[Management of Adult Community-acquired Pneumonia and Prevention - Update 2016]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie und Prävention - Update 2016.

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention.

[PROGNOSIS - The PROspective German NOn-CF BronchiectaSIS Patient Registry]. / PROGNOSIS - das deutsche Bronchiektasen-Register.

Bronchiectasis not due to cystic fibrosis (Non-CF bronchiectasis) represents a heterogeneous disorder with many different underlying diseases. Reliable and mature data referring to prevalence and incidence of Non-CF bronchiectasis in Germany are lacking. Bronchiectasis is often mentioned as rare or orphan disease, although it might be more often than supposed to be. Up to now (May 2015) there is no approved therapy for this disease in Germany. After some preliminary work the German bronchiectasis registry PROGNOSIS (The PROspective German NOn-CF bronchiectaSIS patient registry) will start recruiting patients by the beginning of July. The goals of PROGNOSIS are to build up a national, representative, prospective, observing (non-interventional) and longitudinal patient registry with at least 750 patients within three years in 25-35 centers, to evaluate important epidemiological questions. In addition a German-language guideline for diagnostic and management of Non-CF bronchiectasis will be developed in cooperation with the German respiratory society (DGP).

Dose-ranging study of a single injection of pneumococcal conjugate vaccine (1 ×, 2 ×, or 4 ×) in healthy subjects aged 70 years or older.

Healthy adults aged ≥ 70 years (N=443) with no history of pneumococcal vaccination received 7- or 9-valent pneumococcal conjugate vaccine (PCV7 or PCV9) at 1 × (PCV7 only), 2 × (PCV7+PCV9), or 4 × (2 × PCV7+2 × PCV9) dosage in a randomised, open-label study evaluating pneumococcal protein conjugate vaccine (PnC). Controls received 23-valent pneumococcal polysaccharide vaccine (PPV). Both geometric mean concentration enzyme-linked immunosorbent assay and opsonophagocytic activity antibody titres assessed 1 month after vaccination were significantly increased over baseline titres for all PCV7 serotypes, with a trend toward a dose-dependent immune response. Local reactions for the 4 × dose, but not the 2 × dose, were statistically significantly higher than for the 1 × dose. No treatment-related serious adverse events occurred.

[Intermittent hypoxic training--the state of science]. / Normobare Hypoxie: Aktuelle Implikationen für Pneumologie und Leistungsdiagnostik.

Intermittent hypoxic training (IHT) plays an important role concerning methods of training. Considering the enormous logistic and pecuniary investments for altitude training, there is a high demand for more efficient concepts. The intermittent hypoxic training is a new, alternative form of altitude training. The idea of IHT is to economise the currently most reliable and evaluated method which is known as "live high - train low" (LHTL). Thus, IHT combines a normal training at sea level with short training sessions in a chamber that creates a hypoxic but normobaric environment. Its aim is to initiate a similar level of erythropoesis as that usually achieved through long stays in high altitude with a minimised effort. This study analyses the results of selected studies that deal with IHT, evaluating the performance improvements in general and possible haematological variances/changes specifically.

A prediction model for bacterial etiology in acute exacerbations of COPD.

OBJECTIVES: Bacteria play a leading role in acute exacerbations of chronic obstructive pulmonary disease (COPD), but we lack predictors of bacterial etiology. We developed a prediction model for infection with gram-negative enteric bacteria (GNEB) and Pseudomonas aeruginosa. METHODS: Clinical presentation, sputum characteristics, microbial sputum patterns, lung function and previous and concomitant medication were prospectively recorded in patients with moderate to severe exacerbation of COPD. Risk factors for a specific bacterial etiology were calculated and a prediction model developed. RESULTS: A total of 193 patients with acute exacerbation were included. In 121 (62.6%) of them a microbial etiology could be identified, most frequently Haemophilus influenzae (32 strains), Streptococcus pneumoniae (22 strains) and P. aeruginosa (12 strains). Multivariate analysis identified severe airflow obstruction and use of systemic steroids as predictors for exacerbation due to gram-negative enteric bacilli and P. aeruginosa. A prediction model including FEV1 < 35% of predicted value, systemic steroid use and prior antibiotic therapy within preceeding 3 months had a negative predictive of 89%, being a helpful tool in excluding patients at risk of exacerbation due to gram-negative enteric bacilli and P. aeruginosa when all criteria are absent. CONCLUSION: A simple prediction model based on three factors may identify COPD patients at low risk for exacerbations with gram-negative enteric bacilli and P. aeruginosa. Bacterial Etiology in COPD Exacerbations.

