稳定期慢性阻塞性肺疾病气道炎症的研究

目的 研究稳定期慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)气道炎症和肺功能、下气道细菌定植(lower airway bacterial colonization,LABC)的关系.方法 随机入选45例稳定期COPD门诊患者和28名健康志愿者,行肺功能、血常规和胸片检查.采用痰诱导方法 留取深部合格痰液,COPD患者的痰液行细菌定量培养,两组研究对象的痰液均行细胞因子检测.结果 稳定期COPD组痰液中白介素8(IL-8)、肿瘤坏死因子α(TNF-α)、IL-10、IL-19明显高于对照组(P＜0.05).第1秒用力呼气容积占预计值百分比(FEV1%pred)＜50%组痰液中IL-8、TNF-α、IL-19明显高于FEV1%pred≥50%组(P＜0.05),而IL-10在两组间比较差异无统计学意义.在本实验中LABC量≥107CFU/ml者占总人数的33.33%,主要的下气道定植菌为卡他莫拉菌、副流感嗜血杆菌、肺炎链球菌、流感嗜血杆菌等.LABC量≥107 CFU/ml组痰液中IL-8、TNF-α、IL-19明显高于LABC＜107 CFU/ml组(P＜0.05),而IL-10在两组间比较差异无统计学意义.相关性分析显示,IL-19与IL-10呈负相关,相关系数r=-0.548(P＜0.05),IL-19与IL-8、TNF-α呈正相关,相关系数分别为r=0.702(P＜0.05)、r=0.708(P＜0.05).FEV1%pred＜50%组细菌定植量明显高于FEV1%pred≥50%组(P＜0.05).FEV1%pred＜50%预计值组的吸烟指数明显高于FEV1%pred≥50%组(P＜0.05).结论 稳定期COPD患者存在气道炎症,既与LABC有关,又与吸烟有关,这种与LABC和吸烟相关的气道炎症可能是导致COPD患者肺功能进行性下降的原因.     

稳定期慢性阻塞性肺疾病气道高反应性与下呼吸道细菌定植关系的研究

目的探讨稳定期慢性阻塞性肺疾病（COPD）下呼吸道细菌定植对气道反应性和肺功能的影响。方法34例稳定期COPD病人采用支气管舒张试验测定其气道可逆性。留取深部痰液,在1h内行细菌定量培养,检测其细菌定植量。结果本组COPD病人支气管舒张试验阳性者9例,下呼吸道细菌定植量为7.44±0.26;支气管舒张试验阴性者25例,下呼吸道细菌定植量为5.95±0.39（P〈0.05）。第一秒用力呼气容积（FEV1）〈50%预计值者17例,其细菌定植量为7.11±0.17,FEV1≥50%预计值者共17例,其细菌定植量为5.60±0.54（P〈0.05）。结论气道反应性试验阳性者较气道反应性试验阴性者下呼吸道细窥定植量明显增多。     

稳定期慢性阻塞性肺疾病细菌定植与炎症细胞的关系

目的:对稳定期慢性阻塞性肺疾病(COPD)患者行痰定量细菌培养及痰细胞分类计数,以探讨下呼吸道细菌定植对气道炎症的影响。方法:选择近1个月无急性发作病史的稳定期COPD患者,通过痰诱导留取痰液,行痰定量细菌培养和痰细胞分类计数,比较下呼吸道细菌定植阳性组与阴性组的痰中炎症细胞水平。结果:33例稳定期COPD患者接受痰诱导,其中11例(32.4%)存在下呼吸道细菌定植(A组),22例为阴性(B组),A组痰中的嗜酸性粒细胞和中性粒细胞均高于B组(P<0.05),2组间的淋巴细胞和巨噬细胞水平差异无显著性(P>0.05)。结论:下呼吸道细菌定植可加重稳定期COPD患者的炎症反应,加重气流受限程度。     

