Kai K. Lee

Physiotherapy, and speech and language therapy intervention for patients with refractory chronic cough: a multicentre randomised control trial

Background Physiotherapy, and speech and language therapy are emerging non-pharmacological treatments for refractory chronic cough. We aimed to investigate the efficacy of a physiotherapy, and speech and language therapy intervention (PSALTI) to improve health-related quality of life (HRQoL) and to reduce cough frequency in patients with refractory chronic cough. Methods In this multicentre randomised controlled trial, patients with refractory chronic cough were randomised to four weekly 1:1 sessions of either PSALTI consisting of education, laryngeal hygiene and hydration, cough suppression techniques, breathing exercises and psychoeducational counselling or control intervention consisting of healthy lifestyle advice. We assessed the change in HRQoL at week 4 with the Leicester Cough Questionnaire (LCQ). Secondary efficacy outcomes included 24-hour objective cough frequency (Leicester Cough Monitor) and cough reflex sensitivity. The primary analysis used an analysis of covariance adjusted for baseline measurements with the intention-to-treat population. This study was registered at UK Clinical Research Network (UKCRN ID 10678). Findings Between December 2011 and April 2014, we randomly assigned 75 participants who underwent baseline assessment (34 PSALTI and 41 controls). In the observed case analysis, HRQoL (LCQ) improved on average by 1.53 (95% CI 0.21 to 2.85) points more in PSALTI group than with control (p=0.024). Cough frequency decreased by 41% (95% CI 36% to 95%) in PSALTI group relative to control (p=0.030). The improvements within the PSALTI group were sustained up to 3 months. There was no significant difference between groups in the concentration of capsaicin causing five or more coughs. Interpretation Greater improvements in HRQoL and cough frequency were observed with PSALTI intervention. Our findings support the use of PSALTI for patients with refractory chronic cough. Trial registration number UKCRN ID 10678 and ISRCTN 73039760; Results.

Cough and Sleep

Cough and sleep are vital functions. The effects of cough on sleep and vice versa are important for a number of reasons. Sleep disruption is common in patients with cough and is often the reason why they seek medical attention. Sleep suppresses cough and the biological mechanisms for this action are poorly understood. Cough has recently been reported as a presenting symptom of obstructive sleep apnea. It is uncommon for healthy people to cough at night; however, approximately 50% of patients with chronic cough report sleep disruption due to cough. Cough frequency is much lower at night than during the day. There is reduced exposure to tussive stimuli at night and decreased cough reflex sensitivity. Cough is more difficult to induce in REM sleep compared to slow-wave sleep. Studies of anesthetized humans have shown that the cough reflex is suppressed; however, the expiratory reflex is less affected. The sleep–cough interaction has implications for the physician. The measurement of cough frequency with 24-h ambulatory cough monitors in patients with chronic cough suggests that the presence or absence of nocturnal cough is not helpful in establishing the etiology. Nocturnal cough may be a useful outcome parameter for clinical trials of antitussive drugs since it is under less voluntary control than daytime cough. Most antitussive drugs are sedatives. This suggests that part or all of their action may be through an effect on cortical neural pathways. Unexplained chronic cough has recently been reported as a presenting feature of obstructive sleep apnea. Patients are likely to be female and report gastroesophageal reflux and rhinitis. Continuous positive airway pressure therapy is effective in alleviating cough. Greater awareness of this condition is needed.

