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Since we first described Mycobacterium heckeshornense, a rare species of mycobacteria in 2000, only 21 cases of infection with this mycobacterium have been described in humans. We relate the diagnosis and therapy of another case of this uncommon nontuberculous mycobacterium in an immune-suppressed patient., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Rapid and reliable diagnostic work-up of tuberculosis (TB) remains a major healthcare goal. In particular, discrimination of TB infection from TB disease with currently available diagnostic tools is challenging and time consuming. This study aimed at establishing a standardised blood-based assay that rapidly and reliably discriminates TB infection from TB disease based on multiparameter analysis of TB antigen-reactive CD4 + T-cells acting as sensors for TB stage-specific immune status., Methods: 157 HIV-negative subjects with suspected TB infection or TB disease were recruited from local tertiary care hospitals in Berlin (Germany). Peripheral blood mononuclear cells were analysed for CD4 + T-cells reactive to the Mycobacterium tuberculosis antigens purified protein derivative and early secretory antigenic target 6 kDa/culture filtrate protein 10. The activation state of TB antigen-reactive T-cells, identified by surface expression of CD154, was evaluated according to the expression profile of proliferation marker Ki-67 and activation markers CD38 and HLA-DR. Using data from 81 subjects with clinically confirmed TB infection (n=34) or culture-proven pulmonary or extrapulmonary TB disease (n=47), 12 parameters were derived from the expression profile and integrated into a scoring system., Results: Using the scoring system, our assay (TB-Flow Assay) allowed reliable discrimination of TB infection from both pulmonary and extrapulmonary TB disease with high sensitivity (90.9%) and specificity (93.3%) as was confirmed by Monte-Carlo cross-validation., Conclusion: With low time requirement, ease of sample collection, and high sensitivity and specificity both for pulmonary and extrapulmonary TB disease, we believe this novel standardised TB-Flow Assay will improve the work-up of patients with suspected TB disease, supporting rapid TB diagnosis and facilitating treatment decisions., Competing Interests: Conflict of interest: A. Scheffold and P. Bacher are advisors to Miltenyi Biotec who own IP rights on the use of CD154 for antigen-specific T-cell detection. A. Scheffold, C. Meisel, H-D. Volk, P. Bacher, T. Meyer and A. Mantei are listed as inventors in a patent (10 2018 131 696.8) that has been issued and a patent (PCT/EP2019/084392) that is pending on the discrimination of TB infection and TB disease using the method described herein. The remaining authors declare no competing financial interests., (Copyright ©The authors 2022.)

Background: Immune checkpoint inhibitors (ICIs) are currently one of the most promising therapy options in the field of oncology. Although the first pivotal ICI trial results were published in 2011, few biomarkers exist to predict their therapy outcome. PD-L1 expression and tumor mutational burden (TMB) were proven to be sometimes-unreliable biomarkers. We have previously suggested the analysis of processing escapes, a qualitative measurement of epitope structure alterations under immune system pressure, to provide predictive information on ICI response. Here, we sought to further validate this approach and characterize interactions with different forms of immune pressure., Methods: We identified a cohort consisting of 48 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab as ICI monotherapy. Tumor samples were subjected to targeted amplicon-based sequencing using a panel of 22 cancer-associated genes covering 98 mutational hotspots. Altered antigen processing was predicted by NetChop, and MHC binding verified by NetMHC. The NanoString nCounter® platform was utilized to provide gene expression data of 770 immune-related genes. Patient data from 408 patients with NSCLC were retrieved from The Cancer Genome Atlas (TCGA) as a validation cohort., Results: The two immune escape mechanisms of PD-L1 expression (TPS score) (n = 18) and presence of altered antigen processing (n = 10) are mutually non-exclusive and can occur in the same patient (n = 6). Both mechanisms have exclusive influence on different genes and pathways, according to differential gene expression analysis and gene set enrichment analysis, respectively. Interestingly, gene expression patterns associated with altered processing were enriched in T cell and NK cell immune activity. Though both mechanisms influence different genes, they are similarly linked to increased immune activity., Conclusion: Pressure from the immune system will lay the foundations for escape mechanisms, leading to acquisition of resistance under therapy. Both PD-L1 expression and altered antigen processing are induced similarly by pronounced immunoactivity but in different context. The present data help to deepen our understanding of the underlying mechanisms behind those immune escapes., (© 2022. The Author(s).)

