Do pulmonary rehabilitation programmes improve outcomes in patients with COPD posthospital discharge for exacerbation: a systematic review and meta-analysis.

INTRODUCTION: Previous systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to examine the efficacy of pulmonary rehabilitation programmes initiated within 3 weeks of hospital discharge following an exacerbation of COPD. METHODS: An update of a previous Cochrane review was undertaken using the Cochrane Airways Review Group Specialised Register. Searches were conducted from October 2015 to August 2023 for studies that initiated pulmonary rehabilitation within 3 weeks of hospital discharge. Studies assessing the impact of solely inpatient pulmonary rehabilitation were excluded. Forest plots were generated using a generic inverse variance random effects method. RESULTS: Seventeen studies were included. Posthospital discharge pulmonary rehabilitation reduced hospital re-admissions (OR 0.48, 95% CI 0.30 to 0.77, I2=67%), improved exercise capacity (6 min walk test, mean difference (MD) 57 m, 95% CI 29 to 86, I2=89%; incremental shuttle walk test, MD 43 m, 95% CI 6 to 79, I2=81%), health-related quality of life (St. George's Respiratory Questionnaire, MD -8.7 points, 95% CI -12.5 to -4.9, I2=59%; Chronic Respiratory Disease Questionnaire (CRQ)-emotion, MD 1.0 points, 95% CI 0.4 to 1.6, I2=74%; CRQ-fatigue, MD 0.9 points, 95% CI 0.1 to 1.6, I2=91%), and dyspnoea (CRQ-dyspnoea, MD 1.0 points, 95% CI 0.3 to 1.7, I2=87%; modified Medical Research Council Dyspnoea Scale, MD -0.3 points, 95% CI -0.5 to -0.1, I2=60%). Significant effects were not observed for CRQ-mastery, COPD assessment test, EuroQol-5 Dimension-5 Level and mortality. No intervention-related adverse events were reported. DISCUSSION: Pulmonary rehabilitation delivered posthospital discharge for exacerbation of COPD results in a reduction in hospital re-admissions and improvements in exercise capacity, health-related quality of life and dyspnoea in the absence of any intervention-related adverse events. TRIAL REGISTRATION NUMBER: CRD42023406397.

Pulmonary Rehabilitation for Adults with Chronic Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Despite the known benefits of pulmonary rehabilitation (PR) for patients with chronic respiratory disease, this treatment is underused. Evidence-based guidelines should lead to greater knowledge of the proven benefits of PR, highlight the role of PR in evidence-based health care, and in turn foster referrals to and more effective delivery of PR for people with chronic respiratory disease. Methods: The multidisciplinary panel formulated six research questions addressing PR for specific patient groups (chronic obstructive pulmonary disease [COPD], interstitial lung disease, and pulmonary hypertension) and models for PR delivery (telerehabilitation, maintenance PR). Treatment effects were quantified using systematic reviews. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel made the following judgments: strong recommendations for PR for adults with stable COPD (moderate-quality evidence) and after hospitalization for COPD exacerbation (moderate-quality evidence), strong recommendation for PR for adults with interstitial lung disease (moderate-quality evidence), conditional recommendation for PR for adults with pulmonary hypertension (low-quality evidence), strong recommendation for offering the choice of center-based PR or telerehabilitation for patients with chronic respiratory disease (moderate-quality evidence), and conditional recommendation for offering either supervised maintenance PR or usual care after initial PR for adults with COPD (low-quality evidence). Conclusions: These guidelines provide the basis for evidence-based delivery of PR for people with chronic respiratory disease.

Ten years of the manufacturing classification system: a review of literature applications and an extension of the framework to continuous manufacture.

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications. This article firstly reviews this citing work and considers how the MCS concepts have been received and are being applied. Secondly, we will extend the MCS framework to continuous manufacture. The review structure follows the flow of drug product development focussing first on optimisation of API properties. The exploitation of links between API particle properties and manufacturability using large datasets seems particularly promising. Subsequently, applications of the MCS for formulation design include a detailed look at the impact of percolation threshold, the role of excipients and how other classification systems can be of assistance. The final review section focusses on manufacturing process development, covering the impact of strain rate sensitivity and modelling applications. The second part of the paper focuses on continuous processing proposing a parallel MCS framework alongside the existing batch manufacturing guidance. Specifically, we propose that continuous direct compression can accommodate a wider range of API properties compared to its batch equivalent.

Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations.Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquid-oxygen use in patients who are mobile outside the home and require >3 L/min of continuous-flow oxygen during exertion (very-low-quality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (best-practice statement).Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice.

The definite risks and questionable benefits of liberal pre-hospital spinal immobilisation.

INTRODUCTION: The routine practice of pre-hospital spinal immobilisation (phSI) for patients with suspected spinal injury has existed for decades. However, the controversy surrounding it resulted in the 2013 publication of a Consensus document by the Faculty of Pre-Hospital Care. The question remains as to whether the quality of evidence in the literature is sufficient to support the Consensus guidelines. This critical review aims to determine the validity of current recommendations by balancing the potential benefits and side effects of phSI. METHOD: A review of the literature was carried out by two independent assessors using Medline, PubMed, EMBASE and the Cochrane Library databases. Manual searches of related journals and reference lists were also completed. The selected body of evidence was subsequently appraised using a checklist derived from SIGN and CASP guidelines, as well as Crombie's guide to critical appraisal. RESULTS: No reliable sources were found proving the benefit for patient immobilisation. In contrast there is strong evidence to show that pre-hospital spinal immobilisation is not benign with recognised complications ranging from discomfort to significant physiological compromise. The published literature supports the Consensus guideline recommendations for safely reducing the impact of these side effects without compromising the patient. CONCLUSION: The literature supports the Consensus Guidelines but raises the question as to whether they go far enough as there is strong evidence to suggest phSI is an inherently harmful procedure without having any proven benefit. These results demonstrate an urgent need for further studies to determine its treatment effect.

An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease.

Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results.

An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease.

This systematic review examined the measurement properties of the 6-min walk test (6MWT), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with chronic respiratory disease. Studies that report the evaluation or use of the 6MWT, ISWT or ESWT were included. We searched electronic databases for studies published between January 2000 and September 2013. The 6-min walking distance (6MWD) is a reliable measure (intra-class correlation coefficients ranged from 0.82 to 0.99 in seven studies). There is a learning effect, with greater distance walked on the second test (pooled mean improvement of 26 m in 13 studies). Reliability was similar for ISWT and ESWT, with a learning effect also evident for ISWT (pooled mean improvement of 20 m in six studies). The 6MWD correlates more strongly with peak work capacity (r=0.59-0.93) and physical activity (r=0.40-0.85) than with respiratory function (r=0.10-0.59). Methodological factors affecting 6MWD include track length, encouragement, supplemental oxygen and walking aids. Supplemental oxygen also affects ISWT and ESWT performance. Responsiveness was moderate to high for all tests, with greater responsiveness to interventions that included exercise training. The findings of this review demonstrate that the 6MWT, ISWT and ESWT are robust tests of functional exercise capacity in adults with chronic respiratory disease.

An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation.

BACKGROUND: Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope. PURPOSE: The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field. METHODS: A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02, "Rehabilitation and Chronic Care," determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed on by all members. RESULTS: An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease, and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed. CONCLUSIONS: The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease.

Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

BACKGROUND: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures. However, evidence supporting the increased risk of disease transmission with nebulized treatments is inconclusive, and inconsistent guidelines and differing opinions have left uncertainty regarding their use. Many clinicians opt for alternative devices, but this practice could impact outcomes negatively, especially for patients who may not derive full treatment benefit from handheld inhalers. Therefore, it is prudent to develop strategies that can be used during nebulized treatment to minimize the emission of fugitive aerosols, these comprising bioaerosols exhaled by infected individuals and medical aerosols generated by the device that also may be contaminated. This is particularly relevant for patient care in the context of a highly transmissible virus. RESEARCH QUESTION: How can potential risks of infections during nebulization be mitigated? STUDY DESIGN AND METHODS: The COPD Foundation Nebulizer Consortium (CNC) was formed in 2020 to address uncertainties surrounding administration of nebulized medication. The CNC is an international, multidisciplinary collaboration of patient advocates, pulmonary physicians, critical care physicians, respiratory therapists, clinical scientists, and pharmacists from research centers, medical centers, professional societies, industry, and government agencies. The CNC developed this expert guidance to inform the safe use of nebulized therapies for patients and providers and to answer key questions surrounding medication delivery with nebulizers during pandemics or when exposure to common respiratory pathogens is anticipated. RESULTS: CNC members reviewed literature and guidelines regarding nebulization and developed two sets of guidance statements: one for the health care setting and one for the home environment. INTERPRETATION: Future studies need to explore the risk of disease transmission with fugitive aerosols associated with different nebulizer types in real patient care situations and to evaluate the effectiveness of mitigation strategies.

