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Chronic obstructive pulmonary disease (COPD) is considered the fourth-leading causes of death worldwide; COPD is caused by inhalation of noxious indoor and outdoor particles, especially cigarette smoke that represents the first risk factor for this respiratory disorder. To mimic the effects of particulate matter on COPD, we isolated peripheral blood mononuclear cells (PBMCs) and treated them with combustion-generated ultrafine particles (UFPs) obtained from two different fuel mixtures, namely, pure ethylene and a mixture of ethylene and dimethylfuran (the latter mimicking the combustion of biofuels). UFPs were separated in two fractions: (1) sub-10 nm particles, named nano organic carbon (NOC) particles and (2) primarily soot particles of 20-40 nm and their agglomerates (200 nm). We found that both NOC and soot UFPs induced the release of IL-18 and IL-33 from unstable/exacerbated COPD-derived PBMCs. This effect was associated with higher levels of mitochondrial dysfunction and derived reactive oxygen species, which were higher in PBMCs from unstable COPD patients after combustion-generated UFP exposure. Moreover, lower mRNA expression of the repairing enzyme OGG1 was associated with the higher levels of 8-OH-dG compared with non-smoker and smokers. It was interesting that IL-18 and IL-33 release from PBMCs of unstable COPD patients was not NOD-like receptor 3/caspase-1 or caspase-8-dependent, but rather correlated to caspase-4 release. This effect was not evident in stable COPD-derived PBMCs. Our data suggest that combustion-generated UFPs induce the release of caspase-4-dependent inflammasome from PBMCs of COPD patients compared with healthy subjects, shedding new light into the biology of this key complex in COPD.

Overuse of asthma relievers is associated with significant adverse consequences. This study aimed to better understand the population purchasing and using short-acting beta agonists (SABA) over the counter (OTC); and compare the demographic, clinical and behavioural characteristics of those who overuse SABA with those who do not. Real-world cross-sectional observational study in community pharmacy. Of 412 participants ≥16 years requesting SABA OTC, 289 were SABA overusers (used SABA more than twice per week in the past 4 weeks). Reliever use, Global Initiative for Asthma-defined control, healthcare utilisation, patterns of preventer use. 70.1% of participants were classified as SABA overusers, that is, reporting SABA use more than twice a week within the last 4 weeks, 73.6% reported not using a preventer daily and only 81.6% reported a doctor diagnosis of asthma. SABA overusers were more likely to have moderate-severe nasal symptoms (80.8% vs 63.0%, p<0.001) and a diagnosis of depression (11.1% vs 5.7%, p<0.001), when compared with SABA non-overusers. A higher proportion of SABA overusers had uncontrolled asthma (59.0% vs 15.4%, p<0.001), were more likely to use oral corticosteroids to manage worsening asthma symptoms (26.2% vs 13.5%, p<0.01) and visit the doctor for their asthma in the past 12 months (74.5% vs 62.5%, p<0.01), when compared to SABA non-overusers. This study uncovers a hidden population of people who can only be identified in pharmacy with suboptimal asthma, coexisting rhinitis, poor preventer adherence and, in some cases, no asthma diagnosis.

IntroductionExisting mobility endpoints based on functional performance, physical assessments and patient self-reporting are often affected by lack of sensitivity, limiting their utility in clinical practice. Wearable devices including inertial measurement units (IMUs) can overcome these limitations by quantifying digital mobility outcomes (DMOs) both during supervised structured assessments and in real-world conditions. The validity of IMU-based methods in the real-world, however, is still limited in patient populations. Rigorous validation procedures should cover the device metrological verification, the validation of the algorithms for the DMOs computation specifically for the population of interest and in daily life situations, and the users’ perspective on the device.Methods and analysisThis protocol was designed to establish the technical validity and patient acceptability of the approach used to quantify digital mobility in the real world by Mobilise-D, a consortium funded by the European Union (EU) as part of the Innovative Medicine Initiative, aiming at fostering regulatory approval and clinical adoption of DMOs.After defining the procedures for the metrological verification of an IMU-based device, the experimental procedures for the validation of algorithms used to calculate the DMOs are presented. These include laboratory and real-world assessment in 120 participants from five groups: healthy older adults; chronic obstructive pulmonary disease, Parkinson’s disease, multiple sclerosis, proximal femoral fracture and congestive heart failure. DMOs extracted from the monitoring device will be compared with those from different reference systems, chosen according to the contexts of observation. Questionnaires and interviews will evaluate the users’ perspective on the deployed technology and relevance of the mobility assessment.Ethics and disseminationThe study has been granted ethics approval by the centre’s committees (London—Bloomsbury Research Ethics committee; Helsinki Committee, Tel Aviv Sourasky Medical Centre; Medical Faculties of The University of Tübingen and of the University of Kiel). Data and algorithms will be made publicly available.Trial registration numberISRCTN (12246987).

