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Background Although blood cultures (BCs) are the "gold standard" for detecting bacteremia, the utility of BCs in patients with community-acquired pneumonia (CAP) is controversial. This study describes the proportion of patients with CAP and afebrile bacteremia and identifies the clinical characteristics predicting the necessity for BCs in patients who are afebrile. Methods Bacteremia rates were determined in 4,349 patients with CAP enrolled in the multinational cohort study The Competence Network of Community-Acquired Pneumonia (CAPNETZ) and stratified by presence of fever at first patient contact. Independent predictors of bacteremia in patients who were afebrile were determined using logistic regression analysis. Results Bacteremic pneumonia was present in 190 of 2,116 patients who were febrile (8.9%), 101 of 2,149 patients who were afebrile (4.7%), and one of 23 patients with hypothermia (4.3%). Bacteremia rates increased with the CURB-65 score from 3.5% in patients with CURB-65 score of 0 to 17.1% in patients with CURB-65 score of 4. Patients with afebrile bacteremia exhibited the highest 28-day mortality rate (9.9%). Positive pneumococcal urinary antigen test (adjusted OR [AOR], 4.6; 95% CI, 2.6-8.2), C-reactive protein level > 200 mg/L (AOR, 3.1; 95% CI, 1.9-5.2), and BUN level ≥ 30 mg/dL (AOR, 3.1; 95% CI, 1.9-5.3) were independent positive predictors, and antibiotic pretreatment (AOR, 0.3; 95% CI, 0.1-0.6) was an independent negative predictor of bacteremia in patients who were afebrile. Conclusions A relevant proportion of patients with bacteremic CAP was afebrile. These patients had an increased mortality rate compared with patients with febrile bacteremia or nonbacteremic pneumonia. Therefore, the relevance of fever as an indicator for BC necessity merits reconsideration.

Objectives Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. Methods We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. Results ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P Conclusion PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.

Introduction La granulomatose eosinophilique avec polyangeite (GEPA) (Churg-Strauss) est une vascularite necrosante des vaisseaux de petit calibre caracterisee par une eosinophilie sanguine et tissulaire associee a un asthme.En depit des traitements actuels, la cortico-dependance est frequente chez les patients presentant une GEPA, de meme que les sequelles a long terme. Ces sequelles peuvent etre liees a la maladie (asthme actif, manifestations ORL, neuropathie peripherique, …) ou aux traitements utilises (osteoporose, hypertension arterielle, diabete, …). Nous avons voulu decrire et caracteriser les sequelles associees a la GEPA, et identifier les parametres associes au risque de sequelle. Patients et methodes Nous avons realise une etude multicentrique europeenne incluant 845 patients suivis pour une GEPA, repondant aux criteres de classification de l’ACR et/ou aux criteres de l’essai MIRRA. Les caracteristiques initiales et de suivi ont ete recueillies, notamment les sequelles a 2 et 5 ans evaluees par le Vasculitis Damage Index (VDI). Les sequelles etaient reparties en 3 categories : asthme chronique et/ou manifestations ORL, sequelles de la vascularite (neuropathie peripherique, insuffisance renale chronique, insuffisance cardiaque, …), et sequelles liees au traitement. Nous avons compare les patients en fonction du VDI a 2 ans en les repartissant en 2 groupes (VDI Resultats Le suivi median de la cohorte etait de 74 (37–116) mois. Le VDI moyen etait de 1,8 ± 1,3 a 2 ans et 2,3 ± 1,4 a 5 ans. A 2 ans de suivi, les principales sequelles etaient l’asthme chronique dans 57 %, les manifestations ORL dans 37 %, les sequelles liees a la vascularite dans 37 % et les sequelles liees au traitement dans 25 %. A 5 ans, on observait une augmentation des sequelles liees au traitement (44 %), tandis que l’asthme chronique (61 %), les manifestations ORL (43 %) et les sequelles de vascularite (41 %) restaient stables. Les sequelles liees a la vascularite etaient dominees par la neuropathie peripherique (33 %) et plus rarement une insuffisance renale chronique (5 %) ou une insuffisance cardiaque (7 %). En revanche, les principales sequelles liees au traitement etaient une osteoporose dans 22 %, une hypertension arterielle dans 15 %, une dyslipidemie dans 8 % et un diabete dans 5 %. A 2 ans de suivi, la proportion de patients avec un VDI ≥ 3 etait de 27,4 %. Les variables au diagnostic associes a un VDI ≥ 3 a 2 ans etaient logiquement la presence d’une insuffisance cardiaque (p = 0,0007), d’une atteinte renale (p Conclusion Les sequelles a long terme sont frequentes au cours de la GEPA, et sont largement dominees par l’asthme chronique et/ou les manifestations ORL. Cette etude illustre que les sequelles liees a la maladie sont habituellement fixees a 2 ans de suivi, tandis que seules les sequelles liees aux traitements continuent de s’accumuler au cours du temps. Ces donnees renforcent l’idee de proposer des 2 ans de suivi des strategies d’epargne cortisonique efficaces, au premier rang desquelles les traitements ciblant l’interleukine-5.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg–Strauss) is a small-vessel necrotizing vasculitis characterized by blood and tissue eosinophilia and asthma. Glucocorticoids (GCs) represent the treatment cornerstone. So far, EGPA management has been based on conventional immunosuppressants, but GC-dependence remains frequent. Recently, therapies targeting B cells and interleukin-5 have been prescribed, but data on large cohorts are lacking. Objectives: This study aimed to describe therapeutic management and efficacy of treatments in EGPA patients. Methods: We set up a multicenter European cohort that included 636 EGPA patients. Treatments used, complete remission rates and vasculitis relapse-free survival were recorded. Complete remission was defined as absence of vasculitis relapse and prednisone dose Results: For induction, cyclophosphamide (CYC) was the most frequently prescribed immunosuppressant (36.2%), more often in patients with FFS ≥1 (P Complete remission rates were similar between conventional immunosuppressants (CYC, AZA or MTX) and GCs alone. Vasculitis relapse-free survival was also similar between CYC, AZA or MTX and GCs alone. Similar results were observed for first vasculitis relapse treatments. During follow-up, GC-dependent asthma and/or ENT manifestations were treated with AZA (40%), MTX (25%), mycophenolate mofetil (16%), rituximab (RTX) (21%), CYC (19%), cyclosporine (6%), omalizumab (5.9%) and mepolizumab (5.5%), allowing GC-tapering ≤7.5mg/in 23%, 31%, 17%, 43%, 5%, 71%, 25% and 50%, respectively. Conventional immunosuppressants were mostly used in first and second line, while eosinophil-targeted biotherapies were used in 4th or 5th lines. Conclusion: In EGPA patients, the response to conventional immunosuppressants, in addition to GCs, is often disappointing compared to GCs alone, without clear benefit on complete remission rates and relapse-free survival. In contrast, notwithstanding a small number of treated patients, eosinophil-targeted therapies seemed promising to treat asthma and/or ENT manifestations. Disclosure of Interests: Matthias Papo: None declared, Renato A. Sinico: None declared, Vitor Teixeira: None declared, Maria-Letizia Urban: None declared, Juliane Mahrhold: None declared, Sara Monti: None declared, Giulia Cassone: None declared, Franco Schiavon: None declared, Benjamin Seeliger: None declared, Thomas Neumann: None declared, Claus Kroegel: None declared, Matthieu Groh: None declared, Chiara Marvisi: None declared, Maxime Samson: None declared, Thomas Barba: None declared, David Jayne Grant/research support from: David Jayne has received research grants from Chemocentryx, GSK, Roche/Genentech and Sanofi-Genzyme. He has received consultancy fees from Astra-Zeneca, Boehringer-Ingelheim, Chemocentryx, Chugai, GSK, Infla-RX, Insmed and Takeda, Bernhard Hellmich Consultant for: Roche, Speakers bureau: Abbvie, MSD, Roche, Novartis, Pfizer, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Carlo Salvarani Grant/research support from: Roche, Consultant for: Eli Lilly and Company, Roche, Abbvie, Jean-Emmanuel Kahn: None declared, Bernard Bonnotte: None declared, Cecile-Audrey Durel: None declared, Xavier Puechal: None declared, Luc Mouthon: None declared, Loic Guillevin: None declared, Giacomo Emmi: None declared, Augusto Vaglio: None declared, Benjamin Terrier: None declared

