Caroline Elston

Neural respiratory drive, pulmonary mechanics and breathlessness in patients with cystic fibrosis

Background Neural respiratory drive (NRD) measured from the diaphragm electromyogram (EMGdi) reflects the load/capacity balance of the respiratory muscle pump and is a marker of lung disease severity. EMGdi measurement is invasive, but recording the EMG from the parasternal intercostal muscles using surface electrodes (sEMGpara) could provide a non-invasive method of assessing NRD and disease severity. Objectives To test the hypothesis that NRD measured by sEMGpara correlates with EMGdi, to provide an index of disease severity in cystic fibrosis (CF) and to relate to exercise-induced breathlessness. Methods 15 patients with CF (mean forced expiratory volume in 1 s (FEV1) 53.5% predicted) and 15 age-matched healthy controls were studied. sEMGpara and EMGdi were recorded at rest and during exercise. sEMGpara was recorded using surface electrodes and EMGdi using a multipair oesophageal electrode catheter. Signals were normalised using the peak EMG recorded during maximum respiratory manoeuvres and expressed as EMG%max. The respiratory pattern, metabolic data, oesophageal and gastric pressures and Borg scores were also recorded. Results Mean (SD) resting sEMGpara%max and EMGdi%max were higher in patients with CF than in controls (13.1 (7)% and 18.5 (7.5)% vs 5.8 (3)% and 7.5 (2)%, respectively, p<0.001). In the patients with CF, resting sEMGpara%max and EMGdi%max were related to the degree of airways obstruction (FEV1) (r=−0.91 and r=−0.82, both p<0.001), hyperinflation (r=0.63 and r=0.56, both p<0.001) and dynamic lung compliance (r=−0.53 and r=−0.59, both p<0.001). During exercise, sEMGpara%max and EMGdi%max were strongly correlated with breathlessness in the patients with CF before (r=0.906, p<0.001) and after (r=0.975, p<0.001) the onset of neuromechanical dissociation. Conclusion sEMGpara%max provides a non-invasive marker of neural drive, which reflects disease severity and exercise-induced breathlessness in CF.

Chronic Lung Disease in Adolescents With Delayed Diagnosis of Vertically Acquired HIV Infection

A high burden of chronic lung disease (CLD) was found among 116 consecutive adolescents with vertically acquired human immunodeficiency virus in Zimbabwe. The main cause of HIV-associated CLD appears to be obliterative bronchiolitis, which has not previously been recognized among this patient group.

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.

Chest radiography patterns in 75 adolescents with vertically-acquired human immunodeficiency virus (HIV) infection.

Aim To evaluate lung disease on chest radiography (CR), the relative frequency of CR abnormalities, and their clinical correlates in adolescents with vertically-acquired human immunodeficiency virus (HIV) infection. Materials and methods CRs of 75 patients [59 inpatients (33 males; mean age 13.7 ± 2.3 years) and 16 outpatients (eight males; mean age 14.1 ± 2.1 years)] were retrospectively reviewed by three independent observers. The overall extent of disease (to the nearest 5%), its distribution, and the proportional extents (totalling 100%) of different radiographic patterns (including ring/tramline opacities and consolidation) were quantified. CR features and clinical data were compared. Results CRs were abnormal in 51/75 (68%) with “extensive” disease in 38/51 (74%). Ring/tramline opacities and consolidation predominated (i.e., proportional extent >50%) in 26 and 21 patients, respectively. Consolidation was significantly more common in patients hospitalized primarily for a respiratory illness than patients hospitalized for a non-respiratory illness or in outpatients (p < 0.005, χ2 for trend); by contrast, ring/tramline opacities did not differ in prevalence across the groups. On stepwise logistic regression, predominant consolidation was associated with progressive dyspnoea [odds ratio (OR) 5.60; 95% confidence intervals (CI): 1.60, 20.1; p < 0.01] and was associated with a primary respiratory cause for hospital admission (OR: 22.0; CI: 2.7, 181.1; p < 0.005). Ring/tramline opacities were equally prevalent in patients with and without chronic symptoms and in those admitted to hospital with respiratory and non-respiratory illness. Conclusion In HIV-infected adolescents, evaluated in secondary practice, CR abnormalities are prevalent. The presence of ring/tramline opacities, believed to reflect chronic airway disease, is not linked chronic respiratory symptoms.

Measurement of parasternal intercostal electromyogram during an infective exacerbation in patients with cystic fibrosis

The parasternal intercostal muscle electromyogram (sEMGpara) is a measure of neural respiratory drive and reflects lung disease severity in stable cystic fibrosis (CF). The aim of the study was to measure sEMGpara in acute infective exacerbations of CF and compare changes in sEMGpara with those in conventional lung function measures. 12 patients with CF admitted to hospital with an acute chest infection were studied. There was a significant reduction in mean±sd sEMGpara (&Dgr;sEMGpara -38±19%, p<0.001) between admission and discharge. Spirometery also improved significantly from admission to discharge; &Dgr;forced expiratory volume in 1 s % predicted 39±30%, p<0.001 and &Dgr;vital capacity % pred 22±18%, p<0.001. sEMGpara has potential value as a nonvolitional measure of change in respiratory function in CF.

