[Technological Innovations in Pulmonology - Examples from Diagnostics and Therapy]. / Expertentreffen COPD: Technologische Innovationen in der Pneumologie ­ Facetten aus Diagnostik und Therapie.

A significant proportion of the current technological developments in pneumology originate from the various areas of information technology. The spectrum ranges from smartphone apps to be used in daily life or in patient care to the use of artificial intelligence in screening and early detection of diseases. The diagnostic accuracy of apps for symptom analysis is currently very limited. Research projects are performed on the integration of symptoms and functional parameters into early detection, but also on mobility measurements as a prognostic marker in COPD. Lung cancer screening using computed tomography represents a major challenge. Here, artificial intelligence can help radiologists to cope with huge amounts of data. However, the quality of the software depends on the sufficient training of the system. Technological developments shape all fields of pneumology. For diagnostic and interventional endoscopy, they offer improved biopsy techniques and microstructural imaging. Advances in lung function measurements allow the differentiated analysis of respiratory mechanical disorders, and they could be transferred to ventilation technology. The translation of basic findings about the lung microbiome into patient care may perspectively help to better understand and treat COPD exacerbations.

[Expert Workshop COPD: Lungs and Heart - Quite Often Ill Together]. / Expertentreffen COPD: Lunge und Herz ­ ziemlich oft gemeinsam krank!

When caring for patients with respiratory diseases, always think of the heart! This is especially important for COPD patients, but also for a variety of other disorders of the respiratory system. At the workshop "Luftschlösser", held once more at Wiesbaden, Germany in February 2019 the many and important interactions of the lungs and the heart as well as the therapeutic implications were discussed. Based on pathophysiology, the psycho-social consequences of dyspnea, the leading symptom in patients with lung and heart disease became apparent. A particularly demanding diagnostic and therapeutic situation occurs in patients suffering simultaneously of lung and heart disease. It has been shown how frequently the diagnosis myocardial infarction is missed in COPD patients - and vice versa. Surprisingly, this is also the case in asthmatics with coronary heart disease or heart failure, a fact not readily known in clinical practice. In patients with emphysema and no apparent heart disease, hyperinflation leads to significantly restricted heart function. Reducing hyperinflation by inhaling broncholytics thus improves heart function. Biomarkers are increasingly being used for diagnostic purposes. Their role is being investigated in the large German COPD cohort COSYCONET. Lung patients suffering from more severe heart diseases pose a challenge for therapy in intensive care, especially when ventilated, and weaning from the ventilator is prolonged. Lung vessel diseases are "classic" examples of the intimate interaction of the lungs and the heart. In pulmonary arterial hypertension as well as in chronic thrombo-embolic pulmonary hypertension the lag time between the first symptoms and the definite diagnosis is often unacceptably long. For both diseases of the lung vessels therapeutic options have improved significantly over the last years. Pulmonologists should take care of this increasingly important patient group. Sleep-related breathing disorders and heart function are closely intertwined. Both conditions need special attention after the results of the SERVE-HF trial have been published. But there is no doubt that obstructive sleep apnea represents an independent and important risk factor for cardiovascular disease and needs to be treated according to existing guidelines.This workshop demonstrated impressively the multiple interactions of the respiratory system with cardiac function, resulting diagnostic and therapeutic problems, and means to overcome these problems. Guidelines for respiratory diseases should appropriately address cardiac comorbidity.

[Expert Meeting: Integrated Care of the COPD Patients]. / Expertentreffen COPD: Integriertes Patientenmanagement bei COPD.

Despite considerable progress concerning pharmaceutical therapeutic options, many COPD patients show a markedly reduced quality of life and increased mortality risk. This workshop aimed to identify COPD-specific factors impeding an improved mode of care for patients with COPD. Such factors are: the generally lower social and educational status of the majority of COPD patients; the stigma of COPD as a self-inflicted disease ("smoker's lung"); the strict sectoral separation within the German health care system. In the second part the workshop tried to identify ways to improve the care of COPD patients. Use of health information technology, improved communication between care givers and patients as well as between the health care sectors, integrating rehabilitation and establishing self-management education are factors within an integrated patient-centered approach. In summary, an integrated management of the individual patient with COPD including multi-professional teams should contribute to optimizing the quality of COPD care.

