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Article ; Online: Pediatric pulmonology 2019 year in review: Asthma.

Barber, Andrew T / Loughlin, Ceila E

2021 Volume 56, Issue 8, Page(s) 2449–2454

MeSH term(s)	Asthma/epidemiology ; Child ; Humans ; Pulmonary Medicine
Language	English
Publishing date	2021-06-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632784-9
ISSN	1099-0496 ; 8755-6863
ISSN (online)	1099-0496
ISSN	8755-6863
DOI	10.1002/ppul.25507
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Article ; Online: Pediatric Pulmonology 2020 year in review: Asthma.

Barber, Andrew T / Loughlin, Ceila E

Pediatric pulmonology

2021 Volume 56, Issue 8, Page(s) 2455–2459

Abstract: Pediatric asthma is a heterogeneous and common chronic condition with significant morbidity and burden on the healthcare system. Despite advances in the field, the disease has proven to be increasingly complex to diagnose and management strategies are ... ...

Abstract	Pediatric asthma is a heterogeneous and common chronic condition with significant morbidity and burden on the healthcare system. Despite advances in the field, the disease has proven to be increasingly complex to diagnose and management strategies are constantly evolving. Studies from 2020 have advanced the field even further, particularly with regard to new methods of diagnosis and monitoring, treatment of severe asthma, modifiable risk factors like exercise and obesity, aerosol delivery, and viral respiratory infections contributing to the development of asthma. Continued studies are needed to improve our care for children with asthma and we look forward to future advances. This article is part of our 2020 "Year in Review" series, in which we summarize publications in major topic areas, in the context of selected literature from other journals relevant to our discipline.
MeSH term(s)	Asthma/diagnosis ; Asthma/therapy ; Child ; Exercise ; Humans ; Obesity ; Pulmonary Medicine
Language	English
Publishing date	2021-06-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632784-9
ISSN	1099-0496 ; 8755-6863
ISSN (online)	1099-0496
ISSN	8755-6863
DOI	10.1002/ppul.25510
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Article ; Online: Pediatric Pulmonology 2022 year in review: Rare and diffuse lung disease.

Barber, Andrew T / Liptzin, Deborah R / Gower, William A / Hinds, Daniel M

Pediatric pulmonology

2023 Volume 58, Issue 10, Page(s) 2719–2724

Abstract: The field of rare and diffuse pediatric lung disease continues to evolve and expand rapidly as clinicians and researchers make advancements in the diagnosis and treatment of children's interstitial and diffuse lung disease, non-cystic fibrosis ... ...

Abstract	The field of rare and diffuse pediatric lung disease continues to evolve and expand rapidly as clinicians and researchers make advancements in the diagnosis and treatment of children's interstitial and diffuse lung disease, non-cystic fibrosis bronchiectasis, and primary ciliary dyskinesia. Papers published on these topics in Pediatric Pulmonology and other journals in 2022 describe newly recognized disorders, elucidate disease mechanisms and courses, explore potential biomarkers, and assess novel treatments. In this review, we will discuss these important advancements and place them in the context of existing literature.
MeSH term(s)	Child ; Humans ; Pulmonary Medicine ; Lung Diseases/diagnosis ; Lung Diseases/therapy ; Bronchiectasis/diagnosis ; Bronchiectasis/therapy ; Lung ; Thorax
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632784-9
ISSN	1099-0496 ; 8755-6863
ISSN (online)	1099-0496
ISSN	8755-6863
DOI	10.1002/ppul.26603
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Article ; Online: Use caution interpreting nasal nitric oxide: Overlap in primary ciliary dyskinesia and primary immunodeficiency.

Barber, Andrew T / Davis, Stephanie D / Boutros, Hannah / Zariwala, Maimoona / Knowles, Michael R / Leigh, Margaret W

Pediatric pulmonology

2021 Volume 56, Issue 12, Page(s) 4045–4047

MeSH term(s)	Ciliary Motility Disorders/diagnosis ; Humans ; Kartagener Syndrome/diagnosis ; Nitric Oxide ; Nose
Chemical Substances	Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2021-09-02
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632784-9
ISSN	1099-0496 ; 8755-6863
ISSN (online)	1099-0496
ISSN	8755-6863
DOI	10.1002/ppul.25636
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Article ; Online: Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia.

Kaspy, Kimberley R / Dell, Sharon D / Davis, Stephanie D / Ferkol, Thomas W / Rosenfeld, Margaret / Sagel, Scott D / Milla, Carlos / Olivier, Kenneth N / Barber, Andrew T / Wee, Wallace / Lin, Feng-Chang / Li, Lang / Rampakakis, Emmanouil / Zariwala, Maimoona A / Knowles, Michael R / Leigh, Margaret W / Shapiro, Adam J

Chest

2023 Volume 165, Issue 5, Page(s) 1070–1081

Abstract: Background: Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs ...

