Measuring cough-related quality of life and cough frequency in pulmonary TB.

BACKGROUND: Cough is the key symptom of pulmonary TB (PTB) and is associated with transmission. No tool for measuring the subjective impact of cough in PTB has been previously validated. We sought to measure patientreported cough in PTB and investigate any relationship to objectively quantified daily cough frequency.METHODS: The validity of the Leicester Cough Questionnaire (LCQ) was assessed in sequential patients newly diagnosed with PTB at a UK hospital. Resulting LCQ scores were compared to non-cough clinical variables, and to 24-h, ambulatory, objective cough frequency measured using the Leicester Cough Monitor.RESULTS: The LCQ in 30 patients with PTB was acceptable to users and had high internal reliability (Cronbach's α = 0.93), concurrent validity (correlation with visual analogue scale for cough severity, Spearman's ρ = ???0.69) and responsiveness (substantial median increase score after 2 weeks of TB treatment: 5.1 points, IQR 1.8???9.7; P = 0.003). There was only moderate correlation between patient-reported cough and objectively-measured 24-h cough frequency in PTB (ρ = ???0.48, P = 0.008).CONCLUSION: The LCQ is valid for use in PTB, with applications that include monitoring treatment of the disease. However, there was a mismatch between objective and subjective assessment of cough, which has important implications for delayed diagnosis and transmissibility.

A study of the psychometric properties of the Brazilian...Portuguese version of Bronchiectasis Health Questionnaire.

INTRODUCTION AND OBJECTIVE: The Bronchiectasis Health Questionnaire (BHQ) is a simple, repeatable, and self-reporting health status questionnaire for bronchiectasis. This study aims to cross-culturally adapt the BHQ into Brazilian Portuguese and evaluate its measurement properties. METHODS: The participants answered the Saint George...s Respiratory Questionnaire (SGRQ) and the modified Medical Research Council (mMRC) scale for dyspnea. The Brazilian-Portuguese version of the Bronchiectasis Health Questionnaire (BHQ-Brazil) was used at baseline (test) and after 14 days (retest). The psychometric analyses included internal consistency, test-retest reliability, and construct validity: factorial validity, convergent validity, and discriminative validity, agreement, and ceiling and floor effects. RESULTS: The BHQ-Brazil demonstrated adequate internal consistency (Cronbach...s alpha...=...0.92) and substantial reliability (intraclass correlation coefficient...=...0.86; 95%CI: 0.79...0.90). The exploratory factorial analysis was considered suitable. All items presented a factorial load >0.40. The convergent validity of the BHQ-Brazil with mMRC was moderate (r...=......0.53, p...<...0.001), while concurrent validity with the SGRQ was strong (symptoms: r...=......0.72, activities: r...=......0.60, impact: r...=......0.60, total score: r...=......0.75, all p...<...0.001). The standard error of measurement was 4.81 points. The discriminative validity demonstrated that individuals with more pulmonary exacerbations, colonization by Pseudomonas aeruginosa, worst dyspnea, and a higher number of affected lung lobes presented the lowest quality of life. No floor or ceiling effects were observed. CONCLUSION: The BHQ-Brazil presents adequate measurement properties to evaluate the impact of bronchiectasis on health-related quality of life, and can be used in clinical and research settings.

Association of proangiogenic and profibrotic serum markers with lung function and quality of life in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis. OBJECTIVES: The aim of our study was to determine the association of these markers' serum levels on lung function and the patients' quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis. METHODS: 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King's Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay. RESULTS: Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores. CONCLUSIONS: Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF.

Non-pharmacological interventions for chronic cough: The past, present and future.

Non-pharmacological interventions have been explored in people with refractory chronic cough. Normally delivered by Physiotherapists and or Speech and Language Therapists, these interventions aim to educate patients about their cough, provide them with cough suppression techniques and breathing exercises, improve vocal/laryngeal hydration and psychoeducational counselling to help them gain greater control of their cough. Six key studies have been completed over the past 12 years that have consistently found non-pharmacological interventions help to improve quality of life and reduce cough frequency. Some studies also found improvements in cough reflex sensitivity and severity. Despite promising results there now needs to be further work to optimise these interventions. There is a need to standardise terminology used such as relabelling the intervention as cough control therapy and move away from uni-disciplinary terms. Standardised patient selection, including screening protocols, optimal timing and delivery of the interventions as well as the outcome measures used to evaluate interventions need further exploration.

