Do guidelines influence breathlessness management in advanced lung diseases? A multinational survey of respiratory medicine and palliative care physicians.

BACKGROUND: Respiratory medicine (RM) and palliative care (PC) physicians' management of chronic breathlessness in advanced chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung disease (fILD) and lung cancer (LC), and the influence of practice guidelines was explored via an online survey. METHODS: A voluntary, online survey was distributed to RM and PC physicians via society newsletter mailing lists. RESULTS: 450 evaluable questionnaires (348 (77%) RM and 102 (23%) PC) were analysed. Significantly more PC physicians indicated routine use (often/always) of opioids across conditions (COPD: 92% vs. 39%, fILD: 83% vs. 36%, LC: 95% vs. 76%; all p < 0.001) and significantly more PC physicians indicated routine use of benzodiazepines for COPD (33% vs. 10%) and fILD (25% vs. 12%) (both p < 0.001). Significantly more RM physicians reported routine use of a breathlessness score (62% vs. 13%, p < 0.001) and prioritised exercise training/rehabilitation for COPD (49% vs. 7%) and fILD (30% vs. 18%) (both p < 0.001). Overall, 40% of all respondents reported reading non-cancer palliative care guidelines (either carefully or looked at them briefly). Respondents who reported reading these guidelines were more likely to: routinely use a breathlessness score (χ2 = 13.8; p < 0.001), use opioids (χ2 = 12.58, p < 0.001) and refer to pulmonary rehabilitation (χ2 = 6.41, p = 0.011) in COPD; use antidepressants (χ2 = 6.25; p = 0.044) and refer to PC (χ2 = 5.83; p = 0.016) in fILD; and use a handheld fan in COPD (χ2 = 8.75, p = 0.003), fILD (χ2 = 4.85, p = 0.028) and LC (χ2 = 5.63; p = 0.018). CONCLUSIONS: These findings suggest a need for improved dissemination and uptake of jointly developed breathlessness management guidelines in order to encourage appropriate use of existing, evidence-based therapies. The lack of opioid use by RM, and continued benzodiazepine use in PC, suggest that a wider range of acceptable therapies need to be developed and trialled.

Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction.

BACKGROUND AND AIMS: Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment. DESIGN: A single-subject study over 5 years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses. SETTING: A clinical research facility. Participant Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction. MEASUREMENTS: Physiological measures of oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ) and respiratory rate (RR) were used to indicate severity of respiratory depression. FINDINGS: (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20 sec (maximum 56 sec), elevated ETCO2 (maximum 6.9%) and hypoxaemia (minimum SpO2 80%). (2) Abnormalities were greater with highest diamorphine dose: average SpO2 was 89.3% after 100 mg diamorphine versus 93.6% and 92.8% for the two 30-mg doses. (3) However, long apnoeic pauses and high levels of ETCO2 % were also present after lower doses. CONCLUSIONS: With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

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.

Variations in the cost of formal and informal health care for patients with advanced chronic disease and refractory breathlessness: A cross-sectional secondary analysis.

BACKGROUND: Refractory breathlessness in advanced chronic disease leads to high levels of disability, anxiety and social isolation. These result in high health-resource use, although this is not quantified. AIMS: To measure the cost of care for patients with advanced disease and refractory breathlessness and to identify factors associated with high costs. DESIGN: A cross-sectional secondary analysis of data from a randomised controlled trial. SETTING/PARTICIPANTS: Patients with advanced chronic disease and refractory breathlessness recruited from three National Health Service hospitals and via general practitioners in South London. RESULTS: Of 105 patients recruited, the mean cost of formal care was £3253 (standard deviation £3652) for 3 months. The largest contributions to formal-care cost were hospital admissions (>60%), and palliative care contributed <1%. When informal care was included, the total cost increased by >250% to £11,507 (standard deviation £9911). Increased patient disability resulting from breathlessness was associated with high cost (£629 per unit increase in disability score; p = 0.006). Increased breathlessness on exertion and the presence of an informal carer were also significantly associated with high cost. Patients with chronic obstructive pulmonary disease tended to have higher healthcare costs than other patients. CONCLUSION: Informal carers contribute significantly to the care of patients with advanced disease and refractory breathlessness. Disability resulting from breathlessness is an important clinical cost driver. It is important for policy makers to support and acknowledge the contributions of informal carers. Further research is required to assess the clinical- and cost-effectiveness of palliative care interventions in reducing disability resulting from breathlessness in this patient group.

Breathlessness during daily activity: The psychometric properties of the London Chest Activity of Daily Living Scale in patients with advanced disease and refractory breathlessness.

