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ZusammenfassungInterstitielle Lungenerkrankungen (ILD) sind eine heterogene Gruppe von Pathologien, die zunehmend als relevanter Faktor pulmonaler Morbidität und Mortalität erkannt werden. Verschiedene ILD wie die idiopathische Lungenfibrose (IPF), aber auch durch Autoimmunprozesse oder durch exogene Noxen bedingte ILD können zu progredienter, meist irreversibler Lungenfibrose führen. Die antifibrotischen Substanzen Nintedanib und Pirfenidon können den Krankheitsverlauf bei IPF-Patienten günstig beeinflussen. Dagegen werden ILD, die auf entzündlichen Prozessen wie z. B. rheumatologischen Grunderkrankungen oder exogen-allergischer Alveolitis beruhen, bis dato klassischerweise immunsuppressiv therapiert. Immer wieder kommt es aber trotz einer solchen Behandlung zu progredienter Fibrosierung. Eine positive Wirkung antifibrotischer Medikation auf progredient fibrosierende (pf)ILD abseits der IPF konnte in rezenten Studien demonstriert werden, auch wenn der Stellenwert der Antifibrotika in solchen Situationen noch nicht vollständig geklärt ist. Dieses Consensus-Statement beruht auf einem virtuellen, multidisziplinären Expertenmeeting von Rheumatologen, Pneumologen und Radiologen und wurde durch die jeweiligen ILD-Arbeitskreise der Österreichischen Gesellschaften für Pneumologie sowie Rheumatologie (ÖGP und ÖGR) akkordiert. Ziel war es, den aktuellen Stand von klinischer Praxis und wissenschaftlicher Datenlage zu Definition, Evaluation und Therapie von pfILD darzustellen. Zusammenfassend sollen ILD-Patienten einer standardisierten Abklärung unterzogen, in einem multidisziplinären ILD-Board diskutiert und dementsprechend therapiert werden. Kern dieser Empfehlungen ist, auch Non-IPF-Patienten mit dokumentiert progredient fibrosierendem ILD-Verlauf antifibrotisch zu behandeln, insbesondere wenn Honigwabenzysten oder eine bereits ausgedehnte Erkrankung vorliegen. Patienten mit fibrotischer ILD, die auf Basis der ILD-Board-Empfehlung primär keiner oder ausschließlich einer immunsuppressiven Therapie unterzogen werden, sollten engmaschig hinsichtlich eines progredienten Verlaufes überwacht werden.

Background Although the burden of influenza infection is the highest in older adults, vaccination coverage remains low, despite this age group being more vulnerable than others. Aims Given the current pandemic of SARS-CoV-2, it was the aim of this scope review to update knowledge on factors affecting seasonal influenza vaccine uptake among older adults to strengthen prevention approaches in the context of an overall burden of infectious diseases. Methods We searched bibliographic databases from 2012 to 2019. All studies reviewed one or more social determinant of health listed by WHO, or factors affecting the decision-making process whether to accept influenza vaccine or not. Results Overall, 44 studies were included, 41 determinants were extracted and summarized into six categories. Older age and constitutional factors including multiple chronic diseases as well as preventive lifestyle and frequent routine healthcare utilization positively affected vaccination uptake (VU). Living and working conditions are also researched determinants of influenza vaccine uptake. A small number of studies explored the role of social inclusion and system-based interventions. Discussion and conclusions This scope review provides a comprehensive overview on factors affecting seasonal influenza vaccination uptake among older citizens. The review also clearly shows gaps for evidence on system-based level or political strategies to improve vaccination uptake.

Background There is only limited clinical data on the benefit of intense immunosuppression in patients with severe interstitial pneumonia associated with autoimmune features or new-onset connective tissue disease. Case presentation We here report a series of three consecutive patients suffering from severe interstitial lung disease necessitating endotracheal intubation and mechanical ventilation. The first two patients fulfilled many diagnostic criteria for new-onset antisynthetase syndrome, the third patient for systemic lupus erythematosus. We decided to implement aggressive immunosuppressive strategies in these critically-ill patients including therapeutic plasma exchange, immunoadsorption, cyclophosphamide and rituximab. All three patients improved from respiratory failure, were successfully weaned from the respirator, and eventually dismissed from hospital with ongoing immunosuppressive therapy. Conclusion Patients suffering from severe connective tissue disease-associated interstitial lung disease and respiratory failure may benefit from an aggressive immunosuppressive regimen and extracorporeal blood purification with rapid reduction of circulating autoantibodies. The impressive clinical responses in this small case series warrant a controlled clinical trial.

ZusammenfassungDie Schwere einer SARS-CoV-2-Pneumonie, ihr Verlauf, die Letalität und Mortalität werden multifaktoriell durch den unmittelbaren Parenchymschaden im Bereich der Lungen (inklusive der Pulmonalgefäße), vorbestehende Komorbiditäten, extrapulmonale Komplikationen, sekundäre Infektionen und die Qualität der verfügbaren medizinischen Versorgung bedingt. Diesbezüglich ist COVID-19 vergleichbar mit anderen schweren ambulant erworbenen Pneumonien durch konventionelle Erreger, auch wenn sich die Pathogenese unterscheidet. Die Letalität von hospitalisierten COVID-19-Patienten beträgt näherungsweise 20 % (damit höher als bei anderen Pneumonieerregern), bei intensivpflichtigen Patienten 30–40 % und von invasiv beatmeten Patienten ca. 50 %. Für die Letalität ausschlaggebende Risikofaktoren sind hohes Alter, Übergewicht, männliches Geschlecht und typische altersabhängige kardiopulmonale Grunderkrankungen. Die klinische Risikoeinschätzung im Krankenhaus sollte im Wesentlichen entsprechend den gültigen Pneumonieleitlinien erfolgen. Die Wertigkeit von COVID-19-spezifischen laborchemischen Surrogatmarkern zur Risikoeinschätzung und Behandlungsoptimierung ist noch nicht ausreichend beurteilbar.

