Gas exchange efficiency slopes to assess exercise tolerance in chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the clinical use of the minute ventilation-carbon dioxide production ([Formula: see text]E-[Formula: see text]CO2) slope has been reported as a measure of exercise efficiency, but the oxygen uptake efficiency slope (OUES), i.e., the slope of oxygen uptake ([Formula: see text]O2) versus the logarithmically transformed [Formula: see text]E, has rarely been reported. METHODS: We hypothesized that the [Formula: see text]E-[Formula: see text]CO2 slope is more useful than OUES in clinical use for the pathophysiological evaluation of COPD. Then, we investigated the cardiopulmonary exercise testing parameters affecting each of these slopes in 122 patients with all Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD grades selected from our database. RESULTS: Compared with the GOLD I-II group (n = 51), peak [Formula: see text]O2 (p < 0.0001), OUES (p = 0.0161), [Formula: see text]E at peak exercise (p < 0.0001), and percutaneous oxygen saturation (SpO2) at peak exercise (p = 0.0004) were significantly lower in the GOLD III-IV group (n = 71). The GOLD III-IV group was divided into two groups by the exertional decrease in SpO2 from rest to peak exercise: 3% or less (the non-desaturation group: n = 23), or greater than 3% (the desaturation group: n = 48). OUES correlated only weakly with peak [Formula: see text]O2, [Formula: see text]E at peak exercise, and the difference between inspired and expired mean O2 concentrations (ΔFO2) at peak exercise, i.e., an indicator of oxygen consumption ability throughout the body, in the GOLD III-IV group with exertional hypoxemia. In contrast, the [Formula: see text]E-[Formula: see text]CO2 slope was significantly correlated with ΔFO2 at peak exercise, regardless of the COPD grade and exertional desaturation. Across all COPD stages, there was no correlation between the [Formula: see text]E-[Formula: see text]CO2 slope and [Formula: see text]E at peak exercise, and stepwise analysis identified peak [Formula: see text]O2 (p = 0.0345) and ΔFO2 (p < 0.0001) as variables with a greater effect on the [Formula: see text]E-[Formula: see text]CO2 slope. CONCLUSIONS: The OUES may be less useful in advanced COPD with exertional hypoxemia. The [Formula: see text]E-[Formula: see text]CO2 slope, which is independent of [Formula: see text]E, focuses on oxygen consumption ability and exercise tolerance in COPD, regardless of the exertional hypoxemia level and COPD grade. Therefore, the [Formula: see text]E-[Formula: see text]CO2 slope might be useful in establishing or evaluating tailor-made therapies for individual patient's pathologies in COPD as an indicator focusing on oxygen consumption ability.

Diagnostic value of impulse oscillometry in chronic obstructive pulmonary disease: a multicentre, retrospective, observational study.

OBJECTIVES: Diagnosis and assessment of chronic obstructive pulmonary disease (COPD) rely extensively on spirometry, which necessitates patient cooperation. The clinical value of impulse oscillometry (IOS) as a non-volitional method in patients with COPD remains uncertain. DESIGN: This retrospective observational study was conducted using patient data from between January 2014 and December 2015. SETTING: Five public hospitals in China: West China Hospital, Nuclear Industry 416 Hospital, Suining Central Hospital, Affiliated Hospital, Medical College of Chengdu University and 363 Hospital. PARTICIPANTS: The study included 6307 participants aged>40 years, comprising 2109 COPD patients and 4198 general non-COPD individuals, according to the Global Initiative for Obstructive Lung Disease (GOLD) spirometry standard. Participants with lung cancer, pulmonary tuberculosis, pneumonia or those who underwent lung resection were excluded from the study. OUTCOME MEASURES AND ANALYSIS: Demographic data, spirometry results and IOS results were collected. Spearman's correlation analysis was used to examine the correlation between the IOS and spirometry parameters. Receiver operating characteristic curve analysis was used to evaluate the IOS performance in COPD diagnosis and severity staging. RESULTS: Patients with COPD exhibited significant increases in Z5, R5, R20, R5-R20, Fres and Rp, but a decrease in X5 compared with non-COPD subjects (p<0.0001). IOS parameters, including Z5, R5-R20, Fres, Rp and X5, varied with the GOLD stages, with mild-to-moderate correlations with MMEF25%-75%, forced expiratory volume in one second (FEV1)/forced vital capacity and FEV1%, respectively. However, the combination of these five IOS parameters did not exhibit ideal performance in diagnosing COPD (area under the curve (AUC) 0.78; sensitivity 63.68%; specificity 80.09%), differentiating GOLD stage 1 patients from the general non-COPD population (AUC 0.71; sensitivity 54.71%; specificity 77.49%) or identifying GOLD stages 3 and 4 patients among those with COPD (AUC 0.75; sensitivity 69.51%; specificity 70.32%). CONCLUSION: IOS parameters, while showing good correlation with spirometry in patients with COPD, did not perfectly substitute for spirometry in diagnosing COPD, especially in the early and advanced stages of the disease.