Exacerbations of COPD.

COPD exacerbations are associated with significant morbidity, mortality, and increased health care expenditures. The recently published Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations have further refined the definition of an exacerbation. A better understanding of the risk factors associated with the development of an exacerbation exists, and improvements are being made in earlier detection approaches. Pharmacologic treatment strategies have been the cornerstone of effective therapy. In addition, both pharmacologic and non-pharmacologic strategies have been proven successful in the prevention of future exacerbations. Newer technologies, including the use of artificial intelligence and wearable monitoring devices, are now being used to help in the earlier detection of exacerbations. Such preventive and earlier detection strategies can help to develop a more personalized care model and improve outcomes for patients with COPD.

Sports prehospital-immediate care and spinal injury: not a car crash in sight.

The prehospital management of serious injury is a key skill required of pitch-side medical staff. Previously, specific training in sports prehospital-immediate care was lacking or not of a comparable standard to other aspects of emergency care. Many principles have been drawn from general prehospital care or in-hospital training courses. This article discusses sports prehospital-immediate care as a niche of general prehospital care, using spinal injury management as an illustration of the major differences. It highlights the need to develop the sport-specific prehospital evidence base, rather than relying exclusively on considerations relevant to prolonged immobilisation of multiply injured casualties from motor vehicle accidents, falls from height or burns.

Pulmonary comorbidities in cardiac rehabilitation.

Patients with cardiovascular disease (CVD) benefit greatly from participation in cardiac rehabilitation programs. Many patients with CVD have a concomitant pulmonary disease, yet the latter is often not diagnosed (and thus undertreated). Means to evaluate and manage patients with concomitant cardiovascular and pulmonary disease will be addressed in this article.

A Delphi study of rescue and clinical subject matter experts on the extrication of patients following a motor vehicle collision.

BACKGROUND: Approximately 1.3 million people die each year globally as a direct result of motor vehicle collisions (MVCs). Following an MVC some patients will remain trapped in their vehicle; these patients have worse outcomes and may require extrication. Following new evidence, updated multidisciplinary guidance for extrication is needed. METHODS: This Delphi study has been developed, conducted and reported to CREDES standards. A literature review identified areas of expertise and appropriate individuals were recruited to a Steering Group. The Steering Group formulated initial statements for consideration. Stakeholder organisations were invited to identify subject matter experts (SMEs) from a rescue and clinical background (total 60). SMEs participated over three rounds via an online platform. Consensus for agreement / disagreement was set at 70%. At each stage SMEs could offer feedback on, or modification to the statements considered which was reviewed and incorporated into new statements or new supporting information for the following rounds. Stakeholders agreed a set of principles based on the consensus statements on which future guidance should be based. RESULTS: Sixty SMEs completed Round 1, 53 Round 2 (88%) and 49 Round 3 (82%). Consensus was reached on 91 statements (89 agree, 2 disagree) covering a broad range of domains related to: extrication terminology, extrication goals and approach, self-extrication, disentanglement, clinical care, immobilisation, patient-focused extrication, emergency services call and triage, and audit and research standards. Thirty-three statements did not reach consensus. CONCLUSION: This study has demonstrated consensus across a large panel of multidisciplinary SMEs on many key areas of extrication and related practice that will provide a key foundation in the development of evidence-based guidance for this subject area.

The Physiological Impact of Masking Is Insignificant and Should Not Preclude Routine Use During Daily Activities, Exercise, and Rehabilitation.

