Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

BACKGROUND: A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. METHODS: We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. RESULTS: 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22-1.38; p<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29-1.56; p<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01-1.24; p=0.027), for each increment in sputum purulence. CONCLUSION: Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.

Prevalence of Nontuberculous Mycobacterial Pulmonary Disease, Germany, 2009-2014.

We analyzed routine statutory health insurance claim data to determine prevalence of nontuberculous mycobacterial pulmonary disease in Germany. Documented prevalence rates of this nonnotifiable disease increased from 2.3 to 3.3 cases/100,000 population from 2009 to 2014. Prevalence showed a strong association with advanced age and chronic obstructive pulmonary disease.

Burden and trends of hospitalisations associated with pulmonary non-tuberculous mycobacterial infections in Germany, 2005-2011.

BACKGROUND: Representative population-based data on the epidemiology of pulmonary non-tuberculous mycobacterial (PNTM) infections in Europe are limited. However, these data are needed in order to optimise patient care and to facilitate the allocation of healthcare resources. The aim of the present study was to investigate the current burden and the trends of PNTM infection-associated hospitalisations in Germany. METHODS: International Classification of Diseases, 10th revision (ICD-10) discharge diagnosis codes were extracted from the official nationwide diagnosis-related groups (DRG) hospital statistics in order to identify PNTM infection-associated hospitalisations (ICD-10 code A31.0) between 2005 and 2011. Poisson log-linear regression analysis was used to assess the significance of trends. RESULTS: Overall, 5,959 records with PNTM infection as any hospital discharge diagnosis were extracted from more than 125 million hospitalisations. The average annual age-adjusted rate was 0.91 hospitalisations per 100,000 population. Hospitalisation rates increased during the study period for both males and females, with the highest rate of 3.0 hospitalisations per 100,000 population among elderly men, but the most pronounced average increase of 6.4%/year among females, particularly those of young and middle age, and hospitalisations associated with cystic fibrosis. Overall, chronic obstructive pulmonary disease (COPD) was the most frequent PNTM infection-associated condition in 28.9% of hospitalisations and also showed a significant average annual increase of 4.8%. CONCLUSIONS: The prevalence of PNTM infection-associated hospitalisations is steadily increasing in Germany. COPD is currently the most important associated condition. Our population-based study provides evidence of a changing epidemiology of PNTM infections and highlights emerging clinical implications.

Psychometric Validation of the German Translation of the Quality of Life Questionnaire-Bronchiectasis (QOL-B)-Data from the German Bronchiectasis Registry PROGNOSIS.

Patients with bronchiectasis feature considerable symptom burden and reduced health-related quality of life (QOL). We provide the psychometric validation of the German translation of the disease-specific Quality of Life Questionnaire-Bronchiectasis (QOL-B), version 3.1, using baseline data of adults consecutively enrolled into the prospective German bronchiectasis registry PROGNOSIS. Overall, 904 patients with evaluable QOL-B scores were included. We observed no relevant floor or ceiling effects. Internal consistency was good to excellent (Cronbach's α ≥0.73 for each scale). QOL-B scales discriminated between patients based on prior pulmonary exacerbations and hospitalizations, breathlessness, bronchiectasis severity index, lung function, sputum volume, Pseudomonas aeruginosa status and the need for regular pharmacotherapy, except for Social Functioning, Vitality and Emotional Functioning scales. We observed moderate to strong convergence between several measures of disease severity and QOL-B scales, except for Social and Emotional Functioning. Two-week test-retest reliability was good, with intraclass correlation coefficients ≥0.84 for each scale. Minimal clinical important difference ranged between 8.5 for the Respiratory Symptoms and 14.1 points for the Social Functioning scale. Overall, the German translation of the QOL-B, version 3.1, has good validity and test-retest reliability among a nationally representative adult bronchiectasis cohort. However, responsiveness of QOL-B scales require further investigation during registry follow-up.

Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory.

