Lung Chronic Obstructive Pulmonary Disease Research Articles

Flavonoid intakes, COPD, adult asthma, and lung function: a cohort study in the UK Biobank

IntroductionGiven their antioxidative stress, anti-allergic, anti-inflammatory, and immune-modulating effects, flavonoids are hypothesised to play a role in preventing chronic obstructive pulmonary disease (COPD) and asthma. ObjectiveThe objective of this cohort study was to examine associations between flavonoid intake and COPD, asthma and lung function. MethodsAmong 119,466 participants of the UK Biobank, median [IQR] age of 60 [53, 65], we estimated intakes of flavonoids, flavonoid-rich foods and a flavodiet score from 24-hour diet assessments. Prospective associations with both incident COPD and asthma and cross-sectional associations with measures of lung function [%predicted forced expiratory volume in 1 second (FEV1); and FEV1/forced vital capacity (FVC)] were examined using multivariable-adjusted Cox proportional hazards and linear regression models, respectively. We investigated mediation by inflammation––represented by the INFLA score––and stratified analyses by smoking status. ResultsCompared to low intakes, moderate intakes of total flavonoids, flavonols, theaflavins + thearubigins, and flavanones, and moderate-high intakes of flavanol monomers, proanthocyanidins, anthocyanins, flavones, and the flavodiet score were associated with up to an 18% lower risk of incident COPD [e.g., [HR (95% CI) for total flavonoids: 0.83 (0.75, 0.92)] but not incident asthma. Furthermore, compared to low intakes, higher intakes of all flavonoid subclasses (except theaflavins + thearubigins), and the flavodiet score were associated with better percent predicted FEV1 baseline. Associations were most apparent in ever (current or former) smokers. Flavonoid intakes were inversely associated with the INFLA score, which appeared to mediate 11-14% of the association between intakes of proanthocyanidins and flavones and incident COPD. ConclusionsModerate to high flavonoid intakes were associated with a lower risk of COPD and better lung function, particularly among ever smokers. Promoting intakes of healthy flavonoid-rich foods, namely tea, apples and berries, may improve respiratory health and lower COPD risk, particularly in individuals with a history of smoking.

Palliative care needs and integration in severe COPD and ILD: Protocol of a mixed method study (PCIntegCOPD-ILD)

Background and Aim Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) have high symptom burden, serious health-related suffering, and mortality that necessitate palliative care (PC) integration. There is an information gap on PC needs, symptom burden, anxiety and depression in COPD and ILD, and the feasibility of PC integration from low-middle-income countries (LMICs). The PCIntegCOPD-ILD study aims to identify PC needs, symptom burden, and psychological distress in severe COPD/ ILD and assess the feasibility of PC integration within standard care. It will also explore experiences and unmet needs relating to disease and PC services for patients and informal carers. Methods and Design This mixed-methods study will assess PC needs, symptom burden, and psychological distress in patients with severe COPD (stages C, D) and ILD (stages II, III). Assessment will be done at recruitment (T0) and third (T3) month (face-to-face) and first (T1) and second (T2) month (phone call). After initial recruitment, patients will be provided PC interventions as required. At T3, patients’ and informal carers’ experiences and unmet needs of disease and PC services will be explored through semi-structured interviews. Impact and feasibility of integration of PC within standard care will also be assessed. Discussion The PCIntegCOPD-ILD study will provide robust data on PC needs, symptom burden, psychological distress and understanding of patient and caregiver perspecitves in severe COPD and ILD. An objective information on feasibility of PC integration will inform development and evaluation of similar models in the management of other progressive chronic diseases in LMICs.

Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease

BackgroundMonocytes play a crucial role in innate immune responses for host defense, however, their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6Rhi monocytes in the lungs of COPD patients. MethodsUsing flow cytometry, we assessed the abundance of pulmonary CD14+IL-6Rhi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14+ monocytes isolated from the peripheral blood of patients with COPD was also examined. CD45+CD206–CD14+IL-6Rhi and CD45+CD206–CD14+IL-6R–/lo cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate the IL-6 responsiveness of IL-6R+ monocytes. ResultsThe number of pulmonary CD14+IL-6Rhi monocytes was elevated in COPD patients compared to CNS, whereas CD14+ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14+IL-6Rhi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced changes in the expression of genes linked to chemotaxis and organism development. ConclusionIn patients with COPD, CD14+IL-6Rhi monocytes are increased in lung tissues compared to those in CNS. They exhibit a transcriptome profile different from that of CD14+IL-6R–/lo monocytes.

