Non-severe Chronic Obstructive Pulmonary Disease Research Articles

Paraoxonase 1 and Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

Oxidative stress is a driving factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). While paraoxonase 1 (PON1) is an antioxidant enzyme and a potential biomarker of this disease, data regarding the status of PON-1 in COPD are inconclusive. In this regard, to shed light on this issue, we performed a meta-analysis of data on PON1 activity in COPD. Electronic databases (MEDLINE, Embase and CENTRAL) were searched for available studies on PON1 activity in patients with stable COPD published before October 2021. A meta-analysis was performed using random-effects models. Twelve studies (12 studies on paraoxonase and three on arylesterase) were identified. Patients with COPD had lower levels of paraoxonase activity (standard mean difference [SMD] −0.77, 95% confidence interval [CI] −1.35 to −0.18) and arylesterase activity (SMD −1.15, 95% CI −1.95 to −0.36) in comparison to healthy controls. In subgroup analyses, paraoxonase activity was lower in patients of studies as consisted of mainly non-severe COPD (SMD −1.42, 95% CI −2.04 to −0.79) and, by contrast, slightly higher in patients of studies including severe COPD (SMD 0.33, 95% CI 0.02 to 0.64) in comparison to healthy controls. Arylesterase activity showed a similar trend. Overall, PON1 activity was lower in patients with COPD, suggesting that PON1-related antioxidant defense is impaired in COPD. Future studies are warranted.

Left ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease as a step forward in cardiovascular comorbidome

Abstract Background Chronic obstructive pulmonary disease (COPD) augments the likelihood of having left ventricular diastolic dysfunction (LVDD) – precursor of heart failure with preserved ejection fraction (HFpEF). LVDD shares overlapping symptomatology (cough and dyspnea) with COPD. Purpose Our aim was to evaluate the predictive value of inflammatory, oxidative stress, cardio-pulmonary and echocardiographic parameters at rest for the diagnosis of stress LVDD in non-severe COPD patients, who complain of exertional dyspnea and are free of overt cardiovascular diseases. Methods A total of 104 COPD patients underwent echocardiography before cardio-pulmonary exercise testing (CPET) and 1–2 minutes after peak exercise. Patients were divided into two groups based on peak E/e': patients with stress induced left ventricular diastolic dysfunction (LVDD) - E/e' >15 (HFpEF) and patients LVDD (without HFpEF). CPET and echocardiographic parameters at rest were measured and their predictive value for stress E/e' was analysed. Markers for inflammation (resistin, prostaglandine E2) and oxidative stress (8-isoprostanes) were also determined. Results Stress induced LVDD occurred in 67/104 patients (64%). Those patients had lower work load, lower VO2 consumption, lower minute ventilation and higher VE/VCO2 slope in comparison to patients without. Except for prostglandine E2, none of the inflammatory, oxidative stress markers correlated to stress E/e'. The best independent predictors for HFpEF were RAVI, right ventricular parasternal diameter and RV E/A >0.75. Their combination predicted HFpEF with the accuracy of 91.2%. Conclusion There is a high prevalence of HFpEF in non-severe COPD with exertional dyspnea, free of overt cardiovascular disease. RAVI, right ventricular parasternal diameter and RV E/A >0.75 were the only independent clinical predictors of HFpEF. Funding Acknowledgement Type of funding sources: None.

Protective Role of Genetic Variants in HSP90 Genes-Complex in COPD Secondary to Biomass-Burning Smoke Exposure and Non-Severe COPD Forms in Tobacco Smoking Subjects.

Background: Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory disease characterized by airflow obstruction, commonly present in smokers and subjects exposed to noxious particles product of biomass-burning smoke (BBS). Several association studies have identified single-nucleotide polymorphisms (SNP) in coding genes related to the heat shock proteins family-genes that codify the heat shock proteins (Hsp). Hsp accomplishes critical roles in regulating immune response, antigen-processing, eliminating protein aggregates and co-activating receptors. The presence of SNPs in these genes can lead to alterations in immune responses. We aimed to evaluate the association of SNPs in the HSP90 gene complex and COPD. Methods: We enrolled 1549 participants, divided into two comparison groups; 919 tobacco-smoking subjects (cases COPD-TS n = 294 and, controls SWOC n = 625) and 630 chronic exposed to BBS (cases COPD-BBS n = 186 and controls BBES n = 444). We genotyped 2 SNPs: the rs13296 in HSP90AB1 and rs2070908 in HSP90B1. Results: Through the dominant model (GC + CC), the rs2070908 is associated with decreased risk (p < 0.01, OR = 0.6) to suffer COPD among chronic exposed BBS subjects. We found an association between rs13296 GG genotype and lower risk (p = 0.01, OR = 0.22) to suffer severe COPD-TS forms in the severity analysis. Conclusions: single-nucleotide variants in the HSP90AB1 and HSP90B1 genes are associated with decreased COPD risk in subjects exposed to BBS and the most severe forms of COPD in tobacco-smoking subjects.

