Early Chronic Obstructive Pulmonary Disease Research Articles

Multi-modal transcriptomic analysis reveals metabolic dysregulation and immune responses in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD), a progressive inflammatory condition of the airways, emerges from the complex interplay between genetic predisposition and environmental factors. Notably, its incidence is on the rise, particularly among the elderly demographic. Current research increasingly highlights cellular senescence as a key driver in chronic lung pathologies. Despite this, the detailed mechanisms linking COPD with senescent genomic alterations remain elusive. To address this gap, there is a pressing need for comprehensive bioinformatics methodologies that can elucidate the molecular intricacies of this link. This approach is crucial for advancing our understanding of COPD and its association with cellular aging processes. Utilizing a spectrum of advanced bioinformatics techniques, this research delved into the potential mechanisms linking COPD with aging-related genes, identifying four key genes (EP300, MTOR, NFE2L1, TXN) through machine learning and weighted gene co-expression network analysis (WGCNA) analyses. Subsequently, a precise diagnostic model leveraging an artificial neural network was developed. The study further employed single-cell analysis and molecular docking to investigate senescence-related cell types in COPD tissues, particularly focusing on the interactions between COPD and NFE2L1, thereby enhancing the understanding of COPD's molecular underpinnings. Leveraging artificial neural networks, we developed a robust classification model centered on four genes—EP300, MTOR, NFE2L1, TXN—exhibiting significant predictive capability for COPD and offering novel avenues for its early diagnosis. Furthermore, employing various single-cell analysis techniques, the study intricately unraveled the characteristics of senescence-related cell types in COPD tissues, enriching our understanding of the disease's cellular landscape. This research anticipates offering novel biomarkers and therapeutic targets for early COPD intervention, potentially alleviating the disease's impact on individuals and healthcare systems, and contributing to a reduction in global COPD-related mortality. These findings carry significant clinical and public health ramifications, bolstering the foundation for future research and clinical strategies in managing and understanding COPD.

TGFβ1, SMAD and β-catenin in pulmonary arteries of smokers, patients with small airway disease and COPD: potential drivers of EndMT.

We previously reported pulmonary arterial remodelling and active endothelial-to-mesenchymal transition (EndMT) in smokers and patients with early chronic obstructive pulmonary disease (COPD). In the present study, we aimed to evaluate the role of different drivers of EndMT. Immunohistochemical staining for EndMT drivers, TGF-β1, pSMAD-2/3, SMAD-7, and β-catenin, was performed on lung resections from 46 subjects. Twelve were non-smoker-controls (NC), six normal lung function smokers (NLFS), nine patients with small-airway diseases (SAD), nine mild-moderate COPD-current smokers (COPD-CS) and ten COPD-ex-smokers (COPD-ES). Histopathological measurements were done using Image ProPlus softwarev7.0. We observed lower levels of total TGF-β1 (P<0.05) in all smoking groups than in the non-smoking control (NC). Across arterial sizes, smoking groups exhibited significantly higher (P<0.05) total and individual layer pSMAD-2/3 and SMAD-7 than in the NC group. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared with NC. Total β-catenin expression was significantly higher in smoking groups across arterial sizes (P<0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased total β-catenin was positively correlated with total S100A4 in small and medium arteries (r = 0.35, 0.50; P=0.02, 0.01, respectively), with Vimentin in medium arteries (r = 0.42, P=0.07), and with arterial thickness of medium and large arteries (r = 0.34, 0.41, P=0.02, 0.01, respectively). This is the first study uncovering active endothelial SMAD pathway independent of TGF-β1 in smokers, SAD, and COPD patients. Increased expression of β-catenin indicates its potential interaction with SMAD pathway, warranting further research to identify the deviation of this classical pathway.

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study.

The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. Accord-ingly, with National Heart, Lung and Blood Institute support, we initiated the SPIROMICS Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups 0-2 or with Preserved Ratio Impaired Spirometry (PRISm); and an additional n=40 never-smoker controls. Participants undergo baseline and three-year follow-up visits, each including high-resolution computed tomography; respiratory oscillometry and spirometry (pre- and post-bronchodilator administration), exhaled breath condensate (baseline only); and extensive biospecimen collection, including sputum induction. Symptoms, interim healthcare utilization, and exacerbations are captured every six months via follow-up phone calls. An embedded bronchoscopy sub-study involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

A Qualitative Study of Aboriginal Peoples' Health Care Experiences With Chronic Obstructive Pulmonary Disease.

