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.     

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.     

Pseudomonal Infections in Patients with COPD

COPD is a common disease with increasing prevalence. The chronic course of the disease is characterized by acute exacerbations that cause significant worsening of symptoms. Bacterial infections play a dominant role in approximately half of the episodes of acute exacerbations of COPD. The importance of pseudomonal infection in patients with acute exacerbations of COPD stems from its relatively high prevalence in specific subgroups of these patients, and particularly its unique therapeutic ramifications. The colonization rate of Pseudomonas aeruginosa in patients with COPD in a stable condition is low.A review of a large number of clinical series of unselected outpatients with acute exacerbations of COPD revealed that P. aeruginosa was isolated from the patients’ sputum at an average rate of 4%. This rate increased significantly in COPD patients with advanced airflow obstruction, in whom the rate of sputum isolates of P. aeruginosa reached 8–13% of all episodes of acute exacerbations of COPD. However, the great majority of bacteria isolated in these patients were not P. aeruginosa, but the three classic bacteria Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis. The subgroup of patients, with acute exacerbations of COPD, with the highest rate of P. aeruginosa infection, which approaches 18% of the episodes, is mechanically ventilated patients. However, even in this subgroup the great majority of bacteria isolated are the above-mentioned three classic pathogens.In light of these epidemiologic data and other important considerations, and in order to achieve optimal antibacterial coverage for the common infectious etiologies, empiric antibacterial therapy should be instituted as follows. Patients with acute exacerbations of COPD with advanced airflow obstruction (FEV₁ <50% of predicted under stable conditions) should receive once daily oral therapy with one of the newer fluoroquinolones, i.e. levofloxacin, moxifloxacin, gatifloxacin, or gemifloxacin for 5–10 days. Patients with severe acute exacerbations of COPD who are receiving mechanical ventilation should receive amikacin in addition to one of the intravenous preparations of the newer fluoroquinolones or monotherapy with cefepime, a carbapenem or piperacillin/tazobactam. In both subgroups it is recommended that sputum cultures be performed before initiation of therapy so that the results can guide further therapy.     

Mortality of COPD Patients Infected with Multi-Resistant Pseudomonas aeruginosa : A Case and Control Study

Abstract Background:   The incidence of infections caused by multiresistant Pseudomonas aeruginosa (MDRP) is increasing, especially in critically ill patients. The relevance of MDRP in the prognosis of chronic obstructive pulmonary disease (COPD) acute exacerbation in patients admitted to the hospital’s general ward is not well known. Patients and Methods:   Case and control study. Cases were patients admitted for COPD acute exacerbation in which a MDRP was isolated from spontaneous sputum. MDRP was defined as the absence of susceptibility to three or more antibiotic families (betalactams, quinolones, carbapenems and aminoglycosides). Patients currently or previously admitted to the intensive care unit (ICU), who had a recent surgery, neoplasia or immunosuppressive treatment were excluded from the study. Patients from the control group were admitted for COPD acute exacerbation and matched 1:1 with each case-patient in terms of age, sex, date of admission and degree of airway obstruction. Pseudomonas aeruginosa susceptible to all antimicrobials or other microorganisms was isolated from sputum. Results:   During the study period (2000–2005), 50 casepatients and 50 controls were included. Crude mortality at 2 years was 60% for the case-patients and 28% for the control group. In the logistic regression analysis adjusted for age, FEV₁ and number of previous hospital admissions, MDRP infection was associated to an increased mortality in comparison to patients without MDRP (OR = 6.2; IC 95%: 1.7–22.1; p < 0.01). Conclusions:   In COPD patients admitted to the general ward, acute exacerbation with MDRP in sputum was associated with higher mortality.     

Chitotriosidase Activity in Plasma and COPD Exacerbations

Introduction

This study aimed to determine the association between plasma chitotriosidase activity and the clinical characteristics and exacerbation rate of COPD patients.

Methods

The study comprised 97 patients with COPD. Their clinical characteristics and a history of exacerbations in the last 12 months were noted. Plasma chitotriosidase activity was determined. Patients were followed up for 12 months, and the number of moderate and severe exacerbations during this period was recorded.

