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1. Acute COPD exacerbation treatment with noninvasive ventilation

Author

Ewert Ralf, Alexander Heine, Anne Obst, Karoline Koerner, Veit Hustig-Kittler, Michael Boesche, Mohamed Elhadad, Beate Stubbe, and Michael Westhoff

Subjects
Medicine, Science
Abstract

Abstract The establishment of a guideline for long-term noninvasive ventilation treatment (LTH-NIV) of acute hypercapnic exacerbations of chronic obstructive pulmonary disease (AECOPD) requiring acute ventilation has proven elusive. Most studies thus far have shown no mortality benefit of long-term noninvasive ventilation treatment. Using retrospective analysis of the data of our patients (n = 143) recruited from 2012 to 2019, we aimed to compare patients discharged with and without long-term noninvasive ventilation. The follow-up results showed no significant difference (p = 0.233) between the groups [LTH-NIV (n = 83); non-NIV (n = 60)] regarding readmission due to clinical worsening. However, the first- and second-year survival rates were 82% and 72%, respectively, in the LTH-NIV group and significantly different (p = 0.023) from 67 and 55% in the non-NIV group. The statistical models showed a significant mortality risk for the non-NIV group, with a hazard ratio (HR) of 2.82 (1.31; 6.03). To the best of our knowledge, this is the first study to demonstrate the mortality benefit of long-term NIV therapy for patients with AECOPD under real-world conditions.

Published
2023
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5. Author Correction: New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries

Author

Shrine, Nick, Guyatt, Anna L., Erzurumluoglu, A. Mesut, Jackson, Victoria E., Hobbs, Brian D., Melbourne, Carl A., Batini, Chiara, Fawcett, Katherine A., Song, Kijoung, Sakornsakolpat, Phuwanat, Li, Xingnan, Boxall, Ruth, Reeve, Nicola F., Obeidat, Ma’en, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A., Cook, James P., Sun, Benjamin B., Zhou, Jian, Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E., Marten, Jonathan, Enroth, Stefan, Kerr, Shona M., Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Allen, Richard J., Bakke, Per S., Beaty, Terri H., Bleecker, Eugene R., Bossé, Yohan, Brandsma, Corry-Anke, Chen, Zhengming, Crapo, James D., Danesh, John, DeMeo, Dawn L., Dudbridge, Frank, Ewert, Ralf, Gieger, Christian, Gulsvik, Amund, Hansell, Anna L., Hao, Ke, Hoffman, Joshua D., Hokanson, John E., Homuth, Georg, Joshi, Peter K., Joubert, Philippe, Langenberg, Claudia, Li, Xuan, Li, Liming, Lin, Kuang, Lind, Lars, Locantore, Nicholas, Luan, Jian’an, Mahajan, Anubha, Maranville, Joseph C., Murray, Alison, Nickle, David C., Packer, Richard, Parker, Margaret M., Paynton, Megan L., Porteous, David J., Prokopenko, Dmitry, Qiao, Dandi, Rawal, Rajesh, Runz, Heiko, Sayers, Ian, Sin, Don D., Smith, Blair H., Artigas, María Soler, Sparrow, David, Tal-Singer, Ruth, Timmers, Paul R. H. J., Van den Berge, Maarten, Whittaker, John C., Woodruff, Prescott G., Yerges-Armstrong, Laura M., Troyanskaya, Olga G., Raitakari, Olli T., Kähönen, Mika, Polašek, Ozren, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Probst-Hensch, Nicole M., Schulz, Holger, James, Alan L., Wilson, James F., Stubbe, Beate, Zeggini, Eleftheria, Jarvelin, Marjo-Riitta, Wareham, Nick, Silverman, Edwin K., Hayward, Caroline, Morris, Andrew P., Butterworth, Adam S., Scott, Robert A., Walters, Robin G., Meyers, Deborah A., Cho, Michael H., Strachan, David P., Hall, Ian P., Tobin, Martin D., and Wain, Louise V.