PURPOSE: Masking has been employed as a strategy for reducing transmission of a variety of communicable diseases. With the outbreak of SARS-CoV-2, many countries have implemented mandatory public masking. However, the perceived impact of mask use on pulmonary function has been a deterrent to public compliance with recommendations. COVID-19 has shed light on the impact that comorbid cardiac and pulmonary conditions may have on disease severity. This knowledge has led to increased primary and secondary prevention efforts for which exercise and rehabilitation are central. The importance of safe methods of exercise while mitigating risk of viral transmission is paramount to global recovery from the pandemic and prevention of future outbreaks. METHODS: We constructed a focused literature review of the impact of various masks on pulmonary function at rest and with exercise. This was then incorporated into recommendations for the integration of masks with exercise and rehabilitation in the COVID-19 era. RESULTS: While there is a paucity of evidence, we identified the physiological effects of masking at rest and during exercise to be negligible. The perceived impact appears to be far greater than the measured impact, and increased frequency of mask use leads to a physiological and psychological adaptive response. CONCLUSIONS: Masking during daily activities, exercise, and rehabilitation is safe in both healthy individuals and those with underlying cardiopulmonary disease. Rehabilitation participants should be reassured that the benefits of masking during COVID-19 far outweigh the risks, and increased frequency of mask use invokes adaptive responses that make long-term masking tolerable.

Sleep medicine certification and accreditation.

Sleep-disorders medicine is undergoing substantial evolution in terms of testing and therapy. In order to ensure that the providers of care for patients with sleep disorders provide quality and safe care, various types of individual certification and sleep-disorders-center accreditation programs have been developed. These programs should help to ensure optimal patient care.

Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

BACKGROUND: Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. METHODS: The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. RESULTS: Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. CONCLUSION: The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

The Journal of Cardiopulmonary Rehabilitation and Prevention at 40 Years and Its Role in the Evolution of Pulmonary Rehabilitation.

While the roots of pulmonary rehabilitation (PR) date back to the 1950s, the advent of modern-day PR began in the early 1970s. This commentary describes the important role the Journal of Cardiopulmonary Rehabilitation and Prevention (JCRP) had in the development of PR. Originally, launched as the Journal of Cardiac Rehabilitation in 1981, with the formation of the American Association of Cardiovascular and Pulmonary Rehabilitation, the journal's name was changed to the Journal of Cardiopulmonary Rehabilitation in 1986. This commentary summarizes key publications reported in the journal broken down into 3 time periods, as well as the impact of those publications. It also includes summaries of important scientific statements and reviews including those in collaboration with the American College of Chest Physicians. The development of successful PR programs has been based on the many publications that have been published in JCRP. Further advances in the field will likely be based on the future publications contained within JCRP.

The Effect of Metabolic Syndrome Status on Lung Function and Patient-reported Outcomes in Patients with COPD Receiving Nebulized Glycopyrrolate.

BACKGROUND: Concurrent chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) represent an important clinical phenotype with overlapping symptomology. The effect of MetS in COPD patients was assessed following treatment with nebulized glycopyrrolate (GLY; administered via eFlow® Closed System Nebulizer). METHODS: Posthoc analyses were performed on pooled lung function, patient-reported outcome (PRO) and safety data by MetS status from patients treated with placebo, GLY 25 and 50 mcg twice daily in two 12-week studies (GOLDEN 3 and 4; N=1293). Patients with MetS were characterized as having ≥ 3 of hypertension, hyperlipidemia, diabetes, body mass index (BMI) > 30 kg/m2 risk factors. The results are presented for the Food and Drug Administration-approved GLY 25 mcg dose. RESULTS: A total of25% of patients met MetS criteria.At baseline, the MetS subgroup had higher BMIs, more ex-smokers, greater incidences of cardiovascular risk factors, and MetS-specific risk factors were 2-14 times higher than non-MetS. At 12 weeks, GLY produced significant, clinically important improvements (MetS: 0.121 L; non-MetS: 0.083 L) in trough forced expiratory volume in 1 second. In the non-MetS group, significant improvements occurred in the St George's Respiratory Questionnaire (MetS: -2.28, p=0.157; non-MetS: -3.71) and Evaluating Respiratory Symptoms in COPD tool (MetS: 0.42, p=0.574; non-MetS: -1.61) total scores. Incidence of adverse events was similar with GLY versus placebo regardless of MetS status. CONCLUSION: GLY was well-tolerated and significantly improved lung function regardless of MetS status, while significant PRO improvements occurred in non-MetS patients. These results highlight the importance of comorbidities on bronchodilator responses and patient symptoms in COPD patients.