Left ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease - a step forward in cardiovascular comorbidome.

Chronic obstructive pulmonary disease (COPD) augments the likelihood of having left ventricular diastolic dysfunction (LVDD)-precursor of heart failure with preserved ejection fraction (HFpEF). LVDD shares overlapping symptomatology (cough and dyspnea) with COPD. Stress induced LVDD is indicative of masked HFpEF. Our aim was to evaluate the predictive value of inflammatory, oxidative stress, cardio-pulmonary and echocardiographic parameters at rest for the diagnosis of stress LVDD in non-severe COPD patients, who complain of exertional dyspnea and are free of overt cardiovascular diseases. A total of 104 COPD patients (26 patients with mild and 78 with moderate COPD) underwent echocardiography before cardio-pulmonary exercise testing (CPET) and 1-2 minutes after peak exercise. Patients were divided into two groups based on peak average E/e': patients with stress induced left ventricular diastolic dysfunction (LVDD)-E/e' > 15 masked HFpEF and patients without LVDD-without masked HFpEF. CPET and echocardiographic parameters at rest were measured and their predictive value for stress E/e' was analysed. Markers for inflammation (resistin, prostaglandine E2) and oxidative stress (8-isoprostanes) were also determined. Stress induced LVDD occurred in 67/104 patients (64%). Those patients showed higher VE/VCO2 slope. None of the CPET parameters was an independent predictor for stress LVDD.Except for prostglandine E2, none of the inflammatory or oxidative stress markers correlated to stress E/e'. The best independent predictors for stress LVDD (masked HFpEF) were RAVI, right ventricular parasternal diameter and RV E/A >0.75. Their combination predicted stress LVDD with the accuracy of 91.2%. There is a high prevalence of masked HFpEF in non-severe COPD with exertional dyspnea, free of overt cardiovascular disease. RAVI, right ventricular parasternal diameter and RV E/A >0.75 were the only independent clinical predictors of masked HFpEF. 288.

Autonomic dysfunction, cardio-pulmonary parameters and masked heart failure in non-severe chronic obstructive pulmonary disease

Въведение: Автономната дисфункция (АД) и параметрите при кардиопулмоналното тестване (КПТ) се асоциират със сърдечна недостатъчност със запазена систолна функция (heart failure with preserved ejection fraction – HFpEF) в общата популация. При пациенти с нетежка хронична обструктивна белодробна болест (ХОББ) тяхното клинично значение и връзка с маскираната HFpEF е неизяснено. Цел: Целта на проучването е да се определят връзката и клиничното значение на АД и кардиопулмоналните параметри с HFpEF при пациенти с нетежък ХОББ, които се оплакват от задух при усилие, без клинично изявено сърдечно-съдово заболяване (ССЗ) (исхемична болест, сърдечна недостатъчност, неконтролирана артериална хипертония). Методи и резултати: При 68 пациенти с нетежък ХОББ без изявено ССЗ е приложено КПТ. Проведена е ехокардиография в покой и 1-2 минути след натоварването. Пациентите са разделени на две групи въз основа на стрес-индуцираното съотношение E/e’: пациенти с левокамерна диастолна дисфункция (ЛКДД) – E/e’ > 15 (пациенти с маскирана HFpEF) и пациенти без стрес-ЛКДД (пациенти без маскирана HFpEF). Хронотропната недостатъчност включва намаления индекс на хронотропен отговор (ИХО Заключение: Неправилното възстановяване на сърдечната честота след натоварването е единственият независим предиктор за маскирана HFpEF при пациенти с нетежък ХОББ. По-ниските нива на ’VO2, кислороден пулс, физическо натоварване, както и по-високото ’VE/’VCO2 съотношение се асоциират с маскирана HFpEF, като вероятно са нейно последствие, а не тригер. Background: Autonomic dysfunction (AD) and cardio-pulmonary exercise testing (CPET) parameters have been associated with masked heart failure with preserved ejection fraction (HFpEF) in the general population. Their clinical significance for masked HFpEF in chronic obstructive pulmonary disease (COPD) is however elusive. Aim: The aim of the study was to determine the prevalence, correlation and clinical significance of AD and CPET with masked HFpEF, in non-severe COPD patients, complaining of exertional dyspnea, without clinically overt cardio-vascular (CV) comorbidities (ischaemic heart disease, heart failure, uncontrolled arterial hypertension). Methods and results: We applied CPET and echocardiography in 68 COPD subjects. Echocardiography was performed before CPET and 1-2 minutes after peak exercise. Patients were divided into two groups: patients with and without masked HFpEF. Peak E/e’ – 15 was applied as a cut-off. Chronotropic incompetence (CI) was assumed if both failure to reach the target heart rate (HR) on exercise and diminished heart rate reserve Conclusion: Abnormal HRR is the only independent predictor of masked HFpEF in non-severe COPD patients. Despite of being associated with masked HFpEF, the lower ’VO2, lower oxygen pulse, higher ’VE/’VCO2 slope and lower exercise load seem to be the consequences, rather than the triggers for it.

