Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a real-life setting: the NOVEL observational longiTudinal studY.

BACKGROUND: The relationships between spirometric assessment of lung function and symptoms (including exacerbations) in patients with asthma and/or chronic obstructive pulmonary disease (COPD) in a real-life setting are uncertain. OBJECTIVES: To assess the relationships between baseline post-bronchodilator (post-BD) spirometry measures of lung function and symptoms and exacerbations in patients with a physician-assigned diagnosis of asthma and/or COPD. DESIGN: The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, 3-year observational study. METHODS: Logistic regression analysis was used to evaluate relationships. Spirometry measures were assessed as percent predicted (%pred). Symptoms were assessed at baseline, and exacerbations were assessed at baseline and Year 1. RESULTS: A total of 11,181 patients in NOVELTY had spirometry data (asthma, n = 5903; COPD, n = 3881; asthma + COPD, n = 1397). A 10% lower post-BD %pred forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) - adjusted for age and sex - were significantly associated with dyspnea (modified Medical Research Council ⩾ grade 2), frequent breathlessness [St George's Respiratory Questionnaire (SGRQ)], frequent wheeze attacks (SGRQ), nocturnal awakening (Respiratory Symptoms Questionnaire; ⩾1 night/week), and frequent productive cough (SGRQ). Lower post-BD %pred FEV1 and, to a lesser extent, lower post-BD %pred FVC were significantly associated with ⩾1 physician-reported exacerbation at baseline or Year 1. This association was stronger in patients with COPD than in those with asthma. CONCLUSION: In a real-life setting, reduced lung function is consistently associated with symptoms in patients with asthma, COPD, or asthma + COPD. The relationship with exacerbations is stronger in COPD only than in asthma. TRAIL REGISTRATION: clinicaltrials.gov identifier: NCT02760329 (www.clinicaltrials.gov).

Relationships between symptoms and lung function in asthma and/or chronic obstructive pulmonary disease in a study performed in a real-life setting: the NOVELTY studyBackground: Asthma and chronic obstructive pulmonary disease (COPD) have many symptoms in common. To confirm diagnosis, doctors use spirometry, a test to measure the amount of air that can be breathed out from the lungs and how fast it can be blown out. The relationship between these measurements and symptoms in asthma and COPD is not well understood.Objectives: The aim of this research is to describe the characteristics, treatment, and impact of asthma and/or COPD in patients who are receiving their usual medical care.Methods: NOVELTY is a large study of around 12,000 patients across 19 countries. This analysis of NOVELTY looked at the relationships between two spirometry measurements and the symptoms of asthma and/or COPD experienced by patients. The spirometry measurements were: - forced expiratory volume in 1 second (FEV₁) ­ the amount of air that can be blown out of the lungs in 1 second- forced vital capacity (FVC) ­ the amount of air that can be forcibly breathed out from the lungs after taking the deepest breath possibleResults: The lower the FEV₁ and FVC, the more common the symptoms of breathlessness, wheeze attacks, night-time awakening, and coughing up of phlegm or mucus. These relationships were similar for FEV₁ and FVC. Lower FEV₁ was more strongly associated with worse symptoms in COPD than in asthma.Conclusion: These findings help to improve our understanding of the relationships between spirometry measures and symptoms in patients with asthma and/or COPD.

Acute COPD exacerbations and in-hospital treatment-related problems: An observational study.