Introduction La granulomatose eosinophilique avec polyangeite (GEPA) (Churg-Strauss) est une vascularite necrosante des vaisseaux de petit calibre caracterisee par une eosinophilie sanguine et tissulaire associee a un asthme. Les ANCA sont positifs dans seulement un tiers des cas, le plus souvent diriges contre la myeloperoxydase (MPO). Les patients ANCA+ ont plus de manifestations neurologiques et renales, et moins de manifestations cardiaques que les patients ANCA−. Les ANCA diriges contre la proteinase 3 (PR3) sont rares dans la GEPA, et les caracteristiques des patients avec ANCA-PR3 sont inconnues. L’objectif de cette etude etait d’etudier le phenotype des patients avec GEPA et ANCA-PR3. Patients et methodes Nous avons realise une etude multicentrique europeenne incluant 845 patients suivis pour une GEPA, repondant aux criteres de classification de l’ACR, a la definition de la consensus de Chapel Hill et/ou aux criteres de l’essai MIRRA. Les caracteristiques initiales et de suivi ont ete recueillies, et comparees selon le statut des ANCA. Resultats Le statut des ANCA et leur specificite etaient connus pour 734 patients : 508 (69,2 %) etaient ANCA−, 209 (28,5 %) avaient des ANCA-MPO et 17 (2,3 %) avaient des ANCA-PR3. Au diagnostic, les patients avec ANCA-PR3, comparativement aux ANCA-MPO et aux ANCA−, avaient respectivement : moins d’asthme (71 % vs 91 % ou 93 %, p = 0,004), notamment moins d’asthme corticodependant (21 % vs 34 % ou 46 %, p = 0,007), plus de manifestations cutanees (65 % vs 38 % ou 34 %, p = 0,03), moins d’infiltrats pulmonaires (41 % vs. 40 % ou 58 %, p = 0,03) mais plus de nodules pulmonaires (25 % vs 10 % ou 8 %, p = 0,046), moins de neuropathie peripherique (29 % vs 72 % ou 47 %, p La duree mediane de suivi etait de 74 (37–116) mois pour l’ensemble de la cohorte. Les patients avec ANCA-PR3 presentaient plus de rechute de vascularite que les patients avec ANCA-MPO ou ANCA− (47 % vs 34 % ou 24 %, respectivement ; p = 0,004). La survie sans rechute etait plus courte pour les patients avec ANCA-PR3 (hazard ratio [HR] : 7,32, IC95 % : 2,02–26,5 ; p = 0,002) et ANCA-MPO (HR : 1,71, IC95 % : 1,23–2,37 ; p = 0,002), comparativement aux ANCA− Les doses medianes de prednisone etaient plus elevees a 6 et 24 mois de suivi pour les patients avec ANCA-PR3 que pour les patients avec ANCA-MPO ou ANCA− (p = 0,02 et p = 0,007). A 24 mois de suivi, les patients avec ANCA-PR3, comparativement aux ANCA-MPO et aux ANCA−, avaient moins d’asthme chronique (38 % vs 51 % et 60 %, respectivement, p = 0,04) et plus frequemment de sequelles renales (20 % vs 10 % vs 1 %, p Conclusion Les caracteristiques des patients avec GEPA et ANCA-PR3 different de celles des patients avec ANCA-MPO ou ANCA−, particulierement concernant les manifestations asthmatiques et l’eosinophilie qui sont parmi les signes cardinaux de la GEPA. Une eosinophilie circulante legere a moderee pouvant etre observee au cours de la granulomatose avec polyangeite (GPA), ces patients pourraient plutot correspondre a une forme particuliere GPA qu’a un nouveau phenotype de GEPA, avec un risque de rechute similaire a celui des GPA.