BACKGROUND: The London Chest Activities of Daily Living Scale measures the impact of breathlessness on both activity and social functioning. However, the London Chest Activities of Daily Living Scale is not routinely used in patients with advanced disease. AIM: To assess the psychometric properties of the London Chest Activities of Daily Living Scale in patients with refractory breathlessness due to advanced disease. DESIGN: A cross-sectional secondary analysis of data from a randomised controlled parallel-group, pragmatic, single-blind fast-track trial (randomised controlled trial) investigating the effectiveness of an integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness, known as the Breathlessness Support Service (NCT01165034). All patients completed the following questionnaires: the London Chest Activities of Daily Living Scale, Chronic Respiratory Questionnaire, the Palliative care Outcome Scale, Palliative care Outcome Scale-symptoms, the Hospital Anxiety and Depression Scale and breathlessness measured on a numerical rating scale. Data quality, scaling assumptions, acceptability, internal consistency and construct validity of the London Chest Activities of Daily Living Scale were determined using standard psychometric approaches. SETTING/PARTICIPANTS: Breathless patients with advanced malignant and non-malignant disease. RESULTS: A total of 88 patients were studied, primary diagnosis included; chronic obstructive pulmonary disease = 53, interstitial lung disease = 17, cancer = 18. Median (range) London Chest Activities of Daily Living Scale total score was 46.5 (14-67). No floor or ceiling effect was observed for the London Chest Activities of Daily Living Scale total score. Internal consistency was good, and Cronbach's alpha for the London Chest Activities of Daily Living Scale total score was 0.90. Construct validity was good with 13 out of 15 a priori hypotheses met. CONCLUSION: Psychometric analyses suggest that the London Chest Activities of Daily Living Scale is acceptable, reliable and valid in patients with advanced disease and refractory breathlessness.

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

BACKGROUND AND OBJECTIVE: Peak aerobic capacity (VO2 peak) 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. METHODS: Twenty CF patients (12 males, median (range) age: 22.3 (17.0-43.1) years) performed the 10-m incremental shuttle walk test (ISWT) maximally with contemporaneous measures of aerobic metabolism. EMGpara was recorded from second intercostal space at rest and normalized using peak electromyogram activity obtained during maximum respiratory manoeuvres and expressed as EMGpara%max (EMGpara expressed as a percentage of maximum). RESULTS: VO2 peak was strongly correlated with ISWT distance (r = 0.864, P < 0.0001). Lung gas transfer (TL CO) % predicted was best correlated with VO2 peak (r = 0.842, P < 0.0001) and ISWT distance (r = 0.788, P < 0.0001). EMGpara%max also correlated with VO2 peak (-0.757, P < 0.0001), while the relationships between exercise outcome measures and forced expiratory volume in 1 s (FEV1 ) % predicted and forced vital capacity (FVC) % predicted were less strong. A TL CO% predicted of <70.5% was the strongest predictor of VO2 peak <32 mL/min/kg (area under the curve (AUC): 0.96, 100% sensitivity, 83.3% specificity). ISWT distance and EMGpara%max also performed well, with other pulmonary function variables demonstrating poorer predictive ability. CONCLUSION: TL CO% predicted and EMGpara%max relate strongly to exercise performance markers in CF and may provide alternative predictors of lung disease progression.

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.

Dignity Through Integrated Symptom Management: Lessons From the Breathlessness Support Service.

CONTEXT: Dignity is poorly conceptualized and little empirically explored in end-of-life care. A qualitative evaluation of a service offering integrated palliative and respiratory care for patients with advanced disease and refractory breathlessness uncovered an unexpected outcome, it enhanced patients' dignity. OBJECTIVES: To analyze what constitutes dignity for people suffering from refractory breathlessness with advanced disease, and its implications for the concept of dignity. METHODS: Qualitative study of cross-sectional interviews with 20 patients as part of a Phase III evaluation of a randomized controlled fast-track trial. The interviews were transcribed verbatim, imported into NVivo, and analyzed through constant comparison. The findings were compared with Chochinov et al.'s dignity model. The model was adapted with the themes and subthemes specific to patients suffering from breathlessness. RESULTS: The findings of this study underscore the applicability of the conceptual model of dignity for patients with breathlessness. There were many similarities in themes and subthemes. Differences specifically relevant for patients suffering from severe breathlessness were as follows: 1) physical distress and psychological mechanisms are interlinked with the disability and dependence breathlessness causes, in the illness-related concerns, 2) stigma is an important component of the social dignity inventory, 3) conditions and perspectives need to be present to practice self-care in the dignity-conserving repertoire. CONCLUSION: Dignity is an integrated concept and can be affected by influences from other areas such as illness-related concerns. The intervention shows that targeting the symptom holistically and equipping patients with the means for self-care realized the outcome of dignity.

Patients' experiences of a new integrated breathlessness support service for patients with refractory breathlessness: Results of a postal survey.

