Effect of Pulmonary Rehabilitation on Exercise Capacity, Dyspnea, Fatigue, and Peripheral Muscle Strength in Patients With Post-COVID-19 Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: To establish the effects of pulmonary rehabilitation (PR) in patients with persistent symptoms after COVID-19 infection. In addition, to compare the modalities of PR services (face-to-face and telerehabilitation) and the duration of PR in weeks (4-8 weeks and >8 weeks). DATA SOURCES: PubMed/MEDLINE, Embase (Elsevier), Central/Cochrane Library, SciELO Citation Index (Web of Science), and CINAHL. STUDY SELECTION: Studies determining the effects of PR in patients with post-COVID-19 syndrome were included and grouped according to PR delivery modality. DATA EXTRACTION: Data extraction and quality assessment were independently performed by 2 reviewers. The methodological quality was assessed using the Cochrane Risk of Bias Tool 1 (RoB-1). DATA SYNTHESIS: The literature search retrieved 1406 articles, of which 7 studies explored the effects of PR on patients with post-COVID-19 syndrome, with 188 patients randomized to PR. The mean age of participants was 50 years and 49% were women. Meta-analysis showed an increase in exercise capacity with PR compared with control (6-minute walking test: mean difference: 60.56 m, 95% confidence interval: 40.75-80.36), a reduction in fatigue (Fatigue Severity Scale: -0.90, -1.49 to -0.31) but no change in dyspnea (-0.57, -1.32 to 0.17) and muscle strength (3.03, -1.89 to 7.96). There were no differences between telerehabilitation and face-to-face PR regarding effects on peripheral muscle strength (P=.42), dyspnea (P=.83), and fatigue (P=.34). There were no differences between programs 4-8 weeks and >8 weeks regarding exercise capacity (P=.83), peripheral muscle strength (P=.42), and dyspnea (P=.76). CONCLUSIONS: PR improves exercise capacity and reduces fatigue in patients with post-COVID-19 syndrome. Duration of PR (4-8 weeks vs > 8 weeks) or PR modality (telerehabilitation vs face-to-face) did not affect outcomes but data were limited and based on subgroup analysis. Further evidence is required to determine the optimal delivery mode and duration of PR for post-COVID-19 syndrome.

Use of infection control measures in people with chronic lung disease: mixed methods study.

Background: The introduction of community infection control measures during the COVID-19 pandemic was associated with a reduction in acute exacerbations of lung disease. We aimed to understand the acceptability of continued use of infection control measures among people with chronic lung disease and to understand the barriers and facilitators of use. Methods: Australian adults with chronic lung disease were invited to an online survey (last quarter of 2021) to specify infection control measures they would continue themselves post-pandemic and those they perceived should be adopted by the community. A subset of survey participants were interviewed (first quarter of 2022) with coded transcripts deductively mapped to the COM-B model and Theoretical Domains Framework. Results: 193 people (COPD 84, bronchiectasis 41, interstitial lung disease 35, asthma 33) completed the survey. Physical distancing indoors (83%), handwashing (77%), and avoidance of busy places (71%) or unwell family and friends (77%) were measures most likely to be continued. Policies for the wider community that received most support were those during the influenza season including hand sanitiser being widely available (84%), wearing of face coverings by healthcare professionals (67%) and wearing of face coverings by the general population on public transport (66%). Barriers to use of infection control measures were related to physical skills, knowledge, environmental context and resources, social influences, emotion, beliefs about capabilities and beliefs about consequences. Conclusions: Adults with chronic lung diseases in Australia are supportive of physical distancing indoors, hand hygiene, and avoidance of busy places or unwell family and friends as long-term infection control measures.

Preferences and perspectives regarding telehealth exercise interventions for adults with cystic fibrosis: A qualitative study.