Introduction There are only a few data on the impact of smoking and smoking cessation on the outcome of patients treated with allogeneic hematopoietic stem cell transplantation, a well-established therapy for hematologic malignancies. Methods In a retrospective cohort study design we examined the impact of smoking and smoking cessation on survival among 309 eligible consecutive adults who underwent allogeneic hematopoietic stem cell transplantation using reduced-intensity (n = 179) or myeloablative (n = 130) conditioning between 1999 and 2018. Results Smoking and was independently associated with increased mortality with a five-year overall survival of 25% in current smokers versus 53% in never smokers versus 48% in past smokers. Never smokers lived significantly longer (HR: 2.00, 95%CI: 1.19–3.35, p = .008) and had a better event-free survival (HR: 2.11, 95%CI: 1.27–3.49, p = .004) than current smokers. In the long run, never smokers also lived significantly longer than past smokers (HR: 1.45, 95%CI: 1.16–1.81, p = .001). Patients who quit smoking before allogeneic hematopoietic stem cell transplantation showed a tendency towards increased survival compared to those who continued smoking (HR: 1.53, 95%CI: 0.95–2.45, p = .078). In relation to life-time cigarette dose smokers with low-dose (1–10 pack-years) cigarette consumption lived significantly longer (HR: 1.60, 95%CI: 1.03–2.50, p = .037) and had a better event-free survival (HR: 1.66, 95%CI: 1.07–2.58, p = .025) than patients with high-dose (≥10 pack-years) cigarette consumption. Conclusions In allogeneic hematopoietic stem cell transplantation for hematologic malignancies, smoking history per se, lifetime cigarette dose, and continued smoking, were significantly associated with increased all-cause mortality and reduced event-free survival. Implications Continued and past smoking represent established risk factors for malignant and non-malignant diseases, however, they are also a strong risk factor for a poor outcome after allogeneic hematopoietic stem cell transplantation for hematologic diseases. Our study shows that the hazard ratio for death after such transplantation is doubled if patients continue smoking and even if they have quit smoking, their risk remains significantly elevated. This suggests that the smoking history provides important predictive factors for the outcome of allogeneic hematopoietic stem cell transplantation and that smoking cessation should be implemented in the treatment of hematologic diseases as early as possible.

Despite clinical advances, late onset pulmonary complications in adult recipients of allogenic stem cell transplantation are a major cause of morbidity and mortality. Reported incidence and risk factors in the literature vary broadly and are partly contradictory. Identification of pretransplant factors associated with major complications would be helpful to define individual treatment strategies and early initiation of preventive measures. To evaluate incidence and risk factors of late onset noninfectious pulmonary complications, with special regard to small airways disease (SAD) and bronchiolitis obliterans syndrome (BOS), indicating graft-versus-host disease, following myeloablative versus nonmyeloablative allogenic stem cell transplantation. We reviewed the clinical records and assessed the course of lung function and pulmonary complications in adults who underwent allogenic stem cell transplantation for hematological malignancies between 1999 and 2015 using nonmyeloablative (n = 179) or myeloablative (n = 130) conditioning at the Division of Hematology of the Medical University of Graz. All patients underwent body plethysmography pulmonary function test (PFT), diffusion capacity for carbon monoxide, and arterial blood gas analysis before and repeatedly after transplant. SAD was defined as maximal expiratory flow at 50% and 25% of forced vital capacity70% predicted. Ventilatory disorders and gas transfer abnormalities were common before and after allogenic stem cell transplantation, independent of conditioning regimen. SAD was common in the nonmyeloablative (34%) and myeloablative (29%) groups. The 100-day post-transplant mortality was significantly associated with reduced pretransplant total lung capacity80%. Mortality 100 days post-transplant was significantly associated with pretransplant SAD and a pretransplant smoking history. In this subset, a smoking history was independently associated with increased mortality, with a 5-year mortality of 45% compared with 26% in never-smokers. Pretransplant SAD was not predictive for the later development of BOS. Smoking history, pretransplant restrictive PFT, and pre-existing SAD are important risk factors for death following allogenic stem cell transplantation. However, pretransplant SAD is not a predictor of long-term complications, including BOS.

Chronic pulmonary aspergillosis (CPA) is a severe fungal infectionwith a highmorbidity andmortality, and is usuallyseen in immunocompetent patients with respiratory disorders. Clinical presentation is nonspecific and often overlapswith the symptoms and the radiological pattern caused by the underlying disease. Clinical management ofCPA is further hampered by limited information about the epidemiology, disease dynamics, sensitivity and specificityof differentmycological tests,mechanisms of antifungal resistance, efficient treatment andmanagement strategies.In order to contribute to a better understanding and to improve CPA patientmanagement and outcome, weestablished the Chronic Pulmonary Aspergillosis Network (CPAnet), a self-organizedmultinational research collaboration.Key research priorities, defined by using a modified Delphi process, include the establishment of a multinationalweb-based registry, the validation of different diagnostic tests, the establishment of a culture collection fromsamples of patientswith proven CPA and the establishment of a consensus on a treatment outcome definition.