ObjectivesMetered-dose inhalers (MDIs) contain propellants which are potent greenhouse gases. Many agencies propose a switch to alternative, low global warming potential (GWP) inhalers, such as dry powder inhalers (DPIs). We aimed to analyse the impact on greenhouse gas emissions and drug costs of making this switch.SettingWe studied National Health Service prescription data from England in 2017 and collated carbon footprint data on inhalers commonly used in England.DesignInhalers were separated into different categories according to their mechanisms of action (eg, short-acting beta-agonist). Within each category we identified low and high GWP inhalers and calculated the cost and carbon impact of changing to low GWP inhalers. We modelled scenarios for swapping proportionally according to the current market share of each equivalent DPI (model 1) and switching to the lowest cost pharmaceutically equivalent DPI (model 2). We also reviewed available data on the carbon footprint of inhalers from scientific publications, independently certified reports and patents to provide more accurate carbon footprint information on different types of inhalers.ResultsIf MDIs using HFA propellant are replaced with the cheapest equivalent DPI, then for every 10% of MDIs changed to DPIs, drug costs decrease by £8.2M annually. However if the brands of DPIs stay the same as 2017 prescribing patterns, for every 10% of MDIs changed to DPIs, drug costs increase by £12.7M annually. Most potential savings are due to less expensive long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) inhalers. Some reliever inhalers (eg, Ventolin) have a carbon footprint over 25 kg CO2e per inhaler, while others use far less 1,1,1,2-tetrafluoroethane (HFA134a) (eg, Salamol) with a carbon footprint of <10 kg CO2e per inhaler. 1,1,1,2,3,3,3-Heptafluoropropane (HFA227ea) LABA/ICS inhalers (eg, Flutiform) have a carbon footprint over 36 kg CO2e, compared with an equivalent HFA134a combination inhaler (eg, Fostair) at <20 kg CO2e. For every 10% of MDIs changed to DPIs, 58 kt CO2e could be saved annually in England.ConclusionsSwitching to DPIs would result in large carbon savings and can be achieved alongside reduced drug costs by using less expensive brands. Substantial carbon savings can be made by using small volume HFA134a MDIs, in preference to large volume HFA134a MDIs, or those containing HFA227ea as a propellant.

ObjectivesOccupational dust exposure may induce various lung diseases, including pneumoconiosis and chronic obstructive pulmonary disease (COPD). The features of combined COPD and pneumoconiosis have not been well described, and this may hamper the management. This study aimed to describe the prevalence and characteristics as well as the risk factors of the combined diseases.DesignA cross-sectional study.Setting and participants758 patients with pneumoconiosis were recruited at a single-medical centre. Of these, 675 patients with pneumoconiosis, including asbestosis, silicosis, coal workers’ pneumoconiosis and other pneumoconiosis, was eligible for analysis.Primary outcome measuresCOPD was diagnosed based on clinical features and/or history of exposure to risk factors and post bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. Clinical data were collected from predesigned medical reports. The patients underwent both chest radiograph and high-resolution CT scans. Risk factors for combined COPD and pneumoconiosis were analysed using regression analysis.ResultsCOPD prevalence overall was 32.7% (221/675) and was the highest in silicosis (84/221) and coal workers’ pneumoconiosis (100/221). COPD prevalence increased with smoking pack-years, dust exposure duration and pneumoconiosis stage. Patients with combined diseases had lower body mass index, higher smoking index and worse pulmonary function. Risk factors for combined diseases included heavy smoking, silica or coal exposure and advanced pneumoconiosis. The interaction between dust exposure and smoking in COPD was also identified. The risk of combined COPD significantly increased with heavy smoking and silica or coal exposure (OR 5.49, 95% CI 3.04 to 9.93, p<0.001).ConclusionsCOPD is highly prevalent in patients with pneumoconiosis, especially patients with silicosis and coal workers’ pneumoconiosis. Occupational dust exposure as well as heavy smoking is associated with an increased risk of combined COPD and pneumoconiosis, which demands an effective preventive intervention.

