Aberrant cellular communities underlying disease heterogeneity in chronic obstructive pulmonary disease.

Towards better management of COPD

SummaryThe problem of timely diagnosis of chronic obstructive pulmonary disease (COPD)remains relevant. The priority of timely diagnosis is to reduce mortality and morbidity.COPD is often detected very late. Only 5 years before diagnosis, the possibility ofCOPD diagnosis was missed in 85% of cases. Global late diagnosis is due to lack oftypical clinical symptoms and expectant medical tactics. Implementation of the conceptof early COPD can help to solve the problem. Early COPD is defined as a disease withminimal symptoms or no symptoms at all, which is combined with a slight restriction ofair flow. Most commonly, the development of COPD is associated with tobaccosmoking. Caused by other environmental factors, the decline in lung function from earlyadulthood forms a classic COPD. The combined influence of genetic and environmentalrisk factors leads to a decrease in lung function from birth. Such a ventilatory defectincreases genetic susceptibility, and COPD can begin during pregnancy, continue intoinfancy and early childhood, in adults, and with aging. The clinical diagnosis of earlyCOPD involves a comprehensive assessment of respiratory symptoms, environmentaland genetic risk factors for the prenatal period, childbirth, childhood and adolescence,premorbid factors as well as concomitant diseases. The criteria for early COPD includeage ≥40 years, postbroncholytic expiratory volume for the first second/forced lungcapacity <0.7, and forced expiratory volume for the first second ≥50% of the predictedvalue. High-resolution computer imaging can detect parenchymal changes andthickening of the bronchial wall before loss of lung function. The earlier diagnosis ofCOPD in the preclinical period is also ensured by the use of biomarkers. Known geneticrisk factors are mutations of the α1-antitrypsin gene, low levels of which are consideredbiomarkers of early basal emphysema and genetic COPD. Genetic risk factors that areunrelated to gene mutations relate to the heterogeneity of the primary structure ofdeoxyribonucleic acid. Single-nucleotide allelic polymorphisms of genes encoding majorpathological mechanisms are biomarkers of genetically associated COPD. Genetic riskfactor for COPD according to computed tomography is variations of the bronchial tree.Such inherited changes in the distal lung structure also a biomarker of geneticallyassociated COPD. The practical side of the diagnosis of early COPD and itsoptimization will require the development of comprehensive measures to maximize thestructure and function of the lungs in the early period of life, and now they shouldconcern measures to modify the disease in adults in the preclinical period.

Early chronic obstructive pulmonary disease (COPD) is emerging in importance for the clinical and research settings. This review will highlight a proposed definition of early COPD, examine early and midlife factors that lead to development of early COPD and review the literature pertaining to the treatment of mild COPD to gain insight into potential therapeutic approaches for early disease. Early COPD can be defined as disease occurring in patients younger than 50 years in age with a 10-pack-year or more smoking history and abnormal spirometry, imaging or lung function decline. Childhood exposures (maternal smoking and recurrent respiratory infections), childhood and adult asthma, and smoking affect middle-age lung function. Multiple studies of long-acting muscarinic antagonists (LAMAs) in mild COPD have shown improvements in lung function and symptoms scores. Smoking cessation also has a beneficial effect on longitudinal lung function. Early COPD is an important manifestation of COPD, with a newly proposed definition and associated risk factors identified. Inferring from studies on mild COPD cohorts, LAMAs and smoking cessation may have a positive effect on longitudinal lung function and symptomatic improvement.

Maintenance pharmacotherapy of mild and moderate COPD: What is the Evidence?

Management of chronic obstructive pulmonary disease: Moving beyond the asthma algorithm

Objective: This study explored the correlation between a Th1/Th2 cytokines imbalance and 25-hydroxy-vitamin D (vit D) level in early chronic obstructive pulmonary disease (COPD), provided experimental rationales for the role of vit D in the prevention and control of COPD, and elucidated the potential anti-inflammatory mechanism involved.Methods: This study was based on the results of the “Screening and Early Diagnosis of COPD” public health project conducted through Shenzhen Municipal Qianhai Shekou Free Trade Zone Hospital. Patients with early COPD were selected as study participants. A prospective, randomized, and controlled method was employed for assigning eligible participants into three groups, i.e., a COPD lung function (LF) I, COPD LF II, and a healthy group, respectively (n = 40 each). The serum content of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin 4 (IL-4), and IL-6 were measured by enzyme-linked immunosorbent assay, and the ratio of IFN-γ/IL-4 treated as a marker for Th1/Th2. The serum concentration of 25-hydroxyl-vit D (25 [OH]D) was quantified by a chemiluminescence assay. Statistical processing was performed, and the correlations between changes in the above parameters with vit D level and LF parameters were examined.Results: There were differences in FEV1pred%, FEV1/FVC, IFN-γ, IL-4, IL-6 and IFN-γ/IL-4 between the healthy group, the COPD LF I group and the COPD LF II group (p < 0.05). In early COPD, Th1/Th2 cytokines was positively correlated with forced expiratory volume/expected value (FEV1pred%) (r = 0.485, p < 0.001) and forced expiratory volume/forced vital capacity (FEV1/FVC) (r = 0.273, p = 0.018); Th1/Th2 cytokines levels positively correlated with vit D level (r = 0.27, p = 0.02), and 25(OH)D level positively correlated with FEV1pred% (r = 0.695, p < 0.001).Conclusion: Vitamin D deficiency was ubiquitous in patients with early COPD. It was positively correlated with the FEV1pred% and FEV1/FVC LF parameters. Accordingly, this study provides experimental rationales for the role of vit D in the prevention and control of COPD and the potential anti-inflammatory mechanisms involved.