Exploring the relationship between sarcopenia and 11 respiratory diseases: a comprehensive mendelian randomization analysis.

BACKGROUND: Sarcopenia (SP) is an aging-related loss of muscle mass and function, affecting the respiratory system. However, the causality of the association between sarcopenia on lung diseases remains elusive. METHODS: The bidirectional univariate Mendelian randomization (UVMR), multivariate MR (MVMR) analysis, and mediation MR were utilized to systematically investigate the genetic causal relationship of SP and 11 respiratory diseases. Independent genomic variants related to sarcopenia or respiratory diseases were identified as instrumental variables (IVs), and the summary level data of genome-wide associated studies (GWAS) were obtained from the UK biobank and FinnGen. MVMR analysis was conducted to explore the mediation effects of body mass index (BMI), Alcohol Use Disorders Identification Test (AUDIT), smoking, education attainment (EA), physical activity, and Type 2 Diabetes Mellitus (T2DM). RESULTS: Forward UVMR analysis based on the primary method revealed that pneumoconiosis was associated with a higher risk of appendicular lean mass (ALM) (OR = 1.01, p = 0.03), and BMI (10.65%), smoking (10.65%), and physical activity (17.70%) had a mediating role in the effect of pneumoconiosis on ALM. In reverse MR analysis, we found that genetically predicted ALM was significantly associated with an increased risk of pulmonary embolism (PE) (OR = 1.24, p = 7.21E-05). Chronic obstructive pulmonary disease (COPD) (OR = 0.98, p = 0.002) and sarcoidosis (OR = 1.01, p = 0.004) were identified to increase the loss of left-hand grip strength (HGS). Conversely, the increase in left- HGS presented a protective effect on chronic bronchitis (CB) (OR = 0.35, p = 0.03), (OR = 0.80, p = 0.02), and asthma (OR = 0.78, p = 0.04). Similarly, the loss of the right-HGS elevated the risk of low respiratory tract infection (LRTI) (OR = 0.97, p = 0.02) and bronchiectasis (OR = 1.01, p = 0.03), which is also an independent protective factor for LRTI and asthma. In the aspects of low HGS, the risk of LRTI was increased after MVMR analysis, and the risk of sarcoidosis and pneumoconiosis was elevated in the reverse analysis. Lastly, asthma was found to be related to the loss of the usual walking pace, and the reverse MR analysis suggested a causal relationship between the usual walking pace and LRTI (OR = 0.32, p = 2.79 × 10-5), asthma (OR = 0.24, p = 2.09 × 10-6), COPD (OR = 0.22, p = 6.64 × 10-4), and PE(OR = 0.35, p = 0.03). CONCLUSIONS: This data-driven MR analysis revealed SP was bidirectional causally associated with lung diseases, providing genetic evidence for further mechanistic and clinical studies to understand the crosstalk between SP and lung diseases.

Benefit of dual bronchodilator therapy on exacerbations in former and current smokers with chronic obstructive pulmonary disease in real-world clinical practice: a multicenter validation study (TOReTO).

BACKGROUND: Dual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups. METHODS: The TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed. RESULTS: Data from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study. CONCLUSIONS: The three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution.

Bidirectional Causal Association Between Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: A Mendelian Randomization Study.

