The evidence to date: implications of l-ascorbic acid in the pathophysiology of aging.

L-Ascorbic acid, commonly known as vitamin C, has been used not only for disease prevention and in complementary and alternative medicine, but also for anti-aging purposes. However, the scientific evidence is not yet sufficient. Here, we review the physiological functions of vitamin C and its relationship with various pathological conditions, including our previous findings, and discuss the prospects of its application in healthy longevity. In summary, vitamin C levels are associated with lifespan in several animal models. Furthermore, clinical studies have shown that the blood vitamin C levels are lower in middle-aged and older adults than in younger adults. Lower blood vitamin C levels have also been observed in various pathological conditions such as chronic kidney disease and chronic obstructive pulmonary disease in the elderly. These observations suggest the implications of vitamin C in age-related pathological mechanisms owing to its physiological functions.

Race Adjustment of Pulmonary Function Tests in the Diagnosis and Management of COPD: A Scoping Review.

Aim: Increasing evidence suggests that the inclusion of self-identified race in clinical decision algorithms may perpetuate longstanding inequities. Until recently, most pulmonary function tests utilized separate reference equations that are race/ethnicity based. Purpose: We assess the magnitude and scope of the available literature on the negative impact of race-based pulmonary function prediction equations on relevant outcomes in African Americans with COPD. Methods: We performed a scoping review utilizing an English language search on PubMed/Medline, Embase, Scopus, and Web of Science in September 2022 and updated it in December 2023. We searched for publications regarding the effect of race-specific vs race-neutral, race-free, or race-reversed lung function testing algorithms on the diagnosis of COPD and COPD-related physiologic and functional measures. Joanna Briggs Institute (JBI) guidelines were utilized for this scoping review. Eligibility criteria: The search was restricted to adults with COPD. We excluded publications on other lung disorders, non-English language publications, or studies that did not include African Americans. The search identified publications. Ultimately, six peer-reviewed publications and four conference abstracts were selected for this review. Results: Removal of race from lung function prediction equations often had opposite effects in African Americans and Whites, specifically regarding the severity of lung function impairment. Symptoms and objective findings were better aligned when race-specific reference values were not used. Race-neutral prediction algorithms uniformly resulted in reclassifying severity in the African Americans studied. Conclusion: The limited literature does not support the use of race-based lung function prediction equations. However, this assertion does not provide guidance for every specific clinical situation. For African Americans with COPD, the use of race-based prediction equations appears to fall short in enhancing diagnostic accuracy, classifying severity of impairment, or predicting subsequent clinical events. We do not have information comparing race-neutral vs race-based algorithms on prediction of progression of COPD. We conclude that the elimination of race-based reference values potentially reduces underestimation of disease severity in African Americans with COPD.

[Differences in the elastic work of breathing of the pulmonary parenchyma in patients with bronchial asthma and COPD].

AIM: To determine and compare the work of breathing to overcome elastic resistance (Ael) in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) with similar changes in the elastic properties of the parenchyma in the same settings of ventilation disorders (grade 1). MATERIALS AND METHODS: Differences in the manifestations of similar changes in the elastic properties of the lungs in patients with BA and COPD were evaluated. To identify differences, a comparative study was conducted on Аel overcome in BA patients with positive bronchodilator (with salbutamol) and bronchoconstrictor (with methacholine) tests, with reduced and preserved bronchial conductance (groups 1 and 2, respectively), and in COPD patients with negative bronchodilator and bronchoconstrictor tests (group 3). All study patients showed a grade 1 lung ventilation disorder (a decrease in the one-second forced expiratory volume by 15-35%). The results were compared with each other and with the control group (group 4, healthy non-smokers). All study patients were comparable by age and sex. The respiration mechanics was studied using simultaneous registration of spirogram and transpulmonary pressure, and the parameters of bronchial conductance and ventilation were determined using body plethysmopressography using the Jager software and hardware system. RESULTS AND CONCLUSION: In COPD patients, Ael was significantly increased (p>0.05), whereas in both BA groups, it was unchanged. Increased elastic work of breathing in patients with COPD may be associated with the involvement of certain types of contractile elements, which are preserved in patients with BA at the initial stages of the disease.