OBJECTIVE: Physical activity and exercise are key components in the management of cystic fibrosis (CF). Completing exercise programs online may minimize the risk of cross-infection and increase access for people with CF. This study aimed to understand the perspectives of people with CF regarding intervention content for a telehealth exercise program. METHODS: Individual semistructured qualitative interviews were conducted in adults with CF purposefully sampled for age, disease severity, and social demographics. Interviews were recorded, transcribed verbatim, and analyzed thematically by two researchers independently. RESULTS: Participants were 23 adults with CF (14 females) aged from 21 to 60 years. Three major themes (subthemes) were generated: "Personalizing components to an exercise program" (customizing an exercise program to the individual person and their unique health and exercise needs, enjoyment and variety of exercise activities, accessibility and exercise fitting around competing demands or commitments), "The importance of maintaining connections" (challenges regarding face-to-face interactions for people with CF, accountability of scheduled exercise sessions with others, shared experiences between people with CF and specialist support from the CF care team), and "Monitoring health and exercise" (perception of health status and monitoring and recording exercise participation and health). CONCLUSION: This study provides important information regarding the preferences of adults with CF for telehealth exercise interventions. Interventions should be tailored to the individual person with CF, include an opportunity to maintain connections with peers and the CF multidisciplinary team, and provide a method to monitor progress over time.

Self-management interventions for people with pulmonary fibrosis: a scoping review.

BACKGROUND: The most effective method for encouraging self-management in individuals with pulmonary fibrosis (PF) is unclear. This review aimed to identify common self-management components, the outcome measures used and the impact of these components in PF. METHODS: A scoping review was conducted according to the Joanna Briggs Institute Manual for Evidence Synthesis using Medline, Embase, PsychInfo, CINAHL and the Cochrane Central Register of Controlled Trials. Eligible studies included those with educational, behavioural or support components aimed at facilitating self-management among adults with PF and employed quantitative and/or qualitative methods. RESULTS: 87 studies were included. Common self-management components included education (78%), managing physical symptoms (66%) and enhancing psychosocial wellbeing (54%). Components were predominantly delivered in a pulmonary rehabilitation setting (71%). No studies tested a PF-specific self-management package. Common outcome measures were 6-min walk distance (60%), St George's Respiratory Questionnaire (37%) and the Medical Research Council Dyspnoea scale (34%). Clinically significant improvements in these outcomes were seen in ≥50% of randomised controlled trials. Qualitative data highlighted the importance of healthcare professional and peer support and increased confidence in managing PF. CONCLUSION: Self-management components are commonly incorporated into pulmonary rehabilitation programmes rather than being offered as standalone packages. Future research should focus on testing PF-specific self-management packages and employ standardised outcome assessments that include self-efficacy and health-related behaviours.

Vitamin D status modulates innate immune responses and metabolomic profiles following acute prolonged cycling.

PURPOSE: The influence of vitamin D status on exercise-induced immune dysfunction remains unclear. The aim of this study was to investigate the effects of vitamin D status (circulating 25(OH)D) on innate immune responses and metabolomic profiles to prolonged exercise. METHODS: Twenty three healthy, recreationally active males (age 25 ± 7 years; maximal oxygen uptake [[Formula: see text]max] 56 ± 9 mL·kg-1·min-1), classified as being deficient (n = 7) or non-deficient n = 16) according to plasma concentrations of 25(OH)D, completed 2.5 h of cycling at 15% Δ (~ 55-60% [Formula: see text]max). Venous blood and unstimulated saliva samples were obtained before and after exercise. RESULTS: Participants with deficient plasma 25(OH)D on average had lower total lymphocyte count (mean difference [95% confidence interval], 0.5 cells × 109 L [0.1, 0.9]), p = 0.013) and greater neutrophil:lymphocyte ratio (1.3 cells × 109 L, [0.1, 2.5], p = 0.033). The deficient group experienced reductions from pre-exercise to 1 h post-exercise (- 43% [- 70, - 15], p = 0.003) in bacterial stimulated elastase in blood neutrophils compared to non-deficient participants (1% [- 20, 21], p = 1.000) Multivariate analyses of plasma metabolomic profiles showed a clear separation of participants according to vitamin D status. Prominent sources of variation between groups were purine/pyrimidine catabolites, inflammatory markers (linoleic acid pathway), lactate and tyrosine/adrenaline. CONCLUSION: These findings provide evidence of the influence of vitamin D status on exercise-induced changes in parameters of innate immune defence and metabolomic signatures such as markers of inflammation and metabolic stress.

Exercise-based rehabilitation programmes for pulmonary hypertension.