BACKGROUND: High functional antibody responses, establishment of immunologic memory, and unambiguous efficacy in infants suggest that an initial dose of conjugated pneumococcal polysaccharide (PnC) vaccine may be of value in a comprehensive adult immunization strategy. METHODS: We compared the immunogenicity and safety of 7-valent PnC vaccine (7vPnC) with that of 23-valent pneumococcal polysaccharide vaccine (PPV) in adults >/=70 years of age who had not been previously vaccinated with a pneumococcal vaccine. One year later, 7vPnC recipients received a booster dose of either 7vPnC (the 7vPnC/7vPnC group) or PPV (the 7vPnC/PPV group), and PPV recipients received a booster dose of 7vPnC (the PPV/7vPnC group). Immune responses were compared for each of the 7 serotypes common to both vaccines. RESULTS: Antipolysaccharide enzyme-linked immunosorbent assay antibody concentrations and opsonophagocytic assay titers to the initial dose of 7vPnC were significantly greater than those to the initial dose of PPV for 6 and 5 of 7 serotypes, respectively (P < .01 and P < .05, respectively). 7vPnC/7vPnC induced antibody responses that were similar to those after the first 7vPnC inoculation, and 7vPnC/PPV induced antibody responses that were similar to or greater than antibody responses after administration of PPV alone; PPV/7vPnC induced significantly lower antibacterial responses, compared with those induced by 7vPnC alone, for all serotypes (P < .05). CONCLUSION: In adults, an initial dose of 7vPnC is likely to elicit higher and potentially more effective levels of antipneumococcal antibodies than is PPV. In contrast with PPV, for which the induction of hyporesponsiveness was observed when used as a priming dose, 7vPnC elicits an immunological state that permits subsequent administration of 7vPnC or PPV to maintain functional antipolysaccharide antibody levels.

Impact of alcohol abuse in the etiology and severity of community-acquired pneumonia.

BACKGROUND AND STUDY OBJECTIVES: Alcohol consumption is known to affect both systemic and pulmonary immunity, predisposing the patient to pulmonary infections. The aim of this study was to compare the etiology of disease, the antibiotic resistance of Streptococcus pneumoniae, the severity of disease, and the outcome of patients with alcohol abuse to those of nonalcoholic (NA) patients who have been hospitalized for community-acquired pneumonia (CAP). METHODS: From 1997 to 2001, clinical, microbiological, radiographic, and laboratory data, and follow-up variables of all consecutive patients who had been hospitalized with CAP were recorded. Patients were classified as alcoholic (A) [n = 128] or ex-alcoholic (EA) patients (n = 54) and were compared to NA patients (n = 1,165). RESULTS: S pneumoniae was found significantly more frequently in all patients with alcohol misuse. As regards the rates of antibiotic resistance, invasive pneumococcal disease, and other microorganisms, no differences were found. The severity criteria for CAP according to the American Thoracic Society were more frequent in A patients, but mortality did not differ significantly. Multivariate analysis showed an independent association between pneumococcal CAP and alcoholism (A patients: odds ratio [OR], 1.6; p = 0.033; EA patients: OR, 2.1; p = 0.016). CONCLUSIONS: We found an independent association between pneumococcal infection and alcoholism. Current alcohol abuse was associated with severe CAP. No significant differences were found in mortality, antibiotic resistance of S pneumoniae, and other etiologies.

Apoptosis of peripheral blood neutrophils in COPD exacerbation does not correlate with serum cytokines.

The study investigated the relationship between apoptosis of peripheral blood neutrophils during exacerbation of chronic obstructive pulmonary disease (COPD) and the inflammatory response that characterises this condition. Twenty-six hospitalised patients with COPD exacerbation and 13 controls were included. Three sequential blood and sputum samples were obtained from patients at admission, after 3 days and at discharge. Blood apoptotic neutrophils were measured by flow-cytometry and light microscopy. Serum and sputum levels of IL-6, IL-8 and TNF-alpha were determined by an immunoassay technique. We found a significantly reduced percentage of apoptotic neutrophils at the onset of COPD exacerbation which increased over time (1.1+/-0.4% at admission vs. 2.4+/-0.4% at discharge, P<0.0001). Patients presented no changes in serum cytokines neither during exacerbation nor in comparison to controls. In contrast, sputum levels of cytokines were significantly increased compared to serum levels. There was no significant correlation between the apoptotic neutrophils and the cytokine concentrations in serum or sputum. None of the clinical parameters, such as smoking, microbial infection, corticosteroids or hypoxemia showed a correlation with neutrophil apoptosis. No relationship could be found between the reduced percentage of apoptotic neutrophils in blood and serum concentration of IL-6, IL-8 and TNF-alpha or other clinical parameters in patients with COPD exacerbation.

[New and Current Concepts of Therapy in Non-CF Bronchiectasis]. / Non-CF-Bronchiektasen: Aktuelle therapeutische Entwicklungen.

