Intensity Of Systemic Inflammation Research Articles

The improvement of endothelial function by inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension

In accordance with modern ideas about the pathogenesis of thrombotic complications of cardiovascular diseases (myocardial infarction, stroke), it should be noted that platelets and platelet humoral factors play a key role in the development of thrombosis. Activated platelets are able to activate both endotheliocytes and pro-inflammatory cells - monocytes/macrophages, which take a direct part in the formation and progression of atherosclerotic plaque. The purpose of the study is to investigate the potential improvement of endothelial function through the inhibition of platelet activity using acetylsalicylic acid in patients with arterial hypertension and established atherosclerotic cardiovascular diseases. Materials and methods. We enrolled 41 patients with arterial hypertension and established atherosclerotic cardiovascular diseases in our study. The participants were divided into two groups. Group 1 comprised 20 patients who were already taking acetylsalicylic acid (ASA) before the study, while Group 2 consisted of 21 patients who had not received ASA before participating. During the 6-month study period, patients from both groups received ASA (75 mg once a day) as part of their basic therapy, which included antihypertensive and statin therapy. Platelet activity was assessed in all patients before the study and at the final stage by determining the expression of glycoproteins GPIIb-IIIa and P-selectin on their surface. Additionally, the content of endothelial progenitor cells (phenotype CD45-CD31+CD133+) and desquamated endothelial cells (phenotype CD45-CD31+CD133-) in the blood was analyzed using flow cytometry. ELISA was employed to measure the content of C-reactive protein, cytokines TNF-α and IL-10, as well as asymmetric dimethylarginine (ADMA) in the blood. Finally, all patients underwent a test with flow-dependent vasodilation of the brachial artery. Results. In patients who did not receive ASA before the study, there was a higher level of platelet activity in peripheral blood flow, along with signs of more pronounced endothelial dysfunction compared to those who received it. After 6 months of taking ASA alongside standard antihypertensive therapy, the activation level of circulating blood platelets decreased in both groups. Specifically, in patients of group 1, the expression level of CD41 (GPIIb) decreased by 31.8 % (p < 0.01), and CD61 (GPIIIa) decreased by 15.2 % (p < 0.01). In group 2 patients, the suppression of platelet activity was even more pronounced, with the expression level of CD41 (GPIIb) decreasing by 55.2 % (p < 0.001), and CD61 (GPIIIa) decreasing by 27.5 % (p < 0.05). Furthermore, in patients of group 1, the percentage of platelets carrying P-selectin on the surface decreased by 78.1 % (p < 0.01). In group 2, the number of such platelets also significantly decreased by 42.5 % (p < 0.05). The number of progenitor cells of endothelial cells in the circulating blood increased significantly in both groups, showing a 3-fold increase in patients of group 1 (p < 0.001) and a 2.3-fold increase in patients of group 2 ( p< 0.001). In patients of both groups, a significant 2-fold increase in the endothelium-dependent vasodilatation index was observed (p < 0.01). At the end of the study, there was a decrease in the blood level of CRP by 12.2 % and 18.8 %, and pro-inflammatory cytokine TNF-α decreased by 50% and 57 %, respectively, in patients of groups 1 and 2 (p < 0.001). Conclusion. The reduction in blood platelet activity triggered by ASA in patients with arterial hypertension and atherosclerotic cardiovascular diseases was associated with notable alterations in the intensity of systemic inflammation and the restoration of endothelial functions. These findings suggest a potential therapeutic role for ASA in modulating both platelet function and endothelial health in individuals with these conditions.

Diabetes mellitus in rheumatic diseases: clinical characteristics and treatment considerations.

New pathophysiological insights are now available on comorbidities in rheumatic diseases (RDs). Several nationwide studies point to the fact that comorbid diabetes mellitus (DM) increases the risk of adverse outcomes in patients with various RDs. Genetic factors, intensity of systemic inflammation, anti-inflammatory potential of therapeutic agents, and duration of RDs have been insufficiently explored in the context of comorbidities. Some disease-modifying antirheumatic drugs (DMARDs) have demonstrated a potential to improve the glycemic control while glucocorticoids (GCs) have worsened it, particularly in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Anti-TNFalpha agents in combination with hydroxychloroquine (HCQ) have been associated with a reduced risk of DM in patients with RA, ankylosing spondylitis (AS), Sjögren syndrome (SS), and SLE. Better understanding of confounding factor of currently available antirheumatic therapies in patients with DM and RDs willpave the way for a tailored approach, limiting the severity of clinical manifestations and reducing the mortality risk.

