Hull Airway Reflux Questionnaire Scores Research Articles

Potassium-Competitive Acid Blocker Versus Proton Pump Inhibitor: A Pilot Study on Comparable Efficacy in the Treatment of Gastroesophageal Reflux-Related Cough.

Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs) have more potent and durable effects on anti-acid secretion. However, whether vonoprazan and esomeprazole have different therapeutic effects on GERC remains unknown. Patients diagnosed with GERC were enrolled in our study and randomly treated with vonoprazan (20 mg, once daily, P-CAB) or esomeprazole (20 mg, twice daily, PPI) for two months. A prokinetic agent was also administered. Patients were followed up once a month. Cough severity visual analogue scale (VAS) was measured as the primary outcome, while cough symptom score (CSS) and scores for cough-related quality-of-life or reflux-related symptoms were the secondary endpoints. A total of 50 patients completed the study, with 25 patients in each group. P-CAB and PPI groups showed similar decreases in cough severity VAS and CSS scores after the 2-month treatment (all P < 0.001). For quality-of-life, the Leicester Cough Questionnaire (LCQ) score increased significantly from baseline in both groups, but the P-CAB group had greater improvement and a higher LCQ score in month 2 (all P ≤ 0.05). For reflux-related symptoms, the Hull Airway Reflux Questionnaire (HARQ) score declined substantially over time in the P-CAB group, while the reflux symptom index (RSI) score decreased in both groups. The P-CAB group tended to have a lower HARQ (P = 0.051) and RSI (P = 0.069) scores in month 2. In conclusion, vonoprazan may be comparable to esomeprazole in cough symptom relief in GERC during the 2-month treatment period, but possibly provides better gains on classic reflux symptoms and quality-of-life. The long-term efficacy of P-CABs on GERC may be worth further exploration. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200067089.

Demographic, clinical, and patient-reported outcome data from 2 global, phase 3 trials of chronic cough

BackgroundThe current characterization of patients with refractory or unexplained chronic cough (RCC and UCC, respectively) primarily stems from relatively small clinical studies. ObjectiveTo report the baseline medical history and clinical characteristics of individuals with RCC or UCC who were enrolled in COUGH-1 and COUGH-2, 2 large, global, phase 3 trials of gefapixant, a P2 × 3-receptor antagonist. MethodsAdults with a chronic cough lasting for more than 1 year, diagnosis of RCC or UCC, and score greater than 40 mm on a 100-mm cough severity visual analog scale at both screening and baseline were eligible for enrollment. Demographics, medical history, and cough characteristics were collected at baseline. Cough-related measures included objective cough frequency, cough severity visual analog scale, Leicester Cough Questionnaire, and Hull Airway Reflux Questionnaire. The data were summarized using descriptive statistics. ResultsOf 2044 participants, 75% were women; mean age was 58 years, and mean cough duration was approximately 11 years. Among all participants, 73% were previously diagnosed with asthma, gastroesophageal reflux disease, or upper airway cough syndrome. The mean Leicester Cough Questionnaire total score was 10.4, with domain scores reflecting impaired cough-specific quality of life across physical, psychological, and social domains. The mean Hull Airway Reflux Questionnaire score was 39.6, with some of the most burdensome reported items being consistent with features of cough-reflex hypersensitivity. Participant characteristics and cough burden were comparable across geographic regions. ConclusionParticipants with RCC or UCC had characteristics consistent with published demographics associated with chronic cough. These data reflect a global population with burdensome cough of long duration and substantial impairment to quality of life. Clinical trial registrationClinicalTrials.gov Identifiers: COUGH-1, NCT03449134 (https://www.clinicaltrials.gov/ct2/show/NCT03449134); COUGH-2, NCT03449147 (https://clinicaltrials.gov/ct2/show/NCT03449147).