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objective: The qSOFA (quick sepsis-related organ failure assessment) score shows similarities to the CRB-65 pneumonia score, but its prognostic accuracy in patients with community-acquired pneumonia (CAP) has not been extensively evaluated. Our aim was to validate the qSOFA (-65) score in a large cohort of CAP patients., Methods: We conducted a retrospective population-based cohort study including all CAP cases hospitalized between 1st January 2014 and 31st December 2018 from the German nationwide mandatory quality assurance programme. We excluded cases transferred from another hospital, with mechanical ventilation present on admission, and without documented respiratory rate. Predefined outcomes were hospital mortality and need for mechanical ventilation., Results: Among the 1,262,250 included cases, hospital mortality was 12.4% and the mechanical ventilation rate was 7.1%. All CRB and qSOFA criteria were associated with both outcomes, but the qSOFA had inferior sensitivity compared to the CRB-65 for mortality prediction. Including the age criterion ≥65 years, qSOFA-65 and CRB-65 performed similarly (AUC 0.69, 95%CI 0.69-0.69 versus 0.68, 95%CI 0.68-0.68). A qSOFA-65 of 0 was associated with fewer missed deaths (3328, 2.0%) compared to a CRB-65 of 0 (5480, 2.4%). The sensitivity of the suggested qSOFA cut-off of ≥2 for sepsis was low (mortality 25.8%, 95%CI 25.6-26.0%; mechanical ventilation 24.1%, 95%CI 23.8-24.4%). Results were similar when frail and palliative patients were excluded., Conclusions: The qSOFA parameters show prognostic accuracy similar to the CRB parameters in CAP, but the sepsis cut-off of ≥2 lacked sensitivity. For sensitive mortality prediction, the age criterion ≥65 years should be added to the qSOFA., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