Cardiovascular issues in rheumatic diseases.

Cardiovascular disease is a major cause of morbidity and mortality in rheumatic diseases, particularly rheumatoid arthritis and systemic lupus erythematosus. Timely detection and monitoring of cardiovascular affections by advanced visualization techniques may improve outcomes across most rheumatic diseases. Although high-grade inflammation and (auto)immune pathways are well known for their negative effects on the heart and vasculature, cardiovascular risk estimation remains one of the unresolved critical issues in rheumatic diseases. The issue is complicated further in view of the latest reports on enhanced atherogenesis in the setting of fibromyalgia and osteoarthritis, where inflammation is seemingly not a major pathogenic factor. The intensity of systemic inflammation has been associated with major vascular events in some large cohort studies of inflammatory rheumatic diseases. Experts advocate for tight control of systemic inflammation and modifiable cardiovascular risk factors for reducing the overall risk of vascular events. Increasing patients' and specialists' knowledge and skills in cardiovascular monitoring and prevention is warranted to solve some of the cardiovascular issues in rheumatic diseases. Key Points • Cardiovascular issues are prevalent across all age groups of patients with rheumatic diseases. • Large cohort studies suggest that the intensity of systemic inflammation is a powerful predictor of vascular events in rheumatic diseases. • Reliable and widely tested tools for predicting vascular events in inflammatory rheumatic diseases are currently unavailable. • Empowering patients with rheumatic diseases and first-contact specialists with knowledge and skills to monitor and reduce cardiovascular risk factors' effects is a promising strategy.

The intensity of oxidative stress and systemic inflammation in patients with a combination of bronchial asthma and chronic obstructive pulmonary disease

Background. Chronic obstructive pulmonary disease and bronchial asthma, when combined in one patient, are characterized by a low level of control. Excess weight aggravates the course of obstructive diseases. The study of the features of this syntropy will improve the effectiveness of therapeutic measures.
 Aim. The study of the level of cytokines and carbonylated proteins in patients with a combination of bronchial asthma and chronic obstructive pulmonary disease with overweight and normal weight during an exacerbation.
 Material and methods. The study included 136 people: the first group a combination of bronchial asthma and chronic obstructive pulmonary disease (n=30), the second bronchial asthma (n=36), the third chronic obstructive pulmonary disease (n=29), the fourth volunteers without respiratory diseases (n=41). Each group was divided into two subgroups depending on the body mass index (less than 25 kg/m2 or 25 kg/m2 and more). The concentrations of interleukins-6 and -8, tumor necrosis factor in blood plasma were determined by enzyme immunoassay. The level of carbonylated plasma proteins was assessed spectrophotometrically. Statistical processing was performed in the Statistica 10.0 program using nonparametric criteria. The correlation of the studied parameters was assessed using the Spearman coefficient.
 Results. In patients with a combination of bronchial asthma and chronic obstructive pulmonary disease, statistically significant positive correlations between the levels of interleukins-6 and -8, tumor necrosis factor and carbonylated proteins were found 0.51, 0.59 and 0.55, respectively (p 0.05). Patients of the first group with overweight differed by 37.5% in higher levels of interleukin-6 compared with patients with body mass index 25 kg/m2.
 Conclusion. The intensity of systemic inflammation in patients with a combination of bronchial asthma and chronic obstructive pulmonary disease during exacerbation correlates with the intensity of oxidative damage.

Methodological bases for assessing the nutritional behavior of the population and the intensity of systemic inflammation

<h3></h3> Пищевые привычки и диета играют значительную роль в модуляции хронического системного воспаления. Привычки, связанные с питанием, являются многомерными величинами с тесными внутренними корреляциями. Сложность оценки влияния факторов может быть упрощена с помощью диетических индексов, которые количественно оценивают диетические различия в одном показателе и предлагают средства контроля рациона питания в клинических исследованиях. В данной обзорной статье рассмотрены особенности применения различных диетических индексов и вопросников о частоте приема пищи в исследованиях по оценке влияния пищевого поведения на показатели хронического низкоинтенсивного воспаления.