慢性阻塞性肺病稳定期患者生活质量与下呼吸道细菌定植及炎症反应的相关性

目的探讨慢性阻塞性肺病(COPD)稳定期患者生活质量与下呼吸道细菌定植及炎症反应的相关性。方法选择中重度COPD稳定期患者30例。对患者进行生活质量(SGRQ)问卷调查,记录各项得分。采集患者与志愿者痰液作为样本,统一进行细菌半定量培养。对受试者进行血清分离、血常规检查、血气分析、肺功能检测,各类检查结果进行统计学分析,探讨生活质量与下呼吸道细菌定植及炎症反应的相关性。结果经显微观察其中主要的定植细菌包括肺炎链球菌、洛菲不动杆菌和铜绿假单胞菌、(副)流感嗜血杆菌。血清化验结果显示,含有细菌定植的患者血清,IL-8的含量高于未含有细菌定植的患者和对照组(P<0.01),FEV1%预计值和FEV1/FVC%要明显低于无细菌定植样品(P<0.05);患者SGRQ问卷调查结果,总分、症状得分、活动得分、影响分的分布情况与IL-8呈正相关,同FEV1%预计值呈负相关(P<0.01)。结论 COPD稳定期患者生活质量较健康人差,且部分患者存在细菌定植。细菌定植患者的生活质量较差,炎症反应较重,三者具有明显的相关性。     

慢性阻塞性肺疾病稳定期患者下呼吸道细菌定植及对血清TNF-α、IL-8的影响

目的 探讨慢性阻塞性肺疾病(COPD)稳定期患者下呼吸道细菌定植(LABC)与炎症反应的关系.方法 选择62例COPD稳定期患者,留取痰液标本并进行培养,检测患者血清肿瘤坏死因子α(TNF-α)、白介素8(IL-8)水平,对患者进行肺功能测定.结果 62例患者中有18例(29.03％)患者存在LABC,存在LABC患者血清TNF α、IL-8水平高于无LABC者(P＜0.05);存在LABC者肺功能FEV1％ pred、FEV1/FVC低于无LABC者,吸烟指数≥400的比例大于无LABC者,差异均有统计学意义(P ＜0.05);LABC定量培养结果与TNF-α及IL-8水平呈正相关(P＜0.05).结论 部分COPD稳定期患者存在LABC,而LABC可加重患者炎症反应,加剧肺功能的损害.     

下呼吸道细菌定植对稳定期COPD患者免疫细胞和炎性因子水平的影响分析

目的探讨下呼吸道细菌定植对稳定期慢性阻塞性肺疾病(COPD)患者免疫细胞和炎性因子水平影响。方法选取2014年2月至2015年12月在我院诊治的稳定期COPD患者为研究对象,根据患者痰培养结果,将患者分为合并有下呼吸道细菌定植的定植组(57例)以及无下呼吸道细菌定植的对照组(37例),检测比较两组患者中性粒细胞、抑制性T细胞、巨噬细胞、辅助T细胞及痰液白介素-6(IL-6)、痰液和血白介素-8(IL-8)、血超敏C反应蛋白(hs-CRP)、血肿瘤坏死因子-α(TNF-α)水平。结果定植组COPD患者中性粒细胞、抑制性T细胞水平(%)高于对照组,巨噬细胞、辅助T细胞水平(%)低于对照组,差异有统计学意义(P0.05);定植组COPD患者痰液IL-6、痰液和血IL-8、血hs-CRP、血TNF-α水平均高于对照组,差异有统计学意义(P0.05)。结论存在下呼吸道细菌定植的稳定期COPD患者免疫功能较低,炎症反应较重,临床上应根据药敏试验等结果,选择敏感抗生素对患者进行针对性治疗,以缓解炎症反应、提高机体免疫力,改善患者的肺功能和生活质量。     