The majority of research within lung cancer is focused on prevention, diagnosis and treatment rather than examining infrastructure or processes of lung cancer centres. Benchmarking is a systematic method for documenting and comparing processes, functions or performance of organisations against the best in the world. ADVANCE-1 is a European Respiratory Society funded pilot study with the main aim of creating a benchmarking tool that can easily document and reflect the structure and process within a lung cancer centre and its associated registry. By doing this we can then compare centres and generate best practice learning points from each centre in order to learn from each other. The ADVANCE-1 study group was constituted by two ERS fellowship-holders and senior lung cancer specialists from the two participating lung cancer services in Glasgow, Scotland, and Berlin, Germany. The study design and benchmarking tools were reviewed externally. Once the benchmarking tools were created, prospective testing was undertaken in the two participating centres in order to allow comparison to ascertain best practice in a so called 'collaborative benchmarking approach'. We were then able to create personalised learning points for each centre. The next phase of the project will be to expand the benchmarking across several European centres in the ADANCE-2 project., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: In Germany the coronavirus disease 2019 (COVID-19) pandemic situation is unique among large European countries in that incidence and case fatality rate are distinctly lower. We describe the clinical course and examine factors associated with outcomes among patients hospitalized with COVID-19 in Germany., Methods: In this retrospective cohort study we included patients with COVID-19 admitted to a national network of German hospitals between February 12 and June 12, 2020. We examined demographic characteristics, comorbidities and clinical outcomes., Results: We included 1904 patients with a median age of 73 years, 48.5% (924/1904) of whom were female. The mortality rate was 17% (317/1835; 95% confidence interval (95%CI) 16-19), the rate of admission to the intensive care unit (ICU) was 21% (399/1860; 95%CI 20-23), and the rate of invasive mechanical ventilation was 14% (250/1850: 95%CI 12-15). The most prominent risk factors for death were male sex (hazard ratio (HR) 1.45; 95%CI 1.15-1.83), pre-existing lung disease (HR 1.61; 95%CI 1.20-2.16), and increased patient age (HR 4.11 (95%CI 2.57-6.58) for age >79 years versus <60 years). Among patients admitted to the ICU, the mortality rate was 29% (109/374; 95%CI 25-34) and higher in ventilated (33% [77/235; 95%CI 27-39]) than in non-ventilated ICU patients (23%, 32/139; 95%CI 16-30; p < 0.05)., Conclusions: In this nationwide series of patients hospitalized with COVID-19 in Germany, in-hospital and ICU mortality rates were substantial. The most prominent risk factors for death were male sex, pre-existing lung disease, and greater patient age., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Immune checkpoint inhibition, especially the blockade of PD-1 and PD-L1, has become one of the most thriving therapeutic approaches in modern oncology. Immune evasion caused by altered tumor epitope processing (so-called processing escapes) may be one way to explain immune checkpoint inhibition therapy failure. In the present study, we aim to demonstrate the effects of processing escapes on immunotherapy outcome in NSCLC patients., Patients and Methods: Whole exome sequencing data of 400 NSCLC patients (AdC and SCC) were extracted from the TCGA database. The ICB cohort was composed of primary tumor probes from 48 NSCLC patients treated with nivolumab. Mutations were identified by targeted amplicon-based sequencing including hotspots and whole exomes of 22 genes. The effect of mutations on proteasomal processing was evaluated by deep learning methods previously trained on 1260 known MHC-I ligands. Cox regression modelling was used to determine the influence on overall survival., Results: In the TCGA cohort, processing escapes were associated with decreased overall survival (p= 0.0140). In the ICB cohort, patients showing processing escapes in combination with high levels of PD-L1 (n=8/48) also showed significantly decreased overall survival, independently of mutational load or PD-L1 status., Conclusion: The concept of altered epitope processing may help to understand immunotherapy failure. Especially when combined with PD-L1 status, this method can be used as a biomarker to identify patients not suitable for immunotherapy., Competing Interests: Wilfried EE Eberhardt reports grants and personal fees from BMS and Astra Zeneca and personal fees from MSD/Merck and Roche, outside the submitted work. Jens Kollmeier reports being an Advisory Board Member (no personal fees) for Roche, Boehringer Ingelheim, Bristol-Meyers Squibb, MSD, and Takeda, outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2020 Wessolly et al.)

Against the background of the pandemic caused by infection with the SARS-CoV-2 virus, the German Respiratory Society has appointed experts to develop therapy strategies for COVID-19 patients with acute respiratory failure (ARF). Here we present key position statements including observations about the pathophysiology of (ARF). In terms of the pathophysiology of pulmonary infection with SARS-CoV-2, COVID-19 can be divided into 3 phases. Pulmonary damage in advanced COVID-19 often differs from the known changes in acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in the respiratory support of ARF. The assessment of the extent of ARF should be based on arterial or capillary blood gas analysis under room air conditions, and it needs to include the calculation of oxygen supply (measured from the variables of oxygen saturation, hemoglobin level, the corrected values of Hüfner's factor, and cardiac output). Aerosols can cause transmission of infectious, virus-laden particles. Open systems or vented systems can increase the release of respirable particles. Procedures in which the invasive ventilation system must be opened and endotracheal intubation carried out are associated with an increased risk of infection. Personal protective equipment (PPE) should have top priority because fear of contagion should not be a primary reason for intubation. Based on the current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. A significant proportion of patients with ARF present with relevant hypoxemia, which often cannot be fully corrected, even with a high inspired oxygen fraction (FiO2) under NHF. In this situation, the oxygen therapy can be escalated to CPAP or NIV when the criteria for endotracheal intubation are not met. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring and readiness for intubation are to be ensured at all times. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a "do not intubate" order., (© 2020 S. Karger AG, Basel.)

