C-Reactive Protein Measurements as a Marker of the Severity of Chronic Obstructive Pulmonary Disease Exacerbations

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs. Acute exacerbations of COPD (AE-COPD) are a result of infectious or non-infectious instances. In our study, we aimed to determine whether serum C-reactive protein (CRP) levels are predictive indicators for disease severity and prognosis in hospitalized patients with AE-COPD. A total of 64 patients (36 regular ward and 28 ICU patients) were included in the study. Cases were identified and classified according to the Global Initiative for COPD. The first CRP test levels at acceptance at the ward or intensive care unit were counted in the study. CRP levels of patients in intensive care were significantly higher than those of patients in the regular ward. Mean values of CRP were detected to be 6.28?±?6.53 mg/dl in the regular ward cases and 16.9?±?12.03 mg/dl in the ICU patients (p?<?0.01). The stage of COPD did not indicate a significant difference in terms of CRP values. Mean CRP values were found to be 16.02?±?6.95 mg/dl in mortal cases and 9.76?±?11.09 mg/dl in survivors (p?<?0.01). High CRP levels were considered as a prognostic parameter and indicator of severity of AE-COPD. Increased mortality risk was found to be associated with high CRP values.     

中性粒细胞CD64指数指导慢性阻塞性肺疾病急性加重期抗生素应用的探讨

目的 研究CD64指数在减少慢性阻塞性肺疾病急性加重期（AECOPD）患者抗生素应用中的意义。方法 选取2017年1月~10月入住我院的120例AECOPD患者,随机分为对照组和实验组,各60例。对照组根据2016年GOLD指南使用抗生素,实验组根据入院2 h内CD64指数水平来决定是否使用抗生素,在第4天、第8天复测CD64指数水平,若第8天CD64指数≤3,则停用抗生素,相反则继续使用抗生素。比较两组不同时间CD64指数、出院时相关指标（临床有效率、抗生素使用时间、住院时间、平均抗生素花费）、出院后1年内相关指标包括:至下次急性加重时间、随访1年内急性加重次数、住院次数及第一秒用力呼气容积（FEV1）变化。结果 治疗后第4天和第8天,实验组CD64指数水平分别为（1.84±0.65）、（0.86±0.05）,对照组CD64指数水平分别为（2.52±0.30）、（1.45±0.03）均较入院时的（3.47±1.00）、（3.04±1.12）降低,且实验组CD64指数在治疗后第4天和第8天均低于对照组,差异有统计学意义（P＜0.05）;②实验组抗生素使用时间、住院时间、平均抗生素花费均少于对照组,差异有统计学意义（P＜0.05）;两组的临床有效率、至下次急性加重时间、随访1年内急性加重次数、住院次数及FEV1变化比较,差异无统计学意义（P＞0.05）。结论 CD64指数可有助于决定AECOPD患者是否使用抗生素,对AECOPD患者抗生素的使用有重要的指导意义     

Chlamydia pneumoniae Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Analysis of 250 Hospitalizations

Two hundred fifty hospitalizations were included in a serologically based prospective study to assess the role of Chlamydia pneumoniae in episodes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the percentage of COPD patients chronically infected with this pathogen. Chlamydia pneumoniae-specific IgG, IgA and IgM antibody titers were determined using a commercial kit with the microimmunofluorescence method. A significantly higher geometric mean titer in the COPD patients compared to the control group was found for IgG (P<0.00001) and IgA (P<0.000001). The serological criterion for chronic Chlamydia pneumoniae infection (IgG ≥128 concomitant with IgA ≥64) was positive in 73 (33.3%) COPD patients compared with 7 (7%) controls (P=0.000001). No difference was found in any serological parameter when the study population was divided by severity of COPD. When the serological profiles were compared between the first and second of 31 pairs of hospitalizations, 7 of the 62 (11.3%) hospitalizations showed evidence of acute infection with Chlamydia pneumoniae around one of the episodes of AECOPD. It is concluded that compared with the control group, the COPD patients had a significantly higher prevalence of chronic Chlamydia pneumoniae infection. In the COPD group, there was no correlation between the severity of the disease and the rate of chronic Chlamydia pneumoniae infection. In a substantial percentage of AECOPD cases, there is serological evidence of acute Chlamydia pneumoniae infection around the time of the exacerbation. The clinical and pathophysiologic implications of these findings should be clarified by further studies. Electronic Publication     

