[Smoking Cessation with E-Cigarettes? - Ad Hoc Statement of the German Respiratory Society (DGP)]. / Tabakentwöhnung mit E-Zigarette?

The German Respiratory Society (DGP) turns against the e-cigarette as a means for harm reduction because of potential health risk and dangers to young people. The aerosol of e-cigarettes contains toxic ingredients that have been shown to be damaging to the lungs, the cardiovascular system and the immune system and are potentially carcinogenic. Studies on e-cigarettes as a means of smoking cessation are not very convincing, in order to favor e-cigarettes over nicotine replacement therapy, which have been tried and tested for many years, or other drugs that reduce the desire to smoke.

[Weaning in a Pandemic Situation - A Position Paper]. / Weaning in der Situation einer Pandemie ­ Ein Positionspapier.

The logistical and infectious peculiarities and requirements challenge the intensive care treatment teams aiming at a successful liberation of patients from long-term mechanical ventilation. Especially in the pandemic, it is therefore important to use all potentials for weaning and decannulation, respectively, in patients with prolonged weaning.Weaning centers represent units of intensive medical care with a particular specialization in prolonged weaning. They are an integral part of a continuous care concept for these patients. A systematic weaning concept in the pandemic includes structural, personnel, equipment, infectiological and hygienic issues. In addition to the S2k guideline "Prolonged weaning" this position paper hightlights a new classification in prolonged weaning and organizational structures required in the future for the challenging pandemic situation. Category A patients with high weaning potential require a structured respiratory weaning in specialized weaning units, so as to get the greatest possible chance to realize successful weaning. Patients in category B with low or currently nonexistent weaning potential should receive a weaning attempt after an intermediate phase of further stabilization in an out-of-hospital ventilator unit. Category C patients with no weaning potential require a permanent out-of-hospital care, alternatively finishing mechanical ventilation with palliative support.Finally, under perspective in the position paper the following conceivable networks and registers in the future are presented: 1. locally organized regional networks of certified weaning centers, 2. a central, nationwide register of weaning capacities accordingly the already existing DIVI register and 3. registration of patients in difficult or prolonged weaning.

[Rehabilitation of orphan diseases in adulthood: osteogenesis imperfecta]. / Rehabilitation seltener Erkrankungen im Erwachsenenalter: Osteogenesis imperfecta.

Osteogenesis imperfecta (brittle bone disease) is an orphan disease caused by a genetic mutation in collagen metabolism. Bone fractures are the most common symptoms; however, the clinical manifestation can vary widely. Additional features can include blue sclera, dwarfism, bone deformities, muscular weakness, scoliosis, hearing loss and hypermobility of joints. Most patients show a reduction of skeletal function. This leads to an increased risk of being unable to continue their former work and to participate in social life. A comprehensive treatment includes drug therapy, surgery and rehabilitation. This article gives an overview of the current status of rehabilitation in adult patients with osteogenesis imperfecta.

[Procalcitonin in the intensive care unit : Differential diagnostic and differential therapeutic possibilities]. / Prokalzitonin auf der Intensivstation : Differenzialdiagnose und Differenzialtherapie.

Procalcitonin (PCT) is formed in IL6-mediated, IL8-mediated, and TNFα-mediated systemic inflammation conditions, in multiple organs and structures of the body. In patients with sepsis, significantly increased PCT levels are found. The PCT levels are highly correlated with the severity of the illness, and decreased PCT levels under therapy correlates with a better prognosis. In the differential diagnosis, measuring the PCT level helps differentiate between bacterial and viral infections. Noninfectious inflammatory reactions can, however, show moderately increased PCT levels. Cut-off values depend on renal and hepatic function. A therapeutic algorithm using PCT levels could be used for determining duration of a course of antibiotics, which can reduce antibiotic usage. In this paper, the differential diagnostic and differential therapeutic possibilities of PCT levels for critically ill patients are discussed.

[The Diagnosis is Obvious]. / Die Diagnose liegt auf der Hand.

