Sputum color as a marker of acute bacterial exacerbations of chronic obstructive pulmonary disease

We analyzed 795 sputa from 315 patients (233 males, mean age 69.3+/-8.8 years, mean number of exacerbations 2.52/patient) with acute exacerbations of moderate-to-severe chronic obstructive pulmonary disease (COPD) (mean steady-state FEV1 42.5+/-7.8% of predicted). 581/795 sputa were considered adequate. Sputum was analyzed by a quali-quantitative colorimetric scale allowing both color distinction and color degree of intensity. Quantitative culture was then performed (threshold: >10(6)CFU/mL). Samples were distinguished in mucoid (145) and purulent (436) sputa. Absence of bacterial growth was observed in 22% and 5% of mucoid and purulent sputa, respectively. Among mucoid sputa, Gram positive bacterial growth occurred more commonly compared to Gram negative and Pseudomonas aeruginosa/Enterobacteriaceae (56%, 24%, 20%, respectively). In purulent sputa, Gram positives were found in 38% of cases, Gram negatives in 38%, and P. aeruginosa/Enterobacteriaceae in 24%. We evaluated whether functional impairment (FEV1) orientates as to the infectious etiology of exacerbations. Significant differences were observed in the distribution of pathogens. Gram negative and P. aeruginosa/Enterobacteriaceae were isolated more frequently in the sputum when FEV1 was <35%. Our study indicates that purulent sputum is strongly associated with bacterial growth in COPD exacerbations. Deepening sputum color (from yellowish to brownish) was associated with increased yield of Gram negative and P. aeruginosa/Enterobacteriaceae.     

降钙素原与支气管扩张急性加重期患者痰培养的相关性

目的 探讨降钙素原与支气管扩张急性加重期患者痰培养结果的相关性.方法 选取从2013年11月至2015年11月由莱芜市人民医院及山东大学齐鲁医院收治、确诊为支气管扩张急性加重期的患者,比较痰培养阳性患者与阴性患者的降钙素原的差别,比较痰培养为铜绿假单胞菌患者与其他细菌或真菌患者的降钙素原的差别.结果 共纳入120例患者,痰培养阳性率为43.3％,最常见的病原菌为铜绿假单胞菌(59.6％).降钙素原＞0.25tμg/L的患者占37.5％.痰培养阳性组患者的降钙素原显著高于痰培养阴性组患者(P＜0.05),而且痰培养阳性组患者中降钙素原＞0.25 μg/L所占比例显著高于痰培养阴性组(P＜o.05).痰培养为铜绿假单胞菌患者的降钙素原与痰培养为其他细菌或真菌的患者差异无统计学意义(P＞0.05).结论 支气管扩张急性加重期患者降钙素原升高与痰培养阳性有相关关系,而降钙素原在铜绿假单胞菌感染及其他病原菌感染的鉴别方面无价值.     

A 1-year prospective study of the infectious etiology in patients hospitalized with acute exacerbations of COPD

INTRODUCTION: Infection is a major cause of acute exacerbations of COPD (AECOPDs). We aimed to study the infectious etiology related to AECOPD. METHODS: Patients admitted to an acute care hospital in Hong Kong with an AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Sputum samples, nasopharyngeal aspirate (NPA) samples, and paired serology specimens were collected. Spirometry was performed with patients in the stable phase 2 to 3 months after hospital discharge. RESULTS: There were 643 episodes of AECOPD among 373 patients. Their mean age was 75.3 years (SD, 7.9 years) with 307 male patients. The mean FEV(1) was 40.4% predicted (SD, 18.7% predicted), and the mean FEV(1)/FVC ratio was 58.4% (SD, 16.0%). Among sputum samples from the 530 episodes of AECOPD hospital admissions that were saved, 13.0%, 6.0%, and 5.5%, respectively, had positive growth of Haemophilus influenzae, Pseudomonas aeruginosa, and Streptococcus pneumoniae. Among the 505 hospital admissions with patients who had NPA samples saved, 5.7%, 2.3%, 0.8%, and 0.8%, respectively, had influenza A, respiratory syncytial virus (RSV), influenza B, and parainfluenza 3 isolated from viral cultures. Paired serology test results revealed a fourfold rise in viral titers in 5.2%, 2.2%, and 1.4% of patients, respectively, for influenza A, RSV, and influenza B. Very severe airflow obstruction (stable-state spirometry) was associated with a higher chance of a positive sputum culture (FEV(1) >/= 30% predicted, 28.2%; FEV(1) < 30% predicted, 40.4%; p = 0.006). CONCLUSION: H influenzae and influenza A were the most common etiologic agents in patients who were hospitalized with AECOPDs. More severe airflow obstruction was associated with a higher chance of a positive sputum culture finding.     

