Delayed ventilation assessment using fast dynamic hyperpolarised Xenon-129 magnetic resonance imaging

Chronic obstructive pulmonary disease (COPD) is common in patients with aortic aneurysms. Severe COPD is associated with an increased risk of aneurysm rupture and perioperative complications. This study assesses the outcomes of COPD and non-COPD patients after fenestrated-branched endovascular aortic aneurysm repair (FBEVAR). A single institution, retrospective study of FBEVAR patients between 2011 and 2020 compared outcomes between COPD and non-COPD patients. COPD patients were stratified by Global Initiative for Chronic Obstructive Lung Disease criteria and oxygen dependence. Outcome measures included 30-day mortality, pulmonary complications, major adverse events (MAE), and mid-term survival. 387 patients (71% male, age 72 years, interquartile range [68-79]) underwent FBEVAR. 181 patients (47%) had COPD. Smoking history was more frequent in COPD patients (P = .022). Among COPD patients, 20.4% were oxygen-dependent. Technical success, defined as successful delivery of the main aortic endograft and all intended side branches, was 98.4%. 30-day mortality (P = .83) and MAE rates (P = .87) were similar between groups. While not statistically significant, COPD patients had more frequent pulmonary complications (6.1% vs. 2.4%, P = .13) and were more frequently discharged on oxygen (P = .002). There were no differences in intensive care unit or hospital length of stay between groups (P = .29; P = .85, respectively). 5-year survival was similar between groups (P = .10). Oxygen-dependent COPD and severe-very severe COPD were associated with decreased mid-term survival (Hazard Ratio 2.39, P = .048). FBEVAR is safe and effective for treating complex aortic pathology in COPD patients, including oxygen-dependent patients. Patients with more severe COPD were more frequently discharged on oxygen. Mid-term survival was slightly reduced in patients with oxygen-dependent and severe-very severe COPD. Level 3, non-randomized controlled cohort/follow-up study.

To investigate the correlations between lipid ratio/oxidative stress status in chronic obstructive pulmonary disease (COPD) patients and pulmonary hypertension as well as the prognosis. Methods: A total of 120 patients with COPD were randomly selected and served as the COPD group and 30 healthy persons were selected as the control group. The ratios of low density lipoprotein (LDL)/high-density lipoprotein (HDL), triglyceride (TG)/HDL and total cholesterol (TC)/HDL were measured. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) level in the control group and COPD patients were detected. Pulmonary hypertension incidence and 3-year survival rate for COPD patients were statistically analyzed. Spearman rank correlation method was used to analyze relationship between lipid ratio /oxidative stress status and pulmonary hypertension. Results: Compared with control group, the ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA level in the COPD group were increased, while the serum SOD and T-AOC level in the COPD group were decreased; compared with stable period, lipid ratios and MDA levels in the acute period were elevated, while serum SOD and T-AOC levels were reduced (P<0.05). Pulmonary hypertension incidence and 3-year survival rates in the COPD group were 56.67% and 81.67% respectively; the lipid ratios and serum MDA levels in COPD patients with pulmonary hypertension were elevated compared with that in COPD patients without pulmonary hypertension; the serum SOD and T-AOC levels in COPD patients with pulmonary hypertension were reduced compared with that in patients without pulmonary hypertension (P<0.05). Spearman rank correlation analysis showed that ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA levels in COPD patients were positively correlated with 3-years pulmonary hypertension incidence (r=0.752, 0.748, 0.752, 0.748; P<0.05), and negatively correlated with 3-years survival rate (r=-0.722, -0.751, -0.736, -0.748; P<0.05); serum SOD and T-AOC levels in COPD patients were negatively correlated with 3-years pulmonary hypertension (r=-0.711, -0.734; P<0.05), and positively correlated with 3-year survival rate (r=0.726, 0.733; P<0.05). Conclusion: Blood lipid ratio and oxidative stress levels in COPD patients are elevated while antioxidant abilities were attenuated. The lipid ratio and oxidative stress status in COPD patients is closely related to the prognosis of pulmonary hypertension. Therefore, blood lipid ratio and oxidative stress status may be used in evaluation of pulmonary hypertension and prognosis for COPD patients.