Prescribing Pathways to Triple Therapy: A Retrospective Observational Study of Adults with Chronic Obstructive Pulmonary Disease in the UK.

PurposeTreatment guidance for chronic obstructive pulmonary disease (COPD) recommends inhaled corticosteroid (ICS)+long-acting muscarinic antagonist+long-acting β2-agonist (LABA) triple therapy for patients who experience recurrent exacerbations, persistent breathlessness, or exercise limitation on dual therapy. However, information is limited on pathways to triple therapy in the UK.Patients and MethodsA retrospective cohort study was conducted using de-identified patient-level data from UK primary care electronic medical records from January 1, 2005 to May 1, 2016. Data were included from patients who had their first triple therapy regimen (index date) recorded during the study period and a minimum of 12 months’ pre-index data. Treatment pathways to triple therapy were recorded, and the proportion of patients on triple therapy before their COPD diagnosis was determined. Adherence to triple therapy was estimated using the proportion of days covered (PDC).ResultsAfter applying eligibility criteria, 82,300 patients were included, with a mean age at COPD diagnosis of 64.7 years. The major treatment pathway (27.9%) was the first initiation of ICS+LABA prior to triple therapy. Following COPD diagnosis, the median time to triple therapy was approximately 3.5 years. The estimated mean adherence to triple therapy was 81.8% PDC. Multivariate analysis showed that the following groups were more likely to have received previous therapy prior to triple therapy: females (versus males), patients with asthma (versus those without asthma), severe COPD (versus those with non-severe COPD), or fewer exacerbations (versus those with more exacerbations).ConclusionTreatment pathways to triple therapy in the UK are diverse, highlighting the need to better understand factors involved in clinical decision-making.

Cardio-pulmonary-exercise testing, stress-induced right ventricular diastolic dysfunction and exercise capacity in non-severe chronic obstructive pulmonary disease

Abstract Background Data regarding echocardiographic structural and functional abnormalities in right ventricular diastolic dysfunction (RVDD), cardio-pulmonary exercise testing (CPET) abnormalities and their association with exercise capacity among non-severe chronic obstructive pulmonary disease (COPD) patients without pulmonary arterial hypertension (PAH) at rest is limited. Purpose The aim of the study was to find echocardiographic parameters of the right ventricle that may be predictors for stress RVDD in non-severe COPD patients without PAH and to determine their correlation with the 6-minute walking test (6-MWT). Methods We applied a ramp protocol of CPET in 104 patients. Dynamic hyperinflation (ICdyn) was measured. Emphysema was evaluated by Goddard score. Echocardiography was performed before and 1–2 minutes after peak CPET. Stress RVDD was assumed if peak E/e'&amp;gt;6.0. Exercise capacity was evaluated by the 6-MWT. ROC analysis detected the best cut-off values of the RV echocardiographic predictors for stress RVDD. Multivariate analysis with covariates left ventricle (LV) (LV E/A at rest; LV E/e' at rest; stress LV E/A; stress LV E/e'), lung function (FEV1), ICdyn, Goddard score, age, sex, and BMI was performed. A p-value &amp;lt;0.05 was accepted of statistical significance. Results 78% of the patients had stress RVDD. RV wall thickness (RVWT), right atrial volume index (RAVI) and exercise systolic PAH were significantly higher in COPD patients with stress RVDD. After multivariable regression analysis RAVI and rest RV E/e' ratio &amp;gt;5.1 remained independent predictors for stress RVDD; RAVI and RVWT were independent predictors for diminished exercise capacity (6-MWT). Conclusion There is a high prevalence of stress induced RVDD in non-severe COPD patients without PAH at rest. RAVI and rest RV E/e'&amp;gt;5.1 are the best predictors for stress E/e' &amp;gt;6; RAVI and RVWT are associated with decrements in exercise capacity. Funding Acknowledgement Type of funding source: None

Echocardiographic predictors for stress induced right ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease