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

Blunted perception of neural respiratory drive and breathlessness in patients with cystic fibrosis

The electromyogram recorded from the diaphragm (EMGdi) and parasternal intercostal muscle using surface electrodes (sEMGpara) provides a measure of neural respiratory drive (NRD), the magnitude of which reflects lung disease severity in stable cystic fibrosis. The aim of this study was to explore perception of NRD and breathlessness in both healthy individuals and patients with cystic fibrosis. Given chronic respiratory loading and increased NRD in cystic fibrosis, often in the absence of breathlessness at rest, we hypothesised that patients with cystic fibrosis would be able to tolerate higher levels of NRD for a given level of breathlessness compared to healthy individuals during exercise. 15 cystic fibrosis patients (mean forced expiratory volume in 1 s (FEV1) 53.5% predicted) and 15 age-matched, healthy controls were studied. Spirometry was measured in all subjects and lung volumes measured in the cystic fibrosis patients. EMGdi and sEMGpara were recorded at rest and during incremental cycle exercise to exhaustion and expressed as a percentage of maximum (% max) obtained from maximum respiratory manoeuvres. Borg breathlessness scores were recorded at rest and during each minute of exercise. EMGdi % max and sEMGpara % max and associated Borg breathlessness scores differed significantly between healthy subjects and cystic fibrosis patients at rest and during exercise. The relationship between EMGdi % max and sEMGpara % max and Borg score was shifted to the right in the cystic fibrosis patients, such that at comparable levels of EMGdi % max and sEMGpara % max the cystic fibrosis patients reported significantly lower Borg breathlessness scores compared to the healthy individuals. At Borg score 1 (clinically significant increase in breathlessness from baseline) corresponding levels of EMGdi % max (20.2±12% versus 32.15±15%, p=0.02) and sEMGpara % max (18.9±8% versus 29.2±15%, p=0.04) were lower in the healthy individuals compared to the cystic fibrosis patients. In the cystic fibrosis patients EMGdi % max at Borg score 1 was related to the degree of airways obstruction (FEV1) (r=−0.664, p=0.007) and hyperinflation (residual volume/total lung capacity) (r=0.710, p=0.03). This relationship was not observed for sEMGpara % max. These data suggest that compared to healthy individuals, patients with cystic fibrosis can tolerate much higher levels of NRD before increases in breathlessness from baseline become clinically significant. EMGdi % max and sEMGpara % max provide physiological tools with which to elucidate factors underlying inter-individual differences in breathlessness perception. Patients with CF can tolerate higher levels of NRD before breathlessness becomes clinically significant http://ow.ly/Xp2q3

Effect of endurance exercise on respiratory muscle function in patients with cystic fibrosis.

During exercise, patients with cystic fibrosis (CF) dynamically hyperinflate, which imposes both elastic and threshold loads on the inspiratory muscles and places them at a mechanical disadvantage due to muscle shortening. Conversely, dynamic hyperinflation imposes a progressively resistive load and lengthens the expiratory muscles potentially increasing their susceptibility to develop low frequency fatigue (LFF). The aim of the study was to determine whether high intensity endurance exercise leads to the development of LFF in either the diaphragm or expiratory abdominal wall muscles in patients with CF. Ten patients and ten healthy individuals were studied. Twitch transdiaphragmatic pressure (TwP(di)) and twitch abdominal pressure (TwT(10)) were measured before and after exhaustive endurance cycle exercise at 80% of their previously determined maximum work rate. There was no difference in TwP(di) or TwT(10) at 20, 40 or 60 min post exercise compared to pre-exercise resting values in any of the participants, indicating that overt LFF of the respiratory muscles did not develop.

WS12.4 Are goal-focused, motivational text messages effective at improving patients’ belief in their own ability (self-efficacy) to complete inhaled therapies in adults with cystic fibrosis

Objectives: It is suggested that the use of digital technologies can improve both patients experience and engagement with health care, especially for patients with chronic conditions. The aim of this study is to explore whether goal-focused, motivational text messages are effective at improving patient’s belief in their own ability (self-efficacy) to complete inhaled therapies in adults with Cystic Fibrosis (CF). This is part of a wider study which was completed as part of a Masters in Clinical Research. Method: Feasibility and acceptability, exploratory study. Inclusion criteria: I-neb user, adherence to inhaled therapy ≤ 50% and ready to change behaviour towards inhaled therapy (assessed using Readiness to Change Scale). Patients excluded were those currently receiving home visits for adherence support. Baseline measures were recorded; including self-efficacy measured using the Generalised Self-Efficacy Scale (GSE). Short and long term SMARTgoals specific to inhaled therapy adherence were set collaboratively. Subsequently patients received twice weekly goal-focused motivational text messages over 1 month. Results: 14 patients were screened. 11 met the inclusion criteria and consented to participate (8 females, 3 males; median FEV1 2.06L). 2 of the 11 participants withdrew from the study early due to an infective exacerbation requiring intravenous antibiotics. Individual patient improvements were observed in GSE scores pre - post intervention in 8/11 participants; GSE pre (median 28, interquartile (IQR) range 26–30), GSE post (median 32, IQR 30–33). Change in GSE (median 2, IQR 0–4). Conclusion: Improvements in patient’s self-efficacy with regards to nebulised therapy were observed following receipt of goal-focused motivational text messages. Further research is needed to explore which patients will respond best to this type of intervention, and whether these short term improvements could be sustained or further improved with a longer intervention.

Physiological markers of exercise capacity and lung disease severity in cystic fibrosis

Peak aerobic capacity (VO2peak) is an important outcome measure in cystic fibrosis (CF), but measurement is not widely available and can be influenced by patient motivation, pain and fatigue. Alternative markers of disease severity would be helpful. Neural respiratory drive, measured using parasternal intercostal muscle electromyography (EMGpara), reflects the load to capacity balance of the respiratory system and provides a composite measure of pulmonary function impairment in CF. The aim of the study was to investigate the relationship between exercise capacity, EMGpara and established measures of pulmonary function in clinically stable adult CF patients.