Objective/Background Obstructive sleep apnea (OSA) is a common disease, which poses a significant health threat. Initial diagnostics with polygraphy or polysomnography are time consuming and expensive. Therefore, there is an unmet medical need for simplification, especially to exclude healthy patients from elaborate and unnecessary diagnostics. Impulse oscillometry (IOS) is a simple, cheap and noninvasive tool to asses upper airway resistance, which is increased in patients with OSA. The objective was to examine the relationship between IOS parameters and polysomnography in order to evaluate the applicability of IOS as a supplementing tool in OSA diagnostics. Patients/Methods We performed a prospective, cross-sectional, observational study across 107 participants. Pulmonary function tests with IOS, bodyplethysmography and overnight polysomnography were performed. We computed direct and partial correlations between IOS- and PSG-results. ROC analysis was performed to evaluate the most impactful predictive IOS parameter for diagnosing OSA. Results In ROC analysis the predicted probability of resistance at 5Hz (R5%) combined with age showed the highest AUC of 0.919, while R5 at 0.4325kPa/(l/s) provided the optimal cut-off. Correlations between IOS parameters and OSA severity as well as the duration and severity of oxygen desaturation were observed. However, they could not be reproduced as partial correlations after eliminating the BMI as confounding variable. Conclusion Our results cannot indicate the usefulness of IOS in OSA diagnostics. The lack of BMI-independent partial correlations between IOS- and PSG-results suggest a correlation without causality fallacy between IOS- and PSG-results. Therefore, the initial impression of good test quality for IOS might be invalid.

IntroductionInfluenza virus infections are a major global health problem. Influenza can result in mild/moderate disease or progress to more severe disease, leading to high morbidity and mortality. Severity is thought to be primarily driven by immunopathology, but predicting which individuals are at a higher risk of being hospitalized warrants investigation into host genetics and the molecular signatures of the host response during influenza infections.MethodsHere, we performed transcriptome and genotype analysis in healthy controls and patients exhibiting mild/moderate or severe influenza (ICU patients). A unique aspect of our study was the genotyping of all participants, which allowed us to assign ethnicities based on genetic variation and assess whether the variation was correlated with expression levels. ResultsWe identified 169 differentially expressed genes and related molecular pathways between patients in the ICU and those who were not in the ICU. The transcriptome/genotype association analysis identified 871 genes associated to a genetic variant and 39 genes distinct between African-Americans and Caucasians. We also investigated the effects of age and sex and found only a few discernible gene effects in our cohort. DiscussionTogether, our results highlight select risk factors that may contribute to an increased risk of ICU admission for influenza-infected patients. This should help to develop better diagnostic tools based on molecular signatures, in addition to a better understanding of the biological processes in the host response to influenza.

Zusammenfassung Hintergrund Die Hochfrequenz-Jetventilation (HFJV) wird in der pneumologischen Endoskopie für starre, diagnostische und therapeutische Bronchoskopien genutzt. Unklar ist hierbei, inwieweit durch den ungehinderten Atemgasstrom aus der Lunge des Patienten eine mikrobielle Belastung der Umgebungsluft entsteht. Material und Methoden Nach Beginn der HFJV (15 min) bei 16 starren Bronchoskopien wurden direkt am distalen Endoskopausgang, auf Untersucherhöhe (40 cm über dem Endoskopausgang), in 2 m Abstand vom Endoskop im Raum sowie am Zuluftauslass des Untersuchungsraums Luftkeimmessungen mit einem RCS-Luftkeimsammler vorgenommen. Anschließend erfolgten die Bestimmung der Anzahl und Art der isolierten Erreger in den Luftproben sowie eine Keimbestimmung in der bronchoalveolären Lavageflüssigkeit (BALF) aus der Patientenlunge. Ergebnisse Direkt am distalen Ende des Endoskops und auf Untersucherhöhe in 40 cm Entfernung wurde eine erhöhte Keimdichte (136 und 114 KBE/m3) nachgewiesen, die mit zunehmendem Abstand vom Bronchoskop deutlich abnahm (in 2 m Entfernung 98 KBE/m3 und am Zuluftauslass 82 KBE/m3). Die am häufigsten nachgewiesenen Bakterien waren Staphylococcus spp., Micrococcus spp. und Bacillus spp. In der BALF konnten nur in 4 von 16 Proben Erreger kultiviert werden, jedoch wurden dieselben Erreger in der BALF und der Umgebungsluft nachgewiesen. Schlussfolgerungen Bei der Durchführung einer starren Bronchoskopie, bei der die Patienten mit einem offenen HFJV-System kontrolliert mechanisch ventiliert werden, entsteht eine erhöhte Erregerbelastung der Umgebungsluft und damit eine potenzielle Gefahr für den Untersucher.

