[German Guideline for Idiopathic Pulmonary Fibrosis]. / S2K-Leitlinie zur Diagnostik der idiopathischen Lungenfibrose.

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since publication of the international IPF guideline in the year 2011 and Update 2018 several studies and technical advances occurred, which made a new assessment of the diagnostic process mandatory. In view of the antifibrotic drugs which have been approved for the treatment of IPF patients, the goal of this guideline is to foster early, confident and effective diagnosis of IPF. The guideline focusses on the typical clinical setting of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardised questionnaires, serologic testing and cellular analysis of bronchoalveolar lavage. High resolution computed tomography remains crucial in the diagnostic work-up. If it is necessary to obtain specimen for histology transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom bronchoscopic diagnosis did not provide the information needed. Despite considerable progress, IPF remains a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis.

[Migration and Tuberculosis]. / Migration und Tuberkulose.

The majority of the people suffering from tuberculosis in Germany are migrants. The treatment of this demographic still presents certain challenges. Only up to a quarter to a fifth of tuberculosis cases in migrants is being diagnosed by the screening methods that were implemented by The German Protection against Infection Act (Infektionsschutzgesetz, IfSG). Reactivation of latent tuberculosis is the most common cause for tuberculosis in migrants. Easy access to health care is vital for the testing and treatment of latent tuberculosis in people with a high risk of reactivation. The level of infection risk, comorbidities and presentation of disease vary depending on the country of origin. Especially during migration people are more susceptible to somatic and mental maladies. Extrapulmonary tuberculosis is frequent in migrants and requires specific diagnostic approaches. Where risk factors for a multi-drug-resistant tuberculosis are present, this condition has to be actively excluded. To facilitate diagnosis and therapy of tuberculosis in migrants a high level of trust has to be established in the doctor-patient relationship. Therefore and despite of cultural and linguistic differences empathy and time are key. Patients need to be encouraged to complete their treatment rather than terminate it prematurely. To that end comorbidities have also to be diagnosed and treated, social and legal aspects have to be considered.

Intra-patient comparison of parietal pleural biopsies by rigid forceps, flexible forceps and cryoprobe obtained during medical thoracoscopy: a prospective series of 80 cases with pleural effusion.

BACKGROUND: There is only few data available on the use of cryotechnique during medical thoracoscopy. METHODS: Medical thoracoscopy was performed in consecutive patients with pleural effusion. Prospectively, biopsies were taken by rigid forceps, flexible forceps and cryoprobe. Specimen size, depth and diagnostic yield were compared. RESULTS: 80 Patients were included. 408 biopsies were taken (205 rigid biopsies, 104 flexible biopsies, 99 cryobiopsies). Mean surface area of rigid biopsies was 22.6 ± 20.4 mm(2) (flexible biopsies: 7.1 ± 9.3 mm(2), cryobiopsies: 14.4 ± 12.8 mm(2)). Rigid biopsies were significantly larger than cryobiopsies (p < 0.001) and flexible biopsies (p < 0.001), crybiopsies were significantly larger than flexible biopsies (p < 0.01). A deep biopsy containing fatty tissue was harvested in 63 % of rigid biopsies (cryobiopsy: 49.5 % flexible biopsy: 39.5 %). In 79/80 cases (98.7 % 95 % CI cannot be calculated) a diagnosis was obtained by rigid biopsy (cryobiopsy: 73/80 cases (91.3 % 95 % CI 86.0 - 96.5 %), flexible biopsy: 74/80 cases (92.5 % 95 % CI 88.6 - 97.4 %)). Diagnostic yield achieved with cryobiopsies was inferior to the yield of rigid biopsies (Difference: 12.7 %), but non-inferior to flexible biopsies (Difference: 6.5 %). CONCLUSION: Cryobiopsies in medical thoracoscopy are safe with high diagnostic yield, non-inferior to flexible biopsies with increased tissue quantity and quality. Cryotechnique can develop an important role in medical thoracoscopy in the near future when rigid thoracoscopy is not available.

[Pneumology and Sports: An Outpatient Endurance Training with Sports Medical Guidance as an Effective Non-pharmacological Therapy in Pneumology - a Feasibility Study]. / Pneumologie und Sport: Ein ambulantes Ausdauertraining mit sportmedizinischer Anleitung als effektive nicht-medikamentöse Therapiemaßnahme in der Pneumologie - eine Projektstudie.

