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1. Perceptions of the impact of individual allergic rhinitis symptoms: A survey of ARIA clinical experts

Author

Sara Gil-Mata, MD, Tatiana Teixeira, MD, Anna Bedbrook, BSc, Jean Bousquet, PhD, Bernardo Sousa-Pinto, PhD, Rafael José Vieira, MD, Julijana Asllani, Habib Douagui, Estrella Asayag, Castro Maria Elizabeth, Carlos D. Crisci, René Maximiliano Gomez, Juan Carlos Ivancevich, Edgardo Jares, Jorge Fernando Máspero, Pablo Moreno, Hugo Eduardo Neffen, Mario Emilio Zernotti, Sinthia Bosnic-Anticevich, Kristin Chahhoud Carson, Biljana Cvetkovski, Janet M. Davies, Vicky Kritikos, Robyn O'Hehir, Brian Oliver, House Rachel Tan, Jessica Tattersall, Celia Zubrinich, Werner Aberer, Verena Niederberger-Leppin, Isabella Pali-Schöll, Virginie Doyen, Didier Ebo, Renaud Louis, Philippe Rombaux, Sophie Scheire, Kazi Bennoor, Bruno A. Barreto, Paulo Camargos, Herberto Jose Chong-Neto, Alvaro A. Cruz, Jane da Silva, Guidacci Marta, José Angelo Rizzo, Nelson Rosario Filho, Sarquis Serpa Faradiba, Dirceu Solé, Marilyn Urrutia-Pereira, George Christoff, Mandazhieva-Pepelanova Mariana, Odjakova Cvetanka, Todor A. Popov, Dilyana Vicheva, do Ceu Teixeira Maria, Jacques Bouchard, Jan Brozek, Derek K. Chu, Judah Denburg, Thomas Eiwegger, Paul K. Keith, Teresa To, Susan Waserman, Nancy Abusada, Emilio Alvarez Cuesta, Mario A. Calvo-Gil, Maria Antonieta Guzmán, Tamara Pérez Gomez, Wing Kin Wong Gary, Luo Zhang, Luis Caraballo, Alfonso Cepeda Sarabia, Dieudonné Nyembue, Manuel Soto-Martinez, Neven Miculinic, Davor Plavec, Constantinos Pitsios, Panayiotis Yiallouros, Petr Panzner, Milan Sova, Martina Vachova, Carsten Bindslev-Jensen, Ronald Dahl, Hans-Jorgen Malling, Lars Münter, Lars K. Poulsen, Suppli Ulrik Charlotte, Line Kring Tannert, Bassam Mahboub, Laila Salameh, Ivan Cherrez-Ojeda, de Guevara Karla Robles, Rasha Hassan El-Owaidy, Zeinab A. El-Sayed, Shereen Saad El-Sayed, Elham Hossny, Badr Eldin Mostafa, Kaja Julge, Nils Eric Billo, Patrik Eklund, Marina Erhola, Tari Haahtela, Jussi Karjalainen, Mika Makela, Sanna Toppila-Salmi, Erkka Valovirta, Tuula Vasankari, Isabella Annesi-Maesano, Isabelle Bossé, Melisande Bourgoin-Heck, Denis Charpin, André Coste, Frédéric de Blay, Philippe Devillier, Alain Didier, Anh Tuan Dinh-Xuan, Jean-François Fontaine, Jocelyne Just, Rachel Nadif, Nhân Pham-Thi, Bernard Pigearias, Nicolas Roche, Van Ganse Eric, Ekaterine Chkhartishvili, Amiran Gamkrelidze, Maia Gotua, Sven Becker, Karl-Christian Bergmann, Thomas Bieber, Randolf Brehler, Roland Buhl, Adam