[A cross-sectional study in three German hospitals regarding oxygen therapy characteristics]. / Eine Querschnittsuntersuchung zur Qualität der Sauerstofftherapie in drei deutschen Krankenhäusern.

BACKGROUND: Oxygen (O2) therapy is one of the most commonly applied medications in German hospitals and rescue services. Both hypoxemia and hyperoxemia can be associated with complications. There is currently a lack of reliable data on the use, documentation and surveillance of O2-therapy in German hospitals. METHODS: We conducted a cross-sectional study on the use of O2 in three hospitals in Hannover, Germany. RESULTS: Of 343 patients included in this study, 20 % received O2 therapy. Twenty-nine percent of patients receiving O2 were at increased risk for hypercapnia. A standard operating procedure (SOP) for O2 therapy was available in only 68 % of patients. In 22 % patients the applied O2-therapy was appropriate in the context of the documented vital parameters. A complete documentation of vital parameters was conducted in only 30 % of all patients and 41 % of patients receiving O2-therapy. A surveillance of O2-therapy using capillary or arterial blood gas analysis was performed in 76 % of patients. Here, 64 % of patients showed normoxemia, 17 % showed hyperoxemia and 19 % of patients showed hypoxemia. The only identifiable predictor for an adequate O2-therapy was a previous invasive ventilation. DISCUSSION: Our data point towards and inadequate prescription, application and documentation of O2 therapy. The recently released German S3-guideline should be used to increase awareness among physicians and nursing staff regarding the use of O2-therapy to improve O2 therapy and consequently patient safety.

Characteristics and clinical implications of pleural effusions after lung transplantation: A retrospective analysis of 195 thoracocenteses in 113 patients.

Despite advances in lung transplantation (LTx), morbidity, and mortality are high. We hypothesized that pleural effusions requiring thoracocentesis lead to poor outcomes after LTx. We performed a single-center retrospective analysis of thoracocenteses after initial hospital discharge in LTx patients between March 2008 and September 2020 to identify risk factors, etiologies, and outcomes. Of the 1223 patients included, 113 patients (9.2%) required a total of 195 thoracocenteses. The cumulative incidence of thoracocentesis was 10.6% at 1 year and 14.2% at 5 years after transplantation. We observed a bimodal distribution of pleural effusion onset with a threshold at 6 months. Late-onset effusions were mostly of malignant or cardiac origin. We observed a high rate of nonspecific effusions (41.5%) irrespective of the timepoint post-transplantation. Patients with late-onset effusions had significantly lower survival compared to a matched controlled group (HR 2.43; 95% CI (1.27-4.62). All pulmonary function parameters were significantly decreased in patients requiring thoracocentesis compared to matched controls. Male sex and re-transplantation were risk factors for pleural effusions. In conclusion, pleural effusions requiring thoracocentesis occur frequently in LTx patients and lead to a reduced long-term allograft function. Late-onset effusions are associated with a lower survival.

Local Effects on Airway Inflammation and Systemic Uptake of 5 nm PEGylated and Citrated Gold Nanoparticles in Asthmatic Mice.

Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood-air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by preexisting airway diseases such as asthma. Here, BALB/c mice are treated according to the ovalbumin (OVA) asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene-glycol-coated (PEGylated) and citrate/tannic-acid-coated (citrated) 5 nm gold nanoparticles are applied intranasally to asthma and control groups, and (i) airway resistance and (ii) local tissue effects are measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs is quantified by inductively coupled plasma mass spectrometry. The asthmatic precondition increases nanoparticle uptake. Moreover, systemic uptake is higher for PEGylated gold nanoparticles compared to citrated nanoparticles. Nanoparticles inhibit both inflammatory infiltrates and airway hyperreactivity, especially citrated gold nanoparticles. Although the antiinflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle-based asthma therapies.

Primary Ciliary Dyskinesia in Adult Bronchiectasis - Data from the German Bronchiectasis Registry PROGNOSIS.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by the malfunction of motile cilia and a specific etiology of adult bronchiectasis of unknown prevalence. A better understanding of the clinical phenotype of adults with PCD is needed to identify individuals for referral to diagnostic testing. CLINICAL RESEARCH QUESTIONS: What is the frequency of PCD among adults with bronchiectasis; how do people with PCD differ from those with other etiologies; and which clinical characteristics are independently associated with PCD? STUDY DESIGN AND METHODS: We investigated the proportion of PCD among the participants of the German Bronchiectasis Registry PROGNOSIS, applied multiple imputation to account for missing data in 64 (FEV1), 58 (breathlessness), 26 (pulmonary exacerbations), and 2 subjects (BMI), respectively, and identified predictive variables from baseline data using multivariate logistic regression analysis. RESULTS: We consecutively recruited 1,000 patients from 38 centers across all levels of the German healthcare system. Overall, PCD was the fifth most common etiology of bronchiectasis in 87 subjects (9%) after idiopathic, post-infective, COPD, and asthma. People with PCD showed a distinct clinical phenotype. In multivariate regression analysis, the chance of PCD being the etiology of bronchiectasis increased with the presence of upper airway disease (chronic rhinosinusitis and/or nasal polyps; aOR, 6.3; 95% CI 3.3-11.9; P < .001); age < 53 years (aOR, 5.3; 95% CI 2.7-10.4; P < .001); radiological involvement of any middle and lower lobe (aOR, 3.7; 95% CI 1.3-10.8; P = .016); duration of bronchiectasis > 15 years (aOR, 3.6; 95% CI 1.9-6.9; P < .001); and a history of Pseudomonas aeruginosa isolation from respiratory specimen (aOR, 2.4; 95% CI 1.3-4.5; P = .007). INTERPRETATION: Within our nationally representative cohort, PCD was a common etiology of bronchiectasis. We identified few easy-to-assess phenotypic features, which may promote awareness for PCD among adults with bronchiectasis.

Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype.

Whole-exome sequencing has expedited the diagnostic work-up of primary ciliary dyskinesia (PCD), when used in addition to clinical phenotype and nasal nitric oxide. However, it reveals variants of uncertain significance (VUS) in established PCD genes or (likely) pathogenic variants in genes of uncertain significance in approximately 30% of tested individuals. We aimed to assess genotype-phenotype correlations in adults with bronchiectasis, clinical suspicion of PCD, and inconclusive whole-exome sequencing results using transmission electron microscopy (TEM) and ciliary image averaging by the PCD Detect software. We recruited 16 patients with VUS in CCDC39, CCDC40, CCDC103, DNAH5, DNAH5/CCDC40, DNAH8/HYDIN, DNAH11, and DNAI1 as well as variants in the PCD candidate genes DNAH1, DNAH7, NEK10, and NME5. We found normal ciliary ultrastructure in eight patients with VUS in CCDC39, DNAH1, DNAH7, DNAH8/HYDIN, DNAH11, and DNAI1. In six patients with VUS in CCDC40, CCDC103, DNAH5, and DNAI1, we identified a corresponding ultrastructural hallmark defect. In one patient with homozygous variant in NME5, we detected a central complex defect supporting clinical relevance. Using TEM as a targeted approach, we established important genotype-phenotype correlations and definite PCD in a considerable proportion of patients. Overall, the PCD Detect software proved feasible in support of TEM.

[A cross-sectional study in three German hospitals regarding oxygen therapy characteristics]. / Eine Querschnittsuntersuchung zur Qualität der Sauerstofftherapie in drei deutschen Krankenhäusern.

BACKGROUND: Oxygen (O2) therapy is one of the most commonly applied medications in German hospitals and rescue services. Both hypoxemia and hyperoxemia can be associated with complications. There is currently a lack of reliable data on the use, documentation and surveillance of O2-therapy in German hospitals. METHODS: We conducted a cross-sectional study on the use of O2 in three hospitals in Hannover, Germany. RESULTS: Of 343 patients included in this study, 20 % received O2 therapy. Twenty-nine percent of patients receiving O2 were at increased risk for hypercapnia. A standard operating procedure (SOP) for O2 therapy was available in only 68 % of patients. In 22 % patients the applied O2-therapy was appropriate in the context of the documented vital parameters. A complete documentation of vital parameters was conducted in only 30 % of all patients and 41 % of patients receiving O2-therapy. A surveillance of O2-therapy using capillary or arterial blood gas analysis was performed in 76 % of patients. Here, 64 % of patients showed normoxemia, 17 % showed hyperoxemia and 19 % of patients showed hypoxemia. The only identifiable predictor for an adequate O2-therapy was a previous invasive ventilation. DISCUSSION: Our data point towards and inadequate prescription, application and documentation of O2 therapy. The recently released German S3-guideline should be used to increase awareness among physicians and nursing staff regarding the use of O2-therapy to improve O2 therapy and consequently patient safety.

COVID-19 in lung transplant recipients-Risk prediction and outcomes.

Patients after lung transplantation are at risk for life-threatening infections. Recently, several publications on COVID-19 outcomes in this patient population appeared, but knowledge on optimal treatment, mortality, outcomes, and appropriate risk predictors is limited. A retrospective analysis was performed in a German high-volume lung transplant center between 19th March 2020 and 18th May 2021. Impact of COVID-19 on physical and psychological health, clinical outcomes, and mortality were analyzed including follow-up visits up to 12 weeks after infection in survivors. Predictive parameters on survival were assessed using univariate and multivariate proportional hazards regression models. Out of 1,046 patients in follow-up, 31 acquired COVID-19 during the pandemic. 12 of 31 (39%) died and 26 (84%) were hospitalized. In survivors a significant decline in exercise capacity (p = 0.034), TLC (p = 0.02), and DLCO (p = 0.007) was observed at follow-up after 3 months. Anxiety, depression, and self-assessed quality of life remained stable. Charlson comorbidity index predicted mortality (HR 1.5, 1.1-2.2; p = 0.023). In recipients with pre-existing CLAD, mortality and clinical outcomes were inferior. However, pre-existing CLAD did not predict mortality. COVID-19 remains a life-threatening disease for lung transplant recipients, particularly in case comorbidities. Further studies on long term outcomes and impact on pre-existing CLAD are needed.

Predictive modeling of nontuberculous mycobacterial pulmonary disease epidemiology using German health claims data.

OBJECTIVES: Administrative claims data are prone to underestimate the burden of non-tuberculous mycobacterial pulmonary disease (NTM-PD). METHODS: We developed machine learning-based algorithms using historical claims data from cases with NTM-PD to predict patients with a high probability of having previously undiagnosed NTM-PD and to assess actual prevalence and incidence. Adults with incident NTM-PD were classified from a representative 5% sample of the German population covered by statutory health insurance during 2011-2016 by the International Classification of Diseases, 10th revision code A31.0. Pre-diagnosis characteristics (patient demographics, comorbidities, diagnostic and therapeutic procedures, and medications) were extracted and compared to that of a control group without NTM-PD to identify risk factors. RESULTS: Applying a random forest model (area under the curve 0.847; total error 19.4%) and a risk threshold of >99%, prevalence and incidence rates in 2016 increased 5-fold and 9-fold to 19 and 15 cases/100,000 population, respectively, for both coded and non-coded vs. coded cases alone. CONCLUSIONS: The use of a machine learning-based algorithm applied to German statutory health insurance claims data predicted a considerable number of previously unreported NTM-PD cases with high probabilty.