BACKGROUND: Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group, several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation. OBJECTIVES: To evaluate the benefits and harms of exercise-based rehabilitation for people with PH compared with usual care or no exercise-based rehabilitation. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 28 June 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people with PH comparing supervised exercise-based rehabilitation programmes with usual care or no exercise-based rehabilitation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. exercise capacity, 2. serious adverse events during the intervention period and 3. health-related quality of life (HRQoL). Our secondary outcomes were 4. cardiopulmonary haemodynamics, 5. Functional Class, 6. clinical worsening during follow-up, 7. mortality and 8. changes in B-type natriuretic peptide. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included eight new studies in the current review, which now includes 14 RCTs. We extracted data from 11 studies. The studies had low- to moderate-certainty evidence with evidence downgraded due to inconsistencies in the data and performance bias. The total number of participants in meta-analyses comparing exercise-based rehabilitation to control groups was 462. The mean age of the participants in the 14 RCTs ranged from 35 to 68 years. Most participants were women and classified as Group I pulmonary arterial hypertension (PAH). Study durations ranged from 3 to 25 weeks. Exercise-based programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise-based rehabilitation was 48.52 metres higher than control (95% confidence interval (CI) 33.42 to 63.62; I² = 72%; 11 studies, 418 participants; low-certainty evidence), the mean peak oxygen uptake was 2.07 mL/kg/min higher than control (95% CI 1.57 to 2.57; I² = 67%; 7 studies, 314 participants; low-certainty evidence) and the mean peak power was 9.69 W higher than control (95% CI 5.52 to 13.85; I² = 71%; 5 studies, 226 participants; low-certainty evidence). Three studies reported five serious adverse events; however, exercise-based rehabilitation was not associated with an increased risk of serious adverse event (risk difference 0, 95% CI -0.03 to 0.03; I² = 0%; 11 studies, 439 participants; moderate-certainty evidence). The mean change in HRQoL for the 36-item Short Form (SF-36) Physical Component Score was 3.98 points higher (95% CI 1.89 to 6.07; I² = 38%; 5 studies, 187 participants; moderate-certainty evidence) and for the SF-36 Mental Component Score was 3.60 points higher (95% CI 1.21 to 5.98 points; I² = 0%; 5 RCTs, 186 participants; moderate-certainty evidence). There were similar effects in the subgroup analyses for participants with Group 1 PH versus studies of groups with mixed PH. Two studies reported mean reduction in mean pulmonary arterial pressure following exercise-based rehabilitation (mean reduction: 9.29 mmHg, 95% CI -12.96 to -5.61; I² = 0%; 2 studies, 133 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: In people with PH, supervised exercise-based rehabilitation may result in a large increase in exercise capacity. Changes in exercise capacity remain heterogeneous and cannot be explained by subgroup analysis. It is likely that exercise-based rehabilitation increases HRQoL and is probably not associated with an increased risk of a serious adverse events. Exercise training may result in a large reduction in mean pulmonary arterial pressure. Overall, we assessed the certainty of the evidence to be low for exercise capacity and mean pulmonary arterial pressure, and moderate for HRQoL and adverse events. Future RCTs are needed to inform the application of exercise-based rehabilitation across the spectrum of people with PH, including those with chronic thromboembolic PH, PH with left-sided heart disease and those with more severe disease.

Implementation of offering choice of pulmonary rehabilitation location to people with COPD: a protocol for the process evaluation of a cluster randomised controlled trial.

BACKGROUND: Pulmonary rehabilitation (PR) is a core component of management people with chronic obstructive pulmonary disease (COPD); yet, people with COPD face significant barriers to attending centre-based PR programs. The emergence of new models of PR, remotely delivered directly into people's homes, has the potential to improve rehabilitation access and completion by providing patients with a choice of rehabilitation location (centre or home). However, offering patients a choice of rehabilitation model is not usual practice. We are undertaking a 14-site cluster randomised controlled trial to determine whether offering choice of PR location improves rehabilitation completion rates resulting in reduced all-cause unplanned hospitalisation over 12 months. The aim of this paper is to describe the protocol for the process evaluation of the HomeBase2 trial. METHODS: A mixed methods process evaluation, to be undertaken in real time, has been developed in accordance with UK Medical Research Council (MRC) recommendations on process evaluation of complex interventions. This protocol describes the intended use of two theoretical frameworks (RE-AIM framework (Reach; Effectiveness; Adoption; Implementation; Maintenance) and Theoretical Domains Framework (TDF)) to synthesise findings and interpret data from a combination of qualitative (semi-structured interviews) and quantitative (questionnaires, clinical outcome data, intervention fidelity) methodologies. Data will be collected at an intervention, patient and clinician level. Qualitative and quantitative data will be used to derive context-specific potential and actual barriers and facilitators to offering patients choice of rehabilitation location. Acceptability and sustainability of the intervention will be evaluated for future scale-up. DISCUSSION: The process evaluation described here will appraise the clinical implementation of offering a choice of rehabilitation program location for people with COPD. It will identify and evaluate key factors for future scale-up and sustainability and scale-up of offering choice of pulmonary rehabilitation program model for people. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217330 Registration date: January 3 2020.