BACKGROUND: Treatment-related problems (TRPs) interfere with the ability to attain the desired goals of treatment, adding cost to healthcare systems. Patients hospitalized with acute conditions are at particular risk to experience TRPs. Data investigating such burden in patients with acute exacerbation of COPD (AECOPD) is generally scarce with no studies ever conducted in Jordan. This study aimed to investigate and categorize TRPs among patients hospitalized with AECOPD in Jordan, and to estimate their cost savings and cost avoidance. METHODS: This was a retrospective population-based cohort study. Patients' cases of AECOPD admitted to the study site from Jan 2017 to Jul 2021 were identified from the electronic clinical database and screened for eligibility. TRPs were identified/categorized using AbuRuz tool and assessed for their severity. Cost saving was estimated by calculating all the extra costs. Cost avoidance was estimated according to Nesbit method. RESULTS: A total of 1243 (mean±SD 3.1±1.5) and 503 (mean±SD 1.3±1.2) TRPs were identified during hospitalization and at discharge respectively, of which 49.4% and 66.7% were classified as "unnecessary drug therapy". In 54.5% of the cases, systemic corticosteroid was administered for a period longer than recommended. Most of the TRPs were of moderate severity. The total direct cost saving, and cost avoidance were estimated to be 15,745.7 USD and 340,455.5 USD respectively. CONCLUSION: The prevalence and cost of TRPs among AECOPD patients is a concern requiring attention. The study results implicate integrating interventions such as embracing clinical pharmacists' role in the respiratory care units to optimize patients' management.

Phenotyping chronic respiratory diseases with airways obstruction.

Given the high prevalence of asthma-chronic obstructive pulmonary disease overlap (ACO) in Vietnam, there is an urgent need to establish a simplified strategy for categorising patients as either having asthma or chronic obstructive pulmonary disease (COPD). This classification would streamline the application of treatment recommendations outlined by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).Patients with obstructive lung function were classified as having COPD, asthma, or ACO based on GINA/GOLD guidelines. We hypothesised that ACO-like asthma (ACO-A) would present with positive skin prick tests (SPTs) or early onset of symptoms without a history of tuberculosis (TB), while those with ACO-like COPD (ACO-B) would exhibit negative SPTs and late onset of symptoms and/or a history of TB.Among 235 patients, the prevalence of asthma, ACO-A, ACO-B, and COPD was respectively 21%, 22%, 17%, and 40%. Allergic history, rhinitis, and childhood asthma were associated with ACO-A, while high cumulative smoking was correlated with ACO-B. Socio-economic and demographic parameters, medical history, clinical features, smoking habits, lung function, and para-clinical investigations significantly differed between "all asthma" (i.e., individuals with asthma combined with ACO-A) and "all COPD" (i.e., individuals with COPD combined with ACO-B).Based on SPTs, history of TB, and onset age, ACO patients may be defined as people with asthma or COPD..

HTR2B as a novel biomarker of chronic obstructive pulmonary disease with lung squamous cell carcinoma.

Chronic obstructive pulmonary disease (COPD) is often associated with lung squamous cell carcinoma (LUSC), which has the same etiology (smoking, inflammation, oxidative stress, microenvironmental changes, and genetics). Smoking, inflammation, and airway remodeling are the most important and classical mechanisms of COPD comorbidity in LUSC patients. Cancer can occur during repeated airway damage and repair (airway remodeling). Changes in the inflammatory and immune microenvironments, which can cause malignant transformation of some cells, are currently being revealed in both LUSC and COPD patients. We obtained the GSE76925 dataset from the Gene Expression Omnibus database. Screening for possible COPD biomarkers was performed using the LASSO regression model and a random forest classifier. The compositional patterns of the immune cell fraction in COPD patients were determined using CIBERSORT. HTR2B expression was analyzed using validation datasets (GSE47460, GSE106986, and GSE1650). HTR2B expression in COPD cell models was determined via real-time quantitative PCR. Epithelial-mesenchymal transition (EMT) marker expression levels were determined after knocking down or overexpressing HTR2B. HTR2B function and mechanism in LUSC were analyzed with the Kaplan‒Meier plotter database. HTR2B expression was inhibited to detect changes in LUSC cell proliferation. A total of 1082 differentially expressed genes (DEGs) were identified in the GSE76925 dataset (371 genes were significantly upregulated, and 711 genes were significantly downregulated). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the DEGs were mainly enriched in the p53 signaling and ß-alanine metabolism pathways. Gene Ontology enrichment analysis indicated that the DEGs were largely related to transcription initiation from the RNA polymerase I promoter and to the regulation of mononuclear cell proliferation. The LASSO regression model and random forest classifier results revealed that HTR2B, DPYS, FRY, and CD19 were key COPD genes. Immune cell infiltration analysis indicated that these genes were closely associated with immune cells. Analysis of the validation sets suggested that HTR2B was upregulated in COPD patients. HTR2B was significantly upregulated in COPD cell models, and its upregulation was associated with increased EMT marker expression. Compared with that in bronchial epithelial cells, HTR2B expression was upregulated in LUSC cells, and inhibiting HTR2B expression led to the inhibition of LUSC cell proliferation. In conclusions, HTR2B might be a new biomarker and therapeutic target in COPD patients with LUSC.