Background: Pulmonary vasculopathy, right heart structural and functional abnormalities occur even in normoxemic chronic obstructive pulmonary disease patients. Despite of being associated with functional limitation, exacerbations and disease progression, their detection and proper management is still delayed. Aim: Our aim was to establish the frequency of stress induced right ventricular diastolic dysfunction (RVDD) in non-severe COPD patients, free of clinically overt cardiovascular diseases (ischaemic heart disease, heart failure, uncontrolled arterial hypertension), who complain of exertional dyspnea and to look for echocardiographic predictors of it. Materials and method: We applied cardio-pulmonary exercise testing (CPET) in 104 non-severe, COPD patients. A ramp protocol was performed. Echocardiography was done before and 1-2 minutes after peak exercise. Cut-off values for stress induced RVDD were right ventricular (RV) E/e’ ratio &gt; 6, measured by PWD of the tricuspid valve. Receiver operating curves were constructed for echo parameters at rest to determine if any of them may discriminate stress induced RV E/e’ &gt; 6 or &amp;лt; 6. Uni- and multivariable linear regression analysis was also performed to assess the predictive power of each of them. Results: 78% of the patients had stress induced RVDD. RAVI (cut-off &gt; 20.55 ml/m2; sensitivity – 86%; specifi city – 86%), RVWT (cut-off &gt; 5.25 mm; sensitivity – 100%; specifi city – 63%) and RV E/A ratio at rest (cut-off &gt; 1.05; sensitivity – 79.7%; specifi city – 90.5%) were the best predictors of stress RV E/e. In univariate regression analysis RV E/A showed the highest OR 19.73; (95% CI – 18.52-21.01); followed by RAVI – OR 3.82; (95% CI – 2.04-7.14). Conclusion: There is a high prevalence of stress induced RVDD in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. RAVI, RVWT, RV E/A and RV E/e’ ratio at rest may be used as predictors for stress RVDD and may facilitate patients’ risk stratifi cation and proper management.

Cardio-pulmonary-exercise testing, stress-induced right ventricular diastolic dysfunction and exercise capacity in non-severe chronic obstructive pulmonary disease

Cardio-pulmonary-exercise testing, stress-induced right ventricular diastolic dysfunction and exercise capacity in non-severe chronic obstructive pulmonary disease

The link between dynamic hyperinflation, autonomic dysfunction and exercise testing parameters with masked heart failure in patients with non-severe obstructive pulmonary disease.

Autonomic dysfunction (AD) and dynamic hyperinflation (DH) have been implicated as pathophysiological mechanisms of heart failure with preserved ejection fraction (HFpEF) in chronic obstructive pulmonary disease (COPD) patients. Their association, however, remains elusive: The aims of the study were: (1) to determine the prevalence of AD and DH in non-severe COPD patients, with exertional dyspnea, without clinically overt cardio-vascular (CV) comorbidities; (2) to analyze the correlation and clinical significance between DH, AD, and maksed HFpEF. We applied CPET in 68 subjects. Echocardiography was performed before CPET and 1-2min after peak exercise. IC manoeuvres were applied. Patients were divided into two groups: patients with and without masked HFpEF. Wilkoff method calculated the meatabolic -chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined. The prevalence of CI was 77 vs. 52% in patients with/without masked HFpEF; of abnormal HRR -98 vs. 62% respectively; of DH -53 vs. 29%. ICdyn was associated with AD. Univariate regression showed association between masked HFpEF, ICdyn, HRR, oxygenuptake ('VO2), 'VO2 at anaerobic threshold, oxygen (O2) pulse and 'VE/'VCO2 slope. None of these parameters is an independent predictor for masked HFpEF. DH, AD, and masked HFpEF are prevalent in non-severe COPD patients, who complain of exertional dyspnea and are free of clinically overt CV comorbidities. DH is independently associated with AD. Neither AD, nor DH and CPET are independent predictors for masked HFpEF.

Right Atrium Volume Index in Non-Severe Chronic Obstructive Pulmonary Disease

Abstract Introduction: Right atrium volume index (RAVI) has recently been reported as a quantitative echocardiographic parameter associated with right ventricular systolic dys-function (RVSD) in patients with pulmonary arterial hypertension (PAH) due to chronic obstructive pulmonary disease (COPD). Aims: The aim of the current study was to assess right atrium remodeling (RAVI) in COPD patients without echocardiographic parameters of RVSD or PAH at rest and to analyse its association with right ventricular diastolic dysfunction (RVDD) at rest and after exercise – stress-induced RVDD. Methods: The study was conducted in 104 COPD patients. Pulmonary function tests, blood gas analysis, incremental, symptom-limited cardio-pulmonary test (CPET) protocol and detailed echocardiographic examinations before and 2-3 minutes after peak CPET were applied. The cut-offvalues for stress-induced RVDD were E/e’ &gt; 6.0. Results: Patients were divided into two groups: patients with stress-induced RVDD (82/104 – 78%) and those without stress-RVDD (22/104 – 22%). RAVI was significantly higher in the group with stress-induced RVDD (23,04 ± 2,67 ml/m2 vs 18,02 ± 2,69 ml/m2) in comparison to those without it. Correlation analysis showed that RAVI was associated with stress-induced RVDD (E/e’) and the distance from the 6 minute walk test (6-MWT), but was not an independent predictor for any of them. Conclusions: RAVI correlates with stress-induced RVDD parameters (E/e’) in non-severe COPD patients without pulmonary arterial hypertension at rest. It corresponds to the diminished distance from the 6-MWT, but was not an independent factor of reduced physical activity.