M. Chaker, Ulf Darsow, Eckard Hamelmann, Joachim Heinrich, Thomas Keil, Ludger Klimek, Pavel Kolkhir, Susanne Lau, Marcus Maurer, Ralph Mösges, Angelos Neou, Oliver Pfaar, Johannes Ring, Martin Wagenmann, Torsten Zuberbier, Aiste Ramanauskaite, Anja Lingnau, Demetrios Christou, Sophia Neisinger, Xenophon Aggelidis, Jannis Constantinidis, Maria Dimou, Christos Grigoreas, Trisevgeni Kapsali, Michael Katotomichelakis, Stelios Loukides, Michael Makris, Emmanouil Manousakis, Nikolaos Mikos, Aris Pagkalos, Nikolaos G. Papadopoulos, Vasileios Papanikolaou, Giannis Paraskevopoulos, Konstantina Piskou, Emmanuel Prokopakis, Fotios Psarros, Konstantinos Samitas, Sofia Stamataki, Evangelia Stefanaki Lina, Ekaterini Syrigou, Ioanna Tsiligianni, Mina Vallianatou, Dimitrios Vourdas, Paraskevi Xepapadaki, Aspasia Karavelia, Fanny Wai San Ko, Gary Wong, Andor Hirschberg, Helga Kraxner, Kristof Nekam, Stephen Lane, Menachem Rottem, Cristina Artesani Maria, Simona Barbaglia, Bianca Beghé, Beatrice Bilo Maria, Attilio Boner, Matteo Bonini, Sergio Bonini, Fulvio Braido, Luisa Brussino, G Walter Canonica, Lorenzo Cecchi, Giorgio Ciprandi, Enrico Compalati, Gennaro D'Amato, Giulia De Feo, Stefano Del Giacco, Alessandro Fiocchi, Enrico Heffler, Carlo Lombardi, Riccardo Monti, Antonella Muraro, Eustachio Nettis, Stefania Nicola, Giovanni Passalacqua, Vincenzo Patella, Francesca Puggioni, Giovanni Rolla, Antonino Romano, Nicola Scichilone, Massimo Triggiani, Teresa Ventura Maria, Giovanni Viegi, Cristina Boccabella, Mattia Giovannini, Anand Mahesh Padukudru, Tomohisa Iinuma, Ken Ohta, Yoshitaka Okamoto, Kimihiro Okubo, Ruby Pawankar, Daiju Sakurai, Maho Suzukawa, Masao Yamaguchi, Zhanat Ispayeva, Yoon-Seok Chang, Hae-Sim Park, Mona Al-Ahmad, Ieva Cirule, Ineta Grisle, Carla Irani, Philip Rouadi, Fares Zaitoun, Ruta Dubakiene, Regina Emuzyte, Violeta Kvedariene, Brigita Gradauskiene, Arunas Valiulis, Markus Ollert, Farah Hannachi, Dejan Dokic, Amir Hamzah Abdul Latiff, Baharudin Abdullah, S.P. Palaniappan, Kent Woo, Stephen Montefort, Martín Bedolla Barajas, María del Carmen Costa Domínguez, Jesús Guillermo Espinoza Contreras, Jose Miguel Fuentes Pèrez, José Luis Gálvez Romero, María de la Luz Hortensia García Cruz, Sandra González Diaz, Yunuen Rocío Huerta Villalobos, Désiree E. Larenas-Linnemann, Jorge Agustin Luna-Pech, Juan José Matta Campos, Daniela Rivero Yeverino, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Battur Lkhagvaa, Sandra Mavale-Manuel, Abrantes Nunes Elizabete, Niels Chavannes, Wytske J. Fokkens, Gerard Koppelman, Anke-Hilse