Non-CF (NCF)-bronchiectasis is a syndrome of chronic inflammation leading to dilatation of airways and structural lung damage. Improvements of diagnostic procedures increase its perceived frequency. In Germany, recent data suggest a prevalence of 67/100 000.The outcome of therapeutic interventions is critically related to thorough diagnostic procedures. Genetical or immunological disorders (cystic fibrosis, alpha-1-AT deficiency, immune deficiency syndromes) require treatment options different from idiopathic NCF-bronchiectasis.Therapy is aimed at suppression of chronic inflammation and includes continuous mobilisation of secretions, immunomodulatory strategies and antibiotic therapy, whenever required. Surgical procedures are limited to specific complications (e. g. destroyed lung after airway obstruction, uncontrolled hemorrhage)Macrolides show a variety of immunological properties with favourable results in reduction of symptoms and frequency of exacerbations. Longtime tolerance is good, if individual risk factors are excluded.Antibiotics are given according to resistance patterns in acute exacerbations and in first-time detection of Pseudomonas aeruginosa and MRSA. Inhaled antibiotics for NCF-bronchiectasis will gain importance, depending on future studies. Currently, they are only used in individualized concepts of therapy.

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

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

Viral community-acquired pneumonia in nonimmunocompromised adults.

INTRODUCTION: Viral community-acquired pneumonia (CAP) has been poorly studied and clinically characterized. Using strict criteria for inclusion, we studied this type of infection in a large series of hospitalized adults with CAP. MATERIALS AND METHODS: All nonimmunocompromised adult patients with a diagnosis of CAP having paired serology for respiratory viruses (RVs) [338 patients] were prospectively included in the study from 1996 to 2001 at our 1,000-bed university teaching hospital, and subsequently were followed up. We compared patients with pure viral (PV), mixed viral (RV + bacteria), and pneumococcal CAP. RVs (ie, influenza, parainfluenza, respiratory syncytial virus, and adenovirus) were diagnosed by means of paired serology. RESULTS: Sixty-one of 338 patients (18%) with paired serology had an RV detected, and in 31 cases (9%) it was the only pathogen identified. Influenza was the most frequent virus detected (39 patients; 64%). Patients with chronic heart failure (CHF) had an increased risk of acquiring PV CAP (8 of 26 patients; 31%) when compared to a mixed viral/bacterial etiology (2 of 26 patients; 8%; p = 0.035) or CAP caused by Streptococcus pneumoniae (1 of 44 patients; 2%; p = 0.001). Multivariate analysis revealed that CHF (odds ratio [OR], 15.3; 95% confidence interval [CI], 1.4 to 163; p = 0.024) and the absence of expectoration (OR, 0.14; 95% CI, 0.04 to 0.6; p = 0.006) were associated with PV pneumonia compared to pneumococcal CAP. CONCLUSION: RVs are frequent etiologies of CAP (single or in combination with bacteria). Patients with CHF have an increased risk of acquiring a viral CAP.

Recent developments in antibiotic treatment.

Antibiotic resistance of gram-positive and gram-negative bacteria remains a major challenge for clinicians treating HAP. Since the recent release of linezolid and QD, treatment options for resistant gram-positive bacteria have improved. The development of new substances continues and it is hoped that some of them will be available soon. Investigation has centered on gram-positive bacteria, although multiresistant gram-negative pathogens, such as A haumanii, S maltophilia, and resistant P aeruginosa, are of major clinical relevance. New treatment options are unfortunately not in sight. No antibiotic, however, is a miraculous magic wand against resistant bacteria. The bugs are smart; they have been on this world far longer than humans. Regardless of how innovative the mechanism of action of new substances is, resistance will emerge. The solution is certainly not a nihilistic approach leading to a fearful restriction in the use of new substances. No antibiotic, regardless of its potency, can free the clinician from keeping the difficult balance between individual undertreatment and general overtreatment.

Bronchiectasis-associated hospitalizations in Germany, 2005-2011: a population-based study of disease burden and trends.

BACKGROUND: Representative population-based data on the epidemiology of bronchiectasis in Europe are limited. The aim of the present study was to investigate the current burden and the trends of bronchiectasis-associated hospitalizations and associated conditions in Germany in order to inform focused patient care and to facilitate the allocation of healthcare resources. METHODS: The nationwide diagnosis-related groups hospital statistics for the years 2005-2011 were used in order to identify hospitalizations with bronchiectasis as any hospital discharge diagnosis according to the International Classification of Diseases, 10th revision, code J47, (acquired) bronchiectasis. Poisson log-linear regression analysis was used to assess the significance of trends. In addition, the overall length of hospital stay (LOS) and the in-hospital mortality in comparison to the nationwide overall mortality due to bronchiectasis as the primary diagnosis was assessed. RESULTS: Overall, 61,838 records with bronchiectasis were extracted from more than 125 million hospitalizations. The average annual age-adjusted rate for bronchiectasis as any diagnosis was 9.4 hospitalizations per 100,000 population. Hospitalization rates increased significantly during the study period, with the highest rate of 39.4 hospitalizations per 100,000 population among men aged 75-84 years and the most pronounced average annual increases among females. Besides numerous bronchiectasis-associated conditions, chronic obstructive pulmonary disease (COPD) was most frequently found in up to 39.2% of hospitalizations with bronchiectasis as the primary diagnosis. The mean LOS was comparable to that for COPD. Overall, only 40% of bronchiectasis-associated deaths occurred inside the hospital. CONCLUSIONS: The present study provides evidence of a changing epidemiology and a steadily increasing prevalence of bronchiectasis-associated hospitalizations. Moreover, it confirms the diversity of bronchiectasis-associated conditions and the possible association between bronchiectasis and COPD. As the major burden of disease may be managed out-of-hospital, prospective patient registries are needed to establish the exact prevalence of bronchiectasis according to the specific underlying condition.

