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Article ; Online: Pathophysiological Concepts and Management of Pulmonary Manifestation of Pediatric Inflammatory Bowel Disease

Florian Schmid / Cho-Ming Chao / Jan Däbritz

International Journal of Molecular Sciences, Vol 23, Iss 7287, p

2022 Volume 7287

Abstract: Pulmonary manifestation (PM) of inflammatory bowel disease (IBD) in children is a rare condition. The exact pathogenesis is still unclear, but several explanatory concepts were postulated and several case reports in children were published. We performed ... ...

Abstract	Pulmonary manifestation (PM) of inflammatory bowel disease (IBD) in children is a rare condition. The exact pathogenesis is still unclear, but several explanatory concepts were postulated and several case reports in children were published. We performed a systematic Medline search between April 1976 and April 2022. Different pathophysiological concepts were identified, including the shared embryological origin, “miss-homing” of intestinal based neutrophils and T lymphocytes, inflammatory triggering via certain molecules (tripeptide proline-glycine-proline, interleukin 25), genetic factors and alterations in the microbiome. Most pediatric IBD patients with PM are asymptomatic, but can show alterations in pulmonary function tests and breathing tests. In children, the pulmonary parenchyma is more affected than the airways, leading histologically mainly to organizing pneumonia. Medication-associated lung injury has to be considered in pulmonary symptomatic pediatric IBD patients treated with certain agents (i.e., mesalamine, sulfasalazine or infliximab). Furthermore, the risk of pulmonary embolism is generally increased in pediatric IBD patients. The initial treatment of PM is based on corticosteroids, either inhaled for the larger airways or systemic for smaller airways and parenchymal disease. In summary, this review article summarizes the current knowledge about PM in pediatric IBD patients, focusing on pathophysiological and clinical aspects.
Keywords	children ; molecular ; inflammation ; immunity ; gut–lung axis ; airways ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma

Gokhan Gorgisen / Malik Aydin / Olivier Mboma / Mira Y. Gökyildirim / Cho-Ming Chao

International Journal of Molecular Sciences, Vol 23, Iss 10113, p

New Potential Perspectives

2022 Volume 10113

Abstract: Insulin receptor substrates (IRSs) are proteins that are involved in signaling through the insulin receptor (IR) and insulin-like growth factor (IGFR). They can also interact with other receptors including growth factor receptors. Thus, they represent a ... ...

Abstract	Insulin receptor substrates (IRSs) are proteins that are involved in signaling through the insulin receptor (IR) and insulin-like growth factor (IGFR). They can also interact with other receptors including growth factor receptors. Thus, they represent a critical node for the transduction and regulation of multiple signaling pathways in response to extracellular stimuli. In addition, IRSs play a central role in processes such as inflammation, growth, metabolism, and proliferation. Previous studies have highlighted the role of IRS proteins in lung diseases, in particular asthma. Further, the members of the IRS family are the common proteins of the insulin growth factor signaling cascade involved in lung development and disrupted in bronchopulmonary dysplasia (BPD). However, there is no study focusing on the relationship between IRS proteins and BPD yet. Unfortunately, there is still a significant gap in knowledge in this field. Thus, in this review, we aimed to summarize the current knowledge with the major goal of exploring the possible roles of IRS in BPD and asthma to foster new perspectives for further investigations.
Keywords	insulin receptor substrates ; asthma ; bronchopulmonary dysplasia ; pediatric lung disease ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	306
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in children under 5 years

Christoph Strumann / Otavio Ranzani / Jeanne Moor / Reinhard Berner / Nicole Töpfner / Cho-Ming Chao / Matthias B. Moor

The Journal of Clinical Investigation, Vol 133, Iss

2023 Volume 21

Keywords	Infectious disease ; Vaccines ; Medicine ; R
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Stem/Progenitor Cells and Related Therapy in Bronchopulmonary Dysplasia

Manuela Marega / Natalia El-Merhie / Mira Y. Gökyildirim / Valerie Orth / Saverio Bellusci / Cho-Ming Chao

International Journal of Molecular Sciences, Vol 24, Iss 11229, p

2023 Volume 11229

Abstract: Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly seen in preterm infants, and is triggered by infection, mechanical ventilation, and oxygen toxicity. Among other problems, lifelong limitations in lung function and impaired psychomotor ... ...