Daily cough frequency in tuberculosis and association with household infection.

SETTING: Although cough in tuberculosis (TB) is presumed to be important for transmission, there is little objective supporting evidence. OBJECTIVE: To describe 24-h cough frequency in a group with TB, and investigate associations with household rates of infection. DESIGN: Patients with a new diagnosis of pulmonary TB underwent 24-h cough frequency measurement at or just before initiation of anti-tuberculosis treatment. A group with latent Mycobacterium tuberculosis infection (LTBI) acted as controls. Rates of infection among household contacts of sputum smear-positive TB were measured using the interferon-gamma release assay and the tuberculin skin test, and compared with variables relating to the contacts themselves, and to the index case, including cough frequency. RESULTS: Daily cough frequency in TB patients (n = 44) was variable (geometric mean [GM] 174, interquartile range [IQR] 68-475 coughs/24 h), higher than in LTBI (n = 17; GM 19 coughs/24 h, IQR 8-53; P < 0.001), and higher during the day than overnight (GM 8.9 coughs/h, IQR 4.1-19.0 vs. GM 2.9 coughs/h, IQR 0.7-13.4; P < 0.0001). Also, 24-h cough frequency in TB was associated with sputum smear status (P = 0.040), but not smoking (P = 0.475). Multivariable logistic regression confirmed that infection in contacts was independently associated with index case sputum smear grade (P = 0.014) and cough frequency (P = 0.022). CONCLUSION: Measurement of 24-h cough frequency in pulmonary TB helps predict infectiousness and transmission patterns.

Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study).

OBJECTIVES: To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. DESIGN: A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. SETTING: 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. PARTICIPANTS: Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0-100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females). INTERVENTIONS: Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough. MAIN OUTCOME MEASURES: The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed. RESULTS: At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was -5.9 mm (-14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was -4.2 mm (-12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference -11.6 mm (-20.6 to 2.7), p=0.01) and cough frequency (mean difference -8.1 mm (-16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely stopped treatment due to cough improvement in the CS1002 group (24.4%) compared with SL (10.7%; p=0.02). Adverse events (AEs) were comparable between CS1002 (20.5%) and SL (27.6%) and largely related to the study indication. 6 participants (7%) in the CS1002 group reduced the dose of medication due to drowsiness/tiredness, which subsequently resolved. These events were not reported by participants as AEs. CONCLUSIONS: Although the primary end point was not achieved, CS1002 was associated with greater reductions in cough frequency, sleep disruption and improved health status compared with SL. TRIAL REGISTRATION NUMBER: EudraCT number 2014-004255-31.

[German Validation of the "King's Brief Interstitial Lung Disease (K-Bild) Health Status Questionnaire"]. / Deutschsprachige Validierung des "Kingʼs Brief Interstitial Lung Disease (K-BILD)" Lebensqualitätsfragebogens für interstitielle Lungenerkrankungen.

Background: Health status and quality of life are impaired in patients with interstitial lung disease (ILD). To assess these parameters in ILD patients no valid and reliable questionnaire exists in German language so far. The K-BILD questionnaire is a brief and valid tool to evaluate health status in ILD patients, with no validated German version. Method: The linguistic validation of K-BILD was carried out in a multistage process in collaboration with the developer of the questionnaire and bilingual, professional translators. Review by the developers and back translations as well as clinical assessment by ILD patients ensured that the translated questionnaire reflected the intention of the original K-BILD. Results: A German version of K-BILD with 15 questions concerning the health status was composed. The questions cover the three domains breathlessness and activities, psychological aspects and chest symptoms. Problems in understanding or difficulties in replying to the questions were not stated by the ILD patients. Conclusion: The German version of the K-BILD questionnaire allows the clinical and scientific use to measure reliable health quality in ILD patients.

Validation of the Mandarin Chinese version of the Leicester Cough Questionnaire in bronchiectasis.