Eosinophilic granulocytes form peripheral effector cells controlled by Th2 lymphocytes, which cause local cell, tissue, and functional disorders of infiltrated organs via the release of cytotoxic basic proteins and oxygen radicals. Diseases associated with eosinophilia include systemic and organ-related forms. The lungs are involved in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), acute and chronic eosinophilic pneumonia, as well as in an organ manifestation in hypereosinophilic syndrome and certain parasitic diseases. In particular, the lungs are frequently affected in vasculitis of small vessels, including EGPA, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Among these, EGPA is the most frequent pulmonary eosinophil vasculitis representative. In addition, there are various overlap syndromes in which characteristic features of EGPA can be detected in the context of other anti-neutrophil cytoplasmic antibody (ANCA-)associated vasculitides. Occasionally, non-ANCA-associated pulmonary vasculitides occur with eosinophilia (e.g., Schönlein-Henoch purpura, Kawasaki disease, drug-induced hypersensitivity, and paraneoplastic syndrome). Herein, the pulmonary vasculitides accompanying eosinophilia are presented with respect to both the lung manifestations and pulmonary eosinophilia.

Background: In patients without diabetes (DM) hyperglycemia is associated with high mortality from community-acquired pneumonia(CAP). Hyperglycemia, however, is a common condition among patients with DM and preexisting hyperglycemia should be accounted for in studies of a possible association between hyperglycemia and mortality in patients with DM. Aim: To investigate the association between the glycemic gap (the difference between admission hyperglycemia and the estimated average glucose (EAG)) and 90-day mortality. Methods: A prospective cohort study. EAG was derived from hemoglobin A1c. The absolute-glycemic gap was defined as; “admittance blood glucose - EAG“. The proportional glycemic-gap was defined as; “((admittance blood glucose/EAG)*100)-100”. The association between the absolute-glycemic gap and the proportional-glycemic gap and 90-day mortality was assessed with Cox proportional hazard model. We categorized the proportional-glycemic gap according to quartiles. Results: 1933 adults were included. The absolute-glycemic-gap was not associated with an increased risk for 90-day mortality, HR 1.02 (95% CI 0.93-1.11). Compared to the 2nd quartile, the 1st and 4th proportional-glycemic gap quartile was associated with a higher risk with HR 2.7 (95% CI 1.11-6.65) and HR 2.5 (95% CI 1.05-5.69), respectively. No interaction between DM and the proportional-glycemic gap or the absolute-glycemic gap was found (p=0.82 and p=0.25, respectively). Conclusion: Patients with the lowest and highest proportional-glycemic gap had the highest risk for 90-day mortality and it was not modified by DM. The proportional-glycemic gap might be incorporated into future risk assessment tools for CAP.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small vessel vasculitis associated with asthma and eosinophilia. Optimal therapy for maintenance of remission is yet to be defined. We present a case-series of three patients with EGPA in whom IFN-α, an immunomodulatory cytokine induced remission, which was maintained even after discontinuation of the drug. In all patients (ages 60, 51, and 50 years), remission was associated with normalisation of eosinophil counts and IgE-levels. Moreover, the patients remained in remission for one to four years. Two patients did not need further immunosuppression, one patient required low dose maintenance therapy.Although reversible side effects occur, IFN-α-therapy induces long-term remission of EGPA even after discontinuation of treatment.

Due to the variability in respect to aetiology, histopathology, lung function, imaging and clinical presentation, as well as overlapping parenchymal processes, bronchiolar disorders are generally difficult to diagnose. Thus, diseases of the small airways should generally be considered in the differential diagnostic approach to respiratory conditions. The diagnostic approach can be devided into several steps: in steps 1 (history and physical examination) and 2 (plain chest radiographs and pulmonary function tests) may point towards a bronchiolar pulmonary process. High-resolution CT (HR-CT) scanning of the chest provides three distinct HR-CT patterns (tree-in-bud sign, ill-defined centrilobular ground-glass nodules and/or pattern of mosaic attenuation, especially visible on expiratory images) which confirm a bronchiolic involvement and help to narrow down a likely diagnosis or more specific bronchiolitic diseases. In inconclusive cases, a histological diagnosis may be required. The paper presents a clinically useful algorithmic approach to diagnosis and differential diagnosis of bronchiolar disorders.