ObjectiveTo identify, characterise and explain common and specific features of the experience of treatment burden in relation to patients living with lung cancer or chronic obstructive pulmonary disease (COPD) and their informal caregivers.DesignSystematic review and interpretative synthesis of primary qualitative studies. Papers were analysed using constant comparison and directed qualitative content analysis.Data sourcesCINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science searched from January 2006 to December 2015.Eligibility criteria for selecting studiesPrimary qualitative studies in English where participants were patients with lung cancer or COPD and/or their informal caregivers, aged >18 years that contain descriptions of experiences of interacting with health or social care in Europe, North America and Australia.ResultsWe identified 127 articles with 1769 patients and 491 informal caregivers. Patients, informal caregivers and healthcare professionals (HCPs) acknowledged lung cancer’s existential threat. Managing treatment workload was a priority in this condition, characterised by a short illness trajectory. Treatment workload was generally well supported by an immediacy of access to healthcare systems and a clear treatment pathway. Conversely, patients, informal caregivers and HCPs typically did not recognise or understand COPD. Treatment workload was balanced with the demands of everyday life throughout a characteristically long illness trajectory. Consequently, treatment workload was complicated by difficulties of access to, and navigation of, healthcare systems, and a fragmented treatment pathway. In both conditions, patients’ capacity to manage workload was enhanced by the support of family and friends, peers and HCPs and diminished by illness/smoking-related stigma and social isolation.ConclusionThis interpretative synthesis has affirmed significant differences in treatment workload between lung cancer and COPD. It has demonstrated the importance of the capacity patients have to manage their workload in both conditions. This suggests a workload which exceeds capacity may be a primary driver of treatment burden.PROSPERO registration numberCRD42016048191.

Epithelial-to-mesenchymal transition (EMT) is a reversible process, in which epithelial cells lose their epithelial traits and acquire a mesenchymal phenotype. This transformation has been described in different lung diseases, such as lung cancer, interstitial lung diseases, asthma, chronic obstructive pulmonary disease and other muco-obstructive lung diseases, such as cystic fibrosis and non-cystic fibrosis bronchiectasis. The exaggerated chronic inflammation typical of these pulmonary diseases can induce molecular reprogramming with subsequent self-sustaining aberrant and excessive profibrotic tissue repair. Over time this process leads to structural changes with progressive organ dysfunction and lung function impairment. Although having common signalling pathways, specific triggers and regulation mechanisms might be present in each disease. This review aims to describe the various mechanisms associated with fibrotic changes and airway remodelling involved in chronic airway diseases. Having better knowledge of the mechanisms underlying the EMT process may help us to identify specific targets and thus lead to the development of novel therapeutic strategies to prevent or limit the onset of irreversible structural changes.