Reflux-related symptoms reflect poor asthma control and the presence of airway neuronal dysfunction

BackgroundGastroesophageal reflux may be associated with the worsening of asthma by increasing cough reflex sensitivity. Hull Airway Reflux Questionnaire (HARQ) consists of 14 prevalent reflux-related symptoms. It may be useful in predicting the presence of cough reflex hypersensitivity in asthma. MethodsFrom August 2018 to July 2020, 266 asthmatic patients completed the HARQ. They underwent blood analysis, spirometry, fraction of exhaled nitric oxide (FeNO) measurement, and the capsaicin cough challenge test. Patients were considered to have reflux-related symptoms if their HARQ scores were 13 points or higher. We evaluated the association between reflux-related symptoms and clinical asthma outcomes. Finally, we performed a multivariate analysis to determine the clinical significance of the HARQ for asthma. This study was registered in the University Hospital Medical Information Network (UMIN000040732). ResultsThe mean HARQ scores were 13.1 (standard deviation 12.0). Patients in the high HARQ scores group (HARQ ≥13, n = 105) showed a lower prevalence of atopic predisposition, lower levels of FeNO, heightened capsaicin cough reflex sensitivity, poorer asthma control, and more frequent admissions due to asthma than those in the low HARQ groups (all p values < 0.05). The HARQ was useful in selecting patients with poor controlled asthma and those with severe cough when the cut-off value was set at 13. Multivariate analysis revealed that heightened capsaicin cough reflex sensitivity affected reflux-related symptoms, as well as lower levels of FeNO and younger age. ConclusionsHigher HARQ scores (≥13) may be useful in predicting not only poor asthma condition but also the presence of airway neuronal dysfunction in patients with asthma to some extent.

Flupentixol/melitracen for chronic refractory cough after treatment failure with other neuromodulators.

BACKGROUND: Gabapentin and baclofen are recommended for the treatment of chronic refractory cough (CRC). We investigated the efficacy of flupentixol/melitracen in patients unresponsive to these neuromodulators.METHODS: A total of 101 patients with CRC who failed to respond to gabapentin and baclofen were recruited, and treated with flupentixol/melitracen. The prevalence of cough resolution and changes in the Cough Symptom Score (CSS), cough thresholds to capsaicin, Hull Airway Reflux Questionnaire (HARQ), Leicester Cough Questionnaire (LCQ), Generalized Anxiety Disorder-7, Hamilton Anxiety Rating Scale, Patient Health Questionnaire-9, and Hamilton Depression Rating Scale-24 were evaluated after treatment.RESULTS: Ninety-eight patients (97.0%) completed the study. The overall successful cough resolution rate was 62.4% (63/101). Cough resolution was accompanied by an obvious decrease in the CSS and HARQ score and a remarkable increase in cough thresholds to capsaicin challenge and LCQ score, whereas anxiety and depression scores did not change significantly. The prevalence of adverse effects (e.g., insomnia and dizziness) was 21.8%. The prevalence of cough recurrence within 2 weeks after treatment cessation was 17.8%.CONCLUSION: Flupentixol/melitracen may be an efficacious option for CRC unresponsive to other neuromodulators.

Cough persistence in adults with chronic cough: A 4-year retrospective cohort study

BackgroundThere is very limited evidence regarding long-term prognosis of chronic cough. We examined longitudinal outcomes among patients with chronic cough, and explored predictors of cough persistence. MethodsA retrospective cohort was constructed of adults who had newly visited a specialist cough clinic in 2012–2013. All had undergone systematic investigation for chronic cough. The Hull Airway Reflux Questionnaire (HARQ) was administered to assess reflux cough symptoms. A follow-up survey was conducted in 2016–2017 to assess cough persistence. ResultsFrom 418 candidates, 323 participated in the follow-up study; main analyses focused on patients with chronic persistent cough (n = 64; 19.8%) and remitted cough (n = 193; 59.8%). Compared with remitted cough group, chronic persistent cough group had more family history of chronic cough (17.2% vs. 4.7%, p = 0.001) and cold air-sensitive cough (62.5% vs. 44.6%, p = 0.013). The total HARQ score did not differ; however, two items (cough with eating and cough with certain foods) scored significantly higher in chronic persistent cough. In multivariate analyses, a family history of chronic cough (adjusted odds ratio 4.27 [95% confidence interval 1.35–9.89]), cold air-sensitive cough (2.01 [1.09–3.73]), and cough with eating (1.22 [1.02–1.45]) were associated with chronic persistent cough at 4 years. ConclusionsCough persists in about 20% of patients after 4 years following systematic assessment and treatments. Several cough characteristics, such as family history, cold air-sensitivity, or reflux cough, may be associated with cough persistence. Larger cohort studies are warranted to further understand long-term prognosis and confirm predictors of persistence in patients with chronic cough.