Correction of systemic inflammation and endothelial dysfunction in patients with chronic obstructive pulmonary disease in combination with arterial hypertension under the influence of the therapy

One of the main pathogenetic mechanisms combining chronic obstructive pulmonary disease (COPD) and arterial hypertension (AH) is a persistence systemic inflammation leading to the formation of endothelial dysfunction (ED), which serves as an independent predictor of the adverse prognosis of most cardiovascular diseases (CVD), while the treatment of patients with COPD in combination with AH requires the inclusion of drugs that have a beneficial effect on these pathological conditions. Prolonged-release indapamide has a number of pleiotropic effects, but most studies to study its effect on the state of endothelium and the intensity of systemic inflammation were conducted in patients with AH without associated bronchial obstructive diseases. The works carried out in conditions of comorbidity with COPD and according to the data of which the influence of diuretic drugs on the markers of systemic inflammation and ET in patients would be evaluated, were not found out, in this connection the present research was initiated and carried out. The aim of the study was to evaluate the dynamics of markers of systemic inflammation and ET in the inclusion of diuretics in the complex therapy of patients with COPD in combination with BA. Materials. Patients (n = 65: 50 men and 15 women) with stage I – IV COPD suffering from arterial hypertension (AH) I – III with initially elevated levels of systemic inflammation markers and ET, in whom the antihypertensive therapy performed was not effective enough, were included in the study. Results. The results of the research on estimation of dynamics of markers of system inflammation – highly sensitive C-reactive protein (hsСRP), an intercellular adhesion molecule of type 1 (sICAM-1) and ET – endothelin-1, sP-selectin at the inclusion of diuretics in the therapy of patients with COPD with AH are presented. When analyzing the dynamics of the studied markers, a decrease in their level was noted, but statistically significant changes were obtained only in patients against the background of prolonged-release indapamide treatment. Additional pleiotropic effects of indapamide, consisting in reduction of activity of markers of systemic inflammation and ET, are also shown. Its high efficiency in achieving and maintaining the target AH levels compared to hydrochlorothiazide has been demonstrated. Conclusion. The expediency of the inclusion of prolonged-release indapamide in the complex therapy of patients with COPD in combination with AH on the first line of antihypertensive therapy has been demonstrated due to its additional pleiotropic properties, which consist in the influence on the general pathogenetic links of the formation and progression of AH in COPD and its high antihypertensive efficiency in comparison with hydrochlorothiazide.

Интегральные показатели антиэндотоксинового иммунитета и системного воспаления у больных бронхиальной астмой при различных биофенотипах воспаления