Abstract	Background: Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]). Research question: Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT? Study design and methods: This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression. Results: In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA. Interpretation: Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both. Trial registry: ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www. Clinicaltrials: gov.
MeSH term(s)	Humans ; Male ; Female ; Child ; Cross-Sectional Studies ; Adolescent ; Child, Preschool ; Situs Inversus/complications ; Infant ; Young Adult ; Kartagener Syndrome/complications ; Kartagener Syndrome/diagnosis ; Heterotaxy Syndrome/complications ; Severity of Illness Index ; Ciliary Motility Disorders/genetics ; Ciliary Motility Disorders/complications ; Ciliary Motility Disorders/diagnosis
Language	English
Publishing date	2023-12-09
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2023.12.005
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Article ; Online: A multi-disciplinary, comprehensive approach to management of children with heterotaxy.

Saba, Thomas G / Geddes, Gabrielle C / Ware, Stephanie M / Schidlow, David N / Del Nido, Pedro J / Rubalcava, Nathan S / Gadepalli, Samir K / Stillwell, Terri / Griffiths, Anne / Bennett Murphy, Laura M / Barber, Andrew T / Leigh, Margaret W / Sabin, Necia / Shapiro, Adam J

Orphanet journal of rare diseases

2022 Volume 17, Issue 1, Page(s) 351

Abstract: Heterotaxy (HTX) is a rare condition of abnormal thoraco-abdominal organ arrangement across the left-right axis of the body. The pathogenesis of HTX includes a derangement of the complex signaling at the left-right organizer early in embryogenesis ... ...

Abstract	Heterotaxy (HTX) is a rare condition of abnormal thoraco-abdominal organ arrangement across the left-right axis of the body. The pathogenesis of HTX includes a derangement of the complex signaling at the left-right organizer early in embryogenesis involving motile and non-motile cilia. It can be inherited as a single-gene disorder, a phenotypic feature of a known genetic syndrome or without any clear genetic etiology. Most patients with HTX have complex cardiovascular malformations requiring surgical intervention. Surgical risks are relatively high due to several serious comorbidities often seen in patients with HTX. Asplenia or functional hyposplenism significantly increase the risk for sepsis and therefore require antimicrobial prophylaxis and immediate medical attention with fever. Intestinal rotation abnormalities are common among patients with HTX, although volvulus is rare and surgical correction carries substantial risk. While routine screening for intestinal malrotation is not recommended, providers and families should promptly address symptoms concerning for volvulus and biliary atresia, another serious morbidity more common among patients with HTX. Many patients with HTX have chronic lung disease and should be screened for primary ciliary dyskinesia, a condition of respiratory cilia impairment leading to bronchiectasis. Mental health and neurodevelopmental conditions need to be carefully considered among this population of patients living with a substantial medical burden. Optimal care of children with HTX requires a cohesive team of primary care providers and experienced subspecialists collaborating to provide compassionate, standardized and evidence-based care. In this statement, subspecialty experts experienced in HTX care and research collaborated to provide expert- and evidence-based suggestions addressing the numerous medical issues affecting children living with HTX.
MeSH term(s)	Anti-Bacterial Agents ; Bronchiectasis ; Child ; Humans ; Intestinal Volvulus
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2022-09-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2225857-7
ISSN	1750-1172 ; 1750-1172
ISSN (online)	1750-1172
ISSN	1750-1172
DOI	10.1186/s13023-022-02515-2
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Article ; Online: Laterality Defects in Primary Ciliary Dyskinesia: Relationship to Ultrastructural Defect or Genotype.

Barber, Andrew T / Shapiro, Adam J / Davis, Stephanie D / Ferkol, Thomas W / Atkinson, Jeffrey J / Sagel, Scott D / Dell, Sharon D / Olivier, Kenneth N / Milla, Carlos E / Rosenfeld, Margaret / Li, Lang / Lin, Feng-Chang / Sullivan, Kelli M / Capps, Nicole A / Zariwala, Maimoona A / Knowles, Michael R / Leigh, Margaret W

Annals of the American Thoracic Society

2022 Volume 20, Issue 3, Page(s) 397–405

Abstract: Rationale: ...

Abstract	Rationale:
MeSH term(s)	Humans ; Dyneins/genetics ; Prospective Studies ; Retrospective Studies ; Heterotaxy Syndrome ; Genotype ; Cilia/ultrastructure ; Ciliary Motility Disorders ; Kartagener Syndrome/genetics
Chemical Substances	Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Multicenter Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2717461-X
ISSN	2325-6621 ; 1943-5665 ; 2325-6621
ISSN (online)	2325-6621 ; 1943-5665
ISSN	2325-6621
DOI	10.1513/AnnalsATS.202206-487OC
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Article ; Online: ATS Core Curriculum 2020. Pediatric Pulmonary Medicine.

ATS scholar

2020 Volume 1, Issue 4, Page(s) 456–475

Abstract: The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 ... ...