Background High-frequency jet ventilation (HFJV) is used in pneumological endoscopy for rigid, diagnostic, and therapeutic bronchoscopies. It is unclear to what extent the unobstructed flow of respiratory gas from the patient's lungs causes microbial contamination of the surrounding air. Material and methods After the start of the HFJV (15 min) in 16 rigid bronchoscopies, airborne pathogen measurements were taken directly at the distal endoscope outlet, at examiner height (40 cm above the endoscope outlet), at a 2 m distance from the endoscope in the room and at the supply air outlet of the examination room using an RCS air sampler. The number and type of pathogens isolated in the air samples were then determined, as well as germs in the bronchoalveolar lavage fluid (BALF) from the patient's lungs. Results An increased bacterial density (136 and 114 CFU/m (3) ) was detected directly at the distal end of the endoscope and at examiner height at a distance of 40 cm, which decreased significantly with increasing distance from the bronchoscope (98 CFU/m (3 )at a distance of 2 m and 82 CFU/m (3) at the supply air outlet). The most frequently detected bacteria were Staphylococcus spp., Micrococcus spp. and Bacillus spp. In the BALF, pathogens could only be cultivated in four of 16 samples, but the same pathogens were detected in the BALF and the ambient air. Conclusion When performing a rigid bronchoscopy, in which patients are mechanically ventilated in a controlled manner using an open HFJV system, there is an increased pathogen load in the ambient air and therefore a potential risk for the examiner.

Abstract Objectives Severe asthma is heterogeneous, with childhood-onset asthma believed more likely to be allergic, whereas adult-onset asthma is considered typically non-allergic. However, the allergic diagnosis is typically by exclusion: if patients do not react to an allergen panel, which is not standardized and often limited to few allergens, they are considered non-allergic. The overall aim of the ATLAS study was to characterize the sensitization to allergens in severe asthma (independent of phenotype). Methods Single-visit, cross-sectional, non-interventional study in adults with severe asthma. Analyses were conducted for total and specific immunoglobulin E against 53 allergens, overall and in subgroups, including age at asthma onset (<20 [childhood-onset] and >40 years of age). Results Among 1010 recruited patients, 28.4% reported childhood-onset asthma and 33.6% onset >40 years of age. After excluding patients receiving omalizumab/anti-IL5 therapy, 27.6% were not sensitized to any tested allergens, whereas 19.1% were sensitized to >10 allergens. All allergens triggered sensitization in some patients. Baseline characteristics in the two onset subgroups were similar; 23.2% with childhood-onset asthma were not sensitized to any allergen, compared to 32.0% with onset >40 years of age. Conclusion When a broad panel of allergens is used for sensitization testing, as many as three quarters of patients with severe asthma display sensitivity to at least one allergen, with substantial overlaps in all characteristics between the two age-at-onset subgroups. All of the tested allergens triggered a response in at least some patients, emphasizing the importance of including a broad range of allergens in any testing panel.

