calca-protein--human and Pulmonary-Disease--Chronic-Obstructive

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. COPD exacerbations have a major impact on morbidity and mortality. The etiology of COPD exacerbations is largely due to viral and bacterial infections in combination with underlying inflammation that is typically neutrophilic, although it is eosinophilic in 10 to 25% of cases. We review the recent studies that have defined novel biological clusters at exacerbation events and consequently identified important biomarkers to direct therapy. These biomarkers include C-reactive protein, procalcitonin, and peripheral blood eosinophil count, which are readily available. We are therefore at a point of making personalized antibiotic and corticosteroid therapy in COPD exacerbations a reality. Integration of the wealth of emerging data to further define the complexity of exacerbations also promises to identify new targets and biomarkers to treat COPD exacerbations.

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Disease Progression; Eosinophils; Humans; Leukocyte Count; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections

The acute exacerbation of COPD (AECOPD) is a life-threatening clinical situation. This review summarizes the definition of AECOPD, the severity assessment, typical clinical signs and symptoms, and refers to clinical pitfalls of diagnosis and therapy. Important aspects of clinical history and physical examination in severe exacerbations are reported. The necessary accompanying examinations like chest X-ray, blood gas analysis, ECG and echocardiography and their differential diagnosis as well as therapeutic significance are described. The most important lab examinations are summarized and controversial parameters, e.g., procalcitonin, are commented upon. The differentiated need for a microbiological sputum screening is emphasized. The authors place special weight on the essential components of the therapeutic management of severe AECOPD. Practical aspects of uncontrolled oxygen therapy, drug selection, and application form of inhalative acute therapy, dose, and duration of glucocorticoids, the indication for antibiotics, mechanical ventilation, and also opiates are summarized.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Analgesics, Opioid; Anti-Bacterial Agents; Bronchodilator Agents; Calcitonin; Calcitonin Gene-Related Peptide; Combined Modality Therapy; Critical Care; Diagnosis, Differential; Disease Progression; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Medical History Taking; Nebulizers and Vaporizers; Oxygen Inhalation Therapy; Physical Examination; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiration, Artificial; Sputum

The aim of this article is to review the current literature examining the use of procalcitonin-guided antibiotic therapy for management of chronic obstructive pulmonary disease (COPD) exacerbations. Procalcitonin is a serum marker that rises in response to bacterial infections, but remains low in nonbacterial infections and other proinflammatory conditions. To date, there are four randomized clinical trials which compare procalcitonin-guided antibiotic therapy to standard therapy in patients with COPD exacerbations. In all four trials the use of procalcitonin was associated with a reduction in antibiotic use (prescription and/or duration) without an increase in the rates of adverse patient outcomes including death, admission to the intensive care unit, re-exacerbation and readmission to the hospital. This data is clinically significant and suggests that the use of procalcitonin-guided antibiotic therapy has the potential to decrease unnecessary antibiotic use in nonbacterial COPD exacerbations, thereby curtailing the spread of antibiotic-resistant bacteria, reducing antibiotic-related adverse reactions, including Clostridium difficile infection, and potentially reducing healthcare costs.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Clostridioides difficile; Disease Progression; Drug Resistance, Bacterial; Humans; Lung; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Outcome

This review aims to provide physicians with an overview of the potential of biomarkers to complement existing clinical severity scores and in conjunction with clinical parameters to improve the diagnosis, risk-stratification and management of lower respiratory tract infections (LRTIs). The usefulness of biomarkers for diagnosing LRTIs is still unclear. However, the specificity of pneumonia diagnosis is high when high sensitivity C-reactive protein (CRP) and procalcitonin (PCT) are used. PCT, CRP and particularly pro-atrial natriuretic peptide (MR-proANP), pro-vasopressin (CT-proAVP) and proadrenomedullin (proADM) levels can reliably predict LRTIs mortality. These markers do not significantly improve the severity scores predictive values, confirming that biomarkers are meant to complement, rather than supersede, clinician's judgment and validated severity scores. Biomarkers, and particularly PCT, are useful tools as antibiotic treatment duration indicators both in pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD). Even if more data are required to fully appreciate the role of biomarkers in LRTIs management, there is emerging evidence that biomarkers have the potential to improve the daily clinical management of LRTIs.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Pneumonia; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Vasopressins

Acute dyspnea is one of the leading causes of emergency hospitalization of elderly patients. Clinical diagnostic procedures are difficult in this geriatric population. Acute heart failure is the most frequent cause of acute dyspnea in geriatric patients. The use of plasma B natriuretic peptide (BNP) assays in the general population has profoundly improved its medical management. There has also been progress recently for other frequent causes of dyspnea in the elderly, including infection and venous thromboembolic disease. Procalcitonin assays may be useful as a prognostic factor for infectious disease. Nevertheless, the real value of BNP assays in geriatric populations must be clarified by interventional studies.