Serum Surfactant Protein D during Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Background: There is a paucity of lung specific biomarkers to diagnose exacerbations of chronic obstructive pulmonary disease (COPD) and to track their progression. Surfactant protein D (SP-D) is a pulmonary collectin regulating the innate immunity of the lung and its serum expression is perturbed in COPD. However, it is not known whether serum levels change during exacerbations. We sought to determine whether serum SP-D levels are raised in COPD exacerbations. Objectives: To determine whether or not patients with exacerbations have elevated serum SP-D levels compared with asymptomatic controls, stable disease. Study design: case control study. Methods: We measured serum SP-D levels from patients with stable COPD (n = 14), patients experiencing acute exacerbations (n = 13) and in control subjects (n = 54) using a specific immunoassay and compared the levels using analysis of variance. Results: Serum SP-D levels were significantly increased in patients who experienced an acute exacerbation (227 ± 120 ng/mL) compared to patients with stable disease (151 ± 83 ng/mL) or control subjects (128 ± 65 ng/mL; p = 0.003). Serum SP-D levels were also found to be inversely related to various lung function parameters including FEV1/FVC% predicted. Conclusions: Our study suggests that serum SP-D levels are increased in patients during exacerbations and may be a potential diagnostic biomarker for COPD exacerbations.     

Prevalence and Clinical Significance of Fever in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Fever is an important, although not always present, sign in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The objective of this study was to determine the prevalence of fever and its clinical significance in these episodes. Two hundred seventeen AECOPD hospitalizations were included in a prospective study and were categorized as febrile (FH) or afebrile (AFH), using as a cutoff a rectal temperature measurement of 37.8°C during hospitalization. Eighty-six hospitalizations (39.6%) were identified as AFH. The patients in this group had significantly more severe airway obstruction and hypoxemia, a higher rate of chronic obstructive pulmonary disease (COPD) complications, a higher rate of type 3 exacerbation, a shorter length of hospitalization and a higher rate of readmissions than patients in the FH group. The results of this study show that more than one-third of AECOPD hospitalizations are attributable to afebrile episodes. These episodes are characterized by lower rates of bronchitis manifestations in patients with more severe disease. Although the length of hospitalization for these episodes is shorter, the readmission rate is higher. Electronic Publication     

Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome.     

CD64感染指数、BODE指数与降钙素原在慢阻肺患者中的水平变化

目的 分析慢阻肺患者的CD64感染指数、BODE指数与降钙素原的水平变化并探究其临床意义。方法 收集2016年1月~2017年3月我院收治的慢阻肺患者80例作为研究组,同时将同期在医院进行检查的稳定期慢阻肺患者作为对照组。分别检测CD64感染指数、BODE指数与降钙素原的水平,分析其临床意义。结果 对照组CD64感染指数为（3.28±0.75）,BODE指数为（1.65±0.39）,降钙素原水平为（0.15±0.09）ng/ml。治疗前,研究组CD64感染指数（5.28±1.99）、BODE指数（3.21±0.63）、降钙素原水平[（0.28±0.13）ng/ml]均高于对照组,差异有统计学意义（P＜0.05）。治疗后,研究组CD64感染指数（3.97±0.81）、BODE指数（1.98±0.41）、降钙素原水平[（0.12±0.12）ng/ml]均下降,与对照组相比,差异无统计学意义（P＞0.05）。结论 CD64感染指数、降钙素原可能是监测慢阻肺住院患者的早期指标,若能在早期进行检测,为用药进行指导,可降低患者住院风险;同时也有利于临床合理应用抗菌药物。而BODE指数则可作为评估患者病情程度及预后的指标。     

老年慢性阻塞性肺疾病急性发作期血中锌、铬含量与免疫功能关系的研究

目的 研究老年慢性阻塞性肺疾病（COPD）急性发作期患者锌、铬与免疫功能的变化及两者间的相关性。方法 老年COPD患者55例，对照组50例。血锌测定用光焰原子吸收法，血铬测定用无光焰原子吸收法，免疫球蛋白采用免疫比浊法检测。结果 老年COPD患者血清Zn、Cr均明显低于对照组（P〈0．05）；老年COPD患者血清IgG、IgA明显低于对照组（P〈0．05），而IgM在两组间差异无统计学意义（P〉0．05）；老年COPD患者CD3、CD4及CD4／CD8明显低于对照组（P均〈0．05），CD8却明显高于对照组（P〈0．05）；老年COPD患者血清Zn水平与血清IgG、IgA质量浓度及CD4／CD8呈正相关（r分别0．619、0．578、0．699，P均〈0．05），血清Cr水平也与血清IgG、IgA质量浓度及CD4／CD8呈正相关（r分别0．617、0．582、0．688，P均〈0．05）。结论 老年COPD患者存在免疫功能低下、紊乱，这种变化可能与机体缺锌、铬有关。     