Predictive Value of Smoking Index Combined with NT-proBNP for Patients with Pulmonary Hypertension Due to Chronic Lung Disease: A Retrospective Study.

Purpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity. Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤50 mmHg) and non-mild (PASP >50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve. Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628). Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.

Factors Associated with Non-Adherence to Self-Management Among Patients with Chronic Obstructive Pulmonary Disease: A Survey Using the Delphi Technique and Analytic Hierarchy Process.

Background: The relevant factors and patterns of non-adherence to self-management among patients with chronic obstructive pulmonary disease (COPD) need to be elucidated to improve self-management. Purpose: This study was a survey to prioritize the relevance of factors associated with non-adherence to COPD self-management using the Delphi technique and analytic hierarchy process (AHP). Patients and Methods: A total of 15 expert panels were established to determine the priority of relevant factors in a three-round Delphi survey and an AHP. To develop the preliminary conceptual framework for non-adherence to COPD self-management, findings from a systematic literature review, a qualitative study using in-depth interviews with COPD patients, and the first round of the Delphi survey were integrated. Based on the preliminary framework, the content validity ratio (CVR) was analyzed to examine the consensus among expert panels in the second and third rounds of the Delphi survey, and the relative weight was determined by pairwise comparisons between alternative factors in the AHP. Results: In developing the preliminary conceptual framework, 8 factor categories and 53 factors were identified as relevant to non-adherence to COPD self-management. Of the 53 factors, 22 factors with a CVR of 0.49 or higher were identified in the Delphi survey. A total of 14 of the 53 factors were common to both the Delphi survey and AHP with high weights. The most notable factors were prolonged treatment, experience of treatment failure, and unknown effects of medication. Conclusion: Through consensus decision-making by experts, 14 factors were identified as relevant factors associated with non-adherence to COPD self-management. A hierarchical and systematic framework incorporating factors associated with non-adherence to COPD self-management was developed in this study. Further research is needed to develop intervention strategies based on factors associated with non-adherence to COPD self-management.

Prediction of clinical risk assessment and survival in chronic obstructive pulmonary disease with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non-invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD-PH). METHODS: This study included 535 patients with COPD-PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD-PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan-Meier curves were used for a survival analysis. The nomograms were developed as online network software. RESULTS: Tricuspid regurgitation velocity, right ventricular diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), the red blood cell count, New York Heart Association functional class and sex were non-invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT-proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD-PH and were used to create a predictive nomogram of overall survival rates. CONCLUSIONS: The proposed nomograms based on a large sample size of patients with COPD-PH could be used as non-invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD-PH. Additionally, the online network has the potential to provide artificial intelligence-assisted diagnosis and treatment. HIGHLIGHTS: A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non-invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD-PH.

Impact of Smoking and Chronic Obstructive Pulmonary Disease on All-Cause, Respiratory, and Cardio-Cerebrovascular Mortality.

