Influence of smoking and obesity on alveolar-arterial gas pressure differences and dead space ventilation at rest and peak exercise in healthy men and women

SummaryBackground and aimsBesides exercise intolerance, the assessment of ventilatory and perfusion adequacy allows additional insights in the disease pathophysiology in many cardiovascular or pulmonary diseases. Valid measurements of dead space/tidal volume ratios (VD/VT), arterial (a′) – end-tidal (et) carbon dioxide (CO2) and oxygen (O2) pressure differences (p(a′-et)CO2) and (p(et-a′)O2), and alveolar (A)–a′ O2 pressure differences (p(A-a′)O2) require using blood samples in addition to gas exchange analyses on a breath-by-breath-basis. Smoking and nutritional status are also important factors in defining disorders. Using a large healthy population we considered the impact of these factors to develop useful prediction equations.Methods and resultsIncremental cycle exercise protocols were applied to apparently healthy volunteer adults who did not have structural heart disease or echocardiographic or lung function pathologies. Age, height, weight, and smoking were analysed for their influence on the target parameters in each gender. Reference values were determined by regression analyses. The final study sample consisted of 476 volunteers (190 female), aged 25–85 years. Smoking significantly influences p(A-a′)O2 and p(a′-et)CO2 at rest and peak exercise, and VD/VT during exercise. Obesity influences upper limits of VD/VT, p(a′-et)CO2 and p(et-a′)O2 at rest as well as p(A-a′)O2 and p(et-a′)O2 at exercise. Reference equations for never-smokers as well as for apparently healthy smokers considering influencing factors are given.ConclusionGender, age, height, weight, and smoking significantly influence gas exchange. Considering all of these factors this study provides a comprehensive set of reference equations derived from a large number of participants of a population-based study

Stellenwert von Mycophenolat-Mofetil zur Behandlung der interstitiellen Lungenerkrankung bei systemischer Sklerose

Interstitial lung disease in systemic sclerosis (SSc-ILD) is a frequent organ complication with considerable mortality. Therapeutically, immunosuppressants are primarily used, particularly cyclophosphamide (CYC) and mycophenolate mofetil (MMF). Recently acquired data also showed an efficacy of the biologics rituximab and tocilizumab. The therapeutic options have most recently been expanded by the approval of the antifibrotic drug nintedanib. It is particularly beneficial in progressive fibrosing courses of ILD despite immunosuppression. The data from controlled trials on the efficacy and safety of CYC and MMF compiled in this review argue for a preferential use of MMF; however, the approval of MMF for this indication is still lacking. This is urgently needed for improved and simplified care of patients with SSc-ILD

Detection of Viral Infection and Bacterial Coinfection and Superinfection in Coronavirus Disease 2019 Patients Presenting to the Emergency Department Using the 29-mRNA Host Response Classifier IMX-BVN-3: A Multicenter Study.

Background Identification of bacterial coinfection in patients with coronavirus disease 2019 (COVID-19) facilitates appropriate initiation or withholding of antibiotics. The Inflammatix Bacterial Viral Noninfected (IMX-BVN) classifier determines the likelihood of bacterial and viral infections. In a multicenter study, we investigated whether IMX-BVN version 3 (IMX-BVN-3) identifies patients with COVID-19 and bacterial coinfections or superinfections. Methods Patients with polymerase chain reaction-confirmed COVID-19 were enrolled in Berlin, Germany; Basel, Switzerland; and Cleveland, Ohio upon emergency department or hospital admission. PAXgene Blood RNA was extracted and 29 host mRNAs were quantified. IMX-BVN-3 categorized patients into very unlikely, unlikely, possible, and very likely bacterial and viral interpretation bands. IMX-BVN-3 results were compared with clinically adjudicated infection status. Results IMX-BVN-3 categorized 102 of 111 (91.9%) COVID-19 patients into very likely or possible, 7 (6.3%) into unlikely, and 2 (1.8%) into very unlikely viral bands. Approximately 94% of patients had IMX-BVN-3 unlikely or very unlikely bacterial results. Among 7 (6.3%) patients with possible (n = 4) or very likely (n = 3) bacterial results, 6 (85.7%) had clinically adjudicated bacterial coinfection or superinfection. Overall, 19 of 111 subjects for whom adjudication was performed had a bacterial infection; 7 of these showed a very likely or likely bacterial result in IMX-BVN-3. Conclusions IMX-BVN-3 identified COVID-19 patients as virally infected and identified bacterial coinfections and superinfections. Future studies will determine whether a point-of-care version of the classifier may improve the management of COVID-19 patients, including appropriate antibiotic use

