Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease

RATIONALE: In addition to pulmonary involvement, stable chronic obstructive pulmonary disease (COPD) is associated with nasal and systemic inflammation. Although exacerbations of COPD are associated with increased pulmonary and systemic inflammation, determinants of the systemic response remain obscure, and nor is it known whether there is nasal involvement. OBJECTIVES: To investigate upper airway, lower airway, and systemic inflammation at exacerbation of COPD. METHODS: We sampled sputum, nasal wash, and serum from 41 exacerbations (East London cohort) for analysis of pathogenic microorganisms and inflammatory indices (sputum/nasal wash leukocytes, interleukin [IL]-6, IL-8, and myeloperoxidase; serum IL-6 and C-reactive protein). Values were compared with stable COPD. MEASUREMENTS AND MAIN RESULTS: Exacerbation of COPD is associated with greater nasal, sputum, and serum inflammation than the stable state. At exacerbation, inflammatory markers were highly correlated within nasal wash and serum (all r >/= 0.62, p < 0.001), but not sputum. The degree of upper airway inflammation correlated with the degree of lower airway inflammation (e.g., nasal wash/sputum myeloperoxidase; r = 0.50, p = 0.001). The degree of systemic inflammation correlated with the degree of lower airway inflammation (e.g., serum IL-6/sputum IL-8; r = 0.35, p = 0.026), and was greater in the presence of a sputum bacterial pathogen (29.0 g/dl C-reactive protein difference, p = 0.002). We did not find relationships between the upper airway and systemic compartments. CONCLUSIONS: Exacerbation of COPD is associated with pan-airway inflammation; the systemic inflammatory response is proportional to that occurring in the lower airway and greater in the presence of a bacterial pathogen.     

稳定期慢性阻塞性肺疾病下呼吸道细菌定植与气道炎症关系的研究

目的:研究稳定期慢性阻塞性肺疾病(COPD)患者下呼吸道细菌定植与气道炎症、吸烟、肺功能的关系。方法:入选34例稳定期COPD门诊患者,测定其肺功能,留取深部痰液进行细菌定量培养。抽取静脉血,检测血清和痰液白细胞介素-8(IL-8)浓度,对他们的相关性进行统计学分析。结果:下呼吸道细菌定植≥107菌落形成单位(CFU)/mL组,其血清及痰液IL-8浓度与下呼吸道细菌定植量<107CFU/mL组相比,2组差异有显著性(P<0.05)。下呼吸道细菌定植≥107CFU/mL组吸烟指数与下呼吸道细菌定植量<107CFU/mL组相比,2组差异有显著性(P<0.05)。第一秒用力呼气量(FEV1)<50%预计值组细菌定植量与FEV1≥50%预计值组比较,2组差异有显著性(P<0.05)。结论:稳定期COPD患者的气道炎症与吸烟和下呼吸道细菌定植有关,吸烟和下呼吸道细菌定植可导致气道炎症加重。     

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.     

Relationship between airway colonization, inflammation and exacerbation frequency in COPD

RATIONALE: To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). RESULTS: BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). CONCLUSION: The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.     

Bronchiectasis, exacerbation indices, and inflammation in chronic obstructive pulmonary disease

Relationships between high-resolution computed tomography (HRCT) findings in chronic obstructive pulmonary disease (COPD) and bacterial colonization, airway inflammation, or exacerbation indices are unknown. Fifty-four patients with COPD (mean [SD]: age, 69 [7] years; FEV(1), 0.96 [0.33] L; FEV(1) [percent predicted], 38.1 [13.9]%; FEV(1)/forced vital capacity [percent predicted], 40.9 [11.8]%; arterial partial pressure of oxygen, 8.77 [1.11] kPa; history of smoking, 50.5 [33.5] smoking pack-years) underwent HRCT scans of the chest to quantify the presence and extent of bronchiectasis or emphysema. Exacerbation indices were determined from diary cards over 2 years. Quantitative sputum bacteriology and cytokine measurements were performed. Twenty-seven of 54 patients (50%) had bronchiectasis on HRCT, most frequently in the lower lobes (18 of 54, 33.3%). Patients with bronchiectasis had higher levels of airway inflammatory cytokines (p = 0.001). Lower lobe bronchiectasis was associated with lower airway bacterial colonization (p = 0.004), higher sputum interleukin-8 levels (p = 0.001), and longer symptom recovery time at exacerbation (p = 0.001). No relationship was seen between exacerbation frequency and HRCT changes. Evidence of moderate lower lobe bronchiectasis on HRCT is common in COPD and is associated with more severe COPD exacerbations, lower airway bacterial colonization, and increased sputum inflammatory markers.     

Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the airways and lung parenchyma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (1) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically stable state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected from patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time point for soluble markers associated with neutrophilic inflammation; myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8). Serologic assays on acute and convalescent sera were performed for respiratory viruses, and induced sputum was also subject to quantitative bacterial cultures, viral cultures, and polymerase chain reaction (PCR) for detection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 15-mo study period. TNF-alpha and IL-8 were significantly elevated in the sputum of patients during acute COPD exacerbation compared with when they were clinically stable (p = 0.01 and p = 0.05, respectively). Concentrations of these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract infections. Patients with documented infection did not demonstrate greater increases in sputum levels of inflammatory cytokines during exacerbations compared with patients without demonstrable infection. We conclude that markers of airway neutrophilic inflammation increase at the time of acute COPD exacerbation and then decline 1 mo later, and that this acute inflammatory response appears to occur independently of a demonstrable viral or bacterial airway infection.     

Eosinophilic airway inflammation in COPD

Chronic obstructive pulmonary disease is a common condition and a major cause of mortality. COPD is characterized by irreversible airflow obstruction. The physiological abnormalities observed in COPD are due to a combination of emphysema and obliteration of the small airways in association with airway inflammation. The predominant cells involved in this inflammatory response are CD8+ lymphocytes, neutrophils, and macrophages. Although eosinophilic airway inflammation is usually considered a feature of asthma, it has been demonstrated in large and small airway tissue samples and in 20%–40% of induced sputum samples from patients with stable COPD. This airway eosinophilia is increased in exacerbations. Thus, modifying eosinophilic inflammation may be a potential therapeutic target in COPD. Eosinophilic airway inflammation is resistant to inhaled corticosteroid therapy, but does respond to systemic corticosteroid therapy, and the degree of response is related to the intensity of the eosinophilic inflammation. In COPD, targeting treatment to normalize the sputum eosinophilia reduced the number of hospital admissions. Whether controlling eosinophilic inflammation in COPD patients with an airway eosinophilia will modify disease progression and possibly alter mortality is unknown, but warrants further investigation.     

慢性阻塞性肺病患者鼻腔与下气道炎症状况相关性研究

目的 探讨慢性阻塞性肺病(COPD)急性加重期患者治疗前后鼻灌洗液炎症细胞、细胞因子与生活质量评分、肺功能和下气道相应指标的相关性.方法 观察29例COPD急性加重期患者治疗前后的肺功能、SNOT-20、SGRQ评分以及鼻灌洗液、痰中性粒细胞、IL-8、IL-6含量差异,比较鼻灌洗液与部分炎症相应指标、FEV1、SNOT-20和SCRQ评分的相关性.结果 COPD患者鼻灌洗液、痰细胞总数、中性粒细胞比例(N%)、IL-8、IL-6含量和SGRQ评分随分级的增加而增高(P＜0.05),重度患者鼻部症状评分(SNOT-20)最高.治疗2周后中、重度患者FEV1%明显升高,鼻灌洗液和痰细胞总数、N%、IL-8含量显著降低;轻度患者仅痰IL-8明显降低,其它各项指标变化不明显.三组患者鼻灌洗液N%、IL-8含量皆与FEV1%呈显著负相关、与痰N%、IL-8呈正相关;中、重度组鼻灌洗液N%、IL-8与SGRQ呈显著正相关.结论 COPD患者鼻腔炎症状况可一定程度反映下呼吸道炎症情况、预测病情严重度并有助于判断预后.     

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...     