Published
2024
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8. Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era

Author

Gerhardt, Felix, Fiessler, Eva, Olsson, Karen M., Kayser, Moritz Z., Kovacs, Gabor, Gall, Henning, Ghofrani, H. Ardeschir, Badr Eslam, Roza, Lang, Irene M., Benjamin, Nicola, Grünig, Ekkehard, Halank, Michael, Lange, Tobias J., Ulrich, Silvia, Leuchte, Hanno, Held, Matthias, Klose, Hans, Ewert, Ralf, Wilkens, Heinrike, Pizarro, Carmen, Skowasch, Dirk, Wissmüller, Max, Hellmich, Martin, Olschewski, Horst, Hoeper, Marius M., and Rosenkranz, Stephan

Published
2024
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25. Preisentscheidungen

Author

Ewert, Ralf, Wagenhofer, Alfred, Rohlfing-Bastian, Anna, Ewert, Ralf, Wagenhofer, Alfred, and Rohlfing-Bastian, Anna

Published
2023
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32. Associations of Pulmonary Function with MRI Brain Volumes: A Coordinated Multi-Study Analysis

Author

Frenzel, Stefan, Bis, Joshua C, Gudmundsson, Elias F, O’Donnell, Adrienne, Simino, Jeannette, Yaqub, Amber, Bartz, Traci M, Brusselle, Guy GO, Bülow, Robin, DeCarli, Charles S, Ewert, Ralf, Gharib, Sina A, Ghosh, Saptaparni, Gireud-Goss, Monica, Gottesman, Rebecca F, Ikram, M Arfan, Knopman, David S, Launer, Lenore J, London, Stephanie J, Longstreth, WT, Lopez, Oscar L, van Lent, Debora Melo, O’Connor, George, Satizabal, Claudia L, Shrestha, Srishti, Sigurdsson, Sigurdur, Stubbe, Beate, Talluri, Rajesh, Vasan, Ramachandran S, Vernooij, Meike W, Völzke, Henry, Wiggins, Kerri L, Yu, Bing, Beiser, Alexa S, Gudnason, Vilmundur, Mosley, Thomas, Psaty, Bruce M, Wolters, Frank J, Grabe, Hans J, and Seshadri, Sudha

Subjects
Brain Disorders, Lung, Neurosciences, Clinical Research, Aging, Humans, Aged, Forced Expiratory Volume, Cross-Sectional Studies, Magnetic Resonance Imaging, Brain, Dementia, epidemiology, magnetic resonance imaging, respiratory function tests, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

BackgroundPrevious studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent.ObjectiveTo study the cross-sectional associations of pulmonary function with structural brain variables.MethodsData from six large community-based samples (N = 11,091) were analyzed. Spirometric measurements were standardized with respect to age, sex, height, and ethnicity using reference equations of the Global Lung Function Initiative. Associations of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio FEV1/FVC with brain volume, gray matter volume, hippocampal volume, and volume of white matter hyperintensities were investigated using multivariable linear regressions for each study separately and then combined using random-effect meta-analyses.ResultsFEV1 and FVC were positively associated with brain volume, gray matter volume, and hippocampal volume, and negatively associated with white matter hyperintensities volume after multiple testing correction, with little heterogeneity present between the studies. For instance, an increase of FVC by one unit was associated with 3.5 ml higher brain volume (95% CI: [2.2, 4.9]). In contrast, results for FEV1/FVC were more heterogeneous across studies, with significant positive associations with brain volume, gray matter volume, and hippocampal volume, but not white matter hyperintensities volume. Associations of brain variables with both FEV1 and FVC were consistently stronger than with FEV1/FVC, specifically with brain volume and white matter hyperintensities volume.ConclusionIn cross-sectional analyses, worse pulmonary function is associated with smaller brain volumes and higher white matter hyperintensities burden.

Published
2022

33. Long-term effects of intravenous iloprost in patients with idiopathic pulmonary arterial hypertension deteriorating on non-parenteral therapy

Author

Knudsen Lars, Schurawlew Alexander, Nickel Nils, Tiede Henning, Ghofrani Hossein A, Wilkens Heinrike, Ewert Ralf, Halank Michael, Klose Hans, Bäzner Carlos, Behr Jürgen, and Hoeper Marius M

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background The majority of patients with idiopathic pulmonary arterial hypertension (IPAH) in functional classes II and III are currently being treated with non-parenteral therapies, including endothelin receptor antagonists (ERA), phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these substances. If these treatments fail, current guidelines recommend the addition of parenteral prostanoid therapy. There is, however, limited evidence for the efficacy of parenteral prostanoids when added to combinations of non-parenteral therapies. Methods In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival. Results During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome. Conclusion In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs.

