@article{TappeLauruschkatStrobeletal.2022, author = {Tappe, Beeke and Lauruschkat, Chris D. and Strobel, Lea and Pantale{\´o}n Garc{\´i}a, Jezreel and Kurzai, Oliver and Rebhan, Silke and Kraus, Sabrina and Pfeuffer-Jovic, Elena and Bussemer, Lydia and Possler, Lotte and Held, Matthias and H{\"u}nniger, Kerstin and Kniemeyer, Olaf and Sch{\"a}uble, Sascha and Brakhage, Axel A. and Panagiotou, Gianni and White, P. Lewis and Einsele, Hermann and L{\"o}ffler, J{\"u}rgen and Wurster, Sebastian}, title = {COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds}, series = {Frontiers in Immunology}, volume = {13}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2022.954985}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283558}, year = {2022}, abstract = {Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.}, language = {en} } @article{GuederBrennerStoerketal.2015, author = {G{\"u}der, G{\"u}lmisal and Brenner, Susanne and St{\"o}rk, Stefan and Held, Matthias and Broekhuizen, Berna D. L. and Lammers, Jan-Willem J. and Hoes, Arno W. and Rutten, Frans H.}, title = {Diagnostic and prognostic utility of mid-expiratory flow rate in older community-dwelling persons with respiratory symptoms, but without chronic obstructive pulmonary disease}, series = {BMC Pulmonary Medicine}, volume = {15}, journal = {BMC Pulmonary Medicine}, number = {83}, doi = {10.1186/s12890-015-0081-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125547}, year = {2015}, abstract = {Background The maximal expiratory flow at 50 \% of the forced vital capacity (MEF50) is the flow where half of forced vital capacity (FVC) remains to be exhaled. A reduced MEF50 has been suggested as a surrogate marker of small airways disease. The diagnostic and prognostic utility of this easy to assess spirometric variable in persons with respiratory symptoms, but without COPD is unclear. Methods We used data from the UHFO-COPD cohort in which 405 community-dwelling persons aged 65 years or over, and a general practitioner's diagnosis of chronic obstructive pulmonary disease (COPD) underwent pulmonary function testing and echocardiography. In total 161 patients had no COPD according to the spirometric GOLD criteria. We considered MEF50 as reduced if < 60 \% of predicted. Results Of the 161 patients without COPD (mean age 72 ± 5.7 years; 35 \% male; follow-up 4.5 ± 1.1 years), 61 (37.9 \%) had a reduced MEF50. They were older, had more pack-years of smoking, more respiratory symptoms, and used more frequently inhaled medication than the remaining 100 subjects. A reduced MEF50 was nearly twice as often associated with newly detected heart failure (HF) at assessment (29.5 \% vs. 15.6 \%, p = 0.045). In age-and sex-adjusted Cox regression analysis, a reduced MEF50 was significantly associated with episodes of acute bronchitis (hazard ratio 2.54 95 \% confidence interval (1.26; 5.13) P = 0.009), and in trend with pneumonia (2.14 (0.98; 4.69) P = 0.06) and hospitalizations for pulmonary reasons (2.28 (0.93; 5.62) P = 0.07). Conclusions In older community-dwelling persons with pulmonary symptoms but without COPD, a reduced MEF50 may help to uncover unrecognized HF, and identify those at a higher risk for episodes of acute bronchitis, pneumonia and hospitalizations for pulmonary reasons. Echocardiography and close follow-up should be considered in these patients.}, language = {en} } @article{HeldHesseGoettetal.2014, author = {Held, Matthias and Hesse, Alexander and G{\"o}tt, Franziska and Holl, Regina and H{\"u}bner, Gudrun and Kolb, Philipp and Langen, Heinz Jakob and Romen, Tobias and Walter, Franziska and Sch{\"a}fers, Hans Joachim and Wilkens, Heinrike and Jany, Berthold}, title = {A symptom-related monitoring program following pulmonary embolism for the early detection of CTEPH: a prospective observational registry study}, series = {BMC Pulmonary Medicine}, volume = {14}, journal = {BMC Pulmonary Medicine}, doi = {10.1186/1471-2466-14-141}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119281}, pages = {141}, year = {2014}, abstract = {Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term complication following an acute pulmonary embolism (PE). It is frequently diagnosed at advanced stages which is concerning as delayed treatment has important implications for favourable clinical outcome. Performing a follow-up examination of patients diagnosed with acute PE regardless of persisting symptoms and using all available technical procedures would be both cost-intensive and possibly ineffective. Focusing diagnostic procedures therefore on only symptomatic patients may be a practical approach for detecting relevant CTEPH. This study aimed to evaluate if a follow-up program for patients with acute PE based on telephone monitoring of symptoms and further examination of only symptomatic patients could detect CTEPH. In addition, we investigated the role of cardiopulmonary exercise testing (CPET) as a diagnostic tool. Methods In a prospective cohort study all consecutive patients with newly diagnosed PE (n=170, 76 males, 94 females within 26 months) were recruited according to the inclusion and exclusion criteria. Patients were contacted via telephone and asked to answer standardized questions relating to symptoms. At the time of the final analysis 130 patients had been contacted. Symptomatic patients underwent a structured evaluation with echocardiography, CPET and complete work-up for CTEPH. Results 37.7\%, 25.5\% and 29.3\% of the patients reported symptoms after three, six, and twelve months respectively. Subsequent clinical evaluation of these symptomatic patients saw 20.4\%, 11.5\% and 18.8\% of patients at the respective three, six and twelve months time points having an echocardiography suggesting pulmonary hypertension (PH). CTEPH with pathological imaging and a mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg at rest was confirmed in eight subjects. Three subjects with mismatch perfusion defects showed an exercise induced increase of PAP without increasing pulmonary artery occlusion pressure (PAOP). Two subjects with pulmonary hypertension at rest and one with an exercise induced increase of mPAP with normal PAOP showed perfusion defects without echocardiographic signs of PH but a suspicious CPET. Conclusion A follow-up program based on telephone monitoring of symptoms and further structured evaluation of symptomatic subjects can detect patients with CTEPH. CPET may serve as a complementary diagnostic tool.}, language = {en} } @article{HeldMittnachtKolbetal.2014, author = {Held, Matthias and Mittnacht, Maria and Kolb, Martin and Karl, Sabine and Jany, Berthold}, title = {Pulmonary and Cardiac Function in Asymptomatic Obese Subjects and Changes following a Structured Weight Reduction Program: A Prospective Observational Study}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {9}, doi = {10.1371/journal.pone.0107480}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119239}, pages = {e107480}, year = {2014}, abstract = {Background The prevalence of obesity is rising. Obesity can lead to cardiovascular and ventilatory complications through multiple mechanisms. Cardiac and pulmonary function in asymptomatic subjects and the effect of structured dietary programs on cardiac and pulmonary function is unclear. Objective To determine lung and cardiac function in asymptomatic obese adults and to evaluate whether weight loss positively affects functional parameters. Methods We prospectively evaluated bodyplethysmographic and echocardiographic data in asymptomatic subjects undergoing a structured one-year weight reduction program. Results 74 subjects (32 male, 42 female; mean age 42±12 years) with an average BMI 42.5±7.9, body weight 123.7±24.9 kg were enrolled. Body weight correlated negatively with vital capacity (R = -0.42, p<0.001), FEV1 (R = -0.497, p<0.001) and positively with P 0.1 (R = 0.32, p = 0.02) and myocardial mass (R = 0.419, p = 0.002). After 4 months the study subjects had significantly reduced their body weight (-26.0±11.8 kg) and BMI (-8.9±3.8) associated with a significant improvement of lung function (absolute changes: vital capacity +5.5±7.5\% pred., p<0.001; FEV1+9.8±8.3\% pred., p<0.001, ITGV+16.4±16.0\% pred., p<0.001, SR tot -17.4±41.5\% pred., p<0.01). Moreover, P0.1/Pimax decreased to 47.7\% (p<0.01) indicating a decreased respiratory load. The change of FEV1 correlated significantly with the change of body weight (R = -0.31, p = 0.03). Echocardiography demonstrated reduced myocardial wall thickness (-0.08±0.2 cm, p = 0.02) and improved left ventricular myocardial performance index (-0.16±0.35, p = 0.02). Mitral annular plane systolic excursion (+0.14, p = 0.03) and pulmonary outflow acceleration time (AT +26.65±41.3 ms, p = 0.001) increased. Conclusion Even in asymptomatic individuals obesity is associated with abnormalities in pulmonary and cardiac function and increased myocardial mass. All the abnormalities can be reversed by a weight reduction program.}, language = {en} } @article{GuederBrennerAngermannetal.2012, author = {G{\"u}der, G{\"u}lmisal and Brenner, Susanne and Angermann, Christiane E. and Ertl, Georg and Held, Matthias and Sachs, Alfred P. and Lammers, Jan Willem and Zanen, Peter and Hoes, Arno W. and St{\"o}rk, Stefan and Rutten, Frans H.}, title = {"GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75193}, year = {2012}, abstract = {Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed postbronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Agedependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis. Methods: In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography. Results: Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28\%) patients, and the three LLNs misclassified 114 (46\%), 96 (39\%), and 98 (40\%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 \% predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50\% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN. Conclusions: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.}, subject = {Medizin}, language = {en} }