Abstract	Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly seen in preterm infants, and is triggered by infection, mechanical ventilation, and oxygen toxicity. Among other problems, lifelong limitations in lung function and impaired psychomotor development may result. Despite major advances in understanding the disease pathologies, successful interventions are still limited to only a few drug therapies with a restricted therapeutic benefit, and which sometimes have significant side effects. As a more promising therapeutic option, mesenchymal stem cells (MSCs) have been in focus for several years due to their anti-inflammatory effects and their secretion of growth and development promoting factors. Preclinical studies provide evidence in that MSCs have the potential to contribute to the repair of lung injuries. This review provides an overview of MSCs, and other stem/progenitor cells present in the lung, their identifying characteristics, and their differentiation potential, including cytokine/growth factor involvement. Furthermore, animal studies and clinical trials using stem cells or their secretome are reviewed. To bring MSC-based therapeutic options further to clinical use, standardized protocols are needed, and upcoming side effects must be critically evaluated. To fill these gaps of knowledge, the MSCs’ behavior and the effects of their secretome have to be examined in more (pre-) clinical studies, from which only few have been designed to date.
Keywords	bronchopulmonary dysplasia ; premature infants ; lung injury ; chronic lung disease ; inflammation ; stem cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The hazardous (mis)perception of Self-estimated Alcohol intoxication and Fitness to drivE—an avoidable health risk

Jöran Köchling / Berit Geis / Cho-Ming Chao / Jana-K. Dieks / Stefan Wirth / Kai O. Hensel

Harm Reduction Journal, Vol 18, Iss 1, Pp 1-

the SAFE randomised trial

2021 Volume 10

Abstract: Abstract Background Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving ... ...

Abstract	Abstract Background Worldwide, alcohol-related road traffic accidents represent a major avoidable health risk. The aim of this study was to evaluate the accuracy of self-estimating the degree of acute alcohol intoxication regarding the legal driving limit, and to identify risk factors for misjudgement. Methods In this prospective randomised controlled crossover trial, 90 social drinkers (mean age 23.9 ± 3.5 years, 50% female) consumed either beer or wine. Study group subjects were made aware when exceeding the legal driving limit (BrAC = 0.05%). Controls received no information about their BrAC. For crossover, beer or wine were consumed in the opposite order. Results 39–53% of all participants exceeded the legal driving limit whilst under the impression to be still permitted to drive. Self-estimation was significantly more accurate on study day 2 (p = 0.009). Increasing BrAC positively correlated with self-estimation inaccuracy, which was reproducible during crossover. Multiple regression analysis revealed fast drinking and higher alcohol levels as independent risk factors for inaccurate self-estimation. Conclusions Social drinkers are commonly unaware of exceeding the legal driving limit when consuming alcohol. Self-estimating alcohol intoxication can be improved through awareness. Dedicated awareness programs, social media campaigns and government advice communications should be utilised to address this avoidable hazard. Trial registration The trial was registered prospectively at the Witten/Herdecke University Ethics Committee (trial registration number 140/2016 on 04/11/2016) and at the DRKS—German Clinical Trials Register (trial registration number DRKS00015285 on 08/22/2018—Retrospectively registered). Trial protocol can be accessed online.
Keywords	Perceived alcohol intoxication ; Road safety ; Public health concern ; Alcohol-related road traffic accident ; Driving under the influence ; DUI ; Public aspects of medicine ; RA1-1270
Subject code	380
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeting Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension (BPD-PH)

Cho-Ming Chao / Lei Chong / Xuran Chu / Amit Shrestha / Judith Behnke / Harald Ehrhardt / Jinsan Zhang / Chengshui Chen / Saverio Bellusci

Cells, Vol 9, Iss 1875, p

Potential Role of the FGF Signaling Pathway in the Development of the Pulmonary Vascular System

2020 Volume 1875

Abstract: More than 50 years after the first description of Bronchopulmonary dysplasia (BPD) by Northway, this chronic lung disease affecting many preterm infants is still poorly understood. Additonally, approximately 40% of preterm infants suffering from severe ... ...