Introduction: Mortality differences in chronic obstructive pulmonary disease (COPD) between nonsmokers and smokers remain unclear. We compared the risk of death associated with smoking and COPD on mortality. Methods: The study included participants aged ≥40 years who visited pulmonary clinics and were categorised into COPD or non-COPD and smoker or nonsmoker on the basis of spirometry results and cigarette consumption. Mortality rates were compared between groups using statistical analysis for all-cause mortality, respiratory disease-related mortality, and cardiocerebrovascular disease-related mortality. Results: Among 5811 participants, smokers with COPD had a higher risk of all-cause (adjusted hazard ratio (aHR), 1.69; 95% confidence interval (CI), 1.23-2.33) and respiratory disease-related mortality (aHR, 2.14; 95% CI, 1.20-3.79) than nonsmokers with COPD. Non-smokers with and without COPD had comparable risks of all-cause mortality (aHR, 1.39; 95% CI, 0.98-1.97) and respiratory disease-related mortality (aHR, 1.77; 95% CI, 0.85-3.68). However, nonsmokers with COPD had a higher risk of cardiocerebrovascular disease-related mortality than nonsmokers without COPD (aHR, 2.25; 95% CI, 1.15-4.40). Conclusion: The study found that smokers with COPD had higher risks of all-cause mortality and respiratory disease-related mortality compared to nonsmokers with and without COPD. Meanwhile, nonsmokers with COPD showed comparable risks of all-cause and respiratory mortality but had a higher risk of cardiocerebrovascular disease-related mortality compared to nonsmokers without COPD.

Non-cardiac comorbidities in heart failure: an update on diagnostic and management strategies.

Managing non-cardiac comorbidities in heart failure (HF) requires a tailored approach that addresses each patient's specific conditions and needs. Regular communication and coordination among healthcare providers is crucial to providing the best possible care for these patients. Poorly controlled hypertension contributes to left ventricular remodeling and diastolic dysfunction, emphasizing the importance of optimal blood pressure control while avoiding adverse effects. Among HF patients with diabetes, SGLT2 inhibitors and mineralocorticoid receptor antagonists have shown promise in reducing HF-related morbidity and mortality. Chronic kidney disease exacerbates HF and vice versa, forming the vicious cardiorenal syndrome, so disease-modifying therapies should be maintained in HF patients with comorbid CKD, even with transient changes in kidney function. Anemia in HF patients may be multifactorial, and there is growing evidence for the benefit of intravenous iron supplementation in HF patients with iron deficiency with or without anemia. Obesity, although a risk factor for HF, paradoxically offers a better prognosis once HF is established, though developing treatment strategies may improve symptoms and cardiac performance. In HF patients with stroke and atrial fibrillation, anticoagulation therapy is recommended. Among HF patients with sleep-disordered breathing, continuous positive airway pressure may improve sleep quality. Chronic obstructive pulmonary disease often coexists with HF, and many patients can tolerate cardioselective beta-blockers. Cancer patients with comorbid HF require careful consideration of cardiotoxicity risks associated with cancer therapies. Depression is underdiagnosed in HF patients and significantly impacts prognosis. Cognitive impairment is prevalent in HF patients and impacts their self-care and overall quality of life.

The association of systemic immune-inflammation index with lung function, risk of COPD and COPD severity: A population-based study.

PURPOSE: The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were not fully understood. We conducted this cross-sectional, population-based study to investigate the complex association between SII and COPD, lung function, and COPD severity among the US adults. METHODS: Overall, 18,349 participants were included in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The exposure variable was SII, calculated from platelet counts, neutrophil counts, and lymphocyte counts. Weighted univariable and multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were performed to assess the relationship between COPD, lung function, COPD severity and SII. Last, we used a propensity score matching (PSM) analysis to reduce selective bias and validate these relationships. RESULTS: Approximately 1,094 (5.96%) of the participants were diagnosed as COPD. The multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) for the Q2 group (Log-SII > 2.740) was 1.39 (1.16 to 1.68). Before and after matching, multivariable logistic regression models revealed that increased Log-SII levels (SII Logarithmic transformation) associated positively with the risk of COPD. The subgroup analysis showed no interaction between Log-SII and a variety of variables (P for interaction > 0.05). RCS showed a reversed L-shaped relationship between Log-SII with COPD (P for nonlinear = 0.001) in individuals. In addition, we observed negative significant correlations between forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) %, FEV1/FVC% predicted and SII, and reversed U-shaped curve relationships between FEV1, FEV1% predicted and SII. High SII level is associated with severity of COPD, especially at Global Initiative on Obstructive Lung Disease (GOLD) 1 and GOLD 3. CONCLUSIONS: In summary, the Log-SII level is associated with COPD risk, lung function, and COPD severity.

Health effects of air pollution on respiratory symptoms: A longitudinal study using digital health sensors.