Abstract	The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the pediatric pulmonary medicine core, including pediatric hypoxemic respiratory failure; modalities in noninvasive management of chronic respiratory failure in childhood; surgical and nonsurgical management of congenital lung malformations; an update on smoke inhalation lung injury; an update on vaporizers, e-cigarettes, and other electronic delivery systems; pulmonary complications of sarcoidosis; pulmonary complications of congenital heart disease; and updates on the management of congenital diaphragmatic hernia.
Language	English
Publishing date	2020-12-30
Document type	Journal Article
ISSN	2690-7097
ISSN (online)	2690-7097
DOI	10.34197/ats-scholar.2020-0022RE
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Article ; Online: Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6.

Mouillesseaux, Kevin P / Wiley, David S / Saunders, Lauren M / Wylie, Lyndsay A / Kushner, Erich J / Chong, Diana C / Citrin, Kathryn M / Barber, Andrew T / Park, Youngsook / Kim, Jun-Dae / Samsa, Leigh Ann / Kim, Jongmin / Liu, Jiandong / Jin, Suk-Won / Bautch, Victoria L

Nature communications

2016 Volume 7, Page(s) 13247

Abstract: Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD ...

Abstract	Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation.
MeSH term(s)	Animals ; Bone Morphogenetic Proteins/genetics ; Bone Morphogenetic Proteins/metabolism ; Cell Line ; Human Umbilical Vein Endothelial Cells ; Humans ; Mice ; Neovascularization, Physiologic/physiology ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Smad6 Protein/genetics ; Smad6 Protein/metabolism ; Zebrafish
Chemical Substances	Bone Morphogenetic Proteins ; Receptors, Notch ; SMAD6 protein, human ; Smad6 Protein ; Smad6 protein, mouse
Language	English
Publishing date	2016-11-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2041-1723
ISSN (online)	2041-1723
DOI	10.1038/ncomms13247
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Article ; Online: The Ras activator RasGRP3 mediates diabetes-induced embryonic defects and affects endothelial cell migration.

Randhawa, Paramjeet K / Rylova, Svetlana / Heinz, Jessica Y / Kiser, Stephanie / Fried, Joanna H / Dunworth, William P / Anderson, Amanda L / Barber, Andrew T / Chappell, John C / Roberts, David M / Bautch, Victoria L

Circulation research

2011 Volume 108, Issue 10, Page(s) 1199–1208

Abstract: Rationale: Fetuses that develop in diabetic mothers have a higher incidence of birth defects that include cardiovascular defects, but the signaling pathways that mediate these developmental effects are poorly understood. It is reasonable to hypothesize ... ...

Abstract	Rationale: Fetuses that develop in diabetic mothers have a higher incidence of birth defects that include cardiovascular defects, but the signaling pathways that mediate these developmental effects are poorly understood. It is reasonable to hypothesize that diabetic maternal effects are mediated by 1 or more pathways activated downstream of aberrant glucose metabolism, because poorly controlled maternal glucose levels correlate with the frequency and severity of the defects. Objective: We investigated whether RasGRP3 (Ras guanyl-releasing protein 3), a Ras activator expressed in developing blood vessels, mediates diabetes-induced vascular developmental defects. RasGRP3 is activated by diacylglycerol, and diacylglycerol is overproduced by aberrant glucose metabolism in diabetic individuals. We also investigated the effects of overactivation and loss of function for RasGRP3 in primary endothelial cells and developing vessels. Methods and results: Analysis of mouse embryos from diabetic mothers showed that diabetes-induced developmental defects were dramatically attenuated in embryos that lacked Rasgrp3 function. Endothelial cells that expressed activated RasGRP3 had elevated Ras-ERK signaling and perturbed migration, whereas endothelial cells that lacked Rasgrp3 function had attenuated Ras-ERK signaling and did not migrate in response to endothelin-1. Developing blood vessels exhibited endothelin-stimulated vessel dysmorphogenesis that required Rasgrp3 function. Conclusions: These findings provide the first evidence that RasGRP3 contributes to developmental defects found in embryos that develop in a diabetic environment. The results also elucidate RasGRP3-mediated signaling in endothelial cells and identify endothelin-1 as an upstream input and Ras/MEK/ERK as a downstream effector pathway. RasGRP3 may be a novel therapeutic target for the fetal complications of diabetes.
MeSH term(s)	Animals ; Cell Movement/genetics ; Cells, Cultured ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Embryo Culture Techniques ; Embryonic Development/genetics ; Embryonic Stem Cells/metabolism ; Embryonic Stem Cells/pathology ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pregnancy ; Pregnancy Complications, Cardiovascular/genetics ; Pregnancy Complications, Cardiovascular/metabolism ; Pregnancy Complications, Cardiovascular/pathology ; ras Guanine Nucleotide Exchange Factors/deficiency ; ras Guanine Nucleotide Exchange Factors/genetics ; ras Guanine Nucleotide Exchange Factors/physiology
Chemical Substances	RasGRP3 protein, mouse ; ras Guanine Nucleotide Exchange Factors
Language	English
Publishing date	2011-04-07
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.110.230888
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