Echocardiographic predictors of stress induced right ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease

BackgroundPulmonary vasculopathy, right heart structural and functional abnormalities occur even in normoxemic chronic obstructive pulmonary disease (COPD) patients. Despite being associated with functional limitation, exacerbations, and disease progression, their detection and proper management is still delayed. AimOur aim was to establish the frequency of stress-induced right ventricular diastolic dysfunction (RVDD) in non-severe COPD patients, free of overt cardiovascular disease, who complain of exertional dyspnea and to look for echocardiographic predictors of it. Materials and methodsWe applied cardio-pulmonary exercise testing (CPET) in 104 non-severe, COPD patients. A ramp protocol was performed. Echocardiography was done before and 1−2 min after peak exercise. Cut-off values for stress induced RVDD were E/e’ >6. Receiver operating curves were constructed for echo parameters at rest to determine if any of them may discriminate stress induced RV E/e’>6 or <6. Uni- and multivariable linear regression analysis was also performed to assess the predictive power of each of them. A p-value < 0.05 was considered significant. ResultsA total of 78% of the patients had stress-induced RVDD. Right atrium volume index (RAVI) (cut-off >20.55 ml/m2; sensitivity - 86%; specificity - 86%), RV wall thickness (RVWT) (cut-off >5.25 mm; sensitivity - 100%; specificity - 63%), and RV E/A ratio at rest (cut-off >1.05; sensitivity - 79.7%; specificity - 90.5%) were the best predictors of stress RV E/e. In univariate regression analysis E/A showed the highest OR 19.73 (95% CI – 18.52–21.01); followed by RAVI - OR 3.82; (95% CI – 2.04–7.14). ConclusionThere is a high prevalence of stress-induced RVDD in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. RAVI, RVWT, E/A, and E/e’ ratio at rest may be used as predictors for stress RVDD and may facilitate patients’ risk stratification and proper management.

Autonomic dysfunction, cardio-pulmonary exercise testing and masked heart failure with preserved ejection fraction in non-severe chronic obstructive pulmonary disease.

Autonomic dysfunction (AD) and cardiopulmonary exercise testing (CPET) parameters have been associated with masked heart failure with preserved ejection fraction (HFpEF) in the general population. Their clinical significance for masked HFpEF in chronic obstructive pulmonary disease (COPD) is however elusive. The aim of the study was to determine the prevalence, correlation and clinical significance of AD and CPET with masked HFpEF, in non-severe COPD patients, complaining of exertional dyspnoea, without clinically overt cardio-vascular (CV) comorbidities. We applied CPET and echocardiography in 68 COPD subjects. Echocardiography was performed before CPET and 1-2min after peak exercise. Patients were divided into two groups: patients with and without masked HFpEF. Peak E/e' - 15 was applied as a cut-off. Chronotropic incompetence (CI) was assumed if both failure to reach the target heart rate (HR) on exercise and diminished heart rate reserve <80% occurred. Abnormal HR recovery (HRR) was taken if the decline is <12 beats within the first minute after exercise cessation. Univariate regression showed association between masked HFpEF, HRR, VO2, VO2 at AT, oxygen pulse and VE/VCO2 slope. The multivariate regression demonstrated HRR as the only independent predictor of masked HFpEF - (OR 10.28; 95% CI (3.55-29.80)). Abnormal HRR is the only independent predictor of masked HFpEF in non-severe COPD patients. Despite of being associated with masked HFpEF, the lower VO2, lower oxygen pulse, higher VE/VCO2 slope and lower exercise load seem to be the consequences, rather than the triggers for it.

