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.

Cough hypersensitivity and suppression in COPD.

Cough reflex hypersensitivity and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and cough reflex hypersensitivity in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of patients with COPD to suppress cough during a cough challenge test in comparison to patients with CRC and healthy subjects. This study also investigated whether cough reflex hypersensitivity is associated with chronic cough in COPD.Participants with COPD (n=27) and CRC (n=11) and healthy subjects (n=13) underwent capsaicin challenge tests with and without attempts to self-suppress cough in a randomised order over two visits, 5 days apart. For patients with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured.Amongst patients with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity compared to those without chronic cough (n=11): geometric mean±sd capsaicin dose thresholds for five coughs (C5) 3.36±6.88 µmol·L-1 versus 44.50±5.90 µmol·L-1, respectively (p=0.003). Participants with CRC also had heightened cough reflex sensitivity compared to healthy participants: geometric mean±sd C5 3.86±5.13 µmol·L-1 versus 45.89±3.95 µmol·L-1, respectively (p<0.001). Participants with COPD were able to suppress capsaicin-evoked cough, regardless of the presence or absence of chronic cough: geometric mean±sd capsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36±6.88 µmol·L-1 versus 12.80±8.33 µmol·L-1 (p<0.001) and 44.50±5.90 µmol·L-1 versus 183.2±6.37 µmol·L-1 (p=0.006), respectively. This was also the case for healthy participants (C5 versus CS5: 45.89±3.95 µmol·L-1 versus 254.40±3.78 µmol·L-1, p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5 versus CS5: 3.86±5.13 µmol·L-1 versus 3.34±5.04 µmol·L-1, p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in patients with COPD: ρ= -0.430, p=0.036 and ρ= -0.420, p=0.041, respectively.Patients with COPD-chronic cough and CRC both had heightened cough reflex sensitivity but only patients with CRC were unable to suppress capsaicin-evoked cough. This suggests differing mechanisms of cough between patients with COPD and CRC, and the need for disease-specific approaches to its management.

Noninvasive Assessment of Neuromechanical Coupling and Mechanical Efficiency of Parasternal Intercostal Muscle during Inspiratory Threshold Loading.

This study aims to investigate noninvasive indices of neuromechanical coupling (NMC) and mechanical efficiency (MEff) of parasternal intercostal muscles. Gold standard assessment of diaphragm NMC requires using invasive techniques, limiting the utility of this procedure. Noninvasive NMC indices of parasternal intercostal muscles can be calculated using surface mechanomyography (sMMGpara) and electromyography (sEMGpara). However, the use of sMMGpara as an inspiratory muscle mechanical output measure, and the relationships between sMMGpara, sEMGpara, and simultaneous invasive and noninvasive pressure measurements have not previously been evaluated. sEMGpara, sMMGpara, and both invasive and noninvasive measurements of pressures were recorded in twelve healthy subjects during an inspiratory loading protocol. The ratios of sMMGpara to sEMGpara, which provided muscle-specific noninvasive NMC indices of parasternal intercostal muscles, showed nonsignificant changes with increasing load, since the relationships between sMMGpara and sEMGpara were linear (R2 = 0.85 (0.75-0.9)). The ratios of mouth pressure (Pmo) to sEMGpara and sMMGpara were also proposed as noninvasive indices of parasternal intercostal muscle NMC and MEff, respectively. These indices, similar to the analogous indices calculated using invasive transdiaphragmatic and esophageal pressures, showed nonsignificant changes during threshold loading, since the relationships between Pmo and both sEMGpara (R2 = 0.84 (0.77-0.93)) and sMMGpara (R2 = 0.89 (0.85-0.91)) were linear. The proposed noninvasive NMC and MEff indices of parasternal intercostal muscles may be of potential clinical value, particularly for the regular assessment of patients with disordered respiratory mechanics using noninvasive wearable and wireless devices.