Abstract	More than 50 years after the first description of Bronchopulmonary dysplasia (BPD) by Northway, this chronic lung disease affecting many preterm infants is still poorly understood. Additonally, approximately 40% of preterm infants suffering from severe BPD also suffer from Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH), leading to a significant increase in total morbidity and mortality. Until today, there is no curative therapy for both BPD and BPD-PH available. It has become increasingly evident that growth factors are playing a central role in normal and pathologic development of the pulmonary vasculature. Thus, this review aims to summarize the recent evidence in our understanding of BPD-PH from a basic scientific point of view, focusing on the potential role of Fibroblast Growth Factor (FGF)/FGF10 signaling pathway contributing to disease development, progression and resolution.
Keywords	Bronchopulmonary dysplasia ; pulmonary hypertension ; FGF signaling ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MSC Based Therapies—New Perspectives for the Injured Lung

Judith Behnke / Sarah Kremer / Tayyab Shahzad / Cho-Ming Chao / Eva Böttcher-Friebertshäuser / Rory E. Morty / Saverio Bellusci / Harald Ehrhardt

Journal of Clinical Medicine, Vol 9, Iss 3, p

2020 Volume 682

Abstract: Chronic lung diseases pose a tremendous global burden. At least one in four people suffer from severe pulmonary sequelae over the course of a lifetime. Despite substantial improvements in therapeutic interventions, persistent alleviation of clinical ... ...

Abstract	Chronic lung diseases pose a tremendous global burden. At least one in four people suffer from severe pulmonary sequelae over the course of a lifetime. Despite substantial improvements in therapeutic interventions, persistent alleviation of clinical symptoms cannot be offered to most patients affected to date. Despite broad discrepancies in origins and pathomechanisms, the important disease entities all have in common the pulmonary inflammatory response which is central to lung injury and structural abnormalities. Mesenchymal stem cells (MSC) attract particular attention due to their broadly acting anti-inflammatory and regenerative properties. Plenty of preclinical studies provided congruent and convincing evidence that MSC have the therapeutic potential to alleviate lung injuries across ages. These include the disease entities bronchopulmonary dysplasia, asthma and the different forms of acute lung injury and chronic pulmonary diseases in adulthood. While clinical trials are so far restricted to pioneering trials on safety and feasibility, preclinical results point out possibilities to boost the therapeutic efficacy of MSC application and to take advantage of the MSC secretome. The presented review summarizes the most recent advances and highlights joint mechanisms of MSC action across disease entities which provide the basis to timely tackle this global disease burden.
Keywords	mesenchymal stem cells ; msc ; chronic lung disease ; lung repair ; extracellular vesicles ; bronchopulmonary dysplasia ; asthma ; chronic obstructive pulmonary disease ; idiopathic pulmonary fibrosis ; inflammation ; lung injury ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MSC Based Therapies to Prevent or Treat BPD—A Narrative Review on Advances and Ongoing Challenges

Maurizio J. Goetz / Sarah Kremer / Judith Behnke / Birte Staude / Tayyab Shahzad / Lena Holzfurtner / Cho-Ming Chao / Rory E. Morty / Saverio Bellusci / Harald Ehrhardt

International Journal of Molecular Sciences, Vol 22, Iss 3, p

2021 Volume 1138

Abstract: Bronchopulmonary dysplasia (BPD) remains one of the most devastating consequences of preterm birth resulting in life-long restrictions in lung function. Distorted lung development is caused by its inflammatory response which is mainly provoked by ... ...

Abstract	Bronchopulmonary dysplasia (BPD) remains one of the most devastating consequences of preterm birth resulting in life-long restrictions in lung function. Distorted lung development is caused by its inflammatory response which is mainly provoked by mechanical ventilation, oxygen toxicity and bacterial infections. Dysfunction of resident lung mesenchymal stem cells (MSC) represents one key hallmark that drives BPD pathology. Despite all progress in the understanding of pathomechanisms, therapeutics to prevent or treat BPD are to date restricted to a few drugs. The limited therapeutic efficacy of established drugs can be explained by the fact that they fail to concurrently tackle the broad spectrum of disease driving mechanisms and by the huge overlap between distorted signal pathways of lung development and inflammation. The great enthusiasm about MSC based therapies as novel therapeutic for BPD arises from the capacity to inhibit inflammation while simultaneously promoting lung development and repair. Preclinical studies, mainly performed in rodents, raise hopes that there will be finally a broadly acting, efficient therapy at hand to prevent or treat BPD. Our narrative review gives a comprehensive overview on preclinical achievements, results from first early phase clinical studies and challenges to a successful translation into the clinical setting.
Keywords	chronic lung disease ; bronchopulmonary dysplasia ; preterm ; mesenchymal stem cells ; lung development ; inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Potentials and Caveats of Mesenchymal Stromal Cell-Based Therapies in the Preterm Infant