Previous studies of air pollution and respiratory disease often relied on aggregated or lagged acute respiratory disease outcome measures, such as emergency department (ED) visits or hospitalizations, which may lack temporal and spatial resolution. This study investigated the association between daily air pollution exposure and respiratory symptoms among participants with asthma and chronic obstructive pulmonary disease (COPD), using a unique dataset passively collected by digital sensors monitoring inhaled medication use. The aggregated dataset comprised 456,779 short-acting beta-agonist (SABA) puffs across 3,386 people with asthma or COPD, between 2012 and 2019, across the state of California. Each rescue use was assigned space-time air pollution values of nitrogen dioxide (NO2), fine particulate matter with diameter ≤ 2.5 µm (PM2.5) and ozone (O3), derived from highly spatially resolved air pollution surfaces generated for the state of California. Statistical analyses were conducted using linear mixed models and random forest machine learning. Results indicate that daily air pollution exposure is positively associated with an increase in daily SABA use, for individual pollutants and simultaneous exposure to multiple pollutants. The advanced linear mixed model found that a 10-ppb increase in NO2, a 10 µg m-3 increase in PM2.5, and a 30-ppb increase in O3 were respectively associated with incidence rate ratios of SABA use of 1.025 (95 % CI: 1.013-1.038), 1.054 (95 % CI: 1.041-1.068), and 1.161 (95 % CI: 1.127-1.233), equivalent to a respective 2.5 %, 5.4 % and 16 % increase in SABA puffs over the mean. The random forest machine learning approach showed similar results. This study highlights the potential of digital health sensors to provide valuable insights into the daily health impacts of environmental exposures, offering a novel approach to epidemiological research that goes beyond residential address. Further investigation is warranted to explore potential causal relationships and to inform public health strategies for respiratory disease management.

Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease.

BACKGROUND: COVID-19 is associated with cardiovascular outcomes in the general population, but it is unknown whether people with chronic respiratory disease (CRD) have a higher risk of cardiovascular events post-COVID-19 compared with the general population and, if so, what respiratory-related factors may modify this risk in these people. METHODS: Primary and secondary care data from the National Health Service England were used to define a population of adults in England with COVID-19 (index date) between 1 January 2020 and 30 November 2021. Adjusted Cox proportional hazard regression was used to quantify the association between CRD, asthma-related factors, chronic obstructive pulmonary disease (COPD)-related factors, and risk of cardiovascular events. Asthma-specific factors included baseline asthma control, exacerbations, and inhaled corticosteroid (ICS) dose. COPD-specific risk factors included baseline ICS and exacerbations. Secondary objectives quantified the impact of COVID-19 hospitalisation and vaccine dose on cardiovascular outcomes. RESULTS: Of 3 670 455 people, those with CRD had a higher risk of cardiovascular events [adjusted hazard ratio (HRadj), 1.08; 95% confidence interval (CI) 1.06-1.11], heart failure (HRadj, 1.17; 95% CI, 1.12-1.22), angina (HRadj, 1.13; 95% CI, 1.06-1.20) and pulmonary emboli (HRadj, 1.24; 95% CI, 1.15-1.33) compared with people without CRD. In people with asthma or COPD, baseline exacerbations were associated with a higher risk of cardiovascular outcomes (HRadj, 1.36; 95% CI, 1.27-1.00 and HRadj, 1.35; 95% CI, 1.24-1.46, respectively). Regardless of CRD, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. CONCLUSIONS: Higher risk of cardiovascular events post-COVID-19 might be explained by the underlying severity of the CRD, and COVID-19 vaccines were beneficial to both people with and those without CRD with regards to cardiovascualr events.

Analysis of clinical characteristics and prognosis of lung cancer patients with CPFE or COPD: a retrospective study.