BACKGROUND: In the process of medical rehabilitation muscular endurance training is the main focus. Unfortunately, outpatient rehabilitation opportunities are limited and specialized pulmonary exercise groups ("lung sport groups") rarely available. Therefore we developed an outpatient endurance sports program for patients with respiratory diseases and evaluated its effectiveness. METHODS: In this feasibility study 31 patients (50 ±â€Š15 years) with diverse respiratory diseases were included. By professional functional exercise testing (incl. CPET and lactate measurement according to the standards of DGP and DGSP) the patients optimal training zone was determined and an individualized 12 week lasting aerobic endurance training with ≥ 3 sessions of 20 - 60 min/week realized. RESULTS: After completion of the exercise training program a significant improvement in dyspnoea (Borg-Scale: 65.7 ±â€Š12.2 vs. 62.2 ±â€Š12.6, p = 0.013), body constitution (BMI: 25.7 ±â€Š3.3 vs. 24.3 ±â€Š3.2 kg/m(2), p = 0.018; portion of body fat: 24.8 ±â€Š5.8 vs. 23.8 ±â€Š6.4 %, p = 0.043) as well as physical capacity (VO2 at 4 mmol/l Laktat: 24.2 ±â€Š6.9 vs. 26.5 ±â€Š7.6 ml/min/kg, p < 0.01; performance at 4 mmol/l Laktat: running/walking (n = 14) + 1.1 km/h, p = 0.018 and biking/bicycle ergometer (n = 17) + 8.7 Watt, p = 0.019) was recorded. These positive developments were also observed in mental and physical quality of life (quality of life questionnaire SF-36: physical score + 9.7 points, mental score + 4.5 points). CONCLUSION: The evaluated exercise program can easily be trained by the patient in a self-dependent setting and was seen to be an effective sports medical treatment in patients with diverse pulmonary diseases.

[Non Tuberculous Mycobacteria--a Short Review about Epidemiology, Diagnosis and Treatment]. / Nichttuberkulöse Mykobakterien--eine kurze Übersicht zur Epidemiologie, Diagnostik und Therapie.

Non tuberculous mycobacterial diseases are caused by mycobacteria other than M. tuberculosis complex. NTM are found in the environment and are not transmitted from humans to humans. Infection occurs by the inhalation of dust or aerosols. The finding of NTM is not equal to a diagnosis of active disease. For the diagnosis of active disease well defined clinical and microbiological criteria have to be fulfilled. Gold standard is the detection of NTM by culture, in the case of pulmonary NTM at least two times. There is no established susceptibility testing. Treatment mostly consists of three drugs, given for up to 24 months.

[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.

[50 years WATL (Scientific Working Group for the Therapy of Lung Diseases)]. / 50 Jahre WATL (Wissenschaftliche Arbeitsgemeinschaft für die Therapie von Lungenkrankheiten e.V.).

On the occasion of the 50th anniversary of the Scientific Working Group for the Therapy of Lung Diseases (WATL) the history is described from its foundation to the present situation. Research topics during this long period are specified and the studies are briefly outlined. In the beginning, WATL was engaged mainly in studies on tuberculosis, later on, the spectrum of WATL was broadened considerably to diseases like sarcoidosis, pulmonary Langerhans' cell histiocytosis, pulmonary emphysema due to α1-antitrypsin deficiency, chronic obstructive bronchitis and bronchial asthma as well as nontuberculous mycobacterioses. Finally, realising that the methodological capabilities of WATL were not sufficient to conduct large trials in classical lung diseases considering current requirements, WATL has begun to acquire competence in rare lung diseases such as lymphangioleiomyomatosis and alveolar proteinosis. In addition, WATL is dedicated to educative aims by organising conferences on topics which are not part of main stream respiratory medicine.

[Pathogenicity of Mycobacterium kansasii]. / Pathogenität von Mycobacterium kansasii.