Chronic pulmonary aspergillosis (CPA) is a chronic fungal infection of the lung associated with high morbidity and mortality. The CPA Research network (CPAnet) registry established in 2018 is an international multicenter collaboration aiming to improve CPA knowledge and patient care. This study&rsquo, s aim was to describe the data collection process and content of CPAnet registry with preliminary clinical data. In the CPAnet registry, clinical data are collected through a web-based questionnaire. Data include CPA phenotype, comorbidities, treatment, outcome, and follow-up from several international centers. An exemplary descriptive analysis was performed on 74 patients, who were registered online before April 2020. CPA patients were predominantly (72%) male, 39% had chronic obstructive pulmonary disease, and 68% had a history of smoking. Chronic cavitary pulmonary aspergillosis was the most common CPA subtype (62%). In 32 patients (52%), voriconazole was the preferred first-line therapy. The multicenter multinational CPAnet registry is a valuable approach to gather comprehensive data on a large study population and reflects real-world clinical practice rather than focusing on specific patient populations in more specialized centers. Additional CPA reference centers are being encouraged to join this promising clinical research collaboration.

Background: Chronic pulmonary aspergillosis (CPA) is a chronic fungal infection of the lung associated with high morbidity and mortality. The CPAnet registry established in 2018 is an international multicenter collaboration aiming to improve CPA knowledge and patient care. In 2020, it has been awarded a Clinical Research Collaboration (CRC) by the ERS. This study’s aim was to describe the data collection process and content of CPAnet registry, by presenting preliminary clinical data. Methods: In the CPAnet registry, clinical data are collected through a web-based questionnaire. Data include CPA phenotype, comorbidities, treatment, outcome and follow-up from several international centers. An exemplary descriptive analysis was performed on 74 patients, who were registered online before April 2020. Results: CPA patients were predominantly (72%) male, 39% had chronic obstructive pulmonary disease and 68% had a history of smoking. Chronic cavitary pulmonary aspergillosis was the most common CPA subtype (62%). In 32 patients (52%), voriconazole was the preferred first-line therapy. Conclusion: The multicenter multinational CPAnet registry is a valuable approach to gather comprehensive data on a large study population and reflects real-world clinical practice rather than focusing on specific patient populations in more specialized centers. Additional CPA reference centers are being encouraged to join this promising CRC. * The 2 first (EVB and LVA) and 2 last authors (CBL and JRD) contributed equally.

Background Idiopathic pulmonary fibrosis (IPF) is a disease with high 5-year mortality and few therapeutic options. Prostaglandin (PG) E2 exhibits antifibrotic properties and is reduced in bronchoalveolar lavage from patients with IPF. 15-Prostaglandin dehydrogenase (15-PGDH) is the key enzyme in PGE2 metabolism under the control of TGF-β and microRNA 218. Objective We sought to investigate the expression of 15-PGDH in IPF and the therapeutic potential of a specific inhibitor of this enzyme in a mouse model and human tissue. Methods In vitro studies, including fibrocyte differentiation, regulation of 15-PGDH, RT-PCR, and Western blot, were performed using peripheral blood from healthy donors and patients with IPF and A549 cells. Immunohistochemistry, immunofluorescence, 15-PGDH activity assays, and in situ hybridization as well as ex vivo IPF tissue culture experiments were done using healthy donor and IPF lungs. Therapeutic effects of 15-PGDH inhibition were studied in the bleomycin mouse model of pulmonary fibrosis. Results We demonstrate that 15-PGDH shows areas of increased expression in patients with IPF. Inhibition of this enzyme increases PGE2 levels and reduces collagen production in IPF precision cut lung slices and in the bleomycin model. Inhibitor-treated mice show amelioration of lung function, decreased alveolar epithelial cell apoptosis, and fibroblast proliferation. Pulmonary fibrocyte accumulation is also decreased by inhibitor treatment in mice, similar to PGE2 that inhibits fibrocyte differentiation from blood of healthy donors and patients with IPF. Finally, microRNA 218-5p, which is downregulated in patients with IPF, suppressed 15-PGDH expression in vivo and in vitro. Conclusions These findings highlight the role of 15-PGDH in IPF and suggest 15-PGDH inhibition as a promising therapeutic approach.

Introduction: Treatment of MDRTB is complex: regimens require microbiological data; adverse events are frequent; availability of drugs and authorization for new drugs varies. The aim of this study was to scope the available national resources. Method: A survey to determine whether practising physicians could access MDRTB advice was sent to TBnet members by email. The ERS Office also contacted national respiratory societies. Questions included the name and contact details for their national advisory service, whether it was national policy to use the service for each patient with MDRTB and whether advice was required to access bedaquiline and delaminid. Results: 65 replies were received (14 were uninformative). 26/31 EU/EEA and 10/19 other countries in the WHO European Region were represented. 7 countries referred all MDRTB to a tertiary centre; 12 countries had tertiary referral centres that also gave advice to physicians treating MDRTB. 11 countries had an electronic system for advice, 6 with multidisciplinary team meetings to review patients’ progress. Lead clinicians were identified for a further 8 countries, one of which had no national advisory service and the other 7 had not responded by the time of abstract submission. For 18 (58%) countries, discussion of MDRTB by a national /regional committee was national policy and most (15/18) required consultation to use bedaquiline or delamanid. Electronic platforms had a wide range of functionality but few retained anonymised data and audited patient outcomes. Conclusion: MDRTB management is often concentrated in tertiary centres. Clinical governance, regarding audit and outcome, are at an early stage in managing MDRTB.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection. Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis. Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71-0.95; p < 0.001) for predicting 90-day mortality. Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.