Maitland-van der Zee, Sietze Reitsma, Ramanathan Chandrasekharan, Osman Yusuf, Maria Susana Repka-Ramirez, Juan Carlos Sisul, José E. Gereda, Marysia T. Recto, Slawomir Bialek, Artur Bialoszewski, Marta Chelminska, Radoslaw Gawlik, Ewa Jassem, Marek Jutel, Piotr Kuna, Maciej Kupczyk, Marcin Moniuszko, Marek Niedoszytko, Filip Raciborski, Jan Romantowski, Boleslaw Samolinski, Krzysztof Specjalski, Pedro Carreiro Martins, Jaime Correia de Sousa, Elisio Costa, Joao A. Fonseca, Olga Lourenço, Mario Morais-Almeida, Margarida Pereira Ana, Frederico Regateiro, Carlos Robalo Cordeiro, Jose Rosado Pinto, Bernardo Sousa-Pinto, Luis Taborda Barata, Ana Maria Todo-Bom, José Vieira Rafael, Daniela Carvalho, Maryam Ali Al-Nesf, Ioana Agache, Camelia Berghea Elena, Roxana Bumbacea, Diana Deleanu, Florin Mihaltan, Carmen Panaitescu Bunu, Musa Khaitov, Leyla Namazova-Baranova, Elena Vishneva, Ali Alshaikh Nada, Sanja Dimic-Janjic, Branislava Milenkovic, De Yun Wang, Martin Hrubiško, Natalija Edelbaher, Maja Jošt, Peter Kopac, Mitja Košnik, Nika Lalek, Antonija Poplas Susic, Irma Rozman Sinur, Tanja Soklic Košak, Nadja Triller, Katja Triller, Jure Urbancic, Mihaela Zidarn, Michael Levin, Paul Potter, Heather Zar, Isam Alobid, Aram Anto, Joan Bartra, Irina Bobolea, Paloma Campo, Vicky Cardona, Maria Carriazo Ana, José Antonio Castillo Vizuete, Tomas Chivato, Ignacio Jesus Davila Gonzalez, Joaquim Mullol, Antonio Nieto Garcia, César Picado, Santiago Quirce, Joaquin Sastre, Leticia de las Vecillas, Mikael Benson, Inger Kull, Marianne van Hage, Magnus Wickman, Nikolai Khaltaev, Yousser Mohammad, Pongsakorn Tantilipikorn, Pakit Vichyanond, Cemal Cingi, Bilun Gemicioglu, Ozlem Goksel, Omer Kalayci, Ali Fuat Kalyoncu, Cem Meço, Koyuncu Ilgim Vardaloglu, Arzu Yorgancioglu, Deniz Eyice Karabacak, Bruce Kirenga, Ian Michael Adcock, Hasan S. Arshad, Mike Bewick, Christine Bond, Christopher Brightling, Andrew Bush, Moïses Calderon, Kian Fan Chung, Adnan Custovic, Ratko Djukanovic, Stephen Durham, John Farrell, David Halpin, Michael Hyland, Sebastian Johnston, Brian Lipworth, Alla Nakonechna, David Price, Graham Roberts, Dermot Ryan, Jürgen Schwarze, Aziz Sheikh, Mike Shields, Samantha Walker, Sian Williams, Igor Kaidashev, Andrii Igorevich Kurchenko, Vladyslav Tsaryk, David Bernstein, Jonathan A. Bernstein, Thomas B. Casale, Sharon Chinthrajah, Mark Dykewicz, Gailen D. Marshall, Eli O. Meltzer, Robert M. Naclerio, Alkis Togias, Elina Toskala, Dana Wallace, Dennis M. Williams, Barbara Yawn, Fernan Caballero-Fonseca, Lan Le Thi Tuyet, and Tran Thien Quan Vu