Aboriginal Australians experience a high prevalence of chronic obstructive pulmonary disease (COPD), with high rates of potentially preventable hospitalisations. However, little is known about Aboriginal peoples' experiences of living with COPD and how they navigate health care systems. This study used thematic analysis and Aboriginal methodology to explore Aboriginal peoples' lived experiences of COPD, their health care journey from receiving a diagnosis of COPD to the clinical management, and the impact of COPD on their daily lives. We conducted in-depth semi-structured interviews over a 6-month period with 18 Aboriginal adults diagnosed with COPD from four Aboriginal Community Controlled Health Services (ACCHS) in New South Wales, Australia. Reflexive thematic analysis was employed to ensure rigour. The findings revealed deeply personal and reflective stories shaped by historical, social, and cultural realities of Aboriginal peoples living with COPD. Four themes were identified characterising their experiences. Based on the findings, the following guidance is provided on future COPD care for Aboriginal peoples: Better alignment of existing COPD management with Aboriginal peoples' cultural contexts and perspectives to improve access to culturally safe care; Increased funding for ACCHS to enhance COPD management, such as early detection through case finding and access to ACCHS-led pulmonary rehabilitation; Engaging family members in COPD management and providing culturally centred COPD education that facilitates discussions and builds health literacy and self-management skills; Implementing health promotion initiatives to increase awareness and counteract fear and shame to improve early COPD detection.

Causal inference analysis of the radiologic progression in the chronic obstructive pulmonary disease

There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber’s M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber’s M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China

BackgroundThere are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical...

Clinical Characteristics and 2-Year Outcomes of Chronic Obstructive Pulmonary Disease Patients With High Blood Eosinophil Counts: A Population-based Prospective Cohort Study in China

BackgroundHigh blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. MethodsWe obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/μL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. ResultsOf the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09–1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. ConclusionsCOPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

Participant Selection from the General Japanese Population for Pulmonary Function Tests Using a Questionnaire on Symptoms and Smoking Habits during Annual Health Checkups: The Yamagata-Takahata Study.

Objective Pulmonary function tests are essential for diagnosing respiratory diseases, such as chronic obstructive pulmonary disease (COPD), but are typically not performed in Japan during annual health checkups, which hinders the early diagnosis of respiratory diseases. Methods Individuals who agreed to participate in the Yamagata-Takahata study during medical checkups in Takahata (Yamagata Prefecture, Japan) in 2011 were examined. We interviewed 669 participants (49.0% men; mean age, 67.7 years old) regarding their respiratory symptoms and smoking habits and performed pulmonary function tests during the study. Results Based on pulmonary function test results, 141 participants had pulmonary dysfunction, and 115 had obstructive pulmonary dysfunction. The risk of respiratory dysfunction, particularly obstructive respiratory dysfunction, was examined by referring to a questionnaire tool for an early COPD diagnosis. The associations between age, the smoking history, respiratory symptoms, and obstructive respiratory dysfunction were evaluated. Obstructive respiratory dysfunction was found in 17.6% of participants ≥50 years old and 19.5% ≥60 years old, 30.3% had a smoking history, and 32.8% had respiratory symptoms. Furthermore, the participants with multiple factors had a higher probability of obstructive respiratory dysfunction. Conclusion Subjects with obstructive pulmonary dysfunction are expected to be efficiently identified by extracting individuals by age and smoking habit and through a respiratory symptom questionnaire, although pulmonary function tests cannot be performed for all individuals during health checkups.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study

BackgroundThe clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR.MethodsParticipants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ − 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ − 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model.ResultsThis study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up.ConclusionsThe participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR.Trial registrationChinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Early smoking lead to worse prognosis of COPD patients: a real world study