Published
2011
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34. Peripheral endothelial dysfunction is associated with gas exchange inefficiency in smokers

Author

Ewert Ralf, Völzke Henry, Empen Klaus, Felix Stephan B, Dörr Marcus, Opitz Christian F, Obst Anne, Gläser Sven, Schäper Christoph, and Koch Beate

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Aims To assess the cross-sectional association between exercise capacity, gas exchange efficiency and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in a large-scale population-based survey. Methods The study population was comprised of 1416 volunteers 25 to 85 years old. Oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and ventilatory efficiency (VE vs. VCO2 slope and VE/VCO2@AT) were assessed on a breath-by-breath basis during incremental symptom-limited cardiopulmonary exercise. FMD and NMD measurements at rest were performed using standardised ultrasound techniques. Results Multivariable logistic regression analyses revealed a significant association between FMD and ventilatory efficiency in current smokers but not in ex-smokers or non-smokers. There was no association between FMD and VO2@AT or peak VO2. In current smokers, for each one millimetre decrement in FMD, VE/VCO2@AT improved by -3.6 (95% CI -6.8, -0.4) in the overall population [VE vs. VCO2 slope -3.9 (-7.1, -0.6)]. These results remained robust after adjusting for all major influencing factors. Neither exercise capacity nor ventilatory efficiency was significantly associated with NMD. Conclusion In current smokers, FMD is significantly associated with ventilatory efficiency. This result may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.

Published
2011
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35. Regional differences in prediction models of lung function in Germany

Author

Schäper Christoph, Ewert Ralf, Vogelmeier Claus, Schäfer Torsten, Jörres Rudolf A, Karrasch Stefan, Koch Beate, Chen Chih-Mei, Schnabel Eva, Völzke Henry, Obst Anne, Felix Stephan B, Wichmann H-Erich, Gläser Sven, and Heinrich Joachim

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods Within three studies (KORA C, SHIP-I, ECRHS-I) in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal) but not extremely high or low lung function values in the whole study population. Conclusions Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

Published
2010
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36. Influence of the incremental step size in work rate on exercise response and gas exchange in patients with pulmonary hypertension

Author

Völzke Henry, Opitz Christian F, Koch Beate, Lodziewski Sven, Gläser Sven, and Ewert Ralf

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background 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. Methods 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. VCO2 slope), exercise time, maximal power and work rate were assessed and compared between both protocols. Results 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. VCO2 slope. Conclusion 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.

Published
2008
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37. Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial

Author

White, R James, Jerjes-Sanchez, Carlos, Bohns Meyer, Gisela Martina, Pulido, Tomas, Sepulveda, Pablo, Wang, Kuo Yang, Grünig, Ekkehard, Hiremath, Shirish, Yu, Zaixin, Gangcheng, Zhang, Yip, Wei Luen James, Zhang, Shuyang, Khan, Akram, Deng, CQ, Grover, Rob, Tapson, Victor F, Svetliza, Graciela Noemi, Lescano, Adrian Jose, Bortman, Guillermo Roberto, Diez, Fabian Antonio, Botta, Christian Edgardo, Fitzgerald, John, Feenstra, Eelke, Kermeen, Fiona Dawn, Keogh, Anne Margaret, Williams, Trevor John, Yousseff, Peter Paul, Ng, Benjamin Joh-Han, Smallwood, David McNaughton, Dwyer, Nathan Brent, Brown, Martin Russell, Lang, Irene M, Steringer-Mascherbauer, Regina, Arakaki, Jaquelina Sonoe Ota, Campos, Frederico Thadeu Assis Figueiredo, de Amorim Correa, Ricardo, de Souza, Rogerio, Bohns Meyer, Gisela M, Moreira, Maria Auxiliadora Carmo, Yoo, Hugo Hyung Bok, Lapa, Monica Silveira, Swiston, John, Hirani, Naushad, Mehta, Sanjay, Michelakis, Evangelos, Sepulveda, Pablo Andres, Blancaire, Monica Maria Zagolin, Liu, Jimming, Shuyang, Zhang, Pan, Lei, Chunde, Bao, Qun, Yi, Xiaoshu, Cheng, Zaixin, Yu, Li, Xinli, Hua, Yao, Zhu, Xianyang, Chen, Yundai, Zhaozhong, Cheng, Yang, Yuanhua, Daxin, Zhou, Jieyan, Shen, Nielsen-Kudsk, Jens Erik, Carlsen, Jorn, Bourdin, Arnaud, Hachulla, Eric, Dromer, Claire, Chaouat, Ari, Reynaud-Gauber, Martine, Seronde, Marie-France, Klose, Hans, Halank, Michael, Hoffken, Gert, Ewert, Ralf, Rosenkranz, Stephan, Grunig, Ekkehard, Kruger, Ulrich, Kronsbein, Juliane, Hauptmeier, Barbara Monika, Koch, Andrea, Held, Matthias, Lange, Tobias Johannes, Neurohr, Claus, Wilkens, Heinrike, Wilhelm Wirtz, Hubert Rolf, Konstantinides, Stavros, Argyropoulou-Pataka, Paraskevi, Orfanos, Stylianos, Kerkar, Prafulla Gopinath, Suresh, Pujar Venkateshacharya, Baxi, Hemang Ashwinkumar, Oomman, Abraham, Abhaichand, Rajpal Kanaklal, Arjun, Padma Kumar Edla, Chopra, Vijay, Mehrotra, Rahul, Rajput, Rajeev Kumar, and Sawhney, Jitendra Pal Singh

