James H. Hull

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.

Eucapnic Voluntary Hyperpnea: Gold Standard for Diagnosing Exercise-Induced Bronchoconstriction in Athletes?

AbstractIn athletes, a secure diagnosnis of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the ‘gold standard’. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a ‘gold standard’ test for EIB.

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.

Exercise Ventilatory Irregularity can be quantified by Approximate Entropy to detect Breathing Pattern Disorder

BACKGROUNDnBreathing pattern disorder (BPD) is a prevalent cause of exertional dyspnea and yet there is currently no reliable objective measure for its diagnosis. We propose that statistical analysis of ventilatory irregularity, quantified by approximate entropy (ApEn), could be used to detect BPD when applied to cardiopulmonary exercise test (CPET) data. We hypothesised that ApEn of ventilatory variables (tidal volume (VT), breathing frequency (Bf), minute ventilation (VE)) would be greater, i.e. more irregular, in patients with BPD than healthy controls.nnnMETHODSnWe evaluated ventilatory ApEn in 20 adults (14 female) with exertional dyspnoea, undergoing CPET and independently diagnosed with BPD by a specialist respiratory physiotherapist. Data were compared with 15 age- gender- and BMI-matched controls. ApEn for VT, Bf and VE were calculated for an incremental cycle exercise test.nnnRESULTSnPatients with BPD more frequently rated breathlessness as the reason for exercise limitation and had a lower mean (SD) peak oxygen uptake compared with controls: 80 (18) vs. 124 (27) % predicted (Pu202f<u202f0.001). ApEn was significantly greater for VT (pu202f=u202f.006) and VE (pu202f=u202f.002) in BPD than controls. ApEn VE was inversely related (r2u202f=u202f0.24, pu202f=u202f.03) to peak oxygen uptake in BPD but not controls. ROC analysis revealed that ApEn VEu202f>u202f0.88, conferred a sensitivity and specificity of 70% and 87% respectively, for detection of BPD.nnnCONCLUSIONSnNon-linear statistical interrogation of CPET-acquired ventilatory data has utility in the detection of BPD. A simple calculation of approximate entropy of ventilation, during an incremental cardiopulmonary exercise test, provides a quantitative method to detect BPD.

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P < 0.05) and respiratory neural drive ( P < 0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure ( P < 0.05). Unexpectedly, a ventilatory increase ( P < 0.05), driven by augmented tidal volume ( P < 0.05), was seen in subjects with EILO before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an augmented tidal volume and a rise in minute ventilation.

P134 An evaluation of a new lung function test: tlno in healthy subjects

Background and Aims TLNO, transfer factor for nitric oxide, is a pulmonary function test of gas transfer. The test, in combination with carbon monoxide, allows for calculation of the alveolar membrane diffusing capacity and red blood cell conductance. This allows physicians to recognise physiologically where issues with gas transfer arise. Currently, there are very few papers looking at TLNO reproducibility in healthy subjects and none aiming with a target of 5% repeatability between efforts. This study attempts to look at the reproducibility of TLNO over 10 sessions (7 weeks total) with an intra-session repeatability of 5%. In addition, comparison of TLCO measurements between 10 and 5u2009s breath holds are made. Methods 14 normal subjects were recruited and a baseline spirometry was taken and height, weight, age and sex were recorded. Subjects were asked to perform a TLCO test with 10u2009s breath hold followed by 10 repeated sessions of the TLNO test on different days. Measurements within 5% of each other were considered acceptable repeated Results in one session. A Bland-Altman plot and regression line were constructed to compare TLCO measures between different breath hold times. One-way repeated measures ANOVA, measurement error values, intra and inter-session variability were calculated for TLNO and TLCO recordings obtained over the 10 repeated sessions. Results Bland-Altman plot revealed no statistically significant (p=0.783, p≥0.05) difference between TLCO breath hold times. Coefficient of determination from the regression line, r2=0.860. Repeated measures ANOVA revealed no significant difference for TLNO and TLCO measurements over time at p=0.374u2009and p=0.842 (p≥0.05) respectively. Intra-session and inter-session variability for TLNO were calculated as 15.02u2009ml/min/mmHg and 16.12u2009ml/min/mmHg respectively. TLCO intra-session and inter-session variability were 4.30u2009ml/min/mmHg and 3.70u2009ml/min/mmHg. We have shown that TLCO values recorded with the shorter 5u2009s breath hold agree with the conventional 10u2009s technique. Over a 7u2009week period TLNO and TLCO do not change significantly and calculated session variability is consistent with ERS/ATS guidelines. Conclusion TLNO is a highly reproducible test over a 7u2009week period and a shortened breath hold in healthy people provides the same values as the traditional 10u2009s breath hold for TLCO.