The analysis of circulating cell-free DNA (cfDNA) extracted from peripheral blood can serve as a minimally invasive alternative to tumor tissue biopsies in cases with impaired access to tissue. Its clinical utility has been well demonstrated for EGFR T790M testing in lung cancer patients suffering progress after tyrosine kinase inhibitor treatment. At present, highly sensitive unique molecular identifiers (UMI)-based NGS for liquid biopsy testing is less established compared to single gene assays. However, the critical bottleneck are sufficient cfDNA yields, which are essentially required to obtain meaningful test results. We compared four different cfDNA extraction methods (Qiagen, Promega, Thermo and Stratec) using the same plasma samples in order to evaluate their suitability for further NGS analysis. We managed to draw 60 ml blood from 12 patients each and equally collected 30ml in PAXgene and EDTA tubes at the same time point, sufficient for total of 96 cfDNA extractions. CfDNA concentrations and total amounts were highest for Qiagen and Promega protocols, showing the best read length profiles after sequencing. Known oncogenic driver mutations were identified in 9 out of 12 patients with at least one of the cfDNA extraction methods, again favoring the extraction protocols from Qiagen and Promega. We also uncovered putative sequencing artefacts including known driver genes pointing to a careful consideration for the limit of detection of this methodology. Our study shows that pre-analytical optimization is necessary to achieve the maximum sensitivity of UMI-based sequencing but also highlights the low abundance of tumor-derived cfDNA in lung cancer samples., Competing Interests: Conflicts of interest V.E. is a consultant/advisory board member for ThermoFisher and received lecture fees from AstraZeneca and Novartis. Al.S. is a consultant/advisory board member of Bayer, AstraZeneca, Bristol-Myers Squibb, Novartis, ThermoFisher and Illumina, and received speaker’s honoraria from Bayer, BMS, MSD, Roche, Illumina, AstraZeneca, Novartis and ThermoFisher, Takeda as well as research funding from Chugai and BMS. P.S. received advisory board honoraria from Pfizer, Roche, Novartis and AstraZeneca as well as speaker’s honoraria and research funding from Roche, AstraZeneca and Novartis. O.L. is the owner of TIB Molbiol., (Copyright: © 2019 Streubel et al.)

Since 2015 a significant increase in tuberculosis cases is notified in Germany, mostly due to rising numbers of migrants connected to the recent refugee crisis. Because of the low incidence in previous years, knowledge on tuberculosis is more and more limited to specialized centers. However, lung specialist and healthcare workers of other fields have contact to an increasing number of tuberculosis patients. In this situation, guidance for the management of standard therapy and especially for uncommon situations will be essential. This new guideline on tuberculosis in adults gives recommendations on diagnosis, treatment, prevention and prophylaxis. It provides a comprehensive overview over the current knowledge, adapted to the specific situation in Germany. The German Central Committee against Tuberculosis (DZK e. V.) realized this guideline on behalf of the German Respiratory Society (DGP). A specific guideline for tuberculosis in the pediatrics field will be published separately. Compared to the former recommendations of the year 2012, microbiological diagnostics and therapeutic drug management were given own sections. Chapters about the treatment of drug-resistant tuberculosis, tuberculosis in people living with HIV and pharmacological management were extended. This revised guideline aims to be a useful tool for practitioners and other health care providers to deal with the recent challenges of tuberculosis treatment in Germany., Competing Interests: Interessenkonflikt: Siehe Interessenkonflikterklärung auf www.awmf.org, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin., Methods: For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype., Results: Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00)., Conclusions: Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.