Clinically amyopathic dermatomyositis (CADM) is a rare entity of dermatomyositis. As a rule, CADM presents without muscular involvement. Thus, the level of creatine kinase is most commonly within the normal range. Dermal manifestations of CADM are Gottron's papules and mechanic's hands. In the case of melanoma differentiation-associated gene 5 intracellular pathogen sensor (MDa5 antibodies), CADM is often associated with a rapidly progressive and severe form of interstitial lung disease. Pulmonary function tests reveal restriction and hypoxemia of varying degree. Features of ground-glass opacities, reticulations and consolidations are detected in high-resolution CT scan. Lymphocytes are sometimes predominant in bronchioloalveolar lavage. Pathologists see a picture similar to non-specific interstitial lung disease or organizing pneumonia. Pronounced immunosuppression is the most common therapy. However, sometimes a combination of different immunosuppressive therapies is necessary. A novel strategy to treat CADM with rapidly progressive interstitial lung disease is the Janus kinase inhibitor tofacitinib. Treatment can be monitored with the level of ferritin and MDa5-antibody titer. Mortality is as high as 84 %.

[Diagnostics and Treatment of Cardiac Sarcoidosis - Consensus Paper of the German Respiratory Society (DGP) and the German Cardiac Society (DGK)]. / Diagnostik und Therapie der kardialen Sarkoidose.

Sarcoidosis is a multisystemic granulomatous disorder which affects the respiratory system in the majority of the cases. Symptomatic cardiac manifestations are found in less than 10 % of the affected cohorts and show a large heterogeneity based on the ethnic background. Cardiac sarcoidosis is not only found in patients with rhythmogenic heart disease, such as atrial and ventricular fibrillation but also in all phenotypes of cardiomyopathy. The overall morbidity and mortality caused by cardiac sarcoidosis in Germany remains unclear and large prospective international observational studies.underline the importance of this disease entity. This consensus paper on diagnostic and therapeutic algorithms for cardiac sarcoidosis is based on a current literature search and forms an expert opinion statement under the auspices of the German Respiratory Society and the German Cardiac Society. The rationale of this statement is to provide algorithms to facilitate clinical decision-making based on the individual case situation.

[Joint Statement of the German Radiological Society and the German Respiratory Society on a Quality-Assured Early Detection Program for Lung Cancer with Low-dose CT]. / Positionspapier der Deutschen Röntgengesellschaft und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin zu einem qualitätsgesicherten Früherkennungsprogramm des Lungenkarzinoms mittels Niedrigdosis-CT.

Substantial new data on early detection of lung cancer with low-dose CT has become available since the last joint statement of the German Roentgenological Society and the German Respiratory Society was published in 2011. The German S3 guideline on lung cancer was revised in 2018 and now contains a weak recommendation towards early detection of lung cancer with low-dose CT in a quality-assured early detection program. These new developments required a repositioning of the involved professional societies. This present joint statement describes main features of a quality-assured program for early detection of lung cancer with low-dose CT in Germany.

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview.

In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

[Crazy Paving Pattern of the Lung]. / Pflastersteine in der Lunge.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease. PAP results from impaired surfactant clearance. In adults, autoimmune pulmonary alveolar proteinosis is present in 90 - 95 % of the cases. In 5 - 10 %, other etiologies such as toxins and dust exposure, hematological disorders and infections have to be considered. Men between 30 - 60 years are commonly affected. Typical symptoms are cough, dyspnea and alteration in ventilatory function. CT scan of the lung is characterised by a crazy paving pattern. In serological testing, granulocyte macrophage colony-stimulation factor can be identified in most patients with autoimmune pulmonary alveolar proteinosis. Whole-lung lavage remains the therapy of choice. In the current case, treatment with whole-lung lavage resulted in clinical and functional improvement.

[Expert Knowledge and Supporting Advice for the Clinical Use of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis]. / Erfahrungen und unterstützende Hinweise zur Anwendung von Nintedanib bei Patienten mit idiopathischer Lungenfibrose.