Mixed community-acquired pneumonia in hospitalised patients.

The role of mixed community-acquired pneumonia (CAP) is controversial. The aim of the present study was to determine the incidence, principal microbial patterns, clinical predictors and course of mixed CAP. The current study included 1,511 consecutive hospitalised patients with CAP. Of these, 610 (40%) patients had an established aetiology. One pathogen was demonstrated in 528 patients and 82 (13%) patients had mixed pneumonia. Cases including CAP, by a pyogenic bacteria and a complete paired serology for "atypicals", revealed that 82 (13%) patients had definite single pyogenic pneumonia and 28 patients (5%) had mixed pyogenic pneumonia. In patients with mixed CAP, Streptococcus pneumoniae was the most prevalent microorganism (44 out of 82; 54%). The most frequent combination was S. pneumoniae with Haemophilus influenzae (17 out of 82; 21%). Influenza virus A and S. pneumoniae (five out of 28; 18%) was the most frequent association in the mixed pyogenic pneumonia group. No clinical predictors for mixed pneumonias could be identified. Patients with mixed pyogenic pneumonia more frequently developed shock when compared with patients with single pyogenic pneumonia (18 versus 4%). In conclusion, mixed pneumonia occurs in >10% of cases with community-acquired pneumonia requiring hospitalisation.

[Serologic early diagnosis of pneumonia caused by Mycoplasma pneumoniae]. / Serologische Frühdiagnostik der Mykoplasmenpneumonie.

BACKGROUND AND OBJECTIVE: The definitive diagnosis of M. pneumoniae is encumbered by the lack of a rapid and cost-effective test of detection. The study aimed to determine if a single serological test within the first days of hospital admission may be relevant for the diagnosis of community-acquired pneumonia (CAP) caused by M. pneumoniae. PATIENTS AND METHODS: Patients with suspected of CAP were investigated for microbiological diagnosis based on respiratory samples (bronchoalveolar lavage, bronchial aspirate, sputum, throat rinse), blood culture and serology for detection of atypical organisms and viruses. Patients with M. pneumoniae antibody titers > or = 1:160 were further investigated by polymerase chain reaction (PCR) for detection of M. pneumoniae in respiratory samples. The group of CAP by M. pneumoniae (MP-CAP) included patients with serum titers > 1:160 of M. pneumoniae antibodies (based on a single antibody determination at admission). The control group (non-MP-CAP group) included patients with CAP by pathogens other than M. pneumoniae or with no definitive bacteriological diagnostic. RESULTS: Twenty adults with MP-CAP and 20 controls with non-MP-CAP were included. PCR was positive in 18/20 (90 %) of the MP-CAP group and negative in the 9/9 (100 %) investigated patients of the non-MP-CAP group. The duration of symptoms prior to hospital admission was rather long in both groups (mean 13.2 days in the MP-CAP group and 12,7 days in the non-MP-CAP group). The MP-CAP group was significantly younger (p = 0.002), had subsequently less associated comorbidities (p < 0.001) and less purulent sputum (p = 0.003) than the non-MP-CAP group. CONCLUSION: Single serology at admission with M. pneumoniae antibody titers > 1:160 may be useful for the diagnosis of CAP caused by M. pneumoniae in hospitalized patients with a long duration of symptoms (> 12 days).

Impact of corticosteroids on the immune response to a MF59-adjuvanted influenza vaccine in elderly COPD-patients.