The Relationship Between Cough Reflex Sensitivity and Exacerbation Frequency in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Cough is predictive of exacerbations of chronic obstructive pulmonary disease (COPD). Little is known about cough reflex sensitivity during exacerbation of COPD and whether it is associated with exacerbation frequency. This pilot study aimed to investigate cough reflex sensitivity during and following recovery from exacerbation of COPD, and its association with the frequency of future exacerbations. In addition, the repeatability of cough reflex sensitivity in stable COPD was investigated. METHODS: Twenty participants hospitalised with exacerbation of COPD underwent inhaled capsaicin challenge during exacerbation and after 6 weeks of recovery. The frequency of future exacerbations was monitored for 12 months. The repeatability of cough reflex sensitivity was assessed in separate participants with stable COPD, who underwent 2 capsaicin challenge tests, 6 weeks apart. RESULTS: Cough reflex sensitivity was heightened during exacerbation of COPD. Geometric mean (SD) capsaicin concentration thresholds to elicit 5 coughs (C5) during exacerbation and after 6 weeks of recovery were 1.76 (3.73) vs. 8.09 (6.25) µmol L-1, respectively (p < 0.001). The change in C5 from exacerbation to 6-week recovery was associated with the frequency of future exacerbations (ρ = - 0.687, p = 0.003). C5 was highly repeatable over 6 weeks in stable COPD, and intraclass correlation coefficient was 0.85. CONCLUSION: Cough reflex sensitivity is heightened during exacerbation of COPD and reduces after recovery. The persistence of cough reflex hypersensitivity at recovery was associated with the frequency of future exacerbations.

Impaired cough suppression in chronic refractory cough.

Functional brain imaging in individuals with chronic cough demonstrates reduced activation in cortical regions associated with voluntary cough suppression. Little is known about the ability of patients with chronic cough to suppress cough. This study aimed to compare the ability to voluntarily suppress cough during inhaled capsaicin challenge in participants with chronic refractory cough with that in healthy controls. In addition, this study aimed to assess the repeatability of capsaicin challenge test with voluntary cough suppression.Participants with chronic refractory cough and healthy controls underwent inhaled capsaicin challenge tests while attempting to suppress their cough responses. After 5 days, either a conventional capsaicin challenge test with no cough suppression attempt, or a repeat test with an attempt at cough suppression was performed. Threshold capsaicin concentrations required to elicit one, two and five coughs were calculated by interpolation. Objective 24-h cough frequency was measured in individuals with chronic refractory cough.Healthy controls were able to suppress capsaicin-evoked cough while participants with chronic refractory cough were not. Geometric mean±sd capsaicin dose thresholds for five coughs with (CS5) and without (C5) suppression attempts were 254.40±3.78 versus 45.89±3.95 µmol·L-1, respectively, in healthy controls (p=0.033) and 3.34±5.04 versus 3.86±5.13 µmol·L-1, respectively, in participants with chronic refractory cough (p=0.922). Capsaicin dose thresholds for triggering five coughs with self-attempted cough suppression were significantly lower in participants with chronic refractory cough than in healthy controls; geometric mean±sd 4.94±4.43 versus 261.10±4.34 µmol·L-1, respectively; mean difference (95% CI) 5.72 (4.54-6.91) doubling doses (p<0.001). Repeatability of cough suppression test in both patients and healthy controls was high; intraclass correlation coefficients of log(CS5) values 0.81 and 0.87, respectively. CS5 was associated with objective cough frequency (ρ=-0.514, p=0.029).Participants with chronic refractory cough were less able to voluntarily suppress capsaicin-evoked cough compared to healthy controls. This may have important implications for the pathophysiology and treatment of chronic cough.

Physical Inactivity in Pulmonary Sarcoidosis.