IntroductionUnderstanding patient perspectives on asthma and chronic obstructive pulmonary disease (COPD) is limited, with no prior studies employing such a large-scale, proactive survey to systematically target individuals with a confirmed prescription for inhalation medication. This study aims to explore how patients with asthma or COPD manage their lives, including treatment experiences, symptoms and impacts on daily life.Methods and analysisA nationwide survey will be launched in January 2025, targeting adults (≥18 years) in Denmark diagnosed with asthma or COPD and prescribed or dispensed inhalation medication between 1 October 2023 and 30 September 2024. Data from the Danish Health Data Authority’s Register of Medicinal Product Statistics will identify eligible individuals. The electronic survey will be distributed via e-Boks to approximately 450 000 individuals.The questionnaire integrates validated tools—COPD Assessment Test, Modified Medical Research Council scale, EuroQol 5-Dimension 5-Level and Asthma Control Test—alongside expert-developed questions on symptoms, diagnosis, disease control, treatment and patient experiences. Questionnaire development included 10 cognitive interviews with patients from the Outpatient Clinic at Vejle Hospital.Descriptive statistics will be used to analyse both continuous and categorical data, with sensitivity analyses conducted as well. Data management will be handled in Research Electronic Data Capture, and statistical analyses will be performed using Stata V.18.0.Ethics and disseminationThe study is registered with the Danish Data Protection Agency (24/5229) and Open Patient Data Explorative Network (OP_2094) and follows the Declaration of Helsinki. Results will be published in peer-reviewed journals, presented at national and international conferences and shared through patient associations.

IntroductionCannabis-based medicine may alleviate breathlessness. This study will investigate whether dronabinol, a synthetic form of Δ9-tetrahydrocannabinol (Δ9-THC), reduces breathlessness in patients with severe and very severe chronic obstructive pulmonary disease (sCOPD) compared to placebo.MethodsThis single-centre, randomised, double-blinded, placebo-controlled, crossover trial will enrol 30 patients with sCOPD and persistent breathlessness despite optimal treatment. Patients will be recruited from a pulmonary outpatient clinic in Denmark over 24 months. Eligible patients (aged ≥18 years) will receive either dronabinol or placebo for 4 weeks, followed by a 2-week washout, before crossing over to the other treatment for 4 weeks. Exclusion criteria include ongoing infection, substance abuse and significant comorbidities. Primary outcome is breathing discomfort or unpleasantness measured using the 0–10 Numerical Rating Scale. Secondary outcomes include lung function (forced expiratory volume in one second), hair cortisol concentrations, functional tests, plasma THC blood concentrations and questionnaires assessing breathlessness, activity, quality of life, anxiety and depression. Continuous monitoring of vital signs, activity and sleep will be performed using a Garmin Venu 3 smartwatch. Data will be entered into electronic case report forms and monitored by the Good Clinical Practice (GCP) unit in Odense.DiscussionThis will be the largest randomised, double-blinded, crossover trial to investigate dronabinol in patients with COPD and will provide new knowledge on the efficacy and safety.Ethics and disseminationWritten informed consents will be obtained from study patients. The study has been approved by the Danish Medicines Agency (case number: 2023010659) and the medical research ethics committees (case number: 2301456). It is registered in the European Union Clinical Trials Registry (2024-513593-22-00) and ClinicalTrials.gov (NCT06473701). The trial follows the Declaration of Helsinki II and International Council for Harmonisation-GCP guidelines. Findings will be disseminated in peer-reviewed publications.Trial registration numberThe European Union Clinical Trials Registry (2024-513593-22-00) and ClinicalTrials.gov (NCT06473701).

Respiratory self-care places considerable demands on patients with chronic airways disease (AD), as they must obtain, understand and apply information required to follow their complex treatment plans. If clinical and lifestyle information overwhelms patients’ HL capacities, it reduces their ability to self-manage. This review outlines important societal, individual, and healthcare system factors that influence disease management and outcomes among patients with asthma and chronic obstructive pulmonary disease (COPD)—the two most common ADs. For this review, we undertook a comprehensive literature search, conducted reference list searches from prior HL-related publications, and added insights from international researchers and scientists with an interest in HL. We identified methodological limitations in currently available HL measurement tools in respiratory care. We also summarized the issues contributing to low HL and system-level cultural incompetency that continue to be under-recognized in AD management and contribute to suboptimal patient outcomes. Given that impaired HL is not commonly recognized as an important factor in AD care, we propose a three-level patient-centered model (strategies) designed to integrate HL considerations, with the goal of enabling health systems to enhance service delivery to meet the needs of all AD patients.