of voluntary suppression of cough is discussed in relation to capsaicin challenge and the screening of antitussive medications.