Medication-Induced Central Sleep Apnea: A Unifying Concept.

Medication-induced central sleep apnea (CSA) is one of the 8 categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioids medications including sodium oxybate, baclofen, valproic acid, gabapentin and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.

[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.

[Management of diagnostic procedures and treatment of sleep related breathing disorders in the context of the coronavirus pandemic]. / Diagnostik und Therapie schlafbezogener Atmungsstörungen im Zusammenhang mit der Corona­Pandemie: Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP), Deutsche Gesellschaft für Schlafforschung und Schlafmedizin (DGSM).

When providing sleep medical services special aspects must be taken into account in the context of the coronavirus pandemic. Despite all prevention, due to the high number of unrecognized cases, SARS-CoV2 contacts in the sleep laboratory must be expected and appropriate precautions are necessary. Nevertheless, the continuation or resumption of sleep medical services under the appropriate hygiene measures is strongly recommended to avoid medical and psychosocial complications. There is no evidence for a deterioration of COVID-19 through CPAP therapy. In principle, the application of positive pressure therapy via various mask systems can be accompanied by the formation of infectious aerosols. In the case of confirmed infection with SARS-CoV2, a pre-existing PAP therapy should be continued in an outpatient setting in accordance with the local guidelines for home isolation, since discontinuation of PAP therapy is associated with additional cardiopulmonary complications due to the untreated sleep-related breathing disorder. According to the current state of knowledge inhalation therapy, nasal high-flow (NHF), and PAP therapy can be carried out without increased risk of infection for health care workers (HCW) as long as appropriate personal protective equipment (eye protection, FFP2 or FFP-3 mask, gown) is being used.This position paper of the German Society for Pneumology and Respiratory Medicine (DGP) and the German Society for Sleep Medicine (DGSM) offers detailed recommendations for the implementation of sleep medicine diagnostics and therapy in the context of the coronavirus pandemic.

[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.

[Position Paper for the State of the Art Application of Respiratory Support in Patients with COVID-19 - German Respiratory Society]. / Positionspapier zur praktischen Umsetzung der apparativen Differenzialtherapie der akuten respiratorischen Insuffizienz bei COVID-19.

Against the background of the pandemic caused by infection with the SARS-CoV-2, the German Society for Pneumology and Respiratory Medicine (DGP e.V.), in cooperation with other associations, has designated a team of experts in order to answer the currently pressing questions about therapy strategies in dealing with COVID-19 patients suffering from acute respiratory insufficiency (ARI).The position paper is based on the current knowledge that is evolving daily. Many of the published and cited studies require further review, also because many of them did not undergo standard review processes.Therefore, this position paper is also subject to a continuous review process and will be further developed in cooperation with the other professional societies.This position paper is structured into the following five topics:1. Pathophysiology of acute respiratory insufficiency in patients without immunity infected with SARS-CoV-22. Temporal course and prognosis of acute respiratory insufficiency during the course of the disease3. Oxygen insufflation, high-flow oxygen, non-invasive ventilation and invasive ventilation with special consideration of infectious aerosol formation4. Non-invasive ventilation in ARI5. Supply continuum for the treatment of ARIKey points have been highlighted as core statements and significant observations. Regarding the pathophysiological aspects of acute respiratory insufficiency (ARI), the pulmonary infection with SARS-CoV-2 COVID-19 runs through three phases: early infection, pulmonary manifestation and severe hyperinflammatory phase.There are differences between advanced COVID-19-induced lung damage and those changes seen in Acute Respiratory Distress Syndromes (ARDS) as defined by the Berlin criteria. In a pathophysiologically plausible - but currently not yet histopathologically substantiated - model, two types (L-type and H-type) are distinguished, which correspond to an early and late phase. This distinction can be taken into consideration in the differential instrumentation in the therapy of ARI.The assessment of the extent of ARI should be carried out by an arterial or capillary blood gas analysis under room air conditions and must include the calculation of the oxygen supply (measured from the variables of oxygen saturation, the Hb value, the corrected values of the Hüfner number and the cardiac output). In principle, aerosols can cause transmission of infectious viral particles. Open systems or leakage systems (so-called vented masks) can prevent the release of respirable particles. Procedures in which the invasive ventilation system must be opened, and endotracheal intubation must be carried out are associated with an increased risk of infection.The protection of personnel with personal protective equipment should have very high priority because fear of contagion must not be a primary reason for intubation. If the specifications for protective equipment (eye protection, FFP2 or FFP-3 mask, gown) are adhered to, inhalation therapy, nasal high-flow (NHF) therapy, CPAP therapy or NIV can be carried out according to the current state of knowledge without increased risk of infection to the staff. A significant proportion of patients with respiratory failure presents with relevant hypoxemia, often also caused by a high inspiratory oxygen fraction (FiO2) including NHF, and this hypoxemia cannot be not completely corrected. In this situation, CPAP/NIV therapy can be administered under use of a mouth and nose mask or a respiratory helmet as therapy escalation, as long as the criteria for endotracheal intubation are not fulfilled.In acute hypoxemic respiratory insufficiency, NIV should be performed in an intensive care unit or in a comparable unit by personnel with appropriate expertise. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring with readiness to carry out intubation must be ensured at all times. If CPAP/NIV leads to further progression of ARI, intubation and subsequent invasive ventilation should be carried out without delay if no DNI order is in place.In the case of patients in whom invasive ventilation, after exhausting all guideline-based measures, is not sufficient, extracorporeal membrane oxygenation procedure (ECMO) should be considered to ensure sufficient oxygen supply and to remove CO2.

EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke.

BACKGROUND: Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality. AIM: Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology to critically evaluate the evidence regarding potential links and the impact of therapy. MATERIALS AND METHODS: Thirteen research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 were included. Statements were generated regarding current evidence and clinical practice. RESULTS: Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, whilst CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, whilst the pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, whilst treatment data are scarce. DISCUSSION/CONCLUSION: Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.

Extended evaluation of the efficacy of a proactive forced oscillation technique-based auto-CPAP algorithm.

PURPOSE: Previous studies revealed substantially varying therapy efficacy of automatic continuous positive airway pressure (APAP) devices in the treatment of obstructive sleep apnea (OSA). We evaluated the efficacy of a new APAP device using the forced oscillation technique (FOT) to evaluate upper airway obstruction during apneas and flow contour analyses during hypopneas. METHODS: Forty-six initially diagnosed OSA patients were included and the pressure range was set from 5 to 20 hPa. Therapy efficacy was assessed based on the reduction of apnea-hypopnea index (AHI), improvement of objective sleep quality parameters, and the appropriateness of the device's pressure regulation. RESULTS: AHI and arousal index significantly decreased during APAP therapy (median [interquartile range]: AHI 36 [23-55] vs. 2 [1-6]/h, arousal index 30 [22-45] vs. 15 [10-19]/h, both p < 0.001). The amount of slow wave sleep (SWS) and rapid-eye-movement (REM) sleep significantly increased (SWS 20 [14-29] vs. 29 [19-34]%, REM 16 [11-21] vs. 24 [14-30]%, both p < 0.01). Most residual respiratory events during therapy were of central etiology and attributable to five patients, who presented with treatment-emergent central sleep apnea. The device's pressure regulation abolished most obstructive respiratory events (n = 6.7 residual obstructive events per patient). Of central respiratory events, 534/646 (83%) did not lead to pressure increases. CONCLUSION: This pilot study provides a proof of concept that the APAP device combining FOT and evaluation of flow contour allows for the suppression of obstructive events without relevant false reactions.

[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.

[Different Prevalences of Pneumological Disease Patterns in Outpatient and Inpatient Care]. / Unterschiedliche Häufigkeiten pneumologischer Krankheitsbilder in der ambulanten und stationären Medizin.

BACKGROUND: Evaluating the focus of treatment in pneumological inpatient and outpatient care is of special interest due to its impact on physician, patient and research. This work describes differences and commonalities in the focus of treatment of current pneumological inpatient and outpatient care and discusses their impact on patient, physician and research. METHODS: This study compares the inpatient and outpatient sector based on the prevalence of ICD codes of a pneumological specialist clinic (5.211 cases of 2016) and the most prevalent ICD-10 codes of pneumology practices in the third quarter 2016, published by the Association of Statutory Health Insurance Physicians North Rhine ("Kassenärztliche Vereinigung Nordrhein", 142.431 cases). RESULTS: Whereas the proportion of many pneumological disease patterns treated in physicians' practices and hospitals is similar, the relative frequencies of specific diseases differ considerably between the two. Treatment of allergic conditions such as allergic rhinopathy and bronchial asthma is mostly done on an outpatient basis while respiratory insufficiency and lung carcinoma constitute domains of pneumological inpatient care. CONCLUSION: Despite many commonalities in the focus of treatment in pneumological inpatient and outpatient care, there are also substantial differences between the two. These affect medical training, the conduct of clinical studies, and in particular, patient care. In order to maintain a high level of medical care in all areas of pneumology a close exchange between inpatient and outpatient sector seems crucial. In the end, the availability of medical expertise across both sectors will benefit all: physicians, patients and medical science.

[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.

[Survey of Specialist Pulmonary Medicine Health Care Structures for Patients with Interstitial Lung Disease in Nordrhein-Westfalen, Germany - A Pilot Project of the Western German Respiratory Society (WdGP)]. / Erfassung der pneumologisch-fachärztlichen Versorgungsstrukturen für Patienten mit interstitiellen Lungenerkrankungen in Nordrhein-Westfalen.