In October 2016, a group of German IPF experts were invited by Boehringer Ingelheim to meet in Frankfurt with the aim, (a) to discuss relevant aspects of the management and treatment of idiopathic pulmonary fibrosis (IPF) using nintedanib; and, (b) to provide supportive advice for daily clinical practice with nintedanib. The resulting information compiled in this document is confined to practical issues regarding the use of nintedanib in patients with IPF. Where different therapeutic options were available, the choice of IPF medication was not discussed and the experts alluded to current guidelines for the diagnosis and treatment of IPF.The participants discussed a comprehensive spectrum of clinical questions related to 10 different topics, including patient-related aspects at initiation of IPF therapy, the treatment of anticoagulated IPF patients, and the handling of nintedanib-related adverse events such as gastrointestinal side effects and elevated liver enzymes. In addition, the experts evaluated therapeutic options for IPF patients with continuous disease progression, clinical scenarios that justify discontinuation of nintedanib treatment, and therapeutic options for IPF patients with an acute exacerbation or severe infection. Finally, the participants discussed the handling of nintendanib before/after elective surgical intervention (e. g. lung transplantation) and the current evidence for antifibrotic combination therapy in patients with IPF.For each topic discussed, the resulting information incorporates published evidence from clinical trials. In case of insufficient or lacking evidence, the experts have formulated recommendations based on their personal clinical experience and evaluation.

[A Rare Cause of a Spontaneous Pneumothorax]. / Seltene Ursache eines Spontanpneumothorax.

A young patient presented himself to the emergency department with sudden-onset, breathing-dependent right-sided thoracic pain. The auscultation revealed diminished breath sounds on the right. The radiograph showed a pneumothorax which was immediately dealt with chest tube drainage. The CT scan of the thorax showed minuscule subpleural bullae. Video-assisted thoracoscopic surgery (VATS) was performed due to persistent fistulae formation through the drain. The subpleural, bullous and emphysematous changes were histologically confirmed. Investigations into the cause showed evidence of alpha-1-antitrypsin deficiency (AATD). The patient is a Pi MZ type. Few cases of spontaneous pneumothorax as the first manifestation of alpha-1-antitrypsin deficiency have been described. Conclusion: When diagnosing primary spontaneous pneumothorax, alpha-1-antitrypsin deficiency should be considered.

MLL-ENL-mediated leukemia initiation at the interface of lymphoid commitment.

Translocations involving the mixed lineage leukemia-1 are recurrent events in acute leukemia and associate with lymphoid (ALL), myeloid (AML) or mixed lineage (MLL) subtypes. Despite an association with ALL in humans, murine MLL fusion models are persistently restricted to AML. We here explored this issue using an inducible mixed lineage leukemia-eleven nineteen leukemia (MLL-ENL) mouse model. Although multiple progenitor cell types with myeloid potential are potent AML leukemia-initiating cells, also the earliest lymphoid progenitors were capable of initiating AML. This ability to evoke a latent myeloid potential in the earliest lymphoid progenitors was lost upon further lymphoid commitment. At the same time, more downstream/committed lymphoid precursors also failed to initiate lymphoid leukemia. Co-expression of MLL-ENL with a constitutively active RAS allele, the most common co-mutation in MLL fusion leukemias, could influence on both disease latency and lineage assignment of developing leukemia in what appears to be a mutation-order-dependent manner. Finally, CEBPB-mediated transdifferentation of committed and otherwise leukemia-incompetent B-cell progenitors imbued these cells with leukemic competence for AML. Therefore, apart from providing detailed insight into the differential responsiveness of candidate target cells to a first-hit MLL fusion event, our data warrants caution to therapeutic approaches based on the concept of transdifferentiation.

[Severe therapy refractive osteoporosis : A rare differential diagnosis]. / Schwere therapierefraktäre Osteoporose : Eine seltene Differenzialdiagnose.