Subjects
Allergic rhinitis, Survey, Professional-patient relation, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Allergic rhinitis (AR) is a highly prevalent disease. We aimed to assess the symptoms that physicians who see patients with AR perceive as the most bothersome in their patients. Methods: We performed a cross-sectional study based on an online questionnaire sent to all members of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative. The survey included questions on the physicians' perceptions of patients’ AR symptoms as well as of their own AR symptoms. Results: Among 401 respondents, 155 (38.7%) reported having AR. ARIA members reported nasal symptoms to be the most frequent (89.7%) and bothersome (80.0%) symptoms experienced by themselves. Likewise, nasal symptoms were reported by ARIA members as the most frequent (94.8% in members with AR vs 96.0% in members without AR) and bothersome (57.0% in members with AR vs 67.9% in members without AR) in their patients. We found a significant association (p = 0.001) between physicians’ own symptoms and those perceived as the most bothersome in their patients. Conclusion: Physicians perceive nasal symptoms to be the most frequent and the most bothersome symptoms in AR patients. The physicians' personal experiences with AR may influence their perception of patients’ symptoms.

Published
2024
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2. Managing food allergy: GA2LEN guideline 2022

Author

Antonella Muraro, MD, Debra de Silva, PhD, Susanne Halken, DM DMSc, Margitta Worm, MD∗, Ekaterina Khaleva, MD MSc, Stefania Arasi, MD PhD, Audrey Dunn-Galvin, PhD, Bright I. Nwaru, PhD, Nicolette W. De Jong, PhD, Pablo Rodríguez Del Río, MD PhD, Paul J. Turner, FRCPCH PhD, Pete Smith, FRACP PhD, Philippe Begin, MD MSc, Elizabeth Angier, MSc, Hasan Arshad, DM, Barbara Ballmer-Weber, PhD, Kirsten Beyer, MD, Carsten Bindslev-Jensen, MD PhD DSc, Antonella Cianferoni, MD PhD, Céline Demoulin, Antoine Deschildre, MD, Motohiro Ebisawa, MD PhD, Maria Montserrat Fernandez-Rivas, DM PhD, Alessandro Fiocchi, MD, Bertine Flokstra-de Blok, PhD, Jennifer Gerdts, Josefine Gradman, MD, Kate Grimshaw, PhD, Carla Jones, Susanne Lau, MD, Richard Loh, FRACP, Montserrat Alvaro Lozano, MD, Mika Makela, MD PhD, Mary Jane Marchisotto, Rosan Meyer, PhD, Clare Mills, PhD, Caroline Nilsson, MD PhD, Anna Nowak-Wegrzyn, MD PhD, Ulugbek Nurmatov, PhD, Giovanni Pajno, MD, Marcia Podestà, Lars K. Poulsen, PhD, Hugh A. Sampson, MD, Angel Sanchez, Sabine Schnadt, Hania Szajewska, MD, Ronald Van Ree, PhD, Carina Venter, PhD, Berber Vlieg-Boerstra, PhD, Amena Warner, Gary Wong, MD FRCPC, Robert Wood, MD, Torsten Zuberbier, MD, Graham Roberts, DM, Priya Bansal, Roberto Berni–Canani, Katharina Blumchen, Andreas Bonertz, Melisande Bourgoin-Heck, Ozlem Ceylon, Amandine Divaret-Chauveau, David Fleischer, Maximiliano Gomez, Marion Groetch, Domingo Barber Hernandez, Betina Hjorth, Lydia Collins Hussey, André C. Knulst, Agnes Leung, Douglas Mack, Vera Mahler, Francesca Mori, Leyla Namazova-Baranova, Kati Palosuo, Claudio Alberto Salvador Parisi, Antonio Carlos Pastorino, Odilija Rudzeviciene, Maria Said, Piotr Sawiec, Scott Sicherer, Sakura Sato, and Svitlana Zubchenko

Subjects
Food allergy, Food hypersensitivity, Children, Adolescent, Adults, Immunologic diseases. Allergy, RC581-607
Abstract

Food allergy affects approximately 2–4% of children and adults. This guideline provides recommendations for managing food allergy from the Global Allergy and Asthma European Network (GA2LEN). A multidisciplinary international Task Force developed the guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE) II framework and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We reviewed the latest available evidence as of April 2021 (161 studies) and created recommendations by balancing benefits, harms, feasibility, and patient and clinician experiences. We suggest that people diagnosed with food allergy avoid triggering allergens (low certainty evidence). We suggest that infants with cow's milk allergy who need a breastmilk alternative use either hypoallergenic extensively hydrolyzed cow's milk formula or an amino acid-based formula (moderate certainty). For selected children with peanut allergy, we recommend oral immunotherapy (high certainty), though epicutaneous immunotherapy might be considered depending on individual preferences and availability (moderate certainty). We suggest considering oral immunotherapy for children with persistent severe hen's egg or cow's milk allergy (moderate certainty). There are significant gaps in evidence about safety and effectiveness of the various strategies. Research is needed to determine the best approaches to education, how to predict the risk of severe reactions, whether immunotherapy is cost-effective and whether biological therapies are effective alone or combined with allergen immunotherapy.