Topics: Acute Disease; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Dyspnea; Emergencies; Emergency Service, Hospital; Female; Fibrin Fibrinogen Degradation Products; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Patient Admission; Pneumonia; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Thromboembolism; Troponin

The relevance of antibiotics in the treatment of acute exacerbation has been a matter of debate for several years. Although expert recommendations may vary, there is general agreement about the fact that not all patients will equally experience benefit from antibiotics: apart from decreasing costs, discriminate use of antibiotics is capable of significantly reducing subsequent colonization or infection with antibiotic-resistant bacteria.. Several meta-analyses support the concept that patients with increased dyspnea, increased sputum volume, and increased sputum purulence will benefit from antimicrobial therapy. Evidence from randomized trials substantiates the prescription of antibiotics in patients receiving mechanical ventilation and the avoidance of antibiotics in those admitted with low serum procalcitonin levels.. Most of the proposed criteria for prescribing or withholding antibiotics for acute exacerbation have been analyzed in different retrospective study designs. Patients requiring ICU care and mechanical ventilation for chronic obstructive pulmonary disease exacerbation should receive antibiotics. Conversely, antibiotics can be withheld in patients admitted to the emergency department with low serum procalcitonin levels. Patients with type I Anthonisen exacerbation and those with severe functional impairment are likely to benefit from antibiotics. Further investigations are needed to compare long-term outcome in patients treated according to clinical and functional criteria.

Topics: Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index

The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD.. We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days.. Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098).. ClinicalTrials.gov NCT01125098.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Administration Schedule; Drug Monitoring; Female; Humans; Italy; Male; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Treatment Outcome

Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection. Biomarkers that can identify bacterial infections may reduce antibiotic prescription. We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD.. Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008. Demographics, clinical data, and blood samples were collected. Procalcitonin and CRP concentrations were measured from available sera.. Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied. Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001). Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]). The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00). A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80%-97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia.. Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma. CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Female; Hospitalization; Humans; Male; Middle Aged; Pneumonia, Bacterial; Predictive Value of Tests; Protein Precursors; Pulmonary Disease, Chronic Obstructive; ROC Curve; Young Adult

Rational prescription of antibiotics in acute exacerbations of COPD (AECOPD) requires predictive markers. We aimed to analyze whether markers of systemic inflammation can predict response to antibiotics in AECOPD.. We used data from 243 exacerbations out of 205 patients from a placebo-controlled trial on doxycycline in addition to systemic corticosteroids for AECOPD. Clinical and microbiologic response, serum C-reactive protein (CRP) level (cutoffs 5 and 50 mg/L), and serum procalcitonin level (PCT) (cutoffs 0.1 and 0.25 μg) were assessed.. Potential bacterial pathogens were identified in the majority of exacerbations (58%). We found a modest positive correlation between PCT and CRP (r = 0.46, P < .001). The majority of patients (75%) had low PCT levels, with mostly elevated CRP levels. Although CRP levels were higher in the presence of bacteria (median, 33.0 mg/L [interquartile range, 9.75-88.25] vs 17 mg/L [interquartile range, 5.0-61.0] [P = .004]), PCT levels were similar. PCT and CRP performed similarly as markers of clinical success, and we found a clinical success rate of 90% in patients with CRP ≤ 5 mg/L. A significant effect of doxycycline was observed in patients with a PCT level < .1 μg/L (treatment effect, 18.4%; P = .003). A gradually increasing treatment effect of antibiotics (6%, 10%, and 18%), although not significant, was found for patients with CRP values of ≤ 5, 6-50, and > 50 mg/L, respectively.. Contrary to the current literature, this study suggests that patients with low PCT values do benefit from antibiotics. CRP might be a more valuable marker in these patients.

Topics: Aged; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Doxycycline; Female; Follow-Up Studies; Glycoproteins; Humans; Male; Nephelometry and Turbidimetry; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Recurrence; Retrospective Studies; Treatment Outcome

The induction of C-reactive Protein (CRP) may be attenuated by corticosteroids, whereas Procalcitonin (PCT) appears to be unaltered. We investigated, whether in community-acquired pneumonia (CAP) a combined antibiotic-corticosteroid therapy may actually lead to different slopes of decline of these inflammatory markers.. We studied the slopes of decline of PCT and CRP serum levels during 7 consecutive days as well as clinical parameters in a group of patients with CAP on or off corticosteroids. Patients with underlying COPD received systemic corticosteroids (n = 10), while non-COPD patients (n = 10) presenting with CAP alone formed the control group. All patients were treated with antibiotics.. At baseline, relevant clinical and laboratory characteristics of the two groups were similar. Regarding the decreasing shapes of the curves from PCT and CRP, no significant differences were found (p-value = 0.48 for the groups for CRP, respectively 0.64 for PCT). All patients showed an uneventful recovery.. In patients with COPD and CAP, the time courses over 7 days of PCT and CRP showed a nearly parallel decline compared to non-COPD patients with CAP. Contrary to the induction phase, corticosteroids do not modify the time-dependent decay of PCT and CRP when the underlying infectious disease (CAP) is adequately treated.

Topics: Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Drug Therapy, Combination; Female; Humans; Longitudinal Studies; Male; Methylprednisolone; Middle Aged; Pilot Projects; Pneumococcal Infections; Pneumonia; Prednisone; Protein Precursors; Pulmonary Disease, Chronic Obstructive