Background: A large number of studies have demonstrated links between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVDs). However, the causal relationship between COPD and CVDs and the reverse causality remains divergent. Methods: Exposure and outcome data from the largest available genome-wide association studies were extracted for Mendelian randomization (MR) studies. Univariate MR analysis was performed using IVW as the primary analysis method, and multiple sensitivity analyses were used to enhance the robustness of the results. Furthermore, this was followed by mediation MR analysis of positive results after excluding confounding factors with multivariable MR analysis. Results: The MR estimation based on IVW method indicated a strong association between genetically determined COPD and heart failure (HF) (OR = 1.117, 95% CI: 1.066-1.170, p <0.001), coronary heart disease (CHD) (OR = 1.004, 95% CI: 1.002-1.006, p <0.001), essential hypertension (EH) (OR = 1.009, 95% CI: 1.005-1.013, p <0.001) as well as Stroke (OR = 1.003, 95% CI: 1.001-1.004, p <0.001). The results of multivariable MR analysis revealed that COPD is not significantly associated with CHD after adjusting for IL-6, LDL, or total cholesterol (p>0.05). Our findings indicated that BMI, smoking initiation, smoking status, obesity, and FEV1 played a role in the causal effect of COPD on HF, EH, and Stroke. Conclusion: We found positive causal relationships between COPD and HF, EH, and Stroke essentially unaffected by other confounding factors. The causal relationship exhibited between COPD and CHD was influenced by confounding factors. BMI, obesity, initiation of smoking, smoking status, and FEV1 were the mediators between COPD and CVDs.

Estimating rate of lung function change using clinical spirometry data.

RATIONALE: In chronic obstructive pulmonary disease (COPD), accurately estimating lung function from electronic health record (EHR) data would be beneficial but requires addressing complexities in clinically obtained testing. This study compared analytic methods for estimating rate of forced expiratory volume in one second (FEV1) change from EHR data. METHODS: We estimated rate of FEV1 change in patients with COPD from a single centre who had ≥3 outpatient tests spanning at least 1 year. Estimates were calculated as both an absolute mL/year and a relative %/year using non-regressive (Total Change, Average Change) and regressive (Quantile, RANSAC, Huber) methods. We compared distributions of the estimates across methods focusing on extreme values. Univariate zero-inflated negative binomial regressions tested associations between estimates and all-cause or COPD hospitalisations. Results were validated in an external cohort. RESULTS: Among 1417 participants, median rate of change was approximately -30 mL/year or -2%/year. Non-regressive methods frequently generated erroneous estimates due to outlier first measurements or short intervals between tests. Average change yielded the most extreme estimates (minimum=-3761 mL/year), while regressive methods, and Huber specifically, minimised extreme estimates. Huber, Total Change and Quantile FEV1 slope estimates were associated with all-cause hospitalisations (Huber incidence rate ratio 0.98, 95% CI 0.97 to 0.99, p<0.001). Huber estimates were also associated with smoking status, comorbidities and prior hospitalisations. Similar results were identified in an external validation cohort. CONCLUSIONS: Using EHR data to estimate FEV1 rate of change is clinically applicable but sensitive to challenges intrinsic to clinically obtained data. While no analytic method will fully overcome these complexities, we identified Huber regression as useful in defining an individual's lung function change using EHR data.

Nutritional Support and Physical Activity Intervention Programs with a Person-Centred Approach in People with Chronic Obstructive Pulmonary Disease: a Scoping Review.

Background: The knowledge is sparse in the literature on intervention programs using nutritional support and physical activity for patients with chronic obstructive pulmonary disease within a person-centred approach. We aimed to explore and map the existing evidence on intervention programs with a person-centred approach, focusing on nutritional support and physical activity for people with COPD. Methods: A scoping review was conducted using Arksey & O'Malley's methodological framework. A search in the databases CINAHL and PubMed, and a grey literature search, was conducted in June 2022 and updated in June 2023. We identified studies published between 2012 and 2023. The PRISMA checklist for scoping reviews, supported by The PAGER framework was used for reporting the method. Results: A total of 15 studies were included. The primary interventions comprised behavior of change or self-management, addressing needs assessment, motivation, personal goals, education, and physical activity. Health-related quality of life and hospital stay displayed no clinically significant variances. However, eight studies demonstrated differences in physical function and activity levels. Nutritional outcomes were addressed in one study, and three studies involved relatives. Conclusion: This scoping review addresses a knowledge gap in nutritional support interventions with a person-centred approach. It indicates that there is a need to increase nutritional support and consider the patient's physical and social environmental resources within Behavior of change or Self-management intervention programs for patients with COPD. The review found no clinical effect on health-related quality of life, although there were some effects on physical activity. The results highlight how the interdisciplinary team can include the patients' resources when structuring the management of COPD by applying a person-centred approach.