Objectives: We aimed to identify clinical characteristics and to assess effectiveness of different initial antibiotic regimens in adult patients with community-acquired pneumonia (CAP) caused by Haemophilus influenzae. Methods: Characteristics were compared between patients with H. influenzae monoinfection versus CAP of other and unknown aetiology enrolled by the German prospective cohort study CAPNETZ. Impact of initial antibiotic treatment on "early clinical response" according to FDA criteria and overall clinical cure were analysed. Results: H. influenzae was found in 176 out of 2790 patients with pathogen detection (6.3%). Characteristics significantly associated with a H. influenzae CAP (p

BACKGROUND The study was conducted to assess the rate of suspected pulmonary embolism (PE) prior to death and the diagnostic and therapeutic procedures performed. METHODS Patients with autopsy-confirmed PE between 1998 and 2002 were included. Autopsy register and medical records were reviewed for history, diagnosis and therapy of PE. Patients were categorised into fatal and non-fatal PE according to the autopsy findings. RESULTS 102 patients with fatal and 247 patients with non-fatal PE were eligible for analysis (median age 68 years; 24-95). In 58.8% with fatal and in 32% with non-fatal PE, disease was suspected pre-mortal. Clinical suspicion of PE was significantly enhanced in venous thrombosis (Odds Ratio [OR] = 12.17, p=0.004) and significantly decreased for chronic vascular disease (OR = 0.30, p=0.002). Recurrent PE was demonstrated in 31.4% fatal and in 4.5% non-fatal PE (OR = 9.81, p=0.001). 7% of all PE were localised centrally, 19% centrally and peripherally and 74% peripherally. Dyspnoea and tachycardia were the most frequent symptoms in fatal PE. About half of all patients suffered from malignancies. Suspicion of PE decreased after day 14 of hospitalisation (OR = 0.33, p=0.021). CONCLUSION PE often is not diagnosed pre-mortally. Patients with chronic vascular disease and tumours as well as those hospitalised for over 14 days are at particular risk for PE.

GINA together with many other national guidelines for the clinical management of asthma recommend a disease severity assessment in order to determine the quantity and frequency of medication. This classification scheme groups patients into one of four categories (intermittent, mild-persistent, moderate-persistent, and severe-persistent). However, it is important to recognise that asthma severity includes both severity of the underlying disease and responsiveness to treatment. In addition, severity is not an unvarying feature in any individual asthma patient and disease severity may change over months or years. Thus, for ongoing asthma management, classification using the level of control may be more relevant and useful in clinical practice. The new version of the GINA guidelines 2006 recognises these limitations of severity assessment and classifies the condition according to the level of control as "controlled", "partly controlled", and "uncontrolled" asthma on the basis of daytime symptoms, restrictions of physical activity, nocturnal symptoms/awakening, need for reliever/rescue medication, lung function (PEF or FEV1) and the frequency of exacerbations. In addition, the patient is assigned to one of five treatment "steps". Each step represents treatment options that are alternatives for controlling asthma. Moreover, steps 1 to 5 provide options of increasing efficacy. In order to maintain asthma control regular monitoring and adjustment is essential. In cases where asthma is not or only partially controlled with the current treatment regimen, step-up treatment is recommended whereas disease control allows a gradual stepping-down to the lowest possible dose of medication necessary to maintain control. This novel asthma management approach based on disease control, may facilitate acceptance and use of asthma guidelines in clinical practice.

Ulcerative colitis can be associated with numerous extraintestinal organ manifestations. Pulmonary disease in inflammatory bowel disease (IBD) is supposed to be a rare entity and has to be distinguished from infectious complications and side-effects of medications used in the treatment of IBD. We present the case of a 20-year-old male patient with ulcerative colitis and a 4-week history of respiratory symptoms, malaise, fever and respiratory insufficiency under a medication with mesalazine. Computed tomography showed bilateral subpleural consolidations, bronchoscopy revealed signs of acute bronchitis. The diagnostic work-up ruled out an infectious cause. Under the tentative diagnosis of a mesalazine-induced bronchiolitis obliterans with organizing pneumonia (BOOP) the medication with mesalazine was withdrawn and the patient received a corticosteroid trial. The symptoms quickly improved and prednisone was tapered and stopped after 6 months. Unexpectedly, lung function after complete resolution of respiratory symptoms revealed a residual obstructive ventilatory defect that might be due to an asymptomatic pulmonary manifestation of ulcerative colitis. A review of the literature shows that pulmonary manifestations in IBD as well as pulmonary toxicity of mesalazine might not be as rare as expected and should be included as differential diagnoses in the work-up of respiratory symptoms in patients with IBD. A pragmatic therapeutic approach is reasonable in critically ill patients as it is not always easy to distinguish both entities.