BackgroundSmoking remains a major risk factor for the development and progression of chronic obstructive pulmonary disease (COPD). Due to the adolescent smoking associated with worse health state, the age, at which an individual started smoking, might play a key role in shaping the trajectory of COPD development and the severity.MethodsWe conducted an observational study from September 2016 through January 2023 of eligible patients hospitalized with COPD. Patients who started smoking during the alveolar development stage (ADS, smoking initiation ≤ 24 years old) were defined as early smoking patients, and patients who started smoking after ADS (smoking initiation > 24 years old) were defined as late smoking patients. We collected demographic and clinical data characterizing the patients and documented their condition from hospital discharge to follow-up. The primary endpoints were short-term (within one year), 3-year, and long-term (beyond 3 years) all-cause mortality after discharge.ResultsAmong 697 COPD patients, early smoking patients had a lower smoking cessation rate (P < 0.001) and a higher smoking index (P < 0.001) than late smoking patients. Although adjusted smoking index, early smoking patients still had poorer lung function (P = 0.023), thicker left ventricular diameters (P = 0.003), higher frequency of triple therapy use during stable stage (P = 0.049), and more acute exacerbations in the past year before enrollment (P < 0.05). Survival analysis showed that they had a higher risk of death after discharge within three years (P = 0.004) and beyond three years (P < 0.001). Furthermore, even in early smoking COPD patients who quit smoking after adjusting the smoking index had poorer lung function (P < 0.05) and thicker left ventricular diameters (P = 0.003), and survival analysis also showed that they had a higher long-term mortality rate (P = 0.010) and shorter survival time (P = 0.0128).ConclusionEarly smoking COPD patients exhibited multiple adverse clinical outcomes, including heavy cigarette addiction, compromised pulmonary function, augmented left ventricular diameter, and elevated mortality risk. Additional, smoking cessation could not bring enough improvement of health state in early smoking COPD patients as late smoking COPD patients. Consequently, early intervention and specialized cessation approaches for younger smokers are of paramount importance in this context.

A novel method in COPD diagnosing using respiratory signal generation based on CycleGAN and machine learning

Objective The main goal of this research is to use distinctive features in respiratory sounds for diagnosing Chronic Obstructive Pulmonary Disease (COPD). This study develops a classification method by utilizing inverse transforms to effectively identify COPD based on unique respiratory features while comparing the classification performance of various optimal algorithms. Method Respiratory sounds are divided into individual breathing cycles. In the data standardization and augmentation phase, the CycleGAN model enhances data diversity. Comprehensive analyses for these segments are then implemented using various Wavelet families and different spectral transformations representing characteristic signals. Advanced convolutional neural networks, including VGG16, ResNet50, and InceptionV3, are used for the classification task. Results The results of this study demonstrate the effectiveness of the mentioned method. Notably, the best-performing method utilizes Wavelet Bior1.3 after standardization in combination with InceptionV3, achieving a remarkable 99.75% F1-score, the gold standard for classification accuracy. Conclusion Inverse transformation techniques combined with deep learning models show significant accuracy in detecting COPD disease. These findings suggest the feasibility of early COPD diagnosis through AI-powered characterization of acoustic features. Motivation and Significance The motivation behind this research stems from the urgent need for early and accurate diagnosis of Chronic Obstructive Pulmonary Disease (COPD). COPD is a respiratory disease that poses many difficulties when detected late, potentially causing severe harm to the patient’s quality of life and increasing the healthcare burden. Timely identification and intervention are crucial to reduce the progression of the disease and improve patient outcomes.

Haemodynamic compensations for exercise tissue oxygenation in early stages of COPD: an integrated cardiorespiratory assessment study

BackgroundCardiovascular comorbidities are increasingly being recognised in early stages of chronic obstructive pulmonary disease (COPD) yet complete cardiorespiratory functional assessments of individuals with mild COPD or presenting with COPD risk...

ОНОВЛЕНИЙ ПОГЛЯД НА ЛІКУВАННЯ ХОЗЛ: ЗАПОБІГАННЯ ПЕРЕДЧАСНОЇ СМЕРТІ ЧЕРЕЗ ПОПЕРЕДЖЕННЯ ЗАГОСТРЕНЬ ЗАВДЯКИ РАННЬОМУ ОПТИМІЗОВАНОМУ ЛІКУВАННЮ

Chronic obstructive pulmonary disease (COPD) causes significant burden for all mankind: according to WHO data (2023) about 384 million people suffer from this disease worldwide. COPD is a third leading cause of death. The cost of COPD treatment reaches 100 billion US dollars per year. This review focuses on key changes of 2023-2024 COPD guidelines. Particularly, GOLD guidelines give new definitions of COPD and its exacerbation considering the grade of severity; initial treatment is prescribed based on ABCD assessment has been changed for ABE, based on the number of exacerbations in previous year. New etiotypes, like PRISm and preCOPD, etc have been introduced. The information on chronic bronchitis as an essential from clinician’s perspective component of COPD have been reflected in GOLD 2024 guidelines. Rome classification of COPD exacerbation has been also presented in updated GOLD document. Four special variants of COPD, requiring attention, have been characterized: early COPD, mild COPD, COPD in younger persons and pre-COPD. Despite a significant advance in respiratory medicine COPD diagnosis remains challenging and sometimes inadequate even today, causing the difficulties with therapy (wrong medications or no treatment at all). In contrast, timely and adequate COPD diagnosis may improve public health. Key words: chronic obstructive pulmonary disease (COPD), clinical symptoms, dyspnea, cough, exacerbations, diagnosis, treatment.

