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1. Analysis of questionnaire survey to determine worldwide trends in prescriptions of biologics for the treatment of unresponsive chronic urticaria

Author

Christine J. Rubeiz, MD, Ricardo Asero, MD, Stephen Betschel, HBSc, MD, FRCP (C), Timothy Craig, DO, Anete Grumach, MD, PhD, Michihiro Hide, MD, PhD, David Lang, MD, Michael Levin, MD, PhD, Hilary Longhurst, MA, PhD, FRACP, FRCPath, Eli Magan, MD, Marcus Maurer, MD, Romi Saini, MD, Gordon Sussman, MD, Elias Toubi, MD, Dinh Nguyen Van, MD, PhD, Torsten Zuberier, MD, and Jonathan A. Bernstein, MD

Subjects
Chronic spontaneous urticaria, Clinical research, Safety, Adverse effects, Monitoring, Biologics, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Chronic spontaneous urticaria (CSU) is a common condition treated by allergist/immunologists, but the only FDA-approved biologic medication, omalizumab, may be underutilized globally. Objective: This study was performed to determine the global prescription of omalizumab for treatment of CSU by allergists/immunologists. Methods: Anonymous questionnaire surveys were distributed online to World Allergy Organization (WAO) members worldwide. Categorical data were analyzed for descriptive analysis using one-way frequency tabulation in SAS 9.4. Results: There were 348 respondents (43 missing data); Average age 51 (range 28–90); M/F 48%/52%. 58% had > 15 years of clinical experience and 10%

Published
2024
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2. Global disparities in availability of epinephrine auto-injectors

Author

Luciana Kase Tanno, MD, PhD, Margitta Worm, MD, PhD, Motohiro Ebisawa, MD, PhD, Ignacio J. Ansotegui, MD, PhD, Gianenrico Senna, MD, PhD, Stanley Fineman, MD, PhD, Mario Geller, MD, Alexei Gonzalez-Estrada, MD, Dianne E. Campbell, MBBS, FRACP, PhD, Agnes Leung, MBChB, Antonella Muraro, MD, PhD, Michael Levin, MD, PhD, Jose Antonio Ortega Martell, MD, PhD, Marco Caminati, MD, Pavel Kolkhir, MD, Duy Le Pham, MD, PhD, Razvigor Darlenski, MD, PhD, Ignacio Esteban-Gorgojo, MD, Manuel Rial, MD, PhD, Ivana Filipovic, MD, Sergio E. Chiarella, MD, Lyda Cuervo-Pardo, MD, Christina Kwong, MD, Cezar Fireth Pozo-Beltran, MD, Tu HK. Trinh, MD, PhD, Paul A. Greenberger, MD, Paul J. Turner, FRCPCH, PhD, Bernard Yu-Hor Thong, MBBS, FRCP (Edin), Bryan Martin, MD, and Victoria Cardona, MD, PhD

Subjects
Anaphylaxis, Adrenaline, Adrenaline auto-injector, Epinephrine auto-injector, Management, Treatment, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Anaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis – both acute and preventative – varies by region. Methods: The World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. Results: Responses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. Conclusion: This survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.

Published
2023
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3. Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study

Author

Zeinab A. El-Sayed, MD, PhD, Dalia H. El-Ghoneimy, MD, PhD, José A. Ortega-Martell, MD, Nesrine Radwan, MD, PhD, Juan C. Aldave, MD, Waleed Al-Herz, MD, Maryam A. Al-Nesf, MD, ABHS, Antonio Condino-Neto, MD, PhD, Theresa Cole, MD, PhD, Brian Eley, MD, Nahla H.H. Erwa, DipRCPATH, Sara Espinosa-Padilla, PhD, Emilia Faria, MD, Nelson A. Rosario Filho, MD, PhD, Ramsay Fuleihan, MD, Nermeen Galal, MD, PhD, Elizabeth Garabedian, RN, MSLS, Mary Hintermeyer, BN, Kohsuke Imai, MD, PhD, Carla Irani, MD, MSCE, Ebtihal Kamal, MD, Nadia Kechout, MD, PhD, Adam Klocperk, MD, PhD, Michael Levin, MD, PhD, Tomas Milota, MD, PhD, Monia Ouederni, MD, Roberto Paganelli, MD, Claudio Pignata, MD, PhD, Farah N. Qamar, MBBS, FCPS, MSc, DHPE, FRCP, Isabella Quinti, MD, PhD, Sonia Qureshi, MBBS, FCPS, MSc, Nita Radhakrishnan, MD, PhD, Nima Rezaei, MD, PhD, John Routes, MD, PhD, Surjit Singh, MD, DCH (Lon.), FRCP (Lon.), FRCPCH (Lon.), FAMS, Sangeetha Siniah, MBBS, MRCPCH, Intisar Abdel-Hakam Taha, MD, SMSB, Luciana K. Tanno, MD, Ph.D, Ben Van Dort, BN, Alla Volokha, MD, PhD, DSc, and Kathleen Sullivan, MD, PhD

Subjects
Primary immunodeficiency, Asthma, Atopic dermatitis, IVIG, Omalizumab, Anaphylaxis, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. Results: Thirty centers in 23 countries caring for a total of 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10–28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3–11.3%) had bronchial asthma, 3.6% (1.9–9.1%) atopic dermatitis, 3.0% (1.0–7.8%) allergic rhinitis, and 1.3% (0.5–3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5–25%) and diagnosis delay was reported in 7.5% (0.9–20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2–62.5%) and 20.0% (10–32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.

