[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.

Management of patients with multidrug-resistant tuberculosis.

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

[Inhaled Triple Therapy in Severe Chronic Obstructive Pulmonary Disease (COPD)]. / Dreifachfixkombinationen (LAMA/LABA/ICS) zur inhalativen Dauertherapie der schwergradigen COPD.

COPD (chronic obstructive pulmonary disease) is characterised by persistent airflow obstruction caused by exposure to irritants including cigarette smoke dust, and fumes. Long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) in fixed-dose combination inhalers are the pillars of modern COPD therapy. LABA/inhaled corticosteroids (ICS) inhalers have been proved to be particularly efficient in patients with ≥ 2 exacerbations per year. Until recently, although recommended in guidelines for severe and unstable COPD patients, the clinical usefulness of the LABA/LAMA/ICS combination was a matter of debate. Recent trials with fixed-dose combination inhalers containing fluticasonfuroate/vilanterol/umeclidinium or beclometasone/formoterol/glycopyrronium significantly reduced exacerbation rates and dyspnea scores and improved lung function as well as quality of life better than the LABA/ICS, LABA/LAMA comparators or the single compounds in selected COPD trial patients. Beclometasone/formoterol/glycolpyrronium and fluticasonfuroate/umeclidinium/vilanterol are the first triple combination therapies approved in a fixed-dose inhaler for COPD patients. The domains of triple fixed-dose formulations are COPD patients in groups C and D.

[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.

[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.

[Multifocal Pulmonary Neuroendocrine Tumours: Genesis, Diagnostics and Treatment]. / Multifokale neuroendokrine Lungentumoren: Entstehung, Diagnostik und Behandlung.

Multifocal neuroendocrine lung tumour is a rare diagnosis. Multiple lung foci of different sizes are usually apparent on chest CT scans. It is assumed that multifocal neuroendocrine lung tumours originally develop from diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). This results in cell aggregations formed by proliferation of neuroendocrine cells that are already physiologically present in the bronchial system. If these cell proliferations break through the bronchial basement membrane, they are considered to constitute tumourlets if they measure ≤ 5 mm and carcinoid tumours if they are larger than 5 mm. The speed of proliferation of the cell hyperplasias appears to vary. Many of the patients are completely asymptomatic, the multifocal neuroendocrine lung tumours being diagnosed by chance. However, other patients complain of breathlessness, reduced physical capacity and cough. There may also be reduction of lung function. In these cases, chest HRCT often reveals peribronchial fibrosis or bronchiectasis in addition to the lung foci. Bronchoscopy is usually not helpful. Surgical lung biopsy is considered to be the diagnostic gold standard. Histological examination typically shows a mixture of cell hyperplasias, tumourlets and carcinoid tumours. There is no consensus on the treatment of multifocal neuroendocrine tumours. Taking the clinical situation and the chest HRCT findings as our starting point, we developed a stepwise approach that is guided by the success of the individual therapeutic procedures. The most favourable prognosis is found in affected people without clinical symptoms whose lung foci all measure less than 5 mm. In these cases the 5-year survival rate is over 90%.

[Telemonitoring in patients with COPD and acute exacerbations]. / Die akute Exazerbation der COPD.

A major problem associated with COPD is exacerbation. Symptoms include increased shortness of breathing, coughing, wheezing and sputum production. The frequency and severity of exacerbations are associated with a higher mortality risk. Early recognition and treatment have been shown to reduce severity of exacerbations, consecutive morbidity and hospital admissions. Telemonitoring of (nocturnal) lungsounds, oxygen saturation and frequency of breathing may offer the opportunity to detect symptoms of exacerbations very early. Therefore further research is needed to clarify precisely the role of telemonitoring in patients with COPD and exacerbations.

[Rare diseases in pulmonary medicine and its challenges]. / Seltene Erkrankungen in der Pneumologie und damit verbundene Herausforderungen.

The importance of rare disease is appreciated by all parties and tremendous effort is made to increase the knowledge about the individual disorders and improve the care of affected patients. Political initiatives on a European level aim to improve the structure of medical care for patients with rare diseases in each member state. The provided incentives for the development of medicines for orphan diseases have led to increased research activities and numbers of licensed Orphan Drugs. Patients are organized nationally and internationally in various patient organizations and umbrella organizations. They are involved in health care policy, support the detection and research of rare diseases and offer support to affected patients and families with educational meetings and materials as well as options for discussions. Many experts are engaged in national and international networks and registries that generate and publish high quality research data on rare diseases. A well developed infrastructure is in place to support the search for qualified partners that can be of assistance with specific questions in a rare lung disease.

[Comparison of four identical electronic noses and three measurement set-ups]. / Vergleich von vier baugleichen elektronischen Nasen und drei Messaufbauten.