慢性阻塞性肺疾病稳定期下呼吸道细菌定植与疾病分级、评估的相关性

目的探讨慢性阻塞性肺病(COPD)患者稳定期下呼吸道细菌定植状况与肺功能分级、症状评估和急性加重频率的关系。方法入选中、重度COPD稳定期患者60例,痰液标本行细菌半定量培养,并行血常规、血气分析、肺功能检测及CAT、SGRQ生活质量问卷调查。结果 60例患者中,痰细菌半定量培养≥+++者为30%(18/60),主要定植细菌为副流感嗜血杆菌、铜绿假单胞菌、肺炎链球菌、肺炎克雷伯菌、流感嗜血杆菌;肺功能分级:1级0例,2级24例(40%),3级24例(40%),4级12例(20%);症状和急性加重频率分组:A组6例,B组18例,C组0例,D组36例;存在细菌定植的患者与无细菌定植者在每年急性发作次数、肺功能、SGRQ评分和CAT评分差别有统计学意义(P0.05);稳定期细菌定植与急性加重次数、肺功能分级、CAT评分、SGRQ得分总分、症状得分、日常生活影响得分呈正相关(P0.01、P0.05);与FEV1%预计值、FEV1/FVC存在负相关(P0.01); CAT评分与SGRQ的各项评分均有显著的相关性。结论 COPD稳定期患者中,部分患者存在下呼吸道细菌定植,细菌定植者比无细菌定植者表现出更差的肺功能和生活质量,且更易出现急性加重,CAT评分能较客观地反映患者的临床症状,而且简便易行操作性更强。     

COPD患者与维生素D的关系研究

目的探讨稳定期COPD患者下呼吸道细菌定植(LABC)与维生素D缺乏的关系。方法 56例稳定期COPD患者根据是否存在LABC分为定植组与无定植组,比较两组患者血清25-OH维生素D及肺功能的差异。结果 56例患者存在LABC者有23例,占41.07%;定植组患者FEV1%、FEV1/FVC水平显著低于无定植组,血清25-OH维生素D水平显著低于无定植组,差异均有统计学意义(P0.05);定植组患者血清25-OH维生素D水平与FEV1%、FEV1/FVC呈正相关(P0.05)。结论维生素D水平低的稳定期COPD患者更容易存在LABC,且患者其肺功能更差。     

布地格福吸入气雾剂联合细菌溶解产物对重度COPD稳定期患者气道炎症水平及呼吸功能的影响

目的 探究布地格福气雾剂联合细菌溶解产物对反复急性加重的重度慢性阻塞性肺疾病(COPD)稳定期患者的气道炎症水平及呼吸功能的影响。方法 将120例重度COPD稳定期患者作为研究对象,筛选前12个月有中度或重度COPD急性加重史至少1次,COPD评估测试(CAT)≥10分,使用随机法将其分为对照组和研究组各60例。对照组给予布地格福气雾剂治疗,研究组加用细菌溶解产物治疗,两组观察时间为12个月,评价联合治疗组对重度COPD稳定期患者气道炎症水平及呼吸功能的影响。结果 治疗前两组基线血氧饱和度(SPO₂)、白细胞计数(WBC)、肺功能指标、炎症因子水平、1年内急性加重次数均无统计学差异(P>0.05)。治疗后研究组SPO₂较对照组明显增高,而WBC、C反应蛋白(CRP)、24 h痰液体积、炎症因子水平较对照组均明显下降(P<0.05),治疗后两组6 min步行距离(6MWD)、肺功能指标包括第1秒用力呼气容积(FEV1)、FEV1/用力肺活量(FVC)、FEV1占预计值百分比无统计学差异(P>0.05)。治疗后研究组改良呼吸困难...     

稳定期慢性阻塞性肺疾病患者呼吸道潜在致病微生物特点及对气道炎症的影响

目的探讨稳定期慢性阻塞性肺疾病(COPD)患者呼吸道潜在致病微生物(PPMs)的特点及其与气道炎症、COPD急性加重的关系。方法稳定期COPD患者185例,采用自行咳痰或痰诱导方法留取合格痰液,进行痰白细胞计数和细菌培养。随后进行随访,随访间歇3个月,共随访3次,每次随访均取痰液行痰白细胞计数和细菌培养。记录随访期间COPD急性加重次数。结果总PPMs阳性率为37.3%,其中最常检测到的PPMs为流感嗜血杆菌(HI)。与PPMs阴性组相比,PPMs阳性组的第1秒用力呼气容积(FEV1)、FEV1/预计值、FEV1/用力肺活量(FVC)较低,而外周血中性粒细胞和百分比、痰白细胞、中性粒细胞和百分比较高(P<0.05)。4个时点均完成痰液检测的患者共有163例,PPMs阴性率、1次、2次、多次(3次或4次)PPMs阳性率分别为45.4%、23.3%、18.4%、12.9%,其中19例持续存在HI。与HI阴性组相比,HI阳性组痰白细胞、中性粒细胞和百分比均较高(P<0.05)。结论稳定期COPD患者呼吸道有较高的PPMs阳性率,尤其是流感嗜血杆菌持续存在于呼吸道中,并且与COPD气道炎症关系密切。     

Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis

PURPOSE: Viable bacteria are often isolated from airway secretions in clinically stable patients with chronic bronchitis. We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation. SUBJECTS AND METHODS: We performed quantitative sputum cultures in 160 stable patients [55 with chronic obstructive pulmonary disease (COPD) and normal serum alpha(1)-antitrypsin levels, 62 with COPD and severe alpha(1)-antitrypsin deficiency (PiZ), and 43 with idiopathic bronchiectasis]. The results were related to several indicators of the mechanisms and severity of airway inflammation. RESULTS: Airway bacterial load correlated with sputum myeloperoxidase level, an indirect measure of neutrophil activation and number (r = 0.50, P<0. 001); sputum neutrophil chemoattractants [interleukin-8 level (r = 0. 68, P<0.001) and leukotriene B4 level (r = 0.53, P<0.001)]; sputum leukocyte elastase activity (r = 0.55, P<0.001); and albumin leakage from serum to sputum (r = 0.26, P<0.01). Markers of inflammation increased at bacterial loads of 10(6) to 10(7) colony-forming units per milliliter, and increased progressively with increasing bacterial load. For example, the median (interquartile range) sputum myeloperoxidase level was 0.3 U/mL (0.1 to 0.5 U/mL) for patients who were not colonized or who had mixed normal oropharyngeal flora alone; 0.5 U/mL (0.2 to 0.7 U/mL) for patients with 10(5) to 10(6) colony-forming units per milliliter (P = 0.07); 0.5 U/mL (0.3 to 1.2 U/mL) for patients with 10(6) to 10(7) colony-forming units per milliliter (P<0.01); 0.7 U/mL (0.3 to 1.2 U/mL) for patients with 10(7) to 10(8) colony-forming units per milliliter (P <0.005); and 2.4 U/mL (0.7 to 4.8 U/mL) for patients with 10(8) or greater colony-forming units per milliliter (P<0.0001). The bacterial species influenced airway inflammation; for example, sputum myeloperoxidase activity was greater (P<0.005) in patients colonized with Pseudomonas aeruginosa [median 32 U/mL (interquartile range, 20 to 65 U/mL)] than those colonized with nontypeable Hemophilus influenzae [4 U/mL (2 to 31 U/mL)], which in turn was greater (P = 0.01) than among those colonized with Moraxella catarrhalis [1.1 U/mL (0.6 to 1.8 U/mL)]. We did not find a relation between bacterial load and lung function.CONCLUSIONS: The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis. Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function.     

慢性阻塞性肺疾病稳定期下呼吸道细菌定植与肺功能关系研究

目的 探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者下呼吸道细菌定植(lower airway bacterial colonization,LABC)与气道炎症和肺功能损害之间的关系.方法 在稳定期入选确诊中、重度COPD患者(男性38例,中度24例)46例,于基线期进行痰菌落计数、细菌培养,细胞因子检测和肺功能检查,随访1年后统计患者COPD急性加重次数,并于研究结束时复测肺功能.结果 在基线期痰细菌菌落计数＞104 cfu/ml的患者为15例(32.6%),提示存在LABC,以流感嗜血杆菌为主(7/15).存在LABC患者基线期痰液中的白介素6及肿瘤坏死因子α[分别为(188.33±127.19)pg/ml和(169.33±119.86)pg/ml]显著高于无LABC患者组[分别为(104.84±133.84)pg/ml和(100.97±108.85)pg/ml](P＜0.05);两组1年内急性加重次数分别为(2.92±1.11)次和(2.21±0.49)次,而第1秒用力呼气容积下降值分别为(0.063±0.12)L和(0.044±0.13)L,差异有统计学意义(P＜0.05);肺功能下降水平与急性加重发生次数呈显著正相关(P＜0.05).结论 部分COPD稳定期患者的气道中存在LABC,以流感嗜血杆菌为主,LABC可能是影响COPD病程的重要因素.     

