Specific molecular peak analysis by ion mobility spectrometry of volatile organic compounds in urine of COVID-19 patients: A novel diagnostic approach.

INTRODUCTION: SARS-CoV-2 is usually diagnosed from naso-/oropharyngeal swabs which are uncomfortable and prone to false results. This study investigated a novel diagnostic approach to Covid-19 measuring volatile organic compounds (VOC) from patients' urine. METHODS: Between June 2020 and February 2021, 84 patients with positive RT-PCR for SARS-CoV-2 were recruited as well as 54 symptomatic individuals with negative RT-PCR. Midstream urine samples were obtained for VOC analysis using ion mobility spectrometry (IMS) which detects individual molecular components of a gas sample based on their size, configuration, and charge after ionization. RESULTS: Peak analysis of the 84 Covid and 54 control samples showed good group separation. In total, 37 individual specific peaks were identified, 5 of which (P134, 198, 135, 75, 136) accounted for significant differences between groups, resulting in sensitivities of 89-94% and specificities of 82-94%. A decision tree was generated from the relevant peaks, leading to a combined sensitivity and specificity of 98% each. DISCUSSION: VOC-based diagnosis can establish a reliable separation between urine samples of Covid-19 patients and negative controls. Molecular peaks which apparently are disease-specific were identified. IMS is an additional non-invasive and cheap device for the diagnosis of this ongoing endemic infection. Further studies are needed to validate sensitivity and specificity.

[The problem of long/post-COVID in expert assessments]. / Problematik von Long­/Post-COVID in der Begutachtung.

Assessing long/post-COVID syndrome (PCS) following an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multidisciplinary challenge due to the diverse and complex symptoms. Besides discipline-specific evaluation of infection-related organ damage, the main issue is expert objectivity and causality assessment regarding subjective symptoms. The consequences of long/PCS raise questions of insurance rights in all fields of law. In cases of persistent impairment of performance, determining reduction in earning capacity is crucial for those affected. Recognition as an occupational disease (BK no. 3101) is vital for employees in healthcare and welfare sectors, along with occupational accident recognition and assessing the illness's consequences, including the reduction in earning capacity (MdE) in other sectors or work areas. Therefore, expert assessments of illness consequences and differentiation from previous illnesses or damage disposition are necessary in all areas of law, individually based on corresponding organ manifestations in medical fields and interdisciplinarily for complex late sequelae, for instance, by internists with appropriate qualifications for pulmonary or cardiac manifestations and neurologists, psychiatrists, and neuropsychologists for neurological and psychiatric manifestations, etc.

Prescribing and adjusting exercise training in chronic respiratory diseases - Expert-based practical recommendations.

BACKGROUND: International guidelines recommend endurance (ET) and strength training (ST) in patients with chronic respiratory diseases (CRDs), but only provide rough guidance on how to set the initial training load. This may unintentionally lead to practice variation and inadequate training load adjustments. This study aimed to develop practical recommendations on tailoring ET and ST based on practices from international experts from the field of exercise training in CRDs. METHODS: 35 experts were invited to address a 64-item online survey about how they prescribe and adjust exercise training. RESULTS: Cycling (97%) and walking (86%) were the most commonly implemented ET modalities. Continuous endurance training (CET, 83%) and interval endurance training (IET, 86%) were the frequently applied ET types. Criteria to prescribe IET instead of CET were: patients do not tolerate CET due to dyspnoea at the initial training session (79%), intense breathlessness during initial exercise assessment (76%), and/or profound exercise-induced oxygen desaturation (59%). For ST, most experts (68%) recommend 3 sets per exercise; 62% of experts set the intensity at a specific load that patients can tolerate for a range of 8 to 15 repetitions per set. Also, 56% of experts advise patients to approach local muscular exhaustion at the end of a single ST set. CONCLUSIONS: The experts´ practices were summarized to develop practical recommendations in the form of flowcharts on how experts apply and adjust CET, IET, and ST in patients with CRDs. These recommendations may guide health care professionals to optimize exercise training programs in patients with CRDs.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

[Recommendations from the German Respiratory Society for Pulmonary Rehabilitation in Patients with COVID-19]. / DGP-Empfehlungen zur pneumologischen Rehabilitation bei COVID-19.