[In Exchange with COPD Patients: Towards a Patient-Oriented Communication]. / Im Gespräch mit COPD-Patienten: patientenzentriert kommunizieren.

The quality of life can be severely impaired in patients with COPD. In addition to physical restraints, they often suffer from psychological comorbidities (e. g. anxiety, depression). Psychological comorbidities are often associated with dysfunctional beliefs about the illness and its treatment. Such dysfunctional beliefs, in turn, are likely to negatively affect patients' quality of life as well as their communication with physicians and their illness behavior in general. It is therefore important for physicians to adapt their communication to account for patients' dysfunctional beliefs. This paper will review the role of dysfunctional beliefs and psychological comorbidities in COPD. It will also elaborate on potential ways to adjust communication between physicians and patients accordingly.

[Exacerbation of COPD]. / Expertentreffen COPD: Exazerbation der COPD.

Acute worsenings of chronic obstructive pulmonary disease (COPD) were for a long time regarded as transient deteriorations, although occasionally life-threatening. No connection to disease progression was recognized. Data emerging during the last decade showed that patients had a considerably worse survival outcome after severe exacerbations. This insight was consolidated in 2012 by a large population-based cohort analysis. At present, severe exacerbations are regarded as key risk factors for COPD disease progression. The present article summarises the current knowledge on exacerbations of COPD, as delineated during an expert workshop in February 2017. It comprises pathogenic mechanisms, exacerbation triggers, the characteristics of frequent exacerbators, and the predictors of worse survival outcome. The role of comorbidities is considered more closely. The presentation of the pharmacotherapy of acute exacerbation is supplemented by an overview of ventilatory support. Finally, pharmacological and nonpharmacological preventive measures are summarised.

[Expert Meeting on COPD: Personalized Treatment of COPD - Wishful Thinking or Reality?] / Expertentreffen COPD: Personalisierte Therapie der COPD ­ Wunsch oder Wirklichkeit?

Chronic obstructive pulmonary disease (COPD) is considered to be a complex and heterogeneous disease comprising multiple components. Its clinical presentation, pattern of functional disturbance, disease presentation and pathology varies tremendously between individuals despite the common feature of incompletely reversible airflow obstruction. It is therefore widely accepted that COPD is characterized by discriminable phenotypes that represent specific patterns of these disease features. COPD phenotypes are believed to correlate with outcome parameters such as severity of symptoms, exacerbations, functional loss or death and to require different treatment algorithms.This survey is the result of presentations that were given during an expert conference. It highlights the significance of major comorbidities, genetic, morphologic and inflammatory COPD-phenotypes and their impact on disease progression and treatment modalities.

[Expert meeting obstructive airway disease measuring and evaluating in COPD]. / Expertentreffen obstruktive Atemwegserkrankungen: Messen und Bewerten der COPD.

This report gives an overview on the contributions presented in an expert meeting in February, 2015. They deal with the analysis and evaluation of the multiple dimensions of COPD. This complex disease not only interferes with pulmonary mechanics and gas exchange, but also with cardiopulmonary crosstalk and the ventilator pump. A bulk of inflammatory and microbial activity develops during the progression of disease. As a consequence, systemic effects on muscles, metabolism and psyche develop.The sections consider the value of multiple endpoints in clinical research. Quantifiable parameters of lung mechanics and gas exchange, of exercise tolerance and biomarkers improve the measurability of effects in interventions. However, do we really know in a biological sense what we are measuring? What conclusions can we draw in terms of prognosis?Vice versa, we have to look into the origin and meaning of integrative endpoints e.g. quality or life, dyspnoea and spontaneous physical activity. As a new dimension, the clinical significance of morphological findings in HRCT and MRT is analyzed.