BACKGROUND: We developed a new single point of access to integrated palliative care, respiratory medicine and physiotherapy: the breathlessness support service for patients with advanced disease and refractory breathlessness. This study aimed to describe patients' experiences of the service and identify the aspects valued. DESIGN: We attempted to survey all patients who had attended and completed the 6-week breathlessness support service intervention by sending them a postal questionnaire to self-complete covering experience, composition, effectiveness of the BSS and about participation in research. Data were analysed using descriptive statistics and thematic analysis of free text comments. RESULTS: Of the 70 postal questionnaires sent out, 25 (36%) returned. A total of 21 (84% (95% confidence interval: 69%-98%)) responding patients reported that they definitely found the breathlessness support service helpful and 13 (52% (95% confidence interval: 32%-72%)) rated the breathlessness support service as excellent. A total of 21 (84% (95% confidence interval: 69%-98%)) patients reported that the breathlessness support service helped with their management of their breathlessness along with additional symptoms and activities (e.g. mood and mobility). Four key themes were identified: (1) personalised care, (2) caring nature of the staff, (3) importance of patient education to empower patients and (4) effectiveness of context-specific breathlessness interventions. These were specific aspects that patients valued. CONCLUSION: Patients' satisfaction with the breathlessness support service was high, and identified as important to this was a combination of personalised care, nature of staff, education and empowerment, and use of specific interventions. These components would be important in any future breathlessness service.

Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

Opioids are respiratory depressants and heroin/opioid overdose is a major contributor to the excess mortality of heroin addicts. The individual and situational variability of respiratory depression caused by intravenous heroin is poorly understood. This study used advanced respiratory monitoring to follow the time course and severity of acute opioid-induced respiratory depression. 10 patients (9/10 with chronic airflow obstruction) undergoing supervised injectable opioid treatment for heroin addiction received their usual prescribed dose of injectable opioid (diamorphine or methadone) (IOT), and their usual prescribed dose of oral opioid (methadone or sustained release oral morphine) after 30 minutes. The main outcome measures were pulse oximetry (SpO2%), end-tidal CO2% (ETCO2%) and neural respiratory drive (NRD) (quantified using parasternal intercostal muscle electromyography). Significant respiratory depression was defined as absence of inspiratory airflow >10s, SpO2% < 90% for >10s and ETCO2% per breath >6.5%. Increases in ETCO2% indicated significant respiratory depression following IOT in 8/10 patients at 30 minutes. In contrast, SpO2% indicated significant respiratory depression in only 4/10 patients, with small absolute changes in SpO2% at 30 minutes. A decline in NRD from baseline to 30 minutes post IOT was also observed, but was not statistically significant. Baseline NRD and opioid-induced drop in SpO2% were inversely related. We conclude that significant acute respiratory depression is commonly induced by opioid drugs prescribed to treat opioid addiction. Hypoventilation is reliably detected by capnography, but not by SpO2% alone. Chronic suppression of NRD in the presence of underlying lung disease may be a risk factor for acute opioid-induced respiratory depression.

An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial.

BACKGROUND: Breathlessness is a common and distressing symptom, which increases in many diseases as they progress and is difficult to manage. We assessed the effectiveness of early palliative care integrated with respiratory services for patients with advanced disease and refractory breathlessness. METHODS: In this single-blind randomised trial, we enrolled consecutive adults with refractory breathlessness and advanced disease from three large teaching hospitals and via general practitioners in South London. We randomly allocated (1:1) patients to receive either a breathlessness support service or usual care. Randomisation was computer generated centrally by the independent Clinical Trials Unit in a 1:1 ratio, by minimisation to balance four potential confounders: cancer versus non-cancer, breathlessness severity, presence of an informal caregiver, and ethnicity. The breathlessness support service was a short-term, single point of access service integrating palliative care, respiratory medicine, physiotherapy, and occupational therapy. Research interviewers were masked as to which patients were in the treatment group. Our primary outcome was patient-reported breathlessness mastery, a quality of life domain in the Chronic Respiratory Disease Questionnaire, at 6 weeks. All analyses were by intention to treat. Survival was a safety endpoint. This trial is registered with ClinicalTrials.gov, number NCT01165034. FINDINGS: Between Oct 22, 2010 and Sept 28, 2012, 105 consenting patients were randomly assigned (53 to breathlessness support service and 52 to usual care). 83 of 105 (78%) patients completed the assessment at week 6. Mastery in the breathlessness support service group improved compared with the control (mean difference 0·58, 95% CI 0·01-1·15, p=0·048; effect size 0·44). Sensitivity analysis found similar results. Survival rate from randomisation to 6 months was better in the breathlessness support service group than in the control group (50 of 53 [94%] vs 39 of 52 [75%]) and in overall survival (generalised Wilcoxon 3·90, p=0·048). Survival differences were significant for patients with chronic obstructive pulmonary disease and interstitial lung disease but not cancer. INTERPRETATION: The breathlessness support service improved breathlessness mastery. Our findings provide robust evidence to support the early integration of palliative care for patients with diseases other than cancer and breathlessness as well as those with cancer. The improvement in survival requires further investigation. FUNDING: UK National Institute for Health Research (NIHR) and Cicely Saunders International.

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.

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 (ΔsEMGpara -38 ± 19%, p<0.001) between admission and discharge. Spirometery also improved significantly from admission to discharge; Δforced expiratory volume in 1 s % predicted 39 ± 30%, p<0.001 and Δvital capacity % pred 22 ± 18%, p<0.001. sEMGpara has potential value as a nonvolitional measure of change in respiratory function in CF.

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 (FEV(1)) 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 (FEV(1)) (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.