Background: Diagnosis of chronic pulmonary aspergillosis (CPA) is challenging. Symptoms are unspecific or missing, radiological findings are variable and proof of mycological evidence is limited by the accuracy of diagnostic tests. The goal of this study was to investigate diagnostic performance of galactomannan (GM), the newly formatted Aspergillus-specific lateral-flow-device test (LFD), and a number of cytokines in bronchoalveolar lavage fluid (BALF) samples obtained from patients with CPA, patients with respiratory disorders without CPA and healthy individuals. Methods: Patients with CPA (n = 27) and controls (n = 27 with underlying respiratory diseases but without CPA, and n = 27 healthy volunteers) were recruited at the Medical University of Graz, Austria and the Research Center Borstel, Germany between 2010 and 2018. GM, LFD and cytokine testing was performed retrospectively at the Research Center Borstel. Results: Sensitivity and specificity of GM testing from BALF with a cut off level of ≥0.5 optical density index (ODI) was 41 and 100% and 30 and 100% with a cut off level of ≥1.0 ODI. ROC curve analysis showed an AUC 0.718 (95% CI 0.581-0.855) for GM for differentiating CPA patients to patients with other respiratory diseases without CPA. The LFD resulted positive in only three patients with CPA (7%) and was highly specific. CPA patients did not differ significantly in the BALF cytokine profile compared to patients with respiratory disorders without CPA, but showed significant higher values for IFN-γ, IL-1b, IL-6, IL-8, and TNF-α compared to healthy individuals. Conclusion: Both GM and LFD showed insufficient performance for diagnosing CPA, with sensitivities of BALF GM below 50%, and sensitivity of the LFD below 10%. The high specificities may, however, result in a high positive predictive value and thereby help to identify semi-invasive or invasive disease.

Background: Influenza and pneumococcal vaccination is highly recommended for cardiologic and pneumologic patients. This still ongoing study analyses influenza and pneumococcal vaccination coverage rate in cardiologic and pneumologic inpatients at the University Hospital Graz. Methods: 200 hospitalised patients were surveyed about their vaccination status and asked about reasons for not being vaccinated, and whether physicians did actively endorse vaccination in the last six months. Results: 133 male and 67 female patients were enrolled. Only 17.5% were vaccinated against influenza and 18.5% against pneumococcal infection. Patients who suffered from COPD or asthma were vaccinated against influenza and pneumococcal infection more frequently than non COPD/asthma patients. The reasons mostly mentioned for not being vaccinated was not being convinced of the benefit. Patients who did not have contact to a doctor during the winter season were vaccinated less frequently than patients who did consult a doctor during that time (5.71% vaccinated against influenza versus 9.7% not vaccinated, 4.35% vaccinated against pertussis versus 9.6% not vaccinated, 2.7% vaccinated against pneumococcal infection versus 10.43% not vaccinated). Conclusion: These findings indicate firstly a critical under-supply of vaccinations in high-risk groups, and secondly a dramatic ignorance about the beneficial effects of influenza and pneumococcal vaccination by treating physicians. These data should be used to question the actual national vaccination strategies.

Background: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge on PN is derived from case reports and small case series. Increasing incidence rates of PN have been reported recently. The aim of this study was to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates. Methods: This was a retrospective evaluation (1995–2011) of the clinical course of and risk factors for PN in patients at 11 hospitals in four European countries (Germany, Austria, Switzerland, and the Netherlands). Population-based estimates of hospitalization rates for PN in Germany (2005 to 2011) were calculated using official German nationwide diagnosis-related groups (DRG) hospital statistics. Results: Forty-three patients fulfilled stringent criteria for proven (n = 8) and probable (n = 35) PN; seven had extrapulmonary dissemination. For these 43 patients, the major risk factors for PN were immunocompromising (83.7%) and/or pulmonary (58.1%; as only comorbidity in 27.9%) comorbidities. The median duration of PN targeted therapy was 12 weeks. Distinctive patterns of resistance were observed (imipenem susceptibility: Nocardia farcinica 33.3%; Nocardia asteroides 66.7%). The overall mortality rate was 18.9% (50% in disseminated PN). Over time, annual PN hospitalization rates remained unchanged at around 0.04/100 000, with the highest rate among men aged 75–84 years (0.24/100 000). Conclusions: PN is a rare, but potentially life-threatening disease, and mainly affects immunocompromised elderly males. Overall, annual hospitalization rates remained stable between 2005 and 2011. Keywords: Nocardiosis, Nocardia, Pulmonary nocardiosis

Summary Background Aspergillus spp. induce elevated levels of several cytokines. It remains unknown whether these cytokines hold value for clinical routine and enhance diagnostic performances of established and novel biomarkers/tests for invasive aspergillosis (IA). Methods This cohort study included 106 prospectively enrolled (2014–2017) adult cases with underlying hematological malignancies and suspected pulmonary infection undergoing bronchoscopy. Serum samples were collected within 24 hours of bronchoalveolar lavage fluid (BALF) sampling. Both, serum and BALF samples were used to evaluate diagnostic performances of the Aspergillus-specific lateral-flow device test (LFD), Aspergillus PCR, β-D-glucan, and cytokines that have shown significant associations with IA before. Results Among 106 cases, 11 had probable IA, and 32 possible IA; 80% received mold-active antifungals at the time of sampling. Diagnostic tests and biomarkers showed better performance in BALF versus blood, with the exception of serum interleukin (IL)-8 which was the most reliable blood biomarker. Combinations of serum IL-8 with either BALF LFD (sensitivity 100%, specificity 94%) or BALF PCR (sensitivity 91%, specificity 97%) showed promise for differentiating probable IA from no IA. Conclusions High serum IL-8 levels were highly specific, and when combined with either the BALF Aspergillus-specific LFD, or BALF Aspergillus PCR also highly sensitive for diagnosis of IA.