Efficacy of supervised exercise prehabilitation programs to improve major abdominal surgery outcomes: A systematic review and meta-analysis.

The optimal package of components for a prehabilitation intervention remains unclear. The aim was to determine the efficacy of supervised exercise prehabilitation programs to enhance patient fitness and improve surgical outcomes. The protocol was preregistered (PROSPERO: CRD42020180693). PubMed, MEDLINE, CINAHL, AMED, CENTRAL, PeDro, ClinicalTrials.gov and the WHO International Clinical Trials Registry were searched. Randomized controlled trials (RCTs) of supervised prehabilitation programs before major abdominal surgery were included. Physical function, cardiorespiratory capacity and surgical outcomes were the primary outcomes measures. Risk of bias was assessed according to the Cochrane Risk of Bias 1.0 tool for RCTs. Data are summarized narratively, and where possible, quantitavely. Meta-analyses results are reported as risk ratios (RR), mean difference of changes between baseline and follow-up time points or mean difference between groups and 95% confidence interval (CI). Twenty RCTs were included in the analysis with a total of 1258 patients. The average 6-min walking distance change was +33 m in the prehabilitation group compared to the usual care (UC) group after prehabilitation (95% CI: [13, 53], P < 0.01). Only in studies with more than one supervised session per week changes in 6-min-walk distance were significantly higher in the prehabilitation group compared to the UC group after prehabiliatation (Mean difference: 47 m, 95% [CI]: [20-75], P < 0.01). The change in peak volume of oxygen uptake during a maximum cardiopulmonary test was +1.47 mL·kg-1·min-1 in the prehabilitation group compared to the UC group (95% CI: [0.68, 2.25], P < 0.01). There was no significant difference in the change in oxygen uptake at anaerobic threshold between groups (Mean differences: 0.47, 95% CI: [-0.16, 1.10], P:0.14). Post-operative complications incidence was similar between groups (RR: 0.80, 95% CI: [0.61, 1.05], P:0.11), irrespective of the frequency of supervised session per week (RR: 0.67, 95% CI: [0.43, 1.03], P:0.07). In conclusion, prehabilitation programmes with more than one supervised session per week improved physical function but did not enhance surgical outcomes.

Fibromyalgia and Chronic Fatigue Syndromes: A systematic review and meta-analysis of cardiorespiratory fitness and neuromuscular function compared with healthy individuals.

OBJECTIVE: To determine cardiorespiratory fitness and neuromuscular function of people with CFS and FMS compared to healthy individuals. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Medline, CINAHL, AMED, Cochrane Central Register of Controlled Trials (CENTRAL), and PEDro from inception to June 2022. ELIGIBLE CRITERIA FOR SELECTING STUDIES: Studies were included if presenting baseline data on cardiorespiratory fitness and/or neuromuscular function from observational or interventional studies of patients diagnosed with FMS or CFS. Participants were aged 18 years or older, with results also provided for healthy controls. Risk of bias assessment was conducted using the Quality Assessment Tool for Quantitative Studies (EPHPP). RESULTS: 99 studies including 9853 participants (5808 patients; 4405 healthy controls) met our eligibility criteria. Random effects meta-analysis showed lower cardiorespiratory fitness (VO2max, anaerobic threshold, peak lactate) and neuromuscular function (MVC, fatigability, voluntary activation, muscle volume, muscle mass, rate of perceived exertion) in CFS and FMS compared to controls: all with moderate to high effect sizes. DISCUSSION: Our results demonstrate lower cardiorespiratory fitness and muscle function in those living with FMS or CFS when compared to controls. There were indications of dysregulated neuro-muscular interactions including heightened perceptions of effort, reduced ability to activate the available musculature during exercise and reduced tolerance of exercise. TRAIL REGISTRATION: PROSPERO registration number: (CRD42020184108).