Published
2022
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4. WAO-ARIA consensus on chronic cough – Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19

Author

Philip W. Rouadi, MD, Samar A. Idriss, MD, Jean Bousquet, MD, PhD, Tanya M. Laidlaw, MD, Cecilio R. Azar, MD, Mona S. Al-Ahmad, MD, FRCPCP, Anahi Yañez, MD, Maryam Ali Y. Al-Nesf, MD, MSc R, CABHS, Talal M. Nsouli, MD, FACAAI, FAAAAI, Sami L. Bahna, MD, DrPH, Eliane Abou-Jaoude, MD, Fares H. Zaitoun, MD, FACAAI, Usamah M. Hadi, MD, FACS, ERS, PARS, Peter W. Hellings, MD, PhD, Glenis K. Scadding, MD, FRCP, Peter K. Smith, BMedSci, MBBS, FRACP, PhD, Mario Morais-Almeida, MD, René Maximiliano Gómez, MD, PhD, Sandra N. Gonzalez Diaz, MD, PhD, Ludger Klimek, MD, PhD, Georges S. Juvelekian, MD, FCCP, D’ABSM, Moussa A. Riachy, MD, FCCP, Giorgio Walter Canonica, MD, David Peden, MD, Gary W.K. Wong, MD, James Sublett, MD, Jonathan A. Bernstein, MD, Lianglu Wang, MD, Luciana K. Tanno, MD, PhD, Manana Chikhladze, PhD, Michael Levin, MD, Yoon-Seok Chang, MD, PhD, Bryan L. Martin, DO, Luis Caraballo, MD, PhD, Adnan Custovic, MD, PhD, Jose Antonio Ortego-Martell, MD, Olivia J.Ly Lesslar, MBBS BIR, Erika Jensen-Jarolim, MD, Motohiro Ebisawa, MD, Alessandro Fiocchi, MD, and Ignacio J. Ansotegui, MD, PhD

Subjects
Upper airway cough syndrome, Lower airway disease, Reflux cough, Chronic cough management, Neuromodulators, Speech therapy, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

Published
2022
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5. WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation — Updates in COVID-19

Author

Philip W. Rouadi, MD, Samar A. Idriss, MD, Jean Bousquet, MD, PhD, Tanya M. Laidlaw, MD, Cecilio R. Azar, MD, Mona S. Al-Ahmad, MD, FRCPCP, Anahi Yañez, MD, Maryam Ali Y. Al-Nesf, MD, MSc R, CABHS, Talal M. Nsouli, MD, FACAAI, FAAAAI, Sami L. Bahna, MD, DrPH, Eliane Abou-Jaoude, MD, Fares H. Zaitoun, MD, FACAAI, Usamah M. Hadi, MD, FACS, ERS, PARS, Peter W. Hellings, MD, PhD, Glenis K. Scadding, MD, FRCP, Peter K. Smith, BMedSci, MBBS, FRACP, PhD, Mario Morais-Almeida, MD, René Maximiliano Gómez, MD, PhD, Sandra N. Gonzalez Diaz, MD, PhD, Ludger Klimek, MD, PhD, Georges S. Juvelekian, MD, FCCP, D'ABSM, Moussa A. Riachy, MD, FCCP, Giorgio Walter Canonica, MD, David Peden, MD, Gary W.K. Wong, MD, James Sublett, MD, Jonathan A. Bernstein, MD, Lianglu Wang, MD, Luciana K. Tanno, MD, PhD, Manana Chikhladze, PhD, Michael Levin, MD, Yoon-Seok Chang, MD, PhD, Bryan L. Martin, DO, Luis Caraballo, MD, PhD, Adnan Custovic, MD, PhD, Jose Antonio Ortega-Martell, MD, Erika Jensen-Jarolim, MD, Motohiro Ebisawa, MD, Alessandro Fiocchi, MD, and Ignacio J. Ansotegui, MD, PhD

Subjects
Multifactorial cough, Cough phenotypes, Type 2 inflammation, COVID 19, Reflux-cough, Upper airway cough syndrome, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. Outcomes: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Published
2021
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6. WAO-ARIA consensus on chronic cough – Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways

Author

Philip W. Rouadi, MD, Samar A. Idriss, MD, Jean Bousquet, MD, PhD, Tanya M. Laidlaw, MD, Cecilio R. Azar, MD, Mona Sulaiman AL-Ahmad, MD, FAAAI, FRCPCP, Anahí Yáñez, MD, Maryam Ali Y. AL-Nesf, MD, MSc, R, CABHS, Talal M. Nsouli, MD, FACAAI, FAAAAI, Sami L. Bahna, MD, DrPH, Eliane Abou-Jaoude, MD, Fares H. Zaitoun, MD, FACAAI, Usamah M. Hadi, MD, FACS, ERS, PARS, Peter W. Hellings, MD, PhD, Glenis K. Scadding, MD, FRCP, Peter K. Smith, BMedSci, MBBS, FRACP, PhD, Mario Morais-Almeida, MD, R. Maximiliano Gómez, MD, PhD, Sandra N. González Díaz, MD, PhD, Ludger Klimek, MD, PhD, Georges S. Juvelekian, MD, FCCP, D'ABSM, Moussa A. Riachy, MD, FCCP, Giorgio Walter Canonica, MD, David Peden, MD, Gary W.K. Wong, MD, James Sublett, MD, Jonathan A. Bernstein, MD, Lianglu Wang, MD, Luciana Kase Tanno, MD, PhD, Manana Chikhladze, PhD, Michael Levin, MD, PhD, Yoon-Seok Chang, MD, PhD, Bryan L. Martin, DO, Luis Caraballo, MD, PhD, Adnan Custovic, MD, PhD, José Antonio Ortega-Martell, MD, Erika Jensen-Jarolim, MD, Motohiro Ebisawa, MD, PhD, Alessandro Fiocchi, MD, and Ignacio J. Ansotegui, MD, PhD

Subjects
TRP channel, P2X3, Pathogenesis, Chronic cough, Chemoreceptors, Mechanoreceptors, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. Outcomes: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

Published
2021
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7. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis

Author

Navin P. Boeddha, MD, PhD, Gertjan J. Driessen, MD, PhD, Nienke N. Hagedoorn, MD, Daniela S. Kohlfuerst, MD, Clive J. Hoggart, PhD, Angelique L. van Rijswijk, MSc, Ebru Ekinci, MD, Debby Priem, BSc, Luregn J. Schlapbach, MD, PhD, Jethro A. Herberg, MD, PhD, Ronald de Groot, MD, PhD, Suzanne T. Anderson, MD, PhD, Colin G. Fink, PhD, Enitan D. Carrol, MD, PhD, Michiel van der Flier, MD, PhD, Federico Martinón-Torres, MD, PhD, Michael Levin, MD, PhD, Frank W. Leebeek, MD, PhD, Werner Zenz, MD, PhD, Moniek P. M. de Maat, PhD, Jan A. Hazelzet, MD, PhD, Marieke Emonts, MD, PhD, Willem A. Dik, PhD, on behalf of the EUCLIDS consortium, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, S Bokhandi, Sue Power, Heather Barham, N Pathan, Jenna Ridout, Deborah White, Sarah Thurston, S Faust, S Patel, Jenni McCorkell, P Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, R Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O’Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, A Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, PM Fortune, Phil Hudnott, Federico Martinón-Torres, Antonio Salas, Fernando Álvez González, Ruth Barral-Arca, Miriam Cebey-López, María José CurrasTuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Jacobo Pardo-Seco, Sara Pischedda, Irene Rivero Calle, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Antonio Salas Ellacuriaga, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, J.Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, Mª del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, R. de Groot, A.M. Tutu van Furth, M. van der Flier, N.P. Boeddha, G.J.A. Driessen, M. Emonts, J.A. Hazelzet, T.W. Kuijpers, D. Pajkrt, E.A.M. Sanders, D. van de Beek, A. van der Ende, H.L.A. Philipsen, A.O.A. Adeel, M.A. Breukels, D.M.C. Brinkman, C.C.M.M. de Korte, E. de Vries, W.J. de Waal, R. Dekkers, A. Dings-Lammertink, R.A. Doedens, A.E. Donker, M. Dousma, T.E. Faber, G.P.J.M. Gerrits, J.A.M. Gerver, J. Heidema, J. Homan-van der Veen, M.A.M. Jacobs, N.J.G. Jansen, P. Kawczynski, K. Klucovska, M.C.J. Kneyber, Y. Koopman-Keemink, V.J. Langenhorst, J. Leusink, B.F. Loza, I.T. Merth, C.J. Miedema, C. Neeleman, J.G. Noordzij, C.C. Obihara, A.L.T. van Overbeek – van Gils, G.H. Poortman, S.T. Potgieter, J. Potjewijd, P.P.R. Rosias, T. Sprong, G.W. ten Tussher, B.J. Thio, G.A. Tramper-Strander, M. van Deuren, H. van der Meer, A.J.M. van Kuppevelt, A.M. van Wermeskerken, W.A. Verwijs, T.F.W. Wolfs, Luregn J Schlapbach, Philipp Agyeman, Christoph Aebi, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Christoph Berger, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Marieke Emonts, Rachel Agbeko, Suzanne Anderson, Fatou Secka, Kalifa Bojang, Isatou Sarr, Ngane Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumatta Cole, Gilleh Thomas, Martin Antonio, Werner Zenz, Daniela S. Klobassa, Alexander Binder, Nina A. Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, and Veslava Žukovskaja

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

IMPORTANCE:. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES:. To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN:. Data from two prospective cohort studies. SETTING AND PARTICIPANTS:. Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES:. Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS:. In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE:. In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.

Published
2021
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