Key role of activated platelets in the enhanced adhesion of circulating leucocyte-platelet aggregates to the dysfunctional endothelium in early-stage COPD.

Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Our data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.

International research progress of risk factors, diagnosis and management in early chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) has a high global morbidity and mortality and a severe disease burden, yet progress in treatment and prevention has been slow in recent decades. Early COPD has few symptoms and is severely underdiagnosed and undertreated; it is crucial to search for effective clues of early COPD and provide management interventions. By reviewing the definition, risk factors, diagnosis and management interventions, this study explores the disease evolution of early-stage COPD, which can help clinical practice to develop more effective preventive and therapeutic strategies for stopping or slowing down the natural progression of the disease, improving the long-term prognosis, and reducing the disease burden.

Screening and early diagnosis of chronic obstructive pulmonary disease: a population study

Background and objectiveAlthough chronic obstructive pulmonary disease (COPD) is a common disease leading to further morbidity and significant mortality, there is still limited data on screening for COPD. The purpose of this study was to establish an early chronic obstructive pulmonary disease (COPD) screening system for the community and hospitals in Nanshan District in Shenzhen City, to improve the rate of early diagnosis and treatment of patients with COPD.MethodsWe identified individuals at high risk of COPD using a questionnaire survey and analyzed the relevant influencing factors in the early stages of COPD in high-risk groups.ResultsWe collected a total of 5,000 COPD screening questionnaires, and a total of 449 patients were diagnosed with COPD by pulmonary function examination. The prevalence of COPD in people aged 20 and above in Nanshan District of Shenzhen City was estimated to be 8.98%, with a base of 5000. The severity classification as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria was as follows: GOLD I accounted for 34.74%; GOLD II accounted for 37.64%; GOLD III accounted for 16.04%; and GOLD IV accounted for 11.58%. Common features of early COPD that we identified were: (1) patients were mainly males, accounting for 68.0%; (2) COPD was common among people aged 50–59 years, comprising 31%; (3) 96.0% of patients often had severe respiratory symptoms and had frequent coughs when they did not have a cold; (4) 57.2% of patients experienced shortness of breath when walking quickly on level ground or climbing gentle slopes; (5) 72.6% of patients had a family history of bronchial asthma and COPD. Multivariate ordinal multi-classification logistic regression showed that gender, age, shortness of breath, and the use of firewood, grass, and coal stoves were all influencing factors in pulmonary function grading.ConclusionA screening questionnaire combined with a pulmonary function test should be adopted as a COPD screening strategy to be implemented at the primary level as a public health priority in China to reduce the incidence, disability, and mortality from COPD.

Prevalence and timing of chronic obstructive pulmonary disease (COPD) diagnosis among patients newly diagnosed with lung cancer in the US.

118 Background: COPD is one of the most common comorbidities among patients with lung cancer, and an important determinant of their survival. While COPD is frequently under diagnosed in the general population, less is known about the occurrence of COPD underdiagnosis in patients with lung cancer. Objectives: 1) To estimate prevalence and under diagnosis of COPD among patients newly diagnosed with lung cancer. 2) To quantify the association between timing of COPD diagnosis and stage of lung cancer at diagnosis and whether this association is modified by sex, race, and socioeconomic status (SES). Methods: A secondary data analysis was conducted using the SEER-Medicare database. We included Medicare beneficiaries aged 66+years with primary invasive lung cancer diagnosed from 2008 to 2017 who were alive at the time of cancer diagnosis and had continuous Medicare coverage 12 months prior and 3 months after lung cancer diagnosis. Exposure: Comorbid COPD was determined using Medicare claims and classified as early COPD (evidence of COPD related healthcare utilization (HCU) &gt;3 months before lung cancer diagnosis) versus late COPD (evidence of COPD related HCU only during the +/- 3 months from lung cancer diagnosis). Outcome: Early (localized) versus late (regional and distant) stage of lung cancer diagnosis. Statistical analysis: We used generalized linear models to estimate adjusted absolute (prevalence difference PD) and relative (prevalence ratio PR) association. Results: In a population of 185,405 Medicare beneficiaries with lung cancer, 131,230 (71%) had evidence of COPD. Compared to lung cancer patients without COPD, those with COPD were more likely to be younger, male, White, of lower SES, have more comorbidities, higher HCU, and be diagnosed with early stage lung cancer. Patients with early COPD diagnosis constitute 66,867 (51%) of patients with COPD and lung cancer. They were more likely to be older, female, Non-Hispanic White, of lower SES, and to have more comorbidities, acute exacerbation of COPD, and more early-stage lung cancer compared to patients with late COPD diagnosis. We observed a significant positive association between early COPD diagnosis and early-stage lung cancer diagnosis (PR= 1.27, 95% CI= 1.24 to 1.30; PD= 0.062, 95% CI= 0.057 to 0.066) in models adjusted for age, sex, race, SES, HCU, comorbidities, year of cancer diagnosis, SEER region, and histology. In subgroup analyses, this association was stronger for males, Non-Hispanic Black, American Indian Alaskan Native, and patients of lower SES. Conclusions: Approximately seven out of 10 patients with lung cancer have COPD, and late COPD diagnosis is common. Earlier COPD diagnosis is associated with diagnosis of lung cancer at earlier stages. These findings highlight the need for more structured screening of COPD among individuals at high risk for lung cancer.