BACKGROUND: In a recent prospective study on pulmonary infections with non-tuberculous mycobacteria (NTM) led by the WATL group, disease rates in patients with M. kansasii infection were found to be 100 %. In the present study we re-evaluated the pathogenicity of M. kansasii infections in a large lung diseases treatment center in Berlin (Lungenklinik Heckeshorn). METHODS: All patients in whose respiratory specimen cultures M. kansasii was detected between January 2003 and June 2013 were included. The 2007 ATS diagnostic criteria were applied to differentiate disease from asymptomatic infection. The strains were further investigated by sequencing of the 16S-23S rDNA internal transcribed spacer (ITS) region. RESULTS: We evaluated 43 consecutive cases. Complete patient data were available in 38 cases. In one patient, no culture results were obtained, in 37 patients M. kansasii was isolated and patient data could be retrieved. In 25/37 patients (68 %) clinical disease was present so that a specific treatment was initiated (underlying diseases were COPD in 8/25 (32 %), bronchiectasis in 5/25 (20 %), TB scar or scar due to prior chest surgery in 3/25 (12 %) and alcohol abuse in 4/25 (16 %)). Twelve out of 37 patients (32 %) were found to be colonized or asymptomatically infected (underlying diseases were COPD in 7/12 (58 %), bronchiectasis in 3/12 (25 %) and TB scar or scar due to prior chest surgery in 3/12 (25 %)). Sequencing results identified 30 strains as genotype I, and 2 strains as genotype II. In 22/30 cases (73 %) genotype I was considered pathogenic. CONCLUSIONS: In our cohort, we could not confirm the high M. kansasii pathogenicity of 100 % found in a previous multi-center study; we therefore support the clinical and semiquantitative microbiologic diagnostic criteria also for infection with M. kansasii.

[Resistance to second-line drugs in migrants with multidrug-resistant tuberculosis in the Berlin region]. / Resistenzen gegen Zweitlinienmedikamente bei Migranten mit multiresistenter Tuberkulose in der Region Berlin.

The empiric therapy of multidrug-resistant (MDR) tuberculosis (TB) after rapid molecular testing is rendered difficult by an often several weeks-long period of uncertainty, because results of susceptibility testing for second-line TB drugs are pending. The analysis of regional resistance patterns could lead to a more targeted empiric treatment for migrants depending on their country of origin. The results of the susceptibility testing from 2008 to 2013 of all mycobacteria sent to the Institute of Microbiology, working with the department of Pneumology, Heckeshorn Lung Clinic, Berlin, were reanalysed and tested for regional differences. We found 39 multidrug-resistant Mycobacterium tuberculosis strains among the examined strains. More than half of these strains tested susceptible to the following second line drugs namely, linezolid (97%), clofazimine (95%), cycloserine (95%), capreomycin (90%), p-aminosalicylic acid (82%), moxifloxacin (79%) and amikacin (79%). The proportion of strains susceptible to pyrazinamide (44%), ethambutol (28%), prothionamide (15%), rifabutin (8%) and streptomycin (8%) was lower. The mycobacterial cultures of the Chechen patients (n = 14) showed significantly different susceptibilities to amikacin (57%) and prothionamide (36%) compared to the strains from migrants of other regions. In this study, the regional differences in mycobacterial susceptibility to second line drugs suggest that the initial MDR TB therapy of migrants should be tailored to their country of origin.

Real-life use of delamanid: results from the European post-authorisation safety study.

BACKGROUND: A post-authorisation safety study (PASS) on delamanid (DLM) was conducted as part of a post-approval commitment to the European Medicines Agency. The aim of this study was to evaluate the use of DLM in a real-life setting, its safety, and treatment outcomes in patients with multidrug-resistant TB (MDR-TB). METHODS: This was a prospective, multicentric, non-interventional study conducted in the European Union. MDR-TB Regimen selection and patient monitoring were conducted in accordance with existing medical practices. Data on the use of DLM, related adverse events, and treatment outcomes were collected for up to 30 months after the first DLM dose. Descriptive summary statistics were used for continuous and categorical variables. RESULTS: Out of 86 patients, one had extrapulmonary TB. Two-thirds of the patients were treated with DLM for more than 24 weeks. The most frequent adverse drug reaction to DLM was QT interval prolongation. Resistance to DLM was detected in one patient during treatment. The treatment success rate was 77%. CONCLUSION: No new safety concerns were revealed, including in patients treated with DLM for more than 24 weeks. QT interval prolongations were well managed and did not lead to any clinically significant cardiac effects. The treatment outcomes were in line with the WHO target for Europe.