Background: Identifying comorbidities in chronic obstructive pulmonary disease (COPD) may lead to improved disease management, survival and costs. Objective: To compare comorbidities and associated healthcare use between COPD and non-COPD patients. Methods: COPD patients9 medical records data from primary care in Sweden were linked to primary and secondary care national registries information. Data included prescriptions, mortality, income/social characteristics, and pre- and post-COPD diagnosis comorbidities. Comorbidity prevalence was compared between COPD patients and an age-, gender- and calendar year-matched reference population. Healthcare costs were categorized as COPD- and non-COPD related, and comprised drug costs and primary and secondary care visits. Results: There were 17,545 COPD and 84,514 reference group patients. A higher pre-COPD diagnosis comorbidity of asthma (10.1% vs 5.6%), depression (5.0% vs 2.8%), type II diabetes (5.6% vs 3.8%), osteoporosis (1.3% vs 0.7%), fractures (7.5% vs 5.7%), cardiovascular disease (30.2% vs 21.6%), rheumatoid arthritis (1.5% vs 0.9%), and lung cancer (0.4% vs 0.1%) was observed in COPD patients compared with reference patients. Two years post-diagnosis, the comorbidity rate increased for both the COPD and the reference patients, but the proportion of COPD patients with each comorbidity was considerably higher than for the reference patients. Costs of treating COPD comorbidities were higher than COPD-related costs at all time points (e.g. €8,295 vs €620 for non-COPD vs COPD-related hospital nights, respectively, in 2013). Conclusion: Comorbidities are more prevalent in COPD than non-COPD patients and are the major contributor to healthcare costs.

Introduction: Little is known about protease, anti-protease markers in chronic obstructive pulmonary disease (COPD) patients. Objectives: The objective of present study was to identify and try to correlate serum markers of protease and anti-protease with pulmonary functions in different stages of patients with COPD and to determine the ratio of neutrophil elastase/alpha-1-antitrypsin in different stages of COPD patients. Methods: This prospective observational study was carried out in patients with stable COPD. Activities of serum alpha-1-antitrypsin and neutrophil elastase were measured in 220 stable COPD patients and in 60 healthy controls by ELISA method. 220 COPD patients were divided into 4 stages according to severity: stage I, II, III and IV. Results: An increase in serum neutrophil elastase and neutrophil elastase/alpha-1-antitrypsin ratio was observed in COPD patients with the advancement of the stage. In contrast to that, decreased activity of alpha-1-antitrypsin in serum was observed in different stages of COPD and is correlated positively with lung function parameters. Conclusion: From these findings we conclude that as the severity increases there is decrease in alpha-1-antitrypsin resulting in concomitant increase in neutrophil elastase activity causing imbalance between protease-antiprotease in COPD patients and this imbalance is associated with impairment of lung function. The neutrophil elastase/ α-1-antitrypsin ratio can tell us the severity of the chronic obstructive pulmonary disease it may be in terms of increased fibrosis of the lung. Though the magnitude of neutrophil elatase/alpha-1-antitrypsin ratio is minute, still it can be a good marker of pulmonary function in term of severity of the COPD.

The mechanism responsible for the reversibility of airflow limitation in stable chronic obstructive pulmonary disease (COPD) patients is unknown. The aim of this study is to assess the relationship between the reversibility of airflow limitation, the redox balance and the inflammatory cells in the sputum of patients with stable COPD. For this purpose we examined 15 normal healthy control subjects and 20 nonatopic COPD patients. The COPD patients were divided into two groups: reversible COPD (increase in FEV1> 200 ml and/or > or =12> or = after 200 microg of inhaled salbutamol) or non-reversible COPD. GSH, GSSG were measured in induced sputum and blood. Protein carbonyls were evaluated by WB in sputum and IL-4 and IL-6 and TNF-alpha in plasma and sputum. GSH oxidation and protein oxidation were lower in reversible COPD patients than in those with no reversibility. The sputum eosinophil count was significantly higher in the reversible group than in the non-reversible group, and IL-4 concentration was higher in the same patients both in sputum and in plasma. In contrast, IL-6 and TNF-alpha were increased in non-reversible COPD patients in both biological samples. We conclude that airflow reversibility in COPD patients is associated with airway oxidative stress and activation of eosinophil inflammatory pattern in sputum and blood, suggesting that these patients could respond to specific pharmacological treatment.

The goal of this study was to estimate the prevalence of spirometry testing among patients with asthma and chronic obstructive pulmonary disease (COPD) in general practices (GPs) in Germany. This retrospective cross-sectional study was based on data from the Disease Analyzer database (IQVIA), This retrospective cross-sectional study included all patients with at least one confirmed asthma or COPD diagnosis in one of those 50 general practices in Germany between January 2020, and January 2021, as well as at least one visit to these general practices between January 2021, and January 2022. The main outcomes of the study aimed to ascertain the proportion of spirometry testing among asthma and COPD patients between January 2021, and January 2022, overall, and separately, in men, women, six age groups (≤30, 31-40, 41-50, 51-60, 61, 70, &gt;70), and patients who received at least one prescription of anti-asthma or anti-COPD drugs. This study included 8835 patients with asthma only, 5597 with COPD only, and 1897 with both asthma and COPD diagnoses. Of these, 27.2% of COPD patients, 7% of asthma patients, and 54.7% of asthma + COPD patients, received spirometry testing during the study period. Among COPD and asthma + COPD patients, the prevalence of spirometry testing was much higher in women than in men (COPD: 31.6% vs. 23.2%; asthma + COPD: 59.6% vs. 46.3%) and much higher in treated than in non-treated patients (COPD: 31.7% vs. 15.0%; asthma + COPD: 57.5% vs. 27.8%). The prevalence of spirometry testing was relatively low among COPD and asthma patients followed in GP practices, but usually higher in female patients, treated patients, and patients suffering from both asthma and COPD.