The validity of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis

Background A range of questionnaires have been used to assess health-related quality of life (HRQOL) in bronchiectasis. A systematic review was conducted to evaluate their psychometric properties and assess associations between HRQOL and clinical measures. Methods Five electronic databases were searched. Studies eligible for inclusion were those that investigated the validity of HRQOL questionnaires and/or their association with other outcomes in adults with bronchiectasis. Patients with cystic fibrosis were excluded. The identified questionnaires were assessed for convergent, discriminant and cross-cultural translation validity; missing data, floor and ceiling effects, internal consistency, responsiveness and test-retest reliability. A meta-analysis was conducted to estimate the strength of associations between HRQOL and clinical measures. Results From 1918 studies identified, 43 studies were included in the systematic review, of which 38 were suitable for the meta-analysis. Nine HRQOL questionnaires were identified, with the most widely used being: St Georges Respiratory Questionnaire, Leicester Cough Questionnaire, Quality of Life–Bronchiectasis and Short Form-36. HRQOL questionnaires had moderate to good internal consistency and good test-retest reliability. Only 8 of 18 studies that used translated HRQOL questionnaires reported or referred to the validity of the translated questionnaire. There was a stronger correlation (mean r (95% CI)) between HRQOL and subjective outcome measures, such as dyspnoea (0.55 (0.41 to 0.68)) and fatigue (0.42 (0.23 to 0.58)) compared with objective measures; exercise capacity (−0.41 (−0.54 to −0.24)), FEV1% predicted (−0.31 (−0.40 to −0.23)) and extent of bronchiectasis on CT scan (0.35 (0.03 to 0.61)); all p<0.001. Conclusions This review supports most HRQOL questionnaires used in bronchiectasis have good psychometric properties. There was a weak to moderate association between HRQOL and objective outcome measures. This suggests that HRQOL questionnaires assess a unique aspect of health not captured by objective measures.

Four-Hour Cough Frequency Monitoring in Chronic Cough

BACKGROUND The recent development of automated cough monitors has enabled objective assessment of cough frequency. A study was undertaken to determine whether short-duration recordings( < 6 h) accurately reflect 24-h cough frequency and to investigate their responsiveness. METHODS One hundred adults with chronic cough underwent 24-h cough frequency monitoring with the Leicester Cough Monitor and completed cough visual analog scales (VASs) and the Leicester Cough Questionnaire (LCQ). Cough recordings were analyzed using customized software to derive cough frequencies from 1 to 6 h and 24-h recordings. Responsiveness was assessed with repeat assessments following therapeutic trials. RESULTS The median (interquartile range) 24-h cough frequency was 11.5 (5.8-26.6) coughs/h. Four hours was considered the shortest recording duration that represented 24-h cough frequency( ρ= 0.9, P ≤ .001). Median 4-h cough frequency was 16.6 (7.3-36.8) coughs/h. Both 4-h and 24-h cough frequency correlated moderately with cough VAS ( ρ= 0.49, P ≤ .01 and ρ= 0.44, P ≤ .01)and LCQ ( ρ = - 0.48, P ≤ .01; ρ = - 0.50, P ≤ .01). Four-hour cough frequency was responsive to improvements in cough severity following trials of therapy. CONCLUSIONS Four-hour cough frequency correlates highly with 24-h cough frequency recordings and relates equally well with subjective measures in chronic cough. Short-duration cough monitoring could be a practical tool to validate the presence of cough and assess response to trials of therapy in the clinic setting.

A cohort study to identify simple clinical tests for chronic respiratory failure in obese patients with sleep-disordered breathing

Background Chronic respiratory failure complicating sleep-disordered breathing in obese patients has important adverse clinical implications in terms of morbidity, mortality and healthcare utilisation. Screening strategies are essential to identify obese patients with chronic respiratory failure. Method Prospective data were collected from patients with obesity-related sleep-disordered breathing admitted for respiratory assessment at a UK national sleep and ventilation centre. Hypercapnia was defined as an arterial partial pressure of carbon dioxide of >6kPa. Results 245 obese patients (56±13 years) with a body mass index of 48±12 kg/m2, forced vital capacity (FVC) of 2.1±1.1 L, daytime oximetry (SpO2) of 91±6% and abnormal overnight oximetry were included in the analysis. Receiver operator curve analysis for the whole group showed that an FVC ≤3 L had a sensitivity of 90% and a specificity of 41% in predicting hypercapnia, and an SpO2 ≤95% had a sensitivity of 83% and a specificity of 63% in predicting hypercapnia. Gender differences were observed and receiver operator curve analysis demonstrated ‘cut-offs’ for (1) SpO2 of ≤95% for men and ≤93% for women and (2) FVC of ≤3.5 L for men and ≤2.3 L for women, in predicting hypercapnia. Conclusions The measurement of FVC and clinic SpO2 in obese patients with abnormal overnight limited respiratory studies predicted hypercapnia. This may have clinical utility in stratifying patients attending sleep clinics.