In dieser prospektiven Studie wurde der Stellenwert der transthorakalen Sonographie bei der Diagnostik bzw. beim Ausschluss des Pneumothorax/Seropneumothorax nach transbronchialer Biopsie und Pleuraergussdrainage mittels Pleurakatheter untersucht und mit den Röntgen-Thoraxaufnahmen verglichen. Insgesamt wurden 100 Patienten (38 Frauen, 62 Männner; mittleres Alter 63 Jahre) untersucht, 63 Patienten nach transbronchialer Biopsie und 37 Patienten nach Pleuraerguss-Drainage. Drei Stunden nach der Intervention erfolgte zunächst eine Thoraxsonographie, gefolgt von einer Röntgen-Thoraxaufnahme. Bei einem (1%) der 100 Patienten trat ein post-interventioneller Pneumothorax und bei acht Patienten (8%) ein Seropneumothorax auf. Die Sensitivität, Spezifität und Treffsicherheit der transthorakalen Sonographie bei der Pneumothorax-/Seropneumothorax-Diagnostik betrug 100%. Ein Seropneumothorax konnte röntgenologisch erst auf einer zusätzlich angefertigten seitlichen Röntgenaufnahme im Liegen erkannt werden. Die transthorakale Sonographie ist eine nicht-invasive und strahlenfreie Alternative zum herkömmlichen Vorgehen. Eine Röntgen-Thoraxaufnahme ist weiterhin bei Patienten mit sonographisch diagnostiziertem Pneumothorax (zur Bestimmung der Tiefenausdehnung), bei eingeschränkter sonographischer Beurteilbarkeit (z.B. bei Vorliegen eines Hautemphysems) sowie bei Auftreten einer Diskrepanz zwischen sonographischem und klinischem Befund erforderlich.

Desorientierung und Kachexie in Verbindung mit einem radiologisch nachweisbaren pulmonalen Rundherd lassen wie bei unserem Fall zunachst an eine zerebrale Metastasierung eines fortgeschrittenen Tumorleidens denken. Allerdings konnen diese Symptome auch durch die Kombination eines lokal begrenzten Tumors mit anderen Erkrankungen wie chronisch-entzundlichen Darmerkrankungen, chronischen Infektionen (Tuberkulose oder Morbus Whipple) oder Anorexie hervorgerufen werden. Der Morbus Whipple ist eine seltene bakterielle Erkrankung, die durch das seit 1991 teilweise sequenzierte Bakterium Tropheryma whippelii ausgelost wird. Die Erkrankung manifestiert sich vorwiegend am Verdauungstrakt. Eine monosymptomatische zerebrale Manifestation ist bisher nur in Einzelfallen beschrieben worden. In unserer Kasuistik wurde ein 65-jahriger Mann bei akuter Verwirrtheit und zur Abklarung eines pulmonalen Rundherdes nach langjahrigem Nikotin- und Alkoholabusus eingewiesen. Bei dem Patienten waren seit drei Wochen zunehmende Desorientierung und Apathie aufgefallen. Das zerebrale CT ergab bis auf eine geringe kortikale Atrophie einen unauffalligen Befund, laborchemisch waren lediglich gering erhohte Entzundungsparameter auffallig. Unter Verdacht auf ein Alkoholentzugssyndrom bei bekanntem regelmasigen Alkoholgenuss wurde der Patient bei zunehmender Tachykardie und Hypotonie zunachst mit Benzodiazepinen behandelt, Volumen substituiert und Katecholamine gegeben. Trotz intensivierter Therapie verstarb der Patient innerhalb 48 Stunden nach stationarer Aufnahme. Die Autopsie ergab keinen Hinweis auf eine stenosierende koronare Herzkrankheit oder eine Lungenarterienembolie. Im Rahmen der Hirnsektion fanden sich uberraschend Granulome vor allem im Bereich der Basalganglien sowie im Hirnstamm. Hier liesen sich histologisch Sieracki-Zellen, pathognomonisch fur einen Morbus Whipple, nachweisen. Unser Fall demonstriert noch einmal, dass ein Morbus Whipple sich „atypisch” primar am zentralen Nervensystem manifestieren kann, wobei die Diagnose sogar noch durch eine unauffallige Dunndarmhistologie erschwert werden kann. Obwohl selten, gehort der Morbus Whipple damit in die Differenzialdiagnose konsumierender Erkrankungen sowie des demenziellen Syndroms. A cancer patient with symptoms of confusion and kachexia would lead one to think primarily of cerebral metastasis. However, the combination of these symptoms can also be caused by other diseases such as chronic inflammatory bowel disease, anorexia, or multisystemic infectious diseases, for example tuberculosis, or Whipple's disease. Whipple's disease is a rare infectious disease, caused by the bacterium Tropheryma whippelii, which was partially sequenced in 1991. In most cases involvement of the gastrointestinal tract is the primary manifestation of the disease followed by involvement of the lymph nodes, joints or heart, but an isolated neurologic presentation is uncommon and has only been sporadically described. A 65-year old man was admitted to the hospital due to confusion and a suspicious pulmonary shadow in his chest X-ray. He had a history of cigarette smoking for 30 years and drank 3 bottles of beer each day before admission. Three weeks prior to admission confusion and progressive apathy occurred. The cerebral computer tomography was normal, apart from a minimal cortical atrophy, and inflammatory markers were slightly elevated. He developed hypotension and tachycardia. While alcohol addiction was suspected he received benzodiazepins, fluid substitution and catecholamins. Despite intensive therapy he died within 48 hours after hospital admission. At autopsy there was no evidence for coronary heart disease or pulmonary embolism. Examination of the brain showed multiple granulomas especially within the basal ganglia's and at the brain trunk. Histological investigation of these areas showed Sieracki cells, typically for Whipple's disease. In „atypical” cases, Whipple's disease is first manifested in the central nervous system, although no intestinal involvement can further complicate the correct diagnosis. Despite being rare, Whipple's disease must be discussed in cases of consumption and symptoms of dementia.