P742 The role of oxidative stress and inflammation for stress induced right ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease patients

Abstract Background Oxidative stress and inflammation have been implicated in the pathogenesis of diastolic dysfunction (DD) and are both present in chronic obstructive pulmonary disease (COPD). Aim To evaluate the role of oxidative stress markers (8-isoprostane) and inflammation (prostaglandin E2, resistin) in the pathogenesis of stress induced right ventricular diastolic dysfunction (RVDD) in non-severe COPD. Materials and methods 104 patients with non-severe COPD (FEV1 &amp;gt; 50%) and preserved left ventricular ejection fraction &amp;gt;50% underwent incremental cardio-pulmonary exercise testing (CPET). Echocardiography was performed before CPET and 1-2 minutes after peak exercise. Peak E/e’ ratio &amp;gt; 6 was a marker for stress induced RVDD. Urine concentration of 8-isoprostanes was assumed as surrogate marker for oxidative stress; urine concentration of prostaglandine-E2 and plasma resistin levels as inflammatory markers. Mass spectrometry was applied for 8-isoprostane and prostglandine E2 (Cayman. Chemical) measurement. Values were normalised to urine creatinine (µmol/l/cre). ELISA was applied for resistin measurement (Raybio_Human) (ng/ml). Results Patients were divided into two groups: subjects with stress RVDD (82) and those without stress RVDD (22). In patients with and without RVDD the levels of 8-isoprostane were similar (30.78 vs 30.41µmol/l/cre). The urine concentration of prostaglandin E2 in patients with and without RVDD significantly differed (49.73 vs 62. 19µmol/l/cre; p &amp;lt; 0.05). The same is observed regarding resistin plasma levels - in patients with and without RVDD (18.91 vs 5.47ng/ml). Conclusions In non-severe COPD patients oxidative stress levels are similar in the studied groups. Inflammation (resistin) seems to be the predominant pathogenetic factor, associated with stress induced RVDD. The exact role of prostaglandine E2 for RVDD remains elusive.

P897 The role of oxidative stress and inflammation for stress induced left ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease patients

Abstract Background Oxidative stress and inflammation have been implicated in the pathogenesis of diastolic dysfunction (DD) and are both present in chronic obstructive pulmonary disease (COPD). Purpose To evaluate the role of oxidative stress markers (8-isoprostane) and inflammation (prostaglandin E2, resistin) in the pathogenesis of stress induced left ventricular diastolic dysfunction (LVDD) in non-severe COPD. Materials and methods 104 patients with non-severe COPD (FEV1 &amp;gt; 50%) and preserved left ventricular ejection fraction &amp;gt;50% underwent incremental cardio-pulmonary exercise testing (CPET). Echocardiography was performed before CPET and 1-2 minutes after peak exercise. Peak E/e’ ratio &amp;gt;15 was a marker for stress LVDD. Urine concentration of 8-isoprostanes was assumed as surrogate marker for oxidative stress; urine concentration of prostaglandine-E2 and plasma resistin levels as inflammatory markers. Mass spectrometry was applied for 8-isoprostane and prostglandine E2 (Cayman. Chemical) measurement. Values were normalised to urine creatinine (µmol/l/cre). ELISA was applied for resistin measurement (Raybio_Human) (ng/ml). Results Patients were divided into two groups: subjects with stress LVDD (67) and subjects without stress LVDD (37). 8-isoprostane levels were higher in subjects with LVDD vs those without LVDD (32.9 vs 29.67µmol/l/cre; p&amp;lt; 0.05). The same is observed regarding resistin plasma levels (22.51 vs 15.68ng/ml). Urine concentrations of prostaglandin E2 did not differ between the two groups (50.76 vs 51.07 µmol/l/cre) Conclusions In non-severe COPD patients the levels of oxidative stress (8-isoprostanes) and inflammation (resistin) seem to be associated with stress induced left ventricular diastolic dysfunction.

The 'right way' to the left chamber in non-severe COPD: Echocardiographic predictors for stress-induced left ventricular diastolic dysfunction.

Dyspnea is a major complaint of both chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction (HFpEF). It often remains underdiagnosed in COPD patients when only echocardiography at rest is performed. The aim of this study was to evaluate the predictive value of cardiopulmonary and echocardiographic parameters at rest for the diagnosis of HFpEF in non-severe COPD patients who complain of exertional dyspnea and have no overt cardiovascular disease. A total of 104 COPD patients underwent echocardiography before cardiopulmonary exercise testing (CPET) and 1-2 minutes after peak exercise. The patients were divided into 2 groups based on peak E/e' measurements: patients with masked HFpEF-stress and left ventricular diastolic dysfunction (LVDD; E/e'>15), and patients without masked HFpEF (without stress LVDD). CPET and echocardiographic parameters at rest were measured and the predictive value for stress E/e' was analyzed. Stress LVDD occurred in 67 of 104 patients (64%). These patients achieved a lower work load, lower 'VO2 consumption, lower minute ventilation, and higher 'VE/'VCO2 slope in comparison with patients without stress LVDD. None of the CPET values correlated with stress E/e'. The best independent predictors for stress LVDD were right atrium volume index (RAVI), right ventricle (RV) parasternal diameter, and RV E/A >0.75. The combination of these echocardiographic parameters predicted HFpEF with an accuracy of 91.2%. There is a high prevalence of stress LVDD in non-severe COPD patients with exertional dyspnea who remain free of overt cardiovascular disease. RAVI, RV parasternal diameter, and RV E/A >0.75 were the only independent predictors of stress LVDD.

