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.     

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.     

Relationship between chronic nasal and respiratory symptoms in patients with COPD

The relationship between the upper and lower airways in chronic obstructive pulmonary disease (COPD) is unknown. We examined the prevalence of chronic nasal symptoms and the correlation with lower respiratory symptoms and parameters of severity of COPD such as exacerbation frequency and spirometry. 61 COPD patients from the East London COPD cohort were studied. [Mean (SD) age 70 (6.96) years, FEV1 0.98 (0.38) l, FVC 2.45 (0.72) l, FEV1%Pred 37.0 (12.3), and 47.6 (31.8) smoking pack years, 14 current smokers, 36 males]. COPD patients had a high prevalence of nasal symptoms (75%), more than half reporting nasal discharge (52.5%) and sneezing (45.9%). Associations were found between nasal score and daily sputum production (P = 0.005) and post-nasal drip and sputum production (P = 0.046) with a trend to increased nasal symptoms in frequent exacerbators compared to infrequent exacerbators. No significant relationship was found between nasal symptoms and FEV1 or any other lower respiratory airway symptom. Associations between nasal and respiratory symptoms were found suggesting that there is a relationship between the upper and lower airway 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.     

Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease

Although exacerbations of chronic obstructive pulmonary disease (COPD) are associated with symptomatic and physiological deterioration, little is known of the time course and duration of these changes. We have studied symptoms and lung function changes associated with COPD exacerbations to determine factors affecting recovery from exacerbation. A cohort of 101 patients with moderate to severe COPD (mean FEV(1) 41.9% predicted) were studied over a period of 2.5 yr and regularly followed when stable and during 504 exacerbations. Patients recorded daily morning peak expiratory flow rate (PEFR) and changes in respiratory symptoms on diary cards. A subgroup of 34 patients also recorded daily spirometry. Exacerbations were defined by major symptoms (increased dyspnea, increased sputum purulence, increased sputum volume) and minor symptoms. Before onset of exacerbation there was deterioration in the symptoms of dyspnea, sore throat, cough, and symptoms of a common cold (all p < 0.05), but not lung function. Larger falls in PEFR were associated with symptoms of increased dyspnea (p = 0.014), colds (p = 0.047), or increased wheeze (p = 0.009) at exacerbation. Median recovery times were 6 (interquartile range [IQR] 1 to 14) d for PEFR and 7 (IQR 4 to 14) d for daily total symptom score. Recovery of PEFR to baseline values was complete in only 75.2% of exacerbations at 35 d, whereas in 7.1% of exacerbations at 91 d PEFR recovery had not occurred. In the 404 exacerbations where recovery of PEFR to baseline values was complete at 91 d, increased dyspnea and colds at onset of exacerbation were associated with prolonged recovery times (p < 0.001 in both cases). Symptom changes during exacerbation do not closely reflect those of lung function, but their increase may predict exacerbation, with dyspnea or colds characterizing the more severe. Recovery is incomplete in a significant proportion of COPD exacerbations.     

Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations

RATIONALE: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are major causes of health care costs mostly related to hospitalization. The role of infections in COPD exacerbations is controversial. OBJECTIVES: We investigated whether COPD exacerbations requiring hospitalization are associated with viral and/or bacterial infection and evaluated relationships among infection, exacerbation severity, assessed by reduction of FEV1, and specific patterns of airway inflammation. METHODS: We examined 64 patients with COPD when hospitalized for exacerbations, and when in stable convalescence. We measured lung function, blood gases, and exhaled nitric oxide, and examined sputum for inflammation and for viral and bacterial infection. RESULTS: Exacerbations were associated with impaired lung function (p < 0.01) and increased sputum neutrophilia (p < 0.001). Viral and/or bacterial infection was detected in 78% of exacerbations: viruses in 48.4% (6.2% when stable, p < 0.001) and bacteria in 54.7% (37.5% when stable, p = 0.08). Patients with infectious exacerbations (29.7% bacterial, 23.4% viral, 25% viral/bacterial coinfection) had longer hospitalizations (p < 0.02) and greater impairment of several measures of lung function (all p < 0.05) than those with noninfectious exacerbations. Patients with exacerbations with coinfection had more marked lung function impairment (p < 0.02) and longer hospitalizations (p = 0.001). Sputum neutrophils were increased in all exacerbations (p < 0.001) and were related to their severity (p < 0.001), independently of the association with viral or bacterial infections; sputum eosinophils were increased during (p < 0.001) virus-associated exacerbations. CONCLUSIONS: Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially those with viral/bacterial coinfection. Airway neutrophilia is related to exacerbation severity regardless of viral and/or bacterial infections. Eosinophilia is a good predictor of viral exacerbations.     