Die Pravalenz der autoptisch gesicherten Lungenembolie (LE) ist ungeachtet der diagnostischen und therapeutischen Fortschritte unverandert hoch. Da die LE einerseits mit einer signifikanten Fruhletalitat einhergeht und sich die Mortalitatsrate unter einer adaquaten Therapie von ca. 30% auf 2–8% senken lasst, sollte bereits bei Verdacht auf Vorliegen einer LE eine Therapie mit Heparin eingeleitet werden. Bei Patienten mit nicht-massiver LE stehen heute auch niedermolekulare Heparine fur die Initialtherapie zur Verfugung. Bei massiver LE mit Schock bzw. Hypotonie ist initial eine systemische Thrombolysetherapie indiziert. Ob hamodynamisch stabile Patienten mit den echokardiographischen Zeichen der rechtsventrikularen Dysfunktion (submassive LE) und/oder erhohtem Troponin von einer Lysetherapie profitieren, ist derzeit noch Gegenstand kontroverser Diskussion. Als Sekundarprophylaxe wird in der Regel eine Behandlung mit Vitamin-K-Antagonisten durchgefuhrt.

Idiopathic pulmonary fibrosis is a fatal lung disease with a variable and unpredictable natural history and limited treatment options. Since publication of the ATS-ERS statement on IPF in the year 2000 diagnostic standards have improved and a considerable number of randomized controlled treatment trials have been published necessitating a revision. In the years 2006 - 2010 an international panel of IPF experts produced an evidence-based guideline on diagnosis and treatment of IPF, which was published in 2011. In order to implement this evidence-based guideline into the German Health System a group of German IPF experts translated and commented the international guideline, also including new publications in the field. A consensus conference was held in Bochum on December 3rd 2011 under the protectorate of the "Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin (DGP)" and supervised by the "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF). Most recommendations of the international guideline were found to be appropriate for the german situation. Based on recent clinical studies "weak negative" treatment recommendations for pirfenidone and anticoagulation were changed into "weak positive" for pirfenidone and "strong negative" for anticoagulation. Based on negative results from the PANTHER-trial the recommendation for the combination therapy of prednisone plus azathiorpine plus N-acetlycsteine was also changed into strong negative für patients with definite IPF. This document summarizes essential parts of the international IPF guideline and the comments and recommendations of the German IPF consensus conference.

To study the effect of IL-13 on CD69 expression and cell viability in human eosinophils, purified human peripheral blood eosinophils from healthy donors were incubated with increasing concentrations of IL-13. The expression of CD69 was analyzed by flow cytometry (FACS). Surface expression of CD69, which was absent on untreated eosinophils, was induced by IL-13 at concentrations ranging from 1 ng/ml to 1 microgram/ml in a concentration-dependent manner. In contrast, neutrophils expressed CD69 neither spontaneously nor following incubation with IL-13. Semiquantitative reverse transcription-PCR for CD69 mRNA showed constitutive CD69 mRNA expression in purified human eosinophils. Incubation of eosinophils with IL-13 further increased CD69-specific mRNA. Analysis of intracellularly stored CD69 in eosinophils permeabilized with saponin revealed intracellular binding of anti-CD69 Abs in all isolated eosinophils. After stimulation with 100 ng/ml IL-13 for 24 h, the concentration of intracellular CD69 decreased by 41 +/- 9%. Furthermore, IL-13 at a concentration of 100 ng/ml enhanced eosinophil viability, as assessed by propidium iodide staining after 4 days in culture from 8.6 +/- 5.5% in control medium to 50.7 +/- 6.8% following stimulation with IL-13 treatment. The effect of Il-13 on eosinophil viability as well as that on CD69 expression were both neutralized by anti-IL-13 Abs. In conclusion, our results demonstrate that IL-13 specifically activates human eosinophils, as determined by the expression of CD69 cell surface protein and mRNA expression. Furthermore, IL-13 significantly prolongs eosinophil survival in vitro. The data suggest that IL-13 may play a role in the activation of eosinophils.

This paper describes the possibility of targeting the small airways. In addition to aiding in the therapy for chronic obstructive lung diseases this may prove to be invaluable in the development of treatment strategies for diseases of the bronchioli. Essential factors in peripheral lung deposition include extra-fine particles, a slow and controlled inspiratory flow and an endexspiratory breathhold of 5 - 10 sec (especially for steroids). Due to methodological difficulties, clinical data comparing steroids with larger or extra-fine particles are limited in the field of asthma therapy. However, research suggests a trend for reduced symptoms, positively affected biomarkers and decreased lung hyperinflation when steroids with extra-fine particles are used.