[Influence of chronic obstructive pulmonary disease on hospital outcomes of percutaneous coronary interventions in patients with acute coronary syndrome].

AIM: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019-2020 were included, 418 (67%) - men, 208 (33%) - women. Median age - 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO - in 59 (9%) patients (criteria: blood flow <3 grade according to TIMI flow grade; perfusion <2 points according to Myocardial blush grade; ST segment resolution <70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (<17 points). Groups were compared on unbalanced data (÷2 Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel "weighting" method, logistic regression analysis was carried out using "weighting" coefficients. Results as odds ratio (OR) and 95% confidence interval. RESULTS: The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16-11.12); p=0.03; OR CMVO 0.65 (0.35-1.22); p=0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09-13.74); p=0.04; OR CMVO 0.61 (0.31-1.19); p=0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27-68.84); p=0.004; OR CMVO 0.63 (0.30-1.33); p=0.22. CONCLUSION: The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO.

Prevalence and clinical characteristics of Sarcopenia in older adult patients with stable chronic obstructive pulmonary disease: a cross-sectional and follow-up study.

BACKGROUND: The relationship between sarcopenia and chronic obstructive pulmonary disease (COPD) has been increasingly reported, and there is some overlap regarding their clinical features and pulmonary rehabilitation (PR) strategies. No Korean study has reported the actual prevalence of sarcopenia in patients with stable COPD who are recommended for pulmonary rehabilitation. This study evaluated the prevalence and clinical features of sarcopenia in older adult outpatients with stable COPD and the changes after 6 months. METHODS: In this cross-sectional and 6-month follow-up study, we recruited 63 males aged ≥ 65 diagnosed with stable COPD. Sarcopenia was diagnosed using the AWGS 2019 criteria, which included hand grip strength testing, bioelectrical impedance analysis, Short Physical Performance Battery administration, and Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falling screening tool administration. A 6-minute walk test (6 MWT) was conducted, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and peak expiratory flow (PEF) were assessed, and patient-reported questionnaires were administered. RESULTS: At baseline, 14 (22%) patients were diagnosed with possible sarcopenia, and eight (12.6%) were diagnosed with sarcopenia. There were significant differences in the age; body mass index; Body mass index, airflow Obstruction, Dyspnea, and Exercise index; modified Medical Research Council dyspnea scores; and International Physical Activity Questionnaire scores between the normal and sarcopenia groups. Whole-body phase angle, MIP, MEP, PEF, and 6-minute walk distance (6 MWD) also showed significant differences. Over 6 months, the proportion of patients with a reduced FEV1 increased; however, the proportion of patients with sarcopenia did not increase. CONCLUSION: A relatively low prevalence of sarcopenia was observed in older adult outpatients with stable COPD. No significant change in the prevalence of sarcopenia was found during the 6-month follow-up period. TRIAL REGISTRATION: The study was registered with the Clinical Research Information Service (KCT0006720). Registration date: 30/07/2021.

Doppler-derived pulmonary pulse transit time measurements in chronic obstructive pulmonary disease: Reproducibility and cardiopulmonary function.

