Development of an Italian version of the Leicester cough questionnaire and its relationship with other symptom-specific measures for patients with chronic cough.

OBJECTIVE: To implement subjective methods for measuring the impact of chronic cough on patients' daily life, including an Italian version of the symptom-specific, health status measure for patients with chronic cough, i.e. the Leicester Cough Questionnaire (LCQ). METHODS: Sixty-five chronic cough patients attended a tertiary cough clinic on two separate occasions 8 weeks apart. The visual analogue scale for cough severity (VAS), the LCQ and the cough disturbance score (CDS) were administered on both occasions. The LCQ was adapted for Italian conditions following a forward-backward translation procedure. Concurrent validation, internal consistency, repeatability and responsiveness were determined. RESULTS: The CDS, VAS and LCQ were correlated (r coefficients ranging from 0.69 to 0.94, p < 0.01). The internal consistency for each LCQ domain was high (alpha coefficient range 0.87-0.93), as was the 8-week repeatability of the LCQ in the patients (n = 36, 60 %) who displayed no change in CDS and VAS (intra-class correlation coefficient = 0.86, p < 001) over the same period. Patients who reported an improvement in CDS and VAS after 8 weeks (n = 29) also demonstrated significant improvements in each LCQ domain. The mean difference in LCQ total score before and after improvements was 2.26 (95 % CI: 1.58-4.47). CONCLUSIONS: The Italian version of the LCQ appears to be just as valid as the other language versions of the questionnaire. In addition, the CDS appears to be a clinically useful, symptom-specific measure of the overall disturbance provoked by cough.

First Exploration of the Altered Microbial Gut-Lung Axis in the Pathogenesis of Human Refractory Chronic Cough.

PURPOSE: Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut-lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM). METHODS: 16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances. RESULTS: In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC. CONCLUSION: Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut-lung communication.

Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study.

Background: Current guidelines on the management of chronic cough do not provide recommendations for the operation of specialist cough clinics. The objective of the present study was to develop expert consensus on goals and standard procedures for specialist cough clinics. Methods: We undertook a modified Delphi process, whereby initial statements proposed by experts were categorised and presented back to panellists over two ranking rounds using an 11-point Likert scale to identify consensus. Results: An international panel of 57 experts from 19 countries participated, with consensus reached on 15 out of 16 statements, covering the aims, roles and standard procedures of specialist cough clinics. Panellists agreed that specialist cough clinics offer optimal care for patients with chronic cough. They also agreed that history taking should enquire as to cough triggers, cough severity rating scales should be routinely used, and a minimum of chest radiography, spirometry and measurements of type 2 inflammatory markers should be undertaken in newly referred patients. The importance of specialist cough clinics in promoting clinical research and cough specialty training was acknowledged. Variability in healthcare resources and clinical needs between geographical regions was noted. Conclusions: The Delphi exercise provides a platform and guidance for both established cough clinics and those in planning stages.

Somatically evoked cough responses help to identify patients with difficult-to-treat chronic cough: a six-month observational cohort study.

Background: Recently we identified in patients with chronic cough a sensory dysregulation via which the urge-to-cough (UTC) or coughing are evoked mechanically from "somatic points for cough" (SPCs) in the neck and upper trunk. We investigated the prevalence and the clinical relevance of SPCs in an unselected population of patients with chronic cough. Methods: From 2018 to 2021, symptoms of 317 consecutive patients with chronic cough (233 females) were collected on four visits (V1-V4) 2 months apart at the Cough Clinic of the University Hospital in Florence (I). Participants rated the disturbance caused by the cough (0-9 modified Borg Scale). We attempted to evoke coughing and/or UTC using mechanical actions in all participants who were subsequently categorised as responsive (somatic point for cough positive, SPC+) or unresponsive (SPC-) to these actions. An association was established between chronic cough and its commonest causes; treatments were administered accordingly. Findings: 169 patients were SPC+ and had a higher baseline cough score (p < 0.01). In most of the patients, the treatments reduced (p < 0.01) cough-associated symptoms. All patients reported a decrease (p < 0.01) in cough score at V2 (from 5.70 ± 1.4 to 3.43 ± 1.9 and from 5.01 ± 1.5 to 2.74 ± 1.7 for SPC+ and SPC- patients respectively). However, whilst in SPC- patients the cough score continued to decrease indicating virtually complete cough disappearance at V4 (0.97 ± 0.8), in SPC+ patients this variable remained close to V2 values during the entire follow-up. Interpretation: Our study suggests that the assessment of SPCs may identify patients whose cough is unresponsive and are eligible for specific treatments. Funding: This work was funded by an unrestricted grant from Merck (Italy).