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Clinical Trials and Supportive Activities, Rare Diseases, Patient Safety, Digestive Diseases, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Administration, Oral, Adolescent, Adult, Aged, Antihypertensive Agents, Double-Blind Method, Epoprostenol, Female, Humans, Male, Middle Aged, Placebos, Pulmonary Arterial Hypertension, Young Adult, FREEDOM-EV Investigators, clinical study, combination therapy, oral treprostinil, pulmonary arterial hypertension, sequential therapy, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Published
2020

40. Risk stratification and response to therapy in patients with pulmonary arterial hypertension and comorbidities: A COMPERA analysis

Author

Rosenkranz, Stephan, Pausch, Christine, Coghlan, John G., Huscher, Doerte, Pittrow, David, Grünig, Ekkehard, Staehler, Gerd, Vizza, Carmine Dario, Gall, Henning, Distler, Oliver, Delcroix, Marion, Ghofrani, Hossain A., Ewert, Ralf, Kabitz, Hans-Joachim, Skowasch, Dirk, Behr, Juergen, Milger, Katrin, Halank, Michael, Wilkens, Heinrike, Seyfarth, Hans-Jürgen, Held, Matthias, Scelsi, Laura, Neurohr, Claus, Vonk-Noordegraaf, Anton, Ulrich, Silvia, Klose, Hans, Claussen, Martin, Eisenmann, Stephan, Schmidt, Kai-Helge, Remppis, Bjoern Andrew, Skride, Andris, Jureviciene, Elena, Gumbiene, Lina, Miliauskas, Skaidrius, Löffler-Ragg, Judith, Lange, Tobias J., Olsson, Karen M., Hoeper, Marius M., and Opitz, Christian

Published
2023
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43. Phenotyping of idiopathic pulmonary arterial hypertension: a registry analysis

Author

Hoeper, Marius M, Dwivedi, Krit, Pausch, Christine, Lewis, Robert A, Olsson, Karen M, Huscher, Doerte, Pittrow, David, Grünig, Ekkehard, Staehler, Gerd, Vizza, Carmine Dario, Gall, Henning, Distler, Oliver, Opitz, Christian, Gibbs, John Simon R, Delcroix, Marion, Park, Da-Hee, Ghofrani, Hossein Ardeschir, Ewert, Ralf, Kaemmerer, Harald, Kabitz, Hans-Joachim, Skowasch, Dirk, Behr, Juergen, Milger, Katrin, Lange, Tobias J, Wilkens, Heinrike, Seyfarth, Hans-Jürgen, Held, Matthias, Dumitrescu, Daniel, Tsangaris, Iraklis, Vonk-Noordegraaf, Anton, Ulrich, Silvia, Klose, Hans, Claussen, Martin, Eisenmann, Stephan, Schmidt, Kai-Helge, Swift, Andrew J, Thompson, Alfred A Roger, Elliot, Charlie A, Rosenkranz, Stephan, Condliffe, Robin, Kiely, David G, and Halank, Michael

Published
2022
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44. Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension

Author

Eichstaedt, Christina A., Saßmannshausen, Zoe, Shaukat, Memoona, Cao, Ding, Xanthouli, Panagiota, Gall, Henning, Sommer, Natascha, Ghofrani, Hossein-Ardeschir, Seyfarth, Hans-Jürgen, Lerche, Marianne, Halank, Michael, Kleymann, Janina, Benjamin, Nicola, Harutyunova, Satenik, Egenlauf, Benjamin, Milger, Katrin, Rosenkranz, Stephan, Ewert, Ralf, Klose, Hans, Hoeper, Marius M., Olsson, Karen M., Lankeit, Mareike, Lange, Tobias J., Hinderhofer, Katrin, and Grünig, Ekkehard

Published
2022
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46. Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea–related Quantitative Trait Locus in Men

Author

Chen, Han, Cade, Brian E, Gleason, Kevin J, Bjonnes, Andrew C, Stilp, Adrienne M, Sofer, Tamar, Conomos, Matthew P, Ancoli-Israel, Sonia, Arens, Raanan, Azarbarzin, Ali, Bell, Graeme I, Below, Jennifer E, Chun, Sung, Evans, Daniel S, Ewert, Ralf, Frazier-Wood, Alexis C, Gharib, Sina A, Haba-Rubio, José, Hagen, Erika W, Heinzer, Raphael, Hillman, David R, Johnson, W Craig, Kutalik, Zoltan, Lane, Jacqueline M, Larkin, Emma K, Lee, Seung Ku, Liang, Jingjing, Loredo, Jose S, Mukherjee, Sutapa, Palmer, Lyle J, Papanicolaou, George J, Penzel, Thomas, Peppard, Paul E, Post, Wendy S, Ramos, Alberto R, Rice, Ken, Rotter, Jerome I, Sands, Scott A, Shah, Neomi A, Shin, Chol, Stone, Katie L, Stubbe, Beate, Sul, Jae Hoon, Tafti, Mehdi, Taylor, Kent D, Teumer, Alexander, Thornton, Timothy A, Tranah, Gregory J, Wang, Chaolong, Wang, Heming, Warby, Simon C, Wellman, D Andrew, Zee, Phyllis C, Hanis, Craig L, Laurie, Cathy C, Gottlieb, Daniel J, Patel, Sanjay R, Zhu, Xiaofeng, Sunyaev, Shamil R, Saxena, Richa, Lin, Xihong, and Redline, Susan

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Sleep Research, Clinical Research, Human Genome, Lung, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Phosphatidylethanolamine N-Methyltransferase, Quantitative Trait Loci, Sex Characteristics, Sleep Apnea, Obstructive, Sleep, REM, Sterol Regulatory Element Binding Protein 1, Trans-Activators, Transcription Factors, ras Proteins, obstructive sleep apnea, genetics, genome-wide association studies, multiethnic, sexual dimorphism, Cardiorespiratory Medicine and Haematology, Respiratory System, Biochemistry and cell biology, Cardiovascular medicine and haematology
Abstract

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

Published
2018

47. The Association Between C24:0/C16:0 Ceramide Ratio and Cardiorespiratory Fitness is Robust to Effect Modifications by Age and Sex

Author

Zatloukal, Jule, primary, Zylla, Stephanie, additional, Markus, Marcello R.P., additional, Ewert, Ralf, additional, Gläser, Sven, additional, Völzke, Henry, additional, Albrecht, Diana, additional, Friedrich, Nele, additional, Nauck, Matthias, additional, Peterson, Linda R., additional, Jiang, Xuntian, additional, Schaffer, Jean E., additional, Felix, Stephan B., additional, Dörr, Marcus, additional, Bahls, Martin, additional, and Gross, Stefan, additional

Published
2024
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49. Autorinnen und Autoren