INTRODUCTION: Doppler-derived pulmonary pulse transit time (pPTT) is an auspicious hemodynamic marker in chronic pulmonary diseases. The aim is to compare four distinct pPTT measurements and its relation to right cardiac and pulmonary function. METHODS: Prospectively, 25 chronic obstructive pulmonary disease (COPD) patients (four patients excluded) and 32 healthy subjects underwent repeated distinct pPTT measurements, standard echocardiography, and pulmonary function testing on the same day. pPTT was defined as the interval from the R or Q-wave in the electrocardiogram to the corresponding pulse wave Doppler peak late systolic (S) 2 or diastolic (D) pulmonary vein flow velocity (pPTT R-S, Q-S, R-D, Q-D). Reproducibility was assessed using Bland-Altman analysis, coefficient of variation (COV), intraclass correlation coefficient (ICC), and power calculations. Associations with right ventricular RV tissue and pulse wave Doppler velocities (RV E', RV S', RV A', RV E, RV A, RV E/E', RV E/A), TAPSE, right ventricular fractional area change, left ventricular systolic and diastolic function (LV ejection fraction, E, A, E/A, E/E', septal E', lateral E'), LA diameters, as well as forced expiratory volume in 1 s, forced vital capacity (FVC) predicted (%), and in liters were analyzed. RESULTS: There was no significant difference and no bias between pPTT measures (p range: .1-.9). COV was in COPD 1.2%-2.3%, in healthy subjects 1.0%-3.1%. ICC ranged from .92 (COPD) to .96 (healthy subjects). In COPD significant correlations were found for pPTT R-S, Q-S and R-D with RV E`, (all > ρ: .49, < p = .0364), pPTT R-S, Q-S with RV E/E` (both > ρ: .49, < p = .0291), pPTT Q-S with RV S´ (ρ: .58, p = .0134), RV A (ρ: .59, p = .0339) and heart rate > ρ: -.39, < p = .0297). pPTT R-S, R-D showed significant correlations with FVC predicted (%) (ρ: .48 p = .0224) and FVC (l) (ρ:.47 p = .0347). CONCLUSIONS: All pPTT measures exhibited high reproducibility. In COPD patients pPTT measures correlate with diastolic right ventricular function. Defining Q as starting point seems clinically advantageous considering electromechanical desynchrony in patients with conduction disorders.

Measuring burden of disease in both asthma and COPD by merging the ACQ and CCQ: less is more?

Symptoms of asthma and COPD often overlap, and both diseases can co-exist in one patient. The asthma control questionnaire (ACQ) and clinical COPD questionnaire (CCQ) were developed to assess disease burden in respectively asthma or COPD. This study explores the possibility of creating a new questionnaire to assess disease burden in all obstructive lung diseases by integrating and reducing questions of the ACQ and CCQ. Data of patients with asthma, COPD and asthma-COPD overlap (ACO) were collected from a primary and secondary care center. Patients completed ACQ and CCQ on the same day. Linear regression tested correlations. Principal Component Analysis (PCA) was used for item reduction. The secondary cohort with asthma and COPD patients was used for initial question selection (development cohort). These results were reproduced in the primary care cohort and secondary cohort of patients with ACO. The development cohort comprised 252 patients with asthma and 96 with COPD. Correlation between ACQ and CCQ in asthma was R = 0.82, and in COPD R = 0.83. PCA determined a selection of 9 questions. Reproduction in primary care data (asthma n = 1110, COPD n = 1041, ACO = 355) and secondary care data of ACO patients (n = 53) resulted in similar correlations and PCA-derived selection of questions. In conclusion, PCA determined a selection of nine questions of the ACQ and CCQ: working title 'the Obstructive Lung Disease Questionnaire'. These results suggest that this pragmatic set of questions might be sufficient to assess disease burden in obstructive lung disease in both primary as secondary care.

Does Obstructive Sleep Apnea Lead to Progression of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have important bidirectional relationships that influence the pathophysiology of each disorder. The slim hyperinflated "pink puffer" phenotype of COPD protects against OSA, whereas the heavier "blue bloater" phenotype predisposes to OSA by fluid retention. OSA may aggravate COPD by promoting airway inflammation. COPD-OSA overlap patients have lower quality of life and are at higher risk of cardiovascular comorbidity than either disorder alone due to greater nocturnal oxygen desaturation and sympathetic activation. Management of OSA with positive airway pressure improves COPD outcomes that include lower exacerbation rates compared to untreated patients.

[New clinical guidelines for COPD - a paradigm shift: A review].

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

Factors Associated with Patient Education in Patients with Chronic Obstructive Pulmonary Disease (COPD) - A Primary Health Care Register-Based Study.