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.     

Predictors of positive sputum cultures in exacerbations of chronic obstructive pulmonary disease

Background and objective: Although sputum culture in patients with an acute exacerbation of COPD is of uncertain value, it is routinely done. The ability to clinically identify patients likely or unlikely to yield bacterial sputum isolates would potentially reduce unnecessary tests. The objective of this study was to identify the clinical predictors of positive sputum cultures in this patient population. Methods: Consecutive patients with a COPD exacerbation requiring an emergency visit were prospectively enrolled. Quantitative sputum culture was performed on‐site. Data on current smoking, sputum purulence, FEV₁, Medical Research Council chronic dyspnoea scale, BMI, severe exacerbations in the preceding year requiring hospitalization, PaO₂, PaCO₂, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and oral and inhaled steroid use were recorded. Results: Of the 94 patients enrolled, sputum from 36 yielded bacterial pathogens. These patients were characterized by a higher frequency of purulent sputum, lower FEV₁, BMI and PaO_2, higher APACHE II score and more frequent use of inhaled steroids (P < 0.05). On multivariate regression, purulent sputum, FEV₁ and BMI were independent determinants of a positive sputum culture. Using receiver‐operator‐optimized thresholds for these variables (purulent sputum, FEV₁ < 35% predicted and BMI ≤ 22 kg/m²), we proposed a regression coefficient‐weighted prediction model that accurately determined the likelihood of sputum bacterial isolation. Conclusions: A prediction model based on the variables of purulent sputum, FEV₁ and BMI predicted sputum culture result with about 90% accuracy. Pending further validation, this model may save valuable healthcare resources.     

Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD

STUDY OBJECTIVES: To stratify COPD patients presenting with an acute exacerbation on the basis of sputum color and to relate this to the isolation and viable numbers of bacteria recovered on culture. DESIGN: Open, longitudinal study of sputum characteristics and acute-phase proteins. SETTING: Patients presenting to primary-care physicians in the United Kingdom. Patients were followed up as outpatients in specialist clinic. PATIENTS: One hundred twenty-one patients with acute exacerbations of COPD were assessed together with a single sputum sample on the day of presentation (89 of whom produced a satisfactory sputum sample for analysis). One hundred nine patients were assessed 2 months later when they had returned to their stable clinical state. INTERVENTIONS: The expectoration of green, purulent sputum was taken as the primary indication for antibiotic therapy, whereas white or clear sputum was not considered representative of a bacterial episode and the need for antibiotic therapy. RESULTS: A positive bacterial culture was obtained from 84% of patients sputum if it was purulent on presentation compared with only 38% if it was mucoid (p < 0.0001). When restudied in the stable clinical state, the incidence of a positive bacterial culture was similar for both groups (38% and 41%, respectively). C-reactive protein concentrations were significantly raised (p < 0.0001) if the sputum was purulent (median, 4.5 mg/L; interquartile range [IQR], 6. 2 to 35.8). In the stable clinical state, sputum color improved significantly in the group who presented with purulent sputum from a median color number of 4.0 (IQR, 4.0 to 5.0) to 3.0 (IQR, 2.0 to 4. 0; p < 0.0001), and this was associated with a fall in median C-reactive protein level to 2.7 mg/L (IQR, 1.0 to 6.6; p < 0.0001). CONCLUSIONS: The presence of green (purulent) sputum was 94.4% sensitive and 77.0% specific for the yield of a high bacterial load and indicates a clear subset of patient episodes identified at presentation that is likely to benefit most from antibiotic therapy. All patients who produced white (mucoid) sputum during the acute exacerbation improved without antibiotic therapy, and sputum characteristics remained the same even when the patients had returned to their stable clinical state.     