Author

Abele-Horn, Marianne, primary, Amann, Bruno, additional, Aspöck, Christoph, additional, Barner, Dorina, additional, Barre, Felix, additional, Barth, Fritz, additional, Becker, Karsten, additional, Behrens-Baumann, Wolfgang, additional, Below, Harald, additional, Berens, Milena, additional, Blaschke, Sabine, additional, Bley, Ivonne, additional, Bockholdt, Britta, additional, Borg, Michael, additional, von der Brelie, Christian, additional, Bulitta, Clemens, additional, Caspari, Gregor, additional, Clauberg, Sigrid, additional, Danner, Bernhard, additional, Dietlein, Edeltrud, additional, Dietz, Birgit, additional, Dissemond, Joachim, additional, Durovic, Ana, additional, Ebbecke, Benjamin, additional, Eberlein, Thomas, additional, Eckmann, Christian, additional, Eggers, Maren, additional, Elstner, Matthias, additional, Engelhart, Steffen, additional, Ettl, Brigitte, additional, Ewert, Ralf, additional, Federspil, Philippe, additional, Fengler, Thomas, additional, Fleßa, Steffen, additional, Franke, Steffen, additional, Bondio, Mariacarla Gadebusch, additional, Gastmeier, Petra, additional, Gattringer, Rainer, additional, Gebel, Jürgen, additional, Girndt, Matthias, additional, Gleich, Sabine, additional, Graninger, Wolfgang, additional, Groß, Raoul, additional, Gründling, Matthias, additional, Hagel, Stefan, additional, Hamprecht, Klaus, additional, Harnoss, Julian-Camill, additional, Heckmann, Matthias, additional, Heeg, Peter, additional, Heidecke, Claus-Dieter, additional, Heine, Alexander, additional, Heppner, Hans Jürgen, additional, Heudorf, Ursel, additional, Holzhausen, Jan, additional, Hübner, Claudia, additional, Jabs, Jonas, additional, Jacobshagen, Anja, additional, Jäkel, Christian, additional, Jansen, Bernd, additional, Jatzwauk, Lutz, additional, Kalunga-Peters, André, additional, Kampf, Günter, additional, Kellner, Robert, additional, Kiefel, Volker, additional, Kindler, Stefan, additional, Kirsch, Gerhard, additional, Koch, Stefan, additional, Kohlmann, Thomas, additional, Kohnen, Wolfgang, additional, Kolbe, Claudia, additional, Koller, Walter, additional, Krämer, Irene, additional, Kranz, Jennifer, additional, Krause, Wolfgang, additional, Krey, Karl-Friedrich, additional, Krüger, William H., additional, Kucheryava, Nataliya, additional, Külpmann, Rüdiger, additional, Küster, Helmut, additional, Kuhn, Sven-Olaf, additional, Labs, Eckard, additional, Lafontaine, Jörg, additional, Leiß, Ottmar, additional, Lerch, Markus M., additional, Lippert, Hans, additional, Loczenski, Barbara, additional, Maidhof, Heinrich, additional, Maier, David, additional, Maier, Stefan, additional, Martiny, Heike, additional, Maschmeyer, Georg, additional, Mavridou, Kiriaki, additional, Mellmann, Alexander, additional, Metelmann, Hans-Robert, additional, Mett, Tobias R., additional, Meybohm, Patrick, additional, Meyer, Elisabeth, additional, Mielke, Martin, additional, Müller, Jan-Uwe, additional, von Müller, Lutz, additional, Mutters, Nico T., additional, Nauck, Friedemann, additional, Nienhaus, Albert, additional, Notbohm, Gert, additional, Novotny, Alexander, additional, Ossadnik, Michael, additional, Ostgathe, Christoph, additional, Papke, Roald, additional, Paul, Thomas, additional, Penne, Alexander, additional, Piechota, Hansjürgen, additional, Pilatz, Adrian, additional, Pitten, Frank-Albert, additional, Platz, Thomas, additional, Pleyer, Uwe, additional, Pochhammer, Julius, additional, Pohl, Marcus, additional, Reißhauer, Anett, additional, von Rheinbaben, Friedrich, additional, Rimek, Dagmar, additional, Ritter, Manuel, additional, Ruback, Sylvia, additional, Schneidewind, Laila, additional, Schroeder, Henry W.S., additional, Schulz-Schaeffer, Walter, additional, Schulz-Stübner, Sebastian, additional, Schulze, Marco H., additional, Schwierzeck, Vera, additional, Seebauer, Christian, additional, Seifert, Julia, additional, Seifert, Ulrike, additional, Siegmann, Silvester, additional, Slevogt, Hortense, additional, Sonntag, Hans-Günther, additional, Steinmann, Eike, additional, Steinmann, Jochen, additional, Streitenberg, Lada, additional, Suchomel, Miranda, additional, Thanheiser, Marc, additional, Trautmann, Matthias, additional, Vakil, Richard, additional, Viehöver, Sibylle, additional, Vogt, Peter M., additional, Vonberg, Ralf-Peter, additional, Vossebein, Lutz, additional, Wagenlehner, Florian, additional, Walger, Peter, additional, Weimann, Arved, additional, Wendt, Constanze, additional, Wendt, Michael, additional, Wicker, Sabine, additional, Widmer, Andreas, additional, Wilke, Michael, additional, Wiltfang, Jens, additional, Zacharowski, Kai, additional, Ziech, Patrick, additional, and Zygmunt, Marek, additional