Results

Chitotriosidase activity positively correlated with patient age (rho = 0.217, p = 0.036) and inversely with CAT (rho = − 0.240, p = 0.020). There was no correlation with lung function. Chitotriosidase activity was significantly lower in patients with a history of ≥ 2 exacerbations compared to patients without a history of exacerbations (93 [38–312] vs. 264 [168–408] nmol/h/mL, p = 0.033). Overall, there was no difference in chitotriosidase activity between patients with or without observed exacerbations. Patients with a history of ≥ 1 exacerbation and ≥ 1 observed exacerbation had higher chitotriosidase activity compared to patients without further exacerbations (240 [144–456] vs. 52 [39–240] nmol/h/mL, p = 0.035). Multivariate analysis identified FEV₁ (HR 0.976, 95% CI 0.956–0.996, p = 0.016) and blood eosinophil percentage (HR 1.222, 95% CI 1.048–1.424, p = 0.011) as independent predictors of future exacerbations in the total patient population, while in patients with a history of ≥ 1 exacerbation ,the only independent predictor was chitotriosidase activity (HR per 10 nmol/h/mL 1.028, 95% CI 1.002–1.055, p = 0.037).

Conclusion

While mixed associations between chitotriosidase activity and clinical outcomes were seen, chitotriosidase activity could be a predictor of future exacerbations in patients with a history of ≥ 1 exacerbation in the past  12 months.

     

Bacterial infection and risk factors in outpatients with acute exacerbation of chronic obstructive pulmonary disease: a 2-year prospective study

BACKGROUND AND OBJECTIVES: Acute exacerbations of COPD (AECOPD) are commonly observed in community-based patients worldwide. The factors causing exacerbation are largely unknown. This study was undertaken to determine the predominant bacterial pathogens cultured from sputum in community-based patients with AECOPD, to assess the risk factors associated with exacerbations and to compare these findings with published studies. METHODS: Forty-five patients with stable COPD were prospectively followed in the outpatients' clinic of King Abdulaziz University Hospital. At the first visit, personal data, CXR and measurement of baseline PEF were obtained from each patient. In the subsequent visits, sputum culture and CXR were carried out during exacerbations. RESULTS: Over a period of 24 months, patients made a total of 139 visits for exacerbations, and 69.8% had a positive sputum culture for a single pathogen. Moraxella catarrhalis (25.2%), Pseudomonas aeruginosa (12.2%) and Haemophilus influenzae (11.5%) were the most common isolated organisms. Patients with a lower level of baseline PEF had a significantly increased frequency of exacerbations (r = 0.337, P = 0.024). However, there was a weak correlation between exacerbation frequency and duration of COPD and exposure to cigarette smoking. CONCLUSION: There was a higher incidence of Moraxella catarrhalis and Pseudomonas aeruginosa than reported in previous studies. These findings should influence antibiotic selection for exacerbations. COPD patients with a low baseline PEF are at a higher risk of having repeated exacerbations and gram-negative pathogens.     

Elevated exoenzyme expression by Pseudomonas aeruginosa is correlated with exacerbations of lung disease in cystic fibrosis.

Two studies were conducted to determine whether Pseudomonas aeruginosa exoenzyme expression was increased during pulmonary exacerbations of cystic fibrosis (CF) and if it was reduced by antibiotic therapy. The first study was retrospective comparing in vitro exoenzyme levels expressed by P. aeruginosa sputum isolates from seriously ill, hospitalized patients with CF to those from P. aeruginosa strains isolated from CF clinic patients who were in relatively better health. Exoenzyme values were significantly greater in P. aeruginosa strains isolated from ill, hospitalized patients than in clinic patients (P = 0.0001). In the prospective study, in vitro exoenzyme levels were measured from sputum p. aeruginosa isolates of 9 hospitalized patients with CF. Exoenzyme values were greatest in nonmucoid strains on admission (P < 0.0025), and P. aeruginosa exoenzyme expression decreased significantly during hospitalization (P < 0.0025). Deterioration in CF lung disease was accompanied by increased P. aeruginosa exoenzyme production, especially by nonmucoid strains. Antibiotic treatment during hospitalization resulted in mean improvement of % predicted forced expiratory volume in 1 sec (FEV₁) from 39 to 53% (P = 0.002). Thus, antibiotics may improve pulmonary function in patients with CF by decreasing P. aeruginosa exoenzyme expression. © 1993 Wiley-Liss, Inc.     

Inhaled antibiotics for treatment of adults with non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis

BackgroundInhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations.MethodsWe performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154.ResultsTwelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70–5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81–18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28–1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82–0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV₁, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35–3.27) at the end of therapy, with a number needed to treat of 6.ConclusionsIA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.     