Somatic points for cough and urge to cough in chronic coughers.

In patients with chronic cough and age-matched control subjects, we attempted to evoke coughing and/or an urge to cough (UTC) by finger pressure along the sternocleidomastoid and sternum, on the lower cervical or first dorsal vertebrae, the jugular notch as well as with maximum neck extension and flexion These mechanical actions were ineffective in controls but reproducibly evoked coughing or UTC in about 50% of chronic coughers; sternal and spinal responses were abolished temporarily by local cooling. The results may disclose a novel paradigm of cough sensitisation possibly involving central convergence of somatic and visceral neural stimuli.

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a well-known and widely accepted biomarker of airways inflammation that can be useful in the therapeutic management, and adherence to inhalation therapy control, in asthmatic patients. However, the multiple-flows assessment of FeNO can provide a reliable measurement of bronchial and alveolar production of NO, supporting its potential value as biomarker also in peripheral lung diseases, such as interstitial lung diseases (ILD). In this review, we first discuss the role of NO in the pathobiology of lung fibrosis and the technique currently approved for the measurement of maximum bronchial flux of NO (J'awNO) and alveolar concentration of NO (CaNO). We systematically report the published evidence regarding extended FeNO analysis in the management of patients with different ILDs, focusing on its potential role in differential diagnosis, prognostic evaluation and severity assessment of disease. The few available data concerning extended FeNO analysis, and the most common comorbidities of ILD, are explored too. In conclusion, multiple-flows FeNO analysis, and CaNO in particular, appears to be a promising tool to be implemented in the diagnostic and prognostic pathways of patients affected with ILDs.

The demographic and clinical characteristics of an Italian population of adult outpatients with chronic cough.

BACKGROUND: Chronic cough is a major health problem worldwide and patients are best managed in specialised tertiary centres. Little information is available on the characteristics of chronic cough patients in several European countries, including Italy. AIMS: We report on the demographic, anthropometric and clinical features of a large Italian population of adult chronic cough outpatients (about 1200), who were referred to a specialised clinic in Florence, Italy, from 2008 to 2018. METHODS: Demographic, environmental, lifestyle and clinical information was collected at enrolment by means of a custom-designed electronic questionnaire that only allowed for uniform responses. A subjective measure of cough-related discomfort (cough score) was also obtained using a modified Borg Scale. A multivariable logistic regression model was defined to identify the patients' characteristics associated with the cough score. RESULTS: The characteristics of the examined population (n = 1204 outpatients) were strikingly similar to those described elsewhere. Female patients outnumbered the males [n = 847 females, (70.0%)]; both females and males displayed the same average cough score. The median age of outpatients was 61 (quartile 1 = 48; quartile 3 = 70) years; age and cough duration were unrelated to the cough score. Nasal obstruction, coughing during consultation, coughing during meals, throat clearing and the presence of respiratory abnormalities were correlated with the degree of discomfort caused by coughing. DISCUSSION: The features of chronic cough patients are similar worldwide. The process of cough reflex hypersensitisation may soothe sex-related perceptual differences, leading to similar levels of discomfort. CONCLUSIONS: There seem to be clinical indicators that help in assessing the level of cough-related discomfort.

Effect of Erdosteine on COPD Exacerbations in COPD Patients with Moderate Airflow Limitation.