[Dry powder inhalers in cystic fibrosis]. / Trockenpulverinhalation bei Mukoviszidose.

Inhaled medications play an important role in the daily treatment of patients with cystic fibrosis (CF). The classic route of administration was nebulisation via jet nebulisers. Respiratory delivery of fluid particles should loosen the viscid respiratory secretions, making airway clearance via cough or physiotherapy more efficient. Until recently, only jet nebulisers allowed to administer high doses of aerosolised antipseudomonal antibiotics. Powder inhalers for the treatment of cystic fibrosis have recently been made available. The newly developed powders and inhalers differ considerably from conventional dry powder inhalers used for the treatment of chronic obstructive airway disease. The present article will review two inhaled antibiotics, i. e. tobramycin and colistin, and the hyperosmotic agent mannitol, which increases the hydration of the airways. Topics are particle engineering, efficacy and tolerability results from clinical trials, as well as functional and practical aspects related to these new drugs.

[Expert meeting chronic obstructive airway disease--cardiovascular aspects of COPD]. / Expertentreffen obstruktive Atemwegserkrankungen: Kardiovaskuläre Aspekte der COPD.

This overview presents data that take advantage of a new step of insight into COPD. Large population-based retrospective studies and intensively investigated prospective cohorts are two important sources of knowledge that have been recently developed. One of the contributions introduces the German COSYCONET which is on its way shortly after the American ECLIPSE cohort. The vast amount of new data has also contributed to some corrections of the recommendations of the international GOLD committee. Clinically important are the waiver of the reversibility test for the diagnosis of COPD, the inclusion of sympotom scores to evaluate quality of life and the estimation of exacerbations. The COPD types I through IV were originally the result of expert opinion, but their impact on prognosis has recently been evaluated empirically.The top issues of the expert meeting were cardiovascular aspects of COPD. Besides the comorbidity of two significant chronic diseases, it became clear that cardiovascular events have an outstanding significance for COPD patients. Inversely, advanced COPD is an important risk factor in cardiac and vascular diseases. The mutual influence of both disease entities does not only affect the long term progression but also the outcome of acute events like myocardial infarction and COPD exacerbation. The following contributions investigate the topic with regard to epidemiology, the biology of vessels, and especially with regard to acute COPD exacerbations and pharmakotherapy. Recent evidence enables a fresh view on the cardiovascular toxicity of COPD medication and on possible protective effects of cardiovascular drugs (i.e. statins and ß-receptor antagonists) for patients with COPD.

[Meeting of experts on obstructive airway diseases: targets and methods]. / Expertentreffen Obstruktive Atemwegserkrankungen: Targets und Methoden.

New insights into the pathogenesis and clinical course of chronic obstructive pulmonary disease (COPD) and asthma have become available. Systematic analyses of well-defined and intensively monitored patient cohorts are being published, particularly from the ECLIPSE cohort in the U.S.A. and from the network COSYCONet in Germany. Important articles from 2011 on COPD and asthma put former concepts into question. There is a new understanding of the relationship between parenchymal destruction and bronchial obstruction in COPD as well as on the impact of cardiovascular comorbidity. Computed tomography allows high-resolution imaging of lung structures, and MRI delivers supplementary functional information. Researchers have also investigated the value of patient-reported outcomes, such as quality of life, dyspnoea, or the COPD assessment test (CAT). Members of the GOLD committee are trying to establish a feasible classification of the multiple facets of COPD. With respect to treatment, novel data on beta-adrenergic antagonists in COPD and on muscarinic antagonists in asthma have been published. These aspects were discussed during an expert meeting and are now summarised in the present review article.

[Structured care in an ISO certified centre for patients with cystic fibrosis and their families]. / Strukturierte Versorgung von Mukoviszidosepatienten und ihren Angehörigen in einem ISO-zertifizierten Behandlungszentrum.