The objective of this study was to investigate the prognostic potential of 1,3-beta-d-glucan (BDG) testing in bronchoalveolar lavage fluid (BALF) samples.A total of 300 BALF samples from 252 patients were investigated for BDG (Fungitell(®) assay). Prognostic potential of BALF BDG was evaluated by using: i.) Kaplan-Meier analysis, and ii.) multivariable Cox hazard regression analyses.BALF BDG levels were found to be significantly higher in samples with Candida spp. colonization (p 0.001). A total of 61/252 patients (24.2%) died within 90-days of BALF sampling (18.1% of patients with BALF BDG200 pg/mL, 32.4% with BALF BDG ≥200 pg/mL). Kaplan-Meier analysis revealed that overall cumulative 90-day mortality was significantly higher in those with BALF BDG levels ≥200 pg/mL when compared to those with levels200 pg/mL (log-rank p = 0.006, Breslow p = 0.005 and Tarone-Ware p = 0.005). The multivariable Cox regression analysis showed that BALF BDG levels were a strong predictor of 90-day overall mortality, with a hazard ratio of 1.048 (per 100 pg/mL increase of BALF BDG).False positive BALF BDG results in the presence of Candida spp. colonization of the lower respiratory tract may explain the limited diagnostic potential of BALF BDG testing. In contrast, prognostic potential of BALF BDG may be promising.

Summary We evaluated the performance of the Aspergillus-specific lateral-flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) in patients with underlying haematological malignancies. Participating centres were the two Austrian University Hospitals of Graz and Innsbruck. LFD performance was evaluated with 95 bronchoalveolar lavage fluid (BALF) samples from 72 patients collected prospectively in Graz, and with 24 BALF bio bank samples from 23 patients (21 samples with probable IPA) in Innsbruck. Invasive fungal infections were classified according to the revised European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria. Overall, 27 patients (30 samples) had probable IPA, 32 (43 samples) possible and 36 (46 samples) did not fulfil IPA criteria. The vast majority of patients – in particular those with probable IPA – received mould-active treatment before bronchoscopy. Sensitivity, specificity, positive predictive value and negative-predictive-value for probable IPA diagnosis using the BALF-LFD test were 71%, 76%, 35% and 94% for the Graz cohort. Sensitivity of the BALF-LFD test for probable IPA was 57% in Innsbruck bio bank samples. Our results indicate that the BALF-LFD-test provides fast results with moderate sensitivities in patients with underlying haematological malignancies. Similar to other diagnostic tests and biomarkers sensitivity of the test may be influenced by ongoing systemic mould-active treatment.

Chronic pulmonary aspergillosis (CPA) complicates conditions including tuberculosis, chronic obstructive pulmonary disease and sarcoidosis, and is associated with high morbidity and mortality. Surgical cure should be considered where feasible; however, many patients are unsuitable for surgery due to extensive disease or poor respiratory function. Azoles are the only oral drug with anti-Aspergillus activity and itraconazole and voriconazole are considered as first-line drugs. A randomized controlled trial demonstrated improvement or stability in three-quarters of patients given 6 months of itraconazole, but a quarter relapsed on stopping therapy. Long-term treatment may therefore be required in some cases. Itraconazole, voriconazole and posaconazole require therapeutic drug monitoring. No published data are yet available for isavuconazole. Adverse drug effects of azoles are common, including peripheral neuropathy, heart failure, elevated liver enzymes, QTc prolongation and sun sensitivity. Many serious drug-drug interactions occur, including major interactions with rifamycins, simvastatin, warfarin, clopidogrel, immunosuppressant drugs like sirolimus. Furthermore, drug resistance occurs, including cross-resistance to all azoles, but the true prevalence is not yet determined. Intravenous therapy is possible with echinocandins or amphotericin B, but long-term use is challenging. Hemoptysis complicates CPA and can be fatal. Tranexamic acid should be given acutely to reduce bleeding. Bronchial artery embolization can stop acute bleeds. In some circumstances, emergency surgery may be necessary to resect the source of the bleed. Current CPA treatments can be beneficial but have many drawbacks. New oral anti-Aspergillus agents are needed, along with optimization of currently available treatments.

Real-world studies include a broader patient population for a longer duration than randomised controlled trials (RCTs) and can provide relevant insights for clinical practice. PASSPORT was a multicentre, prospective, post-authorisation study of patients who were newly prescribed pirfenidone and followed for 2 years after initiating treatment. Physicians collected data on adverse drug reactions (ADRs), serious ADRs (SADRs) and ADRs of special interest (ADRSI) at baseline and then every 3 months. Post hoc stepwise logistic regression models were used to identify baseline characteristics associated with discontinuing treatment due to an ADR. Patients (n=1009, 99.7% with idiopathic pulmonary fibrosis) had a median pirfenidone exposure of 442.0 days. Overall, 741 (73.4%) patients experienced ADRs, most commonly nausea (20.6%) and fatigue (18.5%). ADRs led to treatment discontinuation in 290 (28.7%) patients after a median of 99.5 days. Overall, 55 (5.5%) patients experienced SADRs, with a fatal outcome in six patients. ADRSI were reported in 693 patients, most commonly gastrointestinal symptoms (38.3%) and photosensitivity reactions/skin rashes (29.0%). Older age and female sex were associated with early treatment discontinuation due to an ADR. Findings were consistent with the known safety profile of pirfenidone, based on RCT data and other post-marketing experience, with no new safety signals observed., Real-world safety results from 1009 patients in PASSPORT were consistent with the known pirfenidone safety profile http://ow.ly/oXjv30lrzAf