The German Respiratory Society (DGP) has commissioned Assembly 12 "Rehabilitation, Prevention and Tobacco Control" to develop recommendations for the implementation of pulmonary rehabilitation in COVID-19 patients. This position paper is based on the current state of knowledge, which develops daily. This position paper describes the health consequences in COVID-19 as well as the indications for pulmonary rehabilitation. Rehabilitative therapies in COVID-19 are already indicated on the ward or intensive care unit, continue as early pulmonary rehabilitation in the acute hospital and as pulmonary rehabilitation in pulmonary rehabilitation centers. The main focus of this position paper is to propose recommendations for the content-related implementation of a multimodal, interdisciplinary pulmonary rehabilitation in COVID-19 patients.

[Exercise Training in Patients with Pulmonary Hypertension: A Systematic Review and Meta-analysis]. / Körperliches Training bei pulmonaler Hypertonie ­ ein systematisches Review mit Metaanalyse.

BACKGROUND: Pulmonary hypertension (PH) is defined as an elevation of mean pulmonary-arterial pressure by > 20 mmHg at rest, which may lead to right heart failure. Physical exercise has not been regularly recommended for PH patients for fear of symptom deterioration or occurrence of exercise-induced adverse events. METHODS: Three electronic databases were searched for randomized, controlled trials investigating exercise training in PH patients using the following keywords: "pulmonary hypertension" OR "pulmonary arterial hypertension" AND "exercise" OR "pulmonary rehabilitation" AND "randomized". RESULTS: Five studies involving 187 PH patients were included in this systematic review. Exercise programs lasted for 3 - 12 weeks (e. g. endurance training for 10 - 45 minutes; 60 - 80 % of the peak heart rate). PH patients significantly improved exercise capacity compared to controls in 6-minute walk distance (+ 45 m; 95 % CI: 26 m - 64 m) or peak oxygen consumption (+ 2.3 ml/kg/min; 95 % CI: 1.8 - 2.9 ml/kg/min), both p < 0.001. Also, physical and mental quality of life improved significantly by exercise training. No exercise-induced adverse events were observed. CONCLUSION: Supervised exercise training can safely and significantly improve physical performance and quality of life in clinically stable PH patients with optimal drug treatment. However, larger studies including a wider range of PH are mandatory.

[Impact of a Senso-Motoric Intervention in COPD-Patients Participating in an Outpatient Pulmonary Rehabilitation Program: A Randomized Controlled Trial]. / Effektivität eines sensomotorischen Krafttrainings im Rahmen einer ambulanten pneumologischen Rehabilitation bei COPD-Patienten: eine randomisierte kontrollierte Studie.

Objective Exercise training provides a cornerstone of pulmonary rehabilitation (PR) in COPD-patients. However, the components of the training are not yet fully investigated. We conducted a randomized controlled trial to investigate the effectiveness of a sensory-motoric training (SMT) in comparison to a conventional strength training (KT) according to the physical performance. Patients and Methods: 43 COPD patients were randomized and participated either in the intervention group (SMT = 30 minutes SMT per day) or in the control group (KT = 30 minutes KT per day). The SMT was performed as circuit training with five stations. The primary endpoint was the difference between T1 (start of the PR) and T2 (end of the PR) in 5-Times Sit-to-stand test (5-STST) in the intergroup comparison. Secondary endpoints were the intra- and intergroup comparisons of T1 and T2 in the 6-Minute Walk Test (6-MWT), COPD Assessment Test (CAT), St. George Respiratory Questionnaire (SGRQ), Hospital Anxiety- and Depression Scale (HADS) and in lung function. Results No significant differences were seen in the results of the 5-STST between the groups. Likewise, in the 6-MWT, SGRQ, CAT, HADS and lung function. The intragroup comparison between T1 and T2 showed significant differences in 5-STST, 6-MWT, SGRQ, CAT and HADS in both groups. The differences in lung function were not significantly, neither in the inter- nor in the intragroup comparison. Conclusion Similarly to a conventional strength training improvements in exercise capacity could be achieved with a SMT during PR in COPD patients. Further studies are necessary to define the role of the SMT in regards to postural control.

[Outcome predictors for COPD patients hospitalized for acute exacerbation]. / Outcomeprädiktoren für hospitalisierte COPD-Patienten bei akuter Exazerbation.