Assessment of the usefulness of sputum culture for diagnosis of community-acquired pneumonia using the PORT predictive scoring system

BACKGROUND: The usefulness of sputum culture in guiding microbiological diagnosis of community-acquired pneumonia is controversial. We evaluate and assess it using the Patients Outcome Research Team (PORT) predictive scoring system. METHODS: A cohort of 1669 patients with community-acquired pneumonia was studied. Before administering antibiotic therapy, sputum was collected and its quality evaluated. Samples were gram stained and those of good quality were assessed for a predominant morphotype (PM). Sputum cultures were processed according to standard protocols. RESULTS: A sputum sample was obtained from 983 (59%) of the 1669 patients and 532 (54%) of the samples were of good quality. There was a PM in 240 (45%) of the latter samples (ie, for 14.4% of the 1669 patients) and there was no PM in 292 (55%). Culture yielded a microorganism in 207 (86%) of the 240 samples with PM and 57 (19.5%) of the 292 samples without PM (P<.05). Rates of sputum obtained, good-quality sputum specimens, PM identification, and positive culture were not significantly different among the PORT-score groups of patients (P>.05). The sensitivity and specificity of the gram-positive diplococci identification in the sputum culture of Streptococcus pneumoniae were 60% and 97.6%, and the positive and negative predictive values were 91% and 85.3%, respectively. CONCLUSIONS: Good-quality sputum with PM could be obtained in only 14.4% of all patients. A PORT-score group in which sputum could be of greater usefulness in identifying the causative organism could not be identified. The presence of gram-positive diplococci in gram-stained sputum culture was highly specific for S pneumoniae.     

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.     

COPD稳定期肺功能与急性加重期痰细菌学关系探讨

目的探讨COPD稳定期肺功能分级与急性加重期痰培养细菌学状况以及细菌感染之间关系。方法对我院142例有发病前稳定期肺功能检查结果的AECOPD住院病例进行回顾性分析。结果痰培养阳性者73例,阳性率为51.41%。FEV1占预计值百分比(FEV1%)50%时假单胞菌、肠杆菌及不动杆菌出现的机会比FEV1%≥50%时多,FEV1%50%与假单胞菌、肠杆菌和不动杆菌有高度相关性(P0.05)。结论随着COPD患者基础肺功能的降低,特别在FEV1%50%时,发生急性加重时痰菌以假单胞菌和肠杆菌最常见。FEV1%≥50%时痰培养诊断率较低,大多数无菌生长。     

Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis

We examined the correlation between sputum colour and the presence of potentially pathogenic bacteria in acute exacerbations of chronic bronchitis (AECBs). Data were pooled from six multicentre studies comparing moxifloxacin with other antimicrobials in patients with an AECB. Sputum was collected before antimicrobial therapy, and bacteria were identified by culture and Gram staining. Association between sputum colour and bacteria was determined using logistic regression. Of 4,089 sputum samples, a colour was reported in 4,003; 1,898 (46.4%) were culture-positive. Green or yellow sputum samples were most likely to yield bacteria (58.9% and 45.5% of samples, respectively), compared with 18% of clear and 39% of rust-coloured samples positive for potentially pathogenic microorganisms. Factors predicting a positive culture were sputum colour (the strongest predictor), sputum purulence, increased dyspnoea, male sex and absence of fever. Green or yellow versus white sputum colour was associated with a sensitivity of 94.7% and a specificity of 15% for the presence of bacteria. Sputum colour, particularly green and yellow, was a stronger predictor of potentially pathogenic bacteria than sputum purulence and increased dyspnoea in AECB patients. However, it does not necessarily predict the need for antibiotic treatment in all patients with AECB.     