CONTEXTE: Une étude de sécurité post-autorisation (PASS) sur le délamanide (DLM) a été menée dans le cadre d'un engagement post-approbation auprès de l'Agence européenne des médicaments. L'objectif de cette étude était d'évaluer l'utilisation du DLM dans un contexte réel, son innocuité et les résultats du traitement chez les patients atteints de TB multirésistante (MDR-TB). MÉTHODES: Il s'agissait d'une étude prospective, multicentrique et non interventionnelle menée dans l'Union européenne. La sélection du schéma thérapeutique de la MDR-TB et le suivi des patients ont été effectués conformément aux pratiques médicales existantes. Les données sur l'utilisation du DLM, les effets indésirables connexes et les résultats du traitement ont été recueillies jusqu'à 30 mois après la première dose de DLM. Des statistiques sommaires descriptives ont été utilisées pour les variables continues et catégorielles. RÉSULTATS: Sur 86 patients, un avait une TB extrapulmonaire. Les deux tiers des patients ont été traités avec du DLM pendant plus de 24 semaines. L'effet indésirable le plus fréquent du DLM était l'allongement de l'intervalle QT. Une résistance au DLM a été détectée chez un patient pendant le traitement. Le taux de réussite du traitement était de 77%. CONCLUSION: Aucun nouveau problème de sécurité n'a été révélé, y compris chez les patients traités par le DLM pendant plus de 24 semaines. Les allongements de l'intervalle QT ont été bien gérés et n'ont pas entraîné d'effets cardiaques cliniquement significatifs. Les résultats du traitement étaient conformes à l'objectif de l'OMS pour l'Europe.

[Implementation of the German Guideline for the Prevention, Diagnosis, Treatment, and Follow-up of Lung Cancer in the Federal State of Berlin]. / Umsetzung der S3-Leitlinie zur Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms im Land Berlin.

BACKGROUND: In February 2010, the German guideline for the Prevention, Diagnosis and Treatment of Lung Cancer has been published. For the first time in Germany, the implementation of relevant guideline recommendations has been assessed in the federal state of Berlin. METHODS: Based on the quality indicators of the guideline, a questionnaire was designed which aimed at the application of selected diagnostic and therapeutic concepts. This questionnaire was sent out to all outpatient and inpatient units in the federal state of Berlin being presumably involved in lung cancer care. RESULTS: Overall response rate was good (39.8 %), especially from the addressed inpatient units. Inpatient pneumology units showed the highest application rates of guideline recommendations, followed by oncology units. CONCLUSIONS: Taking the methodologically reduced significance of a survey design into account, this study determined a negative trend of decreasing guideline implementation in units with a lesser grade of specialisation in terms of lung cancer care.

[Frequency of thromboembolic complications in patients with lung cancer]. / Häufigkeit thromboembolischer Komplikationen bei Patienten mit Lungenkarzinom.

BACKGROUND: Clinicians are frequently confronted by thromboembolic events in patients with lung cancer, yet few data are available about their incidence. In order to obtain data on the frequency of thromboembolic events in the venous and arterial systems, all patients with lung cancer diagnosed in our hospital were retrospectively evaluated with regard to such an event. PATIENTS/METHODS: All patients with a primary diagnosis of lung cancer between January 2008 and December 2010 were prospectively recorded within our tumour registry and retrospectively evaluated with regard to tumour stage, histology and platinum-based chemotherapy. Thromboembolic complications of the arterial and the venous system were included (pulmonary embolism, deep venous thrombosis, myocardial infarction, mesenterial ischaemia, acute limb ischaemia, ischaemia of the renal artery and ischaemic stroke). RESULTS: Within those 36 months 1940 patients (1209 men, 731 women) were diagnosed with lung cancer. SCLC and NSCLC in 156 (8 %) and 1784 cases (92 %), respectively. Thromboembolic events were documented in 190/1940 (9.8 %) cases, venous thromboembolic complications in 148/190 patients (78 %), arterial thromboembolic complications in 51/190 patients (27 %). We documented 82/148 (55 %) deep venous thrombosis, 98/148 (66 %) pulmonary embolisms and arterial thromboembolic events: ischaemic stroke 23/51 (45 %), coronary arteries 14/51 (28 %), peripheral arteries 12/51 (24 %), mesenterial arteries 4/51 (7.8 %), extracranial cerebral arteries 3/51 (5.9 %). CONCLUSIONS: Thromboembolic complications are a common event in patients with lung cancer. Thus, the benefit of primary prevention anticoagulation in lung cancer patients should be prospectively evaluated.