BACKGROUND: Prognostic factors for clinical failure of acute exacerbation in patients with COPD (AECOPD) are of special importance in order to choose an adequate therapy and resources during inpatient treatment. Our database was analyzed to identify predictors for a negative outcome. MATERIALS AND METHODS: In a retrospective analysis medical records of 616 patients (299 women; 317 men) hospitalized for AECOPD between January 2011 and January 2016 were analyzed in order to evaluate demographic and clinical parameters leading to adverse events. Only the first admission was considered. Logistic regression analysis was performed to determine the relative risk (odds ratio (OR) leading to severe adverse events such as intensive care unit (ICU) admission, mechanical ventilation (invasive or noninvasive), early readmission to ICU and hospital and death). RESULTS: An increased risk of an ICU admission was found for patients with a coronary heart disease (OR = 5.734; p = 0.009) and for patients requiring an antibiotic therapy (OR = 11.721; p = 0.003). An increased risk for rehospitalisation and mortality was found for age (OR = 1.034; p = 0.028) and a longer duration of the hospital stay (OR = 1.063; p = 0.042). A lower C­reactive protein (CRP) level was associated with a lower risk of readmission to the hospital (OR = 0.991; p = 0.03). An increased risk of ventilator therapy was found for patients with chronic heart failure (OR = 6.166; p = 0.02) and sleep apnea syndrome (OR = 6.698; p = 0.003), diabetes (OR = 3.754; p = 0.041) and a long stay in the ICU (OR = 2.018; p = 0.000). CONCLUSIONS: Comorbidities in patients with AECOPD were found to be a major risk factor for ICU admission and mechanical ventilation. Elderly patients and patients with prolonged hospital stay showed a higher risk for readmission and mortality. Patients with a low CRP blood level seemed to have a lower risk for rehospitalisation.

Altered blood levels of vitamin D, cathelicidin and parathyroid hormone in patients with sepsis-a pilot study.

It has been recognised that vitamin D (VitD) has a potential role in the regulation of inflammation and protection from infection. In a prospective clinical observational pilot study, we investigated the serum levels of 25-hydroxyvitamin-D3 (25(OH)D3), 1,25-hydroxyvitamin-D3 (1,25(OH)2D3), parathyroid hormone (PTH), and cathelicidin in intensive care unit (ICU) patients with or without systemic inflammatory response syndrome (SIRS). We included 32 patients with SIRS (septic patients), 16 ICU patients without SIRS, and 16 healthy controls. To substantiate the findings of the clinical study, we stimulated monocyte-derived macrophages with microbial patterns and analysed the impact of VitD on release of cytokines and antimicrobial activity. We found that patients with or without SIRS had relatively low levels of 25(OH)D3 and 1,25(OH)2D3. Patients with sepsis had significantly lower levels of 25(OH)D3 as compared to ICU control patients and healthy controls (10.53 ± 11.3 µg/l versus 16.46 ± 12.58 µg/l versus 24.04 ± 12.07 µg/l); the same was true for 1,25(OH)2D3. Serum levels of PTH and cathelicidin were significantly increased in sepsis patients, as compared to the other groups. In vitro, VitD significantly decreased the release of pro-inflammatory cytokines from macrophages and increased the antimicrobial activity of the cells. We concluded that patients with sepsis have significantly lower VitD levels. In vitro, VitD modulates inflammation and increases the antibacterial activity of innate immune cells. These findings suggest that VitD insufficiency is mechanistically related to increased susceptibility to SIRS and sepsis.

[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.

A dual center study to compare breath volatile organic compounds from smokers and non-smokers with and without COPD.

There is increasing evidence that breath volatile organic compounds (VOC) have the potential to support the diagnosis and management of inflammatory diseases such as COPD. In this study we used a novel breath sampling device to search for COPD related VOCs. We included a large number of healthy controls and patients with mild to moderate COPD, recruited subjects at two different sites and carefully controlled for smoking. 222 subjects were recruited in Hannover and Marburg, and inhaled cleaned room air before exhaling into a stainless steel reservoir under exhalation flow control. Breath samples (2.5 l) were continuously drawn onto two Tenax(®) TA adsorption tubes and analyzed in Hannover using thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). Data of 134 identified VOCs from 190 subjects (52 healthy non-smokers, 52 COPD ex-smokers, 49 healthy smokers, 37 smokers with COPD) were included into the analysis. Active smokers could be clearly discriminated by higher values for combustion products and smoking related VOCs correlated with exhaled carbon monoxide (CO), indicating the validity of our data. Subjects from the study sites could be discriminated even after exclusion of cleaning related VOCs. Linear discriminant analysis correctly classified 89.4% of COPD patients in the non/ex-smoking group (cross validation (CV): 85.6%), and 82.6% of COPD patients in the actively smoking group (CV: 77.9%). We extensively characterized 134 breath VOCs and provide evidence for 14 COPD related VOCs of which 10 have not been reported before. Our results show that, for the utilization of breath VOCs for diagnosis and disease management of COPD, not only the known effects of smoking but also site specific differences need to be considered. We detected novel COPD related breath VOCs that now need to be tested in longitudinal studies for reproducibility, response to treatment and changes in disease severity.