无创呼吸机对慢性阻塞性肺疾病急性加重患者治疗效果的影响

目的探讨飞利浦V60 无创呼吸机对慢阻肺急性加重患者的临床疗效,为慢阻肺急性加重患者的临床治疗提供理论参 考遥方法选取于我院进行治疗的慢阻肺急性加重患者70 例,按随机数字表法平均分成对照组35 例与实验组35 例,对照组采 取常规内科治疗,实验组在对照组的基础上予以无创呼吸机治疗曰观察并分析两组患者临床疗效,利用统计学分析两组患者住 院天数尧使用抗生素药物时间的差异遥结果治疗后,实验组总有效率37 例（92.50%）明显大于对照组总有效率31 例（77.50%）尧 抗生素使用时间及住院天数均显著短于对照组,差异有统计学意义（<0.05）遥结论无创呼吸机治疗能缓解慢阻肺急性加重患 者临床症状,效果显著,还能减少抗生素的使用,提早患者康复出院时间,值得临床推广使用遥     

Complement Factor C5a in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

The complement component C5a is a potent inflammatory peptide, which may be involved in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). We analysed the induced sputum and plasma of 28 patients with stable COPD, 12 healthy smokers and 7 non‐smokers. In 13 of the patients with COPD, we also observed paired samples during acute exacerbation. The concentrations of C5a/C5a desArg and C3a/C3a desArg were measured using cytometric bead array. Both C5a and C3a concentrations in induced sputum of stable patients with COPD were significantly increased compared to the control groups of healthy smokers and non‐smokers. In addition, there was a significant elevation in C5a values in exacerbation of COPD that was independent from the airway C3a levels. Airway C5a levels were negatively correlated with forced expiratory volume in first second (FEV1)% predicted and diffusing capacity of the lung (TLCO). Plasma C5a concentrations in patients with COPD were significantly higher than in healthy smokers, but no further significant systemic C5a elevation was detected with acute exacerbation of COPD. There was no important difference in local or systemic C5a concentrations between healthy smokers and non‐smokers. These in vivo results clearly show that local and systemic C5a concentrations in COPD are elevated, and that the local, in contrast to systemic, C5a concentrations additionally increase in the acute exacerbation of COPD. It seems that the cigarette smoke is not related to C5a increase. The elevated local and systemic C5a levels, and additional individual local C5a increase during the exacerbation support the importance of C5a in COPD.     

慢性阻塞性肺疾病急性加重期与慢性阻塞性肺疾病并发社区获得性肺炎患者的临床对比

目的 探究慢性阻塞性肺疾病急性加重期与慢性阻塞性肺疾病并发社区获得性肺炎患者的临床对比,旨在为临床的诊断和治疗提供科学依据。方法 选取2017年3月~2018年3月于我院接受治疗的82例COPD患者为研究对象,按照随机数表法分为两组,其中观察组42例为AECOPD患者,对照组40例为COPD合并CAP患者,比较两组患者的临床症状、肺功能以及PCT、CRP水平。结果 观察组患者呼吸困难、咳脓痰、精神差、发热等临床症状的发生率均低于对照组,差异具有统计学意义（P＜0.05）。观察组患者FEV1、FVC、FEV1/FVC分别为（64.15±7.26）ml、（62.85±7.29）ml、（62.03±5.54）%,均高于对照组的（52.51±5.75）ml、（50.85±6.74）ml、（52.34±5.61）%,差异具有统计学意义（P＜0.05）。观察组患者PCT和CRP分别为（0.52±0.07）ng/L和（21.51±1.35）mg/L,均低于对照组的（0.97±0.08）ng/L和（40.05±1.57）mg/L,差异具有统计学意义（P＜0.05）。结论 AECOPD患者与COPD合并CAP患者相比,临床症状发生情况较少,肺功能较好,对患者进行相关检测,能够提高治疗效果。     

双水平气道正压通气治疗慢阻肺的临床研究

目的观察双水平气道正压通气对慢性阻塞性肺疾病夜间低氧的治疗作用。方法取60例慢性阻塞性肺疾病患者,随机分成2组。对照组30例使用吸氧、抗感染等常规治疗：治疗组在常规治疗的基础上加用夜间双水平气道正压通气治疗4h,疗程为7d。分别观察2组在治疗前后低氧血症及心率失常发生率和肺动脉压力的变化。结果双水平气道正压通气组在治疗前后自身对照以及与对照组比较,夜间低氧血症及心律失常发生率和肺动脉压力的改变均有统计学意义（P〈0．05～0．01）。结论双水平气道正压通气能改善慢性阻塞性肺疾病患者的夜间低氧血症,减少心律失常的发生率,降低肺动脉压力,可作为治疗慢性阻塞性肺疾病的重要方法之一。     