The development and validation of the Bronchiectasis Health Questionnaire

Health-related quality of life or health status is significantly impaired in bronchiectasis. There is a paucity of brief, simple-to-use, disease-specific health status measures. The aim of this study was to develop and validate the Bronchiectasis Health Questionnaire (BHQ), a new health status measure that is brief and generates a single overall score. Patients with bronchiectasis were recruited from two outpatient clinics, during a clinically stable stage. The development of the questionnaire followed three phases: item generation and item reduction using Rasch analysis, validation, and repeatability testing. The BHQ was translated into 11 languages using standardised methodology. 206 patients with bronchiectasis completed a preliminary 65-item questionnaire. 55 items were removed due to redundancy or poor fit to the Rasch model. The final version of the BHQ consisted of 10 items. Internal consistency was good (Cronbachs α=0.85). Convergent validity of the BHQ with the St Georges Respiratory Questionnaire was high (r= −0.82; p<0.001) and moderate with lung function (forced expiratory volume in 1 s % predicted r= −0.27; p=0.001). There was a significant association between BHQ scores and number of exacerbations of bronchiectasis in the last 12 months (p<0.001), hospital admissions (p=0.001) and computed tomography scan bronchiectasis pulmonary lobe counts (p<0.001). BHQ scores were significantly worse in patients with sputum bacterial colonisation versus no colonisation (p=0.048). The BHQ was highly repeatable after 2 weeks (intraclass correlation coefficient 0.89). The BHQ is a brief, valid and repeatable, self-completed health status questionnaire for bronchiectasis that generates a single total score. It can be used in the clinic to assess bronchiectasis from the patients perspective. The BHQ is a brief, valid measure of health status in patients with bronchiectasis http://ow.ly/ddUJ3089LQV

The Intensity of Voluntary, Induced, and Spontaneous Cough

BACKGROUND The intensity of cough is an important determinant of cough severity. Few studies have quantified cough intensity in patients with chronic cough with objective measures. We investigated the intensity of voluntary, induced, and spontaneous cough in patients with chronic cough and healthy control subjects. METHODS Patients with chronic cough and control subjects underwent physiologic assessment of the intensity of maximum voluntary, capsaicin-induced, and spontaneous cough. Assessments included measurement of gastric pressure (Pga) and esophageal pressure (Pes) during cough, peak cough flow (PCF), expiratory muscle strength (twitch gastric pressure [TwPga]), and cough compression phase duration (CPD). Subjective perception of cough intensity was assessed using a visual analog scale (VAS). RESULTS Pes, Pga, and PCF during maximum voluntary cough were significantly greater in patients with chronic cough compared with control subjects (P = .003-.042). There was no difference in TwPga between patients and control subjects. CPD was increased in female patients compared with control subjects (mean ± SD, 0.50 ± 0.22 s vs 0.28 ± 0.17 s; P = .007). Mean ± SD Pes during spontaneous cough was comparable to induced cough (128 ± 28 cm H2O vs 122 ± 37 cm H2O, P = .686) but less than maximum voluntary cough (170 ± 46 cm H2O, P = .020). Median within-subject correlation coefficients between cough intensity VAS and Pes, Pga, and PCF were r = 0.82 to 0.86. CONCLUSIONS Maximum voluntary cough intensity was increased in patients with chronic cough compared with control subjects. There was no significant difference in expiratory muscle contractility. Further studies should evaluate the compressive phase of cough in more detail. Physiologic measures of cough intensity correlated strongly with subjective perception of intensity in patients with chronic cough and may be relevant objective outcome measures for clinical studies.

Predictors of objective cough frequency in pulmonary sarcoidosis

Cough is a common symptom of pulmonary sarcoidosis. This study aimed to quantify cough frequency, and investigate its relationship with cough reflex sensitivity, pulmonary function and health status. 32 patients with pulmonary sarcoidosis were compared with 40 healthy controls. Cough reflex sensitivity to capsaicin, objective 24-h cough counts, cough-specific health status, cough severity and cough triggers were measured. The predictors of cough frequency in sarcoidosis were determined in a multivariate analysis. Objective cough frequency was significantly raised in patients with sarcoidosis compared with healthy controls (p<0.001) and patients with cough had an impaired health status. Patients with pulmonary sarcoidosis had a heightened cough reflex sensitivity compared with healthy controls (p<0.001). Only cough reflex sensitivity was significantly associated with objective cough frequency in multivariate analysis, explaining 42% of the variance (p<0.001). There was no association between cough frequency, lung function, number of organs involved, chest radiograph stage or serum angiotensin-converting enzyme levels. Cough is a common and significant symptom in patients with sarcoidosis. Ambulatory objective cough monitoring provides novel insights into the determinants of cough in sarcoidosis, suggesting that cough reflex sensitivity may be more important than lung function and other measures of disease severity, and this should be investigated further. Cough reflex hypersensitivity is an important determinant of objective cough frequency in sarcoidosis http://ow.ly/W4q9e