Prediction of therapeutic efficacy of gabapentin by Hull Airway Reflux Questionnaire in chronic refractory cough

Background:Gabapentin is recommended for the treatment of chronic refractory cough (CRC). This study aims to identify its therapeutic predictors in a prospective clinical study.Methods:A total of 179 patients with CRC were treated with gabapentin. Prior to the therapy, all patients were assessed by Hull Airway Reflux Questionnaire (HARQ) and inhaled capsaicin challenge. When the treatment ended and cough resolution was confirmed, a stepwise logistic regression analysis was performed to identify the therapeutic predictors for gabapentin and to establish the prediction equation.Results:Gabapentin treatment achieved a therapeutic success rate of 66.48%. HARQ scores were significantly higher in responders than non-responders to gabapentin (29.79 ± 9.58 versus 21.95 ± 7.83, t = –3.685, p <0.001), which were positively related to the therapeutic efficacy of gabapentin (r = 0.433, p <0.001). The optimal cutoff point of 21.50 in HARQ presented with a moderate ability to predict gabapentin efficacy, with a sensitivity of 84.60% and specificity of 63.60%. Multiple logistic regression identified items of “A tickle in your throat, or a lump in your throat” (OR = 7.927, p = 0.005), “Cough when you get out of bed in the morning” (OR = 7.016, p = 0.045), and “Cough with eating” (OR = 6.689, p = 0.011) as independent predictors. The established logistic regression equation predicted 83.72% of the treatment success rate of gabapentin, which was verified by consequent preliminary revalidating study in 59 patients.Conclusion:HARQ may be useful to screen patients with CRC most likely responsive to gabapentin, and help improve the therapeutic success.Trial registration:http://www.chictr.org/; No.: ChiCTR-ONC-13003123

Effect of Ivacaftor on Objective and Subjective Measures of Cough in Patients with Cystic Fibrosis.

Background and Objectives:Cough is a major symptom in cystic fibrosis. Ivacaftor is a novel drug which targets the G551D mutation and has been demonstrated to improve lung function and weight in the long term. It also improves symptoms of extra-oesophageal reflux. We wanted to evaluate the effect of ivacaftor on cough in cystic fibrosis.Methods:In two patients with cystic fibrosis the Hull Airway Reflux Questionnaire (HARQ) was completed and objective cough counts were measured prior to and within 4 weeks after initiation of treatment with ivacaftor. Spirometry was also undertaken and weight checked at these time frames.Results:In the first patient the HARQ score decreased from 29 to 11 and objective cough counts from 29 to 9 cough events per hour. Similarly in the second patient the HARQ score decreased from 13 to 9 and objective cough count from 76 to 5 cough events per hour. There was no significant change in spirometric parameters or weight.Conclusion:We have observed early subjective and objective improvement in cough measures on treatment with ivacaftor. We suggest that this improvement could be attributed to improvement of gastro-intestinal function and that cough metrics could be used as early and accurate end points of drug efficacy.

Validation of the Chinese version of Hull airway reflux questionnaire and its application in the evaluation of chronic cough