Background:Inhalation therapy is the cornerstone of treatment of bronchial asthma. A patient-specific selection of inhalation devices is necessary, as preference for a device plays an important role in terms of error rates in handling and adherence to therapy. However, there is no industry-independent study providing information on children's preferences for common inhaler types. The aim of the present study was to investigate the preference of asthmatic children for inhaler types commonly used in Germany. The effects of age, gender and the type of school visited on device preferences as well as the frequency of patient education and the role of health care providers in the choice for an inhaler were investigated.Methods:Eighty children were included in this prospective cross-sectional study (age: 10.87 ± 2.62 years). The analysis was based on a questionnaire and validated checklists. All participants tested the use of nine placebo inhalers (Breezhaler, Diskus, Respimat, Spiromax, Turbohaler, Autohaler, metered-dose inhaler, Easyhaler and Novolizer) in a randomized order. For each device, patients were asked to assess handling, rate different device characteristics and name the device they would prefer most or least.Results:The most favored device was the Novolizer. Moreover, the Spiromax scored highest in numerous categories such as suitability in emergencies and "easiest" device to use. Patient preferences with respect to the addressed inhaler features were not significantly related to age, gender or school type.Conclusion:The Novolizer and the Spiromax showed higher preference in pediatric patients as compared to other tested devices. Overall, there were significant differences in terms of preference when comparing the tested inhalers in different aspects.

Das Mediastinal-mass-Syndrom (MMS) ist eine lebensbedrohliche Anästhesiekomplikation, deren Vermeidung und Behandlung eine komplikationsträchtige, interdisziplinäre Aufgabe darstellt. Die Symptomatik variiert je nach Ausdehnung und Größe eines Mediastinaltumors sowie der Beteiligung entsprechender anatomischer Strukturen von asymptomatischen Patienten bis hin zu lebensbedrohlichen, kardiorespiratorischen Einschränkungen. Insbesondere im Rahmen einer Sedierung oder Allgemeinanästhesie besteht das Risiko der akuten kardiopulmonalen oder respiratorischen Dekompensation infolge einer tumorbedingten Kompression zentraler Blutgefäße oder der Atemwege, die nicht selten schwerwiegende Komplikationen bis hin zum Tode nach sich ziehen. In dieser Fallserie werden drei Patientinnen vorgestellt, die uns jeweils mit einem mediastinalen Tumor zur interventionellen bzw. operativen Diagnosesicherung zugewiesen wurden. Anhand der Kasuistiken werden typische Komplikationen demonstriert sowie Strategien zur Vermeidung möglicher Zwischenfälle eines MMS diskutiert. Die spezifischen anästhesiologischen Anforderungen durch das MMS, die Sicherheitsaspekte der Wahl der Operations- und Anästhesieverfahren, das Kreislauf- und Atemwegsmanagement für die erforderliche Einlungenventilation sowie verschiedene Aspekte zur Auswahl der Anästhetika werden in dieser Fallserie erörtert.

Purpose: Pre-operative assessment of thoracic lymphonodal (LN) involvement in patients with lung cancer (LC) is crucial when choosing the treatment modality. Visual assessment of F-18-FDG-PET/CT (PET/CT) is well established, however, there is still a need for prospective quantitative data to differentiate benign from malignant lesions which would simplify staging and guide the further implementation of computer-aided diagnosis (CAD). Methods: In this prospective study, 37 patients with confirmed lung cancer (m/f = 24/13; age: 70 [52–83] years) were analyzed. All patients underwent PET/CT and quantitative data (standardized uptake values) were obtained. Histological results were available for 101 thoracic lymph nodes. Quantitative data were matched to determine cut-off values for delineation between benign vs. malignant lymph nodes. Furthermore, a scoring system derived from these cut-off values was established. Statistical analyses were performed through ROC analysis. Results: Quantitative analysis revealed the optimal cut-off values (p < 0.01) for the differentiation between benign and malignant thoracic lymph nodes in patients suffering from lung cancer. The respective areas under the curve (AUC) ranged from 0.86 to 0.94. The highest AUC for a ratio of lymph node to healthy lung tissue was 0.94. The resulting accuracy ranged from 78.2% to 89.1%. A dedicated scoring system led to an AUC of 0.93 with a negative predictive value of 95.4%. Conclusion: Quantitative analysis of F-18-FDG-PET/CT data provides reliable results for delineation between benign and malignant thoracic lymph nodes. Thus, quantitative parameters can improve diagnostic accuracy and reliability and can also facilitate the handling of the steadily increasing number of clinical examinations.

