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.     

探讨髓系细胞触发受体-1在慢性阻塞性肺疾病急性加重期中的临床应用

目的探讨髓系细胞触发受体-1（triggeringreceptorexpressedonmyeloidcell-1,TREM-1）在慢性阻塞性肺疾病急性加重期（acuteexacerbationofchronicobstructivepulmonarydisease,AECOPD）的临床应用。方法随机抽取在我院门诊或住院部诊治的COPD稳定期患者共40例（n=40）,按GOLD（肺功能）分级：轻度5例,中度16例,重度13例,极重度6例。全部患者均于稳定期、急性加重期测定TREM1、降钙素原（PCT）,急性加重期行痰细菌培养及痰病毒PCR检查。结果AECOPD患者TREM-1水平均较稳定期升高,PCT阳性,差异具有统计学意义（P〈0．05）。痰细菌培养结果阳性患者TREM-1水平、PCT阳性率较阴性患者均升高,差异具有统计学意义（P〈0．05）。痰病毒PCR结果阳性AECOPD患者血清TREM-1水平、PCT阳性率差异无统计学意义。结论TREM-1在AECOPD中是-个敏感的炎症标志物,可作为早期诊断AECOPD的客观指标。在细菌感染相关的AECOPD患者中TREM-1水平升高,但病毒感染相关者无变化,联合PCT可用于判断细菌感染相关的AECOPD,有利于指导临床抗生素的用药。     

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.     

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.     

The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation, poor health status and recurrent infective exacerbations. Macrolide antibiotics have been shown to improve symptoms and exacerbation rate in chronic lung disease, particularly cystic fibrosis (CF) and diffuse pan-bronchiolitis. The effect of long-term oral clarithromycin on health status, sputum bacterial numbers and exacerbation rate in subjects with clinically stable COPD is undetermined. METHODS: Subjects with moderate-to-severe COPD were recruited into a prospective, double-blind, randomised-controlled trial of 3-months oral clarithromycin (Klaricid XL) or placebo once-daily. The effect of clarithromycin on health status (St. George respiratory and Short Form-36 questionnaires), sputum quantitative bacterial numbers and exacerbation rate were investigated. RESULTS: Sixty-seven subjects (46 males) were recruited; 31 and 36 subjects received clarithromycin and placebo, respectively. There were 7(10%) withdrawals. Compared to placebo, clarithromycin did not significantly improve health status, sputum bacterial numbers, or exacerbation rate. CONCLUSIONS: Three months of oral clarithromycin given to subjects with stable COPD does not improve health status, sputum bacterial numbers or exacerbation rate. Treatment of COPD with clarithromycin during the clinical stable state yields no clinical advantages and therefore cannot be recommended as means of eliminating sputum bacteria or preventing infective exacerbations.     

Long-term repeatability of induced sputum cells and inflammatory markers in stable, moderately severe COPD

STUDY OBJECTIVES: Neutrophilic inflammation is a major feature of COPD. Induced sputum is increasingly used to monitor inflammatory airway diseases. Although short-term repeatability of selected sputum markers has been extensively studied in several populations, data on the long-term repeatability of induced sputum markers in stable COPD are scant. DESIGN: Sputum supernatant of 12 patients with stable COPD was analyzed on three separate occasions with 4-weekly intervals. Sputum cells and inflammatory markers interleukin (IL)-8 and soluble intercellular adhesion molecule (sICAM)-1 were measured in supernatant using enzyme-linked immunosorbent assay. Repeatability of sputum markers was expressed by intraclass correlation coefficients (Ri). Measurements and results: Sputum induction was safe in all patients. None of the sputum parameters analyzed changed significantly throughout the study. The repeatability for cell differential counts in stable COPD was as follows: total cells, Ri = 0.07; neutrophils, Ri = 0.66; macrophages, Ri = 0.47; eosinophils, Ri = 0.49; and lymphocytes, Ri = 0.58. The repeatability of soluble markers was as follows: IL-8, Ri = 0.50; and sICAM, Ri = 0.58. Sputum neutrophils were negatively correlated with lung function on each separate occasion, whereas soluble markers were not correlated with sputum cells (p > 0.16, all correlations) or lung function (p > 0.24, all correlations). CONCLUSIONS: Clinically stable, moderate COPD is associated with equally stable sputum inflammatory markers. Repeatability of induced-sputum markers of neutrophilic inflammation in stable COPD is satisfactory, even over extended periods of time. These data support the usefulness of serial monitoring of induced-sputum inflammatory markers in COPD.     