Serological Evidence of Acute Infection with the Chlamydia-Like Microorganism Simkania negevensis (Z) in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

The aims of this study were twofold: (i) to test for possible associations between serological evidence of acute Simkania negevensis (Sn) infection and acute exacerbation of chronic obstructive pulmonary disease and (ii) to examine the prevalence of past infections with Sn in patients with chronic obstructive pulmonary disease. In 120 patients (63%) there was serological evidence of past infection with Sn, which was not significantly different from the rate in a control population. In five hospitalizations serological evidence existed of acute infection with Sn around the time of the exacerbation of chronic obstructive pulmonary disease. In four of these cases, there was serological evidence of acute infection with at least one other respiratory pathogen. It is concluded that Sn can be associated serologically with exacerbation of chronic obstructive pulmonary disease, in most cases together with other respiratory pathogens. The implications of these findings should be investigated further. Electronic Publication     

Reactive Oxygen Species in Peripheral Blood and Sputum Neutrophils During Bacterial and Nonbacterial Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Chronic airway inflammation can be mediated by an enhanced neutrophil oxidative burst. However, the role of bacteria in the pathogenesis of chronic obstructive pulmonary disease (COPD) exacerbations is highly controversial. The aim of this study was to evaluate the production of reactive oxygen species (ROS) in peripheral blood and sputum neutrophils during bacterial and nonbacterial acute exacerbations of COPD (AECOPD). A total of 40 patients with AECOPD, 10 healthy nonsmokers, and 10 “healthy” smokers were enrolled into the study. Peripheral blood and sputum samples were obtained during exacerbation and after recovery. Neutrophils were isolated by high-density gradient centrifugation and magnetic separation. ROS production by neutrophils was investigated after stimulation with phorbol-myristate-acetate and Staphylococcus aureus bacteria. ROS production by neutrophils was assessed as the mean fluorescent intensity using a flow cytometer. IL-8 levels in serum and induced sputum were determinant by ELISA. Spontaneous ROS production was significantly higher in neutrophils from the patients with bacterial AECOPD as compared with nonbacterial AECOPD and stable COPD (P <0.05). ROS production stimulated with PMA and with Staphylococcus aureus was significantly higher in neutrophils isolated from the patients with bacterial AECOPD as compared with nonbacterial and stable COPD (P <0.05). The serum and induced sputum IL-8 levels were significantly increased in the patients with bacterial AECOPD than nonbacterial AECOPD, stable COPS, and “healthy” smokers and nonsmokers (P <0.05) and higher in the induced sputum as the compared with serum in all studied groups (P <0.05). Enlarge CRP level was documented during AECOPD than in all other groups (P <0.05). A markedly increased ROS production in sputum neutrophils during bacterial AECOPD shows an inflammatory response reflecting enhanced local inflammation, which can be mediated by bacterial colonization.     

Viral Infection is Associated with an Increased Proinflammatory Response in Chronic Obstructive Pulmonary Disease

Abstract The development of new diagnostic methods based on molecular biology has led to evidence of the important role of respiratory viruses in chronic obstructive pulmonary disease (COPD) exacerbations. Cytokines and chemokines are recognized as key actors in the pathogenesis of COPD. The objective of this study was to evaluate the association between viral infection and host cytokine responses in 57 COPD patients hospitalized with an acute exacerbation. Seventeen cytokines were profiled using a Luminex-Biorad multiplex assay in plasma samples collected in the first 24?h following hospital admission. Stepwise linear regression analysis was performed, taking into account the influence of seven potential confounding factors in the results. Twenty-four out of 57 showed radiological signs of community-acquired pneumonia (CAP) at hospital admission, 25 patients required admission to the intensive care unit (ICU), 20 had a bacterial infection, and 20 showed a detectable respiratory virus in pharyngeal swabs. Regression analysis showed that viral infection correlated with higher levels of interleukin-6 (IL-6) (log value of the coefficient of regression B, p=0.47, 0.044), and monocyte chemoattractant protein-1 (MCP-1) (p=0.43, 0.019), and increased admission to the ICU. Viral infection also correlated with higher levels of interferon-γ (IFN-γ) (p=0.70, 0.026), which, in turn, was inversely associated with the severity of illness. Finally, viral infection was independently associated with higher levels of tumor necrosis factor-α (TNF-α) (p=0.40, 0.002). Thus our study demonstrates that in patients with COPD exacerbations, viral infection is directly associated with higher systemic levels of cytokines central to the development of the antiviral response, which are also known to contribute to inflammation-mediated tissue damage. These results reveal a potential specific role of viral infection in the pathogenesis of COPD exacerbations.