BACKGROUND: Lung cancer (LC) commonly occurs in patients with combined pulmonary fibrosis and emphysema (CPFE) and chronic obstructive pulmonary disease (COPD), but comparative research is limited. This study examines clinical characteristics, treatments, and prognosis in LC patients with CPFE or COPD. METHODS: The retrospective study involved 75 lung cancer patients with CPFE and 182 with COPD. It analyzed clinical features, tumor pathology, pulmonary function, laboratory parameters, and treatment responses. RESULTS: Notable differences were found between the CPFE + LC and COPD + LC groups. Both groups were mostly elderly, male smokers. The CPFE + LC group had higher BMI and more adenocarcinoma and squamous cell carcinoma, while COPD + LC had predominantly squamous cell carcinoma. CPFE + LC tumors were mostly in the lower lobes; COPD + LC's were in the upper lobes. The CPFE + LC group showed higher tumor metastasis rates, more paraseptal emphysema, and elevated levels of TG, CEA, NSE, and Killer T Cells. In advanced stages (IIIB-IV), the CPFE + LC group receiving first-line treatment had shorter median progression-free survival (PFS) and a higher risk of progression or death than the COPD + LC group, regardless of whether it was non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). No significant PFS difference was found within CPFE + LC between chemotherapy and immunotherapy, nor in immune-related adverse events between groups, with interstitial pneumonia being common. CONCLUSION: This study emphasizes distinct lung cancer characteristics in CPFE or COPD patients, highlighting the need for tailored diagnostic and treatment approaches. It advocates for further research to improve care for this high-risk group.

DNA of neutrophil extracellular traps promote NF-κB-dependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by persistent airway inflammation even after cigarette smoking cessation. Neutrophil extracellular traps (NETs) have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke (CS). However, whether and how NETs contribute to sustained airway inflammation in COPD remain unclear. This study aimed to elucidate the immunoregulatory mechanism of NETs in COPD, employing human neutrophils, airway epithelial cells (AECs), dendritic cells (DCs), and a long-term CS-induced COPD mouse model, alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice (cGAS--/-, TLR9-/-); Additionally, bronchoalveolar lavage fluid (BALF) of COPD patients was examined. Neutrophils from COPD patients released greater cigarette smoke extract (CSE)-induced NETs (CSE-NETs) due to mitochondrial respiratory chain dysfunction. These CSE-NETs, containing oxidatively-damaged DNA (NETs-DNA), promoted AECs proliferation, nuclear factor kappa B (NF-κB) activation, NF-κB-dependent cytokines and type-I interferons production, and DC maturation, which were ameliorated/reversed by silencing/inhibition of cGAS/TLR9. In the COPD mouse model, blocking NETs-DNA-sensing via cGAS-/- and TLR9-/- mice, inhibiting NETosis using mitoTEMPO, and degrading NETs-DNA with DNase-I, respectively, reduced NETs infiltrations, airway inflammation, NF-κB activation and NF-κB-dependent cytokines, but not type-I interferons due to IFN-α/ß receptor degradation. Elevated NETs components (myeloperoxidase and neutrophil elastase activity) in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels, but not type-I interferon levels. In conclusion, NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced COPD. Therefore, targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

Outcomes among patients with chronic obstructive pulmonary disease after recovery from COVID-19 infection of different severity.

While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95-10.15, p < 0.001) and 6.77 (95% CI = 2.08-22.00, p = 0.001) respectively. Patients with severe COVID-19 infection had significantly increased risks of increase in severe COPD exacerbation frequency with adjusted odds ratios of 4.73 (95% CI = 1.55-14.41, p = 0.006) non-COVID-19 respiratory mortality from COPD exacerbation or pneumonia with adjusted hazard ratio of 11.25 (95% CI = 2.98-42.45, p < 0.001). After recovery from COVID-19, worsening of COPD control from worsening of dyspnea, increase in severe exacerbation frequency to non-COVID-19 respiratory mortality (COPD exacerbation and pneumonia) was observed among patients with severe COVID-19. Mild to moderate COVID-19 was also associated with symptomatic deterioration.

Development and validation of a nomogram for assessing survival in acute exacerbation of chronic obstructive pulmonary disease patients.