Moraxella catarrhalis acquisition, airway inflammation and protease-antiprotease balance in chronic obstructive pulmonary disease

Background  

Moraxella catarrhalis causes approximately 10% of exacerbations in chronic obstructive pulmonary disease (COPD) and also colonizes the lower airway in stable patients. Little is known about the effects of colonization by M. catarrhalis on airway inflammation and protease-antiprotease balance, and how these changes compare to those seen during exacerbations. Since COPD is a progressive inflammatory disease, elucidating the effects of bacterial colonization and exacerbation on airway inflammation is relevant to understanding disease progression in COPD. Our aims were (1) Analyze changes in airway inflammation in colonization and exacerbation of COPD due to M. catarrhalis; (2) Explore protease-antiprotease balance in colonization and exacerbation due to M. catarrhalis. Our hypothesis were (1) Acquisition of a new strain of M. catarrhalis in COPD increases airway inflammation from baseline and alters the protease-antiprotease balance towards a more proteolytic environment; (2) These changes are greater during exacerbations associated with M. catarrhalis as compared to colonization.     

Respiratory syncytial virus, airway inflammation, and FEV1 decline in patients with chronic obstructive pulmonary disease

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as an important pathogen in adults with cardiopulmonary disease. It has been associated with acute exacerbations of chronic obstructive pulmonary disease (COPD); however, it has also been detected in the lower airway in the stable state, but the consequences of RSV in stable disease have not previously been determined. We therefore studied the consequences of RSV persistence in adults with COPD and its effect on airway inflammation and lung function decline. METHODS: A total of 241 sputum samples from 74 patients with COPD (FEV(1)% predicted, 39.2%; interquartile range, 29.6-57.8%) were collected quarterly in the stable state over 2 yr. RSV was detected by polymerase chain reaction (PCR), quantitative microbiology was performed, and inflammatory cytokines were quantified by ELISA. RESULTS: RSV RNA was detected in 32.8% of sputum samples. Patients in whom RSV was more frequently detected (> 50% of samples RSV PCR-positive, n=18) had higher airway inflammation and faster FEV(1) decline over the study (101.4 ml/yr [95% confidence interval, 57.1-145.8]) compared with those with less frequent detection of RSV (n=56; 51.2 ml/yr [31.7-70.8]; p=0.01). The observed relationship between RSV detection and accelerated lung function decline was independent of smoking status, exacerbation frequency, and lower airway bacterial load. CONCLUSIONs: Persistent RSV detection in patients with COPD is associated with airway inflammation and accelerated decline in FEV(1). Chronic RSV infection may be a novel therapeutic target to alter the natural history of COPD.     

Characteristics of airway inflammation and bronchodilator reversibility in COPD: a potential guide to treatment

STUDY OBJECTIVES: The management of stable patients with COPD depends on the severity of symptoms and airflow limitation. Regarding inflammation, corticosteroids are the only medications that are recommended for use, and only under restricted circumstances. Corticosteroids tend to undertreat or overtreat patients with COPD when only clinical manifestations and the findings of simple spirometry are considered. Accordingly, our aim was to survey the characteristics of airway inflammation in stable COPD patients, and to assess the interrelations among inflammatory cells, inflammatory mediators, bronchodilator reversibility, and pulmonary function. Factors related to airway inflammation and bronchodilator reversibility may be important in the management of stable COPD patients. METHODS: A total of 88 stable patients with smoking-related COPD were recruited into the study. All patients were steroid-free, and had been treated with theophylline, oral beta(2)-agonist agents, anticholinergic agents, and possibly mucolytic agents. Bronchodilator tests and sputum induction were performed to evaluate bronchodilator reversibility, and numbers of inflammatory cells and mediators (eg, interleukin [IL]-8, eotaxin, and regulated on activation, normal T cells expressed and secreted [RANTES]). RESULTS: Thirty-one of 48 patients (64.6%) who had bronchodilator reversibility, and 19 of 40 patients (47.5%) without bronchodilator reversibility had sputum eosinophilia (median, 8.0% and 7.0%, respectively). FEV(1) showed a significant inverse correlation with the number of sputum neutrophils. The correlation coefficient for postbronchodilator FEV(1) vs the percentage of neutrophils in patients with nonreversible COPD was higher than that in those with reversible COPD. The levels of IL-8 were closely associated with the percentage of neutrophils. The sputum concentrations of IL-8 and albumin were significantly higher in patients with nonreversible COPD than in those with reversible COPD. A significant inverse correlation was found between bronchodilator response (ie, DeltaFEV(1) and DeltaFVC) and prebronchodilator FEV(1). CONCLUSIONS: Eosinophilic inflammation may play a substantial role in COPD, while neutrophils and IL-8 may have a great influence on nonreversible obstructive airways. The assessment of airway inflammation and bronchodilator responses can help the selection of specific therapies and the prediction of clinical outcomes for COPD patients.     

Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by an accelerated decline in lung function and progressive airway inflammation. Bacteria have been isolated from the lower airway of stable COPD patients, and airway inflammation has been related to bacterial load and type. The relationship between bacterial colonization, airway inflammation, and lung function decline remains uncertain. We studied 30 patients with COPD, mean (SD) FEV1 0.947 (0.329), 34.8% (13.6%) predicted, for 12 months. Sputum collected at recruitment and the end of the study was analyzed for cytokines and for quantitative bacteriology. The decline in FEV1 was 57.6 (137.6) ml year-1. Bacterial growth was identified in all subjects, with an initial count of 107.47(0.91) cfu ml-1 rising to 107.93(0.81) cfu ml-1 at the end of the study (p = 0.019). FEV1 decline was related to this increase in airway bacterial load (r = 0.59, p = 0.001). FEV1 decline was greater in subjects who exhibited a change in the colonizing bacterial type compared with those with persistence of a single bacterial species over the study period (p = 0.017). Higher sputum interleukin (IL-8) was associated with greater declines in FEV1 (p = 0.03). Rising airway bacterial load and species changes are associated with greater airway inflammation and accelerated decline in FEV1. Bacterial colonization in COPD is an important factor in disease progression.     

Nasal and sinus inflammation in chronic obstructive pulmonary disease

Epidemiologic studies suggest that as many as 75% of patients with COPD have concomitant nasal symptoms and more than 1/3 of patients with sinusitis also have lower airway symptoms of asthma or COPD. Because the inflammatory response of the upper and lower airways are similar, and both sites have a similar exposure to allergens and irritants, it is not surprising that rhinitis or sinusitis would coexist with COPD. Possible mechanisms of combined upper and lower airway dysfunction include the so-called nasal-bronchial reflex, inflammation caused by smoking, mouth breathing caused by nasal obstruction, and pulmonary aspiration of nasal contents. Patients with chronic sinusitis commonly have nonspecific bronchial hyperresponsiveness, suggesting a neural reflex. Postnasal drainage of nasal inflammatory mediators during sleep also may increase lower airway responsiveness. Therapy of nasal and sinus disease is associated with improved pulmonary function in patients with COPD.     

Airway inflammation, airway responsiveness and cough before and after inhaled budesonide in patients with eosinophilic bronchitis.

Eosinophilic bronchitis is a common cause of chronic cough, characterized by sputum eosinophilia similar to that seen in asthma, but unlike asthma the patients have no objective evidence of variable airflow obstruction or airway hyperresponsiveness. The reason for the different functional associations is unclear. The authors have tested the hypothesis that in eosinophilic bronchitis the inflammation is mainly localized in the upper airway. In an open study the authors measured the lower (provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20)) and upper (PC25 MIF50) airway responsiveness to histamine, lower and upper airway inflammation using induced sputum and nasal lavage, in II patients with eosinophilic bronchitis. The authors assessed changes in these measures and in cough reflex sensitivity to capsaicin and cough severity after 400 microg of inhaled budesonide for 4 weeks. A nasal eosinophilia was present in only three patients with one having upper airway hyperresponsiveness. Following treatment with inhaled corticosteroids the geometric mean sputum eosinophil count decreased from 12.8% to 2.9% (mean difference 4.4-fold, 95% confidence interval (CI) 2.14-10.02), the mean +/- sem cough visual analogue score on a 100 mm scale decreased from 27.2 +/- 6.6 mm to 12.6 +/- 5.7 mm (mean difference 14.6, 95% CI 9.1-20.1) and the cough sensitivity assessed as the capsaicin concentration required to cause two coughs (C2) and five coughs (C5) improved (C2 mean difference 0.75 doubling concentrations, 95% CI 0.36-1.1; C5 mean difference 1.3 doubling concentration, 95% CI 0.6-2.1). There was a significant positive correlation between the fold change in sputum eosinophil count and doubling dose change in C5 after inhaled budesonide (r=0.61). It is concluded that upper airway inflammation is not prominent in eosinophilic bronchitis and that inhaled budesonide improves the sputum eosinophilia, cough severity and sensitivity suggesting a causal link between the inflammation and cough.     