慢性阻塞性肺疾病道炎症变化其与肺功能相关性研究

目的 观察慢性阻塞性肺疾病急性加重期(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)患者气道炎症细胞及细胞因子的变化,探讨其与肺功能恶化的相关性.方法 取AECOPD患者及健康志愿者诱导痰作细胞学计数和分类;测定肺功能,检测诱导痰上清液的肿瘤坏死因子á(tumor necrosis factor-á,TNF-á)、白介素5(interleukin-5,IL-5)等细胞因子.结果 AECOPD组的诱导痰嗜酸粒细胞百分比、中性粒细胞百分比与正常对照组比较,差异有统计学意(P<0.01);与正常对照组比较,AECOPD诱导痰上清液TNF-á浓度差异有统计学意义(P相似文献   

Changes in sputum T-lymphocyte subpopulations at the onset of severe exacerbations of chronic obstructive pulmonary disease

CD8+ve T-cell responses play a primary role in chronic obstructive pulmonary disease (COPD), but there is little information regarding COPD exacerbations. Sputum induction is a relatively non-invasive and safe method to study airway inflammation. The aim of the study was to investigate changes in airway T-lymphocyte subpopulations at the onset of severe COPD exacerbations via analysis of sputum. Induced sputum samples were collected from 12 COPD patients aged (mean+/-sd) 69+/-7 years, ex-smokers (68+/-23 pack-years), mean FEV1 (%predicted) 40+/-14 at the onset of an acute severe exacerbation requiring hospital admission and 16 weeks after remission of the exacerbation. Inflammatory cells and T-lymphocyte subpopulations (CD4, CD8, Tc1, Tc2) were measured using chemical and double immunocytochemical methods. Increased percentages of sputum neutrophils (P=0.002) and decreased CD4/CD8 and CD8-IFNgamma/CD8-IL4+ve (Tc1/Tc2) cell ratios (P=0.03, P=0.02, respectively) were found at the onset of exacerbation compared to stable state. We conclude that a CD8+ve type-2-mediated immune response is induced at the onset of severe COPD exacerbation.     

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.     

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.     

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.     

Role of viruses in exacerbations of chronic obstructive pulmonary disease

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.     

COPD患者血清和诱导痰中前列腺素-E2水平的变化及意义

目的 检测慢性阻塞性肺疾病急性加重期(AECOPD)和稳定期血清和诱导痰中前列腺素-E2(Prostagland E2 PGE2)的水平,探讨PGE2在COPD发病机制中的作用.方法 选择AECOPD患者30例,稳定期患者30例,健康对照组30例.对诱导痰进行炎症细胞分类计数,测定血清和诱导痰上清液中PGE2水平,并分析PGE2与中性粒细胞、气流阻塞之间的相关性.结果 AECOPD患者血清及诱导痰中PGE2水平明显高于COPD缓解期,比较差异有统计学意义(P＜0.05),AECOPD组和COPD缓解期组痰中PGE2水平高于健康对照组,比较差异有统计学意义(P＜0.05).AECOPD患者诱导痰中PGE2水平与中性粒细胞数呈正相关(P＜0.05),与第一秒用力呼气容积占预计值的百分比(FEV1占预计值％)呈负相关(P＜0.05).结论 PGE2参与COPD的炎症过程;诱导痰中PGE2水平可以作为COPD严重程度的指标.     