SCARF2 is a target for chronic obstructive pulmonary disease: Evidence from multi-omics research and cohort validation.

Age-related chronic inflammatory lung diseases impose a threat on public health, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, their etiology and potential targets have not been clarified. We performed genome-wide meta-analysis for IPF with the largest sample size (2883 cases and 741,929 controls) and leveraged the summary statistics of COPD (17,547 cases and 617,598 controls). Transcriptome-wide and proteome-wide Mendelian randomization (MR) designs, together with genetic colocalization, were implemented to find robust targets. The mediation effect was assessed using leukocyte telomere length (LTL). The single-cell transcriptome analysis was performed to link targets with cell types. Individual-level data from UK Biobank (UKB) were used to validate our findings. Sixteen genetically predicted plasma proteins were causally associated with the risk of IPF and 6 proteins were causally associated with COPD. Therein, genetically-elevated plasma level of SCARF2 protein should reduce the risk of both IPF (odds ratio, OR = 0.9974 [0.9970, 0.9978]) and COPD (OR = 0.7431 [0.6253, 0.8831]) and such effects were not mediated by LTL. Genetic colocalization further corroborated these MR results of SCARF2. The transcriptome-wide MR confirmed that higher expression level of SCARF2 was associated with a reduced risk of both. However, the single-cell RNA analysis indicated that SCARF2 expression level was only relatively lower in epithelial cells of COPD lung tissue compared to normal lung tissue. UKB data implicated an inverse association of serum SCARF2 protein with COPD (hazard ratio, HR = 1.215 [1.106, 1.335]). The SCARF2 gene should be a novel target for COP.

Binary fabrication of decellularized lung extracellular matrix hybridgels for in vitro chronic obstructive pulmonary disease modeling

Limited treatments and a lack of appropriate animal models have spurred the study of scaffolds to mimic lung disease in vitro. Decellularized human lung and its application in extracellular matrix (ECM) hydrogels has advanced the development of these lung ECM models. Controlling the biochemical and mechanical properties of decellularized ECM hydrogels continues to be of interest due to inherent discrepancies of hydrogels when compared to their source tissue. To optimize the physiologic relevance of ECM hydrogel lung models without sacrificing the native composition we engineered a binary fabrication system to produce a Hybridgel composed of an ECM hydrogel reinforced with an ECM cryogel. Further, we compared the effect of ECM-altering disease on the properties of the gels using elastin poor Chronic Obstructive Pulmonary Disease (COPD) vs non-diseased (ND) human lung source tissue. Nanoindentation confirmed the significant loss of elasticity in hydrogels compared to that of ND human lung and further demonstrated the recovery of elastic moduli in ECM cryogels and Hybridgels. These findings were supported by similar observations in diseased tissue and gels. Successful cell encapsulation, distribution, cytotoxicity, and infiltration were observed and characterized via confocal microscopy. Cells were uniformly distributed throughout the Hybridgel and capable of survival for 7 days. Cell-laden ECM hybridgels were found to have elasticity similar to that of ND human lung. Compositional investigation into diseased and ND gels indicated the conservation of disease-specific elastin to collagen ratios. In brief, we have engineered a composited ECM hybridgel for the 3D study of cell-matrix interactions of varying lung disease states that optimizes the application of decellularized lung ECM materials to more closely mimic the human lung while conserving the compositional bioactivity of the native ECM. Statement of significanceThe lack of an appropriate disease model for the study of chronic lung diseases continues to severely inhibit the advancement of treatments and preventions of these otherwise fatal illnesses due to the inability to recapture the biocomplexity of pathologic cell-ECM interactions. Engineering biomaterials that utilize decellularized lungs offers an opportunity to deconstruct, understand, and rebuild models that highlight and investigate how disease specific characteristics of the extracellular environment are involved in driving disease progression. We have advanced this space by designing a binary fabrication system for a ECM Hybridgel that retains properties from its source material required to observe native matrix interactions. This design simulates a 3D lung environment that is both mechanically elastic and compositionally relevant when derived from non-diseased tissue and pathologically diminished both mechanically and compositionally when derived from COPD tissue. Here we describe the ECM hybridgel as a model for the study of cell-ECM interactions involved in COPD.

The disruptive effects of COPD exacerbation-associated factors on epithelial repair responses.

Exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory response during exacerbations contributes to worsening of airflow limitation, but whether it also impacts epithelial repair is unclear. Therefore, we studied the effect of the soluble factor micro-environment during COPD exacerbations on epithelial repair using an exacerbation cocktail (EC), composed of four factors that are increased in COPD lungs during exacerbations (IL-1β, IL-6, IL-8, TNF-α). Mouse organoids (primary CD31-CD45-Epcam+ cells co-cultured with CCL206 fibroblasts) were used to study epithelial progenitor behavior. Mature epithelial cell responses were evaluated using mouse precision cut lung slices (PCLS). The expression of epithelial supportive factors was assessed in CCL206 fibroblasts and primary human lung fibroblasts. EC exposure increased the number and size of organoids formed, and upregulated Lamp3, Muc5ac and Muc5b expression in day 14 organoids. In PCLS, EC imparted no effect on epithelial marker expression. Pre-treatment of CCL206 fibroblasts with EC was sufficient to increase organoid formation. Additionally, the expression of Il33, Tgfa and Areg was increased in CCL206 fibroblasts from EC treated organoids, but these factors individually did not affect organoid formation or size. However, TGF-α downregulated Foxj1 expression and upregulated Aqp5 expression in day 14 organoids. EC exposure stimulates organoid formation and growth, but it alters epithelial differentiation. EC changes the epithelial progenitor support function of fibroblasts which contributes to observed effects on epithelial progenitors.

Lipid-Laden Macrophages in Pulmonary Diseases.

Pulmonary surfactants play a crucial role in managing lung lipid metabolism, and dysregulation of this process is evident in various lung diseases. Alternations in lipid metabolism lead to pulmonary surfactant damage, resulting in hyperlipidemia in response to lung injury. Lung macrophages are responsible for recycling damaged lipid droplets to maintain lipid homeostasis. The inflammatory response triggered by external stimuli such as cigarette smoke, bleomycin, and bacteria can interfere with this process, resulting in the formation of lipid-laden macrophages (LLMs), also known as foamy macrophages. Recent studies have highlighted the potential significance of LLM formation in a range of pulmonary diseases. Furthermore, growing evidence suggests that LLMs are present in patients suffering from various pulmonary conditions. In this review, we summarize the essential metabolic and signaling pathways driving the LLM formation in chronic obstructive pulmonary disease, pulmonary fibrosis, tuberculosis, and acute lung injury.

Using spirometry for screening and diagnosis of chronic respiratory diseases in primary health care: findings from a community health project in rural India

Background Chronic respiratory diseases (CRDs) such as Chronic obstructive pulmonary disease (COPD), Asthma and post-tuberculosis lung disease (PTLD) are a growing public health concern in India. Early diagnosis and management of CRDs require a good quality spirometry test, a technician to conduct spirometry and a chest physician to interpret the results. In India, these are not available at the primary care level. This study reports the feasibility of a large-scale CRD diagnosis and management program in primary care using a unique point-of-care spirometry solution, Briota PFT in a Box™. # Methods A community-based cross-sectional study was conducted among 15,602 adults in Dindori Taluka (subdivision), Nashik, Maharashtra state. This study was part of a holistic CRD diagnosis and management program SAVE™ (Spirometry Assisted Virtually Early). Make In India point of care solution Briota PFT in a Box™ was used. A House‐to‐house community-based assessment checklist (CBAC) survey, 4-parameter spirometry test, 15-parameter pre and post-bronchodilator spirometry test and a software-assisted medical examination by the medical officer at primary care were conducted. Software was used to generate CRD diagnosis and lung health score (LHS™). The diagnosis was verified by the chest physician. Confirmed diagnosed patients were provided treatment and offered a patient support program. Interviews were conducted with the patients, nurses, doctors and public health officials for understanding feasibility and documenting learning from program SAVE™. # Results Out of 15,602 adults surveyed, total 4,937 (31.6%) were identified as “CRD high risk”. 1231 participants based on medical examination, spirometry tests and software analysis were identified as CRD candidates by medical officers at primary care. 1154 participants out of 15,602 (7.4%) were confirmed diagnosed as CRD patients post independent evaluation by chest physicians. At the time of follow-up, 537 patients (75% of 712 patients enrolled in patient support program) reported improvement in symptoms and high satisfaction with the program. District health officer, Medical officers, nurses, Accredited Social Health Activist (ASHA) from the primary health care centers confirmed ease of use and feasibility of using Briota PFT in a Box™ in program SAVE™. Outcome and learning from program SAVE™ was documented and submitted to Ministry of Health and Family Welfare Government of India. # Conclusions CRD diagnosis and management in large scale settings in primary healthcare level using a point of care spirometry solution Briota PFT in a Box™ is highly feasible.