[Chronic obstructive pulmonary disease (COPD). Current concepts and new therapeutic options]. / Die chronisch-obstruktive Lungenerkrankung (COPD). Aktuelle Konzepte und neue Therapieoptionen.

Chronic obstructive pulmonary disease (COPD) is a very common chronic disease with increasing prevalence. Inhaled particles and gases (in particular tobacco smoke) induce chronic inflammation of the airways accompanied by a not fully reversible airflow limitation. Destruction of lung tissue and deterioration of gas exchange may follow. In parallel, several comorbidities can be observed. The COPD assessment was revised and now takes into account lung function, the patients' symptoms, and history of exacerbations. More recently, several new long-acting bronchodilators received approval. Combination products, consisting of long-acting ß2-agonists and long-acting anticholinergics, and a new combination of a long-acting ß-agonist and an inhaled corticosteroid will follow in the near future. Smoking cessation is of central importance.

The effects of weekly augmentation therapy in patients with PiZZ α1-antitrypsin deficiency.

BACKGROUND: The major concept behind augmentation therapy with human α(1)-antitrypsin (AAT) is to raise the levels of AAT in patients with protease inhibitor phenotype ZZ (Glu342Lys)-inherited AAT deficiency and to protect lung tissues from proteolysis and progression of emphysema. OBJECTIVE: To evaluate the short-term effects of augmentation therapy (Prolastin) on plasma levels of AAT, C-reactive protein, and chemokines/cytokines. MATERIALS AND METHODS: Serum and exhaled breath condensate were collected from individuals with protease inhibitor phenotype ZZ AAT deficiency-related emphysema (n = 12) on the first, third, and seventh day after the infusion of intravenous Prolastin. Concentrations of total and polymeric AAT, interleukin-8 (IL-8), monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein were determined. Blood neutrophils and primary epithelial cells were also exposed to Prolastin (1 mg/mL). RESULTS: There were significant fluctuations in serum (but not in exhaled breath condensate) levels of AAT polymers, IL-8, monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor within a week of augmentation therapy. In general, augmented individuals had higher AAT and lower serum levels of IL-8 than nonaugmented subjects. Prolastin added for 3 hours to neutrophils from protease inhibitor phenotype ZZ individuals in vitro reduced IL-8 release but showed no effect on cytokine/chemokine release from human bronchial epithelial cells. CONCLUSION: Within a week, augmentation with Prolastin induced fluctuations in serum levels of AAT polymers and cytokine/chemokines but specifically lowered IL-8 levels. It remains to be determined whether these effects are related to the Prolastin preparation per se or to the therapeutic efficacy of augmentation with AAT.

[Chronic obstructive pulmonary disease : new pharmacotherapeutic options]. / Chronisch-obstruktive Lungenerkrankung : Neue Optionen in der Arzneimitteltherapie.

Data about the clinical presentation of chronic obstructive pulmonary disease (COPD) have resulted in a new classification of the disease. The degree of airflow limitation has been amended by symptoms and exacerbation rate. The standard pharmacotherapy of stable COPD is in transition, as fixed combinations of long acting beta agonists and long acting anticholinergics are in the late stages of clinical development. On this background inhaled corticosteroids will need to be re-evaluated. Roflumilast is a recently approved therapeutic option that primarily diminishes exacerbation frequency in patients with chronic bronchitis and severe airflow obstruction (FEV(1) < 50%). In COPD patients with acute exacerbations procalcitonin levels can be used to guide antibiotic therapy. Comparable clinical outcomes can be achieved while using significantly less amounts of antibiotics.

[Pulmonary allergic reactions]. / Allergische Reaktionen der Lunge.

Allergic diseases of the lungs may affect the airways, the pulmonary parenchyma and the pulmonary vessels. The most relevant representatives are allergic asthma, hypersensitivity pneumonitis, bronchopulmonary aspergillosis and the Churg-Strauss syndrome. The type of allergic reaction and the pathophysiological consequences vary considerably between these entities. New drugs target specific mechanisms based on new insights into the pathogenetic processes of the underlying disease.