In vivo and in vitro Models of PM2.5 Induced COPD: Focus on the Role of RTA-408.

Introduction: Inflammation and oxidative stress are important factors in the pathogenesis of Chronic obstructive pulmonary disease (COPD). Current treatments for COPD focus on improving symptoms caused by inflammation rather than curing the disease, therefore, emerging research focusing on upstream pathways may help develop effective treatments. Epidemiological investigations have shown that exposure to fine particulate matter (PM2.5) can cause lung inflammation and oxidative stress through nuclear factor NF-E2-associated factor (Nrf2) pathway, leading to COPD. Nrf2 is an important transcription factor regulating anti-inflammatory and antioxidant stress, and its abnormal expression level or changes in transcriptional activity are related to the occurrence and development of COPD. Omaviloxone - RTA-408, a synthetic oleanane triterpene that acts as an Nrf2 activator, RTA-408 may play an important role in COPD. Purpose: In this study, PM2.5 was used to establish HBE cell model in vitro and rat model in vivo to simulate COPD, and the effect of Nrf2 activator RTA-408 on PM2.5-induced COPD model and its mechanism were investigated. Patients and Methods: The HBE cell model in vitro and rat model in vivo were established to simulate COPD, and the effect of RTA-408 on COPD was detected by various experimental methods. Results: The results showed that RTA-408 could activate Nrf2 both in vivo and in vitro. By activating Nrf2/HO-1 pathway, RTA-408 inhibits NF-κB and IFN-γ pathways, alleviates inflammation and oxidative stress of HBE cells in COPD model rats and PM2.5 exposed cells, and plays a therapeutic role in reversing cell damage and delaying disease progression in COPD. In addition, in vitro experiments, silencing Nrf2 eliminated the protective effect of RTA-408 on COPD cell models, which also confirmed the role of RTA-408. Conclusion: We conclude that RTA-408 is well worth considering as a new strategy for the treatment of COPD, and may also have a positive preventive effect.

Self-report underestimates the frequency of the acute respiratory exacerbations of COPD but is associated with BAL neutrophilia and lymphocytosis: an observational study.

RATIONALE: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. OBJECTIVE: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. METHODS: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). RESULTS: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen's Kappa = 0.47 ± 0.07; P < 0.001). Nevertheless, self-reported and EHR-identified m/s-AECOPD events were both associated with higher BAL neutrophils (ß ± SEM: 3.0 ± 1.1 and 1.3 ± 0.5 per 10% neutrophil increase; P ≤ 0.018) and lymphocytes (0.9 ± 0.4 and 0.7 ± 0.3 per 10% lymphocyte increase; P ≤ 0.041). Exacerbation by either measure combined was associated with a larger estimated effect (3.7 ± 1.2 and 1.0 ± 0.5 per 10% increase in neutrophils and lymphocytes, respectively) but was not statistically significantly different compared to the self-report only approach. Among the 184 TEPS participants, there were fewer moderate to very severe respiratory exacerbations by self-report (n = 15 or 8%) or EHR-documentation (n = 9 or 5%), but a similar level of agreement as those with COPD was observed (Cohen's Kappa = 0.38 ± 0.07; P < 0.001). DISCUSSION: While there is modest agreement between self-reported and EHR-identified m/s-AECOPD, events are missed by relying on either method alone. However, m/s-AECOPD quantified by self-report or health records is associated with BAL neutrophilia and lymphocytosis.

Blood cadmium concentration and pulmonary function injury: potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients.