慢性阻塞性肺疾病患者p38蛋白激酶表达的变化及其临床意义

目的探讨慢性阻塞性肺疾病(COPD)患者诱导痰中p38蛋白激酶(p38MAPK)表达的变化及其临床意义。方法选择COPD急性加重期患者29例、稳定期患者18例及健康对照者15例。3%～5%氯化钠注射液进行痰液诱导,计数诱导痰中细胞总数、细胞分类。分别采用蛋白质免疫印迹、ELISA方法检测诱导痰中细胞核蛋白p38MAPK含量和上清液中IL-8的含量。结果与健康对照者比较,COPD患者诱导痰中细胞总数、中性粒细胞比例、p38MAPK的表达和上清液IL-8浓度明显升高,FEV1%显著降低(P<0.05);各组诱导痰中细胞核蛋白p38 MAPK的表达与上清液IL-8浓度和中性粒细胞比例均呈正相关(r=0.531,0.664,P<0.01),与FEV1呈负相关(r=-0.468,P<0.05)。结论 COPD患者诱导痰中p38 MAPK表达增高,可能与COPD气道炎症发生发展密切相关。     

Effect of tiotropium on sputum and serum inflammatory markers and exacerbations in COPD.

Chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations demonstrate increased stable-state airway inflammation. Tiotropium has been shown to reduce exacerbation frequency, but its effect on airway inflammation is unknown. The aim of the present study was to investigate the effect of tiotropium on sputum inflammatory markers and exacerbation frequency. Patients (n = 142) were randomised to receive tiotropium or placebo in addition to their usual medication for 1 yr. Sputum and serum cytokines were assayed by ELISA and exacerbation frequency calculated using a symptom-based diary. There was no difference in the area under the curve for sputum interleukin (IL)-6 or myeloperoxidase between the groups, but sputum IL-8 level was increased in the tiotropium arm. There was no difference between start and end of study in serum IL-6 or C-reactive protein level. Tiotropium was associated with a 52% reduction in exacerbation frequency (1.17 versus 2.46 exacerbations.yr(-1)). Of patients on tiotropium, 43% experienced at least one exacerbation, compared with 64% on placebo. The total number of exacerbation days was reduced compared with placebo (17.3 versus 34.5 days). Tiotropium reduces exacerbation frequency in chronic obstructive pulmonary disease, but this effect does not appear to be due to a reduction in airway or systemic inflammation.     

Bacteria in exacerbations of chronic obstructive pulmonary disease: phenomenon or epiphenomenon?

Our understanding of the pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased considerably in the past decade. Several new lines of evidence support bacterial causation of approximately half of the exacerbations in COPD. Acquisition of new strains of bacterial pathogens in patients with COPD is associated with a substantial increase in risk of exacerbation. Bacterial pathogens are isolated in significant concentrations from bronchoscopic samples obtained during acute exacerbation. Neutrophilic airway inflammation is associated with isolation of bacterial pathogens from sputum. A specific immune response to the infecting strains of bacterial pathogens isolated from sputum during exacerbations has been demonstrated. Future work should strive to understand better the host-pathogen interaction that leads to an exacerbation and to develop novel therapeutic and preventive measures.     

Anti-inflammatory effects of combined budesonide/formoterol in COPD exacerbations