BACKGROUND: The Leicester Cough Questionnaire (LCQ) has been validated for assessing cough-specific health status in bronchiectasis. We translated the LCQ into Mandarin Chinese and investigated its validity, reliability and responsiveness. METHODS: The LCQ was translated into Mandarin Chinese using the forward-backward translation procedure. A total of 144 out-patients completed the Mandarin Chinese version of the LCQ (LCQ-MC), the Hospital Anxiety and Depression Scale (HADS) and the St George's Respiratory Questionnaire. Reassessments were performed during exacerbations and at 6 months. Concurrent validation, internal consistency, repeatability and responsiveness were determined. RESULTS: Minor cultural adaptations were made to the wording of LCQ-MC. No other difficulties were found during the translation process, with all items easily adapted to acceptable Mandarin Chinese. The questionnaire was not changed in terms of content layout and the order of the questions. In cognitive debriefing interviews, participants reported that the questionnaire was acceptable, relevant, comprehensive and easy to complete. The LCQ-MC showed good concurrent validity, internal consistency and test-retest reliability. Responsiveness was shown by significant changes in LCQ-MC scores between steady state, the first exacerbation and following 2-week antibiotic treatment (both interval changes, P < 0.01) CONCLUSION: The LCQ-MC is a valid, reliable and responsive instrument for determining cough-specific health status in Chinese bronchiectasis patients.

Antitussive drugs--past, present, and future.

Cough remains a serious unmet clinical problem, both as a symptom of a range of other conditions such as asthma, chronic obstructive pulmonary disease, gastroesophageal reflux, and as a problem in its own right in patients with chronic cough of unknown origin. This article reviews our current understanding of the pathogenesis of cough and the hypertussive state characterizing a number of diseases as well as reviewing the evidence for the different classes of antitussive drug currently in clinical use. For completeness, the review also discusses a number of major drug classes often clinically used to treat cough but that are not generally classified as antitussive drugs. We also reviewed a number of drug classes in various stages of development as antitussive drugs. Perhaps surprising for drugs used to treat such a common symptom, there is a paucity of well-controlled clinical studies documenting evidence for the use of many of the drug classes in use today, particularly those available over the counter. Nonetheless, there has been a considerable increase in our understanding of the cough reflex over the last decade that has led to a number of promising new targets for antitussive drugs being identified and thus giving some hope of new drugs being available in the not too distant future for the treatment of this often debilitating symptom.

Chronic cough in patients with sleep-disordered breathing.

Chronic cough can be the sole presenting symptom for patients with obstructive sleep apnoea. We investigated the prevalence, severity and factors associated with chronic cough in patients with sleep-disordered breathing (SDB). We invited 108 consecutive patients who had been referred for evaluation of SDB to complete a comprehensive questionnaire on respiratory and sleep health, which included the Leicester Cough Questionnaire (cough specific quality of life; LCQ), Epworth Sleepiness Scale (ESS) and the Mayo Clinic gastro-oesophageal questionnaire. Chronic cough was defined as cough for a duration of >2 months. 33% of patients with SDB reported a chronic cough. Patients with a chronic cough had impaired cough related-quality of life affecting all health domains (mean+/-sem LCQ score 17.7+/-0.7; normal = 21). Patients with SDB and chronic cough were predominantly females (61% versus 17%; p<0.001) and reported more nocturnal heartburn (28% versus 5%; p = 0.03) and rhinitis (44% versus 14%; p = 0.02) compared to those without SDB. There were no significant differences in ESS, respiratory disturbance index, body mass index, or symptoms of breathlessness, wheeze, snoring, dry mouth and choking between those with cough and those without. Chronic cough is prevalent in patients with SDB and is associated with female sex, symptoms of nocturnal heartburn and rhinitis. Further studies are required to investigate the impact of continuous positive airway pressure therapy on cough associated with SDB to explore the mechanism of this association.

Clinical cough IV:what is the minimal important difference for the Leicester Cough Questionnaire?