PURPOSE: Reduced physical activity in many chronic diseases is consistently associated with increased morbidity. Little is known about physical activity in sarcoidosis. The aim of this study was to objectively assess physical activity in patients with pulmonary sarcoidosis and investigate its relationship with lung function, exercise capacity, symptom burden, and health status. METHODS: Physical activity was assessed over one week in 15 patients with pulmonary sarcoidosis and 14 age-matched healthy controls with a tri-axial accelerometer (ActivPal™) and the International Physical Activity Questionnaire (IPAQ). All participants underwent pulmonary function tests, 6-min walk test (6MWT) and completed the Fatigue Assessment Scale (FAS), Medical Research Council (MRC) Dyspnoea Scale and the King's Sarcoidosis Questionnaire (KSQ). RESULTS: Patients with sarcoidosis had significantly lower daily step counts than healthy controls; mean (SD) 5624 (1875) versus 10,429 (2942) steps (p < 0.01) and a trend towards fewer sit-to-stand transitions each day (p = 0.095). Only two patients (13%) self-reported undertaking vigorous physical activity (IPAQ) compared to half of healthy individuals (p < 0.01). Daily step count was significantly associated with 6MWT distance in sarcoidosis (r = 0.634, p = 0.01), but not with forced vital capacity (r = 0.290), fatigue (r = 0.041), dyspnoea (r = -0.466) or KSQ health status (r = 0.099-0.484). Time spent upright was associated with fatigue (r = -0.630, p = 0.012) and health status (KSQ Lung scores r = 0.524, p = 0.045), and there was a significant correlation between the number of sit-to-stand transitions and MRC dyspnoea score (r = -0.527, p = 0.044). CONCLUSION: Physical activity is significantly reduced in sarcoidosis and is associated with reduced functional exercise capacity (6MWD). Fatigue, exertional symptoms and health status were more closely associated with time spent upright and the number of bouts of physical activity, as compared to step counts. Further studies are warranted to identify the factors that determine different physical activity profiles in sarcoidosis.

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.

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.

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.

Parasternal intercostal electromyography: a novel tool to assess respiratory load in children.

BACKGROUND: Parasternal intercostal muscle electromyography (EMGpara) represents a novel tool to assess respiratory load when volitional techniques are not possible. This study examined the application of EMGpara in healthy, wheezy, and critically ill children. METHODS: Surface EMGpara was measured during tidal breathing in 92 healthy children, 20 wheezy preschool children (with measurements repeated following bronchodilator), and 25 mechanically ventilated children during supported ventilation and on continuous positive airways pressure. RESULTS: EMGpara was related to age, height, and weight in the healthy group (r = -0.623, -0.625, -0.641 respectively, all P < 0.0001). An age-based equation for predicted EMGpara was developed and patient data expressed as z-scores. EMGpara was higher in wheezy children prebronchodilator than healthy controls (median interquartile range (IQR) z-score 0.53 (0.07-1.94), P = 0.0073), falling to levels not different to healthy children postbronchodilator (-0.08 (-0.50-1.00)). In the critically ill children, EMGpara was higher (P < 0.0001) than in healthy subjects during both mechanical ventilation (median (IQR) z-score 1.14 (0.33-1.93)) and continuous positive airways pressure (1.88 (0.91-3.03)). CONCLUSION: EMGpara is feasible in children and infants both healthy and diseased, is raised in those with elevated respiratory load, and is responsive to clinical interventions. EMGpara represents a potential method to assess respiratory status in patients conventionally challenging to assess.

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.

Neural respiratory drive and breathlessness in COPD.

The aim of this study was to test the hypothesis that neural respiratory drive, measured using diaphragm electromyogram (EMGdi) activity expressed as a percentage of maximum (EMGdi%max), is closely related to breathlessness in chronic obstructive pulmonary disease. We also investigated whether neuroventilatory uncoupling contributes significantly to breathlessness intensity over an awareness of levels of neural respiratory drive alone. EMGdi and ventilation were measured continuously during incremental cycle and treadmill exercise in 12 chronic obstructive pulmonary disease patients (forced expiratory volume in 1 s±sd was 38.7±14.5 % pred). EMGdi was expressed both as EMGdi%max and relative to tidal volume expressed as a percentage of predicted vital capacity to quantify neuroventilatory uncoupling. EMGdi%max was closely related to Borg breathlessness in both cycle (r=0.98, p=0.0001) and treadmill exercise (r=0.94, p=0.005), this relationship being similar to that between neuroventilatory uncoupling and breathlessness (cycling r=0.94, p=0.005; treadmill r=0.91, p=0.01). The relationship between breathlessness and ventilation was poor when expansion of tidal volume became limited. In chronic obstructive pulmonary disease the intensity of exertional breathlessness is closely related to EMGdi%max. These data suggest that breathlessness in chronic obstructive pulmonary disease can be largely explained by an awareness of levels of neural respiratory drive, rather than the degree of neuroventilatory uncoupling. EMGdi%max could provide a useful physiological biomarker for breathlessness in chronic obstructive pulmonary disease.

Neural respiratory drive measured during inspiratory threshold loading and acute hypercapnia in healthy individuals.