Does pulmonary rehabilitation address treatable traits? A systematic review.

BACKGROUND: There is growing interest in a "treatable traits" approach to pulmonary rehabilitation in chronic airways disease. The frequency with which pulmonary rehabilitation programmes address treatable traits is unknown. METHODS: Randomised controlled trials of pulmonary rehabilitation compared to usual care in patients with stable chronic airways disease were included. The components of pulmonary rehabilitation delivered were extracted and mapped to treatable traits in pulmonary, extrapulmonary and behavioural/lifestyle domains. Meta-analysis was used to evaluate the impact of addressing >1 treatable trait on exercise capacity and health-related quality of life (HRQoL). RESULTS: 116 trials were included (6893 participants). Almost all pulmonary rehabilitation programmes addressed deconditioning (97% of trials). The most commonly addressed extrapulmonary traits were nutritional status (obesity and cachexia, 18% each) and mood disturbance (anxiety and depression, 10% each). Behavioural/lifestyle traits most frequently addressed were nonadherence (46%), poor inhalation technique (24%) and poor family/social support (19%). Exercise capacity and HRQoL outcomes did not differ between studies that addressed deconditioning alone and those that targeted additional traits, but heterogeneity was high. CONCLUSION: Aside from deconditioning, treatable traits are infrequently addressed in existing trials of pulmonary rehabilitation. The potential of the treatable traits approach to improve pulmonary rehabilitation outcomes remains to be explored.

The Effect of Non-Pharmacological and Pharmacological Interventions on Measures Associated with Sarcopenia in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis provides a synthesis of the available evidence for the effects of interventions on outcome measures associated with sarcopenia in end-stage kidney disease (ESKD). Thirteen databases were searched, supplemented with internet and hand searching. Randomised controlled trials of non-pharmacological or pharmacological interventions in adults with ESKD were eligible. Trials were restricted to those which had reported measures of sarcopenia. Primary outcome measures were hand grip strength and sit-to-stand tests. Sixty-four trials were eligible (with nineteen being included in meta-analyses). Synthesised data indicated that intradialytic exercise increased hand grip strength (standardised mean difference, 0.58; 0.24 to 0.91; p = 0.0007; I2 = 40%), and sit-to-stand (STS) 60 score (mean difference, 3.74 repetitions; 2.35 to 5.14; p < 0.001; I2 = 0%). Intradialytic exercise alone, and protein supplementation alone, resulted in no statistically significant change in STS5 (−0.78 s; −1.86 to 0.30; p = 0.16; I2 = 0%), and STS30 (MD, 0.97 repetitions; −0.16 to 2.10; p = 0.09; I2 = 0%) performance, respectively. For secondary outcomes, L-carnitine and nandrolone-decanoate resulted in significant increases in muscle quantity in the dialysis population. Intradialytic exercise modifies measures of sarcopenia in the haemodialysis population; however, the majority of trials were low in quality. There is limited evidence for efficacious interventions in the peritoneal dialysis and transplant recipient populations.

Implementing a choice of pulmonary rehabilitation models in chronic obstructive pulmonary disease (HomeBase2 trial): protocol for a cluster randomised controlled trial.