Effects of Pulmonary Rehabilitation with Occupational Therapy on Occupational Performance

Aims 1) Explore occupational challenges of individuals participating in pulmonary rehabilitation (PR), and 2) examine impacts of occupational therapy, embedded within PR, on performance of, satisfaction with, dyspnea in and experience of challenging occupations. Methods A mixed methods cohort study recruited adults from a 8-week community-based PR program which incorporated targeted occupational therapy. Participant perspectives of the occupational therapy were explored using the Canadian Occupational Performance Measure (COPM) and Modified Borg Dyspnea Scale. Results Seventeen participants with either Chronic Obstructive Pulmonary Disease, Bronchiectasis, or Interstitial Lung Disease were recruited (age 71 ± 7(SD) identifying 269 problematic occupations. Nine participants completed the program obtaining clinically and statistically significant improvements in COPM performance, satisfaction scores and Modified Borg Dyspnea Scale, maintained at 12 wk, and validated through participants reporting they ‘now do things differently’. Conclusion People with chronic respiratory conditions are occupational beings. Occupational therapy embedded within PR can influence participants’ engagement in challenging occupations.

Understanding the complexities of post-tuberculosis lung disease: Implications for global health

Post-tuberculosis lung disease (PTLD) presents a significant challenge in the management of tuberculosis patients, with far-reaching implications for global health. This editorial explores the multifaceted nature of PTLD, encompassing its pathophysiology, clinical manifestations, diagnostic complexities, and implications for public health. PTLD arises from pulmonary damage due to an active tuberculosis infection, leading to inflammation, scarring, and fibrosis within the lungs. Clinical manifestations vary widely, ranging from chronic respiratory symptoms to severe respiratory failure, often resembling chronic obstructive pulmonary disease or restrictive lung disease. The diagnosis of PTLD is hindered by its heterogeneous presentation and overlap with other respiratory conditions, necessitating a comprehensive evaluation through pulmonary function tests and radiological imaging. PTLD imposes a substantial burden on global health systems, particularly in regions with high tuberculosis prevalence, contributing to increased morbidity and mortality rates. Management strategies focus on alleviating symptoms, preserving lung function, and preventing disease progression through pharmacological interventions, pulmonary rehabilitation, and, in select cases, surgical interventions. Preventive measures include effective tuberculosis control measures, vaccination against respiratory pathogens, and addressing social determinants of health. Overall, a comprehensive understanding of PTLD is essential for improving patient outcomes and reducing disease burden, highlighting the importance of concerted efforts to raise awareness, enhance diagnostic capabilities, and develop effective management strategies for this complex condition.

A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.

Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations. We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons. Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.

Identification of Siglec-1-negative alveolar macrophages with proinflammatory phenotypes in chronic obstructive pulmonary disease.

Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. However, subpopulations of AMs participating in chronic inflammation have been poorly characterized. We previously reported that Siglec-1 expression on AMs, which is important for bacteria engulfment, was decreased in COPD. Here, we show that Siglec-1-negative AMs isolated from COPD lung tissues exhibit a proinflammatory phenotype and are associated with poor clinical outcomes in patients with COPD. Using flow cytometry, we segregated three subsets of AMs based on the expression of Siglec-1 and their side scattergram (SSC) and forward scattergram (FSC) properties: Siglec-1+SSChiFSChi, Siglec-1-SSChiFSChi, and Siglec-1-SSCloFSClo subsets. The Siglec-1-SSCloFSClo subset number was increased in COPD. RNA sequencing revealed upregulation of multiple proinflammatory signaling pathways and emphysema-associated matrix metalloproteases in the Siglec-1-SSCloFSClo subset. Gene set enrichment analysis indicated that the Siglec-1-SSCloFSClo subset adopted intermediate phenotypes between monocytes and mature alveolar macrophages. Functionally, these cells produced TNF-α, IL-6, and IL-8 at baseline, and these cytokines were significantly increased in response to viral RNA. The increase in Siglec-1-negative AMs in induced sputum is associated with future exacerbation risk and lung function decline in patients with COPD. Collectively, the novel Siglec-1-SSCloFSClo subset of AMs displays proinflammatory properties, and their emergence in COPD airways may be associated with poor clinical outcomes.NEW & NOTEWORTHY Alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD) orchestrate persistent inflammation in the airway. We find that Siglec-1-negative alveolar macrophages have a wide range of proinflammatory landscapes and a protease-expressing phenotype. Moreover, this subset is associated with the pathogenesis of COPD and responds to viral stimuli.