Актуальность. Поскольку роль эндотоксина в индукции бронхообструктивного синдрома сегодня уже не вызывает сомнений, представляется целесообразным и определение роли антиэндотоксинового иммунитета (АЭИ) в формировании различных биофенотипов хронического воспаления, которые лежат в основе особенностей течения бронхиальной астмы (БА). Цель настоящего исследования - определение роли гуморального и мукозального звеньев АЭИ и системного воспаления при различных биофенотипах воспаления у больных БА, которые могли бы быть полезны для разработки персонифицированной терапии. Материалы и методы. В исследование включены 109 больных с верифицированным диагнозом среднетяжёлой и тяжёлой бронхиальной астмы. Пациенты были разделены на 3 группы в зависимости от типа воспаления в дыхательных путях: 1-я группа - эозинофильный, 2-я группа - нейтрофильный, 3-я группа - смешанный гранулоцитарный. Гуморальное и мукозальное звенья эндотоксин-связывающих систем оценивали по уровням специфических эндотоксин-связывающих антител классов M, A, G (анти-ЭТ IgM, анти-ЭТ IgA, анти-ЭТ IgG) в периферической крови, и уровню секреторного антиэндотоксинового иммуноглобулина класса A в индуцированной мокроте. Системное воспаление оценивали по концентрации С-реактивного белка (СРБ). Результаты. При нейтрофильном и смешанном биофенотипах воспаления зарегистрированы повышенные уровни анти-ЭТ IgM и анти-ЭТ IgА в периферической крови. В то время как при эозинофильном биофенотипе воспаления не выявлено существенных различий данных показателей от контрольной группы. Концентрация анти-ЭТ IgG во всех группах больных бронхиальной астмы не отличалась от диапазона нормы. При всех биофенотипах воспаления выявлено повышение концентраций секреторного анти-ЭТ IgА и СРБ в рамках низкоинтенсивного воспаления. Наибольший уровень анти-ЭТ IgА и СРБ зарегистрирован при нейтрофильном и смешанном биофенотипах воспаления. Выявлены умеренные прямые корреляционные связи: между уровнем секреторного анти-ЭТ IgA и относительным количеством нейтрофилов в индуцированной мокроте (r = 0,469, р &lt; 0,05); между уровнем СРБ и уровнем секреторного анти-ЭТ IgA (r = 0,427, р &lt; 0,05). Выводы. Наиболее выраженный гуморальный и мукозальный ответ на эндотоксин и интенсивность системного воспаления при нейтрофильном и смешанном биофенотипах воспаления свидетельствуют о значительной роли ингаляционного эндотоксина в формировании тяжёлой астмы. Выявленный дисбаланс гуморального и мукозального звеньев АЭИ систем дополняет современные представления патогенеза бронхиальной астмы с различными биофенотипами воспаления, предоставляет перспективу возможности персонификации лечения и достижения контроля заболевания. Background. Since the role of endotoxin in induction of broncho-obstructive syndrome is above any doubt today, we focused on the role of anti-endotoxin immunity (AEI) in the formation of different phenotypes of chronic inflammation, which underlie characteristics of the course of asthma. The aim of this study was to determine the role of humoral and mucosal components of AEI and systemic inflammation in different inflammatory phenotypes in patients with asthma, which could be useful in developing personalized therapy. Materials and methods. The study included 109 patients with a verified diagnosis of moderate to severe asthma. All patients were divided into 3 groups depending on the type of inflammation in the respiratory tract: Group 1, eosinophilic; Group 2, neutrophilic; and Group 3, mixed granulocytic inflammation. The humoral and mucosal components of endotoxin binding systems were evaluated by levels of specific endotoxin-binding class M, A, and G antibodies (anti-ET IgM, anti-ET IgA, and anti-ET IgG) in peripheral blood and the level of secretory anti-endotoxin IgA in induced sputum. Systemic inflammation was assessed by concentration of C-reactive protein (CRP). Results. Peripheral blood concentrations of anti-ET IgM and anti-ET IgA were elevated in neutrophilic and mixed inflammatory phenotypes. At the same time, in the eosinophilic inflammatory phenotype, these indexes were not significantly different from the control group. In all groups of patients with asthma, concentrations of anti-ET IgG were similar and remained within the normal range. In all inflammatory phenotypes, concentrations of secretory anti-ET IgA and C-reactive protein were increased within the range of low-intensity inflammation. The highest levels of anti-ET IgA and CRP were found in neutrophilic and mixed inflammatory phenotypes. Levels of secretory anti-ET IgA moderately directly correlated with the relative number of neutrophilic leukocytes in induced sputum (r = 0.469, р &lt; 0.05) and levels of CRP moderately directly correlated with levels of secretory anti-ET IgA (r = 0.427, р &lt; 0.05). Conclusions. The most pronounced humoral and mucosal response to endotoxin and the intensity of systemic inflammation in neutrophilic and mixed inflammatory phenotypes evidenced a significant role of inhaled endotoxin in the formation of severe asthma. The observed imbalance of humoral and mucosal components in AEI systems supports modern ideas of the pathogenesis of asthma with different inflammatory phenotypes and provides a promising possibility of individualized treatment and control of the disease.

Time-dependent effects of prognostic biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma.