Pulmonary hemodynamics and lung function in patients with COPD and DPLD

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is characterised by a modified inflammatory response to chronic irritants which is often associated with some degree of systemic inflammation. Exacerbations in COPD are characterized by exaggeration of the ongoing inflammation. A number of inflammatory mediators are found to be raised in COPD exacerbations but most of them are expensive and not readily available. The Neutrophil-lymphocyte Ratio (NLR) is a rapid, easy and cheap biomarker that has been shown to be raised in patients of COPD. Aim: To evaluate the role of NLR in patients of stable and acute exacerbation of COPD. Materials and Methods: This cross-sectional observational study was conducted in Department of Pulmonary Medicine at Government Medical College, Patiala, Punjab, India. Study included 150 patients of stable COPD, 150 patients of Acute Exacerbation COPD (AECOPD) and 100 subjects as controls. NLR was calculated from a peripheral blood sample of the study participants. Continuous variables were summarised as mean with standard deviation and compared between groups using Unpaired t-test. A p-value &lt;0.05 was considered statistically significant. Results: The mean age in AECOPD group was 61.7±10.4 years, in stable COPD group was 63.1±8.9 years and 63.2±7.8 years in controls. Mean NLR was found to be highest in AECOPD group (4.0±1.7) followed by stable COPD (2.9±0.8) and then control (1.8±0.4).NLR showed good predictive value for predicting exacerbations in stable COPD patients with sensitivity and specificity of 75.3% and 70.7% respectively (cut-off 3.4 and AUC=0.806). Conclusion: NLR is an easily available biomarker of inflammation and can be used as a predictor of exacerbation in patients of COPD.

Allele distribution at a highly polymorphic minisatellite adjacent to the c-Hras1 gene as well as deletions of microsatellite markers, D3S966, D3S1298, D9S171, and a microsatellite within p53 gene, were examined in bronchial epithelium specimens obtained from 53 chronic obstructive pulmonary disease (COPD) patients and healthy donors. A higher frequency of rare Hras1minisatellite alleles in COPD patients than in the individuals without pulmonary pathology (6.6% versus 2.2%; P < 0.05) was shown. This difference was most pronounced in the group of ten COPD patients with idiopathic pulmonary fibrosis. Three of these patients had rare Hras1 minisatellite allele (P < 0.02 in comparison with healthy controls). Alterations in at least one of the microsatellite markers (deletions or microsatellite instability) were detected in bronchial epithelium samples obtained from: 4 of 10 COPD patients with pneumofibrosis (40%); 15 of 43 COPD patients (34.9%) without pneumofibrosis; and 8 of 20 tobacco smokers (40%) without pulmonary pathology. These defects were not observed in the analogous samples obtained from healthy nonsmoking individuals. No statistically significant differences were revealed between COPD patients and healthy smokers upon comparison of both the total number of molecular defects and the number of defects in the individual chromosomal loci. The total number of molecular defects revealed in bronchial epithelium samples from the individuals of two groups examined correlated with the intensity of exposure to tobacco smoke carcinogens (r = 0.28; P < 0.05). These findings suggest that rare alleles at theHras1 locus may be associated with hereditary predisposition to COPD and the development of pneumofibrosis, while mutations in microsatellite markers result from exposure to tobacco smoke carcinogens and are not associated with the appearance of these pathologies.