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

The interplay between the immune system and chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is complex and multifaceted. In COPD, chronic inflammation and oxidative stress can lead to immune dysfunction that can exacerbate lung damage, further worsening the respiratory symptoms. In NSCLC, immune cells can recognise and attack the cancer cells, which, however, can evade or suppress the immune response by various mechanisms, such as expressing immune checkpoint proteins or secreting immunosuppressive cytokines, thus creating an immunosuppressive tumour microenvironment that promotes cancer progression and metastasis. The interaction between COPD and NSCLC further complicates the immune response. In patients with both diseases, COPD can impair the immune response against cancer cells by reducing or suppressing the activity of immune cells, or altering their cytokine profile. Moreover, anti-cancer treatments can also affect the immune system and worsen COPD symptoms by causing lung inflammation and fibrosis. Immunotherapy itself can also cause immune-related adverse events that could worsen the respiratory symptoms in patients with COPD-compromised lungs. In the present review, we tried to understand the interplay between the two pathologies and how the efficacy of immunotherapy in NSCLC patients with COPD is affected in these patients.

Integrating palliative care education in pulmonary rehabilitation: a randomized controlled study protocol

BackgroundPalliative care addresses multiple unmet needs of people with chronic obstructive pulmonary disease (COPD) or interstitial lung diseases (ILD) and their family and/or friend caregivers, but it remains highly underused. Pulmonary rehabilitation (PR) may provide a key opportunity to introduce palliative care. We aim to explore the effects of palliative care education as part of PR on knowledge about this field in people with COPD or ILD and their family and/or friend caregivers.MethodsA randomized controlled study will compare PR with palliative care education (experimental) with traditional PR (control) in people with COPD or ILD and their family and/or friend caregivers. Family and/or friend caregivers will be invited to take part in education and psychosocial support sessions. In addition to the usual educational content, the experimental group will have a session on palliative care, a “Peer-to-peer session”, two “Get-apart sessions” and online sessions. The “Peer-to-peer session” and the “Get-apart sessions” will be discussions about topics suggested by participants. The “Get-apart sessions” will be dedicated to people with COPD or ILD apart from their family and/or friend caregivers and vice versa. The online sessions will be zoom meetings to discuss any health-related issues raised by participants, at a flexible time. A mixed-methods approach will be used to evaluate the outcomes. The primary outcome will be knowledge about palliative care. Secondary outcomes will include attitude towards palliative care referral, symptoms, disease impact, health-related quality of life, needs, knowledge about the disease, burden of providing care, adherence, adverse events and referral to a specialist palliative care team. Quantitative and qualitative data will be collected at baseline and end of PR. At 6-months post-PR, only patient-reported outcomes will be collected. For the primary outcome, time*group interaction will be analyzed with mixed analysis of variance.DiscussionThis study aims to demonstrate the impact of integrating palliative care into the PR education program.Trial registrationThe trial was registered in the ClinicalTrials.gov U.S. National Library of Medicine, on 1st September, 2023 (NCT06046547).

The Role of Physiotherapy in Managing Chronic Respiratory Conditions: A Comprehensive Review

Chronic respiratory conditions, including Chronic Obstructive Pulmonary Disease (COPD) and interstitial lung disease, present persistent challenges to respiratory function and holistic well-being. This paper acknowledges the complexity of these conditions and underscores the essential role of physiotherapy interventions within multidisciplinary care approaches. To provide a comprehensive understanding of the management of chronic respiratory conditions, this review explores key physiotherapy interventions such as breathing exercises, airway clearance techniques, and pulmonary rehabilitation programs. The analysis aims to illuminate how these interventions contribute to enhancing respiratory health and overall quality of life. Additionally, this paper briefly outlines its structure, focusing on the evolving landscape of physiotherapeutic strategies. By emphasizing their significance in the comprehensive care paradigm, this review guides individuals navigating the complexities of chronic respiratory diseases towards improved well-being.