Prevention and treatment of chronic respiratory diseases in China

Background: Early chronic obstructive pulmonary disease (COPD) diagnosis may lead to improved disease management and reduced costs. Objective: To assess the clinical and economic impact of early vs late stage COPD diagnosis. Methods: Medical records data were collected from COPD patients in Swedish primary care centers and then linked to primary and secondary care national registries for prescriptions, deaths, hospital care and social characteristics data. Five years of data prior to patients9 first COPD diagnosis were examined for early COPD signs i.e. pneumonia, respiratory diseases, use of oral corticosteroids, prescriptions for respiratory symptoms and spirometry measures. Patients were dichotomized as receiving either an early (ED; 0–2 early signs) or late (LD; ≥3 early signs) COPD diagnosis. A sensitivity analysis was conducted excluding patients with a comorbid asthma diagnosis pre-first COPD diagnosis. Results: 9,160 (72.2%) patients had a LD (mean age=69.4 yrs) and 3,537 (27.8%) had ED (mean age=68.8 yrs). LD was associated with higher prevalence of asthma (21.5% vs 3.5%, p 2/year) exacerbations (12.5% vs 5.0%, p Conclusion: Late COPD diagnosis is associated with increased COPD disease burden, comorbidities and costs.

Chronic obstructive pulmonary disease (COPD) is usually a progressive condition. Undiagnosed early-stage disease, particularly in symptomatic patients, is likely to become more severe with time. Hence, prevention or reduction in disease progression is highly relevant. We evaluated the published data and discussed the potential impact of early intervention on the course of COPD. We performed PubMed searches of studies in early or mild COPD, focusing on those relating to lung function decline. Smoking cessation reduced lung function decline at all stages of COPD, and the earlier the intervention, the greater the impact on lung function. Accumulating data from placebo-controlled trials suggested that long-acting bronchodilators can slow the decline in lung function, as well as reduce exacerbation and mortality rates and improve health-related quality of life (HRQoL) in patients with mild-to-moderate COPD. Inhaled corticosteroids (ICS) do not impact lung function in early COPD, and further research is needed on the role of long-acting β2-agonist-ICS combination therapy in these patients. Initiating treatment early in the course of COPD is likely to slow disease progression and improve HRQoL. Current data support maintenance treatment with a long-acting bronchodilator in this patient group. However, many questions remain unanswered regarding the optimal treatment of mild COPD, and further research is required to develop evidence-based recommendations in this field.

To examine the coping strategies of family carers of people with early and advanced chronic obstructive pulmonary disease and how those relate to their subjective health. Caring for a family member with chronic obstructive pulmonary disease can be a stressful experience. Understanding how carers cope with this is critical for improving outcomes. However, this topic has received little attention in the literature, particularly considering the care-giving experience with early chronic obstructive pulmonary disease. A cross-sectional study with a convenience sample of family carers of people with chronic obstructive pulmonary disease. A structured questionnaire was used to collect data on socio-demographics and care-giving characteristics. Self-rated physical and mental health was measured by two items from the International Classification of Functioning, Disability and Health checklist. Coping strategies were assessed with the Carers' Assessment of Managing Index. Descriptive and inferential analyses were performed. A total of 158 family carers participated: 109 caring for people with early and 49 with advanced chronic obstructive pulmonary disease. The two groups differed significantly on self-rated mental health and on problem-solving, emotional-cognitive and managing stress coping type. Significant correlations between self-rated physical health and problem-solving coping and between self-rated mental health and emotion-cognitive and managing stress coping were found for carers of patients with advanced chronic obstructive pulmonary disease. This study provides a unique insight into family carer coping strategies at different stages of chronic obstructive pulmonary disease. Carers of people with early and advanced chronic obstructive pulmonary disease cope differently with their caring demands. Nevertheless, problem-focused coping strategies were perceived as the most helpful by both groups. The findings are relevant to informing early supportive interventions aiming to prevent burden and promote healthy adjustment to care-giving demands within the specific context of chronic obstructive pulmonary disease.