The Burden Of Chronic Obstructive Pulmonary Disease (COPD) In Finland: Impact Of Disease Severity And Eosinophil Count On Healthcare Resource Utilization.

PurposeThe burden associated with chronic obstructive pulmonary disease (COPD) is substantial. The objectives of this study were to describe healthcare resource utilization (HCRU) and HCRU-associated costs in patients with COPD in Finland, according to disease severity and blood eosinophil count (BEC).Patients and methodsThis non-interventional, retrospective registry study (GSK ID: HO-17-17558) utilized data from the specialist care hospital register. Data extraction was from first hospital visit with a COPD diagnosis (index date) from January 1, 2004 until December 31, 2015 or death. Patients (aged >18 years with ≥1 report of post-bronchodilation forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7) were categorized as having non-severe or severe COPD (FEV1 >50% or ≤50% of reference, respectively). Patients who were initially non-severe but progressed to severe were classified as having progressing COPD. Patients without spirometry registry data were classified as having clinically verified COPD. Patients were grouped according to BEC (≥300 cells/μL, <300 cells/μL or BEC unknown). HCRU, estimated associated costs and mortality were evaluated according to COPD severity and BEC.ResultsThere were 9042 patients with COPD; 340 non-severe, 326 progressing, 394 severe, and 7982 clinically verified. BEC was available for 31.8% of patients. The mean follow-up time was 3.7–6.5 years in the classified patient-groups. All-cause mortality was 46% during follow-up. Severe COPD was associated with more COPD-related HCRU and higher mortality than non-severe COPD. Patients with BEC ≥300 cells/μL had higher overall HCRU but improved survival compared with those with BEC <300 cells/μL. Overall direct costs were similar across COPD severity categories, 3300–3900€/patient-year, although COPD-related costs were higher in patients with severe versus non-severe COPD.ConclusionThis study demonstrated a substantial burden associated with severe and/or eosinophilic COPD for patients in Finland.

Stress echocardiography for left ventricular diastolic dysfunction detection in patients with non-severe chronic obstructive pulmonary disease: a cross-sectional study

AimTo assess whether the simultaneous performance of exercise stress echocardiography and cardio-pulmonary testing (ESE-CPET) may facilitate the timely diagnosis of subclinical left ventricular diastolic dysfunction (LVDD) in patients with non-severe chronic obstructive pulmonary disease (COPD), preserved left ventricular systolic function, and exertional dyspnea or exercise intolerance.MethodsThis cross-sectional study, conducted between May 2017 and April 2018, involved 104 non-severe COPD patients with exertional dyspnea and preserved ejection fraction who underwent echocardiography before CPET and 1-2 minutes after peak exercise. Based on the peak E/e’ ratio, patients were divided into the group with stress-induced LVDD – E/e’>15 and the group without stress-induced LVDD. We assessed the association between LVDD and the following CPET variables: minute ventilation, peak oxygen uptake (VO2), ventilatory efficiency, heart rate reserve, and blood pressure.ResultsDuring ESE-CPET, stress-induced LVDD occurred in 67/104 patients (64%). These patients had lower work load, peak VO2, O2 pulse, and minute ventilation (VE), and higher VE/VCO2 slope than patients without stress-induced LVDD (35.18 ± 10.4 vs 37.01 ± 11.11, P < 0.05). None of the CPET variables correlated with E/e’.ConclusionCombined ESE-CPET may distinguish masked LVDD in patients with non-severe COPD with exertional dyspnea and preserved left ventricular systolic function. None of the CPET variables was a predictor for subclinical LVDD.

ANALYSIS OF PULMONARY-RELATED CLINICAL MANIFESTATIONS AND HEALTH RESOURCE UTILIZATION IN PATIENTS WITH SEVERE AND NON-SEVERE ALPHA-1 ANTITRYPSIN DEFICIENCY IN THE UNITED STATES