C(U)RB-65 (confusion, (urea >7 mol · L(-1),) respiratory frequency ≥ 30 breaths · min(-1), systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥ 65 years) is now the generally accepted severity score for patients with community-acquired pneumonia (CAP) in Europe. In an observational study based on the large database from the German nationwide performance measurement programme in healthcare quality, including data from all hospitalised patients with CAP during 2008-2010, different CRB-age groups (≥ 50 and ≥ 60 years) across the total CAP population and three entities of CAP (younger population aged <65 years, patients aged ≥ 65 years not residing in nursing homes and those with nursing home-acquired pneumonia (NHAP)) were validated for their potential to predict in-hospital death. 660 594 patients were investigated. Mortality was n=93 958 (14.0%). In the total population, CRB-80 had the optimal area under the curve (0.690, 95% CI 0.688-0.691). However, in the younger cohort, CRB-50 performed best (0.730, 95% CI 0.724-0.736), with good identification of low-risk patients (CRB-50 risk class 1: 1.28% deaths, negative predictive value 98.7%). In the elderly, CRB-80 as the optimal age group performed worse (0.663, 95% CI 0.660-0.655 in patients not residing in nursing homes; 0.608, 95% CI 0.605-0.611 in those with NHAP). In the latter group, all CRB-age groups failed to identify low-risk patients (CRB-80 risk class 1: 22.75% deaths, negative predictive value 81.8%). Patients with hospitalised CAP aged <65 years may be assessed by the CRB-50 score. In those aged ≥65 years (not NHAP) assessed by the CRB-65 score, low-risk patients are already are at an increased risk of death. In NHAP patients, even the use of CRB-80 does not identify low-risk patients and should be accompanied by the evaluation of functional status and comorbidity.

In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.

Background: Pneumonia accounts for almost half of intensive care unit (ICU) infections and nearly 60% of deaths from nosocomial infections. It increases hospital stay by 7-9 days, crude mortality by 70% and attributable mortality by 30%., Objective: Our purpose was to assess the impact of standard operating procedures adapted to the local resistance rates in the initial empirical treatment for pneumonia on duration of first pneumonia episode, duration of mechanical ventilation, and length of ICU stay., Design: Prospective observational cohort study with retrospective expert audit., Setting: Five anesthesiologically managed ICUs at University hospital (one cardio-surgical, one neurosurgical, two interdisciplinary, and one intermediate care)., Patients: Of 524 consecutive patients with > or = 36 hr ICU treatment 131 patients with pneumonia on ICU were identified. Their first pneumonia episode was evaluated daily for adherence to standard operating procedures. Pneumonia was diagnosed according to the American Thoracic Society guidelines. Patients with > 70% compliance were assigned to high adherence group (HAG), patients with < or = 70% to low adherence group (LAG)., Measurements and Results: HAG consisted of 45 (49 first episode) patients, LAG of 86 (82 first episode) patients, respectively. Mean duration of treatment of the first pneumonia episode was 10.11 +/- 7.95 days in the LAG and 6.22 +/- 3.27 days in the HAG (p = 0.001). Duration of mechanical ventilation was 317.59 +/- 336.18 hrs in the LAG and 178.07 +/- 191.33 hrs in the HAG (p = 0.017). Length of ICU stay was 20.24 +/- 16.59 days in the LAG and 12.04 +/- 10.42 days in the HAG (p = 0.001)., Limitations: Barriers in compliance need further evaluation., Conclusion: Adherence to standard operating procedure is associated with a shorter duration of treatment of first pneumonia episode, a shorter duration of mechanical ventilation, and a shorter ICU stay.

Introduction: To date, the resistance of infectious agents has been assessed by widely varying criteria in different countries. Therefore, published data on resistance often cannot be meaningfully compared. In Germany, different laboratories can potentially report different results for identical microorganisms, since there is no uniform system for categorization. This situation is unsatisfactory., Methods: Selective literature review and evaluation of committee reports., Results: The new ISO standard 20776 for determination of the resistance of infectious agents and the harmonized evaluation system of the European Society for Clinical Microbiology and Infectious Diseases provide a new basis for susceptibility testing. The categorization of infectious agents as "susceptible," "intermediate," or "resistant" to particular antibiotics will become more reliable and will be consistent throughout Europe., Discussion: For a number of antibiotics, the criteria for evaluation of infectious agents as "susceptible," "intermediate", or "resistant" will change. Comparability with earlier resistance data will be compromised. However, the new evaluation criteria reflect current knowledge on the pharmacokinetics and pharmacodynamics of antimicrobial substances.