The goal of this study was to examine time-dependent effects of prognostic biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma. Retrospective chart reviews were conducted at the Winship Cancer Institute of Emory University and the Atlanta Veterans Administration Medical Center with authorization from the Emory University Institutional Review Board and the Veterans Administration Research and Development Committee. Inclusion criteria included age ⩾18 years, treatment with targeted therapy for clear cell or non-clear cell metastatic renal cell carcinoma and concomitant assessment of C-reactive protein and albumin levels on ⩾3 occasions that were ⩾10 days apart. Discovery, expansion, and external validation cohorts were identified. Established prognostic variables were evaluated by univariate and multivariate analyses. Intensity of systemic inflammation was assessed at all time points with C-reactive protein and albumin as prognostic covariates for overall survival in an extended Cox regression model. Intensity of systemic inflammation was assessed on 3186 occasions in 181 patients. Risk status changed in 131 patients (72%). The hazard ratio for overall survival was 21.41 (95% confidence interval = 8.26-55.50) with a type 3 p value of <0.001 for the reference cohort and 9.68 (2.07-45.31) with a type-3 p value of 0.006 for the external validation cohort when time points associated with severe systemic inflammation were compared to all other time points. The bias-corrected c-statistic was 0.839 (0.773-0.905) and 0.818 (0.691-0.946), respectively. Terminal disease progression with severe systemic inflammation was detected in 87% of the 90 patients who died. In conclusion, time-dependent effects are a prominent feature of intensity of systemic inflammation, a powerful prognostic biomarker for metastatic renal cell carcinoma.

Biomarker study of early death in patients with intermediate and favorable risk metastatic renal cell carcinoma.

530 Background: The primary objective of this study was to determine whether severe systemic inflammation (SSI) could serve as a biomarker for terminal disease progression and early death in patients with intermediate and favorable risk metastatic renal cell carcinoma (mRCC). Methods: Retrospective chart reviews of patients treated with targeted therapy for mRCC were conducted at the Winship Cancer Institute of Emory University (WCIEU) and the Atlanta Veterans Administration Medical Center (AVAMC) after obtaining institutional authorizations. The modified Glasgow Prognostic Score (mGPS) was used to quantify intensity of systemic inflammation (ISI) at baseline and at least two additional time points that were at least 10 days apart. Early death was defined as death within two years of Day 0, the first day ISI was quantified. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: ISI was quantified 2,428 times in 135 patients at the WCIEU with a median of 16 per patient and a range of 3 to 51 versus 758 times in 46 patients at the AVAMC with a median of 12 per patient and a range of 3 to 48. Baseline risk stratification was as follows: favorable (mGPS=0), intermediate (mGPS=1) and poor (mGPS=2) with 96 (51%), 36 (19%), and 53 patients (29%) in the respective risk groups of the combined cohort (n=181). Sixty eight of the 90 patients who died in the time frame of the study did so within 2 years of Day 0. Of these early deaths, only 34 (50%) were among patients with poor risk at baseline versus 18 (26%) and 16 (24%) of the intermediate and favorable risk patients, respectively. Furthermore, 90% of these early deaths were associated with SSI as a terminal event as were 87% of all deaths in spite of the fact that 64% of poor risk patients had died as of Year 2 versus only 27% of patients in the combined group of intermediate and favorable baseline risk. Conclusions: Severe acquired systemic inflammation is a promising biomarker for terminal disease progression and early death in patients with intermediate and favorable risk mRCC. Prospective confirmatory studies are required.

ОСОБЛИВОСТІ МЕТАБОЛІЗМУ СПОЛУЧНОЇ ТКАНИНИ ТА ПРОЗАПАЛЬНИХ ЦИТОКІНІВ У ПАЦІЄНТІВ З ОСТЕОАРТРОЗОМ ТА КОМОРБІДНИМИ ГІПЕРТОНІЧНОЮ ХВОРОБОЮ ТА ОЖИРІННЯМ