INTRODUCTION: There is compelling evidence that either centre-based or home-based pulmonary rehabilitation improves clinical outcomes in chronic obstructive pulmonary disease (COPD). There are known health service and personal barriers which prevent potentially eligible patients from accessing the benefits of pulmonary rehabilitation. The aim of this hybrid effectiveness-implementation trial is to examine the effects of offering patients a choice of pulmonary rehabilitation locations (home or centre) compared with offering only the traditional centre-based model. METHOD AND ANALYSIS: This is a two-arm cluster randomised, controlled, assessor-blinded trial of 14 centre-based pulmonary rehabilitation services allocated to intervention (offering choice of home-based or centre-based pulmonary rehabilitation) or control (continuing to offer centre-based pulmonary rehabilitation only), stratified by centre-based programme setting (hospital vs non-hospital). 490 participants with COPD will be recruited. Centre-based pulmonary rehabilitation will be delivered according to best practice guidelines including supervised exercise training for 8 weeks. At intervention sites, the home-based pulmonary rehabilitation will be delivered according to an established 8-week model, comprising of one home visit, unsupervised exercise training and telephone calls that build motivation for exercise participation and facilitate self-management. The primary outcome is all-cause, unplanned hospitalisations in the 12 months following rehabilitation. Secondary outcomes include programme completion rates and measurements of 6-minute walk distance, chronic respiratory questionnaire, EQ-5D-5L, dyspnoea-12, physical activity and sedentary time at the end of rehabilitation and 12 months following rehabilitation.Direct healthcare costs, indirect costs and changes in EQ-5D-5L will be used to evaluate cost-effectiveness. A process evaluation will be undertaken to understand how the choice model is implemented and explore sustainability beyond the clinical trial. ETHICS AND DISSEMINATION: Alfred Hospital Ethics Committee has approved this protocol. The trial findings will be published in peer-reviewed journals, submitted for presentation at conferences and disseminated to patients across Australia with support from national lung charities and societies. TRIAL REGISTRATION NUMBER: NCT04217330.

Efficacy of unsupervised exercise in adults with obstructive lung disease: a systematic review and meta-analysis.

INTRODUCTION: The benefits of unsupervised exercise programmes in obstructive lung disease are unclear. The aim of this systematic review was to synthesise evidence regarding the efficacy of unsupervised exercise versus non-exercise-based usual care in patients with obstructive lung disease. METHODS: Electronic databases (MEDLINE, CINAHL, Embase, Allied and Complementary Medicine Database, Web of Science, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database) and trial registers (ClinicalTrials.gov, Current Controlled Trials, UK Clinical Trials Gateway and WHO International Clinical Trials Registry Platform) were searched from inception to April 2020 for randomised trials comparing unsupervised exercise programmes with non-exercise-based usual care in adults with chronic obstructive pulmonary disease (COPD), non-cystic fibrosis bronchiectasis or asthma. Primary outcomes were exercise capacity, quality of life, mortality, exacerbations and respiratory cause hospitalisations. RESULTS: Sixteen trials (13 COPD, 2 asthma, 1 chronic bronchitis: 1184 patients) met the inclusion criteria. Only data on COPD populations were available for meta-analysis. Unsupervised exercise resulted in a statistically but not clinically significant improvement in the 6-Minute Walk Test (n=5, MD=22.0 m, 95% CI 4.4 to 39.6 m, p=0.01). However, unsupervised exercise did lead to statistically significant and clinically meaningful improvements in St. George's Respiratory Questionnaire (n=4, MD=-11.8 points, 95% CI -21.2 to -2.3 points, p=0.01) and Chronic Respiratory Disease Questionnaire domains (dyspnoea: n=4, MD=0.5 points, 95% CI 0.1 to 0.8 points, p<0.01; fatigue: n=4, MD=0.7 points, 95% CI 0.4 to 1.0 points, p<0.01; emotion: n=4, MD=0.5 points, 95% CI 0.2 to 0.7 points, p<0.01; mastery: unable to perform meta-analysis) compared with non-exercise-based usual care. DISCUSSION: This review demonstrates clinical benefits of unsupervised exercise interventions on health-related quality of life in patients with COPD. High-quality randomised trials are needed to examine the effectiveness of prescription methods.