Understanding the effects of respiratory load on neural respiratory drive and respiratory pattern are key to understanding the regulation of load compensation in respiratory disease. The aim of the study was to examine and compare the recruitment pattern of the diaphragm and parasternal intercostal muscles when the respiratory system was loaded using two methods. Twelve subjects performed incremental inspiratory threshold loading up to 50% of their maximal inspiratory pressure, and 10 subjects underwent incremental, steady-state hypercapnia to a maximal inspired CO2 of 5%. The diaphragmatic electromyogram (EMGdi) was measured using a multipair oesophageal catheter, and the parasternal intercostal muscle EMG (sEMGpara) was recorded from bipolar surface electrodes positioned in the second intercostal space. The EMGdi and sEMGpara were analysed over the last minute of each increment of both protocols, normalized using the peak EMG recorded during maximal respiratory manoeuvres and expressed as EMG%max. The EMGdi%max and sEMGpara%max increased in parallel during the two loading methods, although EMGdi%max was consistently greater than sEMGpara%max in both conditions, inspiratory threshold loading [bias (SD) 9 (3)%, 95% limits of agreement 4-15%] and hypercapnia [bias (SD) 6 (3)%, 95% limits of agreement -0.05 to 12%]. Inspiratory threshold loading resulted in more pronounced increases in mean (SD) EMGdi%max [10 (7)-45 (28)%] and sEMGpara%max [5.3 (3.1)-40 (28)%] from baseline compared with EMGdi%max [7 (4)-21 (8)%] and sEMGpara%max [4.7 (2.3)-10 (4)%] during hypercapnia, despite comparable levels of ventilation. These data support the use of sEMGpara%max, as a non-invasive alternative to EMGdi%max recorded with an invasive oesophageal electrode catheter, for the quantification of neural respiratory drive. This technique should make evaluation of respiratory muscle function easier to undertake and therefore more readily acceptable in patients with respiratory disease, in whom transduction of neural respiratory drive to pressure generation can be compromised.

Novel breathing pattern analysis: Symmetric Projection Attractor Reconstruction improves identification of impending COPD re-exacerbations - a retrospective cohort analysis.

Respiratory waveforms can be reduced to simple metrics, such as rate, but this may miss information about waveform shape and whole breathing pattern. A novel analysis method quantifying the whole waveform shape identifies AECOPD earlier. https://bit.ly/3M6uIEB.

Patient Global Impression of Severity Scale in Chronic Cough: Validation and Formulation of Symptom Severity Categories.

BACKGROUND: The Patient Global Impression of Severity (PGI-S) scale is a self-reported, single-item categorical scale that is increasingly used when assessing chronic cough (CC). OBJECTIVE: This study aimed to establish validity, repeatability, and responsiveness of the PGI-S scale in CC and use the scale to define discrete categories of severity when measured with other commonly used patient-reported outcome (PRO) tools. METHODS: Consecutive patients with CC completed the PGI-S scale, cough severity and urge to cough visual analog scales (VAS), and cough-specific health status Leicester Cough Questionnaire (LCQ) at a clinic visit. Validity, repeatability, and responsiveness were assessed, and threshold scores for PRO severity categories determined. RESULTS: A total of 482 participants completed the assessments; the median (interquartile range [IQR]) age was 57 (46-67) years, 71% were female, and the median (IQR) duration of cough was 48 (24-120) months. They reported a median (IQR) PGI-S score of 3 (3-4; moderate severity), cough severity VAS of 57 (31-75) mm, urge to cough VAS of 62 (40-81) mm, and LCQ of 11.5 (8.7-14.4). There were strong associations between PGI-S scores and cough severity VAS (ρ = 0.81), urge to cough VAS (ρ = 0.73), and LCQ (ρ = -0.73) (all P < .001). Repeatability of the PGI-S scale was high (n = 77); the intraclass correlation coefficient (95% confidence interval) was 0.85 (0.77-0.91) (P < .001). The PGI-S scale was responsive in participants with a treatment response (P < .001). The suggested PRO thresholds to define severe cough are ≥61 mm (cough severity VAS), ≥71 mm (urge to cough VAS), and ≤10 (LCQ). CONCLUSION: The PGI-S scale is a simple and valid tool that characterizes cough severity and is repeatable and responsive in CC. The proposed categorical severity thresholds for VAS and LCQ can provide intuitive meaning for patients and clinicians.

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study.

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

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.