Aspergillus spp. have been shown to induce T-helper cell (Th) 1 and Th17 subsets resulting in elevated levels of several cytokines. The objective of this study was to analyse a bundle of cytokines in serum and bronchoalveolar lavage fluid (BALF) in patients with and without invasive pulmonary aspergillosis (IPA). This nested case-control analysis included 10 patients with probable/proven IPA and 20 matched controls without evidence of IPA, out of a pool of prospectively enrolled (2014-2017) adult cases with underlying haematological malignancies and suspected pulmonary infection. Serum samples were collected within 24 hours of BALF sampling. All samples were stored at -70°C for retrospective determination of cytokines. IL-6 and IL-8 were significantly associated with IPA in both serum (P = .011 and P = .028) and BALF (P = .006 and P = .012, respectively), and a trend was observed for serum IL-10 (P = .059). In multivariate conditional logistic regression analysis, IL-10 remained a significant predictor of IPA in serum and IL-8 among BALF cytokines. In conclusion, levels of IL-6 and IL-8 were significantly associated with probable/proven IPA, and a similar trend was observed for serum IL-10. Future cohort studies should determine the diagnostic potential of these cytokines for IPA, and evaluate combinations with other IPA biomarkers/diagnostic tests.

Introduction: Chemical pleurodesis is used to treat malignant pleural effusion (MPE). Injection of sclerosing agents into the pleural cavity leads to inflammation and adhesion of pleural layers. Adequate analgesia is mandatory during the procedure, which may be based on the WHO three-step analgesic ladder for cancer pain. However, several experimental studies have reported a negative influence of NSAIDs on chemical pleurodesis, as they impede pro-inflammatory processes. Aims and Objectives: The aim was to retrospectively evaluate the influence of NSAIDs on the efficacy of chemical pleurodesis in MPE. Methods: 120 patients (52 males, 68 females) with MPE undergoing chemical pleurodesis were retrospectively analysed. Clinical, pathological and treatment-related factors were ascertained. Failure of pleurodesis was defined as ipsilateral recurring MPE necessitating re-drainage and/or an MPE exceeding the hilus. Results: During a mean follow-up period of 7.9 months, 25.8% of patients developed a recurrent MPE (n=31). The peri-interventional use of NSAIDs did not increase risk for failure of pleurodesis (univariate; p=0.133). Post-interventional administration of chemotherapy was the only independent factor reducing risk for recurrent MPE (multivariate; HR:0.339, 95%CI: 0.121-0.948; p=0.039). Conclusion: According to this analysis, NSAIDs as part of the standard WHO three-step analgesic ladder do not impair the efficacy of chemical pleurodesis. To maintain freedom from pain, administration of NSAIDs should not be discontinued or withheld during pleurodesis in cancer patients.

Multicenter trials in Southeast Asia have shown better survival rates among patients with severe malaria, particularly those with high parasitemia levels, treated with intravenous (IV) artesunate than among those treated with quinine. In Europe, quinine is still the primary treatment for severe malaria. We conducted a retrospective analysis for 25 travelers with severe malaria who returned from malaria-endemic regions and were treated at 7 centers in Europe. All patients survived. Treatment with IV artesunate rapidly reduced parasitemia levels. In 6 patients at 5 treatment centers, a self-limiting episode of unexplained hemolysis occurred after reduction of parasitemia levels. Five patients required a blood transfusion. Patients with posttreatment hemolysis had received higher doses of IV artesunate than patients without hemolysis. IV artesunate was an effective alternative to quinine for treatment of malaria patients in Europe. Patients should be monitored for signs of hemolysis, especially after parasitologic cure.

Die vorliegende Leitlinie umfasst ein neues und aktualisiertes Konzept der Behandlung und Pravention von erwachsenen Patienten mit ambulant erworbener Pneumonie und lost die bisherige Leitlinie aus dem Jahre 2009 ab. Sie wurde entsprechend den Masgaben zur Methodologie einer S3-Leitlinie erarbeitet und verabschiedet. Hierzu gehoren eine systematische Literaturrecherche und -bewertung, die strukturierte Diskussion der aus der Literatur begrundbaren Empfehlungen sowie eine Offenlegung und Bewertung moglicher Interessenskonflikte. Die Leitlinie zeichnet sich aus durch eine Zentrierung auf definierte klinische Situationen, eine aktualisierte Masgabe der Schweregradbestimmung, Empfehlungen zu einer individualisierten Auswahl der initialen antimikrobiellen Therapie sowie zur primaren und sekundaren Pravention.

Introduction The incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients. Methods A total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Results Two patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%. Conclusion LFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available. Trial registration ClinicalTrials.gov NCT02058316. Registered 20 January 2014.