BACKGROUND: Cystic fibrosis (CF) is a chronic, life-shortening disease of multiple organ systems. Guidelines recommend that patients should be treated in specialised CF centres with multi-professional teams. We describe the organisation of medical care at the CF centre of Innsbruck University as well as results of treatment. PATIENTS AND METHODS: Procedures and delivery of multi-professional care have been elaborated and structured. Since 2006 the Centre has been repeatedly certified according to DIN ISO 9001:2000. The patient database is being used during the doctor's consultation and for the continuous monitoring of treatment results. RESULTS: In 2010, 71 of the 148 patients (48%) were between 18 and 56 years old. The total number of patients has doubled and the proportion of adults tripled since 1995. Nevertheless, median FEV1 remained stable (>80% of predicted) during the last 15 years. Compared with 18 CF centres of the German Benchmarking Group, patients treated in Innsbruck had favourable FEV1 values: 52% of adults had a normal FEV1 (>80% pred.) and only 23% an FEV1 <50% of predicted. CONCLUSIONS: A structured programme of multi-professional care was associated with favourable treatment results, both longitudinally and in comparison to other CF centres.

[Clinical trial endpoints in alpha-1-antitrypsin deficiency: interdisciplinary aspects]. / Studienendpunkte beim Alpha-1-Antitrypsin-Mangel:Interdisziplinäre Aspekte.

Patients with alpha-1-antitrypsin deficiency (AAD) represent a small subgroup of subjects with chronic obstructive pulmonary disease (COPD). Only about 800 patients are registered in the German AAD registry, so that about 90 % of the estimated 8000 afflicted individuals have not yet been diagnosed. Clinical trials to demonstrate the efficacy of alpha-1-antitrypsin augmentation therapy are difficult not only due to the small number of potential participants. As in recent COPD trials, FEV (1) and other standard respiratory function parameters have failed to demonstrate statistically significant differences between treatment groups. The present article reviews and discusses both established and potentially new study endpoints. Novel parameters emerge within the field of diagnostic imaging. IT-supported analysis of lung density allows to quantify the extent of emphysema. The EXACTLE trial has shown that CT densitometry is able to document the progression of emphysema over 2 to 3 years. Magnetic resonance imaging (MRI) can serve as an adjunct to assess lung perfusion, ventilation, and breathing dynamics. In the future, prospective multi-centre studies will rather use imaging endpoints than classical respiratory function measurements such as FEV (1). In addition, diffusion capacity and combined endpoints such as the BODE index, which correlates with mortality in COPD, should be considered.

[COPD and Clinical Trials. Results of an expert meeting "Castles in the Air" 2010]. / COPD und Studien. Ergebnisse des Expertentreffens Luftschlösser 2010, Mainz, 3.­4. Dezember 2010 (Sponsor: Boehringer Ingelheim Pharma GmbH & Co KG).

Clinical trials in COPD patients aim at achieving progress in diagnosis and treatment. Study results should be applicable to a large number of patients. However, an analysis of the methods and design of current and previous trials reveals considerable room for improvement. COPD is a complex disease with different clinical phenotypes. Genetic factors need to be evaluated systematically to allow appropriate stratification of patients. Frequently used endpoints such as the FEV1 that had previously been considered reliable have shown limitations in recent trials. Thus, researchers now aim to identify new surrogate parameters that are related to the prognosis of the disease, e. g., composite endpoints and biomarkers. Physical activity and capacity are becoming increasingly important for the evaluation of disease progression. The focus of pharmaceutical development is long acting bronchodilators and new anti-inflammatory drugs. The value of non-drug interventions will also be evaluated.

[COPD and infection]. / COPD und Infektion.