To validate the effectiveness, repeatability and treatment responsiveness of the Chinese version of Hull airway reflux questionnaire (HARQ), and to determine its clinical value. A standard Chinese version of HARQ was developed by an established translation procedure and its repeatability was assessed in a preliminary study involving 55 untreated patients with stable chronic cough. Thereafter, a total of 132 patients with chronic cough referred to our respiratory clinic were recruited into the study between May 2014 and April 2015. After their cough was evaluated with the HARQ, cough symptom score or cough reflex sensitivity to inhaled capsaicin and the correlations among them were analyzed, and the causes of chronic cough in all the patients were presumptively determined according to an established diagnostic protocol and finally confirmed with the subsequent therapy specific to the etiologies. After two weeks of effective treatment, HARQ, cough symptom score and cough reflex sensitivity to inhaled capsaicin were measured once more, and treatment responsiveness was calculated. The score of the HARQ in 132 patients with chronic cough were compared with that in 104 healthy volunteers. The repeatability of the Chinese version of the HARQ was validated at a week interval with the intraclass correlation coefficients of 0.96 (95%CI: 0.93-0.98, P=0.00) for total score (n=55). No correlation was found between the HARQ and cough symptom score, and the HARQ showed a weak negative correlation with cough threshold C2 (rIgC2=-0.23, P=0.01) but not with C5. The value of HARQ was significantly higher in patients with chronic cough than in healthy volunteers[20.00(14.00, 28.00) vs 4.00 (2.00, 6.00), Z=-12.89, P=0.00], but no difference of HARQ in gender or age existed in chronic cough. Although all the patients with various etiologies of chronic cough had an increased value of HARQ, cough due to gastroesophageal reflux showed the highest HARQ score among them[28.50 (25.00, 32.25) vs 18.50 (14.00, 26.25), Z=4.43, P=0.00]. After two weeks of effective treatment, the HARQ score decreased from 20.00 (14.00, 28.00) pre-treatment to 10.00 (4.25, 17.75) post-treatment (Z=-6.06, P=0.00), with 52.04% of score change ratio, 1.38 of effect side and 1.97 of standard response mean respectively. HARQ is a reliable and valid tool for the management of chronic cough with good treatment responsiveness, and may be used as an easy way to predict cough due to gastroesophageal reflux.

P214 Gastro-Oesophageal Reflux Symptoms During COPD Exacerbations

IntroductionGastro-oesophageal reflux disease (GORD) has been associated with increased COPD exacerbation frequency (Terada et al, Thorax 2008) and was independently associated with the frequent exacerbator phenotype in the ECLIPSE study...

P213 The Prevalence and Impact of Gastro-Oesophageal Reflux Symptoms in Stable COPD Patients

IntroductionGastro-oesophageal reflux disease (GORD) has been associated with increased COPD exacerbation frequency (Terada et al, Thorax 2008) and was independently associated with the frequent exacerbator phenotype in the ECLIPSE study...

Serum LDH in chronic cough: a potential marker of airway inflammation

Lactate dehydrogenase (LDH) is found in almost all tissues of the body and five different isoenzymes are known (LDH-1 to LDH-5). LDH can be elevated in many pathological conditions. We have observed serum LDH to be increased in patients with chronic cough. We wanted to confirm this finding, study the reproducibility and determine the origin of the LDH. Patients prospectively seen at the Hull Cough Clinic had total and specific LDH isoenzyme levels in serum determined. A subgroup of patients also had a serum creatine phosphokinase (CK) measured. Patients completed cough symptom scores and the Hull Airway Reflux Questionnaire (HARQ). Spirometry was performed. Eighty-three patients were included. Forty-two percent had LDH values above the reference range and 78% had LDH values in the fourth quartile of the reference range or above. This increase in LDH was predominantly because of a rise in isoenzymes 4 and 5. The increase in LDH was found to be reproducible at 8 weeks. Ten percent had CK values above the normal range. There was no correlation observed between LDH values and the cough scores, HARQ scores or lung function. Serum LDH levels are elevated in a substantial proportion of patients with chronic cough. This rise is likely to be due to airway inflammation known to be associated with chronic cough.