Systemic mastocytosis is defined as a clonal increase of mast cells. We report on four patients with severe osteoporosis and histologically confirmed systemic mastocytosis. In spite of antiresorptive therapy the patients developed further vertebral fractures and suffered from ostealgia. Systemic mastocytosis is an important differential diagnosis in patients with therapy refractive and unexplained osteoporosis. Skin involvement (urticaria pigmentosa) is a rare occurrence and in most cases an isolated involvement of bone marrow is present. Determination of serum tryptase can provide indications for systemic mastocytosis but the diagnosis is only confirmed by bone marrow biopsy. There is a high risk of vertebral fractures and patients should be treated in specialized centers. Zoledronic acid can be a therapeutic option for indolent osteoporosis associated with systemic mastocytosis.

[Position Paper: Significance of the Forced Vital Capacity in Idiopathic Pulmonary Fibrosis]. / Positionspapier zur Bedeutung der forcierten Vitalkapazität für Patienten mit idiopathischer Lungenfibrose (IPF).

Spirometry is a highly standardized method which allows to measure the forced vital capacity (FVC) with high precision and reproducibility. In patients with IPF FVC is directly linked to the disease process which is characterized by scaring of alveoli and shrinkage of the lungs. Consequently, there is ample evidence form clinical studies that the decline of FVC over time is consistently associated with mortality in IPF. As for the first time effective drugs for the treatment of IPF are available it becomes obvious that in studies which could demonstrate that the drug reduces FVC decline, a numerical effect on mortality was also observed, while in one study where a significant effect on FVC decline was missed, there was also no change in mortality. Based on these studies FVC decline is a validated surrogate of mortality in IPF. It is concluded that FVC decline is not only accepted as an endpoint of clinical treatment trials in IPF but is also valid as a patient related outcome parameter which should be considered for the assessment of the efficacy of an IPF drug.

Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes.

Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials. Both anti-CD22-MMAE and anti-CD79B-MMAE were highly active and induced cell death in the vast majority of activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL cell lines. Similarly, both agents induced cytotoxicity in models with and without mutations in the signaling molecule CD79B. In line with these observations, relapsed and refractory DLBCL patients of both subtypes responded to these agents. Importantly, a strong correlation between CD22 and CD79B expression in vitro and in vivo was not detectable, indicating that patients should not be excluded from anti-CD22-MMAE or anti-CD79B-MMAE treatment because of low target expression. In summary, these studies suggest that pinatuzumab vedotin and polatuzumab vedotin are active agents for the treatment of patients with different subtypes of DLBCL.

[Therapeutic relevance of HRCT findings from a pneumological viewpoint]. / Therapeutische Relevanz des HRCT-Befundes aus pneumologischer Sicht.

The high-resolution computed tomography (HRCT) technique is an essential component in diagnosing interstitial lung disease (ILD) as it provides important and specialized information and a much greater accuracy than chest X-rays. It contributes to a narrowing down of the differential diagnoses and is also important for planning further invasive investigations, e.g. bronchoscopy, bronchoalveolar lavage, transbronchial lung biopsy and surgical lung biopsy, if needed. An accurate diagnosis of ILD is based on a multidisciplinary discussion involving pulmonologists, radiologists and pathologists experienced in the diagnosis of ILD.The therapy approaches of five different entities of ILD are shown as examples. In hypersensitivity pneumonitis the mainstay of treatment is complete avoidance of exposure to the provoking antigen. In cryptogenic organizing pneumonia most patients recover with corticosteroid therapy with prednisolone over a period of 6 months to 1 year. In cases of sarcoidosis therapy depends on organ involvement and functional impairment but there is no durable benefit to routine treatment of patients with acute pulmonary sarcoidosis, even among those with stage II or III chest radiographs. In general, patients with severe or progressive disease will require treatment.In idiopathic pulmonary fibrosis (IPF) a confident radiological diagnosis of definitive usual interstitial pneumonia (UIP) obviates the need for surgical lung biopsy. Other etiologies of a HRCT pattern of UIP, such as domestic and occupational environmental exposure, connective tissue disease and drug toxicity must be ruled out. In IPF antifibrotic therapy with pirfenidone (approval since 2011) or the triple tyrosine kinase inhibitor nintendanib (pending approval in 2015) can reduce disease progression but therapy with acetylcysteine alone or in combination with prednisolone and azathioprine failed to meet efficacy endpoints. In the management of scleroderma associated ILD rapid semiquantitative evaluation of the extent of the disease on HRCT > 20% is useful for identifying patients who require treatment.