Judith Gronbach / Tayyab Shahzad / Sarah Radajewski / Cho-Ming Chao / Saverio Bellusci / Rory E. Morty / Tobias Reicherzer / Harald Ehrhardt

Stem Cells International, Vol

2018 Volume 2018

Abstract: Preponderance of proinflammatory signals is a characteristic feature of all acute and resulting long-term morbidities of the preterm infant. The proinflammatory actions are best characterized for bronchopulmonary dysplasia (BPD) which is the chronic lung ...

Abstract	Preponderance of proinflammatory signals is a characteristic feature of all acute and resulting long-term morbidities of the preterm infant. The proinflammatory actions are best characterized for bronchopulmonary dysplasia (BPD) which is the chronic lung disease of the preterm infant with lifelong restrictions of pulmonary function and severe consequences for psychomotor development and quality of life. Besides BPD, the immature brain, eye, and gut are also exposed to inflammatory injuries provoked by infection, mechanical ventilation, and oxygen toxicity. Despite the tremendous progress in the understanding of disease pathologies, therapeutic interventions with proven efficiency remain restricted to a few drug therapies with restricted therapeutic benefit, partially considerable side effects, and missing option of applicability to the inflamed brain. The therapeutic potential of mesenchymal stromal cells (MSCs)—also known as mesenchymal stem cells—has attracted much attention during the recent years due to their anti-inflammatory activities and their secretion of growth and development-promoting factors. Based on a molecular understanding, this review summarizes the positive actions of exogenous umbilical cord-derived MSCs on the immature lung and brain and the therapeutic potential of reprogramming resident MSCs. The pathomechanistic understanding of MSC actions from the animal model is complemented by the promising results from the first phase I clinical trials testing allogenic MSC transplantation from umbilical cord blood. Despite all the enthusiasm towards this new therapeutic option, the caveats and outstanding issues have to be critically evaluated before a broad introduction of MSC-based therapies.
Keywords	Internal medicine ; RC31-1245
Subject code	610
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evidence for Overlapping and Distinct Biological Activities and Transcriptional Targets Triggered by Fibroblast Growth Factor Receptor 2b Signaling between Mid- and Early Pseudoglandular Stages of Mouse Lung Development

Matthew R. Jones / Arun Lingampally / Jin Wu / Jamschid Sedighi / Negah Ahmadvand / Jochen Wilhelm / Ana Ivonne Vazquez-Armendariz / Susanne Herold / Chengshui Chen / Jin-San Zhang / Saverio Bellusci / Cho-Ming Chao

Cells, Vol 9, Iss 1274, p

2020 Volume 1274

Abstract: Branching morphogenesis is the basic developmental mode common to organs such as the lungs that undergo a process of ramification from a rudimentary tree. However, the precise molecular and cellular bases underlying the formation of branching organs are ... ...

Abstract	Branching morphogenesis is the basic developmental mode common to organs such as the lungs that undergo a process of ramification from a rudimentary tree. However, the precise molecular and cellular bases underlying the formation of branching organs are still unclear. As inactivation of fibroblast growth factor receptor 2b (Fgfr2b) signaling during early development leads to lung agenesis, thereby preventing the analysis of this pathway at later developmental stages, we used transgenic mice to induce expression of a soluble form of Fgfr2b to inactivate Fgfr2b ligands at embryonic day (E) 14.5, corresponding to the mid-pseudoglandular stage of lung development. We identified an Fgfr2b signaling signature comprised of 46 genes enriched in the epithelium, some of which were common to, but most of them distinct from, the previously identified Fgfr2b signaling signature at E12.5. Our results indicate that Fgfr2b signaling at E14.5 controls mostly proliferation and alveolar type 2 cell (AT2) differentiation. In addition, inhibition of Fgfr2b signaling at E14.5 leads to morphological and cellular impairment at E18.5, with defective alveolar lineage formation. Further studies will have to be conducted to elucidate the role of Fgfr2b signaling at successive stages (canalicular/saccular/alveolar) of lung development as well as during homeostasis and regeneration and repair after injury.
Keywords	lung development ; Fgf ; Fgfr2b ; pseudoglandular ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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