Systemic corticosteroids and additional short-acting beta2-agonists are commonly used in exacerbations of chronic obstructive pulmonary disease (COPD). In this double-blind study, the combination of a high-dose inhaled corticosteroid with a rapid-onset long-acting beta2-agonist was evaluated in the treatment of out-patient COPD exacerbations. The primary aim was to compare 14-day treatment effects of budesonide/formoterol to placebo on sputum eosinophils and, secondarily, on other indices of inflammation, forced expiratory flow in one second (FEV(1)), symptoms, health status, and adverse events. Forty-five patients not using steroids (37 male, 21/24 current/ex smoker, median packyears 38, age 65 years, FEV(1) 61% predicted), experiencing a COPD exacerbation, were treated at home with budesonide/formoterol (320/9 microg 4 times daily), prednisolone (30 mg daily), or placebo for 14 days. Sputum eosinophils were significantly reduced by budesonide/formoterol (-57%) compared to placebo (+24%) (p = 0.01). Budesonide/formoterol reduced total symptom scores significantly (p = 0.01) compared to placebo. The increase in FEV(1) by 2 weeks of treatment with budesonide/formoterol (125 ml) was not significantly different from that of placebo (43 ml) (p = 0.07). Budesonide/ formoterol treatment did not suppress morning serum cortisol compared to placebo (-16%; p = 0.50). In conclusion, budesonide/formoterol reduces sputum eosinophils and improves symptoms in the treatment of out-patient COPD exacerbations.     

Changes in bronchial inflammation during acute exacerbations of chronic bronchitis.

There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease. Sputum myeloperoxidase, neutrophil elastase, leukotriene B4 (LTB4), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n = 27) or purulent sputum (n = 42). Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (p < 0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB4 (p < 0.01), but no change in IL-8, suggesting that LTB4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2p < 0.02). The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B4 concentrations.     

Clinical determinants of exacerbations in severe, early-onset COPD.

Chronic obstructive pulmonary disease (COPD) exacerbations impair health. The present authors analysed participants in the Boston Early-Onset COPD Study for familial aggregation and propensity for COPD exacerbations. In the present study, two exacerbation outcomes, episodes of cough and phlegm, and frequent exacerbations were analysed with multivariable modelling and generalised estimating equations. In early-onset COPD probands, passive tobacco smoke exposure within the home was strongly associated with episodes of cough and phlegm. Chronic phlegm production was associated with both exacerbation phenotypes in probands. In first-degree relatives of early-onset COPD probands, chronic bronchitis, episodic wheezing, pneumonia and active smoking were associated with the episodes of cough and phlegm phenotype. In relatives, identical characteristics plus exertional dyspnoea were associated with frequent exacerbations. Exacerbation risk increased with declining lung function. Familial aggregation for episodes of cough and phlegm was observed in relatives with severe obstruction. In conclusion, passive smoke exposure increases morbidity in severe early-onset chronic obstructive pulmonary disease probands, and chronic obstructive pulmonary disease exacerbations correlate with chronic sputum production in probands and relatives. The familial aggregation of exacerbations suggests a genetic basis for susceptibility to chronic obstructive pulmonary disease exacerbations.     

Safety of sputum induction during exacerbations of COPD

Sputum induction (SI) is considered to be a safe tool for assessing airway inflammation in stable patients with COPD, but little is known about its safety during exacerbations. We therefore assessed the safety of SI during COPD exacerbations. SI data from 44 COPD patients were assessed both in the stable phase and during exacerbation. The median FEV1 for the stable phase and exacerbation were 61% predicted (interquartile range [IQR], 49 to 74% predicted) and 51% predicted (IQR, 45 to 60% predicted), respectively. The median decrease in FEV(1) with SI during an exacerbation was 0.27 L (IQR, 0.17 to 0.40 L) vs 0.28 L (IQR, 0.22 to 0.44 L) during the stable phase (p = 0.03). The patients experienced the associated dyspnea well; no other adverse events occurred. All FEV1 values returned to within 90% of their initial value within 30 min. A larger decrease in FEV1 due to SI during an exacerbation was associated with the following parameters in the stable phase of disease: lower total sputum cell count (r = -0.37; p = 0.01); higher percentage of eosinophils (r = 0.33; p = 0.04); and a larger decrease in FEV1 after SI (r = 0.39; p = 0.03). In a multivariate analysis, the only independent association was with the larger decrease in FEV1 in the stable phase. We concluded that SI can be safely carried out in patients with mild-to-moderate COPD who experience an exacerbation, and this occurs with no greater risk than in stable patients with COPD.