BACKGROUND: Early prediction of survival of hospitalized acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients is vital. We aimed to establish a nomogram to predict the survival probability of AECOPD patients. METHODS: Retrospectively collected data of 4601 patients hospitalized for AECOPD. These patients were randomly divided into a training and a validation cohort at a 6:4 ratio. In the training cohort, LASSO-Cox regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of AECOPD patients. A model was established based on 3 variables and visualized by nomogram. The performance of the model was assesed by AUC, C-index, calibration curve, decision curve analysis in both cohorts. RESULTS: Coexisting arrhythmia, invasive mechanical ventilation (IMV) usage and lower serum albumin values were found to be significantly associated with lower survival probability of AECOPD patients, and these 3 predictors were further used to establish a prediction nomogram. The C-indexes of the nomogram were 0.816 in the training cohort and 0.814 in the validation cohort. The AUC in the training cohort was 0.825 for 7-day, 0.807 for 14-day and 0.825 for 21-day survival probability, in the validation cohort this were 0.796 for 7-day, 0.831 for 14-day and 0.841 for 21-day. The calibration of the nomogram showed a good goodness-of-fit and decision curve analysis showed the net clinical benefits achievable at different risk thresholds were excellent. CONCLUSION: We established a nomogram based on 3 variables for predicting the survival probability of AECOPD patients. The nomogram showed good performance and was clinically useful.

Delineating excess comorbidities in idiopathic pulmonary fibrosis: an observational study.

BACKGROUND: Our study examined whether prevalent and incident comorbidities are increased in idiopathic pulmonary fibrosis (IPF) patients when compared to matched chronic obstructive pulmonary disease (COPD) patients and control subjects without IPF or COPD. METHODS: IPF and age, gender and smoking matched COPD patients, diagnosed between 01/01/1997 and 01/01/2019 were identified from the Clinical Practice Research Datalink GOLD database multiple registrations cohort at the first date an ICD-10 or read code mentioned IPF/COPD. A control cohort comprised age, gender and pack-year smoking matched subjects without IPF or COPD. Prevalent (prior to IPF/COPD diagnosis) and incident (after IPF/COPD diagnosis) comorbidities were examined. Group differences were estimated using a t-test. Mortality relationships were examined using multivariable Cox proportional hazards adjusted for patient age, gender and smoking status. RESULTS: Across 3055 IPF patients, 38% had 3 or more prevalent comorbidities versus 32% of COPD patients and 21% of matched control subjects. Survival time reduced as the number of comorbidities in an individual increased (p < 0.0001). In IPF, prevalent heart failure (Hazard ratio [HR] = 1.62, 95% Confidence Interval [CI]: 1.43-1.84, p < 0.001), chronic kidney disease (HR = 1.27, 95%CI: 1.10-1.47, p = 0.001), cerebrovascular disease (HR = 1.18, 95%CI: 1.02-1.35, p = 0.02), abdominal and peripheral vascular disease (HR = 1.29, 95%CI: 1.09-1.50, p = 0.003) independently associated with reduced survival. Key comorbidities showed increased incidence in IPF (versus COPD) 7-10 years prior to IPF diagnosis. INTERPRETATION: The mortality impact of excessive prevalent comorbidities in IPF versus COPD and smoking matched controls suggests that multiorgan mechanisms of injury need elucidation in patients that develop IPF.

Genetic perturbation of IL-6 receptor signaling pathway and risk of multiple respiratory diseases.

Dysregulation of inflammation can lead to multiple chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma. Interleukin-6 (IL6) is crucial in regulating the inflammatory cascade, but the causal link between IL6 signaling downregulation and respiratory diseases risk is unclear. This study uses Mendelian randomization to examine the effects of IL6R blockade on respiratory diseases. Analyzing data from 522,681 Europeans, 26 genetic variants were obtained to mimic IL6R inhibition. Our findings show that IL6R blockade significantly reduces the risk of COPD (OR = 0.71, 95% CI = 0.60-9.84) and asthma (OR = 0.82, 95% CI = 0.74-0.90), with protective trends for bronchitis, pulmonary embolism, and lung cancer. Results were consistent across methods, with no significant heterogeneity or pleiotropy. These insights suggest IL6R downregulation as a potential therapeutic target for respiratory diseases, meriting further clinical investigation.