Smoking and airway inflammation in patients with mild asthma.

STUDY OBJECTIVES: Cigarette smoking is common in asthmatic patients, and we investigated the impact of cigarette smoking on airway inflammation in asthma. DESIGN: Single-center observational study of airway inflammation in asthmatic and healthy smokers and nonsmokers. SETTING: Asthma research unit in a university hospital. PATIENTS OR PARTICIPANTS: Sixty-seven asthmatic and 30 nonasthmatic subjects classified as smokers or nonsmokers. Asthmatics had chronic, stable asthma and were not receiving inhaled or oral steroids at the time of the study. INTERVENTIONS: We examined induced-sputum cell counts and levels of interleukin (IL)-8 and eosinophilic cationic protein (ECP). Bronchial hyperreactivity was assessed using methacholine challenge. MEASUREMENTS AND RESULTS: Asthmatic smokers had higher total sputum cell counts than nonsmoking asthmatics and both smoking and nonsmoking healthy subjects. Smoking was associated with sputum neutrophilia in both asthmatics and nonasthmatics (median, 47% and 41%, respectively) compared with nonsmokers (median, 23% and 22%, respectively), and sputum IL-8 was increased in smokers compared with nonsmokers, both in subjects with asthma (median, 945 pg/mL vs 660 pg/mL, respectively) and in healthy subjects (median, 1,310 pg/mL vs 561 pg/mL, respectively). Sputum eosinophils and ECP levels were higher in both nonsmoking and smoking asthmatics than in healthy nonsmokers. In smoking asthmatics, lung function (FEV(1) percent predicted) was negatively related to both sputum IL-8 (r = - 0.52) and sputum neutrophil proportion (r = - 0.38), and sputum IL-8 correlated positively with smoking pack-years (r = 0.57) and percent neutrophil count (r = 0.51). CONCLUSIONS: In addition to the eosinophilic airway inflammation observed in patients with asthma, smoking induces neutrophilic airway inflammation; a relationship is apparent between smoking history, airway inflammation, and lung function in smoking asthmatics.     

Levels of IL-32 in Serum,Induced Sputum Supernatant,and Bronchial Lavage Fluid of Patients with Chronic Obstructive Pulmonary Disease

Interleukin-32 (IL-32) is a newly described cytokine which is expected to have an important role in autoimmune disorders. It was shown that chronic obstructive pulmonary disease (COPD) has a component of autoimmunity, though the role of IL-32 in its pathogenesis is not known. The aim of this study was to estimate IL-32 concentrations in serum, induced sputum (IS) supernatant and bronchoalveolar lavage (BAL) fluid from patients with COPD, and to compare asthma patients with and healthy subjects. Outpatients with COPD (63.7 ± 8.4 years, n = 51), asthma (58.3 ± 12.4 years, n = 31), and healthy subjects (59.8 ± 8.2 years, n = 9) were studied. The levels of IL-32 in serum, BAL fluid, and IS supernatant samples were analyzed by ELISA. Concentrations of IL-32 were higher in all the studied materials from patients with COPD (BAL 22.46 ± 2.48 pg/ml, IS 19.66 ± 1.69 pg/ml, serum 26.77 ± 2.56 pg/ml) in comparison with patients with asthma (BAL 6.25 ± 1.08 pg/ml, IS 5.82 ± 1.15 pg/ml, serum 6.09 ± 1.16 pg/ml, p < 0.05 respectively) as well as healthy subjects (BAL 4.21 ± 1.13 pg/ml, IS 3.59 ± 0.66 pg/ml, serum 4.63 ± 1.03 pg/ml, p < 0.05 respectively). Moreover, the level of IL-32 was higher in COPD smokers than in COPD ex-smokers in investigated respiratory tissue compartments and serum, and correlated with smoking history. Increased level of IL-32 in serum, IS supernatant, and BAL fluid from patients with COPD in comparison with asthma patients and healthy subjects suggest that IL-32 may play an important role in the pathogenesis of COPD, which depends on the smoking history.     