[Diagnostic yield and safety of bronchoscopic cryotechnique in routine diagnostics for suspected lung cancer]. / Diagnostischer Wert und Sicherheit der bronchoskopischen Kryotechnik im Routineeinsatz bei Verdacht auf Lungenkarzinom.

BACKGROUND: Cryoprobes with flexible catheters are an additional important tool for endobronchial interventional therapy and histologic diagnosis. Different studies compared the diagnostic effectiveness and complications to the forceps as a standard. However, routine endoscopic procedures require a combined use of different methods in order to achieve the highest diagnostic yield. We investigated the impact of cryotechnique in comparison with combined diagnostic tools during routine diagnostics of malignant tumors. PATIENTS AND METHODS: A consecutive series of patients undergoing routine diagnostic for lung cancer was included over a 30 months period (n = 469). The use of the cryotechnique, the complication rates and diagnostic value were prospectively documented. Cryotechnique was used on top of conventional technologies. RESULTS: A histologic proof of tumor by cryotechnique in centrally located tumors was delivered more frequently compared to forceps biopsies alone (81.4 versus 59.9% and 66.2 versus 37.7% in peripheral lesions). However, when the other non-cryotechniques were taken into account, the value was reduced in central probes (7.4%; p = 0.02), but remained high for peripheral findings (19.3%; p < 0.002). The frequency of complications seemed unchanged, however severe bleeding occurred. CONCLUSION: The cryotechnique bears high diagnostic potential beside its therapeutic value, also in routine investigations. The changed complication profile of this technology needs to be addressed in the informed consent and secured airway management may be helpful.

[Recommendations for diagnosis and treatment of nontuberculous mycobacterioses of the German Central Committee against tuberculosis and the German Respiratory Society]. / Empfehlungen zur Diagnostik und Therapie nichttuberkulöser Mykobakteriosen des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose (DZK) und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

Nontuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide a rising prevalence and significance of nontuberculous mycobacterioses can be recognized. The present recommendations summarise actual aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of nontuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.

[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.

A prospective clinical multicentre study on adult pulmonary Langerhans' cell histiocytosis.

BACKGROUND: To date the clinical picture of pulmonary Langerhans' cell histiocytosis has been described only in retrospective reports. For a better understanding, the German Scientific Study Group on the Treatment of Lung Disease (WATL) conducted an open, prospective, clinical observation study. METHODS: During the period between 1994 and 2002 77 patients (40 men and 37 women) were recruited. The median observation period was 38.2 (3.2-86.7) months. RESULTS: At the initial examination 50 patients were active smokers, 26 ex-smokers and 1 had never smoked. 36% of the patients showed reduced vital capacity, 28% signs of airways obstruction. On chest radiography, 74% of the patients who stopped smoking (24/50) showed regression, while 13% remained unchanged and 13% revealed progression. In the group that continued to smoke (25/50) chest radiography showed regression in 58% of cases, no change in 25% and progression in 17%. The difference was not significant, which was also true for lung function values. 3 patients died within the observation period. CONCLUSION: The data underline the key role of smoking as the sole known risk factor. A significant effect of smoking cessation on the course could not be confirmed. The overall prognosis was good in this series as compared to previous reports.

Successful oral desensitization to i.v. para-aminosalicylic acid (PAS) using encapsulated PAS dry substance.

INTRODUCTION: para-Aminosalicylic acid (PAS) is commonly used in the treatment of drug-resistant tuberculosis, including multidrug-resistant tuberculosis. Since its first use in the 1940s, hypersensitivity reactions frequently limit its use in clinical practice. Cases of successful desensitization against PAS using orally administered ascending doses are described in the literature. CASE REPORT: A 25-year-old patient with severe pulmonary multidrug-resistant tuberculosis developed drug fever with rash, acral cyanosis, and shivering immediately after the intravenous application of PAS. Hard gelatine capsules containing PAS dry substance were prepared in order to desensitize this patient. Encapsulated PAS was applied orally in rising doses starting with 10 mg/day and doubling the dose every 2 days until the half-maximal dose of 5,120 mg was reached. Desensitization covers a period of 21 days. Subsequent intravenous application of PAS at the full dose was well tolerated. In a 12-month follow-up period, no more allergic reactions appeared. CONCLUSIONS: PAS dry substance encapsulated in hard gelatine capsules and administered orally in rising concentrations may be useful to archive a successful desensitization for subsequent intravenous applications.