The Use of Airway Clearance Devices in the Management of Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Rationale: Sputum retention in chronic obstructive pulmonary disease (COPD) is a troubling symptom and can lead to reduced quality of life and increased exacerbations. Airway clearance devices are commonly used in COPD; however, their efficacy is unclear and is inconsistent among cohorts.Objectives: This study aims to systematically review the evidence to determine the impact of airway clearance devices in patients with COPD.Methods: Databases for systematic reviews and published evidence were searched. Studies were included if they were randomized and compared an airway clearance device to usual care or control. Studies were required to report at least one of the following: exacerbations, sputum volume, hospitalizations, and health-related quality of life. Data were extracted and assessed for risk of bias, and outcomes were synthesized using RevMan.Results: Eighteen studies with available data were eligible for this review, totaling 855 participants. Airway clearance devices demonstrated significant improvements in sputum volume (-1.07 ml; -0.37 to -1.77). There were significant improvements in the rate of exacerbation frequency at 6 months (rate ratio, 0.50; 95% confidence interval, 0.30-0.83; P < 0.01). No significant improvement was noted for the Saint George's Respiratory Questionnaire (0.30; -1.56 to -3.41; P = 0.10) in stable patients. There was an improvement of -5.73 (-7.30 to -4.15) for the COPD Assessment Test and -1.72 (-2.85 to -0.59) for the Breathlessness Cough and Sputum Score (P < 0.01).Conclusions: Airway clearance devices can improve exacerbation frequency, sputum clearance, and symptoms in stable COPD. The evidence included in this review was predominantly low- to moderate-grade evidence.

Coldzyme® Mouth Spray reduces duration of upper respiratory tract infection symptoms in endurance athletes under free living conditions.

Upper respiratory tract infection (URTI) can compromise athlete preparation and performance, so countermeasures are desirable. The aim of this study was to assess the effects of ColdZyme® Mouth Spray (ColdZyme) on self-reported upper respiratory tract infection in competitive endurance athletes under free-living conditions. One hundred and twenty-three endurance-trained, competitive athletes (recruited across 4 sites in England, UK) were randomised to control (no treatment, n = 61) or ColdZyme (n = 62) for a 3-month study period (between December 2017 and March 2018; or December 2018 and April 2019). They recorded daily training and illness symptoms (Jackson common cold questionnaire) during the study period. A total of 130 illness episodes were reported during the study with no difference in incidence between groups (episodes per person: 1.1 ± 0.9 Control, 1.0 ± 0.8 ColdZyme, P = 0.290). Episode duration was significantly shorter in ColdZyme compared to Control: Control 10.4 ± 8.5 days vs. ColdZyme 7.7 ± 4.0 days, P = 0.016). Further analysis to compare episodes with poor vs. good compliance with ColdZyme instructions for use (IFU) within the ColdZyme group showed a greater reduction in duration of URTI when compliance was good (9.3 ± 4.5 days in ColdZyme poor IFU compliance vs. 6.9 ± 3.5 days in ColdZyme good IFU compliance, P = 0.040). ColdZyme may be an effective countermeasure to reduce URTI duration, which was significantly lower (by 26-34%) in the ColdZyme treatment group (with no influence on incidence). This may have implications for athlete performance.

The predictors, barriers and facilitators to effective management of acute pain in children by emergency medical services: A systematic mixed studies review.

We aimed to identify predictors, barriers and facilitators to effective pre-hospital pain management in children. A segregated systematic mixed studies review was performed. We searched from inception to 30-June-2020: MEDLINE, CINAHL Complete, PsycINFO, EMBASE, Web of Science Core Collection and Scopus. Empirical quantitative, qualitative and multi-method studies of children under 18 years, their relatives or emergency medical service staff were eligible. Two authors independently performed screening and selection, quality assessment, data extraction and quantitative synthesis. Three authors performed thematic synthesis. Grading of Recommendations Assessment, Development and Evaluation and Confidence in the Evidence from Reviews of Qualitative Research were used to determine the confidence in cumulative evidence. From 4030 articles screened, 78 were selected for full text review, with eight quantitative and five qualitative studies included. Substantial heterogeneity precluded meta-analysis. Predictors of effective pain management included: 'child sex (male)', 'child age (younger)', 'type of pain (traumatic)' and 'analgesic administration'. Barriers and facilitators included internal (fear, clinical experience, education and training) and external (relatives and colleagues) influences on the clinician along with child factors (child's experience of event, pain assessment and management). Confidence in the cumulative evidence was deemed low. Efforts to facilitate analgesic administration should take priority, perhaps utilising the intranasal route. Further research is recommended to explore the experience of the child. Registration: PROSPERO CRD42017058960.

Inflammatory responses to acute exercise during pulmonary rehabilitation in patients with COPD.