The effect of mould-active antifungal (AF) therapy/prophylaxis on the performance of the Aspergillus-specific lateral-flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) was evaluated. This was a retrospective analysis of patients diagnosed with probable or proven IPA (according to revised EORTC/MSG criteria) at the Medical University of Graz (Austria) and the University Hospital of Mannheim (Germany) between February 2011 and December 2014. In total, 60 patients with 63 bronchoalveolar lavage fluid (BALF) samples were included in the analysis. Patient charts were reviewed regarding AF treatment at the time of bronchoscopy, and the influence of AFs on the performance of the LFD and BALF galactomannan (GM) ELISA results was calculated. Overall, 54 patients (57 BALF samples) had probable IPA and 6 patients (6 samples) had proven IPA. In 21/63 samples (33%) (from 19 patients), systemic mould-active AFs had been initiated before bronchoscopy. Of 63 BALF samples, 16 (25%) yielded a false-negative LFD result. The sensitivity of the LFD for probable/proven IPA was significantly lower in those receiving mould-active AFs compared with those without (52% vs. 86%; P=0.006). Similar results were found for BALF GM, with sensitivities decreasing under systemic AFs (71% vs. 95%, P=0.013 with the 0.5 ODI cut-off; 52% vs. 81%, P=0.036 with the 1.0 cut-off). These results suggest that the sensitivity of the BALF LFD and BALF GM assays may be reduced in the presence of mould-active AF treatment. Negative results in patients on AFs should therefore be interpreted with caution.

RationaleInvasive pulmonary aspergillosis has been increasingly reported in nonneutropenic patients, including those with underlying respiratory diseases.ObjectivesWe compared the diagnostic performances of galactomannan, 1,3-β-D-glucan, and Aspergillus-specific lateral-flow device tests with that of conventional culture by using bronchoalveolar lavage fluid samples from patients with underlying respiratory diseases.MethodsWe analyzed 268 bronchoalveolar lavage samples from 221 patients with underlying respiratory diseases (and without hematologic malignancy or previous solid organ transplantation) that were collected for routine microbiological workup between February 2012 and May 2014 at the University Hospital of Graz, Austria. Invasive pulmonary aspergillosis was defined according to European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria modified for patients with respiratory diseases.Measurements and main resultsThirty-one patients (14%) had probable or proven, 25 possible, and the remaining 165 patients no invasive pulmonary aspergillosis. Probable/proven aspergillosis was associated with a significantly higher (P = 0.034) 30-day mortality rate of 32%. Sensitivities, specificities, and diagnostic odd ratios differed markedly between galactomannan (cut-off 0.5: optical density index, 0.97, 0.81, 124.4; cut-off 1.0: 0.97, 0.93, 422.1; cut-off 3.0: 0.61, 0.99, 109.8), β-D-glucan (cut-off 80 pg/ml: 0.90, 0.42, 6.57; cut-off 200 pg/ml: 0.70, 0.61, 3.7), lateral-flow device tests (0.77, 0.92, 41.8), and mycological culture (0.29, 0.97, 14).ConclusionsProbable or proven invasive pulmonary aspergillosis was diagnosed in 14% of our study population and associated with significantly higher 30-day mortality rates. Although the performance of β-D-glucan was limited by low specificity and that of mycological culture by low sensitivity, the Aspergillus lateral-flow device seems to be a promising alternative to galactomannan testing, which remains the diagnostic gold standard for aspergillosis. Clinical trial registered with www.clinicaltrials.gov (NCT 02058316).

BackgroundLeptospirosis is one of the world's mostly spread zoonoses causing acute fever. Over years, leptospirosis has been reported to occur rarely in Austria and Germany (annual incidence of 0.06/100,000 in Germany). Only imported cases have been on the increase. Objectives of this case-series study were to retrospectively assess epidemiologic and clinical characteristics of leptospirosis illnesses in South-East Austria, to describe risk exposures for autochthonous infections, and to compare patients with imported versus autochthonous infection.Methodology/principal findingsDuring the 9-year period between 2004 and 2012, 127 adult patients (49 females, 78 males) who tested positive by rapid point-of-care test for Leptospira-specific IgM (Leptocheck®) were identified through electronic hospital databases. Follow-up telephone interviews were conducted with 82 patients. A total of 114 (89.8%) of the 127 patients enrolled had acquired leptospirosis within Austria and 13 (10.2%) had potentially imported infections. Most autochthonous cases were diagnosed during the months of June and July, whereas fewest were diagnosed during the winter months. Exposure to rodents, recreational activities in woods or wet areas, gardening, cleaning of basements or huts were the most common risk exposures found in autochthonous infection. Serogroups Australis (n = 23), Sejroe (n = 22), and Icterohaemorrhagiae (n = 11) were identified most frequently by MAT testing in autochthonous infections. Patients with imported leptospirosis were significantly younger, less likely to be icteric and had significantly lower liver transaminase levels (p = 0.004) than those with autochthonous infections.Conclusions/significanceLeptospirosis is endemic in South-East Austria. In contrast to reports from other countries we found a relatively high proportion of leptospirosis cases to be female (39% vs. ∼ 10%), likely the result of differing risk exposures for South-East Austria.

We report a case of a female patient with alveolar echinococcosis (AE) who presented with progressive pulmonary and hepatic lesions and had a fatal outcome. AE affecting the liver, the lungs and the brain had been diagnosed 20 years ago and treated successfully with albendazole and stereotactic gamma knife therapy. Due to severe hair loss albendazole was stopped 14 years before presentation. Lesions had remained stable in imaging studies for at least 11 years, but then had started to progress. Lifelong anthelmintic maintenance therapy and regular follow-up may therefore be crucial in order to prevent such a dramatic clinical course.

Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate the appropriate antiviral therapy and preventive measures. As PCR assays are time-consuming and rapid antigen tests have a limited sensitivity, official influenza case definitions are used in many clinical settings. These, however, are based exclusively on clinical criteria and have only a moderate potential to differentiate between influenza and other febrile diseases. Only limited data on the differences in clinical and laboratory parameters between influenza and non-influenza febrile diseases are available to date.This was a retrospective case-negative control series that was conducted in Styria, southeast Austria. We analyzed the differences in clinical presentation and laboratory admission parameters between patients with PCR-confirmed H1N1 influenza infection (n = 199) and those with influenza-like disease and negative influenza PCR results (ILD group; n = 252).In the multivariable analysis lower C-reactive protein (CRP) level, lower white blood cell (WBC) count, fever, wheezing, cough, and the absence of nausea or sudden onset remained significant predictors of H1N1 influenza in adult patients (n = 263). Lower CRP level, lower WBC count, and cough remained significant predictors in pediatric patients (16 years; n = 188).Lower CRP level, lower WBC count, and cough were significant predictors of H1N1 in both the adult and pediatric patient group. These data may help to develop an improved case definition for suspected H1N1 infection which combines clinical findings and easily available laboratory parameters.

Nocardia spp. are rarely isolated in extrapulmonary clinical specimens. We describe the first case of olecranon bursitis caused by Nocardia asiatica . The patient, a traveler returning from Thailand, was successfully treated with linezolid.

In recent years galactomannan antigen testing (GM) and also Aspergillus PCR have become increasingly important for diagnosis of invasive aspergillosis (IA). Whether or not these tests need to be performed with bronchoalveolar lavage fluid (BALF; i.e., primary site of infection), or testing of blood samples is sufficient, remains, however, a matter of debate. We evaluated the diagnostic performance of GM ELISA, and Aspergillus PCR by using BALF samples and blood samples obtained at the same day from a total of 53 immunocompromised patients (16 with probable/proven IA and 37 with no evidence of IA according to the revised EORTC/MSG criteria; 38 patients with hematological malignancies were prospectively enrolled at the Medical University of Graz, Austria, 15 patients with mixed underlying diseases at the Mannheim University Hospital). Patients with possible IA were excluded from this analysis. A total of 34/53 (64%) of all patients and 12/16 (75%) of patients with probable/proven IA received mold-active antifungal prophylaxis/therapy at the time of the BALF procedure. Sensitivities of GM and Aspergillus PCR were 38% and 44% in BALF, and 31% and 0% in blood, respectively. Best sensitivity (75%) for detecting proven/probable IA was achieved when BALF Aspergillus PCR, BALF GM (>1.0 ODI), BALF-culture and serum-GM (>0.5 ODI) were combined (specificity 95%). In conclusion, sensitivities of the evaluated diagnostic tests-when interpreted on their own-were low in BALF and even lower in blood, sensitivities increased markedly when diagnostic tests were combined.

Although amoebic liver abscess due to Entamoeba histolytica is one of the most common parasitic infections worldwide, invasive disease remains uncommon in industrialized countries. Metronidazole is the standard of care for complicated and uncomplicated invasive amoebiasis. Puncture of amebic liver abscesses is a treatment option primarily for complicated abscesses (localized in left lobe, multiple, and/or pyogenic abscesses). The role of image-guided percutaneous puncture in initially uncomplicated liver abscess formations still remains unanswered. A subset of patients with uncomplicated amoebic liver abscesses, however, fails to respond to conservative treatment alone. We report two cases of amoebic liver abscess formations in Austrian travelers. Two males, aged 67 and 43, presented with fever, chills and fatigue. Four months prior to admission both patients travelled together to Goa, India, for 4 weeks. Computed tomography showed uncomplicated liver abscess formations and serology for E. histolytica was positive in both patients. Therapy with metronidazole 500 mg four times daily was initiated. Computed tomography then showed an increase in size of liver abscess formations in both patients after 13 and 10 days of intravenous metronidazole therapy, respectively. Patient 1 developed pleural effusion and patient 2 additional liver abscess formations. Therefore CT-guided percutaneous therapeutic catheter drainage of liver abscess formations was performed in both patients without complications. Real time PCR of abscess drainage was positive for E. histolytica in both patients. After completion of metronidazole, paromomycin 500 mg three times daily was initiated for seven days for elimination of cysts and both patients were discharged without further complaints. This report highlights that conservative monotherapeutic treatment alone may not be sufficient in some patients with initially uncomplicated E. histolytica liver abscess. Implementation of additional image guided percutaneous puncture may reduce mortality and disease related costs.

Ascariasis is the most common helminthic infection, with an estimated worldwide prevalence of 25%. The estimated mortality ranges from 0.8 to 1%. Second stage larvae pass through the intestinal wall and migrate via the portal vein system to the liver and then proceed to the lungs, where they may produce pneumonia and eosinophilia. Symptoms include wheezing, dyspnea, nonproductive cough, hemoptysis, and fever. Two cases of pulmonary ascariasis in Austrian males are reported. Both patients presented with dyspnea, nonproductive cough, fever, and eosinophilia (19 and 26%). One patient additionally had pulmonary infiltrates. Recent travel history was unremarkable in both individuals. Serology for Ascaris was positive twice in both patients, while microscopic examination of stool was negative for helminthic ova. Extensive diagnostic procedures were performed to rule out possible differentials for the patients symptoms. Both patients responded well to antiparasitic treatment with albendazole 400 mg and mebendazole 100 mg q12h for 3 days, respectively. This report highlights the importance of considering parasitic infection in patients presenting with eosinophilia and pulmonary symptoms also in Austria.