BackgroundNTMLD is a life-threatening pulmonary infection with increasing incidence and prevalence in Japan. It is associated with progressive lung damage and increased healthcare use. Many patients with NTMLD have comorbid respiratory conditions such as COPD. Treatment of NTMLD in patients with COPD is difficult, however there is limited data on the incremental burden that NTMLD adds to underlying COPD. We assessed the incremental burden associated with NTMLD in Japanese patients with COPD by comparing their hospitalizations to matched COPD patients without NTMLD.MethodsA retrospective cohort study was conducted using claims data provided by the Japan Medical Data Center (2015-2020). COPD patients with NTMLD were matched 1:3 to COPD patients without NTMLD (controls). Hospitalizations (all-cause, respiratory-related, and COPD-related) were accrued over a 1-year follow-up period after NTMLD diagnosis (index). Incremental burden of NTMLD was assessed by comparing hospitalizations between COPD patients with NTMLD and controls with univariate and multivariate analyses adjusting for comorbidities during 1-year pre-index period.ResultsA total of 492 COPD patients with NTMLD were matched by age and sex to 1476 controls. Mean (SD) age on index date was 56.6 (10.3) years and 61.4% were females. Compared to controls, NTMLD patients had higher prevalence of some pulmonary symptoms and comorbidities such as hemoptysis (11% vs 2%), dyspnea (1.6% vs 0.6%) and lung cancer (7% vs 4%). In univariate analyses, a higher percent of COPD patients with NTMLD had hospitalizations compared to controls (Fig 1A); the unadjusted annual hospitalization rates were also higher among patients with NTMLD (Fig 2A). Multivariate regressions after adjusting for pre-index comorbidities showed COPD patients with NTMLD were 1.9 times more likely to have an all-cause hospitalization, 2.8 times more likely to have a respiratory hospitalization, and 3.0 times more likely to have a COPD-related hospitalization (Fig 1B).ConclusionCOPD patients with NTMLD had a higher burden of hospitalization than COPD patients without NTMLD. The statistically significantly incremental burden associated with NTMLD in patients with COPD highlights the acute need for appropriate management of NTMLD in Japan.DisclosuresNaoki Hasegawa, MD, PhD, Insmed Incorporated (Consultant, Scientific Research Study Investigator)Janssen Pharmaceuticals Inc (Consultant, Scientific Research Study Investigator) Kozo Morimoto, MD, Insmed Incorporated (Consultant) Ping Wang, PhD, Insmed Incorporated (Employee) Lu Zhang, PhD, Panalgo (Employee, Other Financial or Material Support, Lu Zhang is an employee of Panalgo which provides the analytic platform Instant Health Data that is used by Insmed) Mariam Hassan, PhD, B. Pharm, Insmed Incorporated (Employee) Anjan Chatterjee, MD, MPH, Insmed Incorporated (Employee)

Respiratory disorders in sulfur mustard (SM)-exposed and chronic obstructive pulmonary disease (COPD) patients are mostly associated with neutrophilic inflammation, severe airflow limitation, and oxidative stress. The objective of this study was to establish whether neutrophil (PMN) proteomes in these diseases were similar or differed. Blood neutrophil proteomes from healthy, SM-exposed, and COPD subjects were analyzed using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS). Elastase activity was determined kinetically. The results showed that levels of S100 calcium-binding protein (CBP) A12, S100 CBP A8, glyceraldehyde-3-phosphate dehy-drogenase, superoxide dismutase, and protein disulfide isomerase proteins – as well as elastase activity – were significantly increased in PMN from ‘diseased’ hosts compared to in cells from healthy controls. In contrast, coactosin-like protein, RhoGDP dissociation inhibitor, and actin isoforms were significantly decreased in diseased subjects’ PMN compared to PMN of healthy controls. Moreover, serpin B1 and coronin-1A were expressed only in PMN of the healthy subjects. Lastly, S100 CBP A9, endoplasmic reticulum (ER)-60 protease, and glutathione-S-transferase isoforms were differentially expressed in the cells from the SM-exposed and COPD subjects. These results show that serpin B1, an efficient inhibitor of neutrophil serine proteases, was not detectable, and elastase activity significantly increased in PMN from both SM-exposed and COPD patients. It seems that, apart from inflammation and oxidative stress, a protease:anti-protease imbalance exists within PMN of both COPD and SM-exposed patients.

Association between Chronic Obstructive Pulmonary Disease and Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome

Exhaled breath condensate levels of 8-isoprostane, growth related oncogene α and monocyte chemoattractant protein-1 in patients with chronic obstructive pulmonary disease

Objective To explore the relationship between fat-free mass (FFM) and peak exercise performance in chronic obstructive pulmonary disease(COPD) patients. Methods 26 healthy subjects and 62 stable COPD patients performed incremental cardiopulmonary exercise testing with cycle ergometer. 62stable COPD patients were divided three groups(mild COPD,moderate COPD,severe COPD) according to FEV1%pred, peakVO2, peakLoad, peakO2 pulse, AT were measured during exercise. FFM and routine subjects, peakVO2 ,peakVO2 %pred,peakLoad,peakLoad%pred,peakO2 pulse,peakO2 pulse% pred and AT peakLoad%pred,AT and peakO2 pulse% pred ( r =0. 671,0. 478,0. 423,0. 618, P＜0. 05) in COPD patients.Conclusions FFM is significantly associated with muscle aerobic capacity and exercise tolerance in COPD patients. Key words: Fat-free mass; Chronic obstructive pulmonary disease; Cardiopulmonary exercise testing

The effect of coexisting chronic heart failure (CHF) in exercise ventilatory inefficiency in patients with COPD