Mobile Air Quality Studies (MAQS)-an international project.

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"-exposure in relation to non-"traffic zone"-exposure.Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including NO2, SO2, nanoparticles and ozone.

New antibiotics for the treatment of severe staphylococcal infection in the critically ill patient.

PURPOSE OF REVIEW: Infection by Staphylococcus aureus in critically ill patients is usually associated with antimicrobial resistance and high mortality. A more effective antibiotic treatment is needed to replace older drugs that have limited efficacy. Novel substances active on methicillin-resistant Staphylococcus aureus, which are already available on the market or are still in development, are discussed in this review, with emphasis on nosocomial infections. RECENT FINDINGS: A number of new antibiotics are on the market (linezolid, quinupristin-dalfopristin, daptomycin) and there is good evidence regarding their efficacy, especially in methicillin-resistant Staphylococcus aureus infections. Linezolid is, to date, the best alternative in treating nosocomial pneumonia by methicillin-resistant Staphylococcus aureus. It is cost-effective; resistance levels are still very low but there are some concerns regarding its adverse events. Quinupristin-dalfopristin shows good activity in vitro but its efficacy in patients with pneumonia by methicillin-resistant Staphylococcus aureus is modest. Daptomycin is not recommended for pulmonary infections because of its reduced penetration in the lung tissue. Under current phase III trials in patients with nosocomial infections are tigecycline, ceftobiprole, and three new glycopeptides, all with particular activity against methicillin-resistant Staphylococcus aureus. SUMMARY: For the moment, there are limited and rather expensive therapeutic options for the infections by Staphylococcus aureus in the critically ill. No dramatic superiority of the new drugs in comparison to the standard therapies was observed in most of the clinical trials. Better results on the efficacy of the drugs under investigation are expected.

Early bactericidal activity of moxifloxacin in treatment of pulmonary tuberculosis: a prospective, randomized study.

Moxifloxacin is the most active fluoroquinolone against Mycobacterium tuberculosis in vitro. However, data about the efficacy in patients are not available. We enrolled 17 patients with tuberculosis in a prospective, randomized study. After 5 days of monotherapy with either moxifloxacin or isoniazid, we detected significant decreases in mean CFU per milliliter in sputum in both groups. The calculated early bactericidal activities for isoniazid and moxifloxacin were 0.209 and 0.273 log(10) CFU per ml of sputum per day, respectively. According to the data from our study, moxifloxacin exhibits an early bactericidal activity that is comparable to that of isoniazid.

Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers.

The pharmacokinetics of ertapenem and ceftriaxone were investigated in an open, randomized, two-period crossover study after single- and multiple-dose administration in 10 healthy volunteers (five women and five men). Both antibiotics were administered intravenously once daily for 7 days at dosages of 1 g (ertapenem) and 2 g (ceftriaxone). The concentrations of the antibiotics in serum and urine were quantified by the agar well diffusion method bioassay and, in addition, for ertapenem only, by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). For ertapenem the maximum concentration of the drug in plasma (C(max)) was 256 mg/liter, the half-life was 20.7 h, and the area under the plasma concentration-time curve (AUC) was 830 mg. h/liter. The concentrations in fecal samples were (mean value) 37.2 and 32.7 mg/kg on day 4 and day 8, respectively. Ceftriaxone exhibited a mean C(max) of 315 mg/liter, a half-life of 7.6 h, and an AUC of 1,556 mg. h/liter. The mean concentrations in fecal samples were 153 and 258 mg/kg on day 4 and day 8, respectively. No accumulation of ertapenem or ceftriaxone was detected at steady state. A slightly but significantly decreased AUC for ertapenem was detected for the female volunteers. No serious adverse event was observed. Both antibiotics induced a marked decrease in the anaerobic microflora (4-log-unit decreases in lactobacilli, bifidobacteria, clostridia, and bacteroides) and Escherichia coli, whereas the number of enterococci increased (4 log units). A slight overgrowth of yeasts was observed with both regimens. In all cases the microflora returned to normal levels on days 21 to 35.