Background: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine - a muco-active antioxidant that modulates bacterial adhesiveness - reduced the rate and duration of exacerbations in moderate and severe COPD with a history of exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear. Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted) examined exacerbation rate and duration, time to first exacerbation, and exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann-Whitney U-tests, or log rank tests. Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an exacerbation. There was a 47% reduction in the mean exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 exacerbations per-patient per-year, respectively, P=0.003), and a 58.3% reduction in the mild exacerbation rate (0.23 vs 0.53 mild exacerbations per-patient per-year, P=0.001). Mean duration of exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P=0.022), with significant reductions in the duration of mild and moderate-to-severe exacerbations. Mean time to first exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P<0.001) and the mean exacerbation-free time was increased by 51 days (279 days for erdosteine vs 228 days for placebo; P<0.001). Conclusion: These results indicate that adding erdosteine to usual COPD maintenance therapy reduces the number of mild, and duration of all, exacerbations in patients with moderate COPD and a history of exacerbations.

The lung microbiome: clinical and therapeutic implications.

The human respiratory tract, usually considered sterile, is currently being investigated for human-associated microbial communities. According to Dickson's conceptual model, the lung microbiota (LMt) is a dynamic ecosystem, whose composition, in healthy lungs, is likely to reflect microbial migration, reproduction, and elimination. However, which microbial genera constitutes a "healthy microbiome" per se remains hotly debated. It is now widely accepted that a bi-directional gut-lung axis connects the intestinal with the pulmonary microbiota and that the diet could have a role in modulating both microbiotas as in health as in pathological status. The LMt is altered in numerous respiratory disorders such as obstructive airway diseases, interstitial lung diseases, infections, and lung cancer. Some authors hypothesize that the use of specific bacterial strains, termed "probiotics," with positive effects on the host immunity and/or against pathogens, could have beneficial effects in the treatment of intestinal disorders and pulmonary diseases. In this manuscript, we have reviewed the literature available on the LMt to delineate and discuss the potential relationship between composition alterations of LMt and lung diseases. Finally, we have reported some meaningful clinical studies that used integrated probiotics' treatments to contrast some lung-correlated disorders.

Antitussive therapy: A role for levodropropizine.

Cough is a protective reflex that serves to clear the airways of excessive secretions and foreign matter and which sometimes becomes excessive, and troublesome to patients. Cough is one of the most common reasons why individuals seek medical attention. A range of drugs have been developed in the past with antitussive activity and different mechanisms of action, but there are still very few safe and effective treatments available. The poor tolerability of most available antitussives is closely related to their action on the central nervous system (CNS). An international group of experts specialized in cough met to discuss the need to identify an effective antitussive treatment with a good tolerability profile. The aim of this expert review is to increase the knowledge about the cough mechanism and the activity of levodropropizine, a peripherally acting antitussive drug.

The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a peripheral subpleural interstitial lung disorder limited to the lung not involving the airways. It has a poor prognosis (survival less than 5 years) and commonly an interstitial pneumonia radiological pattern. Patients complain of a chronic dry cough in 80% of cases. A cough is often the first symptom of this rare disease, preceding dyspnea by years, and is associated with a poor prognosis, high dyspnea scores and low FVC percentages. The pathogenetic mechanisms leading to coughing in IPF are unclear. This review focuses on recent evidence of cough pathophysiology in this disease. Gastroesophageal reflux may promote coughing in IPF patients; bile salts and pepsin may be abundant in BAL of these patients, inducing overproduction of TGF-ß by airway epithelial cells and mesenchymal transition with fibroblast recruitment/activation and extracellular matrix deposition. Patients have an enhanced cough reflex to capsaicin and substance P with respect to control subjects. Moreover, patients with the MUC5B polymorphism show more severe coughing as MUC5B encodes for the dominant mucin in the honeycomb cysts of IPF patients. Comorbidities, including asthma, gastroesophageal reflux, hypersensitivity pneumonitis, bronchiectasis, chronic obstructive pulmonary disease and emphysema, can induce coughing in IPF patients. There is no clear explanation of the causes of coughing in IPF. Further research into the pathophysiology of IPF and the pathogenetic mechanisms of coughing is necessary to improve survival and quality of life.

Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study.

Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations·patient-1·year-1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient-1·year-1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient-1·year-1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.

A Randomized Clinical Trial Comparing the Effects of Antitussive Agents on Respiratory Center Output in Patients With Chronic Cough.

BACKGROUND: Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO2 rebreathing test in patients with chronic cough of any origin. METHODS: Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg levodropropizine, 15 mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93% oxygen and 7% CO2 for 5 min. Fractional end-tidal CO2 (Fetco2) and inspiratory minute ventilation (V˙i) were continuously monitored. Changes in breathing pattern variables were also assessed. RESULTS: At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia (P < .01). The ventilatory increases by hypercapnia were mainly accounted for by a rise in the volume components of the breathing pattern. CONCLUSIONS: The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO2 may represent a useful tool to investigate the central respiratory effects of antitussive agents. TRIAL REGISTRY: European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/.

Antitussive effect of carcainium chloride in patients with chronic cough and idiopathic interstitial pneumonias: A pilot study.

BACKGROUND: Cough is a common presenting symptom in patients with idiopathic interstitial pneumonia (IIP); it is often disabling, and lacks effective treatment. Studies in animals suggest that carcainium chloride, a quaternary derivative of the local anesthetic lidocaine, is able to inhibit experimentally induced cough by a mechanism of action distinct from that of lidocaine. OBJECTIVE: To determine the effectiveness of aerosolised carcainium chloride (VRP700) in controlling cough in patients with IIP. METHODS: Eight female patients (mean age 71 years) with IIP were investigated in a double blind, randomised, placebo controlled crossover, adaptive contingency study design (EudraCT Number 2010-021350-19). The study consisted of a screening visit to assess the eligibility of patients, and two separated (48-72 h) study days. On the two study days, patients were randomised to receive either nebulized VRP700 (1.0 mg/kg) on the first study visit followed by nebulised placebo (sodium chloride 0.9%) on the second visit, or placebo on the first visit followed by VRP700 on the second visit. The primary endpoint was cough frequency over a 4-h assessment period; secondary endpoints were subjective cough-related level of discomfort as assessed by a visual analogue scale (VAS) and the subjective response to treatment as assessed by a quality of life question. Safety (ECG, spirometry, urine and blood tests) and adverse events occurring during the trial were also investigated. RESULTS: In all patients both VRP700 and placebo decreased cough frequency; however, mean decreases in cough frequency after treatment with VRP700 were significantly (P < 0.001) higher than with placebo. Similarly, mean reductions in VAS score were significantly (P < 0.001) higher after treatment with VRP 700 compared with placebo. All but one patient indicated that they felt better after receiving VRP700. No adverse events were reported during the study, nor were any changes in ECG variables, spirometry, urine and blood tests noted. CONCLUSION: The results of this exploratory study indicate that nebulised VRP700 improved cough and quality of life in hospitalised IIP patients with no significant side effects. A larger trial is warranted to assess these promising results.

Prospective study of the efficacy of antibiotics versus antitussive drugs for the management of URTI-related acute cough in children.

BACKGROUND: Acute cough is one of the most frequent symptoms prompting a visit to a health care provider, usually following a viral upper respiratory tract infection (URTI). The disproportionate use of antibiotics in children with URTIs, recently highlighted in the medical literature, could lead to associated side effects, without any beneficial effect. Although an early, albeit inappropriate, antibiotic prescription increases parental satisfaction, URTIs are predominantly viral infections and are generally self-limiting. Therefore the aim of this study was to analyze the effectiveness of antibiotics compared to symptomatic drugs (central and peripheral antitussives) on URTI-related cough in a pediatric population. METHODS: This is a prospective observational study of 330 children who required pediatric consultation for acute cough. Severity, frequency and type of cough were assessed at baseline and after 6 days of treatment (antitussives n = 123, antibiotics n = 89 or combination of them n = 38) or no treatment (n = 80). The outcome of cough management after 6 days was analyzed in terms of resolution, improvement, no change or worsening of symptoms. Study assessments were performed using a standardized questionnaire administered to parents. RESULTS: Between children treated with antitussives or antibiotics, there was a statistically significant difference in the resolution of cough. Moreover, if considering peripheral antitussives, the resolution of cough was significantly higher with antitussives than with antibiotics (p < 0.01). There was no difference in cough resolution between children treated with antitussives and those receiving a combination of antibiotics and antitussives, either central and peripheral antitussives. CONCLUSION: Antibiotics are generally not useful nor appropriate in treating acute cough due to the common cold. Furthermore, inappropriate antibiotic use introduces the possibility of adverse side effects as well as promotion of antibiotic resistance. The findings of the present study suggest that antitussives, especially peripherally acting agents, represent an effective treatment option for acute pediatric cough caused by URTIs.