BACKGROUND: Volatile organic compounds (VOCs) can be used as biomarkers in exhaled air. VOC profiles can be detected by an array of nanosensors of an electronic nose. These profiles can be analysed using bioinformatics. It is, however, not known whether different devices of the same model measure identically and to which extent different set-ups and the humidity of the inhaled air influence the VOC profile. METHODS: Three different measuring set-ups were designed and three healthy control subjects were measured with each of them, using four devices of the same model (Cyranose 320™, Smiths Detection). The exhaled air was collected in a plastic bag. Either ambient air was used as reference (set-up Leipzig), or the reference air was humidified (100% relative humidity) (set-up Marburg and set-up Munich). In the set-up Marburg the subjects inhaled standardised medical air (Aer medicinalis Linde, AGA AB) out of a compressed air bottle through a demand valve; this air (after humidification) was also used as reference. In the set-up Leipzig the subjects inhaled VOC-filtered ambient air, in the set-up Munich unfiltered room air. The data were evaluated using either the real-time data or the changes in resistance as calculated by the device. RESULTS: The results were clearly dependent on the set-up. Apparently, humidification of the reference air could reduce the variance between devices, but this result was also dependent on the evaluation method used. When comparing the three subjects, the set-ups Munich and Marburg mapped these in a similar way, whereas not only the signals but also the variance of the set-up Leipzig were larger. CONCLUSION: Measuring VOCs with an electronic nose has not yet been standardised and the set-up significantly affects the results. As other researchers use further methods, it is currently not possible to draw generally accepted conclusions. More systematic tests are required to find the most sensitive and reliable but still feasible set-up so that comparability is improved.

[Chronic obstructive pulmonary disease (COPD) as a systemic disease]. / Die chronisch obstruktive Lungenerkrankung (COPD) als Systemerkrankung.

Chronic obstructive pulmonary disease (COPD) is defined as a progressive, usually only partially reversible, obstruction of the airways The disease is associated with an inflammatory response of the lungs to noxious particles, particularly cigarette smoke. Numerous epidemiological studies have shown a significant association between impaired lung function and the presence of cardiovascular, metabolic or other extrapulmonary comorbidities. Systemic inflammation may be the missing link between COPD and its extrapulmonary manifestations, although the exact mechanism of this relationship remains unclear. The development and validation of score systems that classify COPD severity, not only by changes in lung function, is an important step. The BODE score (body-mass index, airways obstruction, dyspnea, exercise capacity) is such a system. Based on the concept of COPD as a systemic disease, a concept is needed which describes in detail the pharmacological treatment of the pulmonary and extrapulmonary manifestations of the disease. In addition, the part of the disease that is treatable with physiotherapy and rehabilitation must be fully taken into account. Such multimodal treatment regimens have so far not been implemented into clinical guidelines.

[The German registry of individuals with alpha-1-antitrypsin deficiency--a source for research on patient care]. / Das Deutsche Register für Personen mit Alpha-1-Antitrypsin-Mangel--eine Ressource für die Versorgungsforschung.

BACKGROUND: alpha-1-Antitrypsin deficiency (AATD) is a rare condition with a prevalence of about 1/4000 individuals in Germany. The clinical manifestations are the early development of pulmonary emphysema or of liver cirrhosis. The low prevalence of AATD suggested the establishment of a registry with the aim to learn more details about the natural history and the quality of care for these patients. METHODS, PATIENTS, RESULTS: Since 2004 the German registry for individuals with AATD is maintained in Marburg. Up to May 2008, 548 individuals were registered, 455 with the genotype PiZZ and 46 with PiSZ. The age range of the registered individuals extends from 2 to 82 years (mean 55, SD 20; men 54 [SD 19] years, women 55 [SD 21] years). Most patients are affected by chronic obstructive pulmonary disease (COPD, distribution to the GOLD stages: GOLD I = 16 %, GOLD II = 30 %, GOLD III = 33 %, GOLD IV = 21 %). Currently 109 subjects are under substitution therapy. The time period between the first symptom and the establishment of the correct diagnosis was on average 5.6 years. CONCLUSIONS: The data of the registry allow a detailed characterisation of the natural course of the disease and the levels of the patient care.

[Pathogenesis of chronic obstructive pulmonary disease]. / Pathogenese der COPD.

It is currently believed that the most important factor in the pathogenesis of chronic obstructive pulmonary disease (COPD) is inflammation of the small airways caused by inhaled particles and gases. In this context, a disturbance of the physiological balance between proteases and antiproteases develops that may cause lung emphysema. Moreover, oxidative stress seems to be important, as it may enhance the inflammatory reaction. The development of emphysema may also involve a loss of alveolar cells by apoptosis. Finally, several studies have indicated that a systemic inflammation is induced by COPD that may be of relevance to the development of systemic components that are observed in COPD patients.