Airway iron and iron-regulatory cytokines in cystic fibrosis.

Iron availability is critical to Pseudomonas aeruginosa. The current authors determined sputum iron, ferritin, microalbumin levels and total cell counts (TCC) in 19 adult patients with cystic fibrosis (CF) during an acute exacerbation and repeated analyses following a median of 12 days antibiotic treatment. The current authors also determined sputum interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha levels because of their putative role in intracellular iron homeostasis. Additional data were obtained from 17 stable CF patients, eight patients with stable chronic obstructive pulmonary disease (COPD) and six normal subjects. Overall, sputum iron, ferritin, microalbumin, IL-1beta and TNF-alpha concentrations and TCCs were significantly elevated in the CF patients compared to those with COPD and normal controls. Sputum ferritin levels were significantly elevated in acute versus stable CF patients and there was a trend for sputum TCC to be higher, but all other inflammatory indices were similar. In the CF patients, sputum iron was positively and strongly related to IL-1beta, TNF-alpha, ferritin and microalbumin levels, but negatively related to forced expiratory volume in one second % predicted. In those acute patients who clinically improved with antibiotics (n=14), there were significant decreases in sputum TCC, iron, ferritin and IL-1beta content, but not TNF-alpha or albumin levels. However, changes in sputum TNF-alpha in acute patients were still closely related to changes in iron, ferritin and albumin content, and changes in IL-1beta were related to changes in sputum ferritin content. Iron and iron-regulatory cytokines may play a role in cystic fibrosis lung disease and the increased iron content may even facilitate Pseudomonas aeruginosa infection.     

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.     

Influence of beclomethasone dipropionate inhalation therapy on respiratory bacterial infection in patients with an acute exacerbation of COPD]

The aim of this clinical study was to investigate the influence of beclomethasone dipropionate (BDP) inhalation therapy on respiratory bacterial infections in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). We studied 30 patients who had been admitted twice, (before and after the beginning BDP inhalation therapy) to our hospital because of an exacerbation of COPD by respiratory tract infection. No differences were observed before and after BDP inhalation therapy in values for PaO2, PaCO2, body temperature, CRP, WBC count, number of admission days, and bacterial culture of sputum on admission. These results suggest that BDP inhalation therapy has little influence on respiratory bacterial infection during exacerbation of COPD.     

Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with 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.     

Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma.

Acute exacerbations of asthma are frequently caused by viral infections, but the inflammatory mechanisms in virus-induced asthma are poorly understood. The aim of the present study was to determine whether viral infection in acute asthma was associated with increased sputum neutrophil degranulation and increased cellular lysis and whether these changes are related to clinical severity. Adults (n=49) presenting to the emergency department with acute asthma were examined for infection by means of sputum direct-fluorescence antigen detection, sputum culture, and sputum polymerase chain reaction for Mycoplasma, Chlamydia and Legionella pneumophila, and all common respiratory viruses. Subjects infected with one of these agents were classed as having an infective exacerbation. Spirometry and sputum induction were performed on presentation and 4-5 weeks later. Thirty-seven subjects (76%) had virus infection and acute asthma. Those with virus infection had increased sputum neutrophils (p<0.05) and increased neutrophil elastase (p<0.05), this was related to increased elevated sputum lactate dehydrogenase (LDH). Subjects with noninfective asthma had an increase in the proportion of sputum eosinophils. Both groups had elevated sputum eosinophil cationic protein (ECP) concentrations. Higher levels of sputum LDH and ECP were associated with a longer hospital stay. Virus infection and acute asthma is associated with neutrophilic inflammation, cell lysis and more severe clinical disease.     

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.     