AIM OF THE STUDY: Survey of specialist pulmonary medicine health care structures for patients with interstitial lung disease (ILD) in Nordrhein-Westfalen, Germany. METHODS: The Western German Respiratory Society initiated a voluntary registration of ILD expert centers. Structural quality and processes were evaluated by questionnaire. RESULTS: 49 centers were registered, 46 allowed analysis of their center data (15 pulmonology specialist practices, 34 hospital pulmonology departments). Specialist practices saw a median of 360 ILD patients per year (26 % first diagnosis), hospital departments a median of 105 ILD patients per year (63 % first diagnosis). 10 centers diagnose more than 100 new ILD cases per year. Specialist practices report median 50 bronchoscopies per year, hospital departments median 1396. 78 % of the centers participate in a multidisciplinary ILD case conference. CONCLUSION: Several ILD expert centers were identified in Nordrhein-Westfalen. Outpatient care mainly involves the monitoring of ILD patients, inpatient services focus on complex initial diagnostics or cases with unusual disease behaviour. ILD centers meeting regional health care needs should be supported in their development.

First case report of a curative wedge resection in epithelial-myoepithelial carcinoma of the lung.

Epithelial-myoepithelial carcinoma is a well differentiated malignant neoplasm, which originates from the salivary glands. The primary pulmonary manifestation is rare-about 30 cases have been reported worldwide. In the literature, anatomical resection has been described as the standard surgical approach. In the presented case, a wedge resection was performed, with no evidence for tumor relapse in the follow-up reevaluation after 24 months. This is the first case report of a primary pulmonary epithelial-myoepithelial carcinoma that has been treated with a non-anatomical wedge resection and lymph node dissection as a curative approach.

[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.

[Positionpaper on Telemonitoring in Sleep-Related Breathing Disorders]. / Positionspapier zum Telemonitoring bei schlafbezogenen Atmungsstörungen.

The use of telemonitoring in the care of patients with Sleep-related Breathing Disorders (SBD) can enhance medical support significantly. Telemonitoring aims at helping physicians to detect therapy problems early and thus improve patients' therapy adherence. Diagnostics and therapy decisions in the telemonitoring process nevertheless remain the responsibility of sleep specialists. The selection of data monitored, their evaluation and resulting consequences fall to the physician, who makes decisions and prescribes therapy in consultation with the patient. In light of professional legal and ethical requirements, it must be ensured that the extensive changes to the process flow in sleep medicine are designed in a way to guarantee high-quality patient care. In this position paper, the German Sleep Society, the German Respiratory Society, the Association of Pneumological Hospitals and the Federal Association of German Pneumologists comment on important aspects for implementation of telemonitoring for SRBD and describe the basic conditions required for its use.

[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.

[Preliminary Short-term Results of an All-day Outpatient Pulmonary Rehabilitation Program in an Acute Hospital on Patients with Mild to Very Severe COPD]. / Erste Kurzzeitergebnisse eines ganztägigen ambulanten pneumologischen Rehabilitationsprogramms an einer Akutklinik bei Patienten mit leicht- bis schwerstgradiger COPD.

INTRODUCTION: Positive effects of pulmonary rehabilitation on chronic obstructive pulmonary disease (COPD) are well known, and inpatient rehabilitation programs are the preferred modality in Germany. In this paper, we report on the recent results of a daily outpatient rehabilitation program offered at an acute hospital, the first of this kind in Germany. It is not known whether this kind of rehabilitation is an effective approach. METHODS: 32 consecutive COPD patients GOLD-stage II-IV, phenotype B-D (mean 64.5±21.9 years; 18 male, 14 female) completed a rehabilitation program of 19 (15-21) days conducted according to the recommendations of the National Accociation for Rehabilitation. In this prospective observational study, data (walking distance in the 6-MWD, BODE-Index, HADS-, BDI/TDI-, CAT-questionnaire) were collected at the beginning (T1) and at the end (T2) of the program and the results are presented in a pre- vs. post-analysis. RESULTS: We found significant positive effects for most of the measured parameters, except for body plethysmography, diffusion capacity and blood gas. Especially the increase in the 6 min walking distance (6-MWD) was remarkable (T1: 485.78±158.24, T2: 527.97±146.75 m, p=0.0212). There were no adverse events or complications. All participants were able to complete the program properly. CONCLUSION: Most of the measured parameters in COPD patients with stage II or worse disease improved significantly during the comprehensive outpatient rehabilitation program. A limitation of this study is the small number of cases, and further conclusions can only be made after examining a larger sample. The setting of this rehabilitation program in an acute hospital seems to be meaningful in an organisational and structural sense.