In the recent years growing interest has focused on the involvement of the distal airways (internal diameter2 mm) in obstructive lung diseases and other pulmonary conditions. Inflammation in the small airways seems to play a major role in severe and uncontrolled asthma as a major determinant of airflow obstruction. Thus, small airways represent an important target for inhalation therapy. Currently there is no accepted single lung function parameter to detect small airway dysfunction. Various invasive and non-invasive techniques have been described. In future, non-invasive lung function testing will gain more importance. Using spirometry or body plethysmography, lung function parameters such as the ratio of forced vital capacity to slow vital capacity (FVC/SVC) and the residual volume (RV) can provide information about air trapping in small airway disease. Recent data show that techniques such as impulse oscillometry, nitrogen washout testing and analysis of exhaled nitric oxide are promising tools to assess involvement of the small airways. Impulse oscillometry is a sensitive method to calculate peripheral airway resistance, nitrogen washout allows one to detect air trapping and inhomogeneous ventilation in the distal lung, and the alveolar nitric oxide concentration represents a marker of peripheral inflammation. Further studies are needed to validate these functional tests or their combination for diagnosis and assessment of treatment response in pulmonary diseases involving small airways.

The term "bronchiolitis" refers to a broad spectrum of common conditions related to the small airways associated with a miscellaneous aetiology, histology, clinical features and course. Due to their variability, bronchiolar disorders are generally difficult to diagnose. History (smoking, collagen vascular disease, inhalational injury, medication usage, and organ transplant) may point towards a bronchiolar process. In addition, signs of systemic and pulmonary infection and evidence of air trapping may provide diagnostic hints. Although clinical presentation, physical examination, pulmonary function tests (obstructive ventilatory defect), and plain chest radiographs may demonstrate abnormalities suggesting small airways involvement, they are often non-specific and rarely diagnostic. In contrast, the high-resolution CT (HR-CT) scanning of the chest provides three distinct HR-CT patterns that assist in the diagnosis and differential diagnosis of bronchiolar conditions: (i) a tree-in-bud pattern, (ii) ill-defined centrilobular ground-glass nodules, and (iii) a mosaic attenuation pattern (best visible on expiratory images). The present paper summarises the current knowledge, the classification, imaging, and the clinical presentation of bronchiolar disorders.

Mast cells and basophils are multifunctional immune cells and have been implicated in the pathogenesis of asthma and other pulmonary diseases. Although they are derived from distinct lineages, they share a number of important features which justifies discussing them collectively. This review covers the cellular characteristics and biological properties of both cell types, including origin, maturation and differentiation, morphological and phenotypical properties, as well as their capacity to secrete preformed and newly generated mediators of inflammation. In addition, the mechanisms of cell activation and priming of mast cells and basophils will be outlined, as well as the putative mechanisms through which both cell types communicate with other inflammatory cells. The final section of the review focuses on the possible pathogenetic role of mast cells and basophils in several pulmonary diseases, such as parasitic infections, allergic diseases, pulmonary fibrosis and malignant disorders.

Tracheobronchial complications following lung transplantation are defined as local structural or infectious alterations of the airways, which occur early or several months after lung transplantation (LTx). They preferentially develop in the region of the bronchial anastomosis. The most frequently reported complications are bronchial stenosis, bronchial dehiscence, exophytic excessive granulation tissue formation, tracheo-bronchomalacia, bronchial fistulas, and endobronchial infections. Airway complications are mainly attributed to ischaemia of the donor bronchus during the immediate post-transplant period. The most relevant risk factors for the development of airway complications include local infections, surgical techniques, and the immunosuppressive regimen. Thus, management of post-transplant bronchial complications requires early interventional bronchoscopic procedures including balloon bronchoplasty, cryotherapy, laser photoresection, endobronchial brachytherapy, and bronchial stents. In addition, antibiotic treatment, or non-invasive positive-pressure ventilation may be necessary. The procedures required depend on the time of occurrence, the type, and clinical relevance of the airway complication. This review summarises clinical presentation, risk factors, the diagnostic methods as well as management options for the most common LTx-associated airway complications.

The study was conducted to assess the rate of suspected pulmonary embolism (PE) prior to death and the diagnostic and therapeutic procedures performed.Patients with autopsy-confirmed PE between 1998 and 2002 were included. Autopsy register and medical records were reviewed for history, diagnosis and therapy of PE. Patients were categorised into fatal and non-fatal PE according to the autopsy findings.102 patients with fatal and 247 patients with non-fatal PE were eligible for analysis (median age 68 years; 24-95). In 58.8% with fatal and in 32% with non-fatal PE, disease was suspected pre-mortal. Clinical suspicion of PE was significantly enhanced in venous thrombosis (Odds Ratio [OR] = 12.17, p=0.004) and significantly decreased for chronic vascular disease (OR = 0.30, p=0.002). Recurrent PE was demonstrated in 31.4% fatal and in 4.5% non-fatal PE (OR = 9.81, p=0.001). 7% of all PE were localised centrally, 19% centrally and peripherally and 74% peripherally. Dyspnoea and tachycardia were the most frequent symptoms in fatal PE. About half of all patients suffered from malignancies. Suspicion of PE decreased after day 14 of hospitalisation (OR = 0.33, p=0.021).PE often is not diagnosed pre-mortally. Patients with chronic vascular disease and tumours as well as those hospitalised for over 14 days are at particular risk for PE.