BACKGROUND: Exposure to cadmium (Cd) is associated with a reduction in lung function among patients with chronic obstructive pulmonary disease (COPD). The longitudinal relationship and mechanism underlying the link between Cd exposure and lung function changes among COPD patients are yet unknown. METHODS: The cohort study included 259 eligible patients who underwent regular professional follow-ups. Blood Cd levels and serum 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) levels were assessed. Lung function was determined at baseline and follow-up research. The associations between changes in lung function and blood Cd concentration were analysed using multivariate linear and logistic regression models. RESULTS: Each 1-ppb elevation in blood Cd content resulted in a 0.420 L decrease in forced vital capacity (FVC), a 0.424 L decrease in forced expiratory volume in 1 s (FEV1), a 4.341% decrease in FEV1/FVC%, and a 8.418% decrease in FEV1% predicted in patients with COPD. Blood Cd concentration showed a positive correlation with serum 8-iso-PGF2α levels in a specific range. The relative contribution of increased serum levels of 8-iso-PGF2α to Cd-induced declines in FEV1, predicted FEV1%, and FEV1/FVC% were 2.08%, 8.08%, and 13.19%, respectively. CONCLUSION: Blood Cd levels are associated with lung function changes in COPD patients. Oxidative stress is thought to be an important mediator in Cd-induced reduction of pulmonary function.

Tracking Real-World Physical Activity in Chronic Obstructive Pulmonary Disease Over One Year: Results from a Monocentric, Prospective, Observational Cohort Study.

Introduction: Lung function constraints and comorbidities such as coronary heart disease, sarcopenia, and mood disorders make chronic obstructive pulmonary disease (COPD) patients avoid physical activity (PA). However, PA represents an important pillar of COPD management and is explicitly recommended by professional associations to enhance physical functioning and positively modulate disease progression. Methods: In this monocentric, prospective, observational feasibility study, it was our primary objective to investigate the association between PA and the evolution of the COPD assessment test (CAT) and the occurrence of acute exacerbations of COPD (AECOPD), respectively. To this end, we equipped 42 COPD patients with an activity tracking wearable and telemonitored their daily PA levels over one year using a dedicated web-based interface. Patients additionally provided weekly CAT scores using the same telehealth platform and came in for 3 study visits to assess functional parameters and biochemical markers related to nutrition and inflammation. Results: A principal study finding was that PA was inversely associated with CAT score (drop of 0.21 points associated with an increase of 1000 daily steps, p = 0.004), and that the 50% of patients with higher PA levels showed less CAT score progression over time (0.42 points per year) than the 50% of patients with lower PA levels (3.26 points per year) (p < 0.001). In addition, higher PA levels were significantly associated with a lower likelihood of experiencing a moderate-to-severe AECOPD (31% risk reduction associated with an increase of 1000 daily steps, p = 0.0097). Discussion: Our study demonstrates the relevance of PA for key COPD outcome metrics in a real-world setting and underpins the importance of PA for COPD self-management in everyday life. Our study paves the way for future intervention trials to prospectively identify medically relevant PA thresholds and establish training recommendations for different patient subgroups.

The effect of nebulized N-acetylcysteine on the phlegm of chronic obstructive pulmonary disease: the NEWEST study.

BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial.

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

Prevalence and Associated Factors of Paroxysmal Atrial Fibrillation and Atrial Arrhythmias During Hospitalizations for Exacerbation of COPD.

Purpose: This study aimed to investigate the proportion and risk factors of paroxysmal atrial fibrillation (AF) and atrial arrhythmias (AA) in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Vietnam. Patients and Methods: A prospective observational study was conducted at two major hospitals in Hanoi, Vietnam, from January 2022 to January 2023. A total of 197 AECOPD patients were recruited. ECG and 24-hour Holter ECG were used to diagnose paroxysmal AF and AA. Results: The prevalence of paroxysmal AF and AA were 15.2% and 72.6%, respectively. Factors associated with a higher likelihood of paroxysmal AF included aging 75 years old and above (aOR = 3.15; 95% CI: 1.28 to 8.48), Premature atrial complex (PAC) with 500 or more (aOR = 3.81; 95% CI: 1.48 to 10.97) and severity of COPD as group C and D (aOR = 3.41; 95% CI: 1.28 to 10.50). For AA, aging 75 years old and above (aOR = 2.25; 95% CI: 1.28 to 5.20), smoking (aOR = 2.10; 95% CI: 1.07 to 4.23) and P wave dispersion (PWD) with 40 milliseconds or more (aOR = 3.04; 95% CI: 1.54 to 6.19) were associated with a higher likelihood of AA. Conclusion: Overall, our findings highlight the associated factors with the paroxysmal AF and AA among AECOPD patients. This underscores the importance of a multifaceted approach to risk assessment and management in this vulnerable population, focusing not only on respiratory symptoms but also on comprehensive cardiovascular evaluation and intervention.