稳定期慢性阻塞性肺疾病气道可逆性与气道炎症关系的研究

目的了解稳定期慢性阻塞性肺疾病(COPD)气道炎症与气道可逆性的关系。方法入选34例稳定期COPD门诊病人。测定其气道可逆性。检测痰液与血清中干细胞因子(SCF)、白细胞介素-8(IL-8)、嗜酸粒细胞阳离子蛋白(ECP)浓度。结果支气管舒张试验阳性组与阴性组比较,两者的IL-8浓度有显著性差异(P<0.05),但与SCF、ECP浓度无显著性差异。结论稳定期COPD病人的气道可逆性与IL-8浓度有关,而与嗜酸粒细胞、肥大细胞关系不明显。     

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.     

Local inflammation occurs before systemic inflammation in patients with COPD

Background and objective: COPD is associated not only with an abnormal inflammatory response in the lung but also with systemic inflammation, including systemic oxidative stress, activation of circulating inflammatory cells and increased circulating levels of inflammatory cytokines. Understanding the nature and course of systemic inflammation in COPD is important given the potential for anti‐inflammatory therapy. This study explored whether local and systemic inflammation occur concurrently in patients with COPD. Methods: Forty‐four patients with stable COPD, 10 smoking controls and 10 non‐smoking controls were enrolled in this observational study. Induced sputum and peripheral blood samples were obtained simultaneously for measurement of inflammatory cell numbers and the concentrations of IL‐6 and CRP. Results: The total number of cells in the sputum total cell number, percentage of neutrophils and the concentration of IL‐6 were significantly higher in smoking controls and patients with COPD than in non‐smoking controls (P < 0.05 and P < 0.01, respectively). As the disease stage progressed, airway inflammatory cells and IL‐6 levels increased. CRP levels in sputum were significantly higher in stage II, III and IV COPD patients than in smoking and non‐smoking controls (P < 0.01). However, the peripheral WCC and percentage of neutrophils were similar in patients with COPD, smoking and non‐smoking controls. Circulatory concentrations of IL‐6 and CRP in stages III and IV COPD patients were significantly higher than in smoking and non‐smoking controls (P < 0.05 and P < 0.01, respectively). Additionally, there were positive correlations between sputum and blood IL‐6 and CRP levels (r = 0.566, P < 0.01 and r = 0.443, P < 0.01, respectively). Conclusions: The increase in the inflammatory cell population and IL‐6 and CRP levels in the airway may occur earlier than in the peripheral blood, and reflect the degree of airflow limitation better than do peripheral blood measurements. Systemic inflammation may be present in patients with severe or very severe COPD.     

Inflammatory changes, recovery and recurrence at COPD exacerbation.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days. Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35 days post-exacerbation. In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8 mg.L(-1) versus 3.4 mg.L(-1). Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators. Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.     

Effect of bronchial colonisation on airway and systemic inflammation in stable COPD

The recovery of potentially pathogenic microorganisms (PPMs) from bronchial secretions is associated with a local inflammatory response in COPD patients. The objective of this study was to determine the relationships between bronchial colonisation and both bronchial and systemic inflammation in stable COPD. In COPD patients recruited on first admission for an exacerbation, bacterial sputum cultures, interleukin (IL)-1β, IL-6 and IL-8 levels, and blood C-reactive protein (CRP) were measured in stable condition. Bronchial colonisation was found in 39 of the 133 (29%) patients and was significantly related to higher sputum IL-1β (median [percentile 25-75]; 462 [121-993] vs. 154 [41-477] pg/ml, p = 0.002), IL-6 (147 [71-424] vs. 109 [50-197] pg/ml, p = 0.047) and IL-8 values (15 [9-19] vs. 8 [3-15] (×103) pg/ml, p = 0.002). Patients with positive cultures also showed significantly elevated levels of serum CRP (6.5 [2.5-8.5] vs. 3.5 [1.7-5.4] mg/l, p = 0.016). Bronchial colonisation by Haemophilus influenzae was associated with higher levels of IL-1β and IL-8 and clinically significant worse scores on the activity and impact domains of the St. George's Respiratory Questionnaire. In conclusion, bronchial colonisation is associated with bronchial inflammation and high blood CRP levels in stable COPD patients, being Haemophilus influenzae related to a more severe inflammatory response and impairment in health-related quality of life.