Optimising Inhaled Pharmacotherapy for Elderly Patients with Chronic Obstructive Pulmonary Disease: The Importance of Delivery Devices.

Chronic obstructive pulmonary disease (COPD) is common in older people. Inhaled medications are the mainstay of pharmacological treatment of COPD, and are typically administered by handheld inhalers, such as pressurised metered-dose inhalers and dry powder inhalers, or by nebulisers. For each of the three major categories of aerosol delivery devices, several new inhalers have recently been launched, each with their own particularities, advantages and disadvantages. Consequently, broader availability of new drug-device combinations will increase prescription opportunities. Despite this, however, there is limited guidance available in published guidelines on the choice of inhalers, and still less consideration is given to elderly patients with COPD. The aim of this article is to provide a guide for healthcare professionals on device selection and factors to be considered for effective inhaled drug delivery in elderly COPD patients, including device factors (device type and complexity of use), patient factors (inspiratory capabilities, manual dexterity and hand strength, cognitive ability, co-morbidities) and considerations for healthcare professionals (proper education of patients in device use).

TRP functions in the broncho-pulmonary system.

The current understanding of the role of transient receptor potential (TRP) channels in the airways and lung was initially based on the localization of a series of such channels in a subset of sensory nerve fibers of the respiratory tract. Soon after, TRP channel expression and function have been identified in respiratory nonneuronal cells. In these two locations, TRPs regulate physiological processes aimed at integrating different stimuli to maintain homeostasis and to react to harmful agents and tissue injury by building up inflammatory responses and repair processes. There is no doubt that TRPs localized in the sensory network contribute to airway neurogenic inflammation, and emerging evidence underlines the role of nonneuronal TRPs in orchestrating inflammation and repair in the respiratory tract. However, recent basic and clinical studies have offered clues regarding the contribution of neuronal and nonneuronal TRPs in the mechanism of asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cough, and other respiratory diseases.

The Clinical Value of Deflation Cough in Chronic Coughers With Reflux Symptoms.

BACKGROUND: Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms. METHODS: A total of 157 consecutive outpatients underwent DC assessment and 24-h multichannel intraluminal impedance pH (MII-pH) monitoring; 93/157 also had chronic cough. Patients performed two to four slow vital capacity maneuvers and DC was detected aurally. Subsequently, they underwent 24-h MII-pH monitoring, the outcomes of which were defined as abnormal when acid or non-acid reflux events were > 73. RESULTS: DC occurred in 46/157 patients, 18 of whom had abnormal MII-pH outcomes; 28 of the remaining 111 patients without DC also had abnormal MII-pH findings. Thus, in the patients as a group, there was no association between DC and MII-pH outcomes. DC occurred in 40/93 of the chronic coughers; 15 of whom had acid reflux. All but 2 of the 53 patients without DC had normal MII-pH outcomes (P < .001), and the negative predictive value of DC for excluding acid reflux was 96.2%. At follow-up, 65% of coughers showed significant improvement after treatment. CONCLUSIONS: The overall prevalence of DC was 29%, increasing to 43% in chronic coughers in whom the absence of DC virtually excludes acid reflux. Therefore, DC assessment may represent a useful screening test for excluding acid reflux in chronic coughers with reflux symptoms.