Therapy with antibiotics influences recovery only in selected cases of COPD exacerbations. We evaluated the efficacy and safety of procalcitonin guidance compared to standard therapy with antibiotic prescriptions in patients experiencing exacerbations of COPD.. A total of 208 consecutive patients requiring hospitalization for COPD exacerbation were randomized at the index exacerbation to procalcitonin-guided or standard antibiotic therapy. Patients receiving procalcitonin-guided therapy were treated with antibiotics according to serum procalcitonin levels; standard-therapy patients received antibiotics according to the attending physician. The primary outcome was the antibiotic exposure at the index exacerbation and the subsequent antibiotic requirement for COPD exacerbation within 6 months. Secondary outcomes were clinical recovery, symptom scores, length of hospitalization, ICU stay, death, lung function, exacerbation rate, and time to next exacerbation.. At the index exacerbation, procalcitonin guidance reduced antibiotic prescription (40% vs 72%, respectively; p < 0.0001) and antibiotic exposure (relative risk [RR], 0.56; 95% confidence interval [CI], 0.43 to 0.73; p < 0.0001) compared to standard therapy. Moreover, procalcitonin guidance at the index exacerbation allowed a significant sustained reduction in total antibiotic exposure for up to 6 months (RR, 0.76; 95% CI, 0.64 to 0.92; p = 0.004). Clinical outcome and improvement in FEV(1) at 14 days and 6 months did not differ between groups. Within 6 months, the exacerbation rate (0.62 vs 0.64, respectively), the rehospitalization rate (0.21 vs 0.24, respectively), and mean (+/- SD) time to the next exacerbation (70.0 +/- 46.1 vs 70.4 +/- 51.9 days, respectively; p = 0.523) were similar in both groups.. Procalcitonin guidance for exacerbations of COPD offers a sustained advantage over standard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Spirometry; Statistics, Nonparametric; Treatment Outcome

Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay.. 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat.. Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%).. Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.

Topics: Acute Disease; Aged; Anti-Bacterial Agents; Bacterial Infections; Bronchitis; Calcitonin; Calcitonin Gene-Related Peptide; Drug Utilization Review; Female; Humans; Male; Middle Aged; Pneumonia; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Single-Blind Method; Treatment Outcome

Although pharmacological treatment of COPD exacerbation (COPDE) includes antibiotics and systemic steroids, a proportion of patients show worsening of symptoms during hospitalization that characterize treatment failure. The aim of our study was to determine in-hospital predictors of treatment failure (≤ 7 days). Prospective data on 110 hospitalized COPDE patients, all treated with antibiotics and systemic steroids, were collected; on the seventh day of hospitalization, patients were divided into treatment failure (n = 16) or success (n = 94). Measures of inflammatory serum biomarkers were recorded at admission and at day 3; data on clinical, laboratory, microbiological, and severity, as well data on mortality and readmission, were also recorded. Patients with treatment failure had a worse lung function, with higher serum levels of C-reactive protein (CRP), procalcitonin (PCT), tumour necrosis factor-alpha (TNF-α), interleukin (IL) 8, and IL-10 at admission, and CRP and IL-8 at day 3. Longer length of hospital stay and duration of antibiotic therapy, higher total doses of steroids and prevalence of deaths and readmitted were found in the treatment failure group. In the multivariate analysis, +1 mg/dL of CRP at admission (OR, 1.07; 95% CI, 1.01 to 1.13) and use of penicillins or cephalosporins (OR, 5.63; 95% CI, 1.26 to 25.07) were independent variables increasing risk of treatment failure, whereas cough at admission (OR, 0.20; 95% CI, 0.05 to 0.75) reduces risk of failure. In hospitalized COPDE patients CRP at admission and use of specific class of antibiotics predict in-hospital treatment failure, while presence of cough has a protective role.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Disease Progression; Female; Forced Expiratory Volume; Glucocorticoids; Hospitalization; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Length of Stay; Logistic Models; Male; Mental Status Schedule; Middle Aged; Mortality; Multivariate Analysis; Patient Readmission; Pneumonia, Bacterial; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk Factors; Time Factors; Treatment Failure; Tumor Necrosis Factor-alpha

Viral or bacterial upper respiratory infections are the most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Based on available data, no reliable parameter has been presented to distinguish between bacterial and nonbacterial exacerbations. Therefore, we compared the diagnostic value of procalcitonin (PCT) level, which is a newer marker for predicting bacterial infections in patients with AECOPD, to routine parameters such as C-reactive protein (CRP) levels and the neutrophil/lymphocyte (N/L) ratio.. This study included all consecutive patients who were admitted for a diagnosis of AECOPD between January 1 and March 31, 2014. PCT, CRP, and the N/L ratio were assessed in addition to cultures from tracheal aspirates or sputum on the first day of admission. Patients with a pneumonic infiltration on chest radiographs, or an extrapulmonary infection focus, or whose blood samples were not obtained for PCT and/or CRP at the same time as sputum culture were excluded from the study.. A total of 77 patients were included with a mean age of 71.7 ± 9.5 years. Bacteria were isolated in 37.4 % of the patients. Mean PCT levels were significantly higher in patients with positive sputum cultures than in patients with negative sputum cultures. The cut-off values for PCT, CRP, and the N/L ratio for predicting a bacterial infection were 0.40 ng/mL, 91.50 mg/L, and 11.5, respectively; sensitivity was 61, 54, and 61 % respectively; specificity was 67, 52, and 58 %, respectively; and the area under the curve (AUC) values were 0.64, 0.52, and 0.58, respectively. The AUC value of PCT was significantly better for predicting bacterial infection compared with the CRP level or the N/L ratio (p = 0.042).. PCT was better than CRP and the N/L ratio for predicting a bacterial infection in hospitalized patients with AECOPD. However, we find PCT not so reliable in predicting bacterial infection in AECOPD due to sensitivity and specificity of less than 80 % and a low AUC value.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Comorbidity; Female; Hospitalization; Humans; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Pneumonia, Bacterial; Prevalence; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Turkey

Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD) exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED) visits remains controversial.. Viral culture and polymerase chain reaction (PCR) were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC) counts, serum C-reactive protein (CRP), procalcitonin (PCT), and clinical symptoms were compared among patients with different types of infections.. Viruses were isolated from 16 (22.2%) of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7%) patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9%) had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria-negative groups were not statistically different. Multivariate analysis showed that patients with increased sputum volumes during the COPD exacerbations had higher risks of recurrent exacerbations in the 1-year period following the first exacerbation.. WBC, CRP, or PCT could not differentiate between bacterial and viral infections in patients with COPD exacerbation requiring ED visits. Those with increased sputum during a COPD exacerbation had higher risks for recurrent exacerbations.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Diagnosis, Differential; Disease Progression; Emergency Service, Hospital; Female; Humans; Inflammation Mediators; Kaplan-Meier Estimate; Leukocyte Count; Male; Multivariate Analysis; Oropharynx; Predictive Value of Tests; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Risk Factors; Sputum; Time Factors

A shortcut review was carried out to establish whether a procalcitonin-guided algorithm could safely reduce antibiotic consumption for patients with an exacerbation of chronic obstructive pulmonary disease attending the emergency department. Four randomised controlled trials were found directly relevant to the three-part question, combined within a later systematic review and meta-analysis. A further prospective cohort study was also found relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that a procalcitonin algorithm appears to be a useful strategy to guide initiation and duration of antibiotics and can reduce consumption without conferring additional risk. However, no cost effectiveness data are available as yet and further validation studies are required prior to widespread recommendation.

Topics: Aged; Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Evidence-Based Emergency Medicine; Female; Humans; Protein Precursors; Pulmonary Disease, Chronic Obstructive

Saliva is increasingly promoted as an alternative diagnostic bio-sample to blood; however its role in respiratory disease requires elucidation. Our aim was to investigate whether C-reactive protein (CRP), procalcitonin (PCT) and neutrophil elastase (NE) could be measured in unstimulated whole saliva, and to explore differences between COPD patients and controls with normal lung function. We also determined the relationship between these salivary biomarkers and self-reported COPD-relevant metrics.. Salivary CRP, PCT and NE levels were measured at each of 3 visits over a 14-day period alongside spirometry and a daily self-assessment dairy in 143 subjects: 20 never-smokers and 25 smokers with normal spirometry; 98 COPD patients [GOLD Stage I, 16; Stage II, 32; Stage III, 39; Stage IV, 11]. Twenty-two randomly selected subjects provided simultaneous blood samples.. Levels of each salivary biomarker could distinguish between the above cohorts. Significant differences remained for salivary CRP and NE (p < 0.05) following adjustment for age, gender, sampling time, gum disease and total co-morbidities; but not for BMI except for salivary NE, which remained higher in smokers compared to non-smokers and stable COPD subjects (p < 0.001). Patients with acute COPD exacerbations had a median increase in all 3 salivary biomarkers (p < 0.001); CRP: median 5.74 ng/ml, [interquartile range (IQR) 2.86-12.25], PCT 0.38 ng/ml, [IQR 0.22-0.94], and NE 539 ng/ml, [IQR 112.25-1264]. In COPD patients, only salivary CRP and PCT levels correlated with breathing scores (r = 0.14, p < 0.02; r = 0.13, p < 0.03 respectively) and sputum features but not with activities of daily living. Salivary CRP and PCT concentrations strongly correlated with serum counterparts [r = 0.82, (95% CI: 0.72-0.87), p < 0.001 by Spearman's; and r = 0.53, (95% CI: 0.33-0.69), p < 0.006 respectively]; salivary NE did not.. CRP, PCT and NE were reliably and reproducibly measured in saliva, providing clinically-relevant information on health status in COPD; additionally NE distinguished smoking status. All 3 salivary biomarkers increased during COPD exacerbations, with CRP and PCT correlating well with patient-derived clinical metrics. These results provide the conceptual basis for further development of saliva as a viable bio-sample in COPD monitoring and exacerbation management.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Leukocyte Elastase; Male; Middle Aged; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Random Allocation; Saliva; Self Report; Smoking

Chronic obstructive pulmonary disease (COPD) is associated with cognitive decline, but the molecular link between COPD and dementia or Alzheimer's disease (AD) remains unclear. This study was aimed to investigate whether serum Aβ levels are correlated with COPD. 77 cognitively normal COPD patients and 45 age- and gender-matched normal controls were admitted to the study. Serum Aβ40 and Aβ42 levels were measured using ELISA kits. Serum C-reactive protein (CRP), interleukin 6 (IL-6), and procalcitonin (PCT) measurements were done using standard laboratory methods. Pulmonary function tests were performed to assess the pulmonary function and determine the degree of lung damage. Significantly increased levels of serum Aβ40, Aβ42, and total Aβ levels were found in patients with COPD in comparison with normal controls. In COPD patients, serum Aβ levels were higher in subjects with serum CRP, IL-6, and PCT upper the limit of normal. Moreover, serum Aβ levels were dramatically higher in COPD patients with worse pulmonary function. Our study suggests that cognitively normal COPD patients may undergo AD-related pathological changes, and COPD might facilitate AD-type pathogenesis.