OBJECTIVE: Pulmonary rehabilitation is a cornerstone treatment in the management of chronic obstructive pulmonary disease (COPD). Acute bouts of exercise can lead to short bursts of inflammation in healthy individuals. However, it is unclear how COPD patients respond to acute bouts of exercise. This study assessed inflammatory responses to exercise in COPD patients at the start (phase 1) and end (phase 2) of pulmonary rehabilitation. METHODS: Blood samples were collected before and after an acute exercise bout at the start (phase 1, n = 40) and end (phase 2, n = 27) of pulmonary rehabilitation. The primary outcome was change in fibrinogen concentrations. Secondary outcomes were changes in CRP concentrations, total/differential leukocyte counts, markers of neutrophil activation (CD11b, CD62L and CD66b), and neutrophil subsets (mature, suppressive, immature, progenitor). RESULTS: Acute exercise (phase 1) did not induce significant changes in fibrinogen (p = 0.242) or CRP (p = 0.476). Total leukocyte count [mean difference (MD), 0.5 ± 1.1 (109 L-1); p = 0.004], neutrophil count [MD, 0.4 ± 0.8 (109 L-1); p < 0.001], and immature neutrophils (MD, 0.6 ± 0.8%; p < 0.001) increased post-exercise. Neutrophil activation markers, CD11b (p = 0.470), CD66b (p = 0.334), and CD62L (p = 0.352) were not significantly altered post-exercise. In comparison to the start of pulmonary rehabilitation (phase 2), acute exercise at the end of pulmonary rehabilitation led to a greater fibrinogen response (MD, 84 mg/dL (95% CI - 14, 182); p = 0.045). CONCLUSION: An acute bout of exercise does not appear to induce significant alterations in the concentrations of inflammatory mediators but can increase white blood cell subsets post-exercise. A greater fibrinogen response to acute exercise is seen at the end of pulmonary rehabilitation when compared to the start. Further research is required to understand the clinical context of these acute inflammatory responses to exercise.

Clinical Outcomes and Inflammatory Responses of the Frequent Exacerbator in Pulmonary Rehabilitation: A Prospective Cohort Study.

Frequent exacerbators of Chronic Obstructive Pulmonary Disease (COPD) is a distinct clinical phenotype characterised by systemic inflammation. Study objectives were to determine clinical outcomes of pulmonary rehabilitation in frequent exacerbators and the impact this has on the key surrogate markers of this phenotype. Eighty-five mild-very severe COPD patients (FEV1 pred, 52 ± 18%) were categorised as frequent (≥2 exacerbations per year, n = 50) or infrequent exacerbators (≤1 exacerbation per year, n = 35). The primary outcomes were completion rates of pulmonary rehabilitation (clinical) and plasma fibrinogen (biological). Secondary outcomes were: incremental shuttle (ISWT) & endurance shuttle walk tests (ESWT), chronic respiratory disease questionnaire (CRQ), hospital anxiety and depression scale (HADS), plasma C-reactive protein (CRP), blood leukocyte counts, blood neutrophil activation (CD11b, CD62L, CD66b) and subsets (mature, immature, suppressive, progenitor). Fibrinogen and CRP concentrations were determined via ELISA's with neutrophil activation markers assessed using flow cytometry. Frequent exacerbators were less likely to complete pulmonary rehabilitation (44% vs 69%; p = 0.025). Both groups experienced improvements in ISWT (p < 0.001), ESWT (p < 0.001), all domains of the CRQ (p < 0.001) and Depression (p = 0.017). Pulmonary rehabilitation reduced resting concentrations of fibrinogen (frequent exacerbators = 12%, infrequent exacerbators = 4%, p = 0.033) and % of progenitor blood neutrophils (p = 0.015) in both groups, with reductions in total blood leukocyte (p = 0.018) and neutrophil counts (p = 0.018) also observed in frequent exacerbators. No significant reductions in CRP concentration (p = 0.937), neutrophil activation (CD11b, p = 0.553; CD62L, p = 0.070; CD66b, p = 0.317), or other neutrophil subsets (mature, p = 0.313; immature, p = 0.756; suppressive, p = 0.259) were observed. Frequent exacerbators of COPD were less likely to complete pulmonary rehabilitation, but those who complete experience similar benefits to infrequent exacerbators. Pulmonary rehabilitation may serve to have immune-modulatory properties for frequent exacerbators.