Hintergrund Das Mediastinal Mass Syndrom (MMS) kann durch die Kompression der großen Blutgefäße oder Atemwege, hervorgerufen durch einen großen mediastinalen Tumor, zu einer akuten fatalen kardiopulmonalen Dekompensation führen. Diese tritt insbesondere im Rahmen einer Sedierung oder Narkose auf, so dass das Behandlungsteam aus Onkologen, Anästhesisten und Chirurgen vor eine komplexe Herausforderung gestellt wird.

To the editorAlthough β-lactam antibiotics (AB) are effective and well-tolerated [1], an estimated 12% of the population report allergy to penicillin [2].Of these, only 10-20% can be confirmed, bearing a strong need for de-labelling [3,4].We performed a cross-sectional study in 106 patients (44 men; age 59 ± 18 years) claiming AB allergy K. Luwich and E. Lücke contributed equally to the manuscript.

Amino acids and their metabolites are key regulators of immune responses, and plasma levels may change profoundly during acute disease states. Using targeted metabolomics, we evaluated concentration changes in plasma amino acids and related metabolites in community-acquired pneumonia (CAP, n = 29; compared against healthy controls, n = 33) from presentation to hospital through convalescence. We further aimed to identify biomarkers for acute CAP vs. the clinically potentially similar infection-triggered COPD exacerbation (n = 13). Amino acid metabolism was globally dysregulated in both CAP and COPD. Levels of most amino acids were markedly depressed in acute CAP, and total amino acid concentrations on admission were an accurate biomarker for the differentiation from COPD (AUC = 0.93), as were reduced asparagine and threonine levels (both AUC = 0.92). Reduced tryptophan and histidine levels constituted the most accurate biomarkers for acute CAP vs. controls (AUC = 0.96, 0.94). Only kynurenine, symmetric dimethyl arginine, and phenylalanine levels were increased in acute CAP, and the kynurenine/tryptophan ratio correlated best with clinical recovery and resolution of inflammation. Several amino acids did not reach normal levels by the 6-week follow-up. Glutamate levels were reduced on admission but rose during convalescence to 1.7-fold above levels measured in healthy control. Our data suggest that dysregulated amino acid metabolism in CAP partially persists through clinical recovery and that amino acid metabolism constitutes a source of promising biomarkers for CAP. In particular, total amino acids, asparagine, and threonine may constitute plasma biomarker candidates for the differentiation between CAP and infection-triggered COPD exacerbation and, perhaps, the detection of pneumonia in COPD.

ZusammenfassungDie kongenitale Muskeldystrophie Typ Ullrich (UCMD) ist eine seltene Erkrankung. Weltweit wurden bislang 50 Fälle genetisch gesichert. Autosomal-dominante und rezessive Mutationen des COL6A1/COL6A2 im Chromosom 21q22.3 oder des COL6A3 im Chromosom 2q37.3 führen zu einem Mangel an Kollagen VI. Typische Merkmale der UCMD sind Muskelschwäche von Körperstamm und Extremitäten, Hyperflexibilität der distalen und Kontrakturen der proximalen Gelenke, Rollstuhlpflichtigkeit im Alter von 9 bis 11 Jahren, Versteifung und Skoliose der Wirbelsäule und eine progrediente restriktive Ventilationsstörung. Etwa 50 % der Kinder benötigen im Alter von 11 bis 12 Jahren eine nichtinvasive Ventilation (NIV), wozu auch eine gestörte Funktion des Diaphragmas beiträgt. Es wird über die Narkose bei einer 21-jährigen Patientin mit einer UCMD berichtet, die seit dem 6. Lebensjahr rollstuhlpflichtig war und bei der seit 2018 eine lebenserhaltene NIV erfolgte. Wegen einer subpleuralen Einblutung in den linken Lungenunterlappen nach Entlastung eines Pneumothorax wurde eine videoassistierte thorakoskopische Chirurgie (VATS) vorgenommen. Die spezifischen Anforderungen durch die UCMD, das Atemwegsmanagement für die Einlungenventilation sowie Aspekte zur Auswahl der Anästhetika werden diskutiert. Nach erfolgreicher VATS konnte die Patientin am 7. postoperativen Tag in die Häuslichkeit entlassen werden.