Published
2022
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50. Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Author

Caneva, Jorge, Tuhay, Graciela, Diez, Mirta, Talavera, Maria Lujan, Acosta, Adriana, Vulcano, Norberto, Bosio, Martin, Maldonado, Lorena, Deleo, Sabino, Melatini, Luciano, Keogh, Anne, Kotlyar, Eugene, Feenstra, John, Dwyer, Nathan, Adams, Heath, Stevens, Wendy, Steele, Peter, Proudman, Susanna, Minson, Robert, Reeves, Glenn, Lavender, Melanie, Ng, Benjamin, Mackenzie, Michele, Barry, Lisa, Gruenberger, Margarethe, Huber, Charlotte, Lang, Irene, Tilea, Ioana, Sadushi-Kolici, Roela, Löffler-Ragg, Judith, Feistmantl, Lisa-Theresa, Evrard, Patrick, Louis, Renaud, Guiot, Julien, Naldi, Marco, De Pauw, Michel, Mehta, Sanjay, Camacho, Rafael Conde, Tovar, Patricia Parada, Londoño, Alejandro, Campo, Felipe, Garcia, Paula, Lema, Camila, Orozco-Levi, Mauricio, Martinez, William, Gomez, Juan Esteban, Nielsen-Kudsk, Jens Erik, Mellemkjaer, Soren, Anton, Ly, Altraja, Alan, Vihinen, Tapani, Vasankari, Tuija, Sitbon, Olivier, Cottin, Vincent, Têtu, Laurent, Noël-Savina, Elise, Shearman, Nicole, Tayler, Susanne, Olzik, Ilona, Kulka, Christine, Grimminger, Jan, Simon, Marcel, Nolde, Anna, Oqueka, Tim, Harbaum, Lars, Egenlauf, Benjamin, Ewert, Ralf, Schulz, Christian, Regotta, Sabine, Kramer, Tilmann, Knoop-Busch, Susanne, Gerhardt, Felix, Konstantinides, Stavros, Pitsiou, Georgia, Stanopoulos, Ioannis, Sourla, Evdokia, Mouratoglou, Sofia, Karvounis, Haralambos, Pappas, Athanasios, Georgopoulos, Dimitrios, Fanaridis, Michail, Mitrouska, Ioanna, Michalis, Lampros, Pappas, Konstantinos, Kotsia, Anna, Gaine, Sean, Vizza, Carmine Dario, Manzi, Giovanna, Poscia, Roberto, Badagliacca, Roberto, Agostoni, Piergiuseppe, Bruno, Noemi, Farina, Stefania, D'Alto, Michele, Argiento, Paola, Correra, Anna, Di Marco, Giovanni Maria, Cresci, Chiara, Vannucchi, Vieri, Torricelli, Elena, Garcea, Alessio, Pesci, Alberto, Sardella, Luca, Paciocco, Giuseppe, Pane, Federico, D'Armini, Andrea Maria, Pin, Maurizio, Grazioli, Valentina, Massola, Giulia, Sciortino, Antonio, Prediletto, Renato, Bauleo, Carolina, Airò, Edoardo, Ndreu, Rudina, Pavlickova, Ivana, Lunardi, Claudio, Mulè, Massimiliano, Farruggio, Silvia, Costa, Serena, Galgano, Giuseppe, Petruzzi, Mario, De Luca, Anna, Lombardi, Francesco, Roncon, Loris, Conte, Luca, Picariello, Claudio, Wirtz, Gil, Alexandre, Myriam, Vonk-Noordegraaf, A., Boogaard, H., Mager, J., Reesink, H., van den Toorn, Leon M., Boomars, Karin, Andreassen, Arne K., Castro, Graça, Tania, Gonçalves, Baptista, Rui, Marinho, António, Shiang, Teresa, Oliveira, Ana, Coutinho, Daniel, Sousa, Joana, Loureiro, Maria José, Repolho, Débora, Martins Jesus, Susana