BACKGROUND: The Leicester Cough Questionnaire (LCQ) is a valid, reproducible, responsive self-reported cough-specific health status measure. It has been used to assess overall efficacy of treatments for cough, but its threshold for clinical significance, or patient importance, is unknown. The aim of this study was to determine the minimal important difference (MID) of the LCQ for patients with chronic cough; this is the smallest change in quality-of-life score considered to be clinically meaningful. METHODS: The LCQ MID was first estimated by a multidisciplinary panel of experts who reviewed two cases of chronic cough. It was subsequently determined using a standardized method. Fifty-two patients with chronic cough of more than 8 weeks' duration attending a respiratory outpatient clinic were recruited. Participants completed the LCQ at initial evaluation and repeated the LCQ with four Global Rating of Change Questionnaires (GRCQ) more than 2 months later. The LCQ total score ranges from 3 to 21 and from 1 to 7 for physical, psychological and social domains; a higher score indicates a better health-related quality of life. The GRCQ, a 15-point scale scored between +7 (a great deal better) and -7 (a great deal worse), was used to record patient ratings of change in cough symptoms. The MID was defined as the change in LCQ health status corresponding to a small change in the GRCQ score. RESULTS: The mean (standard deviation) LCQ MID corresponding to a small change in the GRCQ score was 1.3 (3.2); the MIDs for domains were as follows: physical 0.2 (0.8), social 0.2 (1.1) and psychological 0.8 (1.5). This MID for LCQ total score was similar to that determined by the expert panel. The global rating of change scores correlated significantly with the change in LCQ total and domain scores (r=0.4-0.5; p<0.005). CONCLUSION: We have demonstrated that the LCQ MID is 1.3. The LCQ MID should aid clinicians and researchers to make meaningful interpretations of health-related quality-of-life data relating to chronic cough.

Prevalence of inflammatory bowel disease in patients with airways disease.

BACKGROUND: Case reports and case series have suggested an association between inflammatory bowel disease (IBD) and airways disease, but there are no data demonstrating a higher prevalence of IBD among patients with airways disease. Furthermore, no consistent radiological, pulmonary or pathological abnormalities have been demonstrated in patients with both conditions. AIMS: To determine the prevalence of IBD among patients with airways disease and to evaluate clinical and pathophysiological features. METHODS: A retrospective analysis of outpatients with airways disease over a 10-year period. RESULTS: IBD was four times more prevalent among patients with airways disease compared with published local IBD prevalence [Odds Ratio 4.26, 95% CI 1.48, 11.71, p=0.006; Crohn's disease OR 5.96, 95% CI 1.94, 18.31, p=0.002 and ulcerative colitis OR 4.21, 95% CI 1.71, 10.41, p=0.001]. IBD was more frequent in all types of airways disease except asthma; the association was particularly strong for conditions associated with productive cough. All except 1 patient had established IBD before the onset of respiratory symptoms. There were no obvious radiological differences between ulcerative colitis and Crohn's disease cases. There was a trend for a higher lymphocyte count (despite a tendency to lower blood lymphocyte count) but lower sputum neutrophil count in patients with Crohn's disease compared with ulcerative colitis. There were no significant differences in physiological measurements of pulmonary function between the two types of IBD. CONCLUSION: Our findings support an association between airways disease and inflammatory bowel disease, particularly non-asthmatic airways disease with productive cough.

The Leicester Cough Monitor: preliminary validation of an automated cough detection system in chronic cough.

Chronic cough is a common condition that presents to both primary and secondary care. Assessment and management are hampered by the absence of well-validated outcome measures. The present study comprises the validation of the Leicester Cough Monitor (LCM), an automated sound-based ambulatory cough monitor. Cough frequency was measured with the LCM and compared with coughs and other sounds counted manually over 2 h of a 6-h recording by two observers in nine patients with chronic cough in order to determine the sensitivity and specificity of the LCM. Automated cough frequency was also compared with manual counts from one observer in 15 patients with chronic cough and eight healthy subjects. All subjects underwent 6-h recordings. A subgroup consisting of six control and five patients with stable chronic cough underwent repeat automated measurements > or = 3 months apart. A further 50 patients with chronic cough underwent 24-h automated cough monitoring. The LCM had a sensitivity and specificity of 91 and 99%, respectively, for detecting cough and a false-positive rate of 2.5 events x h(-1). Mean+/-SEM automated cough counts x patient x h(-1) was 48+/-9 in patients with chronic cough and 2+/-1 in the control group (mean difference 46 counts x patient x h(-1); 95% confidence interval (CI) 20-71). The automated cough counts were repeatable (intra-subject SD 11.4 coughs x patient x h(-1); intra-class correlation coefficient 0.9). The cough frequency in patients undergoing 24-h automated monitoring was 19 coughs x patient x h(-1); daytime (08:00-22:00 h) cough frequency was significantly greater than overnight cough frequency (25 versus 10 coughs x patient x h(-1); mean difference 15 coughs x patient x h(-1), 95% CI 8-22). The Leicester Cough Monitor is a valid and reliable tool that can be used to assess 24-h cough frequency in patients with cough. It should be a useful tool to assess patients with cough in clinical trials and longitudinal studies.