Gastroesophageal Reflux and Idiopathic Pulmonary Fibrosis: A Prospective Study

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. There is evidence of the increased prevalence of gastroesophageal reflux disease in patients with IPF. The aim of this prospective study was to evaluate reflux in patients with IPF by analyzing the scores of the reflux cough questionnaire, measurement of pepsin in exhaled breath condensate (EBC) to detect extraesophageal reflux, and Helicobacter pylori serology to evaluate the prevalence of this stomach bacterium in patients with IPF. The Hull airway reflux questionnaire (HARQ) was completed by 40 patients with IPF and 50 controls in order to evaluate reflux symptoms. EBC was collected from 23 patients (17 patients with IPF and 6 controls) for measurement of pepsin by the lateral flow technique. A prospective study of 57 subjects (34 patents with IPF and 23 controls) for H. pylori antibody detection by ELISA was preformed. Significantly higher HARQ scores (maximum score, 70) were recorded in patients with IPF compared with controls (19.6 [SD, 12.4] vs. 3 [SD, 2.9], P<0.001). There was no significant difference in EBC pepsin positivity between patients with IPF and controls (2 of the 17 patients vs. none of the 6 controls, P=0.38). There was no significant difference in H. pylori serology between patients with IPF and controls (17 of the 34 patients vs. 14 of the 23 controls, P=0.42). Patients with IPF had significantly increased scores of airway reflux symptoms. However, no objective evidence of extraesophageal reflux or H. pylori infection in patients with IPF was obtained in this study. The role of gastroesophageal and extraesophageal reflux in pathogenesis of IPF should be evaluated in a larger prospective study.

Symptoms induced by environmental irritants and health-related quality of life in patients with chronic cough - A cross-sectional study

BackgroundChronic cough is a common condition, but some patients have no evident medical explanation for their symptoms. A group of patients has been identified, characterized by upper and lower airway symptoms triggered by chemicals and scents, and heightened cough sensitivity to inhaled capsaicin. Chronic cough is usually a prominent symptom in these patients, and it has been suggested that they suffer from sensory hyperreactivity.Our main aim was to analyse, in a group of patients with chronic cough, the presence of symptoms induced by environmental factors such as chemicals, scents, and cold air, and to measure the social and emotional influences of these symptoms in relation to quality of life. A second aim was to pilot-test a Swedish translation of a cough-specific questionnaire.MethodsA total of 119 patients with chronic cough were asked to answer three different questionnaires: a local symptom questionnaire, the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR), and the Nottingham Health Profile (NHP). In addition, a Swedish version of the Hull Airway Reflux Questionnaire (HARQ) was developed and answered by a subgroup of patients and healthy controls.ResultsSixty-two patients (52%) with mean cough duration of 10.6 years answered the local symptom questionnaire, the CSS-SHR, and the NHP. Of these, 39 (63%) claimed to have cough and other symptoms induced by chemicals and scents. Compared to population-based findings, the patients scored higher on the CSS-SHR, and the CSS-SHR score was significantly higher among chemical-sensitive individuals (p < 0.001). The NHP showed that the patients had a significantly reduced quality of life, which was most pronounced among chemical-sensitive individuals. The 31 patients who answered the HARQ had significantly higher scores (p < 0.0001) than 59 healthy controls.ConclusionsAmong patients with chronic cough, a majority claimed that environmental factors induced coughing. Both the CSS-SHR and the HARQ score systems seem to be valuable instruments in the mapping of cough patients, supporting the novel paradigm of a cough hypersensitivity syndrome. Our results emphasize that cough is a substantial burden to the patient, influencing daily living and quality of life.

Cough Hypersensitivity Syndrome: A Distinct Clinical Entity

We postulate that most patients with chronic cough have a single discrete clinical entity: cough hypersensitivity syndrome. We constructed a questionnaire that elicits the major components of the syndrome. Here we describe the validation of this questionnaire. Following iterative development, the Hull Airway Reflux Questionnaire (HARQ) was administered to patients and normal volunteers. It is self-administered and comprises 14 items with a maximum score of 70. Unselected patients were recruited sequentially from the Hull Cough Clinic. Preclinic questionnaires were compared with those obtained at the clinic. Responsiveness was assessed 2 months after the clinic visit. One hundred eighty-five patients and 70 normal volunteers were included in this study. There was a marked difference in HARQ scores between patients with chronic cough and normal volunteers. The sensitivity (94%) and specificity (95%) of the HARQ was high, with an area under the ROC curve of 0.99. All items of the scale significantly correlated positively with others in the scale and with the total score. On repeatability testing using Cohen's kappa with quadratic weights, significant agreement was noted for all items. Good correlation was observed between the total scores (r = 0.78). The questionnaire was also responsive to treatment; the minimum clinically significant change was estimated to be 16 points. We have demonstrated the HARQ to have good construct and criterion validity. It is both reproducible and responsive to change. It can be used as a diagnostic instrument and demonstrates that chronic cough represents a single coherent entity: cough hypersensitivity syndrome.