The influence of steroids on the antibody response to a MF59-adjuvanted influenza vaccine in elderly COPD patients has not been studied previously. In the influenza season 2001/02 (October-February) elderly COPD patients were recruited at 14 doctor's offices and our 250-bed hospital. Patients were stratified into three groups according to current treatment regimen: (a) > 10 mg of prednisolone/day (SS); (b) inhaled steroids (IS); (c) no steroid treatment (control group, CG). All patients were vaccinated with the MF59-adjuvanted influenza vaccine. Antibodies against the influenza strains A/H1N1, A/H3N2, and B were measured at baseline, 4 and 24 weeks after vaccination by hemagglutination inhibition (HI) assay. One-hundred and sixty-two patients completed the study (CG n = 42; IS n = 87; SS n = 33). Mean age was 71.3 years (range 60-89). Twenty-one percent of all patients reported local reactions; no serious adverse events were observed. Four weeks after vaccination, mean geometric HI titres (GMT) for A/H1N1, A/H3N and B increased significantly in all groups (p < or = 0.05). After 24 weeks, GMTs to A/H1N1 and A/H3N2 returned to baseline, while GMTs to type B remained significantly higher than baseline in all groups. Significant differences between the groups as regards GMTs, seroconversion (56-89%) or seroprotection rates (64-93%) were not observed. Systemic steroids did not influence the antibody response towards the MF59-adjuvanted influenza vaccine. We found that the strains included in the vaccine showed varying long-term immunogenicity.

[Pneumococcal vaccination in obstructive lung diseases -- what can we expect?]. / Pneumokokken-Schutzimpfung bei obstruktiven Lungenerkrankungen -- Was können wir erwarten?

Many countries' guidelines recommend pneumococcal vaccination for patients suffering from obstructive airway disease. This paper reviews the literature as to immunogenicity and safety of this immunization. There is no evidence for a negative effect of pneumococcal vaccination on these patients. Only a few data exist on the preventive impact of pneumococcal vaccination as to exacerbations of obstructive airway diseases. Existing studies mostly took up this question as a side aspect. The effect in children and adults appears limited. On the other hand, the pneumococcal conjugate vaccine prevents life-threatening invasive infections in children younger than 5 years, and pneumococcal polysaccharide vaccine protects healthy adults against bacteriaemic pneumonia. Thus, pneumococcal vaccination of patients suffering from obstructive airway disease is recommendable.

Immunogenity of the pneumococcal polysaccharide vaccine in COPD patients. The effect of systemic steroids.

RATIONALE: To investigate if systemic steroids influence the antibody response to the 23-valent pneumococcal polysaccaride vaccine (23-PPV) in COPD patients. PATIENTS AND METHODS: COPD patients on: (a) > or =10mg of prednisolone/day (SS, n = 30); (b) inhalative steroids (IS, n= 30); (c) controls without COPD (CG, n= 29) were vaccinated with 23-PPV. The concentration (microg/ml) of capsular specific anti-pneumococcal IgG antibodies (AB) for the serotypes (PNC) 4,6B,9V,14,18C,19F,23F were measured by Elisa technique before, 3 and 12 months (m) after vaccination. Non-responders were defined when AB-concentrations did neither doubled nor reach > or = 1 microg/ml. RESULTS: N=24 (CG), n=29 (IS), n= 18 (SS) patients completed the study (mean age 64yrs.). Serious adverse events were not observed. Geometric mean (GM) AB-concentration of all serotypes increased significantly (CG, IS, SS) 3 and 12m after vaccination (P<0.05). The percentage of non-responders ranged between 16% (PNC 19F, IS) and 65% (PNC 4, SS) after 3 m and 21% (PNC 19F, IS) and 82% (PNC 4, CG) after 12m. Neither post-vaccine AB-concentrations (3 and 12m) nor the rate of non-responders differed significantly between patients on systemic steroids and the other groups (IS, CG). CONCLUSIONS: Systemic steroids did not influence the AB-response. In all groups mean AB-concentration increased significantly after vaccination but an important percentage of subjects of all three groups were non-responders.

Validation of predictive rules and indices of severity for community acquired pneumonia.