Purpose of Review: Dust-induced occupational lung diseases comprise a vast variety of causative agents. These largely preventable illnesses not only afflict lung parenchyma but also bronchi, bronchioles, as well as mediastinal and pleural structures. Chest radiography undisputedly has value in screening thoracic manifestations of occupational diseases, but also has its limitations. Obviously, modern high-resolution computed tomography improves the visibility of tissue changes, in particular in early disease stages; however, the crucial correlation of radiologic and clinical findings in this heterogeneous group of patients has been seldom addressed in the past., Recent Findings: The most encouraging results of a Medline search for the years 2004-2007 are presented. Beside an international standardized high-resolution computed tomography classification for pneumoconiosis, several other innovative scoring systems are highlighted. Furthermore, the clinical impact of high-resolution computed tomography is stressed in the context of the limited applicability of conventional radiography., Summary: High-resolution computed tomography is a powerful diagnostic and prognostic tool for assessment of dust-induced occupational lung diseases in compliance with promising recent findings. Novel evidence, however, is limited for these occupational diseases.

The effect of food components on degradation of DNA by DNase I (EC 3.1.21.1) was monitored by electrotransformation of Escherichia coil, making it possible to determine the number of plasmid molecules capable of giving rise to transformed cells. The transformation frequency increased linearly with the plasmid number within the range of 2 x 10(6) to 2 x 10(10). DNA degradation was reduced by one order of magnitude in the presence of 0.05% (w.v(-1)) maltol or 1 mM putrescine. Complete inhibition of degradation was observed with > or = 0.2% (w.v(-1)) maltol, > or = 0.01% (w.v(-1)) octyl gallate or > or = 0.5 mM of spermine. To monitor degradation of plant DNA during food processing, a real-time PCR system was established. The ratio of copy numbers of a potato gbss DNA fragment of 325 bp and a nested 96 bp fragment was determined. The latter served as internal reference for normalization. The system made it possible to exclude process-dependent changes of DNA concentration in the food matrix. Processing of genetically modified potatoes to dried potato sticks, crisps or flakes was studied and drying steps were shown to exert the strongest effect on DNA degradation, resulting in a drop of the ratio from 0.73 to 0.16.

Soymilk, tofu, corn masa, and cooked potato were produced from transgenic raw materials and the effect of processing on the degradation of DNA was studied. Major degrading factors were for soymilk and tofu the mechanical treatment of soaked soybeans and for corn masa and cooked potatoes the thermal treatment. In the processed foods no DNA fragments > 1.1 kb were detected. We included in our studies the effect of the size of donor DNA and length of the homologous sequence on the marker rescue transformation of B. subtilis LTH 5466, which was monitored by restoration of deleted nptII. When DNA fragments (168, 414, 658, and 792 bp) of nptII and linearized plasmid DNA (pGEM-T-1, 3168 bp and pGEM-T-2, 3792 bp) containing the 168 bp or 792 bp fragments, respectively, were used as donor DNA, it was observed that the efficiency of marker rescue decreased with decreasing length of homologous sequence. The use of a larger plasmid (pMR2, 5786 bp) containing the 792 bp fragment revealed higher efficiency of marker rescue compared to pGEM-T-2. The nptII fragments resulted in lower efficiencies compared to plasmid DNA containing the same fragment. For the 792 bp fragment and the linearized plasmid pMR2 a first-order dependency of the frequency of marker rescue transformation on the DNA concentration was observed. Based on the acquired data, the hypothetical frequency of transformation of transgenic DNA to B. subtilis in cooked potatoes was calculated to be equal to 8.5 x 10(-19) and 1.2 x 10(-27) for homologous and illegitimate recombination, respectively. These data permit to roughly estimate the time after which a person (10(8) years) or the world population (15 days) is exposed to one transformant generated by homologous recombination event, when the daily consumption per person is 130 g of cooked potatoes.