Purpose: Patient education in chronic obstructive pulmonary disease (COPD) is recommended in treatment strategy documents, since it can improve the ability to cope with the disease. Our aim was to identify the extent of and factors associated with patient education in patients with COPD in a primary health care setting. Patients and Methods: In this nationwide study, we identified 29,692 COPD patients with a registration in the Swedish National Airway Register (SNAR) in 2019. Data on patient education and other clinical variables of interest were collected from SNAR. The database was linked to additional national registers to obtain data about pharmacological treatment, exacerbations and educational level. Results: Patient education had been received by 44% of COPD patients, 72% of whom had received education on pharmacological treatment including inhalation technique. A higher proportion of patients who had received education were offered smoking cessation support, had performed spirometry and answered the COPD Assessment Test (CAT), compared with patients without patient education. In the adjusted analysis, GOLD grade 2 (OR 1.29, 95% CI 1.18-1.42), grade 3 (OR 1.41, 95% CI 1.27-1.57) and grade 4 (OR 1.79, 95% CI 1.48-2.15), as well as GOLD group E (OR 1.17, 95% CI 1.06-1.29), ex-smoking (OR 1.70, 95% CI 1.56-1.84) and current smoking (OR 1.45, 95% CI 1.33-1.58) were positively associated with having received patient education, while cardiovascular disease (OR 0.92, 95% CI 0.87-0.98) and diabetes (OR 0.93, 95% CI 0.87-1.00) were negatively associated with receipt of patient education. Conclusion: Fewer than half of the patients had received patient education, and the education had mostly been given to those with more severe COPD, ex- and current smokers and patients with fewer comorbidities. Our study highlights the need to enhance patient education at an earlier stage of the disease.

Reliability, Validity, Modification and Expansion of the Chinese Version of the Disease-Specific Anxiety Questionnaire for Chronic Obstructive Pulmonary Disease.

Purpose: To translate a disease-specific anxiety questionnaire on chronic obstructive pulmonary disease (COPD) and test its reliability and validity in China. Patients and Methods: The German version of the revised COPD Anxiety Questionnaire (CAF-R) was initially validated using step-by-step translation, back-translation, and cross-cultural adaptation. The reliability and validity of the Chinese version of the CAF-R (CAF-R-CN) were tested among 448 patients with COPD (mean age =71.42±9.33 years, 17.2% female) from four medical institutions in Suzhou, Jiangsu Province, using convenience sampling, from April 2022 to June 2023. Results: The CAF-R-CN included six dimensions with a total of 25 items. The item-level content validity index was 0.860-1.000; the scale-level content validity index was 0.920. The structural validity χ2/df was 2.326, the root mean square error of approximation was 0.077, the comparative fit index was 0.924, and the Tucker-Lewis index was 0.912. The six-dimensional internal consistency index Cronbach's α coefficient was 0.696-0.910, and the test-retest reliability was 0.949. An optimal cut-off score of 50.5 was selected with a sensitivity of 0.786 and specificity of 0.870. Conclusion: The CAF-R-CN had satisfactory reliability and validity and can be used to identify and assess anxiety in COPD patients with a Chinese cultural background.

Effects of Ninjin'yoeito on Patients with Chronic Obstructive Pulmonary Disease and Comorbid Frailty and Sarcopenia: A Preliminary Open-Label Randomized Controlled Trial.

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.

Underdiagnosis of COPD: The Japan COPD Real-World Data Epidemiological (CORE) Study.

Purpose: The prevalence of airflow obstruction in Japan is 3.8%-16.9%. This epidemiological study based on a large database aimed to reassess the prevalence of airflow obstruction in Japan and the diagnosis rate of chronic obstructive pulmonary disease (COPD). Patients and Methods: We used data regarding claims from the health insurance union and health checkups provided by JMDC. The present study included a subgroup of individuals aged ≥40 years who underwent health checkups involving spirometry between January and December 2019. The study endpoints were the prevalence of airflow obstruction, COPD diagnosis rate, disease stage, and respiratory function test results. Results: Among 102,190 participants, 4113 (4.0%) had airflow obstruction. The prevalence of airflow obstruction was 5.3% in men and 2.1% in women. Among the study population, 6.8% were current smokers, while 3.4% were never or former smokers. Additionally, the prevalence of COPD increased with age. Approximately 8.4% of participants with airflow obstruction were diagnosed with COPD. Regarding the COPD diagnosis status, participants with airflow obstruction who were diagnosed with COPD were at a more advanced stage than those not diagnosed. Finally, patients diagnosed with COPD had significantly lower FEV1/FVC and FEV1 (p < 0.0001; Wilcoxon rank sum test). Conclusion: The epidemiological study based on a large database determined the COPD diagnosis rate related to airflow obstruction. The COPD diagnosis rate was extremely low among individuals who underwent health checkups, indicating the need for increased awareness about this medical condition. Moreover, primary care physicians should identify patients with suspected COPD and collaborate with pulmonologists to facilitate the early detection of COPD and enhance the COPD diagnosis rate.

Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up.

BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

Physiotherapy interventions on chest wall mobility in obstructive lung diseases: A systematic review.

PURPOSE: The aim of this systematic review was to investigate the effectiveness of physiotherapy interventions on chest mobility in obstructive lung diseases. METHODS: Searches were performed in PEDro, Pubmed and Cochrane Central Register of Controlled Trials databases without language restrictions between 2010 and 25th December 2020. Randomized controlled trials (RCTs) investigating physiotherapy interventions on chest wall mobility were included. Two independent reviewers screened studies, extracted data, and assessed methodological quality of included studies. The assessment of risk of bias was conducted using the PEDro scale for RCTs. The articles were excluded if they have less than 5 out of 10 score. RESULTS: Five studies included had good to excellent quality. A total of 139 patients were included in all RCTs. Intervention duration ranged from a single session to 12 weeks and the intervention schedules varied, consisting of 1-24 sessions, lasting 5-45 min per sessions. Three studies used respiratory muscle stretching and releasing techniques, one study combined respiratory muscle stretching with aerobic training, and one study planned diaphragmatic breathing. Four studies assessed chest wall mobility with optoelectronic plethysmography, whereas one study used measuring tape. CONCLUSIONS: The result of this first systematic review that investigates the effects of physiotherapy interventions on chest wall mobility in obstructive lung diseases suggests that more and better quality RCTs with objective measurement tools are required.

Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Bioinformatics analysis of hypoxia associated genes and inflammatory cytokine profiling in COPD-PH.

Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is associated with worse clinical outcomes and decreased survival rates. In absence of disease specific diagnostic/therapeutic targets and unclear pathophysiology, there is an urgent need for the identification of potential genetic/molecular markers and disease associated pathways. The present study aims to use a bioinformatics approach to identify and validate hypoxia-associated gene signatures in COPD-PH patients. Additionally, hypoxia-related inflammatory profile is also explored in these patients. Microarray dataset obtained from the Gene Expression Omnibus repository was used to identify differentially expressed genes (DEGs) in a hypoxic PH mice model. The top three hub genes identified were further validated in COPD-PH patients, with chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL12 showing significant changes in comparison to healthy controls. Furthermore, multiplexed analysis of 10 inflammatory cytokines, tumor necrosis factor alpha (TNF-α), transforming growth factor ß (TGF-ß), interleukin 1-beta (IL-1ß), IL-4, IL-5, IL-6, IL-13, IL-17, IL-18 and IL-21 was also performed. These markers showed significant changes in COPD-PH patients as compared to controls. They also exhibited the ability to differentially diagnose COPD-PH patients in comparison to COPD. Additionally, IL-6 and IL-17 showed significant positive correlation with systolic pulmonary artery pressure (sPAP). This study is the first report to assess the levels of CXCL9 and CXCL12 in COPD-PH patients and also explores their link with the inflammatory profile of these patients. Our findings could be extended to better understand the underlying disease mechanism and possibly used for tailoring therapies exclusive for the disease.

Identification of sleep phenotypes in COPD using machine learning-based cluster analysis.