Published
2022
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3. Influence of Moderate Hyperbilirubinemia on Cardiorespiratory Control in Preterm Lambs

Author

Sally Al-Omar, Virginie Le Rolle, Nathalie Samson, Marie-Laure Specq, Melisande Bourgoin-Heck, Nathalie Costet, Guy Carrault, and Jean-Paul Praud

Subjects
hyperbilirubinemia, prematurity, heart rate variability, respiratory rate variability, cardiorespiratory interrelations, Physiology, QP1-981
Abstract

Hyperbilirubinemia (HB) is responsible for neonatal jaundice in 60% of term newborns and 90% of preterm infants. Neonatal HB can induce neurological damage (acute HB encephalopathy) and has been associated with persistent apneas. The objective of the present study was to investigate the immediate and delayed effects of moderate, clinically-relevant HB on cardiorespiratory control in preterm lambs. Two groups of five preterm lambs, namely control and HB, were studied. At day five of life, moderate HB (150–250 μmol/L) was induced and maintained during 17 h in the HB group while control lambs received a placebo solution. Six hours after HB onset, 7-h polysomnographic recordings with electrocardiogram (ECG) and respiratory (RESP) signals were performed to assess the immediate effects of HB on heart rate variability (HRV), respiratory rate variability (RRV), and cardiorespiratory interrelations. Identical recordings were repeated 72 h after HB induction to examine the delayed effects of HB on HRV, RRV and cardiorespiratory interrelations. Our results demonstrate a higher HRV and vagal activity immediately after induction of moderate HB. Meanwhile, a decrease in respiratory rate with an increase in both long- and short-term RRV was also noted, as well as a higher amplitude of the respiratory sinus arrhythmia and cardiorespiratory coupling. Seventy-two hours later, the alterations in HRV, RRV, and cardiorespiratory interrelations were attenuated, although a number of them were still present, suggesting a lasting influence of HB on the basal control of the cardiorespiratory system. Our results pave the way for studies in human preterms to assess the relevance of monitoring HRV, RRV, and cardiorespiratory interrelations to detect the acute neurological effects of HB and consequently adapt the treatment of neonatal jaundice.

Published
2019
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4. Effects of Moderate Hyperbilirubinemia on Nutritive Swallowing and Swallowing-Breathing Coordination in Preterm Lambs

Author

François Corbin, Jean-Paul Praud, Nathalie Samson, Marie-Laure Specq, Charlène Nadeau, Melisande Bourgoin-Heck, and Martin Prodel

Subjects
Male, Apnea, Swallowing, Respiration, otorhinolaryngologic diseases, medicine, Animals, Respiratory inductance plethysmography, Hyperbilirubinemia, Sheep, medicine.diagnostic_test, business.industry, digestive, oral, and skin physiology, Neurotoxicity, medicine.disease, Bottle Feeding, Deglutition, Plethysmography, Pulse oximetry, Animals, Newborn, Anesthesia, Pediatrics, Perinatology and Child Health, Breathing, Female, medicine.symptom, business, Somnolence, Developmental Biology
Abstract

Background: Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. HB induces acute neurological disorders (somnolence, abnormal tone, feeding difficulties, auditory dysfunction) and alterations in respiratory control. These findings suggest brainstem neurotoxicity that could also affect swallowing centers. Objective: To test the hypothesis that HB impairs nutritive swallowing (NS) and swallowing-breathing coordination. Methods: Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. On day 5 of life (D0), moderate HB (150-250 µmol/l) was induced during 17 h in the HB group. Swallowing was assessed via recording of pharyngeal pressure and respiration by respiratory inductance plethysmography and pulse oximetry. The effect of HB on NS was assessed during standardized bottle-feeding. A second recording was performed 48 h after recovery from HB (D3). Results: Swallows were less frequent (p = 0.003) and of smaller volume (p = 0.01) in HB lambs while swallowing frequency was decreased (p = 0.004). These differences disappeared after HB normalization. Swallowing-breathing coordination was impaired in HB lambs, with a decrease in percent time with NS burst-related apneas/hypopneas at D0 and D3. Simultaneously, HB lambs tended to experience more severe desaturations (Conclusions: Swallowing and swallowing-breathing coordination are altered by acute moderate HB in preterm lambs. Decreased efficiency at bottle-feeding is accompanied by continuation of breathing during swallow bursts, which may promote lung aspiration.