Inflammatory Response in Acute Viral Exacerbations of COPD

Background  Respiratory viruses are important triggers of acute exacerbations of COPD (AE-COPD). However, the inflammatory response in virus-positive exacerbations is still not fully understood. Methods  We investigated CRP, IL-6, IL-8, IL-10, IFN-γ, blood and sputum cells in patients with acute exacerbation (n = 36) and in stable disease (n = 20) and correlated these parameters to virus detection in respiratory secretions. Results  Similar to other studies we found a significant increase in systemic CRP and absolute numbers of blood leukocytes in AE-COPD patients. Sputum IL-6 levels and sputum eosinophils tended to be higher during exacerbation. In patients with detection of respiratory viruses in nasal lavage, local IL-6 production in sputum was significantly increased; FEV₁ was significantly decreased and both parameters were inversely correlated to each other. Conclusion  This study supports previous findings of both, increased local and systemic inflammation in acute exacerbation of COPD. In virus-associated exacerbations, IL-6 is significantly increased and negatively correlated to FEV₁ indicating a relation between virus-induced inflammation and airway obstruction. However, regarding our finding and previous data, it is becoming increasingly clear that the mediators investigated so far do not permit identifying the etiology of AE-COPD. Hence, further studies are needed to better define the inflammatory response in AE-COPD in general and in viral exacerbations in particular. Supported by Bundesministerium für Bildung und Forschung (BMBF) grant #01GC0101.     

慢性阻塞性肺疾病和支气管哮喘患者诱导痰中白细胞介素-17水平及其意义

目的　通过检测白细胞介素 (IL) 17在慢性阻塞性肺疾病 (COPD)和支气管哮喘 (以下简称哮喘 )患者诱导痰中的水平 ,了解其与气道炎性细胞的关系。方法　对 30例COPD急性加重期患者、31例COPD稳定期患者、32例哮喘急性发作期患者以及 14例健康自愿者进行痰诱导 ,计数诱导痰中细胞总数并分类 ,ELISA测诱导痰中IL 17、IL 8、IL 6水平。结果　与健康对照组比较 ,COPD急性加重期与哮喘急性发作期患者诱导痰中IL 17水平增高 (P <0 0 0 1)。COPD急性加重期患者诱导痰中IL 17水平与IL 8、嗜中性粒细胞数呈正相关 (r =0 381,P =0 0 38;r=0 4 4 6 ,P =0 0 10 ) ;哮喘患者诱导痰中IL 17水平与嗜酸性粒细胞呈正相关 (r =0 4 77,P =0 0 0 6 )。结论　IL 17可能参与COPD、哮喘的炎症过程。     

Relation Between Amoxicillin Concentration in Sputum of COPD Patients and Length of Hospitalization

Amoxicillin is a widely used antibiotic in COPD. Little is known about the transfer of amoxicillin into sputum of COPD patients. The objective was to investigate the relationship between the concentration of amoxicillin in sputum in hospitalized COPD patients and length of hospitalization. To be effective against bacterial pathogens, the amoxicillin concentration in target tissues should be higher than the Minimal Inhibiting Concentration (MIC) of 2 mg/l. Therefore, this was also used as the cut-off value for the amoxicillin concentration in sputum, as a marker for lung tissue concentration. Fifty-two COPD in-patients with an exacerbation, treated with amoxicillin clavulanic acid, were included in this cohort study. Of these patients 7 also had pneumonia. Patients were divided in patients with an amoxicillin sputum concentration ≥ 2 mg/l and < 2 mg/l. Furthermore, inflammation markers in sputum and serum and clinical parameters were obtained. Of the 33 patients with usable sputum, 11 had a concentration in sputum ≥ 2 mg/l. The mean length of hospitalization for patients with concentrations below the MIC90 to common respiratory pathogens was 11.0 days, while for patients with concentrations at or above the MIC90 this was 7.0 days (p = 0.005). COPD patients admitted for an acute exacerbation of COPD, with a sputum concentration of amoxicillin ≥ 2 mg/l had a markedly reduced length of hospitalization compared to patients with a concentration < 2 mg/l. It is worthwhile testing whether individualized treatment based on sputum amoxicillin concentrations of patients during hospitalization for acute exacerbations can effectively reduce hospital stay.     