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.     

Sputum substance P and neurokinin A are reduced during exacerbations of chronic obstructive pulmonary disease

Involvement of tachykinins in airway inflammation has been demonstrated in animal models, but evidence in humans is sparse. The aim of this study was to quantify the levels of substance P and neurokinin A in induced sputum of patients with chronic obstructive pulmonary disease (COPD) and to compare them with the levels in smokers with normal lung function and healthy nonsmokers. Content of tackykinins was measured in 12 sputum samples collected during stable condition and nine sputum samples collected during exacerbations from 13 COPD patients, in eight sputum samples from smokers with normal lung function and in nine from healthy nonsmokers. Patients with COPD exacerbations had a lower sputum content of substance P compared with the other 3 groups (p<0.05). No differences were found between patients with stable COPD, smokers with normal lung function, and nonsmokers. Sputum levels of neurokinin A were trending in the same direction of substance P, but the significant difference was reached for the paired sputum samples collected from the same COPD patients (n=8) during exacerbation and in stable condition. COPD exacerbations are associated with a reduced sputum content of substance P and neurokinin A. These tackykinins might be involved in COPD exacerbations.     

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.     

Clinical predictors of exacerbation frequency in chronic obstructive pulmonary disease

Introduction: Reduction of exacerbation frequency plays an increasingly important role in interventions in chronic obstructive pulmonary disease (COPD). To reduce this frequency efficiently, patients at risk for frequent exacerbations need to be identified. Objective: The objective of the study was to identify predictors for frequent exacerbations from multiple domains of COPD during a stable phase of the disease. Methods: Data of multiple domains of COPD were collected from 121 patients with moderate to severe COPD. Patients were divided into infrequent (<2 exacerbations per year) and frequent (≥2 exacerbations) exacerbators. Results: St. George's Respiratory Questionnaire (SGRQ) total score and a course of oral corticosteroid within 3 months prior to the study together predicted best whether patients would be infrequent or frequent exacerbators over the course of the next year. Each unit increase in total SGRQ score was associated with a 3% higher risk of being a frequent exacerbator [odds ratio (OR) = 1.03; 95% confidence interval (CI): 1.00–1.06; P = 0.047]. Patients who received a course of oral corticosteroids in the period of 3 months prior to the study had a three‐fold increased risk of being a frequent exacerbator (OR = 3.17; 95% CI: 1.20–8.34; P = 0.02). Furthermore, we observed that a sizable number of patients switched from being a frequent to an infrequent exacerbator and vice versa. Conclusions: Health‐related quality of life and a course of oral corticosteroid in the past 3 months are the best predictors of future exacerbator status. The predictive value of the model is, however, still insufficient. Furthermore, our data suggest, in contrast to previous observations, that exacerbation frequency is not a constant feature. Please cite this paper as: Brusse‐Keizer MGJ, van der Palen J, van der Valk PDLPM, Hendrix R, Kerstjens HAM. Clinical predictors of exacerbation frequency in chronic obstructive pulmonary disease. Clin Respir J 2011; 5: 227–234.     

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.     

Prulifloxacin versus levofloxacin in the treatment of severe COPD patients with acute exacerbations of chronic bronchitis

RationaleAntimicrobial therapy of chronic bronchitis exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) is based on empiric antibiotic treatment.ObjectivesTo evaluate the efficacy of prulifloxacin versus levofloxacin therapy in severe COPD patients with exacerbations of chronic bronchitis.MethodsThis study involved a multicenter, parallel, double-blind, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers (>10 pack-years) with spirometrically confirmed severe COPD (FEV₁ ≤ 50% predicted and FEV₁/FVC ratio < 0.7) and diagnosed with an acute exacerbation of chronic bronchitis were enrolled in the study. Patients were randomized to receive prulifloxacin 600 mg once a day or levofloxacin 500 mg once a day for 7 days.Measurements and main resultsThe primary outcome measure was clinical assessment at the TOC visit (7–10 days after the end of treatment) of signs and symptoms of exacerbation, namely sputum purulence, sputum volume, dyspnoea, cough and body temperature assessed through semi-quantitative scales. The ITT population included 346 (174 prulifloxacin, 172 levofloxacin) out of 351 treated subjects. A total of 161 patients with prulifloxacin (92.5%) and 166 with levofloxacin (96.5%) were considered cured at TOC (the difference in the percentage of cured patients was ?3.98 with 95%CI of ?8.76; 0.79). At the 6-month follow-up, the rates of patients with no relapse of AECB were higher than 95% in both the prulifloxacin and levofloxacin groups.ConclusionsBoth prulifloxacin and levofloxacin showed efficacy rates higher than 90% in the treatment of severe COPD patients with exacerbations of chronic bronchitis, with no statistically significant differences between the two antibiotics. The long-term follow-up confirmed a very low incidence of relapse, endorsing the appropriateness of this therapeutic approach.EUDRACT no. 2006-004167-56.     

Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease

RATIONALE: Increased bacterial concentration (load) in the lower airways and new bacterial strain acquisition have been posited as mechanisms for chronic obstructive pulmonary disease (COPD) exacerbations. Bacterial concentrations are higher during exacerbation than during stable disease; however, these studies are cross sectional and devoid of strain typing. OBJECTIVES: To determine if the increased bacterial concentrations function as a separate mechanism for exacerbation induction independent of new strain acquisition. METHODS: In a prospective, longitudinal cohort of patients with COPD, the relationship between exacerbation occurrence, sputum bacterial concentrations, and new strain acquisition was examined. MEASUREMENTS AND MAIN RESULTS: Clinical information, quantitative sputum cultures, and molecular typing of potential bacterial pathogen isolates. Over 81 months, 104 subjects completed 3,009 clinic visits, 560 (19.6%) during exacerbations and 2,449 (80.4%) during stable disease. Among preexisting strains, sputum concentrations of Nontypeable Haemophilus influenzae and Haemophilus haemolyticus were not different in exacerbation versus stable disease. Moraxella catarrhalis (stable, 10(8.38 +/- 0.13) [mean +/- SEM] vs. exacerbation, 10(7.78 +/- 0.26); p = 0.02) and Streptococcus pneumoniae (stable, 10(8.42 +/- 0.21) vs. exacerbation, 10(7.76 +/- 0.52); p = 0.07) concentrations were lower during exacerbations compared with stable periods. Concentrations of new strains of H. influenzae (stable, 10(7.28 +/- 0.15) vs. exacerbation, 10(7.76 +/- 0.17); p = 0.04) and M. catarrhalis (stable, 10(7.85 +/- 0.15) vs. exacerbation, 10(8.37 +/- 0.14); p = 0.02), were increased during exacerbations; however, the differences were small. CONCLUSIONS: Change in bacterial load is unlikely to be an important mechanism for exacerbations. Better understanding of the host-pathogen interaction, rather than enumerating bacteria in respiratory samples, is required to provide new insights into bacterial infection in COPD.     

Poor clinical outcomes associated with a multi-drug resistant clonal strain of Pseudomonas aeruginosa in the Tasmanian cystic fibrosis population

Background and objective: Clonal strains of Pseudomonas aeruginosa have been identified in large cystic fibrosis (CF) centres. Whether such strains are more virulent or whether cross‐infection between patients explains their widespread prevalence is unknown. This study described the epidemiology of P. aeruginosa infection in CF patients in Tasmania, Australia, an area with a high CF birth incidence. Patients in Tasmania are geographically dispersed and when this study was conducted (2003) there was no central CF clinic, with patients receiving treatment in regional hospitals. Methods: P. aeruginosa isolates from CF adults aged 15 years and over in Tasmania were genotyped using random amplified polymorphic DNA (RAPD)‐PCR and clonal strains confirmed with pulsed field gel electrophoresis. Results: Airway samples were obtained from 41 patients (82% of the adult CF population). P. aeruginosa was isolated from 34 patients and nine (26%) of these individuals harboured P. aeruginosa strains with identical RAPD‐PCR and pulsed field gel electrophoresis patterns (Australian Epidemic Strain III – AES III). AES III was isolated from patients in all regions of Tasmania and was distinct from the epidemic CF strains described on mainland Australia (AES I and II). The possible link between CF adults infected with AES III was attendance at family camps more than 12 years previously. Patients harbouring AES III had suffered significantly more exacerbations requiring hospitalisation during the 2 years prior to the study compared with patients infected with unique strains (P < 0.01). AES III displayed increased multi‐antibiotic resistance compared with other strains (P < 0.001). Conclusions: Clonal strains of P. aeruginosa may arise even in isolated CF populations. The increased exacerbation rate in patients infected with AES III and its antibiotic resistance profile strongly suggest increased virulence.     