稳定期慢性阻塞性肺疾病气道炎症与系统性炎症关系的研究

目的 初步探讨稳定期慢性阻塞性肺疾病(COPD)气道炎症与系统性炎症的关系.方法 入选符合中华医学会呼吸病学分会2007年COPD指南的稳定期COPD患者35例.检测肺功能、痰定量细菌培养及痰细胞计数与分类、测定血浆纤维蛋白原、血清C反应蛋白(C-reactive protein,CRP)水平,分析气道炎症与系统性炎症...     

Relationships among bacteria, upper airway, lower airway, and systemic inflammation in COPD

STUDY OBJECTIVE: The upper and lower airways are continuous. While upper airway symptoms are common in COPD patients, with accumulating evidence to suggest increased nasal inflammation, the relationships among upper airway, lower airway, and systemic inflammatory indexes have not been studied. We aimed to confirm that there is heightened nasal inflammation in COPD patients, to test the hypothesis that the degree of upper airway inflammation relates to the degree of lower airway inflammation, and to investigate the underlying associations with bacterial carriage and the systemic inflammatory response. DESIGN: Prospective cohort study. SETTING: Outpatient Department, London Chest Hospital, London, UK. PARTICIPANTS: Forty-seven patients with COPD and 12 control subjects of similar age, sex, and smoking status. MEASUREMENTS: Serum, nasal wash fluid, and sputum samples were obtained from 47 stable patients with COPD for the analysis of inflammatory indexes and bacterial colonization. Nasal wash fluid specimens were obtained from 12 control subjects. RESULTS: COPD patients had an increased nasal interleukin (IL)-8 concentration compared to control subjects (difference, 97.2 pg/mL; p = 0.009). The nasal IL-8 concentration in COPD patients correlated with that in sputum (r = 0.30; p = 0.039). In both the upper and lower airways of patients with COPD, the IL-8 concentration was associated with indexes of bacterial colonization. Patients colonized with a sputum potentially pathogenic microorganism had a higher total nasal bacterial load (difference, 1.5 log cfu/mL; p = 0.016). We did not find significant relationships between the degree of upper or lower airway inflammation, or bacterial carriage, and the systemic inflammatory response. CONCLUSIONS: COPD is associated with an increased nasal concentration of the neutrophil chemoattractant protein IL-8, the degree of which reflects that present in the lower airway. A relationship between lower airway bacterial colonization, postnasal drip, and higher nasal bacterial load may suggest a mechanism underlying this finding. This study is the first to report a correlation between the degree of upper and lower airway inflammation in COPD.     

Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD

STUDY OBJECTIVES: The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD. DESIGN: Prospective cohort study. SETTING: Outpatient Department, London Chest Hospital, London, UK. PATIENTS: Thirty-nine patients with COPD. MEASUREMENTS: We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed. RESULTS: A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H. influenzae had higher bacterial loads (10(8.56) cfu/mL vs 10(8.05)cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone. CONCLUSIONS: The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.     