Lipoblastoma is a rare benign, but highly proliferative tumor most commonly seen in early childhood. Recur-rence rates are high when complete resection is unfeasible and systemic therapy is necessary. We report the case of a large, aggressive thoracic and mediastinal lipoblastoma in a 20-year-old woman, which was surgically not resectable. The tumor has been characterized extensively including molecular pathology, molecular karyotyping, conventional chromosomal analysis and in vitro-chemosensitivity testing in search for alternative therapies. Nevertheless, this did not reveal treatable targets and systemic therapies, which were based on chemosensitivity testing proved ineffective. Despite all treatment attempts, the disease showed a progressive fatal course.

BACKGROUND:In amyotrophic lateral sclerosis (ALS) prognosis is poor due to progressive weakening of the respiratory muscles. Survival and quality of life can be improved by noninvasive ventilation (NIV), which is initially applied while sleeping. The indication for NIV is based on pulmonary function testing (PFT) and polysomnography (PSG) with capnography (tCO2). While it is desirable to predict nocturnal ventilation by waking PFT in ALS, the parameters suited for reliable predictions remain elusive. METHODS:We retrospectively analyzed parameters derived from PFT (spirometry, body plethysmography, diffusion capacity, respiratory muscle testing) and blood gas analysis, PSG and tCO2 in 42 patients with ALS (27 men, 15 women, age 69 ± 12.1 years) and performed Spearman's correlation analysis of daytime waking parameters and nighttime sleep parameters. RESULTS:28 patients (66.7%) showed restrictive impairment of ventilation and 15 patients (48.3%) showed insufficiency of the respiratory musculature. There was no obstructive impairment of ventilation. We did not observe any significant correlations between any single daytime PFT parameter with nocturnal pCO2. However, there were significant correlations between the ratios PIF/PEF, MEF50/MIF50, DLCO/VA as well as FEV1/FVC and nocturnal pCO2. Highly normal FEV1/FVC and Krogh-Factor (DLCOc/VA) indicated nocturnal hypercapnia. Furthermore, waking hypercapnia, concentrations of bicarbonate and base excess were each positively correlated with nocturnal hypercapnia. CONCLUSIONS:Waking PFT is not a good predictor of nocturnal ventilation. Inspiratory parameters as well as the ratios FEV1/FVC and DLCO/VA performed best and should be included in the interpretation. Our analyses confirm the relevance of inspiratory muscle weakness in ALS. PSG and tCO2 remain the gold standard for the assessment of nocturnal ventilation.

The polypeptide TFF3 belongs to the trefoil factor family (TFF) of lectins. TFF3 is typically secreted from mucous epithelia together with mucins. Both intestinal and salivary TFF3 mainly exist as disulfide-linked heterodimers with IgG Fc binding protein (FCGBP). Here, we investigated bronchial tissue specimens, bronchial secretions, and bronchoalveolar lavage (BAL) fluid from patients with a chronic obstructive pulmonary disease (COPD) background by fast protein liquid chromatography and proteomics. For the first time, we identified different molecular forms of TFF3 in the lung. The high-molecular mass form represents TFF3-FCGBP oligomers, whereas the low-molecular mass forms are homodimeric and monomeric TFF3 with possibly anti-apoptotic activities. In addition, disulfide-linked TFF3 heterodimers with an Mr of about 60k and 30k were detected in both bronchial secretions and BAL fluid. In these liquids, TFF3 is partly N-terminally truncated probably by neutrophil elastase cleavage. TFF3-FCGBP is likely involved in the mucosal innate immune defense against microbial infections. We discuss a hypothetical model how TFF3 might control FCGBP oligomerization. Furthermore, we did not find indications for interactions of TFF3-FCGBP with DMBT1gp340 or the mucin MUC5AC, glycoproteins involved in mucosal innate immunity. Surprisingly, bronchial MUC5AC appeared to be degraded when compared with gastric MUC5AC.