Clinical applications of forced oscillation technique (FOT) for diagnosis and management of obstructive lung diseases in children.

Obstructive lung diseases such as bronchial asthma, COPD, and cystic fibrosis are a burden on many patients across the globe. Spirometry is considered the gold standard for diagnosing airflow obstruction, but it can be difficult for pediatric patients to do and requires a lot of effort. As a result, healthcare providers need new, effortless methods to diagnose airway obstructions, particularly in young children and individuals unable to perform the spirometry maneuver. The forced oscillation technique is a modern method requiring only tidal breathing combined with the application of external, source of low-amplitude oscillations to evaluate the respiratory system's response. It might be essential for identifying early respiratory changes caused by smoking, childhood asthma, and may prove more sensitive than spirometry in identifying peripheral airway disturbances or evaluating the long-term success of therapy. This review describes the methodology and the indications for the forced oscillation technique and outlines its relevance in clinical practice.

Phase angle measured by bioelectrical impedance analysis in patients with chronic obstructive pulmonary disease: Associations with physical inactivity and frailty.

BACKGROUND: Factors associated with early-stage frailty (pre-frailty) in patients with chronic obstructive pulmonary disease (COPD) remain unestablished. In addition to skeletal muscle quantity, skeletal muscle dysfunction can be estimated using an angular metric from bioelectrical impedance analyzer (BIA), termed the phase angle, that reflects cell membrane reactance representing the structural stability. This study examined whether the phase angle was more closely associated with pre-frailty compared with skeletal muscle quantity in patients with COPD. METHODS: This cross-sectional analysis included stable smokers with and without COPD whose frailty status was assessed using the Japanese version of the Cardiovascular Health Study criteria. The phase angle and skeletal muscle index (SMI) were measured using BIA, and physical activity over one week was assessed using triaxial accelerometers. RESULTS: A total of 159 patients were categorized into robust, pre-frail, and frail groups (n = 38, 92, and 29, respectively). The phase angle was significantly smaller in the pre-frail and frail groups than in the robust group after adjusting for age, sex, height, body mass index, smoking history, and lung function. In contrast, SMI did not differ between the robust and pre-frail groups. When combining the pre-frail and frail groups into a non-robust group, 4.8° was determined as the cutoff phase angle value to identify non-robust status. A phase angle <4.8° was associated with shorter durations of moderate-intensity physical activity but not with light physical activity. CONCLUSIONS: A smaller phase angle was associated with pre-frailty and impaired moderate-intensity physical activity in smokers with and without COPD.

Prevalence and etiotypes of persistent airflow obstruction in the general population across the lifetime.

BACKGROUND AND OBJECTIVES: Different factors (etiotypes) can lead to persistent airflow obstruction (PAO) across the lifetime, including genetic factors, abnormal lung development, cigarette smoking, traffic pollution exposure, respiratory infections and asthma. Here we explore the prevalence of PAO and associated etiotypes in the general population in different age bins. METHODS: We studied 664 individuals with PAO (FEV1/FVC post bronchodilation (post-BD) below the lower limit of normal (LLN)) and 11,522 with normal lung function (FEV1/FVC, FEV1 and FVC ≥ LLN and ≤ upper limit of normal (ULN) post-BD) included in the LEAD Study (NCT01727518), a general population cohort in Vienna (Austria). For analysis, participants were stratified in three age bins (<25, 25-<50 and ≥ 50 years of age). RESULTS: PAO occurred in 3.8 % in females and 5.6 % in males of the cohort, and it increased with age. Most participants with PAO (57.5 %) reported respiratory symptoms, indicating a high burden of disease. PAO was associated with male sex (25-<50 years), ever smoking (>50 years), increased number of pack years (25-<50 years, >50 years), not being breastfed (<25 years) and ever diagnosis of asthma (in all age bins). Etiotypes varied by age bins with cigarette smoking being the most prevalent one, often in combination with traffic pollution exposure. CONCLUSION: In the general population PAO occurs in about 5 % of participants with a higher prevalence in older individuals. Etiotypes and associated factors for PAO accumulate with age.