CXCR3 and CCR5 chemokines in induced sputum from patients with COPD

BACKGROUND: COPD is associated with increased numbers of CD4(+) and CD8(+) lymphocytes and macrophages in the small airways and lung parenchyma. The chemokines regulating T-cell recruitment into the lung are unknown but may involve CXCR3 and CCR5 chemoattractants. The aims of this study were to determine the concentrations of CXCR3 chemokines CXCL9, CXCL10, CXCL11, and the CCR5 chemokine CCL5 in induced sputum from patients with COPD, smokers, and nonsmokers, and to examine the relationship between chemokine expression, inflammatory cells, and airway obstruction. METHODS: Differential cell counts were performed and concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were measured in induced sputum from nonsmokers (n = 18), smokers (n = 20), and COPD patients (n = 35) using an enzyme-linked immunosorbent assay. RESULTS: Concentrations of CXCL9, CXCL10, CXCL11, and CCL5 were significantly increased in the sputum of patients with COPD when compared with nonsmokers but not smokers without obstruction: CXCL9 (median, 14.3 pg/mL; interquartile range [IQR], 6.5 to 99.3; vs median, 1.4 pg/mL; IQR, 0 to 10.4 [p < 0.001]; vs 8.5 pg/mL; IQR, 0 to 16.0, respectively); CXCL10 (16.9 pg/mL; IQR, 6.2 to 148.8; vs 3.7 pg/mL; IQR, 0 to 18.8 [p < 0.05]; vs 11.3 pg/mL; IQR, 3.7 to 46.7); CXCL11 (58.1 pg/mL; IQR, 34.5 to 85.3; vs 33.5 pg/mL; IQR, 23.2 to 49.7 [p < 0.05]; vs 49.8 pg/mL; IQR, 32.6 to 105.6); and CCL5 (59.9 pg/mL; IQR, 57.1 to 67.8; vs 33.5 pg/mL; IQR, 31.6 to 36.9 [p < 0.001]). CCL5 in sputum from smokers was also significantly increased compared with that from nonsmokers (median, 63.0 pg/mL; IQR, 60.8 to70.2; p < 0.001). There was a negative correlation between FEV(1) percentage of predicted, FEV(1)/FVC ratio, and percentage of macrophages, and all the chemokines analyzed. Neutrophil numbers correlated positively with the concentrations of chemokines. CONCLUSIONS: CXCR3 chemokines and CCL5 are increased in sputum from COPD patients compared with nonsmokers, and may be important in COPD pathogenesis.     

Leukotriene B4 in exhaled breath condensate and sputum supernatant in patients with COPD and asthma

STUDY OBJECTIVES: Some patients with COPD present with significant reversibility of airflow limitation after receiving bronchodilation therapy. Leukotriene B(4) (LTB(4)) has been implicated in the pathophysiology of both COPD and asthma. We tested the hypothesis that COPD patients with airflow reversibility and asthmatic patients who smoke might have similar levels of LTB(4) in exhaled breath condensate (EBC) and sputum supernatant. The repeatability and stability of LTB(4) measurements were additionally studied. DESIGN: Prospective, cross-sectional study. PATIENTS OR PARTICIPANTS: We studied 30 patients with COPD (15 smokers [FEV(1), 56% predicted; SD, 6% predicted]; 15 patients with significant reversibility in airway obstruction after bronchodilation [FEV(1), 14% predicted; SD, 2% predicted]). Fifteen asthmatic patients who smoked, with similar FEV(1) and reversibility were also studied. Ten healthy smokers served as control subjects. SETTING: A hospital research laboratory. INTERVENTIONS: Spirometry and reversibility testing were performed on the first visit. On the following day, EBC was collected for the measurement of LTB(4), and induced sputum was collected for differential cell counts and LTB(4) measurement in the sputum supernatant. MEASUREMENTS AND RESULTS: LTB(4) levels in EBC [mean (SD)] were increased in COPD patients (mean, 86.7 pg/mL; SD, 19 pg/mL) and asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL) compared to control subjects (mean, 32.3 pg/mL; SD, 10 pg/mL; p < 0.0001 for both groups). COPD patients with airflow reversibility (mean, 99.8 pg/mL; SD, 12 pg/mL) had values similar to those of asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL; p = 0.2) and higher than those of COPD patients without airflow reversibility (mean, 73.7 pg/mL; SD, 17 pg/mL; p = 0.002). Similar results were observed in the sputum supernatant. Measurements of LTB(4) in EBC and sputum were repeatable on two consecutive days, but measurements in the frozen samples of EBC and sputum were not stable after 3 weeks. CONCLUSIONS: Patients with asthma and reversible COPD presented with higher LTB(4) values compared to patients with nonreversible COPD and healthy smokers. This difference may be mainly attributed to the presence of reversibility in airway obstruction, probably as part of a common underlying inflammatory process.