Published
2015
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5. Moderate Hyperbilirubinemia Alters Neonatal Cardiorespiratory Control and Induces Inflammation in the Nucleus Tractus Solitarius

Author

Jean-Paul Praud, François Corbin, Nathalie Samson, Maxime M. Richer, Hazim Kadhim, Marie Laure M.L. Specq, Melisande Bourgoin-Heck, Christian Gestreau, Département de pédiatrie [Sherbrooke] (UdeS), Faculté de médecine et des sciences de la santé [Sherbrooke] (UdeS), Université de Sherbrooke (UdeS)-Université de Sherbrooke (UdeS), Université de Sherbrooke (UdeS), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Respiratory rate, hyperbilirubinemia, Bilirubin, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, brain, Pathophysiology, lcsh:Physiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Physiologie générale, 030225 pediatrics, Physiology (medical), Internal medicine, medicine, Pulmonary and laryngeal chemoreflexes, Hypoxia, nucleus tractus solitarius, pathophysiology, Hyperbilirubinemia, Original Research, Calcium metabolism, pulmonary and laryngeal chemoreflexes, lcsh:QP1-981, business.industry, hypoxia, prematurity, Brain, Nucleus tractus solitarius, Apnea, Cardiorespiratory fitness, Hypoxia (medical), Endocrinology, chemistry, Anesthesia, Brainstem, medicine.symptom, Prematurity, business, 030217 neurology & neurosurgery
Abstract

Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. At day 5 of life, moderate HB (150-250 μmol/L) was induced during 17 h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia. Recordings were repeated 72 h after HB induction, just before euthanasia. In addition, neuropathological studies were performed to investigate for cerebral bilirubin deposition as well as for signs of glial reactivity in brainstem structures involved in cardiorespiratory control. Results revealed that sustained and moderate HB: (i) decreased baseline respiratory rate and increased the time spent in apnea; (ii) blunted the cardiorespiratory inhibition normally observed during both laryngeal and pulmonary chemoreflexes; and (iii) increased heart rate in response to acute hypoxia. These acute physiological changes were concurrent with an activation of Alzheimer type II astrocytes throughout the brain, including the brainstem. Concomitantly, bilirubin deposits were observed in the leptomeninges, but not in brain parenchyma. While most cardiorespiratory alterations returned to normal 72 h after HB normalization, the expression of glial fibrillary acid protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) was still increased within the nucleus tractus solitarius. In conclusion, moderate and sustained HB in preterm lambs induced cardiorespiratory alterations, the latter of which were associated with neurohistopathological changes. These changes are indicative of an inflammatory response in the brainstem neuroanatomical substrates involved in cardiorespiratory control., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016
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6. Moderate Hyperbilirubinemia Alters Neonatal Cardiorespiratory Control and Induces Inflammation in the Nucleus Tractus Solitarius

Author

Marie-Laure Specq, Mélisande Bourgoin-Heck, Nathalie Samson, François Corbin, Christian Gestreau, Maxime Richer, Hazim Kadhim, and Jean-Paul Praud

Subjects
Brain, Hyperbilirubinemia, hypoxia, pathophysiology, prematurity, Pulmonary and laryngeal chemoreflexes, Physiology, QP1-981
Abstract

Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. At day 5 of life, moderate HB (150-250 µmol/L) was induced during 17h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia. Recordings were repeated 72 hours after HB induction, just before euthanasia. In addition, neuropathological studies were performed to investigate for cerebral bilirubin deposition as well as for signs of glial reactivity in brainstem structures involved in cardiorespiratory control. Results revealed that sustained and moderate HB: i) decreased baseline respiratory rate and increased the time spent in apnea; ii) blunted the cardiorespiratory inhibition normally observed during both laryngeal and pulmonary chemoreflexes and iii) increased heart rate in response to acute hypoxia. These acute physiological changes were concurrent with an activation of Alzheimer type II astrocytes throughout the brain, including the brainstem. Concomitantly, bilirubin deposits were observed in the leptomeninges, but not in brain parenchyma. While most cardiorespiratory alterations returned to normal 72 hours after HB normalization, the expression of glial fibrillary acid protein (GFAP) and Ionized calcium binding adaptor molecule 1 (Iba1) was still increased within the nucleus tractus solitarius. In conclusion, moderate and sustained HB in preterm lambs induced cardiorespiratory alterations, the latter of which were associated with neurohistopathological changes. These changes are indicative of an inflammatory response in the brainstem neuroanatomical substrates involved in cardiorespiratory control.

Published
2016
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