Multiple inflammatory hits and the pathogenesis of severe airway disease.

Refractory or difficult-to-control asthma is associated with some clinical and pathological features normally associated with chronic obstructive pulmonary disease (COPD), raising the possibility that there are similarities in their pathogenesis. It is suggested that the coexistence of two or more inflammatory stimuli to the airway (multiple hits) is a key factor leading to the development of more severe airway disease. Airway inflammation in response to chronic inflammatory conditions elsewhere may be a particularly important additional inflammatory stimulus. The "multiple hit" hypothesis for the origins of severe airway disease has important implications for treatment and prevention, since identification and removal of additional inflammatory stimuli may delay progression of the underlying airway disease.

Airway function and markers of airway inflammation in patients with treated hypothyroidism.

BACKGROUND: There is increasing evidence of an association between organ specific autoimmune diseases, particularly autoimmune thyroid disease and respiratory morbidity. A study was undertaken to determine whether patients with autoimmune thyroid disease have objective evidence of airway inflammation and dysfunction. METHODS: Twenty six non-smoking women with treated hypothyroidism and 19 non-smoking controls completed a symptom questionnaire and underwent full lung function tests, capsaicin cough reflex sensitivity measurement, methacholine challenge test, and sputum induction over two visits. RESULTS: Symptoms of cough (p = 0.01), dyspnoea (p = 0.01), sputum production (p = 0.004), and wheeze (p = 0.04) were reported more commonly in patients than controls. Patients with hypothyroidism had heightened cough reflex sensitivity compared with controls (geometric mean concentration of capsaicin causing five coughs: 40 v 108 mmol/l; mean difference 1.4 doubling doses; 95% confidence interval of difference 0.4 to 2.5; p = 0.008) and a significantly higher proportion of patients had airway hyperresponsiveness (methacholine provocative concentration (PC(20)) <8 mg/ml: 38% v 0%; p = 0.016). Patients with hypothyroidism also had a significantly higher induced sputum total neutrophil cell count (p = 0.01), total lymphocyte count (p = 0.02), and sputum supernatant interleukin-8 concentrations (p = 0.048). CONCLUSION: Patients with treated hypothyroidism report more respiratory symptoms and have objective evidence of airway dysfunction and inflammation.

Sputum eosinophilia in idiopathic pulmonary fibrosis.

OBJECTIVES AND DESIGN: Cough is a common symptom in idiopathic pulmonary fibrosis that is difficult to treat and has a major impact on quality of life. We tested the hypothesis that the cough and increased cough reflex sensitivity seen in patients with idiopathic pulmonary fibrosis may be due to airway inflammation in a prospective, cross-sectional study. SUBJECTS AND METHODS: We measured the induced sputum inflammatory cell profile and cell-free supernatant inflammatory mediator concentrations in 15 patients with idiopathic pulmonary fibrosis, 17 healthy controls and 15 patients with chronic obstructive pulmonary disease. RESULTS: Both the geometric mean sputum differential eosinophil cell count and median eosinophilic-cationic-protein concentration were significantly higher in patients with idiopathic pulmonary fibrosis than controls (2.1% vs 0.3%; p <0.001 and 1.1 mg/ml versus 0.2 mg/ml; p=0.03 respectively). There were no significant differences in sputum eosinophil counts and eosinophilic-cationic-protein concentrations between patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Sputum leukotriene-B4 concentrations were significantly lower in patients with idiopathic pulmonary fibrosis (p=0.03) and chronic obstructive pulmonary disease (p=0.008) compared to controls. CONCLUSIONS: Idiopathic pulmonary fibrosis is characterised by the presence of active eosinophilic airway inflammation raising the possibility that airway inflammation may contribute to symptoms such as cough.