SESSION TITLE: Monday Electronic Posters 1 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Pulmonary manifestations (PM) of alpha-1 antitrypsin deficiency (AATD) can inflict a severe clinical course for patients and require increased healthcare resource use (HRU). This study aimed to describe the real-world burden of AATD with PM in the U.S. METHODS: Patient-level healthcare claims from the Truven Health MarketScan® database were retrospectively analyzed. Patients with a second primary diagnosis of AATD between 6/1/2008-12/31/2017 and continuous enrollment in the 6 months preceding the second diagnosis date were included. Patient characteristics and AATD-associated PM events of Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, emphysema and bronchiectasis were assessed among all identified patients. All-cause HRU was assessed separately among patients with severe PM (≥1 event with hospitalization within 1 calendar day) and non-severe PM (events with no hospitalization within 1 calendar day). Incidence rates (IR) and associated 95% confidence intervals (CI) of the defined PM and HRU were measured from day 1 after the date of hospital discharge for severe events and the date of first PM event claim for non-severe events to the end of data or continuous eligibility. IR were summarized descriptively and compared using standardized differences (d). RESULTS: Of 5109 cases, 2674 (52.3%) had ≥1 of the defined PM events. Severe AATD patients (N=711) were older (mean age 57.9 vs 52.8 years; d=0.37) vs non-severe patients (N=1963), had a greater baseline morbidity (higher mean CCI score [2.2 vs 1.4; d=0.497]), had a higher prevalence of baseline COPD (75.8% vs 56.9%; d=0.41) and emphysema (33.8% vs 23.8%; d=0.22), and increased hospitalization frequency (mean 0.7 vs 0.13; d=0.70). Pulmonary exacerbations were the most frequent manifestation. IR for severe exacerbations was 522.4 (95% CI: 485.4-562.2) and 231.6 (221.6-242.1) for non-severe per 100 person-years. The IR for severe and non-severe COPD, chronic bronchitis, emphysema, and bronchiectasis were: 234.5 [216.8-253.6] and 82.3 [78.2-86.6], 65.9 [60.4-71.8] and 26.6 [24.8-28.4], 46.8 [42.5-51.6] and 20.4 [18.9-22.0], and 7.9 [6.6-9.5] and 4.3 [3.7-5.0] per 100 person-years respectively. Patients with severe PE had intensified HRU based on significantly higher mean annual frequencies of emergency room (1.2 vs 0.5; d=0.16), inpatient (1.3 vs 0.08; d=0.68), outpatient (10.3 vs 6.4; d=0.28), other visits (4.0 vs 2.0; d=0.21), and significantly longer hospitalizations (mean, 8.8 days vs 5.4 days; d=0.49). CONCLUSIONS: Patients with severe AATD-related PM requiring hospitalization are substantially burdened by more frequent events, more severe clinical course and higher HRU. CLINICAL IMPLICATIONS: These findings characterize patients with pulmonary-related AATD and highlight the importance of strategies to reduce the frequency and severity of PM through disease modification. DISCLOSURES: Employee relationship with Takeda Pharmaceuticals Please note: >$100000 Added 03/18/2019 by Emily Brouwer, source=Web Response, value=Stocks Employee relationship with Takeda Please note: >$100000 Added 03/18/2019 by Emily Brouwer, source=Web Response, value=Salary Employee relationship with Takeda Pharmaceuticals Please note: $1-$1000 Added 03/15/2019 by Corey Joseph, source=Web Response, value=I am an employee of Takeda Employee relationship with Takeda Pharmaceutical Company Limited Please note: >$100000 Added 03/12/2019 by Ernesto Mayen Herrera, source=Web Response, value=Salary

Blood global DNA methylation is decreased in non-severe chronic obstructive pulmonary disease (COPD) patients

BackgroundAlterations in global DNA methylation have been associated with oxidative stress (OS). Since chronic obstructive pulmonary disease (COPD) is characterized by increased oxidative stress we aimed to evaluate the levels of global DNA methylation in this patient group. MethodsWe assessed methylcytosine (mCyt) levels in DNA from blood collected in 43 COPD patients (29 with mild and 14 with moderate disease) and 43 age- and sex-matched healthy controls. ResultsDNA methylation was significantly lower in COPD patients vs. controls (4.20 ± 0.18% mCyt vs. 4.29 ± 0.18% mCyt, p = 0.02). Furthermore, DNA methylation in COPD patients with moderate disease was significantly lower than that in patients with mild disease (4.14 ± 0.15% mCyt vs. 4.23 ± 0.19% mCyt, p < 0.05). Univariate logistic regression analysis showed that lower DNA methylation levels were associated with presence of COPD (crude OR = 0.06, 95% CI 0.00 to 0.67, p = 0.023). This relationship remained significant after adjusting for several confounders (OR 0.03, 95% CI 0.00 to 0.67; p = 0.028). Receiver operating characteristics (ROC) curve analysis demonstrated the area under the curve of mCyt was 0.646, with 46.6% sensitivity and 79.1% specificity for presence of COPD. ConclusionsThere were no significant correlations between methylation and OS indices. The presence and severity of COPD is associated with progressively lower DNA methylation in blood. However, this epigenetic alteration seems independent of oxidative stress.