Vardenafil alleviates cigarette smoke-induced chronic obstructive pulmonary disease by activating autophagy via the AMPK/mTOR signalling pathway: an in vitro and in vivo study.

Chronic obstructive pulmonary disease (COPD) has always attracted global attention with its high prevalence, incidence rate, and mortality. Exposure to cigarette smoke is one of main causes of COPD. Therefore, it is still necessary to study its pathogenesis and find new therapeutic strategies for early COPD prevention and treatment. Vardenafil, a type 5 phosphodiesterase (PDE5) inhibitor, is known to have an efficient therapy in some cardiovascular, pulmonary, and vascular diseases, which is an important mechanism for COPD. However, it still loss relevant research on whether vardenafil is effective in COPD and its mechanism. In this study, the cigarette smoke inhalation was performed to establish cigarette smoke-induced COPD model using C57BL/6 mice and 16HBE cells were treated with cigarette smoke extract (CSE). Mice were treated with vardenafil for 30 d. Then condition of lung injury was evaluated using histological analysis. The content of cytokines and the number of inflammatory cells in lung tissues or bronchoalveolar lavage fluid were measured. Additionally, western blot analysis was employed to evaluate the activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)-mediated autophagy in vitro. The results showed that vardenafil abolished CSE's effect by activating autophagy via the AMPK/mTOR signalling pathway in vitro. Vardenafil attenuated cigarette smoke-induced lung injury and inflammation response by activating autophagy via the AMPK/mTOR signalling pathway in vivo. These results provide valuable insights into the molecular mechanisms underlying vardenafil's beneficial effects in cigarette smoke-induced COPD treatment. In conclusion, vardenafil alleviates cigarette smoke-induced experimental COPD by activating autophagy via the AMPK/mTOR signalling pathway.

Clinical significance of normalized airflow obstruction in patients with chronic obstructive pulmonary disease

BackgroundThere is ongoing debate regarding the diagnostic criteria for chronic obstructive pulmonary disease (COPD); recent studies have focused on the early COPD detection and management. Here, we compared clinical features and prognosis in patients with FEV1/FVC<0.70 at baseline, according to normalized airflow obstruction status during follow-up. MethodsWe used the Korea COPD Subgroup Study (KOCOSS) cohort database, a prospective nationwide observational COPD study. Normalized obstruction (NO) was defined as FEV1/FVC ≥0.7 in the 2-year follow-up period, whereas fixed obstruction (FO) was defined as FEV1/FVC <0.7. Demographic and clinical data, 1-year exacerbation risk and difference in FEV1 decline over 2 years were compared between NO and FO groups. ResultsAmong the 670 COPD patients with post-bronchodilator FEV1/FVC <0.7 in this study, 95 (14.2%) displayed NO. Compared with the FO group, the NO group had higher FEV1, and DLCO, body mass index, as well as lower Saint George Respiratory Questionnaire, Beck Depression Index, and Beck Anxiety Index. Blood eosinophil count, IgE level, and FeNO did not significantly differ between two groups. There was no significant difference in exacerbation frequency between the two groups, but the NO group had a significant increase in FEV1 compared with the FO group during follow-up. ConclusionTransient airflow obstruction in the NO group may represent a clinical manifestation of early COPD; close monitoring is needed for such patients.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.