BACKGROUND: Disturbed sleep in patients with COPD impact quality of life and predict adverse outcomes. RESEARCH QUESTION: To identify distinct phenotypic clusters of patients with COPD using objective sleep parameters and evaluate the associations between clusters and all-cause mortality to inform risk stratification. STUDY DESIGN AND METHODS: A longitudinal observational cohort study using nationwide Veterans Health Administration data of patients with COPD investigated for sleep disorders. Sleep parameters were extracted from polysomnography physician interpretation using a validated natural language processing algorithm. We performed cluster analysis using an unsupervised machine learning algorithm (K-means) and examined the association between clusters and mortality using Cox regression analysis, adjusted for potential confounders, and visualized with Kaplan-Meier estimates. RESULTS: Among 9992 patients with COPD and a clinically indicated baseline polysomnogram, we identified five distinct clusters based on age, comorbidity burden and sleep parameters. Overall mortality increased from 9.4 % to 42 % and short-term mortality (<5.3 years) ranged from 3.4 % to 24.3 % in Cluster 1 to 5. In Cluster 1 younger age, in 5 high comorbidity burden and in the other three clusters, total sleep time and sleep efficiency had significant associations with mortality. INTERPRETATION: We identified five distinct clinical clusters and highlighted the significant association between total sleep time and sleep efficiency on mortality. The identified clusters highlight the importance of objective sleep parameters in determining mortality risk and phenotypic characterization in this population.

Comparison of a portable, pneumotach flow-sensor-based spirometer (Spirofy™) with the vitalograph alpha Touch™ spirometer in evaluating lung function in healthy individuals, asthmatics, and COPD patients-a randomized, crossover study.

BACKGROUND: Spirofy™ is India's first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices. METHODS: In a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV1/FVC ratio distribution of < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers. RESULTS: Ninety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV1/FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices. CONCLUSION: Spirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma. TRIAL REGISTRATION: CTRI/2021/09/036492 (Clinical Trials Registry - India).

Aerobic exercise training engages the canonical wnt pathway to improve pulmonary function and inflammation in COPD.

BACKGROUND: We studied whether the exercise improves cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) in mice through inhibition of inflammation mediated by Wnt/ß-catenin-peroxisome proliferator-activated receptor (PPAR) γ signaling. METHODS: Firstly, we observed the effect of exercise on pulmonary inflammation, lung function, and Wnt/ß-catenin-PPARγ. A total of 30 male C57BL/6J mice were divided into the control group (CG), smoke group (SG), low-intensity exercise group (LEG), moderate-intensity exercise group (MEG), and high-intensity exercise group (HEG). All the groups, except for CG, underwent whole-body progressive exposure to CS for 25 weeks. Then, we assessed the maximal exercise capacity of mice from the LEG, MEG, and HEG, and performed an 8-week treadmill exercise intervention. Then, we used LiCl (Wnt/ß-catenin agonist) and XAV939 (Wnt/ß-catenin antagonist) to investigate whether Wnt/ß-catenin-PPARγ pathway played a role in the improvement of COPD via exercise. Male C57BL/6J mice were randomly divided into six groups (n = 6 per group): CG, SG, LiCl group, LiCl and exercise group, XAV939 group, and XAV939 and exercise group. Mice except those in the CG were exposed to CS, and those in the exercise groups were subjected to moderate-intensity exercise training. All the mice were subjected to lung function test, lung histological assessment, and analysis of inflammatory markers in the bronchoalveolar lavage fluid, as well as detection of Wnt1, ß-catenin and PPARγ proteins in the lung tissue. RESULTS: Exercise of various intensities alleviated lung structural changes, pulmonary function and inflammation in COPD, with moderate-intensity exercise exhibiting significant and comprehensive effects on the alleviation of pulmonary inflammation and improvement of lung function. Low-, moderate-, and high-intensity exercise decreased ß-catenin levels and increased those of PPARγ significantly, and only moderate-intensity exercise reduced the level of Wnt1 protein. Moderate-intensity exercise relieved the inflammation aggravated by Wnt agonist. Wnt antagonist combined with moderate-intensity exercise increased the levels of PPARγ, which may explain the highest improvement of pulmonary function observed in this group. CONCLUSIONS: Exercise effectively decreases COPD pulmonary inflammation and improves pulmonary function. The beneficial role of exercise may be exerted through Wnt/ß-catenin-PPARγ pathway.