Sound: a non-invasive measure of cough intensity

Introduction Cough intensity is an important determinant of cough severity reported by patients. Cough sound analysis has been widely validated for the measurement of cough frequency but few studies have validated its use in the assessment of cough strength. We investigated the relationship between cough sound and physiological measures of cough strength. Methods 32 patients with chronic cough and controls underwent contemporaneous measurements of voluntary cough sound, flow and oesophageal pressure. Sound power, peak energy, rise-time, duration, peak-frequency, bandwidth and centroid-frequency were assessed and compared with physiological measures. The relationship between sound and subjective cough strength Visual Analogue Score (VAS), the repeatability of cough sounds and the effect of microphone position were also assessed. Results Sound power and energy correlated strongly with cough flow (median Spearman’s r=0.87–0.88) and oesophageal pressure (median Spearman’s r=0.89). Sound power and energy correlated strongly with cough strength VAS (median Spearman’s r=0.84–0.86) and were highly repeatable (intraclass correlation coefficient=0.93–0.94) but both were affected by change in microphone position. Conclusions Cough sound power and energy correlate strongly with physiological measures and subjective perception of cough strength. Power and energy are highly repeatable measures but the microphone position should be standardised. Our findings support the use of cough sound as an index of cough strength.

P150 The Development of a Cough Hypersensitivity Questionnaire (CHQ)

Introduction and objectives Cough reflex hypersensitivity (CRH) is a key feature of most patients with a refractory chronic cough and has distinct clinical features of hypertussia, allotussia (cough due to nontussive stimuli e.g. talking) and laryngeal paraesthesia (throat tickle). Cough challenge tests, the gold standard used to identify CRH, are limited for clinical use because of the wide overlap between healthy subjects and chronic cough. We aimed to develop a patient reported cough hypersensitivity questionnaire (CHQ) to identify abnormal CRH symptoms and evaluated it in subjects with and without cough. Methods The CHQ was developed following literature review, MDM and patient interviews. It assessed the presence and severity of cough triggers and laryngeal sensations on a Likert scale. It contained 35 items, score range 0–150. 38 Subjects (16 healthy, 10 refractory chronic cough (RCC: rhinitis, gastro-oesophageal reflux disease, asthma/eosinophilic bronchitis) and 12 respiratory disease (RD: bronchiectasis, sarcoidosis, interstitial lung disease and emphysema) with cough) completed the CHQ, LCQ (health status), capsaicin cough reflex sensitivity (C5) and urge to cough VAS during capsaicin test. Results Capsaicin cough reflex sensitivity, compared to healthy subjects, was increased in both RCC (geometric mean(logSD) C5 for RCC 18.1 (1.1) vs Normal 134.3 (0.8) p=0.0084) and RD (p=0.0126); figure 1. CHQ scores were raised in RCC compared to healthy subjects (p=0.0001) and RD (p=0.0068), figure 1. The upper limit of normal for CHQ score was 46. CHQ identified subjects with RCC better than C5. There was no significant relationship between CHQ and age or gender. CHQ was associated with logC5 (all subjects) r= –0.33, p=0.045 and health status (LCQ in RCC and RD) r= –0.58, p=0.006. There were no significant differences in mean(SD) urge to cough VAS during capsaicin test between subjects; healthy 52(25), RCC 39(24) and RD 54(29); p= 0.2317. Abstract P150 Figure 1 Conclusion In conclusion, this preliminary study suggests that laryngeal sensations and cough triggers assessed with the CHQ may identify patients with CRH. Further work is needed to repeat the study in a larger number of subjects, investigate whether the number of CHQ items could be reduced and to develop better objective tests of CRH.