[Smoking cessation in patients with COPD]. / Tabakentwöhnung bei COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Cigarette smoking is the main cause of COPD. Quitting smoking is thus the most effective treatment strategy and central in COPD prevention. A number of guidelines on prevention, diagnosis, therapy and rehabilitation of COPD have been published. To help implementing and standardizing smoking cessation in COPD a guideline was published 2008 in Germany focusing on this complex issue. The present guideline is an update of the 2008 guideline and has a high grade of evidence (S3 according to the AWMF; Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften). The guideline gives comprehensive and practical information on how to integrate smoking cessation as an central part of COPD therapy.

The clinical significance of anaemia and disturbed iron homeostasis in chronic respiratory failure.

BACKGROUND: Anaemia is a frequent, clinically relevant condition in various chronic diseases. It seems also to be prevalent in patients with chronic respiratory failure (CRF). We studied the characteristics of anaemia in CRF and its associations with clinical outcome. METHODS: In a prospective design, 271 consecutive patients with CRF were evaluated; patients with other conditions often associated with anaemia were excluded. Haematological laboratory and physiological parameters, health-related quality of life (HRQL), dyspnoea and 48-month survival were determined. Anaemia was defined according to WHO [haemoglobin (Hb)< 13 g/l (male); Hb< 12 g/dl (female)] and using an established algorithm. RESULTS: Among 185 patients included, 18.4% showed anaemia, not depending on chronic obstructive pulmonary disease (COPD) vs. non-COPD (17.6% vs. 19.0%; p = 0.851) or on gender [16.5% (female) vs. 19.8% (male); p = 0.702]. Anaemic patients had higher age, creatinine (p < 0.05 each) and erythropoietin levels (p < 0.001), but lower transferrin saturation (TSAT), serum iron and vitamin B12 levels (p < 0.01 each). By definition, most anaemic patients (67.6%) had disturbances in iron homeostasis according to 'anaemia of chronic disease' and/or true iron deficiency anaemia. Hb was independently related to dyspnoea and HRQL, while TSAT ≥ 20% was linked to less dyspnoea and better subjective exercise capability. Non-survivors had lower Hb and serum iron levels (p < 0.05 each). In multivariate analysis, lower serum iron levels and TSAT were independently associated with mortality (p < 0.05 each). CONCLUSION: Anaemia was common in patients with CRF and often because of disturbed iron homeostasis. Hb and TSAT were linked to functional outcome and HRQL. Lower serum iron levels and TSAT were independent prognostic parameters.

[Chronic critically ill patients from a pneumological perspective]. / Der kritisch chronisch kranke Patient aus pneumologischer Sicht.

Epidemiological estimates predict an increase in patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) or asthma; therefore, increasing numbers of patients with preexisting lung diseases who require intensive care treatment are to be expected. These patients tend to have complex disease patterns and are difficult to wean from mechanical ventilation after intubation. It is not uncommon for these patients to need permanent mechanical ventilation after an acute illness. Also the question of limiting therapy, the need for treatment with a palliative objective and supervision of patients as well as their relatives at the end of life is a challenge for intensive care physicians when treating acutely ill patients with chronic pulmonary diseases.

[German guideline for diagnosis and management of idiopathic pulmonary fibrosis]. / S2K-Leitlinie zur Diagnostik und Therapie der idiopathischen Lungenfibrose.

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.