慢性支气管炎患者肺泡巨噬细胞及诱导痰中内皮素的研究

目的研究慢性支气管炎(慢支炎)患者诱导痰中、肺泡巨噬细胞(AM)培养上清液中及在氨茶碱和脂多糖(LPS)干预下培养上清液中内皮素(ET)的浓度变化,探讨AM源性ET在慢支炎及慢性阻塞性肺疾病(COPD)病理进展过程中的作用.方法选择慢支炎患者14例,COPD患者13例,同时选择14名健康人作为正常对照.支气管肺泡灌洗技术收集支气管肺泡灌洗液(BALF),对其细胞成分进行计数和分类;对其中26例用高渗盐水诱痰法取痰标本,放射免疫法测定诱导痰中和AM培养上清液中的ET浓度.结果(1)慢支炎组、COPD组BALF中细胞总数、中性粒细胞数、肺泡巨噬细胞数均明显高于正常对照组(P均<0.01);(2)慢支炎组和COPD组AM培养上清液中ET浓度和诱导痰中ET浓度明显高于正常对照组(P均<0.01),但慢支炎组与COPD组之间差异无显著性(P均>0.05);(3)三组的诱导痰ET浓度与AM培养上清液ET浓度呈正相关(r=0.741,P<0.01),与AM数呈正相关(r=0.597,P<0.01);(4)COPD组AM培养上清液ET浓度、诱导痰ET浓度均与一秒钟用力呼气容积占预计值%(FEV1占预计值%)呈负相关(r=-0.828,P<0.01;r=-0.748,P<0.05);(5)氨茶碱对AM培养上清液中ET浓度无影响(P>0.05),而LPS使其浓度明显升高(P<0.01).结论(1)慢支炎、COPD患者气道腔内存在非特异性气道炎症,其特点表现为中性粒细胞和巨噬细胞数目增多;(2)AM为肺内ET的重要来源之一,LPS可刺激AM分泌ET,AM源性ET可能参与了COPD阻塞性通气功能障碍的病理进展过程.     

Clinical applications of induced sputum

The development of standardized methods for sputum induction has improved the quality and reproducibility of sputum samples. This technique has been used to optimize samples in the investigation of pulmonary tuberculosis and lung cancer, but its clinical application as a noninvasive measure of airway inflammation has highlighted the enormous potential of this technique. Sputum induction has allowed researchers to characterize the inflammatory profiles of a variety of airway diseases including asthma, COPD, and chronic cough. To date, the identification of sputum eosinophilia has the greatest clinical value as this predicts a favorable response to corticosteroids and can therefore guide treatment. In asthma and COPD management, protocols aimed at normalizing the sputum eosinophil count have markedly reduced exacerbations without an overall increase in therapy. Currently, no other noninvasive measure of airway inflammation has demonstrated a benefit in reducing exacerbations. The value of sputum induction and analysis is not restricted to the recognition of sputum eosinophilia but also may be used to direct novel antineutrophilic therapies. Thus, it is time for sputum induction to move from the research laboratory to the clinic.     

Safety of sputum induction in moderate-to-severe chronic obstructive pulmonary disease

This retrospective study was designed to evaluate the safety and efficacy of a bronchoprotective sputum induction protocol in moderate to severe chronic obstructive pulmonary disease (COPD). Forty-two adults with COPD (FEV1 = 51.7 +/- 3.2% predicted (mean +/- SEM)) under went sputum induction using a protocol designed to minimize hypertonic saline-induced bronchoconstriction. Hypertonic (3%) saline was used for subjects with FEV1 > or = 50%, and normal (0.9%) saline was used for subjects with FEV1 < 50%. Primary outcomes were change in peak flow, FEV1 and oxygen saturation. Mean decline in peak flow during sputum induction was 13.2 +/- 2.1%. FEV1 fell by 11.4 +/- 2.3%, an absolute fall of 0.14 +/- 0.031. Oxygen saturation did not change. A fall in peak flow of > or = 20% reliably predicted a fall in FEV1 of > or = 20%. Thirty-five of 42 subjects (83.3%) produced an acceptable sputum sample. Sputum eosinophil and neutrophil percentages were 2.8 +/- 0.9 and 73.0 +/- 3.0%, respectively, and were not correlated with changes in peak flow, FEV1 or oxygen saturation. A protocol for sputum induction which restricts the use of hypertonic saline based on lung function is both safe and effective in subjects with moderate to severe COPD.     