Sex-Specific associations of brain-derived neurotrophic factor and cardiorespiratory fitness in the general population

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Sex-Specific Associations of Brain-Derived Neurotrophic Factor and Cardiorespiratory Fitness in the General Population

The brain-derived neurotrophic factor (BDNF) was initially considered to be neuron-specific. Meanwhile, this neurotrophin is peripherally also secreted by skeletal muscle cells and increases due to exercise. Whether BDNF is related to cardiorespiratory fitness (CRF) is currently unclear. We analyzed the association of serum BDNF levels with CRF in the general population (Study of Health in Pomerania (SHIP-TREND) from Northeast Germany; n = 1607, 51% female; median age 48 years). Sex-stratified linear regression models adjusted for age, height, smoking, body fat, lean mass, physical activity, and depression analyzed the association between BDNF and maximal oxygen consumption (VO2peak), maximal oxygen consumption normalized for body weight (VO2peak/kg), and oxygen consumption at the anaerobic threshold (VO2@AT). In women, 1mL/min higher VO2peak, VO2peak/kg, and VO2@AT were associated with a 2.43 pg/mL (95% confidence interval [CI]: 1.16 to 3.69 pg/mL; p = 0.0002), 150.66 pg/mL (95% CI: 63.42 to 237.90 pg/mL; p = 0.0007), and 2.68 pg/mL (95% CI: 0.5 to 4.8 pg/mL; p = 0.01) higher BDNF serum concentration, respectively. No significant associations were found in men. Further research is needed to understand the sex-specific association between CRF and BDNF. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Digitization in Catalysis Research: Towards a Holistic Description of a Ni/Al2O3 Reference Catalyst for CO2 Methanation

There is considerable motivation in the catalysis community and chemical industry to envision a future where rational catalyst design and targeted chemical process optimization become standard. Achieving this goal for heterogeneous catalysis requires a cultural shift centered around effective research data management. The core elements of modern catalysis research are synthesis, characterization, and testing, while all can be elevated by effective collection, correlation, interoperation, and exploitation of data between disciplines and stakeholders. Here, first steps are made towards a holistic picture of an industrial Ni/Al$_2$O$_3$ reference catalyst for CO$_2$ methanation. A range of conventional and advanced characterization tools are applied to probe metal particle size and pore characteristics of the support, selected as crucial parameters for catalyst performance. Challenges are shown with respect to current reporting of characterization data and metadata, which ultimately influences the development and reliability of digital twins in catalysis research. Furthermore, the cooperation and combined expertise of diverse research groups from different fields is recognized as essential to deliver meaningful progress towards the digital future of catalysis research

Influence of the incremental step size in work rate on exercise response and gas exchange in patients with pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Cardiopulmonary exercise testing (CPET) has become increasingly important as a routine procedure in daily clinical work. So far, it is generally accepted that an individualized exercise protocol with exercise duration of 6 to 12 minutes is preferable to assess maximal exercise performance. The aim of this study was to compare an individualized NYHA adapted exercise protocol with a fixed standard protocol in patients with severe pulmonary arterial hypertension.</p> <p>Methods</p> <p>Twenty-two patients (17 female, 5 male; mean age 49 ± 14 yrs) underwent symptom limited CPET on a bicycle. On two consecutive days each subject performed a stepwise CPET according to a modified Jones protocol (16 Watt per minute stages) as well as an individualized NYHA adapted protocol with 5 or 10 Watt/min stages in a randomized order. Oxygen uptake at peak exercise (peakVO₂) and anaerobic threshold (VO₂AT), maximal ventilation (VE), breathing reserve (VE/MVV), ventilatory efficiency (VE vs. VCO₂slope), exercise time, maximal power and work rate were assessed and compared between both protocols.</p> <p>Results</p> <p>Comparing both, adapted NYHA protocol and standardized Jones protocol, we found significant differences in maximal power (56.7 ± 19 W vs. 74 ± 18 W; p < 0.001) and exercise time (332 ± 107 sec. vs. 248 ± 72 sec.; p < 0.001). In contrast, no significant differences were obvious comparing both protocols concerning work rate, VE, VE/MVV, peakVO₂, VO₂AT and VE vs. VCO₂slope.</p> <p>Conclusion</p> <p>Variations of incremental step size during CPET significantly affect exercise time and maximal power, whereas relevant parameters for clinical judgement and prognosis such as oxygen uptake, ventilation and ventilatory efficiency remain unchanged. These findings have practical implications for the exercise evaluation of patients with pulmonary hypertension. To reach maximal results for ventilation, oxygen uptake and gas exchange an individualization of incremental step size appears not to be mandatory.</p

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naive healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4(+) T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function