Topics: Aged; Amyloid beta-Peptides; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

To investigate the value of C-reactive protein (CRP) and procalcitonin (PCT) in diagnosis of the bacterial infection in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients by detecting the change of CRP and PCT.. A total of 369 AECOPD patients were divided into infective group and non-infective group. The values of CRP, PCT, WBC, N and ESR were tested and compared before and after treatment in each group.. Before treatment, the levels of CRP, PCT, WBC, and N in the infective group were significantly higher than that in the non-infective group (P<0.05 or P<0.01), while there was no significant difference in ESR level between the 2 groups (P>0.05). In the infective group, the levels of CRP, PCT, WBC, N and ESR after the treatment were much lower than those before treatment (P<0.05). After treatment, the levels of CRP, PCT, WBC, and N in the infective group were significantly higher compared with that in the non-infective group (P<0.05), while there was no significant difference of ESR level between the 2 groups (P>0.05). There was a positive relationship between PCT and CRP, ESR and WBC (r=0.46, 0.38, 0.20; P<0.05), CRP and WBC as well as N and ESR (r=0.56, 0.43, 0.30; P<0.05).. It is a sensitive method for diagnosis and treatment of the bacterial infection in AECOPD patients through the combination of CRP with PCT and also for evaluation of the prognosis of patients with AECOPD.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive

Serum procalcitonin levels have been used as a biomarker of invasive bacterial infection and recently have been advocated to guide antibiotic therapy in patients with chronic obstructive pulmonary disease (COPD). However, rigorous studies correlating procalcitonin levels with microbiologic data are lacking. Acute exacerbations of COPD (AECOPD) have been linked to viral and bacterial infection as well as noninfectious causes. Therefore, we evaluated procalcitonin as a predictor of viral versus bacterial infection in patients hospitalized with AECOPD with and without evidence of pneumonia.. Adults hospitalized during the winter with symptoms consistent with AECOPD underwent extensive testing for viral, bacterial, and atypical pathogens. Serum procalcitonin levels were measured on day 1 (admission), day 2, and at one month. Clinical and laboratory features of subjects with viral and bacterial diagnoses were compared.. In total, 224 subjects with COPD were admitted for 240 respiratory illnesses. Of these, 56 had pneumonia and 184 had AECOPD alone. A microbiologic diagnosis was made in 76 (56%) of 134 illnesses with reliable bacteriology (26 viral infection, 29 bacterial infection, and 21 mixed viral bacterial infection). Mean procalcitonin levels were significantly higher in patients with pneumonia compared with AECOPD. However, discrimination between viral and bacterial infection using a 0.25 ng/mL threshold for bacterial infection in patients with AECOPD was poor.. Procalcitonin is useful in COPD patients for alerting clinicians to invasive bacterial infections such as pneumonia but it does not distinguish bacterial from viral and noninfectious causes of AECOPD.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Disease Progression; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; New York; Pneumonia; Pneumonia, Bacterial; Predictive Value of Tests; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Time Factors; Up-Regulation; Virus Diseases

In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a prospective non-randomised interventional pilot study applying a sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers. In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. The primary end-point was rate of therapeutic failure during hospitalisation. Secondary end-points were parameters reflecting short- and long-term outcomes. We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulent versus 10% purulent (p=0.51)). Serum C-reactive protein (CRP) was significantly increased in the purulent group at admission (11.6 versus 5.3, p=0.006) and at day 3 (2.7 versus 1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group. These results support the hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospitalization; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory System; Sputum; Time Factors; Treatment Outcome

The identification of biological markers in order to assess different aspects of COPD is an area of growing interest. The objective of this study was to investigate whether levels of procalcitonin (PCT), C-reactive protein (CRP), and neopterin in COPD patients could be useful in identifying the etiological origin of the exacerbation and assessing its prognosis.. We included 318 consecutive COPD patients: 46 in a stable phase, 217 undergoing an exacerbation, and 55 with pneumonia. A serum sample was collected from each patient at the time of being included in the study. A second sample was also collected 1 month later from 23 patients in the exacerbation group. We compared the characteristics, biomarker levels, microbiological findings, and prognosis in each patient group. PCT and CRP were measured using an immunofluorescence assay. Neopterin levels were measured using a competitive immunoassay.. PCT and CRP showed significant differences among the three patient groups, being higher in patients with pneumonia, followed by patients with exacerbation (P < 0.0001). For the 23 patients with paired samples, PCT and CRP levels decreased 1 month after the exacerbation episode, while neopterin increased. Neopterin showed significantly lower levels in exacerbations with isolation of pathogenic bacteria, but no differences were found for PCT and CRP. No significant differences were found when comparing biomarker levels according to the Gram result: PCT (P = 0.191), CRP (P = 0.080), and neopterin (P = 0.109). However, median values of PCT and CRP were high for Streptococcus pneumoniae, Staphylococcus aureus, and enterobacteria. All biomarkers were higher in patients who died within 1 month after the sample collection than in patients who died later on.. According to our results, biomarker levels vary depending on the clinical status. However, the identification of the etiology of infectious exacerbation by means of circulating biomarkers is encouraging, but its main disadvantage is the absence of a microbiological gold standard, to definitively demonstrate their value. High biomarker levels during an exacerbation episode correlate with the short-term prognosis, and therefore their measurement can be useful for COPD management.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Chi-Square Distribution; Female; Fluorescent Antibody Technique; Forced Expiratory Volume; Humans; Immunoassay; Inflammation Mediators; Kaplan-Meier Estimate; Lung; Male; Middle Aged; Neopterin; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Severity of Illness Index; Spain; Sputum; Time Factors