The purpose of this study was to evaluate the long-term safety and therapeutic effects of IFN-alpha in patients with severe persistent uncontrolled asthma on long-term oral glucocorticoid (GC) treatment.The study included 16 patients (2 male, 14 female; age 39 years [range: 24 - 63]) with severe persistent asthma. Diagnosis and severity classification of asthma were established according to the guidelines of the "Deutsche Atemwegsliga". Eight patients stopped the therapy within 7 months due to side effects (n = 3), costs not covered by health insurance (n = 2), non-compliance (n = 2), and change of residence (n = 1). 8 patients (8 female, age 49 years [range: 35 - 68], duration of disease 16 years [range: 5 - 24]) were treated for at least 12 months with IFN-alpha (9 microg) 3 times/week. All patients were on oral glucocorticoids (GCs) for more than 5 years (average dose 17.5 [range: 5.0 - 64.0] mg/d). Clinical signs, lung function, need for reliever medication, number of emergency visits and hospitalisations and diary were assessed prior to and after 12 months of treatment. Data are given as percent of normal or median [range].IFN-alpha improved lung function after 12 months: FEV1 64 vs. 75 %; FEV1/IVC 76 vs. 89 %; RV 153 % vs. 129 %; Rtot 193 vs. 111 % and morning PEF by 50 - 190 L/min. IFN-alpha also significantly reduced the use of reliever medication (10 [2 - 20] vs. 1 [0 - 3] puffs/d), nocturnal awakening (11 [4 - 30] vs. 1 [0 - 5]/month), emergency visits (7 [2 - 15] vs. 0 [0 - 5]/month) and hospitalisations (4 [1 - 8] vs. 0 [0 - 5]/year). In 5 patients the asthma attacks and nightly disturbances disappeared completely. The improvements were achieved despite a tapering of the oral GCs in all patients from 17.5 (5.0 - 64.0) to 2 (0 - 16) mg/d. In 5 patients GC treatment could be discontinued. The number of blood eosinophils decreased from 0.46 to 0.28 Gpt/L. Adverse events were transient and usually decreased within 3 to 4 weeks. Two patients developed an autoimmune thyreoiditis.In severe persistent, uncontrolled, and GC-dependent asthma, treatment with IFN-alpha leads to sustained clinical improvement and allows the reduction or discontinuation of oral GCs. Severe side effects may occur in isolated cases.

The ability of three different peptides, substance P (SP), FMLP and melittin, to activate eosinophils purified from the peritoneal cavity of human serum-treated guinea pigs was investigated. Degranulation (eosinophil peroxidase, EPO), oxidative burst (O2-), [Ca2+]i mobilization, and arachidonic acid metabolism (thromboxane B2, TXB2) were used as indices of eosinophil activation. SP (100 nM to 100 microM), FMLP (1 to 100 microM) and melittin (10 nM to 100 microM) induced EPO release but only FMLP (1 to 100 microM) led to an elevation of [Ca2+]i. The melittin- and SP-induced EPO secretion occurred at both cytotoxic and noncytotoxic concentrations as assessed by lactate dehydrogenase release. In addition, the effect of SP was not inhibited by the SP analogue (D-Pro4, D-Trp7,9,10)SP(4-11) and SP failed to promote the generation and subsequent release of TXA2. In contrast, FMLP (10 to 100 microM) stimulated the release of TXB2 from guinea pig eosinophils that was selectively inhibited by pretreatment of the cells with BOC-FMLP. On an equimolar basis (1 microM), melittin was approximately fivefold more active at promoting TXB2 release than FMLP. The results indicate that eosinophils respond to the three peptides, SP, melittin, and FMLP in differential fashion. We conclude that activation of guinea pig eosinophils by FMLP is likely to be receptor-mediated whereas the actions of SP and melittin may act through nonspecific peptide-membrane phospholipid interactions.

The effect of platelet activating factor (PAF) on the generation of cyclo-oxygenase-derived arachidonic acid metabolites was examined on purified eosinophils harvested from the peritoneal cavity of male guinea pigs. PAF produced a concentration-dependent increase in the amount of immunoreactive thromboxane B2 (TXB2) and PGE1/E2 released from these inflammatory cells at a relative molar ratio of 30:1. The EC50 of PAF was 20 to 40 nM and maximum stimulation (4.5-fold) of both prostanoids occurred at 1 microM PAF. The ability of PAF to generate TXA2 was rapid (t 1/2 = 9 s), transient (40 s), noncytotoxic, and noncompetitively antagonized by the PAF-receptor blocking drug, WEB 2086. On an equimolar (100 nM) basis, PAF was significantly more effective than C5a, fMLP, and PMA at stimulating TXB2 release but markedly less potent than the calcium ionophore, calcimycin. Pretreatment of eosinophils with the cyclo-oxygenase inhibitor flurbiprofen (8 microM for 5 min) abolished the ability of PAF to promote both TXB2 and PGE1/E2 release. Likewise, dazmegrel (50 microM for 5 min), a selective inhibitor of thromboxane synthetase, abolished PAF-stimulated TXB2 release but markedly augmented the elaboration of PGE1/E2. Inhibition of cyclo-oxygenase with flurbiprofen affected neither the ability of PAF to elevate the intracellular calcium ion concentration (measured by fura-2 fluorescence) nor its appetency to generate superoxide anions at any PAF concentration examined. It is concluded that activation of guinea pig eosinophils by PAF is receptor-mediated and independent of the concomitant generation of cyclo-oxygenase-derived excitatory prostanoids. Inasmuch as TXA2 may contribute to the pathogenesis of bronchial hyperreactivity, then these data implicate the eosinophil as a potential source of this lipid mediator.