S49 Ventilatory irregularity quantified by approximate entropy identifies disordered breathing in patients with unexplained dyspnoea

Introduction Patients with idiopathic persistent exertional dyspnoea are often labelled as having a breathing pattern disorder (BPD). There are no agreed objective diagnostic measures for BPD, which complicates its characterisation and response to therapy. Approximate entropy (ApEn) is a measure of unpredictability, based on chaos theorem, which quantifies the degree of irregularity in time-series data. Objectives To measure ApEn of ventilatory variables during a cardiopulmonary exercise test (CPET) in patients referred with unexplained dyspnoea. We hypothesised that ApEn of tidal volume and breathing frequency would be greater (i.e. more irregular) in patients with BPD than healthy controls. Methods We studied 20 adults (14 female) with unexplained dyspnoea referred for CPET and diagnosed with BPD (by a senior respiratory physiotherapist blinded to ApEn data) and 15 age- gender- and BMI-matched healthy controls. Underlying cardiorespiratory disease was excluded using various investigations (e.g. imaging and echocardiography) prior to referral, in addition to tests performed on the day of CPET; namely pulmonary function and blood gas analysis. ApEn of various ventilatory parameters including tidal volume, breathing frequency and minute ventilation was calculated at rest and during a cycle-ergometer CPET. Results BPD patients had greater dyspnoea (modified BORG) at rest (1.4 ± 1.2 vs 0.2 ± 0.6; P < 0.01) and lower peak oxygen uptake (VO2) (P < 0.01; Table 1). Peak exercise respiratory exchange ratio was similar between groups (1.14 ± 0.17 vs 1.13 ± 0.08, P = 0.84) as were nadir values for ventilatory equivalent for CO2 (28.5 ± 5.2 vs 25.5 ± 3.6, P = 0.07) and end-exercise arterial PCO2 (4.21 ± 0.68 vs 4.1 ± 0.67, P = 0.68). ApEn was significantly greater in the BPD cohort for the duration of the test (Table 1); however differences were not apparent at rest. There was no relationship between ApEn and baseline symptom scores.Abstract S49 Table 1 Participant characteristics and exercise responses BPD (N = 20) Healthy Controls (N = 15) Age (years) 49 (14) 50 (18) BMI (kg/m2) 26.0 (5.0) 24.5 (3.7) FEV1 (% predicted) 107 (18) 95 (18)* FEV1/FVC 0.78 (0.06) 0.75 (0.12) VO2/kg Peak (ml/min/kg) 20.7 (7.1) 37.9 (14.9)** VO2 Peak (% Predicted) 79.8 (17.5) 124.8 (27.3)** ApEn Tidal Volume 1.31 (0.23) 1.04 (0.28)** ApEn Breathing Frequency 1.42 (0.22) 1.24 (0.24)* ApEn Minute Ventilation 1.01 (0.29) 0.64 (0.22)** Conclusion Measurement of ventilatory ApEn in patients referred with unexplained dyspnoea quantified irregularity of breathing pattern and was significantly greater (more irregular) in BPD than controls. These differences were not apparent from resting phase analysis. Quantifying increased dys-regulation in exercise hyperpnoea using ApEn can be applied to ventilatory variables collected during standard CPET, and thus could aid in diagnosis and evaluating treatment response in BPD. Further work should explore how ventilatiory ApEn relates to perception of symptoms.