Relation between amoxicillin concentration in sputum of COPD patients and length of hospitalization

Amoxicillin is a widely used antibiotic in COPD. Little is known about the transfer of amoxicillin into sputum of COPD patients. The objective was to investigate the relationship between the concentration of amoxicillin in sputum in hospitalized COPD patients and length of hospitalization. To be effective against bacterial pathogens, the amoxicillin concentration in target tissues should be higher than the Minimal Inhibiting Concentration (MIC) of 2 mg/l. Therefore, this was also used as the cut-off value for the amoxicillin concentration in sputum, as a marker for lung tissue concentration. Fifty-two COPD in-patients with an exacerbation, treated with amoxicillin clavulanic acid, were included in this cohort study. Of these patients 7 also had pneumonia. Patients were divided in patients with an amoxicillin sputum concentration ≥ 2 mg/l and < 2 mg/l. Furthermore, inflammation markers in sputum and serum and clinical parameters were obtained. Of the 33 patients with usable sputum, 11 had a concentration in sputum ≥ 2 mg/l. The mean length of hospitalization for patients with concentrations below the MIC90 to common respiratory pathogens was 11.0 days, while for patients with concentrations at or above the MIC90 this was 7.0 days (p = 0.005). COPD patients admitted for an acute exacerbation of COPD, with a sputum concentration of amoxicillin ≥ 2 mg/l had a markedly reduced length of hospitalization compared to patients with a concentration < 2 mg/l. It is worthwhile testing whether individualized treatment based on sputum amoxicillin concentrations of patients during hospitalization for acute exacerbations can effectively reduce hospital stay.     

Different expression ratio of S100A8/A9 and S100A12 in acute and chronic lung diseases

Calgranulins are a family of powerful chemoattractants, which have been implicated as biomarkers in inflammatory diseases. To determine how different respiratory diseases affect the expression of calgranulins, we measured the expression of S100A8/A9 and S100A12 in bronchoalveolar lavage fluid (BALF) of acute respiratory distress syndrome (ARDS) patients and healthy volunteers by ELISA. Analysis of calgranulin expression revealed a high level of S100A12 in the lavages of patients suffering from ARDS compared to controls (p<0.001). Based on the hypothesis that the increased expression of S100A12 relative to the S100A8/A9 heterodimer was a characteristic of respiratory diseases with neutrophilic inflammation, we measured calgranulin expression in BALF of cystic fibrosis (CF) patients. Despite similarly elevated levels of S100A8/A9, S100A12 was significantly higher in ARDS compared to CF BALF (p<0.001). The differential expression of calgranulins was unique for inflammatory markers, as an array of cytokines did not differ between CF and ARDS patients. Since ARDS is an acute event and CF a chronic inflammation with acute exacerbations, we compared calgranulin expression in sputum obtained from CF and patients with chronic obstructive lung disease (COPD). Levels of S100A12 and S100A8/9 were elevated in CF sputum compared to COPD sputum, but the ratio of S100A12 to S100A8/A9 was similar in COPD and CF and reflected more closely than seen in healthy controls. The results indicate that the regulation of human calgranulin expression and the ratio of S100A8/A9 to S100A12 may provide important insights in the mechanism of respiratory inflammation.     

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.     

Changing Pattern of Sputum Cell Counts During Successive Exacerbations of Chronic Obstructive Pulmonary Disease

Background: Chronic Obstructive Pulmonary Disease exacerbations are associated with worsening of airway inflammation, the nature of which may be neutrophilic, eosinophilic, or both.

Objective: The primary objective was to examine the cellular nature of airway inflammation in successive COPD exacerbations in order to ascertain if they changed in individual patients. The secondary objective was to estimate the relative risk indicating the extent to which a particular type of exacerbation changed as a function of the most recent exacerbation. Design: This was a retrospective survey performed on a computerised sputum cell count database of a referral respiratory service in Hamilton, Canada. Recurrent event analyses were used to model the incidence of exacerbations and subtypes of exacerbations. Results: 359 patients and 148 patients had sputum examined during stable condition and during exacerbations, respectively. It was found 65 patients had sputum examined during both situations. The exacerbations were eosinophilic in 15.9%, neutrophilic in 18%, combined in 2.6%, of unknown clinical significance in 19.6% and normal in 19.6%. There were missing counts for 24.3% samples. In 85.2% of patients, a different subtype of bronchitis was noted in successive exacerbations. The relative risk of a subsequent neutrophilic or eosinophilic exacerbation was 6.24 (p = 0.02) and 2.8 (p = 0.24) when the previous exacerbation was neutrophilic or eosinophilic respectively. Conclusions: This non-intervention study suggests that the cellular nature of bronchitis is largely unpredictable and needs to be examined at each COPD exacerbation This has important implications in choosing the appropriate therapy. Future intervention studies would provide further evidence.