&lt;p&gt;РЕЗЮМЕ. У статті викладено результати дослідження показників обміну сполучної тканини та прозапальних&lt;br /&gt;цитокінів у хворих на остеоартроз з коморбідними есенціальною артеріальною гіпертензією та ожирінням.&lt;br /&gt;Встановлено, що перебіг остеоартрозу супроводжується підвищенням активності системного запалення,&lt;br /&gt;інтенсивність якого за наявності супутніх гіпертонічної хвороби та ожиріння вірогідно зростає. У хворих на&lt;br /&gt;остеоартроз вміст прозапальних цитокінів у крові є вірогідно підвищеним і зростає із приєднанням ожиріння.&lt;/p&gt;&lt;p&gt;&lt;br /&gt;КЛЮЧОВІ СЛОВА: остеоартроз, артеріальна гіпертензія, ожиріння, сполучна тканини, цитокіни.&lt;/p&gt;

Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure

Patients with heart failure (HF) have evidence of chronic systemic inflammation. Whether inflammation contributes to the exercise intolerance in patients with HF is, however, not well established. We hypothesized that the levels of C-reactive protein (CRP), an established inflammatory biomarker, predict impaired cardiopulmonary exercise performance, in patients with chronic systolic HF. We measured CRP using high-sensitivity particle-enhanced immunonephelometry in 16 patients with ischemic heart disease (previous myocardial infarction) and chronic systolic HF, defined as a left ventricular ejection fraction ≤ 50% and New York Heart Association class II-III symptoms. All subjects with CRP >2 mg/L, reflecting systemic inflammation, underwent cardiopulmonary exercise testing using a symptom-limited ramp protocol. CRP levels predicted shorter exercise times (R = -0.65, p = 0.006), lower oxygen consumption (VO2) at the anaerobic threshold (R = -0.66, p = 0.005), and lower peak VO2 (R = -0.70, p = 0.002), reflecting worse cardiovascular performance. CRP levels also significantly correlated with an elevated ventilation/carbon dioxide production slope (R = +0.64, p = 0.008), a reduced oxygen uptake efficiency slope (R = -0.55, p = 0.026), and reduced end-tidal CO2 level at rest and with exercise (R = -0.759, p = 0.001 and R = -0.739, p = 0.001, respectively), reflecting impaired gas exchange. In conclusion, the intensity of systemic inflammation, measured as CRP plasma levels, is associated with cardiopulmonary exercise performance, in patients with ischemic heart disease and chronic systolic HF. These data provide the rationale for targeted anti-inflammatory treatments in HF.

Abstract 593: Kinetic risk assessment with biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma

Abstract Background: Empiric prognostic scoring systems for metastatic renal cell carcinoma (mRCC) are routinely employed as baseline risk stratification tools for clinical trials. However, these systems have limited clinical utility after therapeutic intervention has begun. The goal of the current study was to develop clinically useful, hypothesis-driven, kinetic risk assessment tools based exclusively on biomarkers of systemic inflammation. Methods: A retrospective chart review was conducted with authorization from the Emory University Institutional Review Board. Inclusion criteria included treatment at the Winship Cancer Institute with a targeted agent for mRCC as well as concomitant serum C-reactive protein (CRP) and albumin levels on at least three occasions that were at least 10 days apart. The modified Glasgow Prognostic Score (mGPS) was used to quantify the intensity of systemic inflammation and to formulate the Inflammation Intensity Index for kinetic risk assessment. Findings: Intensity of systemic inflammation was assessed 2465 times in 135 patients with cohorts used for training (n = 55; cutoff date 06/30/2012) and validation (n = 80; cutoff date 06/30/2014). Kinetic risk was assigned on the basis of time to onset of refractory systemic inflammation. The median overall survival (OS) was 44.7, 19.8, 13.0, and 6.7 months for kinetic risk categories A, B, C and D, respectively, with a median follow up of 29.3 months for the combined cohorts and none lost to follow up (censored log rank p &amp;lt;.0001). OS was 40.6 months for whites (n = 99) vs. 9.8 months for blacks (n = 30; p &amp;lt;.0001). Conclusions: The correlation of dramatic differences in OS with the onset of refractory systemic inflammation provides strong evidence in support of the clinical utility of the Inflammation Intensity Index and, as a consequence, the underlying theoretical constructs, including a plausible biological hypothesis for differences in clinical outcome by race. Citation Format: Wayne B. Harris, Omer Kucuk, Bradley Carthon, Yuan Liu, John Pattaras, Kenneth Ogan, Viraj Master. Kinetic risk assessment with biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 593. doi:10.1158/1538-7445.AM2015-593