Infections are frequent and important causes of exacerbations in patients with COPD. This article reviews underlying mechanisms and therapeutic consequences. A complex interaction exists between COPD, co-morbidities, physical inactivity and systemic inflammation. The components of the postulated chronic inflammatory systemic syndrome need to be identified in more detail; physical inactivity seems to be the least common denominator. The patient's adaptive and innate immune systems play a role for the pathogenesis of infections. When interpreting positive bacterial cultures, it is important to differentiate between colonisation and infection. The impact of viral infections in COPD exacerbation needs further clarification, including the task to distinguish acute infection from viral persistence. Community acquired pneumonias pose a special risk for patients with COPD. Clinical scores and procalcitonin serum concentrations can support decisions on whether or not to start antibiotic treatment. Antibiotics probably do not need to be taken for longer than 5 days, since their efficacy does not increase after longer treatment, while adverse events rise in frequency. Hospitalisations for respiratory exacerbations are associated with increased mortality in COPD.

[Update: Alpha-1-antitrypsin deficiency. Summary of a scientific symposium at the conference of the Swiss Pneumologic Society on April 16th, 2009]. / Alpha-1-Antitrypsin-Mangel: Update. Ergebnisse eines wissenschaftlichen Symposiums beim Kongress der Schweizerischen Gesellschaft für Pneumologie am 16. April 2009.

The time delay between the start of respiratory symptoms and the correct diagnosis of alpha-1-antitrypsin (AAT) deficiency is often 6 to 8 years. Most patients are misdiagnosed as having COPD or asthma. Recent estimates suggest that only 15 % of patients have already been identified. The PiZZ genotype leads to severely decreased AAT serum concentrations, and is associated with a high risk of pulmonary emphysema. Disease manifestation is earlier in smokers than in non-smokers. Since cigarette smoke is able to reduce AAT activity by a factor of 2000, it can accelerate the progression of emphysema. Patients are therefore recommended to stop smoking. The EXACTLE study assessed the development of emphysema by means of CT densitometry in 77 patients with severe AAT deficiency over a period of 2.5 years. CT densitometry was able to detect the progressive loss of lung tissue, and it was found to be more sensitive than pulmonary function or quality of life variables. With weekly intravenous supplementation of alpha-1-antitrypsin, emphysema progressed more slowly compared to placebo (albumin) infusions. In Germany, of about 900 patients are currently receiving supplementation therapy with human AAT. The treatment is well tolerated and well accepted by the patients. Symptomatic treatment consists of long- and short-acting beta-agonists, anticholinergic bronchodilators, and inhaled corticosteroids. Alpha-1 centres provide particular expertise, and it is recommended that every patient should be seen in one of these specialised outpatient clinics.

[Assessment and outcome parameters in COPD]. / Beurteilungs- und Prognosekriterien bei COPD1.

BACKGROUND: A standard outcome parameter for pharmacological trials in COPD has not yet been defined. Therefore, it is the aim of this review to evaluate frequently used parameters for their eligibility as assessment and outcome parameters in COPD. METHODS: A review of the actual scientific literature was performed. RESULTS: It is recommended to continue to rely primarily on the FEV (1), which has been used as a primary variable in the vast majority of trials. In addition, further parameters, such as FVC and IC/TLC should be determined. If available, additional information is provided by RV/TLC, K (co), PaO (2) and PaCO (2). FEV (1) is not a surrogate parameter for dyspnoea, quality of life, and exercise tolerance, which should therefore be assessed separately. Frequency and severity of exacerbations and mortality are important outcome parameters in long-term trials. Complex indices, such as the BODE index, may be superior to single variables. CONCLUSIONS: No single additional parameter has been evaluated sufficiently in order to substitute FEV (1) as the standard parameter for the assessment and outcome in COPD.

Prospective evaluation of emerging bacteria in cystic fibrosis.

