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.

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.

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.

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.

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.

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.

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.

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.

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 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.

Medical Director Responsibilities for Outpatient Pulmonary Rehabilitation Programs in the United States: 2019: A STATEMENT FOR HEALTH CARE PROFESSIONALS FROM THE AMERICAN ASSOCIATION OF CARDIOVASCULAR AND PULMONARY REHABILITATION (AACVPR).

Clinical guidelines have been developed recognizing pulmonary rehabilitation (PR) as a key component in the management of patients with chronic lung disease. The medical director of a PR program is a key player in every program and is a requirement for operation of the program. The medical director must be a licensed physician who has experience in respiratory physiology management. The purpose of this document is to provide an update regarding the clinical, programmatic, legislative, and regulatory issues that impact PR medical directors in North America. It describes the clinical rationale for physician involvement, relevant legislative and regulatory requirements, and resources available that the medical director can utilize to promote evidence-based and cost-effective PR services. All pulmonary rehabilitation (PR) programs must include a medical director. There are many clinical, programmatic, legislative, and regulatory issues that impact the PR medical director. The purpose of this document is to concentrate on the unique roles and responsibilities of the PR medical director.

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.

2018 Year in Review: Sleep.

Sleep-disordered breathing affects a significant portion of the population worldwide. It is associated with many comorbid conditions, including heart failure and depression. Advances in the field regarding the diagnosis and treatment of sleep-disordered breathing are occurring on an increasing basis. This review will discuss the latest findings in the field with an emphasis on people who have obstructive sleep apnea.

Results of a Pulmonologist Survey Regarding Knowledge and Practices With Inhalation Devices for COPD.

BACKGROUND: COPD guidelines advise on inhaled medication use, yet no advice is offered on when to use and which type of patient could benefit from a specific delivery device. We investigated pulmonologists' perception of their knowledge and practices with delivery devices for COPD management. METHODS: An online survey was designed by a steering committee of American Thoracic Society clinicians and scientists and conducted by a national market research firm between January 7 and 29, 2016. RESULTS: Two hundred and five respondents completed the survey. Nearly 80% of the respondents believed that they were very knowledgeable in COPD management and the use of medications; 68% believed that they were knowledgeable about preventing exacerbations. Ninety-eight percent of the respondents stated that they were at least somewhat knowledgeable about devices. Many respondents (70%) stated that small-volume nebulizers were more effective than dry powder inhalers and pressurized metered-dose inhalers in the management of COPD exacerbations, and 63% believed that these were more effective in severe COPD (modified Medical Research Council dyspnea scale grade 4). Only 54% of the respondents discussed device options with their patients. Physician screening for physical or cognitive impairments that could impact device choices was 53% and 16%, respectively. Seventy percent of the respondents discussed device use, whereas 9% discussed cleaning and storage during a patient's first visit. Few respondents were very knowledgeable in teaching patients how to use devices (43%) and, specifically, how to use (32%) or clean and/or maintain (20%) small-volume nebulizers. CONCLUSIONS: Most respondents were confident in their knowledge about treating COPD. Fewer respondents were confident about the use and maintenance of inhalation devices, and most respondents desired to learn more about inhalation devices.

Results of a Patient Survey Regarding COPD Knowledge, Treatment Experiences, and Practices With Inhalation Devices.

BACKGROUND: Successful inhalation therapy depends on the ability of patients with COPD to properly use devices. We explored subjects' COPD knowledge, including education they receive from health care providers, treatment experiences, and practices with inhalation devices. METHODS: A multiple-choice online survey, developed by a steering committee of American Thoracic Society clinicians and scientists, was administered to subjects with COPD who were sourced from the Harris Poll Online panel. RESULTS: Of the 254 respondents (mean age 61.8 y; 49% males), most subjects (82%) claimed to understand their disease and available treatments, yet COPD symptoms and causes were well known to only 45% and 44% of subjects, respectively. Forty-three percent of subjects had ever used a pressurized metered-dose inhaler or dry-powder inhaler. Of the 54% of subjects who had ever used a small-volume nebulizer (SVN), 63% considered this device to be easy to use, 55% considered it to be fast-acting, 53% considered it to be convenient, and 38% considered it to be essential for treatment. Among subjects who had ever used them, SVNs were preferred by 54% over other devices. One third of subjects desired more extensive education during office visits; 25% felt the time was insufficient to cover questions, and 15% felt their concerns about COPD treatment(s) were ignored. Subjects believed physicians (32%), nurses (26%), and no single provider (28%) were primarily responsible for training and assessing proper inhalation technique. CONCLUSION: The survey showed differences between patients' beliefs and knowledge of COPD; the need for continuous education from health care providers, particularly on inhalation devices; and extensive use of pressurized metered-dose inhalers and dry-powder inhalers despite positive perceptions of SVNs.

Office Spirometry in Primary Care for the Diagnosis and Management of COPD: National Lung Health Education Program Update.

The use of office spirometry was recommended by the National Lung Health Education Program (NLHEP) consensus conference in 1999 for detection and management of COPD. Since that time, spirometry utilization has increased, but its role in the diagnosis of COPD is still evolving. This update reviews the role of spirometry for screening and case finding in COPD as well as for asthma. Spirometry has been used for disease management in patients with airway obstruction, with varying results. The diagnostic criteria for COPD using spirometry have also evolved in the past 17 years, with differences arising between the Global Initiative for Chronic Obstructive Lung Disease and NLHEP recommendations. More sophisticated spirometers as well as new reference equations are widely available. Standardization guidelines from the American Thoracic Society/European Respiratory Society published in 2005 provide a robust framework for performing and interpreting spirometry, but clinicians still need hands-on training and meaningful feedback to perform high-quality spirometry in the office setting.