Effect of Systemic Inflammation on Inspiratory and Limb Muscle Strength and Bulk in Cystic Fibrosis

Diaphragm thickness is increased in cystic fibrosis (CF), but it shows a marked variability between patients. The variable response of the diaphragm to loading may reflect the combined and opposite effects of training by the respiratory disease and systemic inflammation. To assess the impact of systemic inflammation on diaphragm and limb muscle strength and bulk in adult patients with CF. In 38 stable patients with CF and 20 matched control subjects, we measured fat-free mass (FFM), inspiratory muscle strength, diaphragm thickness, quadriceps and biceps strength and cross-sectional area, and circulating levels of leukocytes, C-reactive protein, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, tumor necrosis factor-alpha soluble receptors, and immunoglobulin G. Patients had increases in several inflammatory markers that correlated with the severity of lung disease and nutritional depletion. Compared with control subjects, patients with CF had increased diaphragm thickness and inspiratory muscle strength and showed a trend toward a reduction in limb muscle strength and bulk. Multiple regression analyses identified FFM and airway resistance as independent predictors of diaphragm thickness, but systemic inflammation had no (or only a minor) predictive effect on FFM, inspiratory muscle strength, diaphragm thickness, and limb muscle strength and bulk. In patients with CF, the intensity of systemic inflammation does not account significantly for the variance of FFM and diaphragm or limb muscle strength and bulk. Training of the diaphragm in CF occurs despite the presence of systemic inflammation.

ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: ADVANTAGES OF CALCIUM ANTAGONISTS

Aim. To study effect of antihypertensive therapy with amlodipine maleat (Stamlo® M, “Dr. Reddy’s”, India) on morphofunctional heart indices, intensity of systemic inflammation and oxidative stress in patients with arterial hypertension (HT) with chronic obstructive pulmonary disease (COPD). Material and methods . 20 patients with COPD II-III stage (GOLD 2006) in remission and HT 1-2 stage were involved in the study. Morphofunctional heart indices, respiratory function, levels of C-reactive protein (CRP) and oxidative stress (lipid peroxidation products (LPP) – acilhydroperoxides) were evaluated. Results. Amlodipine maleat therapy provides target level of blood pressure (BP) according to ambulatory BP monitoring with improvement of pathological type of daily BP profile. Reduction of diastolic dysfunction of left and right ventricles was revealed. Therapy was safe in terms of respiratory function. Significant CRP and LPP levels reduction was observed. Conclusion . Amlodipine maleat therapy has high antihypertensive effect, organoprotective properties and safety in hypertensive patients with COPD. Besides this therapy demonstrates systemic anti-inflammatory action and reduces oxidative stress.

Effects of Corticosteroids on Systemic Inflammation in Chronic Obstructive Pulmonary Disease

Patients with chronic obstructive pulmonary disease (COPD) are predisposed to atherosclerosis and coronary artery disease, but the underlying mechanisms are unclear. Although there is wide acceptance that atherosclerosis is related to systemic inflammation, the cause(s) and mechanism(s) of pulmonary inflammation in stable COPD remain unknown. Infectious (bacterial and viral) as well as noninfectious agents can cause acute exacerbations in COPD, and they intensify local and systemic inflammation. Although it is not known how systemic inflammation develops in stable COPD, there is good evidence to suggest that it occurs and that the intensity of systemic inflammation is linked to the severity of airflow obstruction. We postulate that systemic inflammation provides the linkage between COPD and atherosclerosis. Inhaled corticosteroids have been shown to improve health outcomes in COPD, but the mechanism by which this occurs is a pivotal and challenging question that has yet to be answered. To prove the concept that inhaled corticosteroids could suppress systemic inflammation (as exemplified by serum C-reactive protein [CRP] levels), a double-blind, placebo-controlled clinical trial was conducted in a group of patients with mild to moderate COPD. We found that withdrawal of inhaled corticosteroids increased serum CRP levels, and that reintroduction of inhaled fluticasone could suppress CRP levels.