Respiratory viruses frequently are recovered in the upper-respiratory tract during acute exacerbations of COPD (AECOPD), but their role as contributing pathogens remains unclear. The usefulness of procalcitonin and C-reactive protein as indicators of the presence or absence of viral infection in this setting also needs to be evaluated.. The study was of a prospective cohort of patients with COPD admitted to the ED for AECOPD. Reverse transcriptase-polymerase chain reaction (RT-PCR) for 14 respiratory viruses was performed on nasopharyngeal swabs collected at admission and after recovery in stable condition.. Eighty-six patients (mean age, 72 years; male, 64%) were included. During AECOPD, upper-respiratory viral infections were detected in 44 (51%) patients: picornavirus in 22, metapneumovirus in seven, coronavirus in eight, influenza A/B in two, parainfluenza in two, and respiratory syncytial virus in three. A dual infection was present in three patients. After recovery, viruses were detected in only eight (11%) of 71 patients (P < .001 compared with AECOPD phase). In five of these patients, no virus had been identified during the initial exacerbation, thus suggesting a new viral infection acquired during follow-up. During AECOPD, procalcitonin and C-reactive protein levels did not differ significantly between patients with or without a proven viral infection.. Prevalence of upper-respiratory viral infection, as detected from nasopharyngeal swab by RT-PCR, is high in AECOPD and low after clinical recovery, suggesting that AECOPD frequently are triggered by viral infections initiated in the upper-respiratory tract. In our study, serum procalcitonin and C-reactive protein did not discriminate virus-associated exacerbations from others.. clinicaltrials.gov; Identifier: NCT00448604.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Female; Humans; Male; Proportional Hazards Models; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Reverse Transcriptase Polymerase Chain Reaction

Little is known about the value of procalcitonin in predicting mortality in patients with an exacerbation of COPD. This study evaluated the clinical and biological predictors of intensive care unit (ICU) mortality in patients with a severe acute exacerbation of COPD.. A prospective observational cohort study was conducted of consecutive patients with severe acute exacerbation of COPD requiring intubation and mechanical ventilation. At ICU admission, data were collected on the patients' clinical condition, blood leukocyte count, C-reactive protein and procalcitonin. Cox proportional hazards model was used to determine the risk factors for ICU mortality.. One hundred and sixteen patients were included in this study. Mean age was 67 years. The mean simplified acute physiology score was 43. Sixty-five per cent of study patients had chronic respiratory insufficiency. Bacteria were cultured at levels considered significant in 36% of study patients. Logistic organ dysfunction score (hazard ratio (95% CI) = 1.19 (1.03-1.37), P = 0.013), rapidly fatal underlying disease (3.33 (1.40-7.87), P = 0.003) and procalcitonin level (1.01 (1-1.03), P = 0.018) were independently associated with increased risk for ICU mortality. Non-invasive mechanical ventilation use before intubation was independently associated with reduced risk for ICU mortality (0.34 (0.14-0.84), P = 0.020).. In patients with severe acute exacerbation of COPD requiring intubation and mechanical ventilation, logistic organ dysfunction score, rapidly fatal underlying disease and procalcitonin are independently associated with increased risk for ICU mortality. Non-invasive mechanical ventilation use before intubation was independently associated with reduced risk for ICU mortality.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Intensive Care Units; Intubation, Intratracheal; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiration, Artificial; Retrospective Studies; Risk Factors; Severity of Illness Index

Serum procalcitonin (PCT) is considered useful in predicting the likeliness of developing bacterial infections in emergency setting. In this study, we describe PCT levels overtime and their relationship with bacterial infection in chronic obstructive pulmonary disease (COPD) critically ill patients with pneumonia.. We conducted a prospective cohort study in an ICU of a University Hospital. All consecutive COPD patients admitted for pneumonia between September 2005 and September 2006 were included. Respiratory samples were tested for the presence of bacteria and viruses. Procalcitonin was sequentially assessed and patients classified according to the probability of the presence of a bacterial infection.. Thirty four patients were included. The PCT levels were assessed in 32/34 patients, median values were: 0.493 microg/L [IQR, 0.131 to 1.471] at the time of admission, 0.724 microg/L [IQR, 0.167 to 2.646] at six hours, and 0.557 microg/L [IQR, 0.123 to 3.4] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 3/32 (9%) patients and greater than 0.25 microg/L in 22/32 (69%) patients, suggesting low and high probability of bacterial infection, respectively. Fifteen bacteria and five viruses were detected in 15/34 (44%) patients. Bacteria were not detected in patients with PCTmax levels < 0.1 microg/L. In contrast, bacteria were detected in 4/7 (57%) patients estimated unlikely to have a bacterial infection by PCT levels (PCTmax > 0.1 and < 0.25 microg/L).. Based on these results we suggest that a PCT level cut off > 0.1 microg/L may be more appropriate than 0.25 microg/L (previously proposed for non severe lower respiratory tract infection) to predict the probability of a bacterial infection in severe COPD patients with pneumonia. Further studies testing procalcitonin-based antibiotic strategies are needed in COPD patients with severe pneumonia.