Background: The mechanisms underlying the link between nasal colonization with Staphylococcus aureus (S. aureus) and allergic asthma remain elusive. S. aureus can produce superantigen toxins and S. aureus enterotoxin B (SEB) has been proposed a central player in the interplay between S. aureus and allergic asthma. Its long-term effects on respiratory immunity are unknown. Aims and objectives: We aimed to elucidate SEB-mediated modulation of allergic airway inflammation (AAI). Methods: In an ovalbumin (OVA)-mediated mouse model (C57BL/6) for AAI, SEB was administered at a low (50ng) and a high (500 ng) dose alone or before sensitization against OVA. We assessed the recruitment of leukocytes and lymphocyte activation in the respiratory tract, respiratory cytokines and allergen‑specific IgE and IgG levels. Results: At the lower dose, SEB significantly boosted the OVA-specific IgE response. At the higher dose, SEB led to a significantly reduced recruitment of immune cells, including eosinophils, and a significantly dampened Th-2 cytokine response without inducing an overt Th-1 or pro-inflammatory response. OVA-specific IgE and IgG following sensitization alone were not affected by previous SEB administration, suggesting these effects were due to lasting modulation of the local respiratory immune milieu. Dependent on the dose, administration of SEB alone indeed resulted in a significantly altered respiratory cellular composition and cytokine milieu up to 14 days after treatment. Conclusions: SEB holds a previously unrecognized potential to sustainably modulate the respiratory immune milieu affecting allergic airway inflammation.

Fallbericht Ein 60-jähriger Patient mit COVID-19 (ohne bekannte Allergie oder Asthma) wurde beatmet auf die ITS verlegt. Die Entzündungswerte waren erhöht, die Eosinophilen und Lymphozyten waren normwertig. Ein Thorax-CT 5 Tage nach Intubation wies bipulmonale Milchglastrübungen und vereinzelte Konsolidierungen mit deutlichem Progress im Verlauf auf. Bei respiratorischer Verschlechterung wurde die venovenöse ECMO notwendig. Eine an Tag 32 durchgeführte BAL ergab 30% Lymphozyten (<13%), 25% Neutrophile (<3%) und 36% Eosinophile (<1%). BAL-Lymphozyten waren 97% CD3+T-Zellen (60–85%) und 53% zytotoxische CD8+CD3+T-Zellen (20–40%). Es wurde eine Prednisolontherapie mit 100 mg täglich begonnen. Die peripheren Eosinophilen stiegen konstant an, blieben dabei aber normwertig. Aufgrund eines massiven Hämatothorax unter Antikoagulation wurde an Tag 40 eine Thorakotomie durchgeführt. Das resezierte Lungenparenchym zeigte eine ausgeprägte eosinophile Vaskulitis, einen in Organisation befindlichen diffusen Alveolarschaden mit Zeichen der interstitiellen Inflammation und eine akute intraalveoläre Hämorrhagie, explizit ohne fortbestehende Entzündungsreaktion.

Background: Vitamin D deficiency has been associated with chronic disorders including chronic obstructive pulmonary disease (COPD) but the relationships with inflammation, exacerbations and disease progression remain unclear. Methods: In this monocentric cross-sectional observational study we analyzed the disease status, systemic inflammation, prior exacerbation frequency and loss in lung function in relation to serum 25-hydroxyvitamin D (25-OHD) levels in a cohort of 94 patients with COPD. Serum 25-OHD, C-reactive protein, interleukin-6 and tumor necrosis factor-alpha were quantified. Exacerbation frequencies and sunlight exposure were assessed. These parameters were analyzed in correlation to the current forced expiratory volume in 1 s (FEV1), the individual average 3-year FEV1 decline and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Results: We observed fair correlation between serum 25-OHD and the current FEV1 (r=0.38, P<0.001). Furthermore, mean serum 25-OHD was significantly altered between patients of GOLD stages I-IV (P=0.013). There was weak negative correlation of 25-OHD and the average annual change of the FEV1 (r=-0.26, P<0.05). Furthermore, we observed fair negative correlation between 25-OHD and C-reactive protein (r=-0.32, P<0.01) as well as weak negative correlation with interleukin-6 (r=-0.23, P<0.05). While the exacerbation frequency significantly differed between GOLD stages (P=0.04), there was no direct association between exacerbations and 25-OHD levels. Conclusion: Our data confirm frequent vitamin D deficiency in COPD and point out correlations between 25-OHD levels, systemic inflammation, disease severity and progression.