Neutrophil-to-Lymphocyte Ratio and Blood Eosinophil Levels As Inflammatory Indicators in Smoker and Non-smoker Young Adult Patients With Chronic Obstructive Pulmonary Disease at a Tertiary Care Hospital.

Background Inflammatory markers are elevated in chronic obstructive pulmonary disease (COPD) and can be quantified to detect severity, prognosis, mortality risk, and response to treatment. However, the estimation costs are high. The blood neutrophil-to-lymphocyte ratio (NLR) and eosinophil levels are emerging as biomarkers in COPD, yet there is a paucity of data. Aim and objectives This study was designed to elucidate the roles of the NLRand eosinophil levels in smokers and non-smokers with stable COPD male subjects, correlating them with lung functions. Materials and methods A prospective observational clinical study was conducted from January to June 2023, after receiving approval from the Institutional Ethics Committee, on 73 COPD patients aged 30-60 years who gave voluntary informed consent. Complete blood counts and spirometry were performed. Patients with a forced expiratory volume in one second(FEV1) % predicted <70% and an FEV1/forced vital capacity (FVC) % <70% based on the pulmonary function test (MIR Spirolab) were included. They were further divided into mild (n=10), moderate (n=27), severe (n=26), and very severe (n=10) categories as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Subjects were also categorized into smoker (n=45) and non-smoker (n=28) groups. The complete blood count was analyzed using an automated analyzer (Beckman Coulter). Analysis was also carried out with an NLR of more or less than three. A P-value of less than 0.05 was considered significant. Results Smokers constituted 61.65% (n=45) of the subjects, and non-smokers 38.35% (n=28). Among smokers, 17.78% had very severe airflow obstruction. In all COPD subjects (n=73), lymphocytes, eosinophils, and lung functions were lower in the group where the NLR was greater than three. NLR in smokers (3.52±1.43) was higher than in non-smokers (3.39±0.94). In non-smokers (n=28), blood eosinophils and lymphocytes were elevated. In smokers (n=45), blood neutrophils, monocytes, and basophils were increased. Smokers showed a non-significant increase in RBC, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Neutrophils, monocytes, eosinophils, and NLR increased with disease severity. NLR negatively correlated with FEV1 (r=-0.350, p=0.034) and positively with pack-years (r=0.546, p<0.001) in smokers. NLR negatively correlated with eosinophils, FVC, FEV1/FVC, and FEV1 % predicted. In all COPD subjects (n=73), NLR negatively correlated with blood eosinophils (r=-0.184, p=0.12), BMI, and lung functions. Conclusion NLR is elevated in COPD subjects and can serve as a marker of inflammation and a predictor of the risk and severity of airflow limitation. NLR correlates both positively and negatively with pack-years and lung functions, respectively.

Feasibility and Design Factors for Home-Based Pulmonary Rehabilitation of Patients With Chronic Obstructive Pulmonary Disease and Chronic Lung Diseases Based on a People-Object-Environment Framework: Qualitative Interview Study.

The feasibility of implementing home-based pulmonary rehabilitation (PR) can be assessed from the perspectives of patients with chronic lung disease and health care professionals involved in PR. Through a qualitative inquiry using interviews and the adoption of the people-object-environment framework, this study aims to understand the influences of interpersonal, environmental, and situational factors on the perceptions and considerations of individuals involved in home-based PR for patients with chronic lung disease. One-on-one interviews were conducted with 20 patients with chronic lung disease and 20 health care professionals for investigating their attitudes and opinions based on their experiences regarding home-based PR as well as for identifying the key factors affecting the benefits and drawbacks of such therapies. This study further evaluates the feasibility of using digital tools for medical diagnosis and treatment by examining the technology usage of both parties. The 4 key issues that all participants were the most concerned about were as follows: distance to outpatient medical care, medical efficiency, internet connectivity and equipment, and physical space for diagnosis and treatment. Interviews with patients and health care professionals revealed that the use of technology and internet was perceived differently depending on age and area of residence. Most participants reported that digital tools and internet connectivity had many benefits but still could not solve all the problems; moreover, these same digital tools and network transmission could lead to problems such as information security and digital divide concerns. This study also emphasizes the significant impact of human behavior and thinking on shaping the design of health care interventions and technologies. Understanding user perspectives and experiences is crucial for developing effective solutions for unmet needs. The results of this study indicate that despite the different perspectives of patients and health care professionals, their considerations of the key issues are very similar. Therefore, the implementation of plans related to telemedicine diagnosis, treatment, or rehabilitation should take the suggestions and considerations of both parties into account as crucial factors for telehealth care design.