Topics: Aged; Aged, 80 and over; Bacteria; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Pneumonia, Bacterial; Predictive Value of Tests; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive

Biomarkers in exacerbated chronic obstructive pulmonary disease may be useful in aiding diagnosis, defining specific phenotypes of disease, monitoring the disease and evaluating the effects of drugs. The aim of this study was the characterization of metallic elements in exhaled breath condensate and serum as novel biomarkers of exposure and susceptibility in exacerbated chronic obstructive pulmonary disease using reference analytical techniques. C-Reactive protein and procalcitonin were assessed as previously validated diagnostic and prognostic biomarkers which have been associated with disease exacerbation, thus useful as a basis of comparison with metal levels. Exhaled breath condensate and serum were obtained in 28 patients at the beginning of an episode of disease exacerbation and when they recovered. Trace elements and toxic metals were measured by inductively coupled plasma-mass spectrometry. Serum biomarkers were measured by immunoassay. Exhaled manganese and magnesium levels were influenced by exacerbation of chronic obstructive pulmonary disease, an increase in their concentrations--respectively by 20 and 50%--being observed at exacerbation in comparison with values obtained at recovery; serum elemental composition was not modified by exacerbation; serum levels of C-reactive protein and procalcitonin at exacerbation were higher than values at recovery. In outpatients who experienced a mild-moderate chronic obstructive pulmonary disease exacerbation, manganese and magnesium levels in exhaled breath condensate are elevated at admission in comparison with values at recovery, whereas no other changes were observed in metallic elements at both the pulmonary and systemic level.

Topics: Aged; Biomarkers; Breath Tests; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Magnesium; Male; Manganese; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Spirometry; Statistics, Nonparametric

Strategies aiming at reducing antibiotic use are required in the intensive care unit (ICU). Although antibiotic treatment is recommended in patients with severe exacerbation of chronic obstructive pulmonary disease (COPD), a bacterial etiology is found in only a half of these patients.. The aim of this study was to determine factors predicting bacterial isolation in severe acute exacerbations of COPD.. All patients with severe acute exacerbation of COPD requiring intubation and mechanical ventilation were included in this prospective observational cohort study. At ICU admission, information on endotracheal aspirate purulence and hyperthermia was collected. In all patients, Gram stain and quantitative endotracheal aspirate culture (positive at 10(6) cfu/ml) were performed. In addition, leukocyte count, C-reactive protein and procalcitonin (PCT) levels were measured.. Ninety-eight severe acute exacerbations of COPD requiring intubation and mechanical ventilation were studied. Forty-nine bacteria were isolated at significant threshold in 40 exacerbations. Streptococcus pneumoniae (16%), methicillin-sensitive Staphylococcus aureus (16%) and Hemophilus influenzae (14%) were the most frequently isolated bacteria. PCT >0.5 ng/ml and positive Gram stain of endotracheal aspirate were independently associated with bacterial isolation in severe acute exacerbation of COPD. Positive Gram stain and PCT >0.5 ng/ml had a negative predictive value >95%. Similar results were found after excluding patients with prior antibiotic treatment.. Positive Gram stain of endotracheal aspirate and PCT >0.5 ng/ml are independently associated with bacterial isolation in severe acute exacerbation of COPD. These results could be helpful for future interventional studies aiming at reducing antibiotic use in these patients.

Topics: Acute Disease; Aged; Algorithms; Bronchoalveolar Lavage Fluid; Calcitonin; Calcitonin Gene-Related Peptide; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Intensive Care Units; Intubation, Intratracheal; Male; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiration, Artificial; Sensitivity and Specificity

Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population.. We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay.. Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%-75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 microg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 microg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 microg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 14/35 (40%) patients and more than 0.25 microg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 microg/L and three had a PCTmax less than 0.1 microg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 microg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 microg/L respectively, P = 0.80).. The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 microg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Sputum; Virus Diseases

Topics: Acute Disease; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Respiratory Tract Infections

A novel approach to estimate the severity of COPD exacerbation and predict its outcome is the use of biomarkers. We assessed circulating levels of copeptin, the precursor of vasopressin, C-reactive protein (CRP), and procalcitonin as potential prognostic parameters for in-hospital and long-term outcomes in patients with acute exacerbation of COPD (AECOPD) requiring hospitalization.. Data of 167 patients (mean age, 70 years; mean FEV(1), 39.9 +/- 16.9 of predicted [+/- SD]) presenting to the emergency department due to AECOPD were analyzed. Patients were evaluated based on clinical, laboratory, and lung function parameters on hospital admission, at 14 days, and at 6 months.. Plasma levels of all three biomarkers were elevated during the acute exacerbation (p < 0.001), but levels at 14 days and 6 months were similar (p = not significant). CRP was significantly higher in patients presenting with Anthonisen type I exacerbation (p = 0.003). In contrast to CRP and procalcitonin, copeptin on hospital admission was associated with a prolonged hospital stay (p = 0.002) and long-term clinical failure (p < 0.0001). Only copeptin was predictive for long-term clinical failure independent of age, comorbidity, hypoxemia, and lung functional impairment in multivariate analysis (p = 0.005). The combination of copeptin and previous hospitalization for COPD increased the risk of poor outcome (p < 0.0001). Long-term clinical failure was observed in 11% of cases with copeptin < 40 pmol/L and no history of hospitalization, as compared to 73% of patients with copeptin >/= 40 pmol/L and a history of hospitalization (p < 0.0001).. We suggest copeptin as a prognostic marker for short-term and long-term prognoses in patients with AECOPD requiring hospitalization.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Follow-Up Studies; Glycopeptides; Glycoproteins; Hospitalization; Humans; Male; Middle Aged; Prognosis; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Recurrence; Retrospective Studies; Time Factors