BACKGROUND: A study was undertaken to validate the modified American Thoracic Society (ATS) rule and two British Thoracic Society (BTS) rules for the prediction of ICU admission and mortality of community acquired pneumonia and to provide a validation of these predictions on the basis of the pneumonia severity index (PSI). METHOD: Six hundred and ninety six consecutive patients (457 men (66%), mean (SD) age 67.8 (17.1) years, range 18-101) admitted to a tertiary care hospital were studied prospectively. Of these, 116 (16.7%) were admitted to the ICU. RESULTS: The modified ATS rule achieved a sensitivity of 69% (95% CI 50.7 to 77.2), specificity of 97% (95% CI 96.4 to 98.9), positive predictive value of 87% (95% CI 78.3 to 93.1), and negative predictive value of 94% (95% CI 91.8 to 95.8) in predicting admission to the ICU. The corresponding predictive indices for mortality were 94% (95% CI 82.5 to 98.7), 93% (95% CI 90.6 to 94.7), 49% (95% CI 38.2 to 59.7), and 99.5% (95% CI 98.5 to 99.9), respectively. These figures compared favourably with both the BTS rules. The BTS-CURB criteria achieved predictions of pneumonia severity and mortality comparable to the PSI. CONCLUSIONS: This study confirms the power of the modified ATS rule to predict severe pneumonia in individual patients. It may be incorporated into current guidelines for the assessment of pneumonia severity. The CURB criteria may be used as an alternative tool to PSI for the detection of low risk patients.

Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.

A major feature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is the accumulation of activated neutrophils in the bronchial tree. This phenomenon can be explained by an increased migration and/or by a prolonged survival due to an inhibition of spontaneous apoptosis. The aim of this study was to assess the apoptotic behaviour of peripheral blood neutrophils in COPD patients during an acute exacerbation. Thirty-six hospitalised COPD patients with an acute exacerbation and 10 healthy volunteers were included. Blood samples were obtained at admission, after 3-5 days and at discharge. Spontaneous apoptosis of isolated neutrophils was measured based on Annexin V-PE binding and nuclear morphology after culturing for 18 h. At admission, significantly lower rates of spontaneous apoptosis were noted in COPD patients compared with healthy volunteers (mean +/- SD 31 +/- 13% versus 44 +/- 18%). The mean percentages of apoptotic neutrophils were 31 +/- 13% at admission, 39 +/- 15% after 3-5 days and 47 +/- 18% at discharge. There was a statistically significant difference between the rates of spontaneous apoptosis on the first day and at discharge. Neither forced expiratory volume in one second < 35% predicted, smoking habit, corticosteroid therapy nor evidence of bacterial infection showed any influence on the spontaneous apoptosis in this study. In conclusion, during acute exacerbations of chronic obstructive pulmonary disease, neutrophil granulocytes show a reduced spontaneous apoptosis that increases progressively after treatment and clinical remission. This raises the question of the importance of neutrophil apoptosis in the development and resolution of exacerbations of chronic obstructive pulmonary disease.

C-reactive protein levels in community-acquired pneumonia.

The diagnostic value of C-reactive protein (CRP) admission serum levels as an indicator of the aetiology of community-acquired pneumonia (CAP) was evaluated. A cohort of 1,222 patients with CAP was assessed. CRP levels were analysed in 258 patients with a single aetiological diagnosis. The mean CRP values in patients with pyogenic, atypical, viral and Legionella pneumophila pneumonia were: 16 mg x dL(-1), 13 mg x dL(-1), 14 mg x dL(-1) and 25 mg x dL(-1), respectively. CRP levels were not significantly different among patients outcome research team (PORT) groups (19 mg x dL(-1) in groups I-II, 16 mg x dL(-1) in group III and 16 mg x dL(-1) in groups IV-V). A cut-off point of 25 mg x dL(-1) had a sensibility, specificity, positive predictive value and negative predictive value of 0.6, 0.83, 0.3, and 0.94, respectively. After controlling for age and PORT score, the odds of having a CRP level >25 mg x dL(-1) was 6.9 times higher in patients with L. pneumophila pneumonia than in those with non-L. pneumophila pneumonia. Patients with Legionella pneumophila pneumonia had higher C-reactive protein levels than those with pneumonia of any other aetiology, independently of severity of infection. Being a cheap and readily available test, C-reactive protein may be a useful adjunctive procedure in the diagnosis of community-acquired pneumonia.