Genetics of chronic respiratory disease.

Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and interstitial lung diseases are frequently occurring disorders with a polygenic basis that account for a large global burden of morbidity and mortality. Recent large-scale genetic epidemiology studies have identified associations between genetic variation and individual respiratory diseases and linked specific genetic variants to quantitative traits related to lung function. These associations have improved our understanding of the genetic basis and mechanisms underlying common lung diseases. Moreover, examining the overlap between genetic associations of different respiratory conditions, along with evidence for gene-environment interactions, has yielded additional biological insights into affected molecular pathways. This genetic information could inform the assessment of respiratory disease risk and contribute to stratified treatment approaches.

Wedge resection, segmentectomy, and lobectomy: oncologic outcomes based on extent of surgical resection for ≤2 cm stage IA non-small cell lung cancer.

Long-standing controversy has existed over whether sublobar resection is an adequate oncological procedure for clinical stage IA non-small cell lung cancer (NSCLC) ≤2 cm, despite the recent randomized trial reports of Japanese Clinical Oncology Group (JCOG) 0802 and Cancer and Leukemia Group B (CALGB) 140503 demonstrating non-inferior outcomes with sublobar resection compared to lobectomy. As practice patterns shift, we sought to compare oncologic outcomes in patients with these early-stage tumors after wedge resection, segmentectomy, or lobectomy in a contemporary, real-world, cohort. A retrospective review of a prospectively maintained database from a single institution was conducted from 2011 to 2020 to identify all patients with clinically staged IA1 or IA2 NSCLC (tumors ≤2 cm with no nodal involvement). The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS), with secondary outcomes of lung cancer-specific survival (LCSS), recurrence patterns, and perioperative morbidity and mortality. A total of 480 patients were identified; 93 (19.4%) patients underwent wedge resection, 90 (18.7%) received segmentectomy, and 297 (61.9%) underwent lobectomy. Patients who underwent wedge resection had worse Eastern Cooperative Oncology Group (ECOG) performance status (23.7% ECOG 1 or 2 vs. 5.6% among segmentectomy and 5.4% among lobectomy, P<0.05). Both wedge resection and segmentectomy patients had lower preoperative mean percentage of predicted forced expiratory volume in one second (%FEV1) compared to the lobectomy group (81.8% and 82.6% vs. 89.6%, P=0.002), a higher proportion of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), and a higher Charlson Comorbidity Index. There were no statistically significant differences in 5-year OS, DFS, or LCSS between groups: 90%, 61%, 78% for wedge resections compared with 85%, 75%, 86% for segmentectomy, and 87%, 77%, 87% for lobectomy, respectively. Recurrence was observed in 17 patients who underwent wedge resection (18.3%, 8 local, 9 distant), 12 patients who received segmentectomy (13.4%, 6 local, 6 distant), and 38 patients who underwent lobectomy (12.8%, 11 local, 27 distant), which was not significantly different (P=0.36). Patients with inferior performance status or lower baseline pulmonary function are more likely to receive wedge resection for clinical stage IA NSCLC ≤2 cm in size. For these small tumors, lobectomy, segmentectomy, and wedge resection provide comparable oncologic outcomes.

Alterations in the molecular control of mitochondrial turnover in COPD lung and airway epithelial cells

Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, in this study, the abundance of key molecules controlling mitochondrial turnover were assessed in peripheral lung tissue from non-COPD patients (n = 6) and COPD patients (n = 11; GOLDII n = 4/11; GOLDIV n = 7/11) and in both undifferentiated and differentiated human primary bronchial epithelial cells (PBEC) from non-COPD patients and COPD patients (n = 4–7 patients/group). We observed significantly decreased transcript levels of key molecules controlling mitochondrial biogenesis (PPARGC1B, PPRC1, PPARD) in peripheral lung tissue from severe COPD patients. Interestingly, mRNA levels of the transcription factor TFAM (mitochondrial biogenesis) and BNIP3L (mitophagy) were increased in these patients. In general, these alterations were not recapitulated in undifferentiated and differentiated PBECs with the exception of decreased PPARGC1B expression in both PBEC models. Although these findings provide valuable insight in these pathways in bronchial epithelial cells and peripheral lung tissue of COPD patients, whether or not these alterations contribute to COPD pathogenesis, underlie changes in mitochondrial function or may represent compensatory mechanisms remains to be established.