To investigate the changes and clinical implications of serum procalcitonin in exacerbation of chronic obstructive pulmonary disease (COPD).. We have evaluated PCT measurement in 45 patients with an exacerbation of COPD (group A) and 25 patients with stable COPD (group B), quantitative sputum culture was performed, too. PPMs were only regarded as significant if they reached a growth of > or =10(7) cfu/mL, indicating the presence of bacterial infection.. In patients with an exacerbation, 15 patients, sputum yielded a high (> or =10(7) cfu/mL) bacterial load (group A1), 30 patients, sputum yielded a low (<10(7) cfu/mL) bacterial load or a negative bacterial culture (group A2). The levels of procalcitonin in sera from patients of group A1 were significantly higher than those from group A2 and group B [0.24 (0.17, 0.28) microg/L vs. 0.125 (0.10, 0.18) microg/L vs. 0.12 (0.10, 0.145) microg/L, P= 0.000, 0.000]. The levels of procalcitonin in sera from patients of group A2 were similar to those from group B (P>0.05). Using a cut-off point of 0.155 microg/L for PCT, the sensitivities and specificities for bacterial infection in patients with an exacerbation of COPD were 93.3% and 60% respectively.. Serum procalcitonin measurements in patients of an exacerbation of chronic obstructive pulmonary disease play a role in the diagnosis of bacterial infection.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Pneumonia, Bacterial; Predictive Value of Tests; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Sputum

To investigate the changes and clinical implications of serum procalcitonin (PCT) in acute exacerbations of chronic obstructive pulmonary disease (COPD).. A total of 45 patients with an acute exacerbation of COPD were studied. On presentation, serum PCT concentrations were measured, and quantitative sputum culture was also performed. The patients were reevaluated when they had returned to their stable clinical state. Potentially pathogenic microorganism (PPM) was only regarded as significant if they reached a growth of >or= 10(7) CFU/ml, indicating the presence of bacterial exacerbation of COPD.. (1) On presentation, sputum samples from 21 (46.7%) patients yielded PPM. When reevaluated in stable clinical state, sputum samples from 9 (20%) patients had a positive PPM culture [2.8 x 10(6) (1.3 x 10(6), 1.9 x 10(7)) CFU/ml], but with a significantly lower bacterial load than on presentation [7.0 x 10(7) (4.5 x 10(7), 7.1 x 10(8)) CFU/ml, Z = -2.666, P = 0.008]. (2) The patients were classified into two groups: group A included patients with bacterial exacerbation of COPD (n = 15), group B included patients with nonbacterial exacerbation of COPD (n = 30). The levels of PCT for patients of group A [0.24 (0.17, 0.28) microg/L] were significantly higher than group B [0.13 (0.10, 0.18) microg/L, Z = -3.531, P = 0.000]. When they had returned to their stable state, the levels of PCT for patients of group A decreased to 0.12 (0.10, 0.14) microg/L, which was significantly lower than in exacerbation [0.24 (0.17, 0.28) microg/L, Z = -3.298, P = 0.001]; But compared with exacerbation [0.13 (0.10, 0.18) microg/L], the levels of PCT for patients of group B did not changed [0.13 (0.10, 0.15) microg/L, Z = -1.614, P = 0.107]. In the stable state, there were no differences in the PCT measurement between the two groups (Z = -0.382, P = 0.703).. In patients presented with an acute exacerbation of COPD, the elevation of serum PCT is associated with bacterial infection.

Topics: Aged; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Serum

To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome.. Prospective observational study. Setting. Emergency department of a university hospital.. A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay.. MR-proANP levels (median [IQR], in pmol L(-1)) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1-279.0] vs. 72.7 [62.5-89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score (P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0-633.0] vs. 129.0 [71.4-255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07).. MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; Biomarkers; Bronchitis; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chronic Disease; Community-Acquired Infections; Female; Humans; Leukocyte Count; Male; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; ROC Curve; Severity of Illness Index

Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis. So far the relevance of PCT in healthy individuals or patients with local infections is unclear due to the lack of highly sensitive assays. The aim of our study was the characterization of a new sensitive PCT assay, the establishment of reference values and the assessment of diagnostic accuracy.. We assessed PCT values in 522 patients with different infectious and non infectious conditions and 410 healthy controls by a new coated tube sandwich chemiluminescence assay B.R.A.H.M.S ProCa-S (2 step assay, time to result 2.5 hours).. The lower detection limit was 6.0 ng/L, with a functional assay sensitivity below 7 ng/L. Samples above 250 ng/L gave excellent correlation to the LUMItest PCT (r = 0.98, p < 0.0001). There was no high dose hook effect up to a concentration of 21,300 ng/L. The 410 healthy controls had a median concentration of 12.7 ng/L (95% CI: 12.6-14.7 ng/L). 65 controls had non-detectable PCT values (defined as 5 ng/L). The 2.5th percentile of the normal population was 5 ng/L and the 97.5th percentile was 46.7 ng/L. ROC plot analysis resulted in an area under the curve (AUC) of 0.90. The optimal decision threshold was at 50 ng/L, with a sensitivity for infection of 77.8% and a specificity of 98.5% (positive predictive value 97.7%, negative predictive value 84.9%). There was a highly significant (p < 0.0001) difference in the PCT median between healthy individuals and patients with infections (e.g. pneumonia, peritonitis) but not non-infectious controls (e.g. pregnancy, autoimmune disease).. The new PCT assay is 30 times more sensitive than the established routine assay LUMItest PCT, thus allowing for the first time PCT detection in healthy individuals. First results indicate that the assay is suitable to differentiate local bacterial infections from other non-infectious diseases.

Topics: Adult; Appendicitis; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Humans; Infections; Luminescent Measurements; Lung Diseases; Male; Middle Aged; Pregnancy; Protein Precursors; Pulmonary Disease, Chronic Obstructive; Reference Values; Reproducibility of Results; Respiratory Distress Syndrome; Sensitivity and Specificity