Maria, Capinha, Marta, Agostinho, João, Cardoso, Tania, Rocha, Andreia, Espinha, Mafalda, Ivanov, Kyundyul Ivanovich, Alexeeva, Dalyana Eduardovna, Batalina, Marina Vadimovna, Hegya, Daria Viktorovna, Zvereva, Tatyana Nikolaevna, Avdeev, Sergey Nikolaevich, Tsareva, Natalia Anatolievna, Galyavich, Albert Sarvatovich, Nikolaevich, Bykov Aleksander, Filippov, Evgeny Vladimirovich, Yakovleva, Olga Eduardovna, Pavlova, Olga Borisovna, Skripkina, Elena Sergeevna, Martynyuk, Tamila Vitalievna, Bukatova, Irina Fedorovna, Tregubova, Anna Viktorovna, Platonov, Dmitry Yurievich, Kolomeytseva, Tatyana Mikhaylovna, Al Dalaan, Abdullah, Abdelsayed, Abeer Abeer, Weheba, Ihab, Saleemi, Sarferaz, Sakkijha, Hussam, Bohacekova, Marcela, Valkovicova, Tatiana, Farkasova, Iveta, Quezada, Carlos Andres, Piccari, Lucilla, Blanco, Isabel, Sebastian, Laura, Roman, Antonio, Lopez, Manuel, Otero, Remedios, Elias, Teresa, Jara, Luis, Asencio, Isabel, Arjona, Josefa Jiménez, Almagro, Raúl Menor, Cárdenas, Salvador López, García, Salvador Alcaraz, Rodríguez, Patricia Villanueva, Lopez, Raquel, Garcia, Alberto, Avilés, Francisco Fernandez, De La Pava, Sebastian, Yotti, Raquel, Peñate, Gregorio Pérez, Marrero, Fernando León, Cifrián Martínez, José Manuel, Martinez-Meñaca, Amaya, Alonso, Lecue Pilar, Rozas, Sonia Fernandez, Fernandez, David Iturbe, Cuesta, Victor Mora, Söderberg, Stefan, Bartfay, Sven-Erik, Rundqvist, Bengt, Alfetlawi, Monthir, Wodlin, Peter, Schwarz, Esther Irene, Speich, Rudolf, Lador, Frédéric, Rochat, Thierry, Gasche-Soccal, Paola, Hsu, Chih-Hsin, Lin, Tsung-Hsien, Su, Ho-Ming, Lai, Wen-Ter, Chu, Chun Yuan, Hsu, Po-Chao, Voon, Wen-Chol, Yen, Hsueh-Wei, Yih-Jer Wu, Jacob, Wu, Shu-Hao, Huang, Wen-Pin, Fong, Man-Cai, Huang, Chien-Lung, Kuo, Ping-Hung, Lin, Yen-Hung, Lin, Jiunn-Lee, Hung, Chi-Sheng, Wu, Cho-Kai, Sung, Shih-Hsien, Huang, Wei-Chun, Cheng, Chin-Chang, Kuo, Shu-Hung, Wang, Wen-Hwa, Ho, Wan-Jing, Hsu, Tsu-Shiu, Mutlu, Bülent, Atas, Halil, Ongen, Gul, Un, Zeynep, Okumus, Gulfer, Hanta, Ismail, Corris, Paul, Peacock, Andrew, Church, Colin, Toshner, Mark, Newnham, Michael, Ghofrani, Hossein-Ardeschir, Gomez Sanchez, Miguel-Angel, Humbert, Marc, Pittrow, David, Simonneau, Gérald, Gall, Henning, Grünig, Ekkehard, Klose, Hans, Halank, Michael, Langleben, David, Snijder, Repke J., Escribano Subias, Pilar, Mielniczuk, Lisa M., Lange, Tobias J., Vachiéry, Jean-Luc, Wirtz, Hubert, Helmersen, Douglas S., Tsangaris, Iraklis, Barberá, Joan A., Pepke-Zaba, Joanna, Boonstra, Anco, Rosenkranz, Stephan, Ulrich, Silvia, Steringer-Mascherbauer, Regina, Delcroix, Marion, Jansa, Pavel, Šimková, Iveta, Giannakoulas, George, Klotsche, Jens, Williams, Evgenia, Meier, Christian, and Hoeper, Marius M.

Published
2021
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