BACKGROUND: Bacteria contribute considerably to the progression of lung disease in cystic fibrosis. In this prospective, multi-centre study, we aimed to evaluate the occurrence of emerging bacteria and the physicians' assessments of the clinical importance of these findings. METHODS: Twelve CF centres (total number of patients: 1419) reported the detection of any Stenotrophomonas maltophilia, Burkholderia cepacia complex, MRSA, Alcaligenes xylosoxidans, Klebsiella species and Mycobacteria during an observation period of 6 months. RESULTS: 213 specimens with emerging bacteria were reported from 145 different patients. The proportion of patients with emerging bacteria differed between centres (3-38%, mean: 12.6%) and increased with age. The predominant bacterium was S. maltophilia (n=106 positive specimens), followed by Klebsiellae (n=36), B. cepacia complex (n=31), A. xylosoxidans (n=16), Mycobacteria (n=11), MRSA (n=11), and others (n=2). In many instances the same microorganisms had already been reported earlier, indicating intermittent or chronic colonisation. The clinical status was reported to be stable in 70% of patients, and antibiotic treatment was anticipated for 46% of positive specimens. Comparison of clinical data to age matched controls did not reveal any significant differences with regard to pulmonary and nutritional status prior to detection of emerging bacteria. CONCLUSION: These data suggest a high variability between centres regarding the prevalence of emerging bacteria. Most patients maintained a stable clinical condition during the 6-month study period despite being colonised with emerging bacteria.

Resting energy expenditure before and after treatment for Pseudomonas aeruginosa infection in patients with cystic fibrosis.

To investigate whether metabolic rates change after antipseudomonal treatment, resting energy expenditure (REE) was measured in 29 patients with cystic fibrosis (CF) aged 5-27 y before and after a 2-wk course of intravenous antibiotics for the treatment of chronic Pseudomonas aeruginosa infection. Before therapy, mean (+/- SD) REE was increased to 119.0 +/- 11.4% of the predicted normal value (REE%). Seventeen of the 29 patients were classified as having increased baseline REE% (> 115% of predicted, group I), whereas 12 patients had resting energy expenditures within the normal range (group N). After antipseudomonal therapy, mean REE% decreased significantly by 6.2% of predicted. This decline was negatively correlated with the baseline REE% (r = 0.70, P < 0.001). It was most pronounced (-11.3%) in group I whereas patients of group N showed no major changes. These results suggest that antipseudomonal therapy can reduce increased energy requirements of moderately ill CF patients with chronic Pseudomonas aeruginosa infection.

Cystic fibrosis: the impact of analytical technology for genotype-phenotype studies.

The generalized exocrinopathy cystic fibrosis (CF) is the most common severe genetic disease in Caucasian populations. A panel of more than 700 chromosomes from German and Turkish CF patients was screened for disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene by chemical cleavage of mismatch, single strand conformation polymorphism, restriction analysis and direct sequencing of genomic DNA amplified by polymerase chain reaction. Besides the major 3-bp deletion, delta F508 that was found on 73% of German CF chromosomes, more than 50 other missense, nonsense, frame-shift, and splice-site mutations have already been identified. In general, a CFTR mutation is linked with a single 10-marker haplotype which indicates that in most cases a particular mutation spread from a common ancestor. The comparison of mutation genotypes with the disease phenotype emphasized the causative role of the type and localization of the CFTR mutation for clinical course and prognosis. Pancreatic status and the risk of colonization of airways with opportunistic pathogens are genetically determined. Most patients who are harbouring mutations in the nucleotide binding folds were suffering from severe CF disease. Mild or even aberrant forms of CF were observed for many missense mutations located in the putative transmembrane domains or for mutations that are expected to result in a truncated protein of half of wild-type CFTR.

Nutrition in patients with cystic fibrosis: a European Consensus.

This document is the result of an European Consensus conference which took place in Artimino, Tuscany, Italy, in March 2001 involving 33 experts on nutrition in patients with cystic fibrosis, organised by the European Cystic Fibrosis Society, and sponsored by Axcan-Scandipharm, Baxter, Dr Falk Pharma, Fresenius, Nutricia, SHS International, Solvay Pharmaceuticals (major sponsor). The purpose of the conference was to develop a consensus document on nutrition in patients with cystic fibrosis based on current evidence.