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.     

Acute purulent exacerbation of chronic obstructive pulmonary disease and Chlamydia pneumoniae infection.

In order to investigate the role of bacteria, including Mycoplasma pneumoniae and especially Chlamydia pneumoniae in acute purulent exacerbations of chronic obstructive pulmonary disease (COPD), we examined sputum specimens and acute and convalescent sera taken 26 d apart from 49 outpatients experiencing an acute purulent exacerbation of COPD. The sera were tested for antibodies to C. pneumoniae with the microimmunofluorescence test, and for antibodies to M. pneumoniae with the indirect fluorescence antibody test. Routine microbiologic culture of sputum yielded potentially pathogenic microorganisms in 12 of the 49 patients (24%). Three patients (6%) showed serologic evidence of recent M. pneumoniae infection. Seven patients showed high IgG titers of >/= 1:1,024 to C. pneumoniae, and an additional four had a fourfold increase in IgG titer, suggesting reinfection with C. pneumoniae. Sputum from two of these 11 patients also grew Streptococcus pneumoniae, and one grew Moraxella catarrhalis. Patients with and without serologic evidence of current C. pneumoniae infection showed no significant differences in clinical features or pulmonary function. The high incidence of infection with C. pneumoniae (the sole causal agent in 16% of cases, and the causal agent with other agents in 6%) provides insight into the importance of this organism among agents leading to exacerbations of COPD in Turkey.     

Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis

BACKGROUND: Bronchiectasis remains a major public health problem, but factors influencing its natural history are not well characterized. The objective of our study was to explore modifiable and nonmodifiable factors associated with lung function decline in a clinical cohort of patients with stable non-cystic fibrosis (CF) bronchiectasis. METHODS: Seventy-six stable adult patients (mean age, 69.9 years; 48.7% men) with bronchiectasis were included. The diagnosis of bronchiectasis was established in all cases by high-resolution CT scanning. Baseline data were collected on clinical history, symptoms, disease extension, treatment, sputum volume, microbiological aspects, laboratory findings, and exacerbations. All patients were invited to attend the clinic every 6 months for 24 months to conduct full spirometry and microbiological analysis of sputum, and to report the number of exacerbations. RESULTS: Overall, the group experienced a rate of decline of lung function (FEV1) of 52.7 mL per year. Independent factors associated with an accelerated decline of lung function were chronic colonization with Pseudomonas aeruginosa (PA) [odds ratio (OR), 30.4; 95% confidence interval (CI), 3.8 to 39.4; p=0.005], more frequent severe exacerbations (OR, 6.9; 95% CI, 2.3 to 10.5; p=0.014), and more systemic inflammation (OR, 3.1; 95% CI, 1.9 to 8.9; p=0.023). Regrettably, none of the long-term treatment strategies evaluated, including the use of long-acting inhaled bronchodilators, inhaled or oral steroids, oxygen therapy, secretion clearance maneuvers, or antibiotics had a significant effect on FEV1 decline. CONCLUSION: Chronic colonization by PA, severe exacerbations, and systemic inflammation are associated with disease progression in non-CF bronchiectasis.     

Bacterial infections in patients requiring admission for an acute exacerbation of COPD; a 1-year prospective study

STUDY OBJECTIVE: To investigate the frequency of respiratory bacterial infections in hospitalized patients, admitted with an acute exacerbation of chronic obstructive pulmonary disease (COPD), to identify the responsible pathogens by sputum culture and to assess patient characteristics in relation to sputum culture results. METHODS: We prospectively evaluated clinical data and sputum culture results of 171 patients, admitted to the pulmonology department of the University Hospital Maastricht with an acute exacerbation of COPD from 1st January 1999 until 31st December 1999. RESULTS: Eighty-five patients (50%) had positive sputum cultures, indicating the presence of bacterial infection. Pathogens most frequently isolated were: Haemophilus influenzae (45%), Streptococcus pneumoniae (27%), and Pseudomonas aeruginosa (15%). Patients with more severely compromised lung function had a higher incidence of bacterial infections (P = 0.026). There were no significant differences in age, lung function parameters, blood gas results and length of hospital stay between patients with and without bacterial infection. There were no correlations between the type of bacteria isolated and clinical characteristics. CONCLUSION: Incidence of bacterial infection during acute exacerbations of COPD is about 50%. Patients with and without bacterial infection are not different in clinical characteristics or in outcome parameters. Patients with lower FEV1 have a higher incidence of bacterial infections, but there is no difference in the type of bacterial infection. In the future, the pathogenic role of bacterial infection in exacerbations of COPD should be further investigated, especially the role of bacterial infection in relation to local and systemic inflammation.     

Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum

Chronic obstructive pulmonary disease (COPD) is characterized by significant chronic inflammation in the pulmonary compartment as well as in the circulation. This study aimed to elucidate the relationship between local and systemic inflammation in smoking-induced COPD by assessing levels of soluble (s) tumor necrosis factor (TNF) receptors, TNF-alpha, and interleukin-8 (IL-8) in induced sputum and in plasma. Sputum induction was performed in 18 subjects with COPD (FEV(1) 56% predicted) and 17 healthy smokers (FEV(1) 99% predicted). Patients with COPD showed significantly higher percentages of neutrophils and levels of sTNF-R55 and IL-8 in sputum as compared with control subjects, whereas sputum sTNF-R75 levels tended to be higher in COPD. Sputum TNF-alpha levels were similar in both groups. When comparing sTNF receptors in sputum and plasma, no direct correlations were found despite elevation of circulating sTNF-R75 levels in patients with COPD. In addition, sputum sTNF receptors were inversely related to the FEV(1) in patients with COPD, whereas circulating sTNF receptors were not, suggesting different regulation of inflammation in the pulmonary and systemic compartment. When subjects were divided according to their current smoking status, levels of sTNF-R55, sTNF-R75, and IL-8 in sputum were significantly elevated in ex-smoking versus currently smoking patients with COPD, suggesting ongoing inflammation in airways and circulation of patients with COPD after smoking cessation.     

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 bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Study Group of Bacterial Infection in COPD.

STUDY OBJECTIVES: To investigate the possible relationship between functional respiratory impairment measured by FEV1 and isolation of diverse pathogens in the sputum of patients with exacerbations of COPD. DESIGN: Multicenter, cross-sectional, epidemiologic study. SETTING: Pneumology units in six secondary or tertiary hospitals in Spain. PATIENTS: Ninety-one patients with acute exacerbation of COPD were included. INTERVENTIONS: A quantitative sputum culture was performed, and bacterial growth was considered significant only when the germ was isolated at concentrations > 10(6) cfu (> 10(5) for Streptococcus pneumoniae) in samples with < 10 epithelial cells and > 25 leukocytes per low magnification field (x 100). RESULTS: Germs isolated were the following: Haemophilus influenzae (20 cases; 22%), Pseudomonas aeruginosa (14 cases; 15%), S. pneumoniae (9 cases; 10%), Moraxella catarrhalis (8 cases; 9%), other gram-negative bacteria (7 cases; 7%), and non-potentially pathogenic microorganisms (non-PPMs; 33 cases; 36%). P. aeruginosa and H. influenzae were isolated more frequently among the patients with FEV1 < 50% than among those with FEV1 > 50% (p < 0.05). All patients with P. aeruginosa in sputum had FEV1 < 1,700 mL. FEV1 < 50% was associated with a very high risk of P. aeruginosa or H. influenzae isolation: the odds ratios (ORs) are 6.62 (95% confidence interval [CI], 1.2 to 123.6) and 6.85 (95% CI, 1.6 to 52.6), respectively. Furthermore, active tobacco smoking was associated with a high risk of H. influenzae isolation (OR, 8.1; 95% CI, 1.9 to 43.0). CONCLUSIONS: Patients with the greatest degree of functional impairment, as measured by their FEV1, presented a higher probability of having an isolation of P. aeruginosa or H. influenzae in significant concentrations in sputum during an exacerbation. The diagnostic yield of sputum in patients with an FEV1 > 50% was low, with a predominance of non-PPMs. Low FEV1 and active tobacco smoking are data that should be considered when establishing an empiric antibiotic treatment for exacerbated COPD.