Lung function parameters in overweight patients with COPD in relation to body mass index and waist circumference and impact on quality of life.

OBJECTIVE: We investigated the correlation of lung function parameters with increased body mass index (BMI) and waist circumference (WC) and determined the impact on health-related quality of life (HRQoL). METHODS: We conducted a cross-sectional analytical study at a teaching hospital among 173 individuals. We assessed anthropometric measurements, dynamic lung function, clinical history, and HRQoL using the Airway Questionnaire. Correlations of dynamic lung function parameters with BMI and WC were analyzed. RESULTS: In total, 51% were men (mean patient age 47.8 ± 10.5 years, median 48 years). The average BMI was 30.3 ± 8 kg/m2. Among 173 participants, 49% were smokers, with 16 ± 9 pack-years smoked; 80% of participants had chronic obstructive pulmonary disease (COPD). We observed compromised mid-expiratory flow (MEF), especially in young and overweight smokers. A moderately strong positive relationship was observed between WC and HRQoL scores, indicating a decline in HRQoL with increased WC. CONCLUSION: In our study, HRQoL declined with increasing WC. We found a decrease in MEF among young and overweight smokers who were otherwise healthy and whose other lung function parameters were normal; this finding can be regarded as a pre-COPD marker. These individuals should be reassessed for the development of COPD. Further prospective studies are needed to verify our findings.

The Lymphatic Highway: How Lymphatics Drive Lung Health and Disease.

The pulmonary lymphatic system has emerged as a critical regulator of lung homeostasis and a key contributor to the pathogenesis of respiratory diseases. As the primary conduit responsible for maintaining fluid balance and facilitating immune cell trafficking, the integrity of lymphatic vessels is essential for preserving normal pulmonary structure and function. Lymphatic abnormalities manifest across a broad spectrum of pulmonary disorders, underscoring their significance in respiratory health and disease. This review provides an overview of pulmonary lymphatic biology and delves into the involvement of lymphatics in four major lung diseases: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, and lung transplant rejection. We examine how lymphatic abnormalities manifest in each of these conditions and investigate the mechanisms through which lymphatic remodeling and dysfunction contribute to disease progression. Furthermore, we explore the therapeutic potential of targeting the lymphatic system to ameliorate these debilitating respiratory conditions. Despite the current knowledge, several crucial questions remain unanswered, such as the spatial and temporal dynamics of lymphatic changes, the molecular crosstalk between lymphatics and the lung microenvironment, and the distinction between protective versus detrimental lymphatic phenotypes. Unraveling these mysteries holds the promise of identifying novel molecular regulators, characterizing lymphatic endothelial phenotypes, and uncovering bioactive mediators. By harnessing this knowledge, we can pave the way for the development of innovative disease-modifying therapies targeting the lymphatic highway in lung disorders.

Efficacy and safety of bronchoscopic lung volume reduction for chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

BACKGROUND: Various bronchoscopic lung volume reduction (BLVR) methods have been developed to treat chronic obstructive pulmonary disease (COPD). The efficacy and safety of these interventions remain unclear. This study assessed the efficacy and safety of various BLVR interventions in COPD patients. METHODS: PubMed and Embase were searched from inception to 21 October 2023. The primary outcomes assessed included the 6-min walking distance (6MWD), St. George Respiratory Questionnaire (SGRQ) score, lung function, and adverse events (AE). A frequentist approach with a random-effects model was used for a network meta-analysis. RESULTS: Twelve randomized controlled trials (RCTs) with 1646 patients were included in this meta-analysis. Patients treated with an endobronchial valve (EBV) achieved a minimum clinically important difference (MCID) in 6MWD and SGRQ at 6 months. Patients treated with coils achieved MCID in the SGRQ score at 12 months. Patients with aspiration valve system and bronchoscopic thermal vapor ablation (BTVA) achieved MCID in the SGRQ score at 6 months. CONCLUSIONS: In COPD patients, EBV should be considered first, while being wary of pneumothorax. Coil and BTVA are potential therapeutic alternatives. Although BTVA demonstrates a safer procedural profile than coils, additional studies are imperative to clarify its efficacy.