COPD—more than just tobacco smoke

Chronic obstructive pulmonary disease (COPD) is a disease with high incidence rate and mortality rates worldwide. It is the third leading cause of death in the world. Nevertheless, little progress has been made in treating and preventing the disease. Under these circumstances, the concept of “early COPD” was proposed. Although this concept is not new, most health-care workers do not fully understand early COPD and tend to confuse it with mild COPD. In this review, we mainly discuss the definition of early COPD and the developmental trajectory of lung function. Although patients with early COPD have no symptoms, their lung function is already lower than that of normal people. A relatively complete definition is needed to identify this group of people. Reduced lung function is the diagnostic criterion for COPD, but lung development is a long-term dynamic process. In addition to smoking and air pollution, we should pay more attention to prenatal and childhood risk factors, for example, parents smoking, birth weight, preterm birth, mode of delivery, childhood respiratory infections and childhood asthma. Health-care workers need to be fully aware of early COPD, to reduce the morbidity of COPD and take effective measures to prevent these risk factors.

Some patients suffer from clinical symptoms of chronic obstructive pulmonary disease (COPD) but their pulmonary function tests are in the normal range (at risk group). The objective of this study was to discover a practical test to distinguish these patients from non-COPD subjects. A total of 77 subjects including 40 COPD patients, 37 subjects at risk for developing COPD, and 32 control subjects were entered in this study. The accuracy of maximal-mid expiratory flow (MMEF)/forced vital capacity (FVC) for the diagnosis of COPD in at risk patients and its capability to differentiate from early COPD and normal patients were evaluated. Body plethysmography was used for measurement of lung volume as the Global Initiative for Obstructive Lung Disease standard. MMEF/FVC in the at risk group of COPD (0.73±0.19) was significantly lower than the normal control group (0.9±0.24, respectively), and also, it was significantly higher than the COPD group (0.31±0.17). There was significant correlation between the MMEF/FVC and amount of smoking measured by pack year (r2=0.112, p=0.005) and stages of COPD (Spearman's ρ=0.82, p=0.0001). Early stage COPD (smoker subjects without spirometry derangement) can be diagnosed by MMEF/FVC. Using this tool we may be able to detect this highly preventable disease at an earlier stage.

Background: Patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed and potentially unknown until the more advanced stages of the disease. The rate of FEV1 decline was greater in patients with less severe disease than those with more severe disease. We aim to investigate the cost-effectiveness of inhaled treatment in early COPD. Methods: We reviewed the database of Korean adults recording less than 0.7 of FEV1/FVC from the Korean National Health and Nutritional Examination Survey (KNHANES) and Korean National Health Insurance (NHI) from 2007 to 2009. The early COPD was determined with more than 50% of FEV1. Results: 0f 1,919 patients who identified with early COPD in KNANES, 120 patients were confirmed that they visited hospital within the next year after diagnosis in NHI database. 58 (48%) patients were on inhaler for COPD. The others took only oral medications. In patients using inhaler regularly, medical costs of outpatient clinic were significantly higher(P=0.012). However, totally medical costs including admission and emergency room were not different whether using inhaler or not. Multiple linear regression adjusting with age, sex, using inhaler, FEV1, income showed that only smoking status was significant factors affecting the number of medical utilizations(s=4.26, P=0.008) and cost(s=658352, P=0.022). Conclusions: In early COPD patient, using inhaler increase medical cost of only outpatient clinic. Using inhaler in early COPD patients did not increase total medical cost because they decrease admission and emergency room visit. The uncontrolled aggravating factors such as smoking increased directly medical costs in early COPD.

Chronic obstructive pulmonary disease (COPD) is projected to become the third leading cause of death globally by 2030, accounting for 71.9% of chronic respiratory diseases cases in 2019. Early COPD (ECOPD) diagnosis heavily relies on clinically monitoring of lung functions, with a strong influence from smoking exposures, which may not align well with disease progression. As such, the GOLD 2022–2024 guidelines emphasize the discovery of biological markers over clinical symptoms for early detection. This study explores the biological characteristics of ECOPD in a cohort of 176 adults from China Pulmonary Health Study, consisting 88 healthy controls (HC) and 88 clinically diagnosed ECOPD, matched for age, gender and smoking history. While lung function tests revealed differences between HC and ECOPD, no significant distinctions were observed in routine blood tests. Proteomics analysis identified 377 plasma proteins common to both groups, with low-intensity proteins driving group-specific differences. Univariable logistic regression and gene set enrichment analysis identified 248 proteins associated with ECOPD, particularly those involved in inflammation process. Validation in an independent cohort confirmed the association of 15 proteins with ECOPD. Metabolomics analysis of the plasma identified 1788 metabolites, 137 of which were found linked to ECOPD. Machine learning models indicated that a multi-omics approach provided the best predication of lung function (R2 = 0.74), while proteomics alone effectively diagnosed ECOPD (AUC = 0.949). Similarity network fusion and clustering revealed two ECOPD subgroups: one by markers of inflammatory-immune response, and the other by the presence of those related to hemostasis or the vascular smooth muscle function. These findings underscore the potential of multi-omics integration in distinguishing ECOPD subgroups and predicting disease risk.