Rapid urinary antigen test for diagnosis of pneumococcal community-acquired pneumonia in adults.

Streptococcus pneumoniae is suspected to cause an important proportion of community-acquired pneumonia (CAP) whose aetiology cannot be detected with conventional tests. In this study, the authors evaluated the diagnostic yield of a new immunochromatographic membrane test (ICT) for the detection of the S. pneumoniae antigen in the urine of patients admitted with diagnosed CAP. ICT was performed in unconcentrated and concentrated urine from all the patients. ICT was repeated 1 month after discharge in a group initially testing positive. The authors also studied the ICT in clinically stable human immunodeficiency virus type 1 (HIV1)-infected patients. S. pneumoniae antigen was detected in all of the 68 (100%) patients tested with definitive pneumococcal pneumonia. In five of these cases ICT was only positive when it had been performed on the patients. The S. pneumoniae antigen was also detected in 36 (69.2%) of 52 patients with probable pneumococcal pneumonia and in 50 of 277 (18%) patients without pneumococcal pneumonia. ICT remained positive in 16 (69.5%) of 23 patients, 1 month after hospital discharge. Nasopharyngeal colonisation with S. pneumoniae was detected in 8 (12%) of 68 clinically stable HIV1 infected patients, but none tested ICT positive. The Binax NOW it immunochromatographic membrane test is a rapid, sensitive and specific test for detecting pneumococcal community-acquired pneumonia in adults. The test may remain positive for several weeks after pneumococcal pneumonia.

Factors associated with unknown aetiology in patients with community-acquired pneumonia.

Despite comprehensive diagnostic work-up, the aetiology of community-acquired pneumonia (CAP) remains undetermined in 30-60% of cases. The authors studied factors associated with undiagnosed pneumonia. Patients hospitalised with CAP and being evaluated by two blood cultures, at least one valid lower respiratory tract sample, and serology on admission were prospectively recorded. Patients who had received antimicrobial pretreatment were excluded. Patients with definite or probable aetiology were compared to those with undetermined aetiology by uni- and multivariable analysis. A total 204 patients were eligible for the study. The aetiology remained undetermined in 82 (40%) patients, whereas a definite aetiology could be established in 89 (44%) and a probable one in 33 (16%). In multivariable analysis, factors associated with undetermined aetiology included age >70 yrs, renal and cardiac comorbidity, and nonalveolar infiltrates on the chest radiograph. There was no association of undiagnosed pneumonia with mortality. Age and host factors were associated with unknown aetiology of community-acquired pneumonia. Some of these cases may also represent fluid volume overload mimicking pneumonia.

[Antimycotic treatment of pulmonary aspergilloma in patients without neutropenia]. / Antimykotische Therapie pulmonaler Aspergillome bei nicht neutropenischen Patienten.

BACKGROUND AND OBJECTIVE: Pulmonary aspergillomas are associated with a high morbidity and mortality. There are only very few data about non-surgical treatment in immunocompetent patients. METHODS: We evaluated 30 patients (19 male/11 female; mean age: 54 years) with pulmonary aspergillosis, their symptoms, treatment and outcome during a time period of 9 years. All patients had either definitive (18/60 %) or probable (12/40 %) aspergillosis with a cultural confirmation. RESULTS: Underlying diseases were tuberculosis (16/53 %), malignancy (8/30 %), COPD (15/50 %), pneumonia (3/10 %). Only five patients were immunocompromised (steroid medication: n = 4, chronic lymphatic leukemia: n = 1) All patients had a contraindication against surgery, 26 received antifungal treatment (mostly with voriconazole or itraconazole). The overall response was 61 %, there was an improvement of radiological signs in seven (23 %). Especially hemoptysis and dyspnea resolved. 12 patients died during the 9 years (40 %), nine from their underlying disease, three from the pulmonary aspergilloses (hemoptysis: n = 2, secondary invasive aspergillosis: n = 1). CONCLUSION: Pulmonary aspergilloma in its chronic form is a disease of patients with pulmonary disease but who are immunocompetent. Antifungal treatment seems to be a therapeutic option, if surgery is not possible.