慢性阻塞性肺疾病患者肺炎衣原体感染的研究

目的 探讨肺炎衣原体感染与慢性阻塞性肺疾病（COPD）的相关性。方法 选择61例COPD急性加重期患者,35例COPD稳定期患者,26名正常对照者,采用微量免疫荧光法测定血清肺炎衣原体特异性抗体IgA,IgM,IgG,套式聚俣酶链反应检测痰中的肺炎衣原体DNA。结果 COPD急性加重期患者的急性肺炎衣原体的感染率为31．1％,明显高于COPD稳定期和且（P＜0．05）。COPD急性加重期组和稳定期组的慢性肺炎衣原体感染率分别为21．3％和31．4％,明显高于对照组（P均＜0．05）,同时IgA的几何平均滴度在COPD急性加重期中最高（20．5）,COPD稳定期组中次之（10．8）,对照组最低（3．6）,三组间差异有显著性（P＜0．05）。结论 急性肺炎衣原体感染为COPD急性加重的一个重要诊因,慢性肺炎衣原体感染可能参与COPD的发病机制。     

Antibiotic Resistance in Sputum Isolates of Streptococcus pneumoniae in Chronic Obstructive Pulmonary Disease is Related to Antibiotic Exposure

ABSTRACT

Streptococcus pneumoniae (S. pneumoniae) is recovered from sputum of patients with chronic obstructive pulmonary disease (COPD) during stable disease and exacerbations. In patients with community acquired pneumonia, antibiotic exposure in the prior 3–6 months is associated with recovery of antibiotic resistant isolates of S. pneumoniae. Whether the same relationship is seen in COPD is not known. From April 1994 to June 2004, 127 adults with COPD were enrolled in a prospective longitudinal study. Sputum isolates of S. pneumoniae were characterized with susceptibility testing and pulsed-field gel electrophoresis (PFGE). The relationship between antibiotic use in the previous 3 and 6 months with either new acquisition of a resistant pneumococcal isolate or development of resistance (4-fold increase in MIC) in a pre-existing colonizing pneumococcal strain was determined. A total of 194 pneumococcal isolates were recovered from 38 patients. Among 71 newly acquired and 4 resistance-emergent strains analyzed further, rates of resistance to penicillin (MIC ≥2), erythromycin (MIC ≥1), tetracycline (MIC ≥8) and trimethoprim/sulfamethoxazole (MIC ≥4) were 8%, 24%, 17% and 16% respectively. Flouroquinolone resistance was not seen. Among strains isolated from patients exposed to a macrolide within 6 months, 53.6% displayed erythromycin resistance vs. 14% of strains without such exposure (p = 0.00085). Similar associations were not seen for other antibiotics. Macrolide use in the previous 6 months is associated with macrolide resistance in sputum isolates of S. pneumoniae. Recent antibiotic exposure may help in determining appropriate antibiotic treatment in these patients.     

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.     

The Economic Impact of Exacerbations of Chronic Obstructive Pulmonary Disease and Exacerbation Definition: A Review

ABSTRACT

Chronic obstructive pulmonary disease (COPD) poses a significant economic burden on society, and a substantial portion is related to exacerbations of COPD. A literature review of the direct and indirect costs of COPD exacerbations was performed. A systematic search of the MEDLINE database from 1998–2008 was conducted and supplemented with searches of conference abstracts and article bibliographies. Articles that contained cost data related to COPD exacerbations were selected for in-depth review. Eleven studies examining healthcare costs associated with COPD exacerbations were identified. The estimated costs of exacerbations vary widely across studies: $88 to $7,757 per exacerbation (2007 US dollars). The largest component of the total costs of COPD exacerbations was typically hospitalization. Costs were highly correlated with exacerbation severity. Indirect costs have rarely been measured. The wide variability in the cost estimates reflected cross-study differences in geographic locations, treatment patterns, and patient populations. Important methodological differences also existed across studies. Researchers have used different definitions of exacerbation (e.g., symptom- versus event-based definitions), different tools to identify and measure exacerbations, and different classification systems to define exacerbation severity. Unreported exacerbations are common and may influence the long-term costs of exacerbations. Measurement of indirect costs will provide a more comprehensive picture of the burden of exacerbations. Evaluation of pharmacoeconomic analyses would be aided by the use of more consistent and comprehensive approaches to defining and measuring COPD exacerbations.